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HIV Physician Training Course 2002,
Christian Medical College, Vellore
DISTANCE LEARNING COURSE
NERVOUS SYSTEM
IN
HIV INFECTION
Author: O. C. Abraham
Course Organiser : Anand Zachariah
Distance Learning Expert: Janet Grant, Open University, UK
This course is supported by the European Commission through grant number
IND/B76211/1B/1999/0379 provided to the HIV/STI Prevention and Care Research
Programme of the Population Council India.
MODULE 1
1
MODULE 1
OVERVIEW
HIV enters the brain immediately after infection, is present throughout the
course of the disease, and, in the later stages, often manifests at every level of
the neurological system. Central nervous system (CNS) and peripheral
nervous system (PNS) disorders in HIV-infected individuals may result from:
(1) opportunistic infections (OI), (2) neoplasms and (3) primary effects of
HIV itself. The nervous system may also be damaged (4) as a result of the
toxic effects of various treatments.
The primary HIV-associated neurologic diseases include: AIDS dementia,
myelopathy, peripheral neuropathy, and myopathy. Secondary neurologic
complications include: cryptococcal meningitis, tuberculous meningitis,
neurosyphilis. Toxoplasma encephalitis (TE), progressive multifocal
leukoencephalopathy (PML), cytomegalovirus (CMV) encephalitis and
radiculomyelitis and primary CNS lymphoma. Both primary and secondary
complications should be considered when neurologic changes are observed in
patients with HIV.
The common presenting symptoms of neurological disease are: (a) headache;
(b) seizures and weakness; (c) limb pain and (d) memory loss. The main
neurological syndromes occurring in HIV infection are: (i) meningitis; (ii)
focal neurological deficit; (iii) peripheral neuropathy and (iv) dementia.
This module aims to improve your skills in approaching these symptoms and
neurological syndromes.
J
MODULE 1
2
OBJECTIVES
After completion of this module you should be able to:
1. List the common HIV related neurological diseases.
2. Recognize the different clinical syndromes and the main causative
agents/disease conditions responsible for these syndromes.
3. Use clinical algorithms to diagnose and manage these conditions.
CONTENTS
Activity
Title
Time (min.)
Page No.
10
3
and Opportunistic Infections
20
34
1.2
Meningitis in HIV infection
10
6
Reading
Approach to meningitis
15
35
1.3
CSF analysis
10
9
1.4
Cryptococcal Meningitis
10
11
Reading
Cryptococcal meningitis
15
36
1.5
Approach to limb weakness
10
15
1.6
CT Scan
10
17
Reading
Approach to
Focal cerebral syndrome
15
38
1.7
Toxoplasma encephalitis
10
19
Reading
Toxoplasma encephalitis
20
39
1.8
Approach to limb pain
10
23
Reading
Approach to neuropathy
15
41
1.9
Neuropathy
10
24
1.10
Approach to forgetfulness
10
25
1.11
AIDS dementia complex
10
28
Reading
AIDS dementia complex
15
42
Tutor marked assignment
60
32
TOTAL TIME (min)
285
1.1
Approach to headache
Reading
Neurological Syndromes
3
MODULE 1
Let us start with an activity for you to learn the approach of
a patient presenting with headache.
Study the table:
"Table:
Neurological Syndromes and Opportunistic Infections in AIDS"
(page 34) in the reader. Once you have finished reading this
you should be able to undertake this activity.
ACTIVITY 1.1
APPROACH TO HEADACHE (10 min)
Mr. S. is a 32-year old truck driver, He was diagnosed to
have HIV infection 8 years ago. He had remained well till
about one year ago, when he started losing weight, He was
seen by a doctor in his hometown who, after tests
revealed
absolute
lymphocyte
count
(ALC)
880
cells/p-L,
had prescribed co-trimoxazole (one double-strength tablet
daily) . He was on no other medicines. He now presents to
your clinic with a 4-week history of headache,
which had
really worsened over the last one week. His wife reports
that he has become progressively drowsy and disoriented
over the last three days.
1.
Which of the neurological syndromes do you think the
patient is suffering from?
- 2
4
2.
Now,
MODULE 1
list your differential diagnoses
(most to least
common) for Mr. S in the space provided below.
Meningitis
Focal cerebral lesion
1.
1.
A
2.
2.
3.
4.
3.
H P^iL
4.
3.
you
What
additional history and clinical
like
to
elicit
in Mr
Mr..
findings would
S to find out
neurological syndrome and its etiology?
HISTORY
EXAMINATION
1.
1.
2.
2.
3.
3.
4.
the
type
of
5
MODULE 1
^FEEDBACK 1.1
1. Which neurological syndrome do you think the patient
is suffering from?
This patient may be having meningitis or a focal cerebral lesion.
The history of worsening headache and worsening sensorium in HIV
infection should make you consider a diagnosis of meningitis. Usually
meningitis is associated with fever but this may not always be true in HIV
infection.
The worsening sensorium and headache should also make you consider a
focal cerebral lesion. This would present with a history of seizures or
focal neurological symptoms (such as hemiplegia). This may therefore be
considered less likely in him.
2. Differential Diagnoses
AAeningitis
Focal cerebral lesion
1. Cryptococcal meningitis
1. Cerebral toxoplasmosis
2. TB meningitis
2. Tuberculoma
3. Syphilitic meningitis
3. Lymphoma
A.Progressive multi-focal
leucoencephalopathy (PAAL)
J
3. History and physical examination
HISTORY
EXAMINATION
1. Seizures
1. Neck stiffness
2. Focal neurological symptoms
2. Level of consciousness
3. Papilloedema
4. Weakness of limbs (focal deficit)
6
MODULE 1
5.
Skin involvement (cryptococcal
infection)
6. Lung signs, lymphadenopathy (TB
or cryptococcal infection)
Before you undertake the next activity study the figure:
^Approach to patient with meningitis in HIV infection"
(page 35). Then start the activity.
ACTIVITY 1.2
MENINGITIS IN HIV INFECTION (10 min)
On
physical
pulse
rate
examination,
Mr.
S
appears
emaciated.
is
blood
pressure
140/95
72/min,
His
mmHg,
7
temperature 38 ° C (100.4° F) . He is very drowsy, localizes
pain and opens eyes to pain. He appears pale, but has no
lymphadenopathy. Oral thrush is present and there are few
umbilicated, papular skin lesions on the face
(see photo
1A page 44) and anterior chest wall.
of
normal.
examination shows
CNS
neurological
9
cardiovascular,
Examination
deficits,
respiratory
system
no papi11edema,
bilaterally
reflexes and terminal neck stiffness.
extensor
no
are
focal
plantar
€
7
MODULE 1
w
1.
What is your diagnosis? What is the reason you are
considering this diagnosis?
1.Diagnosis:
2. Reason for diagnosis:
•
tT?r
’
’
'/.SA*
2. What tests will you order to confirm your diagnosis
and rule out other differential diagnoses?
1.
1
2.
c j
3.
4.
5.
JU.
z
o
X
8
MODULE 1
»
FEEDBACK 1.2
1.
What is your diagnosis? What is the reason you are
considering this diagnosis?
Diagnosis: Cryptococcal meningitis
Reason for diagnosis: Molluscum-like skin lesions should make think of
cryptococcal infection.
2. What tests will you order to confirm your diagnosis
and rule out other differential diagnoses?
1. CSF - opening pressure
2. CSF -total and differential WBC count
3. CSF - Gram stain, India ink test, Cryptococcal antigen (if available),
AFB smear
4. Blood and CSF VDRL
5. Routine bacterial, fungal and mycobacterial cultures (if available)
—t3 A
______—-—
>
<
"
9
s
MODULE 1
ACTIVITY 1.3
CSF ANALYSIS (10 min)
A
lumbar
puncture
was
done
for
Mr.
S.
The
opening
pressure was 290 mm water. His CSF analysis showed 8 WBC
(all lymphocytes), glucose 30 mg/dl and protein 95 mg/dl.
1. What is the differential diagnosis of the CSF picture?
2.
The
(page
India
44) .
ink preparation
Describe
organism.
Description -
Identification
what
is
you
shown
see
in the photo
and
identify
IB
the
MODULE 1
10
^FEEDBACK 1.3
1. What is the differential diagnosis of the CSF picture?
The CSF shows: mildly increased WBC count and protein and low glucose
(<40 mg/dl). The differential diagnosis includes:
Cryptococcal meningitis
TB meningitis
Syphilitic meningitis
2.
Describe what you see and identify the organism
Description - Budding yeast like organism with capsule surrounding it.
Identification
-This
is
the
typical
appearance
of
Cryptococcus
neoformans
A positive India Ink test is confirms the diagnosis of cryptococcal
meningitis. A negative test does not rule out the diagnosis.
MODULE 1
11
Before you undertake the next activity read ^Cryptococcal
Meningitis"
(page 36) in the reader.
ACTIVITY 1.4
CRYPTOCOCCAL MENINGITIS (10 min)
1.
The
relatives
of
the
patient
ask
you
what
the
prognosis of the patient is like. Would you describe the
prognosis to be good or poor?
I'
'xJk. f
2. Which therapy would you choose for Mr. S.
Drug:
?
Dose:
Duration:
i
Total cost:
i
Hr
12
3. Mr.
S
MODULE 1
's
sensorium worsens on treatment and headache
and
vomiting
increase.
What
additional
therapeutic
intervention would you perform?
4. What side effects of treatment will you monitor for
and how will you manage these?
13
MODULE 1
^FEEDBACK 1.4
\
1. Would you describe the prognosis to be good or poor?
Poor prognosis: low CSF cell response, India Ink positive, extra-neural
disease, altered consciousness, low CSF glucose
2. Which therapy would you choose for Mr. S?
Amphotericin 0.7 mg/kg/day (IV) with Flucytosine 100 mg/Kg in 4 divided
doses (orally) for 2 weeks followed by fluconazole 400 mg Ob (orally) for
10 weeks.
Maintenance therapy 200 mg Ob life long
In view of the poor prognostic features Amphotericin therapy is
preferred. If flucytosine is not available, then Amphotericin alone can be
given for 2 week alone followed by fluconzole.
To start Amphotericin give first dose 1 mg in 100 ml 5% dextrose over 1
hour, monitoring vital signs every 15 minutes. If no serious adverse events
occur, this is followed 4 hours later with 0.7 mg/Kg in 500 ml 5%
dextrose infusion over 4-6 hours.
Total cost of Amphotericin (2weeks) followed by fluconazole (10 weeks):
Rs. 7900.
If he cannot afford Amphotericin treatment then oral
fluconazole may
be an alternative option. In a patient without poor prognostic features
oral fluconazole may be considered one of the first options. It has fewer
side effects is less costly and can
be administered in the outpatient
setting.
3.Mr.
S
vomiting
's
sensorium worsens
increase,
would you perform?
What
on
treatment
additional
and
therapeutic
headache
and
intervention
14
MODULE 1
In view of the elevated CSF pressure >280 mm a
therapeutic lumbar puncture is recommended at 2-3 day intervals
removing 10-20 ml CSF at a time. Following therapeutic LP the closing
pressure should be checked.
4. What side effects of treatment will you monitor for and how
will you manage these?
Amphotericin
Febrile reaction- Aspirin or paracetamol. Can be reduced by administering
hydrocortisone 10-50 mg prior to the infusion.
Hypotension, nausea and vomiting 1-3 hours post-infusion (initial test dose
may predict patients who develop hypotension)
Nephrotoxicity- Monitor creatinine twice a week. Reduce dose or stop if
creatinine > 3 mg/dl, Prevent by ensuring hydration, normal saline infusion
1 L/day, avoid concurrent nephrotoxic drugs.
Hypokalemia- check K+ 2 times/week; correct with oral KCI
Anaemia-does not require dose alteration.
Phlebitis or pain at the infusion site- may be prevented by using central
line.
15
MODULE 1
ACTIVITY 1.5
APPROACH TO LIMB WEAKNESS (10 min)
Mr.
G,
works
a
as
butcher.
He
was
detected
to
HIV
be
seropositive 5 years ago, when he attended an STD clinic
for
recurrent
genital
herpes progenitalis.
ulcers
which
Two years ago,
were
he was diagnosed to
have tuberculous
lymphadenitis
(cervical),
was
on
anti-tuberculous
therapy
year
(3HREZ/9HR).
regular
prophylaxis,
He was
as
diagnosed
for which he
(ATT)
for
one
also prescribed co-trimoxazole
which he discontinued after
the
course of
ATT was over. One week ago, he had an episode of seizures
involving the
right
side of face
while working in his shop.
recurrent
seizures
noticed progressive
and
and right upper
limb
Over the next few days he had
could not
weakness
of
attend work.
right
upper
He
also
and
lower
limbs over the last two days. When seen in the clinic, he
was
confused,
restless
and
examination
revealed
motor
aphasia and right-sided hemiparesis.
1. Which type of neurological syndrome does this patient
have? Write down the differential diagnosis in order of
probability.
Neurological syndrome:
Differential diagnosis:
I
'A?
16
MODULE 1
^FEEDBACK 1.5
i. Which type of neurological syndrome does this patient
have? Write down the differential diagnosis in order of
probability.
Focal cerebral lesion- in view of the focal neurological deficit. The right
side hemiplegia and motor aphasia localize the lesion to the left frontal
lobe.
Differential diagnosis'.
T.E.
Tuberculoma
CNS lymphoma
Progressive multi-focal leukoencephalopthy
Toxoplasma encephalitis would be the most likely diagnosis because it is
the commonest cause of focal cerebral lesions in PLWHA. Also, he had
discontinued prophylaxis (co-trimoxazole) which may have resulted in
reactivation of latent infection.
Before
doing
the
next
exercise
study
the
figure,
^Approach
to focal
(page 38) .
Once you have finished reading you are ready
cerebral
to start the exercise.
syndrome in HIV infection"'
17
MODULE 1
ACTIVITY 1.6
CT SCAN (10 min)
Study the
Photo
1C
(see page 44)
which is a brain CAT
scan (contrast plus) image of Mr. G.
1. Describe the appearance of these lesions.
Site Shape -
Isodense/hypodense/hyperdense -
Pressure effect and oedema
2.
What
are
all
the
differential diagnoses
of
lesions
with similar appearance on CAT scan?
3. Which blood test will help you identify which of these
diagnoses Mr. G is likely to have?
MODULE 1
18
^FEEDBACK 1.6
1.
Given
images
of
below
is
the brain
CAT
scan
Mr.
G.
Describe
the
appearance
(contrast
plus)
of
these
lesions.
Multiple ‘ring-enhancing' (a hypodense lesion which enhances on contrast
administration only along the periphery) lesions with surrounding edema
and mass effect.
2.
What
are
all
the
differential
diagnoses
of
lesions
with similar appearance on CAT scan?
•
Toxoplasma encephalitis
•
Primary CNS lymphoma
•
CNS tuberculoma
•
Neurocysticercosis
Brain abscess
•
Glioblastoma and other brain tumours
3. Which blood test will help you identify which of these
diagnoses Mr. G is likely to have?
IgG toxoplasma antibody titre. The absence of these antibodies excludes
the diagnosis of toxoplasma encephalitis. The presence of antibodies with
a ring enhancing lesion on the CT scan should lead to a presumptive
diagnosis of toxoplasma encephalitis.
19
Prior
to
doing
the
next
MODULE 1
exercise
read.
"Toxoplasma
encephalitis" (page 39) in the reader. Following this you
can proceed to the next exercise.
ACTIVITY 1.7
TOXOPLASMA ENCEPHALITIS (10 min)
i.
Mr.
Gz s
anti-toxoplasma antibody test
could not be
done, as it was not available in the hospital laboratory.
What treatment will you start for Mr. G?
Drugs
4'
/
ct
T
0-
Dose:
4 Pr
>
Side- effects
Secondary prophylaxis -
Cost:
^-7
<ro
7
20
2.How will
you
MODULE 1
follow up the
treatment? How quickly do
you expect a response to treatment?
I -
/
r
3. If Mr. G fails to improve what will you do next?
7^7 /s C
21
MODULE 1
FEEDBACK 1.7
1.
Mr.
done
G's
anti-toxoplasma
it
was
as
not
antibody
available.
What
could not
be
treatment will
you
test
start for Mr. G?
Drugs, dose and duration
Pyramethamine 100-200 mg stat followed by 50-100 mg 00
(Available is AAetakelfin -each tablet contains 25 mg Pyrimethamine)
Sulphadiazine 1-1.5 G q6h
Folinic acid 10-15 mg OD (If too expensive T. Folic aicdin higher doses
may be used).
All for 3-6 weeks followed by secondary prophylaxis.
Alternative treatment - Co-trimoxazole (TMP 5 mg/Kg BO)
Secondary prophylaxis - Sulphadiazine 500 mg- 1G gid,
Pyramethamine 75-100 mg 00, Folinic acid 10-25 mg 00 (life long)
Side effects - Orug rash, drug fever, crystalluria, anemia, bone marrow
suppression
Cost: (8 tablets of sulphadiazine + 4 tablets of metakelfin/day for 6
weeks)- Rs. 8048
2.
How will you follow-up the treatment? How quickly do
you expect a response to treatment?
Follow-up treatment by clinical response
Response is usually seen in 7-10 days. CT scan at 2 weeks is advised if the
22
MODULE 1
test is available and cost of test permits it being repeated.
3. If Mr. G fails to improve what will you do next?
If Mr. G fails to respond it may indicate a diagnosis other than
toxoplasma encephalitis. The lesion needs to be biopised using stereotaxic
brain biopsy at a higher centre. However studies have shown that the
etiological diagnosis obtained through brain biopsy are not readily
treatable. Therefore the clinical usefulness of brain biopsy in focal
cerebral lesions non-responsive to anti-toxoplasma treatment may be low.
23
Before
doing
the
next
MODULE 1
exercise
study
the
figure:
Approach to neuropathy with HIV infection"’ (page 41).
completion
of
the
reading,
you
can
start
the
On
next
exercise.
ACTIVITY 1.8
APPROACH TO LIMB PAIN (10 min)
Mr.
P.
is a bank manager, who was diagnosed to have HIV
infection 3 years ago.
antiretroviral
Efavirenz)
has
He was started on highly active
therapy
(Stavudine,
six months ago.
Didanosine
and
For the past two months,
noticed burning pain and a sensation of
"pins
he
and
needles", beginning on the fingers and toes and gradually
ascending till the level of the wrists and knees. He is a
non-smoker,
does
not
consume
alcohol
and
is
not
a
diabetic or hypertensive.
1. What is the diagnosis that explains Mr. P's symptoms?
-
2.
<>
Mention
the
differential
diagnosis
of
neurological syndrome and its most likely etiology?
this
24
MODULE 1
FEEDBACK 1.8
1. What is the diagnosis that explains Mr. P's symptoms?
Peripheral neuropathy, paresthesias of glove and stocking pattern
2.
Mention
the
differential
diagnosis
of
this
neurological syndrome and its most likely etiology?
Drug induced neuropathy by stavudine and ddl
Other causes- Other ARV drugs, INAH, alcohol, HIV induced neuropathy,
CAAV induced neuropathy, B12 deficiency, other associated conditions
eg. Diabetes AAellitus
ACTIVITY 1.9
NEUROPATHY (10 min)
Refer back to Mr. P's case in activity 1.8.
1. What treatment can you offer for Mr. P?
25
MODULE 1
FEEDBACK 1.9
1. What treatment can you offer for Mr. P?
Provide drug holiday - stop all ARV drugs together.
Reduce dose
Change regimen - use a non-ddl and d4T containing regimen
Loose footwear
Graduated walking
Soaking feet in ice
Drug treatment:
Paracetamol / Non-steroidal anti-inflammatory drugs
Tricyclic anti-depressants
Opioid analgesics
Carbamazepine
ACTIVITY 1.10
APPROACH TO FORGETFULNESS (10 min)
Mr.
S. r
a
28-year
old lorry cleaner,
was
diagnosed to
have AIDS 6 months ago when he presented with weight loss
and
chronic
diarrhea
due
to
isosporiasis.
He
had
symptomatic improvement after a course of co-trimoxazole
and loperamide treatment.
His wife had noticed that the
patient had become increasingly forgetful over the last
couple of months. She had also noticed slowness of gait,
26
MODULE 1
deterioration of his handwriting and that S.
very withdrawn.
had become
She had not noticed any fever, headache,
seizures
or
aphasia.
Physical
neurological
deficits
examination
like
revealed
hemiplegia
a
thinly
or
built
male, who was conscious and alert. His recent memory was
impaired
and
concentration.
movements.
he
poor
had
attention
span
and
He was unable to perform fine repetitive
There
were
no
focal
neurological
deficits,
papilledema or signs of meningeal irritation.
1. What
type
of neurological
syndrome
do
you
think
the
patient is suffering from?
2. What is the differential diagnosis of this syndrome in
order of probability?
1.
2.
<4,
3.
‘ £
4.
7A
3. What investigations would you order? Why?
c
(csp
/J.
1 ^1
27
MODULE 1
FEEDBACK 1.10
1. What type of neurological syndrome do you think the
patient is suffering from?
Dementia - the patient's symptoms are impaired memory, attention and
concentration and motor difficulty.
2. What is the differential diagnosis of this syndrome
in order of probability?
1. HIV associated dementia complex
Toxoplasmosis, PAAL and severe depression (pseudo-dementia) can present
as dementia like picture
3. What investigations would you order? Why?
CSF - to rule out chronic meningitis
CT scan brain or AARI - to rule out focal cerebral lesion
MODULE 1
28
Before
proceeding
to
Dementia
Complex"
(page
the
next
42)
in
activi ty
the
read:
reader.
After
"AIDS
you
complete this go on to your next activity.
ACTIVITY 1.11
AIDS DEMENTIA COMPLEX (ADC) (10 min)
The CT scan of brain (C+) study did not show any focal
lesions.
There was bilateral cortical atrophy. The CSF
showed 8 cell/mm3 CSF protein 70 mg/dl and CSF glucose
80 mg/dl.
What
treatment
dementia?
may
be
effective
in
reversing
his
29
MODULE 1
^FEEDBACK 1.11
What
treatment
may
be
effective
in
reversing
his
dementia?
Highly active anti-retroviral treatment is the only definitive treatment
for this condition. AZT and stavudine should be among the drugs that are
used as they cross the blood brain barrier more effectively.
30
NOTES
MODULE 1
31
NOTES
MODULE 1
34
MODULE 1
»
READINGS
N:
Table 1: Neurological Syndromes and Opportunistic Infections in AIDS
Syndrome
Clinical features
Etiology
Meningitis
Headache
Cryptococcosis
Fever
Tuberculosis
Nausea/ vomiting
Syphilis
Altered consciousness
Neck stiffness
Focal cerebral lesions
Headache
Toxoplasmosis
Focal neurological deficits Tuberculosis/tuberculoma
(hemiplegia, hemianopia)
Cysticercosis
Seizures
Progressive multifocal
leukoencephalopathy (PML)
Lymphoma
Encephalitis
Cognitive impairment
CMV
Psychiatric features
Altered consciousness
Dementia
Cognitive impairment
HIV
Psychomotor slowing
Behavioural disturbances
Myelitis
Paraparesis
CMV
Sensory changes
HIV
Sphincter disturbances .
35
MODULE 1
FIG. 1 - APPROACH TO MENINGITIS IN HIV INFECTION
Headache
± Fever
± neck stiffness
Does the patient have focal neurological deficits?
Yes
______________
See next algorithm
No
Lumbar puncture:
Opening pressure, WBC - Total & Differential
Glucose, Protein
Gram stain, acid fast stain,
India ink preparation, Cryptococcal antigen
Routine culture, fungal, and mycobacterial
culture (if available)
Serum and CSF VDRL
India Ink positive
Increased cells/protein
~--------------------------Increased cells/Proteins/
Cryptococcal Antigen positive,
Culture positive for Cryptococcus
VDRL positive
VDRL negative
Cryptococcal meningitis
Syphillitic meningitis
4-
Evidence of TB elsewhere
TB meningitis
36
MODULE 1
CRYPTOCOCCAL MENINGITIS
Cryptococcosis is a systemic or CNS fungal infection caused by the organism
Cryptococcus neoformans. The commonest manifestation is meningitis (cryptococcosis
is the most common cause of meningitis in AIDS). Other manifestations are skin
lesions (flesh coloured, umbilicated papules resembling molluscum contagiosum),
pulmonary manifestations and fungemia.
The organism is ubiquitous, but particularly plentiful in soils enriched with bird
droppings.
The incidence of cryptococcal meningitis in PLWHA is estimated to be 6 - 10% in the
US. It is much more frequent in Africa and India, probably because of the increased
environmental exposure to the pathogen. It occurs in HIV-positive patients with CD4
cell counts <100/ p.L.
Clinical manifestations and Diagnosis: (See further reading) Patients present with
headache, fever, nausea and vomiting. The onset of symptoms is subacute over 7 -
14 days. Confusion and impaired consciousness occur in later stages. Signs of
meningeal irritation (neck stiffness, Kernig's sign) are unusual (<40%). The diagnosis
is confirmed by CSF examination. Positive India ink staining or CSF cryptococcal
antigen will provide rapid diagnosis, which is confirmed by CSF culture. In
situations where CSF culture and cryptococcal antigen are not available, India Ink
test may be used as the confirmatory test.
Prognosis: It is associated with 100% mortality without specific anti-fungal
treatment. Poor prognostic features include a high opening pressure of CSF, low CSF
glucose levels, CSF cell count <20 leukocytes/mm3, altered mental status, positive
India ink preparation and cryptococci isolated from extra-neural sites.
Treatment:
a. Severe cases (high opening pressure of CSF, low CSF glucose levels, <20
leukocytes/mm3, altered mental status,); Admit for 2-week induction with
Amphotericin B intravenously, 0.7 mg/kg/day, (with or without flucytosine 100
mg/kg/day in 4 divided doses).
37
MODULE 1
b. Mild cases: Fluconazole 800 mg p.o. loading dose, followed by 400 mg p.o. once
daily x 8 weeks.
Maintenance therapy: Fluconazole by 200 mg once daily (indefinitely)
Management of elevated CSF pressure:
If initial opening pressure >250 mm CSF, repeat LP at 1-3 day intervals as needed for
pressure reduction; removing 10-20 ml of fluid may be required. Check closing
pressure. Occasionally, lumbar drains or ventricular-peritoneal shunt may be
indicated if raised intra-cranial tension is refractory to medical treatment (consult
Neurosurgery).
I \
\ ' \
n
38
MODULE 1
FIG. 2 - APPROACH TO FOCAL CEREBRAL SYNDROME
IN HIV INFECTION
Hemipariesis
Monopariesis
Cranial nerve deficit
Seizures
CAT Scan & M R I
Multiple ring enhancing lesion
Atypical lesions
No lesions
Brain biopsy
CSF examination
Toxoplasma antibody positive
Toxoplasma encephalitis
$
39
MODULE 1
TOWPLASMA ENCEPHALITIS
Toxoplasma gondii is a protozoan parasite which causes latent infection of
central nervous system worldwide in the normal population. In patients with
severe defects in the cellular immune response such as HIV infection, the
parasite can become reactivated. HIV patients are at risk of developing
toxoplasma encephalitis at CD count <100/pL. The infection of the CNS is
multi-focal causing pathology of enlarging nodules and areas of necrosis with
predeliction for the cortex and basal ganglia. The primary neurological
presentation of toxoplasma encephalitis (TE) is a focal cerebral syndrome.
Studies from other countries have shown that nearly half of AIDS patients
who are toxoplasma antibody positive will develop TE. In our own hospital
TE is the fifth most common discharge diagnosis for patients with
HIV
infection. TE can be effectively prevented by primary prophylaxis with
cotrimoxazole or sulphadiazine with pyrimethamine.
Clinical manifestations and Diagnosis:
Toxoplasma encephalitis presents subacutely (over weeks) with symptoms of
headache, fever, altered mental status(70%), hemipariesis or other focal signs
(60%) and seizures (30%). It occurs in advanced
immunodeficiency
(CD<100/pL).
The diagnosis is based on: (a) CT/MRI imaging showing multiple ring
enhancing lesions in the basal ganglia and cortex often with mass effect and
(b) IgG toxoplasma antibody titre positive. A negative CT/MRI scan rules out
the diagnosis of TE. The differential diagnosis of ring enhancing lesions
includes: lymphoma brain, tuberculoma, cryptocococcis, neurocysticercosis,
brain abscess and brain tumours. In patients with advanced HIV infection, TE
is the most frequent cause of ring enhancing lesions.
40
MODULE 1
Prognosis: 85% respond to specific therapy usually within 7 days. Failure to
respond within 7 days should make you consider an alternative diagnosis and
is an indication for brain biopsy.
Treatment:
Pyrimethamine 100-200 mg stat, then 50 — 100 mg daily
Folinic acid 10 mg OD+ Sulfadiazine 4-6 G/day x 6 weeks
AlternativesPyrimethamine + Folinic acid + Clindamycin or
Primethamine + Folinic acid + Azithromycin or Clarithromycin
Co-trimoxazole (TMP 5 mg/kg BD)
Clinical response usually occurs within 2 weeks
CT/MRI response also occurs within 2 weeks
Corticosteroids are indicated if there is mass effect
Suppressive treatment (secondary prophylaxis)
Pyrimethamine 25-75 mg daily +
Folinic acid 10 mg OD +
Sulfadiazine 0.5 G Q6H daily life long
Primary prophylaxis
Indication: IgG Toxoplasma antibody positive & CD 4 < 100
Bactrim DS I daily
Alternative: DDS + Pyrimethamine + Folinic acid
41
MODULE 1
FIGURE 3 - APPROACH TO NEUROPATHY IN HIV
Burning pain
Tingling and numbness
Decreased sensations
Dropped ankle jerks
Peripheral Neuropathy
No ♦
On
Drug holiday
Reduce dose
> Yes
Change regimen
ddI/d4T
Look for other causes
Drugs
Alcohol
Diabetes
B12 deficiency
Avoid tight footwear
Walk short distance
Soak feet in ice
NSAID/Opiods
Tricyclic anti-depressant
Carbamezapine
42
MODULE 1
AIDS DEMENTIA COMPLEX (ADC)
HIV virus enters the central nervous system early in the infection and infects
macrophages and microglial cells sparing the neurons. The mechanism by
which the virus produces damage to the neurons is not known but is thought
to be due to secretion of factors (cytokines) by stimulated macrophages which
cause neuronal death. As the disease progresses (CD4 count<200/pL)z HIV
produces a slowly progressive encephalitis manifested by (a) cognitive
decline; (b) motor difficulty and (c) behavioral changes. About one-third of
adults and half of children develop ADC in western countries.
The common symptoms are: (a) cognitive decline - decreased attention and
concentration, forgetfulness and slowing of thought; (b) motor difficultyslowed movements, ataxia and clumsiness and (c) behavioral changes-
apathy, agitation and blunting of personality.
In a patient presenting with these symptoms, chronic meningitis and
toxoplasma encephalitis need to be ruled out. The tests of choice are CT/MRI
imaging and CSF examination. In ADC there is mild increase in CSF WBC
count and elevated CSF protein levels. The CT scan and MRI show cerebral
atrophy and the absence of contrast enhancement and mass effect
The definitive treatment of ADC is HAART with drugs which penetrate the
blood brain barrier including zidovudine or stavudine.
43
MODULE 1
REFERENCES
1. Price R.W. (1999) Management of neurological complications of HIV-1 and
AIDS. In Sande M.A and Volberding P.A. (eds) The Medical Management of
AIDS. W.B. Saunders Company, Philadelphia.
2.
Saag M.S.
(1999) Cryptococcosis
and
other
fungal
infections
(Histoplasmosis, Coccidioidomycosis). In Sande M.A and Volberding P.A.
(eds) The Medical Management of AIDS. W.B. Saunders Company, Philadelphia.
3. Subauste C.S and Remington J.S. (1999) AIDS associated toxoplasmosis. In
Sande M.A and Volberding P.A. (eds) The Medical Management of AIDS. W.B.
Saunders Company, Philadelphia.
44
Photo 1A
II '^1«
ft
' '-1
sr;! w
Photo 1B
Photo 1C
MODULE 1
HIV Physician Training Course 2002,
Christian Medical College, Vellore
DISTANCE LEARNING COURSE
HIV
AND
WOMEN
Author: Jessie Lionel
Course Organiser : Anand Zachariah
Distance Learning Expert: Janet Grant, Open University, UK
This course is supported by the European Commission through grant number
IND/B76211/1B/1999/0379 provided to the HIV/STI Prevention and Care Research
Programme of the Population Council India.
MODULE 2
INSTRUCTION SHEET- HIV AND WOMEN (MODULE 2)
1. In addition to this module you will find:
Envelope addressed to Course Coordinator, HIV Physician Training
Program, CMCH, Vellore-632004 which has stamps required for registered
post.
2. After you complete the module tear (a) Tutor marked assignment (page
25); (b) the module evaluation form (at the end of the module) and enclose it
in this envelope. Send it by registered post to CMCH by: December 21, 2002.
1
MODULE 2
OVERVIEW
Women comprise 4 % of adults living with HIV/AIDS worldwide. Most women
are infected at a childbearing age through heterosexual transmission. In India the
prevalence of HIV among pregnant women varies from 0.13 - 1.75 cases/100
pregnant women. The risk of mother-to-child transmission (MTCT) from an HIV
infected mother varies from 25 to 35%. Several interventions including antenatal
screening for HIV infection, anti-retroviral therapy, caesarian section and
avoiding breastfeeding have been shown to reduce the risk of MTCT. Ninety
percent of pediatric HIV infection is due to MTCT and this can almost entirely be
prevented by these interventions.
HIV affected women are also prone to gynecological problems including
infertility, reproductive tract infections and cervical cancer. Special attention has
to be paid to the evaluation, treatment and prevention of these disorders. The
treatment of STD's in women will be covered in Module 8 HIV and STD's.
This module aims to improve your skills in planning out obstetric and
gynecological management of HIV affected women and to develop your clinical
services in relation to these.
OBJECTIVES
After completion of this module you should be able to outline:
1. The steps of organizing an antenatal screening program in your own clinic.
2. The approach to pre-test and post-test counselling in the antenatal setting.
3. How to choose appropriate measures to reduce mother to child transmission
(MTCT) for an individual patient with HIV infection.
4. The steps of initiating anti-retroviral therapy to reduce MTCT.
5. How to choose appropriate contraception for an HIV affected woman.
6. The approach to routine gynecological care of an HIV affected women.
2
MODULE 2
CONTENTS
Activity
Title
Time (min.)
Page
No.
Activity 2.1
HIV Screening in Pregnancy
10
3
Reading
HIV screening in pregnancy
5
27
Activity 2.2
Counselling
10
5
Reading
Informed consent
Patient information sheet
5
38-39
Activity 2.3
HIV Testing strategies
10
8
Reading
Strategies for HIV testing in India
20
40
41
HIV testing strategies
Activity 2.4
MTCT: risk factors
10
11
Reading
Mother to child transmission
15
29
30
Factors which increase MTCT
Activity 2.5
Prevention of MTCT
20
13
Reading
Efficacy of single drug ART
20
31
MTCT -mode of delivery
32
Single drug ART-dosing
33
Combination ART in pregnancy
34
Activity 2.6
Contraception
10
19
Reading
Contraception
15
35
Activity 2.7
Gynecological Care
10
21
Reading
Gynecological Care
10
36
TMA
60
25
Total estimated study time
245
3
Let
us
start
pregnancy"
wi th
a
(page 27) .
short
MODULE 2
reading
"HIV
screening
in
Once you have finished reading this,
you should be able to undertake your first activity.
ACTIVITY 2.1
HIV SCREENING IN PREGNANCY (10 MIN)
Write
down the
advantages
and disadvantages
screening in an antenatal clinic.
UNIVERSAL SCREENING
ADVANTAGES
DISADVANTAGES
1.
2.
3.
4.
3.
(Uy
-
4.
4
of universal
4
MODULE 2
^^FEEDBACK 2.1
UNIVERSAL SCREENING
ADVANTAGES
DISADVANTAGES
1. Identifies all women affected
1. Costly
2.Required for program to prevent
2. Requires system for informed
AATCT
consent and counselling
3. Prevents horizontal transmission
3. Requires system for instituting
to partner
measures to reduce AATCT
4. The person can access medical
4. Increased stigma and possibility
care
of refusal of care
The
next
counselling
clinic
of
aims
activity
services
your
you
that
hospital
help
to
or
you
require
think
in
institution.
about
the
do
To
the
antenatal
the
next
exercise you will need to read the following readings.
1.
Guidelines
and
policies
Infection Control Committee,
in
HIV
care,
CMCH
Christian Medical
Hospital
College and
Hospital 2001.
Page 38-39
Informed consent
Page 28
Patient information sheet
Once you have finished reading
next activity.
this you
can
undertake
the
5
MODULE 2
ACTIVITY 2.2
COUNSELLING (10 MIN)
Design a patient information sheet on HIV testing for your
antenatal clinic based on the information sheet given in the
reading.
This may be used as a pamphlet; or it can provide
key messages for a health education program.
HIV
INFORMATION
SHEET
FOR
THE
ANTENATAL
CLINIC
AT
Introduction
'^i’Aa^/
--- j
<^^.0!
yo^ /yA
A>-/
cu-e
What is an HIV test?
V fc-Yf o£ oa<.^
c' Z/
Why is it being done?
/^/LAa/Q .
v 'x
rf r
As
If the test is positive r what treatment can be offered?17
^^P-ZA.
ci'c.Z.,
-■
t'
<-x4
.<Gv.y
^TvA-C*
b <2 -/ /■
A^XAA<zA>A^/x.,^r\n
Reassurance that care will not be refused
~
TTm. c/-^5yAv'’t<v-vM 5
'
Options
more
for
counsellor/ doctor
„
‘
f—
fn
—^7
Ci/L^'AA
’
■A
0
detailed
discussion
with
nurse/
Lcv^i/vwJj.
6
______________________ □
MODULE 2
AV FEEDBACK 2.2______________________
Design a patient information sheet on HIV testing for your
antenatal clinic based on the information sheet given in the
reading.
This may be used as a pamphlet;
or it can provide
key messages for a health education program.
Introduction
In the evaluation for your pregnancy we require to screen you for the
following infections'. Hepatitis B, HIV (the infection that causes AIDS)
and sexually transmitted diseases. These infections can be transmitted to
your husband or partner as well as to your child.
What are these tests:
These are screening blood tests that look for evidence of these
infections. If they are positive, then you may require other tests to
confirm the presence of any of these infections.
Why is it being done
If any of these infections are there, we can institute treatments to cure
them or precautions to prevent spread to your child and spouse.
Reassurance that care will not be refused
If any of these tests are positive, then your results will be kept
confidential and will be explained to you or those whom you may want to
be informed. We will ensure that all necessary treatments are provided
to you.
Options for more detailed discussion with nurse/ counsellor/ doctor
If you would like to have more detailed information or discussion please
contact the nurse or doctor.
7
The
next
activity aims
MODULE 2
to help you
identify
the
testing
protocol that you would like to use in your antenatal clinic
of your hospital or institution.
To do
the next exercise,
you will need to read the below readings and also visit the
laboratory which does your HIV test,
Once you have finished
reading this you can undertake the next activity.
1. NACO guideline for HIV testing page 40
Strategies for HIV testing in India page 41
MODULE 2
8
ACTIVITY 2.3
HIV TESTING STRATEGIES (10 MIN)
1.
Which
of
the
testing
strategies
I, II
or
III
of
the
WHO/UNAIDS recommendations are you using in your laboratory?
2. Which type of tests do you use for Al and A2 or Al, A2
and A3 in your laboratory (eg. Rapid test eg. Tridot, ELISA
eg. Genedia, Western blot)?
/
A
A
i) j-
4S -
3. If a result is indeterminate what would you do?
4. What is the cost of testing strategy II and III?
9
MODULE 2
FEEDBACK 2.3
1.
Which of the testing
strategies
I, II or
III will
you
use?
You could use strategy II or Ill depending on the availability of tests
and costs involved.
If you had access only to rapid tests then you would use strategy II.
2. Which tests will you use for Al, A2 and A3?
Strategy II
Al- Rapid test (eg. Tridot, Capillus, HIV spot) or ELISA (eg. Genedia,
Detect HIV, Microlisa)
A2 - Rapid test by another method or ELISA by another method
A3- ELISA by a 3rd method or rapid test by a 3rd method or western blot
test
The sequence of tests that could be done are:
One rapid test followed by 2 ELISAs (Strategy III)
Two rapid tests followed by 1 ELISA (Strategy III)
Two ELISAs followed by one rapid test (strategy III)
Three ELISAs (Strategy III)
Two rapid tests (Strategy II)
One rapid test and 1 ELISA (Strategy II)
3. What would you do if a result is indeterminate at the end
of the algorithm?
Western blot test should be done if you have access to it. Otherwise you
could wait for a period of 2-3 months and repeat the HIV test.
10
MODULE 2
What is the cost of testing strategy II and III?
Strategy II
Two rapid tests - Rs.200
One rapid test + 1 ELISA - Rs.150
Strategy III
Two rapid tests + 1 ELISA - Rs.250
Two ELISAs + 1 Western Blot - Rs. 1,100
Two ELISAs + 1 rapid test - Rs.200
The next activity will help you explain the risks of mother
to
transmission
child
pregnancy.
To do
child
"Mother
to
"Factors
which
increase
reader.
Once
you
have
affected
exercise you
the next
tables:
HIV
a
to
transmission"
risk
of MTCT"
fini shed
undertake the next activity.
will
mother
need to study
(page
(page
reading
during
30)
this
29)
and
in
the
you
can
11
MODULE 2
ACTIVITY 2.4
MTCT: RISK FACTORS (10 MIN)
Mrs .
Saraswathy
antenatal
a
23
for
clinic
year
her
lady
old
first
is
pregnancy
attending
your
14
of
at
weeks
gestation. She had a routine antenatal HIV test and her HIV
ELISA was found to be positive. You have initiated her post
test counselling and are reviewing her for the second time
after the test report. Mrs . Saraswathy is keen to know what
the actual risk of her baby acquiring HIV infection is and
what she can do to prevent this from happening.
1. How will you explain to her the risks of mother to child
transmission?
Ante-natal
b"- i o Tq
During labour
I 0 —
After delivery- with breast feeding
^^"4 ■
Overall
2. How will you explain to her what she can do to reduce the
risk of mother to child transmission?
f
1.
2.
3.
4.
4-^,^ ■
La
5.
I
12
MODULE 2
%FEEDBACK 2.4
i. How will you explain to her the risks
of mother to child
transmission
Ante-natal
: 5 -10%
During labour
: 10 - 20%
After delivery, with breast feeding : 5 -10%
Overall
: 30 - 45%
2. How will you explain to her what she can do to reduce the
risk of mother to child transmission?
1. Maintain good diet
2. Take vitamins and minerals
3. Continue regular ante-natal care under you
4. Avoid breast-feeding if she can afford to give formula feeding or cows
milk.
5. Use barrier method of contraception.
6. Consider the option of anti-retroviral treatment to reduce MTCT.
The next
measure
next
activity will
to
reduce mother
exercise you
single
help you
drug ART
will
choose
to
the appropriate
transmission.
to child
need to study tables:
to reduce MTCT"
(page
child transmission-mode of delivery"
31)
the
"Efficacy of
and
(page 32)
To do
"Mother
and
to
"Dosing
schedules for single drug ART" (page 33) in the reader. Once
you have finished reading
activity.
this you
can
undertake
the next
MODULE 2
13
ACTIVITY 2.5
PREVENTION OF MTCT (20 MIN)
Choose the appropriate treatment modalities
1.
given in the table below.
prophylaxis and (d)
No.
to
reduce the MTCT
Mode of delivery
(b)
in relation to:(a)ART to mother;
for the clinical settings
(c)
Infant feeding.
ART
Case scenario
22-year old primi
to mother
InfantProphylaxis
Delivery
Infant Feeding
4£_T
gravida with HIV
•
z-7
»
infection at 12
1
weeks of gestation
HIV
30-year
lady.
infected,
presenting at
’i
2
32 weeks of
gestation
Unbooked lady in
3
Infant
t^r
early labour, rapid
. AJo
HIV test positive
C9
’ I
>)
14
MODULE 2
Unbooked lady
4
delivered
before
HIV
result became available
2.
Calculate the cost of the treatment for the above cases:
SI.
No.
1
2
3
4
ART
Delivery
Infant
Prophylaxis
Feeding
15
MODULE 2
3.
What modifications to the delivery procedure would you
undertake
to
reduce
the
risk
of
mother
to
child
transmission?
1.
2.
3.
4.
5.
4.
Write down:
(a)Advantages of breast feeding
ii.
ill.
/'’Aa <VVUa‘V'
(b)
Factor
which
determines
advice
to
feed:
© Qualifications to the advice to breast feed.
i.
ii.
iii.
breast
16
MODULE 2
- ^FEEDBACK 2.5
1.
Choose
the appropriate treatment modalities
to reduce
the MTCT for the following settings:
No.
Case
Treatment ART
Mode
Scenario
1
12
Infant Prophylaxis
Delivery
Primi
AZT 300 mg bd from 14
at weeks
gravida
of
weeks
or
any
time
Elective
Syrup AZT 2 mg/kg Q6H x 6 wk
C.S. at 38
hrs. of birth
after- wards
weeks
30 yrs lady
AZT 300 mg BD from
Elective
Syrup AZT 2mg/kg Q6H x 6 wk:
at 32 weeks
34 weeks for 4 weeks
C.S. at
hrs. of birth
SA.
2
SA.
38 weeks
Unbooked
3
lady,
early
labour
Single
dose
oral
Vaginal
Syrup AZT 2 mg/kg Q6H x 6 wee
Nevirapine 200 mg stat
delivery
8
with
all hrs. of birth
precautions
to decrease
MTCT
4
Unbooked
Syrup AZT 2 mg/kg Q6H x 6 wk
lady
hrs. of birth or Single dose 2 mg /
delivered
Syrup Nevirapine
before
HIV result
17
2.
MODULE 2
Calculate the cost of the treatment for the above cases:
SI.
ART
delivery
Infant Pro Feeding
No.
1
phylaxis
a) From 14 weeks - Rs.7,660 Rs.8-10,000
Rs.403
b) From 20 weeks - Rs.5,745
Rs.1,500
Approx.
c) From 28 weeks - Rs.3,192
2
From 34 weeks - Rs.1,277
Rs.8-10,000
Rs.403
Rs.1,500
3
Nevirapine 200 mg - Rs.19
Rs.2,500
Rs.403
Rs.1,500
Rs.2,500
Rs.403
Rs.1,500
4
3.
What modifications
undertake
to
reduce
to the delivery procedure would you
the
risk
of
mother
to
child
transmission?
1. Elective L5CS if patient can afford it and your set up is equipped.
2. Avoid artificial rupture of membranes, perineal tear, episiotomy, fetal
scalp monitoring, suction cup, forceps application.
3. Avoid umbilical blood sampling
4. Bathe baby immediately after delivery.
5. Avoid emergency Caeserian section.
4. Write down:
18
MODULE 2
(a) Advantages of breast feeding
i. Good nutrition/well balanced easily digestible
ii. Breast milk protection against gastroenteritis and respiratory
infections.
iii. Preservation of gastrointestinal barrier against infection by HIV
(b) Factor which determines advice to breast feed:
Low socio-economic status which may prevent the mother from
being able to give sterile and clean formula feeds or cow's milk.
(c) Qualifications to the advice to breast feed.
i. Exclusive breast feeding (no cows milk or formula feeds) for 4
months.
ii. Treat infections of breast, check for cracking of nipples and oral
candidiasis in the mouth of the child.
iii. Weaning at 4 months with rice or ragi kangi with palladai or spoon.
19
MODULE 2
The next activity will help you to choose
the appropriate
method of contraception for an HIV infected woman.
next
exercise
will
you
need
^Contraception in HIV infection"
to
the
study
(page 35)
in
Once you have finished reading this you can
To do the
table:
the reader.
undertake the
next activity.
ACTIVITY 2.6
CONTRACEPTION (10 MIN)
A 23 year old lady with HIV infection has one 2 year old
child. Her husband is also infected. On discussion with her
regarding contraception she expresses the desire to adopt a
temporary method.
Which
contraceptive
methods
your reasons.
Method of contraception
Reason
would
you
choose
and explain
20
MODULE 2
^WfEEDBACK 2.6
Method of contraception:
Barrier method (condoms) with oral contraceptive pills or IUCD
Reason
Of the temporary methods the most safe are barrier methods but their
efficacy is not high. In addition barrier methods reduce risk of STD's.
Therefore a combination of hormonal contraception and barriers method
may be used. Since it is difficult to sustain motivation to take OCR's
everyday,
IUCD
with
a short
thread
may
be
supplementation with iron to correct anaemia is advised.
inserted.
Regular
21
The
next
will
activity
MODULE 2
you
help
understand
to
the
appropriate gynecological care for a HIV infected woman,
do
the
next
exercise
you
will
HIV
infection"
Gynecological
Care
in
reader.
you
have
Once
need
finished
to
read:
(pages
reading
To
"Routine
36)
in
the
this
you
can
to
have
HIV
the
OPD
wi th
undertake the next activity.
ACTIVITY 27
GYNECOLOGICAL CARE (10 MIN)
30
year
infection
old
Mrs .
3
years
Revathy
was
ago.
presented
She
diagnosed
to
history of vaginal discharge.
On
examination:
there is
curdy white vaginal
discharge
and on the vulva there is evidence of external warts.
1. What tests will you do for her?
VDRL
test
mount
for
is
negative.
trichomonas
The
are
gnonococcal
negative.
The
smear
and
wet
KOH
test
is
positive. The pap smear shows evidence of severe atypia.
2. What treatment will you administer?
22
MODULE 2
5^'FEEDBACK 2.7
1. What tests will you do for her?
Blood VDRL, urine microscopy, vaginal smear for wet mount, gnonococcal
smear, potassium hydroxide (KOH) preparation and pap smear.
2 . What treatment will you administer?
1. T. Clotrimazole 100 mg vaginal pessaries I OD for 10 days.
2. Imodium solution or cryotherapy for warts.
3. Refer for colposcopy and biopsy for the severe atypia to rule out
cervical intraepithelial neoplasia.
T1
MODULE 2
READINGS
HIV SCREENING IN PREGNANCY
Ninety percent of pediatric HIV infection is due to perinatal and MTCT.
Pediatric HIV infection can be prevented effectively through strategies to
reduce MTCT and perinatal transmission.
Selective or universal screening at antenatal clinics is advised to identify
HIV affected women. Selective screening in women who are known to be at
risk is advised in low prevalence areas but may miss women who are not
aware that they are at risk. Universal screening is advocated in high
prevalence areas but is more costly and associated with practical and ethical
problems. In our hospital universal screening is performed. In your center
you will have to decide your policy based on knowledge of local prevalence,
cost and practicality.
28
MODULE 2
HIV PATIENT INFORMATION SHEET IN THE ANTE-NATAL CLINIC
Counselling and voluntary testing is practiced in the Obstetrics and Gynecology
department at Christian Medical College and Hospital.
In view of the large
number of patients, individual pretest counselling for each woman receiving
antenatal care is not practical. Therefore printed information sheets (in different
languages) are used to provide information about the HIV test to women
attending the antenatal clinic.
Women who request more information are
referred to a counsellor. Any woman who tests positive on an HIV test is referred
to a senior obstetrician for disclosure of results, counselling and further
management. No woman or her family is discriminated against on the basis of
her HIV status.
In the case of a women testing positive, screening of the
husband/partner is recommended before the woman is informed about the test
result. This is done to avoid refusal of screening for HIV by the husband/partner
and the possible implications this may have on the woman.
PATIENT INFORMATION SHEET (Guidelines and Policies in HIV CARE)
Among the investigations required for your care, we may need to test you for the
presence of HIV and Hepatitis B infection. HIV infection spreads through sexual
contact, sharing needles and contaminated blood or blood products. An HIV
positive individual can transmit the infection to the husband/wife/partner. A
pregnant mother who has the infection can transmit it to her child. Therefore it
will help you to know your HIV status and will help us plan your treatment.
We look for HIV infection in your body by testing a sample of your blood. If this
test suggests the presence of the virus in your body, you may have to have
another test to confirm this. If the first test is positive, then it is advisable that
your husband / wife / partner is also tested. Once the test result is confirmed,
we will make the result known to you.
*
Please keep in mind that this test is done for your own and your family's
wellbeing. If this test reveals the presence of disease, then you will be advised
regarding appropriate treatment. Your care will not be compromised if you test
positive. If you have any concerns regarding this test, do not hesitate to discuss
them with the doctor treating you.
29
MODULE 2
MOTHER TO CHILD TRANSMISSION
Estimated mother to child transmission (MTCT) rates (%) in breast feeding
and
non-breast feeding populations who have not received
any
intervention to reduce transmission.
TIME
NON-BREAST
BREAST FEEDING TO BREAST
POINTS
FEEDING
6 MONTHS
TO 18-24 MONTHS
MTCT rate (%)
MTCT rate (%)
MTCT rate (%)
Intrauterine
5-10
5-10
5-10
Intrapartum
10-20
10-20
10-20
5-10
5-10
1-5
5-10
25-35
30-45
Postpartum
FEEDING
(< 2 Months)
Post-partum
(> 2 months)
Overall
15-30
The overall MTCT rate provides the actual rate of transmission according
to patient group: non-breast feeding, breastfeeding to 6 months and
breast-feeding to 18-24 months. The rate according to different time points
in pregnancy: intra-uterine, intrapartum, post-partum (< 2 months and >
2months) are estimated rates.
Source: Modified from De Cook et al 2000
30
MODULE 2
FACTORS WHICH INCREASE RISK OF MTCT
HIV disease
Maternal
Obstetric
factors
factors
Increased
Viral load
Malnutrition
•
Vitamin
•
Advanced
•
Drug
resistance
Cigarette
•
rupture
membranes
STD
Invasive
•
No
feeding
of
regular fetal
access to ANC
•
Breast
Premature
smoking
disease
•
Pre-term
A labour
Low CD4 deficiency
count
Newborn
monitoring
Uterine
Unprotected
sexual
manipulation
intercourse
•
Abruptio
placenta
•
Episiotomy
•
Forceps
• Vacuum
extraction
•
Emergency
caesarian
section
IUGR
Premature
baby
31
MODULE 2
STUDIES OF SINGLE DRUG ART TO REDUCE MTCT
Drug regimen
076 regime
(See
Article
MTCT (%)
AZT started 14-34 weeks 83%
1
in + IV intrapartum + oral
Readings)
neonatal for 6 weeks
(non-breastfed)
Thai short
(See
Article
AZT started at 36 weeks 8.6%
2
in until
Readings)
delivery
(non
breast fed) +
Neonatal for 6 weeks
(non-breast fed)
Nevirapine
(See
Article
Single oral dose
3
readings)
in
15.7%
Mother 200 mg in labour
Neonate:
mg/kg
2
within 72 hours of birth
(breast fed)
NY AIDS Institute
Mother: no ART
9.3%
Neonate: AZT within 48
hours
for
standard
duration
(Non-breast fed)
See references for details of study methodology, control groups and efficacy of
reducing MTCT.
32
MODULE 2
MOTHER TO CHILD TRANSMISSION: - MODE OF DELIVERY
French cohort
Swiss cohort
Read et al
Elective
Vaginal
Emergency
LSCS
delivery
LSCS
With AZT
0.8%
With AZT
0.1%
Without AZT
8.0%
With AZT
2.0%
Without AZT
8.2%
6.6%
20.0%
11.4%
33
Drug
MODULE 2
DOSING SCHEDULES FOR SINGLE DRUG ART
Ante-natal
Intra-partum
Neonate
(immediately after
birth)
Option 1
AZT 300 mg bd 300
from 14 weeks
Option 2
during labour
AZT 300 mg bd 300
from 36 weeks
mg
mg
during labour
Option 3
q3h 2 mg/kg qid for 6
weeks
q3h 2 mg/kg qid for 6
weeks
2 mg/kg qid for 6
weeks
Option 4
T.
Nevirapine Syr.
200mg
labour
stat
Nevirapine
in 2mg/kg
within
72hr of birth /
oral AZT 2mg/kg
qid for the infant
for 6 weeks
Cost
Tab. AZT 300 mg - Rs.22.80
Tab. Nevirapine (Cipla) 200 mg - Rs.18.86
Syr. AZT (Cipla) 15 mg/5 ml (100 ml) - Rs.100.70
34
MODULE 2
HAART THERAPY IN PREGNANT WOMEN
1. The principles of HAART are the same in pregnancy as in the normal HIV
infected patient.
2. The indications of HAART are: (a) clinical deterioration (opportunistic
infections, constitutional symptoms); (b) immunological deterioration
(CD4 < 500 or < 350 cells/pl); or (c) virological deterioration (>10,000
copies/ml).
3. HAART regimens should consist of 2 nucleoside reverse transcriptase
inhibitor (NRTIs) with one non-nucleoside reverse transcriptase inhibitor
(NNRTI) or one protease inhibitor (PI).
4. Efavirenz is contraindicated in pregnancy due to its teratogenicity.
5. Nevaripine is better avoided due to increase risk of development of drug
resistance.
6. In patients who are on HAART before pregnancy, discontinuation of all
drugs together until 14 weeks is advised.
The safety of anti-retroviral drugs in pregnancy is not fully established. Therefore
detailed discussion with the patient is required before starting on HAART.
35
MODULE 2
CONTRACEPTION IN HIV INFECTION
HORMONAL
ADVANTAGES
DISADVANTAGES EFFICACY
•
Easy to use
•
Drug interactions •
Reduces
•
Increased genital
anemia
HIV shedding
•
•
Regular
cycles
High
Cervical ectopy
Need
to
use
barrier contraception
Needs
motiva
tion to take regularly
•
Failure due to
low compliance
IUCD
•
Easy to put in
Increased:
One
HIV shedding
time
motivation
Anemia
• Small thread
STD/PID
reduces
Need
ascending
to
•
High
use
barrier contraception
infections
CONDOM
Reduces risk •
Best used with
Moderate
of HIV and STD another method
transmission
TUBAL
LIGATION
Permanent
Need
to
use •
barrier contraception
High
36
MODULE 2
ROUTINE GYNECOLOGICAL CARE OF HIV INFECTED WOMEN
1. Perform a pelvic examination and PAP smear every 6 months with careful
vulval, vaginal and anal inspection.
2. Refer for colposcopic evaluation women with any atypia, atypical
squamous cells of undetermined significance (ASCUS), atypical glandular
cells of undetermined significance (AGCUS), low grade and high grade
squamous intraepithelial lesion (SIL)/ cervical intra-epithelial neoplasia
(CIN) or persistent inflammation (that is unresolved after treatment for
gonococcus or chlamydia ) on any Pap smear.
3. Assess and treat vaginal discharge, genital warts, STDs (the treatment of
STD's will be covered in more detail in Module 8 ,"HIV and STD's).
4. Counsel on STDs, cervical cancer, human papilloma virus (HPV),
contraception, pregnancy and safer sex.
Among the gynecological conditions four are more frequent, more severe and
less responsive to treatment
Treatment
Genital warts
5 % Imodium solution / Cryotherapy - liquid nitrogen
Vaginal
Topical clotrimazole/ miconazole /Nystatin for 10 days
candidiasis
Or T. Fluconazole 150 mg weekly/monthly
for
recurrence of infection (6 doses)
Pelvic
Mild infections:
inflammatory
Doxycycline 100 mg bd
disease (PID)
Metronidazole 400 mg bd for 5 days with T. Ofloxacin
for 1
week or
Tab.
400 mg bd for 7 days
Acute and severe PID:
Admission and parenteral therapy with (Crystalline
Penicillin /Gentamycin/Metronidazole)
Cervical
intra- Low grade - Electrosurgical excision/ Conisation
epithelial
Recurrent / High grade - Hysterectomy
neoplasia (CIN)
37
MODULE 2
REFERENCES
1. Newman M.G. and Wofsy C.B. (1999) Women and HIV disease. In Sande M.A
and Volberding P.A. (eds) The Medical Management of AIDS. W.B. Saunders
Company, Philadelphia.
FURTHER READING
1. Jean Anderson, (ed) (2000) A guide to the clinical care of women with HIV
infection. Health Resources and Services Administration, Maryland.
2. Pitkin R.M. and Scott J.R. (eds) (2001) HIV and pregnancy. In Clinical
Obstetrics and Gynecology 44:1-422.
3. CDC (2001) Revised recommendations for HIV screening of pregnant women.
Preinatal counselling and guidelines consultation. MMWR 50 (RR19): 59-86.
4. Public Health Service Task Force (2002) Recommendations for use of anti
retroviral drugs in pregnant HIV-l infected women for maternal health and
interventions to reduce perinatal HIV transmission in the United States.
http://hivatis.org
5. De Cock K.M., Fowler M.G., Mercier E et al. (2000) Prevention of mother to
child HIV transmission in resource-poor countries. Translating research into
policy and practice. JAMA 283:1175-1182.
Translating research into policy and practice. JAMA
2000, 283:9 1175-1182.
38
Informed consent:
Obtaining consent is the basic minimum requixemSnt for HIV testing.
Exceptions to this rule are outlined in Chapter 4. In minors, testing should
1
proceed only with the informed consent of a responsible parent or guardian.
Informed consent cannot be implied or presumed. Obtaining informed
consent involves educating, disclosing advantages and disadvantages of
testing for HIV, listening, answering questions and seeking permission to
proceed through each step of counselling and testing.
The basic steps involved in obtained informed consent are listed
below:
1. Ensure the competence of the individual to understand relevant
information and appreciate consequences.
2. Explain the reasons for HIV testing in that particular instance.
E.g.: For prevention of mother to child transmission, clinical
indications of HIV related disease, hospital policy for selected
surgical procedures.
3. Assess the individual’s understanding of the routes of HIV
transmission. If needed, educate the patient in this regard.
Enquire about the individual’s assessment of their risk of being
positive for HIV infection and reasons for believing so.
4. Explain the components of HIV testing. E.g.: that a blood test
would be done and the details of obtaining the result.
5. Explain that a positive result (or refusal for testing) will not result
in refusal of care. Explain that the result would be kept
confidential.
6. Ensure that the individual understands the above information.
7. Assess whether the individual has any concerns or questions
regarding the above. If the individual does not express any
concerns and consent to the test, proceed with the test.
In busy clinics like ours, information about HIV/AIDS and the test
can be provided by the use of pamphlets, brochures, information sheets
or audio-visual aids. This should be supplemented by one to one
communication between the patient and care provider in all instances to
ensure opportunities for clarifications and expression of concerns.
(Information sheet is given as in Appendix)
The decision of whether to obtain informed consent for HIV testing
in writing is left to the individual department /unit. It is good clinical practice
to document that consent was obtained for testing after providing relevant
information, irrespective of whether the patient signs or not. Observing
the spirit of informed consent is more important than merely obtaining the
patient’s signature.
Informed consent is differ :nt from pre-test counselling. The
former is essential in all instances when HIV testing is done in the clinical
context. Results of sero-surveillance in the institution and surveys of
opinions of individuals tested suggest that the majority of patients are not
at risk for HIV and readily consent to testing, provided the reasons of
testing are explained and confidentiality and the non-discriminatory policies
of the institution are emphasised. Not all patients require or want detailed
pre-test counselling, provided they understand the details and implications
of the test and correctly assess their risk of being positive. It is
recommended that all patients detected to be HIV positive are offered
post-test counselling and a personalised management plan, either by a
senior clinician or by staff at the infectious diseases clinic.
--------------------------------------------------- - --------:-------- L------
6.12.5 Strategies of HIV testing in India
|
Because of the enormous risk involved in transmission of HIV through blood, safety
of blood and blood products is of paramount importance. Since the PPV is low in populations,
with low HIV prevalence, WHO/GOI have evolved strategies to detect HIV infection in different
population
groups
to fulfil different' objectives
(Annexure
6.1).
. . '"
.
. and...................
': '
■;
: : The
’ various strategies,. sG
j
■ i
designated, involve the use of categories of tests in various permutations and combination^
•vil
1.
2.
ELISA/Simple/Rapid tests (E/R/S) used in strategy I, II & III
-J
•H’
Supplemental test like Western Blot and Line Immunoassay are used in problem
cases e.g. in cases of indeterminate/discordant result of E/R/S.
Strategy I: Serum is subjected once to E/R/S for HIV. If negative, the serum is to bq
considered free of HIV and if positive, the sample is taken as HIV infected for all practical
purposes. This strategy is used for ensuring donation safety (blood/blood products;organ;
tissues, sperms etc.). The unit of blood testing reactive (positive) is discarded. Donor is riot;
informed.
;
Strategy II: A serum sample is considered negative for HIV if the first ELISA report*
is so, but if reactive, it is subjected to a second ELISA which utilizes a system different from,
the first one. It is reported reactive only if the second ELISA confirms the report of the first;
This strategy is used for surveillance and for diagnosis only if some AIDS indicator disease’
is present.
Strategy III: It is similar to strategy II, with the added confirmation of a third reactive
ELISA test being required for a sample to be reported HIV positive. The test to be utilized
for the first ELISA is one with the highest sensitivity and for the second and third ELISAgj
tests with the highest specificity are to be used.
‘.2;
Strategy II & III are to be used for diagnosis of HIV infection. ELISA 2 and ELISASj
ought to be tests with the highest PPV possible' to eliminate any chances of false positive!
results. Strategy III is used to diagnose HIV infection in asymptomatic individuals indulging’
in high risk behaviour.
3
J
M
J
Zfl
Chapter 6 - Annexure 1
Schematic representation of the UNAIDS and WHO HIV testing strategies
Strategy I
Strategy II
Strategy 111
-Transfusion/transplant safety
•Surveillance
•JAl
Surveillance
Diagnosis
Diagnosis ..
Al
I
A1 +
7- Consider2
J. positive
A1Report3
negative
A1Report
negative
A1 +
A2
A2
A1+A2^
A1+A2+
Report
positive4
A1Report
negative
A1+A2+
A1+A2/ s
I
Repeat Al and A2
Repeat Al and A2
<
Report
positive4
r
n
I
A1+A2+
A1+A2Consider
indeterminate5
A1-A2Report
negative
I
A1+A2+
A1+A2-
A1-A2Report
negative
A3
A1+A2+A3+
A1+A2+A3- or
Report
positive4
Consider
indeterminate5
A1+A2-A3-
r n
High risk
Low risk
Consider
indeterminate5
Consider
negative®
'Assay Al, A2, A3 represent 3 different Assays
’Such a result is not adequate for diagnostic purposes: use strategies II or III. Whatever the final diagnosis, donations which were
initially reactive should not be used for transfusions or transplants.
• ’Report: Result may be reported.
*For newly diagnosed individuals, a positve result should be confirmed on a second sample.
’Testing should be repeated on a second sample taken after 14 days.
’Result is considered negative in the absence of any risk of HIV infection.
65 '
4
O?>o ]
HIV Physician Training Course 2002,
Christian Medical College, Vellore
DISTANCE LEARNING COURSE
HIV
AND
CHILDREN
Authors : Verghese VP and Cherian Thomas
Course Organiser : Anand Zachariah
Distance Learning Expert: Janet Grant, Open University, UK
This course is supported by the European Commission through grant number
IND/B76211/1B/1999/0379 provided to the HIV/STI Prevention and Care Research
Programme of the Population Council India.
MODULE 3
INSTRUCTION SHEET- HIV AND CHILDREN (MODULE 3)
1. In addition to this module you will find:
a. X-rays 3A-C (in 3 covers required for Activity 3.9).
b. Envelope addressed to Course Coordinator, HIV Physician
Training Program, CMCH, Vellore-632004 which has stamps
required for registered post.
2. After you complete the module tear (a) Tutor marked assignment (page
35); (b) the module evaluation form (at the end of the module) and enclose it
in this envelope. Send it by registered post to CMCH by: December 28, 2002.
4
1
MODULE 3
OVERVIEW
This module we hope will enable you improve your skills in the clinical
management of children of mothers with HIV infection and children having
HIV infection. The module aims to enable you to develop your clinical
services in relation to these two topics.
In India about 1-2% of pregnant mothers are infected by HIV infection and the
rate of perinatal transmission is between 25-35%. Ninety per cent of pediatric
infection occurs through mother-to-child transmission. Paediatric infection
may almost entirely be prevented by anti-retroviral therapy during
pregnancy and in the perinatal period, elective caesarian section, and
avoidance of breastfeeding by the mother.
The newborn infant of an HIV-positive mother should receive 6 weeks of
zidovudine, cotrimoxazole from 6 to 8 weeks of life (PCP prophylaxis) and
routine immunizations. Serological testing can confirm the diagnosis of HIV
infection only after 18 months of age.
The signs and symptoms in HIV infection in children are non-specific and the
commonest presentations are failure to thrive, tuberculosis, persistent
orophryngeal candidiasis and recurrent bacterial infections. Since the
disease progresses faster in children, the affected child may often be the index
case in the family. Maintenance of nutritional status, immunization,
treatment of recurrent bacterial infections and PCP prophylaxis are the keys
to prolonging life in children. Most of the opportunistic infections can be
diagnosed using clinical criteria and treated with commonly available drugs.
Antiretroviral therapy is recommended for all children with advanced HIV
infection and for those with significant immunosuppression especially
those who have access and can pay for the drugs.
2
MODULE 3
OBJECTIVES
After completion of this module you should be able to manage:
1. an infant born of an HIV positive mother
(a) recommendations for breast feeding
(b) opportunistic infection prophylaxis
(c) testing protocol.
2. a child with suspected HIV infection:
Specifically you will learn about
(a) when to suspect HIV infection
(b) how to diagnose HIV infection
(c) how to counsel parents
(d) advice regarding immunization, OI prophylaxis and nutrition
(e) diagnosis and treatment of common opportunistic infections
(f) when to consider initiation of anti-viral therapy
CONTENTS
No.
Title
Time (Min.)
Page
10
4
10
37
15
6
Statement on breast feeding
20
50
Activity 3.3
OI Prophylaxis and immunisation
20
10
Reading
PCP Prophylaxis in Newborn
5
37
of HIV positive mother
5
38
HIV testing in newborn
15
13
15
39
Activity 3.1
Post-exposure prophylaxis for newborn
Reading
Post-exposure prophylaxis for babies
born of HIV positive mothers
Activity 3.2
Breast feeding of child of
HIV positive mother
Reading
WHO, UNICEF, UNAIDS
Immunisation for newborn baby
Activity 3.4
Reading
Lab confirmation of HIV infection
3
Activity 3.5 Initial evaluation
MODULE 3
15
15
5
40
clinical categories
10
40
Clinical & Lab Findings
10
41
Reading
Natural History of HIV infection
in children
1994 Revised HIV Pediatric
Classification System:
Activity 3.6
Counselling of family
10
19
Reading
Counselling of HIV positive child
20
43
Activity 3.7
Lab evaluation of HIV positive child
Opportunistic infection prophylaxis
10
21
Lab evaluation of child
20
39
Opportunistic infection
10
47
Activity 3.8 Nutrition for HIV positive child
10
23
Reading
5
44
Activity 3.9 Respiratory problems - recognition
10
25
Reading Respiratory problems
20
45
Activity 3.10 Respiratory problems - treatment
15
29
Activity 3.11 Indications for anti-viral therapy
15
31
10
46-48
60
35
Reading
prophylaxis
Reading
Nutrition of a HIV positive child
Indications for anti-viral therapy
TMA
Total estimated study time
375 minutes
4
MODULE 3
Let us start with
an activity to help you to choose the
appropriate anti-viral prophylaxis for a child born of a
HIV positive mother.
Turn to the reading, nPost-exposure
prophylaxis
for
babies
born
of
HIV positive mothers"
(page 37) . Once you have finished reading this you should
be able to undertake the following activity.
ACTIVITY 3.1
POST-EXPOSURE PROPHYLAXIS FOR NEWBORN
(10 min)
23 year old Meena is a known patient with HIV infection
who delivered a 2.8 Kg baby boy at home. Meena had not
received any anti-viral therapy during her pregnancy or
delivery.
She has
come to the hospital
to
take your
advice regarding care of the child.
1. What
anti-viral
treatment would you advice
for the
child?
J
cd-
j
o
j (J/. >
Dose-
0-/
h-c
Duration-
If0
'T
x 6 u/L, •
5
MODULE 3
FEEDBACK 3.1
2 . What
anti-viral
treatment would you advice
for the
child?
Drug- Zidovudine
Dose- at 2 mg/kg Q6H or 4 mg/kg bd to be started within 48 hours of
birth.
Duration- 4-6 weeks
6
The
aim
of
this
activity
MODULE 3
to
is
help
develop
you
recommendations for breastfeeding of the newborn child of
a HIV positive mother.
need
to
read
To do the next exercise, you will
^WHO/UNICEF/UNAIDS
Statement
on
breast
feeding" in reader at the end of this module .
Once you
have
the
finished reading
this
you
can
undertake
next
activi ty.
Activity 3.2
BREAST FEEDING OF CHILD OF HIV POSTITIVE
MOTHER (15 min)
Refer back to Meena's case in Activity 3.1.
below
1. Circle
whether
you
would
for
providing
advise
Meena
to
line
of
breast feed or not.
'ZYES^
2. What
NO
/
is
advice?
your
reason
this
7
3. If
your
is
advice
for her
MODULE 3
to
breast
feed,
what
specific instructions would you give Meena?
Breast feeding:
7 ~ ~
Top-up feeds:
Duration of breast feeding:
Weaning:
4. If you were to advise her not to breast feed, what
specific instructions would you give her?
Type of replacement feeding:
c>U--^Aw.
(^'L-Ov
Bottle / Paladai:
I
8
MODULE 3
' ^FEEDBACK 3.2
1. Whether you would advise Meena to breast feed or not.
You would advise not to breast feed.
2.What
is
your
reason
for
providing
this
line
of
advice?
AZT prophylaxis is being used to reduce mother to child transmission.
Breast feeding would reduce the benefit of AZT prophylaxis.
Therefore breast feeding may be withheld.
3. If
your
advice
is
for
her
to
breast
feed
what
specific instructions would you give Meena?
Breast feeding: Exclusive breast feeding
Top-up feeds: No water or milk substitutes
Duration of breast feeding: 4-5 months
Weaning: Abrupt weaning
4. If you were to advise her not to breast
feed what
specific instructions would you give her?
Type of replacement feeding: Cows milk is a cheaper option than
formula feeds.
Bottle / Paladai: Palladai to be preferred to bottle as there is reduced
chance of gastroenteritis.
MODULE 3
9
The
next
will
activity
learn
you
help
about
prophylaxis and immunisation for the new born,
oi
To do the
the
sections
"Pneumocystis carinii prophylaxis in Newborn^
(page 37)
next
exercise
you
need
will
newborn
read
to
baby
of
HIV
positive
the
back
of
"Immunisation
for
mother"
(page
in
module.
Once you have finished reading this information
and
38)
the
reader
you can undertake the next activity.
at
this
10
MODULE 3
Activity 3.3
OI PROPHYLAXIS AND IMMUNISATION OF
NEWBORN (20 min)
1. What OI prophylaxis would you give to Meena's baby?
Drug:
I
Dose:
I*
(rv\
r3
Duration:
a
Infection to be prevented:
2.
Indicate
with
a
tick
AJ)
mark
which
of
vaccinations you would give the baby:
i/DPT
vOPV
-. Hepatitis B
, Haemophilus influenzae type B vaccines
x/ BCG vaccination
Measles
the
following
11
MODULE 3
^FEEDBACK 3.3
1. What 01 prophylaxis would you give to Meena's baby?
drug: Bactrim (trimethoprim-sulfamethoxazole)
Dose: TMP 10 mg/Kg/day, 3 days a week
Duration: From 6-8 weeks to 1 year
Infection to be prevented: P. carini
2. Indicate below which of the vaccinations you would you
give the baby?
DPT
OPV^
Hepatitis
Haemophilus influenzae typeb vaccines
BCG vaccination^/
Measles
(at 6 and 9months)
MODULE 3
12
The
activity
next
of
diagnosis
HIV
positive mother.
to
read
the
infection^
module.
Once
infection
To do
you
39)
you
in
a
the next
learn
about
baby
born
exerciser
in
have
the
reader
finished
undertake the next activity.
the
lab
a
HIV
of
you will need
confirmation
nLaboratory
section
(page
help
will
of
HIV
at the end of this
reading
this
you
can
13
MODULE 3
ACTIVITY 3.4
HIV TESTING IN NEWBORN (15 min)
i.
test would you
What
order
and when,
to
diagnose
HIV
infection?
kl Ld-O
2.
What
advanced
test
2. A C
can
be
used
for
an
earlier
diagnosis of HIV infection?
- pC
3.
How
months?
can
you
exclude
HIV
infection
earlier
than
18
14
MODULE 3
^FEEDBACK 3.4
i.
What
test
would
you
order
and
when
to
can
be
used
for
diagnose
HIV
infection?
ELISA test at 18 months of age
2.
What
advanced
test
an
earlier
diagnosis of HIV infection?
PCR test for HIV infection which is positive on 2 separate occasions, the
second after 4 months of age.
3 . How
can
you
exclude
HIV
infection
earlier
than
18
months?
If 2 ELISA's after 6 months are negative at Imonth interval of each
other then the diagnosis of HIV infection can reasonably be excluded.
The
next
eval nation
next
activi ty
aims
of
suspected HIV infection.
exercise,
child
you
will
to
teach
need
to
you
read
about
the
To
initial
do
the
sections
^Natural History of HIV infection in children" (page 40),
u1994
Revised
HIV
Pediatric
Classification
System :
15
clinical
categories"
(page
MODULE 3
40)
and.
"Clinical
Findings:
Suspect HIV Infection" (page 41)
the
this module.
end of
Once you have
and
Lab
in reader at
finished reading
these, you can undertake the next activity.
ACTIVITY 3.5
INITIAL EVALUATION OF CHILD (15 min)
5
year
old
Nesan
was
brought
by
his
parents
with
complaints of failure to thrive for the last one year,
poor
appetite,
itchy
skin
lesions
and
recurrent
respiratory infections.
On examination:
Pallor,
bilateral
oral
thrush
generalised
enlargement r
parotid
lymphadenopathy,
papular
urticaria,
hepatosplenomegaly.
Laboratory tests:
Haemoglobin 9 g/dl,
Total WBC count 4200 Lymphocytes 25
Neutrophils 70 Eosinophils 3 Basophils 2.
Platelet count
20,000/cmm. Total protein 6.5 g/dl. Albumin 3 g/dl.
1.
What
clinical
and
laboratory
features
presence of HIV infection in this boy?
Clinical:
7
point
to
the
16
MODULE 3
Laboratory:
r
'9
1 to
2.Nesan's Tridot test and ELISA test were positive. Which
type
of
natural
history
do
you
think
Nesan's
illness
follows?
3.Which clinical stage of the 1994 Revised HIV Pediatric
Classification System do you think he fits into?
17
MODULE 3
FEEDBACK 3.5
1.What
clinical
and laboratory
presence of HIV infection?
features
point
to
the
Clinical:
failure to thrive
itchy skin lesions-papular urticaria
recurrent respiratory infections.
Pallor-anaemia
Oral thrush
generalised lymphadenopathy
bi lateral parotid enlargement
hepatosplenomegaly
Laboratory.
Lymphopenia
Thrombocytopenia
Hypergammaglobulinemia
2.Nesan's Tridot test and ELISA test were positive.
Which
type of natural history do you think Nesan's
illness
follows?
Intermediate progression
18
MODULE 3
3.Which clinical stage of the 1994 Revised HIV Pediatric
Classification System do you think he fits into?
Category B
The next activity will help you learn about counselling
the parentsf laboratory testing and treatment of a child
with suspected HIV infection.
To do
the next
exercise,
you will need to read the section "Counselling the family
of an HIV positive child" (page 30) in reader at the end
of this module.
Once you have finished reading this you
can undertake the next activity.
19
MODULE 3
z treatment and followup:
_
rV^VvUT^
z
ACTIVITY 3.6
COUNSELLING OF FAMILY
i.
How would
you
counsel
parents
the
of
Nesan
in
the
listed areas listed below?
1. Reassurance:
Ia^at^)
Lt ^z'z
I VvAZAXd
—3
2. Explaining diagnosis and prognosis:
3. Screening of parents/siblings:
__ I-
0,
(fveL<^/
t
f/G’-AA I
4 . Tests,
5. Nutrition:
C^Xxr^'v'u
CHa tAzt)
Jk xa-^aX? — VOf H
6. Schooling:
aA-v n
7. Recreation:
>
( (
,'^1a
<
|-vw\ ( 7-aa^c
n
-
20
MODULE 3
^FEEDBACK 3.6
i. How would you counsel the parents of Nesan?
1. Reassurance: regarding diagnosis that it is HIV disease not AIDS;
treatment available; disease will not spread to other children
2. Explaining diagnosis and prognosis: Survival up to 8 years; can be
improved
with treatment
3. Screening of parents/siblings: both parents have to be screened; if
parents are positive the other children need to be screened.
4. Tests, treatment and followup: should come for regular followup
and treatment; importance of 01 treatment and prevention will be
stressed.
5. Nutrition: Discussion on good nutrition vitamins and micronutrient
replacement in improving immune function.
6. Schooling: Should go to school; need not inform the teacher
7. Recreation: can play all games within physical capacity
The
aim
of
will
next:
testing
laboratory
suspected
the
activity
and
infection.
HIV
is
to
teach
you
about
a
child
wi th
exercise,
you
treatment
of
To
next
the
do
need to re-read the section
"Lab Evaluation of the
HIV positive child"(page 39) and "Opportunistic infection
prophylaxis"
Once
you
(47)
have
in reader at
finished
reading
the
end of this module.
these
sections
you
can
undertake the next activity.
C
21
MODULE 3
ACTIVITY 3.7
LAB EVALUATION OF CHILD
OPPORTUNISTIC INFECTION PROPHYLAXIS
l.What further tests would you order for Nesan?
)
2.
I
Nesan's
normal.
PPD is
6 mm at 48 hours
and chest x-ray is
He cannot afford to have a CD4 count and viral
load test done.
What treatment would you initiate for Nesan?
t>-
3 . What 01
prophylaxis would you start?
22
MODULE 3
FEEDBACKS.?
l.What further tests would you order for Nesan?
PPD and Chest X-ray
2.
Nesan's
normal.
PPD is
6 mm at 48 hours
He cannot afford to have
and chest x-ray is
a CD4
count and viral
load test done.
What treatment would you initiate for Nesan?
Papular urticaria- Liquid paraffin and anti-histamines
Oral candidiasis- Topical clotrimazole or Syr. Fluconazole
3.What 01 prophylaxis would you start?
PCP- Bactrim TAAP 10 mg/Kg/day in 2 doses for 3 consecutive days/week
TB - Rifampicin 10 mg/Kg/day and INAH 5 mg/Kg/day for 6 months
The
next
activi ty
will
help
you
to
1 earn
about
nutritional therapy for a child with HIV infection.
To do
the
next
exercise ,
"Nutrition
of
a
you
will
HIV positive
need
to
read
the
child"
(page
44)
reader at the end of this module.
reading
activi ty.
these
sections
you
can
sections
in
the
Once you have finished
undertake
the
next
23
MODULE 3
7
_^ACTIVITY 3.8
NUTRITION FOR HIV POSITIVE CHILD
What nutritional advice would you suggest?
) -h
gu
Lv^'
‘L
1
J
Ovo nAA>vA^u>^X/
iL
P
'< 'yb-^
24
MODULE 3
FEEDBACK 3.8
What nutritional advice would you suggest?
Nutritional monitoring
Dietary advice -Calories 150-200 Kcal/Kg/day
Protein 2-3 g/Kg/day
Vitamins and micronutrient - Vitamin A, zinc and iron supplementation
Lactose free diet for chronic diarrhea and secondary lactose intolerance.
Nasogastric feeding in a case of severe malnutrition.
The next activity aims
to
teach you about
the clinical
diagnosis of common opportunistic infections. To do the
next exercise, you will need to read the sections
"Respiratory Problems"
this
module.
Once
you
(page 45) in reader at the end of
have
finished
reading
sections you can undertake the next activity.
these
25
MODULE 3
ACTIVITY 3.9
RESPIRATORY PROBLEMS - RECOGNITION
1.Read
the
case
scenarios
in
column.
Match
Study the following
x-rays
X-ray 3A
(X-ray in cover at
end of the module)
X-ray
finding
the
second
the
case
provided.
A
0^ I rJ
oo y
In
Case History
7 year old Vani is brought with
a history of failure to thrive
for the past 1 year, persistent
cough for the past 3 months and
gradually increasing dyspnoea
for
the past
15
days.
On
examination, she is emaciated,
weighing
14
and
her
kg
respiratory rate is 60/minute
with
no
other
findings
on
auscultation.
Her
oxygen
saturation by pulse oximetry is
80% and her serum LDH is > 1000
U/l. Her chest Xray is given
alongside.
Diagnosis:
PC
image
scenarios
to
the
X-ray
MODULE 3
26
B
C
4 year old Radhika comes with a
history of
persistent fever
for a month and cough for the
past 10 days. On examination,
she has a respiratory rate of
40/min, diminished air entry,
dullness on percussion and fine
crepitations over the left lung
base.
Diagnosis:
T 6
X-ray 3B
(X-ray in
the
end
module)
5 year old Gunasekaran has come X-ray 3C
with a history of high-grade (X-ray in
end
fever for the past 3 days with the
cough and breathlessness. On module)
a
examination
he
has
respiratory rate of 60/min, and
fine crepitations heard over
both infrascapular regions. His
total
WBC
count
is
20,000/cu.mm.
LI •
«
.AArAJ •
Diagnosis: h
cover at
the
of
•U A
cover at
the
of
27
MODULE 3
/^FEEDBACK 3.9
Chest X-ray Diagnosis
image
finding_____
Diffuse
PCP
infiltrates
seen in both
lung
fields
extending to
the
peripheries.
Case A
Case
history
Case B
Case
history
Bilateral
upper
mediastinal
adenopathy,
infiltrates in
the
left
midzone and
opacification
of the left
lower zone
with
obliteration
of
the
costophrenic
angle.
Pulmonary
tuberculosis
with
hilar
lymphadenopathy
and left lower
lobar
consolidation
with
pleural
effusion.
Case C
Case
history
Right upper
lobe
consolidation
Bacterial
pneumonia
probably
pneumococcal
X-ray 3A
28
MODULE 3
29
MODULE 3
ACTIVITY 3.10
TREATMENT OF RESPIRATORY PROBLEMS
Write
down
the
appropriate
treatment
against
diagnosis.
Condition
Treatment
Bacterial pneumonia
I
Pulmonary TB
'hv^'v'J'b
. INfr-w dip
y
/^z 'v^evvT
)
Pneumocystis
pneumonia
carinii
* Cc> -
1^/
y. 0
I
3
u
each
30
MODULE 3
^FEEDBACK 3.10
Write
down
the
appropriate
treatment
against
each
diagnosis.
Condition
Treatment
Bacterial pneumonia
Conventional antibiotics
Pulmonary TB
INAH/Rifampicin/Pyrazinamide/Ethambutol
2 months, Isoniazid /Rifampicin 4 months,
extended upto 7 months in slow responders
Pneumocystis
carinii
Trimethoprim-sulfamethoxazole (15 - 20
pneumonia
mg/kg per day TMP)
in four divided doses for 2 to 3 weeks,
T. prednisolone 2 mg/kg/day for 2 weeks
tapered and stopped by Srdweek
The
next
indications
activi ty
for
is
aimed
anti-viral
at
teaching
treatment.
To
do
you
the
about
next
exercise you will need to read the sections "Anti-viral
treatment"
(pages46-48) in the reader at the end of this
module. Once you have finished reading this. you can
undertake the next activity.
31
MODULE 3
ACTIVITY3.il
INDICATIONS FOR ANTI-VIRAL TREATMENT
Put a tick mark against the following situations do you
think that anti-viral treatment is indicated?
Case Scenario
Yes
/No
One year old Arun has tested HIV Elisa-positive twice
1 after the age of 6 months. His parents cannot afford CD4
A/b'
testing, and virologic testing is not available. Arun
has a history of 3 to 4 upper respiratory infections in
the past 1 year. On examination, his weight is 9 kg, and
he has no lymphadenopathy, oral candidiasis or
hepatosplenomegaly. Systemic examination is normal.
4 year old Ravi has been brought to you with a history
2 of recurrent skin infections and otitis media,
and one
episode of pneumonia documented on chest Xray 6 months
earlier.
On
examination,
he
cervical
has
and
axillary
adenopathy, enlarged parotids, and a liver palpable 3 cm
below the right costal margin. Investigations reveal the
following:
HIV
positive
ELISA
and
Western
Blot,
CD4
count of 400 cells/cu.mm.
year
8
old
child
is
well
and
has
been
remarkably
3 aymptomatic. CD 4 count 550/mm3
3
year
old
Arun
has
brought
been
with
4 regression of milestones over the past
a
history
of
6 months he has
lost the ability to run and says only "amma" and "appa
whereas
previously
examination,
he
he
has
had
a
a
large
broad-based
vocabulary.
On
gait
and
ataxic
exaggerated deep tendon reflexes in the lower limbs.
was
7
found to HIV ELISA reactive and his
He
CT scan shows
bilateral basal ganglia calcifications.
7
C
I
Jo
32
MODULE 3
FEEDBACK3.il
Put
a
tick mark against the following situations
for
which in your opinion anti-viral treatment is
indicated?
Yes/No
1
No
2
Yes
3
No
4
Yes
For
more
detailed
discussion
of
neurological
manifestations of HIV infection see Verghese VP et al
(reference 3).
33
NOTES
MODULE 3
34
NOTES
MODULE 3
37
MODULE 3
READINGS
POST-EXPOSURE PROPHYLAXIS FOR BABIES BORN OF HIV
POSITIVE MOTHERS
All newborn babies born of HIV positive mothers should receive ART
prophylaxis according to MTCT protocol
(a) Infants whose mothers have received AZT during pregnancy and labour should
receive Zidovudine (at 2 mg/kg Q6H or 4 mg/kg bd) within 48 hours of
delivery for a duration of 4-6 weeks
(tylnfants whose mothers have received single dose Nevirapine during labour may
receive Nevirapine (2 mg/Kg stat dose) within 72 hours of delivery
or Zidovudine (at 2 mg/kg Q6H or 4 mg/kg bd) within 48 hours of delivery
for a duration of 4-6 weeks
© Infants whose mothers have not received any ART during pregnancy or delivery
should receive Zidovudine (at 2 mg/kg Q6H or 4 mg/kg bd) within 48 hours
of delivery for a duration of 4-6 weeks.
PNEUMOCYSTIS CARINII PROPHYLAXIS IN NEWBORN
At 6 to 8 weeks of age prophylaxis for Pneumocystis carinii pneumonia (PCP),
usually
with
trimethoprim-sulfamethoxazole
(at
lOmg/kg/day
of
Trimethoprim in 2 divided doses daily, 3 days a week) should be started and
given until the age of 1 year. Trimethoprim-sulfamethoxazole is avoided in
the first few weeks of life as it can cause neutropenia.
38
MODULE 3
IMMUNISATION FOR THE BABY OF A MOTHER WHO IS HIV
POSITIVE
•
All routine vaccinations as recommended by the WHO need to be given to
the baby of a mother who is HIV positive
DPT
OPV
Hepatitis B
Haemophilus influenzae type b vaccines
BCG vaccination
(It is usually given in the first 2 months of life. Older children with
symptomatic HIV disease should not receive BCG vaccination because of
the risk of disseminated tuberculosis.)
•
Measles vaccination
First dose- 6 months of age
Second dose - 9 months of age
(measles antibody response to vaccination is lower in HIV-infected
children)
• Varicella vaccination may be given to asymptomatic children after 12
to 15 months of age if the family can afford it.
•
Pneumococcal vaccine may be given to children older than 2 years of
age.
I
39
MODULE 3
LABORATORY CONFIRMATION OF HIV INFECTION
Child >18 months of age: A positive ELISA or Western blot test is indicative of
HIV infection
Child < 18 months of age:
1. A positive ELISA test cannot be used to make a diagnosis of HIV infection
in these children.
(Exposed infants and children younger than 18 months of age maintain HIV
seropositivity due to the persistence of transmitted maternal antibodies)
2. Two or more negative antibody tests (ELISA or Western Blot) can
reasonably exclude HIV infection in non-breastfed infants with no evidence of
clinical infection.
> Tests performed beyond 6 months of age
> Interval of 1 month between assays
3. Definitive diagnosis can be made in case of perinatal transmission if two
HIV PCR assays drawn at separate times are positive. This can be performed
as early as the first 48 hours of life using HIV DNA PCR or HIV culture, both
of which are very sensitive and specific in determining HIV infection.
4. Negative PCR assays after 4 months of age can exclude HIV infection in the
absence of breastfeeding.
40
MODULE 3
NATURAL HISTORY OF HIV INFECTION IN CHILDREN
Proportion (%)
Rapid progression (AIDS in 2 years)
20~~
Intermediate progression (AIDS in 7-8
60-75
years)
Slow progression (AIDS>8 years)
5-10
median survival time of perinatally HIV-infected children- 8 to 9 years
(not on antiretroviral therapy)
1994 REVISED HIV PEDIATRIC CLASSIFICATION SYSTEM: CLINICAL
CATEGORIES
Category A_______
Mildly
Symptomatic_____
Lymphadenopathy
Hepatomegaly
Dermatitis
Parotitis
Recurrent/
persistent
URI, sinusitis or
otitis media.
Category B____________
Moderately symptomatic
Category C_________
Severely symptomatic
Recurrent or chronic Diarrhea
Serious
bacterial
Failure to thrive
infections
Persistent oropharyngeal
Esophageal candidiasis
candidiasis
Cryptococcal meningitis
Anaemia, neutropenia
Diarrhea > 1 month
thrombocytopenia
Encephalopathy
Bacterial meningitis
Persistent HSV ulcer (> 1
Pneumonia
month)
Sepsis
Tuberculosis,
0
Cardiomyopathy
disseminated
or
extrapulmonary
Hepatitis
Pneumocystis
carinii
Recurrent herpes stomatitis
Multi-dermatomal herpes zoster
pneumonia
Salmonella (nontyphoid)—
Complicated chickenpox
Lymphoid interstitial pneumoni septicemia, recurrent
Cerebral Toxoplasmosis
(LIP)
Persistent fever (> 1 month)______
Category N: Not Symptomatic
In situations where CD4 testing is not available or affordable, the presence
of a Category B or Category C illness may be taken as an indirect indicator
of the presence of moderate or severe immunosuppression, for purposes of
monitoring disease progression and deciding when to start PCP
prophylaxis in children older than 18 months of age (unpublished data).
*5
f
41
MODULE 3
CLINICAL AND LAB FINDINGS: SUSPECT HIV INFECTION
Clinical suspicion of HIV infection
The following clinical manifestations and laboratory findings should lead to
the suspicion of HIV infection in children, especially when present in
combination and where other causes cannot be found. It must be emphasized
that many of these manifestations may also be seen in children in developing
countries due to other infections or illnesses in the absence of HIV infection.
History of
•
•
1
•
•
•
•
•
•
•
•
Failure to thrive
Recurrent bacterial infections (pyoderma, sinusitis, otitis media,
pneumonia, meningitis)
Recurrent or chronic diarrhea
Recurrent or persistent oral candidiasis
Developmental delay or loss of milestones
Progressive respiratory distress during the first 6 months (PCP)
Recurrent vaginal candidiasis (older girls)
Bruising or epistaxis
Recurrent varicella or herpes zoster
Mycobacterial infections
Examination Findings
Generalized lymphadenopathy
Unexplained hepatomegaly, splenomegaly or both
Chronic or recurrent enlargement of parotid glands
Oral thrush
Papular urticaria (HIV dermatitis)
Hyperreflexia, spasticity, rigidity, increased muscle tone
Candida dermatitis
Bruising or petechiae
Unexplained digital clubbing
Chronic lung disease or lymphoid interstitial pneumonitis (LIP)
Unexplained congestive heart failure
Renal failure or nephrotic syndrome
Laboratory Findings
•
•
•
Unexplained anemia, neutropenia or thrombocytopenia
Hypergammaglobulinemia (frequent)
Hypogammaglobulinemia (in advanced disease)
42
•
•
•
•
•
Failure to form antibodies following vaccination
Increased liver transaminases
Increased amylase (due to parotitis)
Increased lactic dehydrogenase levels (in LIP and PCP)
Persistently abnormal chest X ray
MODULE 3
43
MODULE 3
COUNSELLING THE FAMILY OF AN HIV POSITIVE CHILD
Child
Preschool
Encourage the child to ask about the tests and procedures and attempt to allay
fears about the same. Use simple diagrams to explain issues like injections,
and health consequences and steps that have to be taken.
School age
Plan information commensurate to the developmental level.
Adolescents
Try to establish a sense of trust with a view towards therapy and its
compliance.
At all ages encourage recreational activities that health permits.
Regular follow up with developmental and neurological assessments.
Continue school.
Family
Parents
Understand the despair and anxiety and allow them to speak about their
concerns.
Educate them regarding injections and treatments to help them to move
towards acceptance and realistic expectations.
Tackle parental guilt and help them to understand that it was not their intent
to cause harm to the child.
If depressed or in suicidal risk treat depression and seek psychiatric help.
Assess stresses on other members of the family like the grand parents.
Check both the parents for HIV status if it is unknown.
Siblings
Assess fears in the siblings.
Encourage older children to help in the care of the affected child.
Check the siblings for HIV infection.
44
MODULE 3
LAB EVALUATION OF THE HIV POSITIVE CHILD
Mantoux testing and a radiograph of the chest are essential in the initial
evaluation of the HIV-infected child. Annual TB testing with PPD and chest
roentgenogram is recommended for both HIV-infected and non-infected
siblings. A PPD reaction of 5 mm or greater should be considered positive in
HIV-infected children. A positive PPD with a normal chest X-ray indicates
infection with TB but not disease. A positive PPD is an indication for initiating
TB prophylaxis with Rifampicin 10 mg/Kg/day and Isoniazid 5 mg/Kg/day
for 6 months.
Other investigations may be done as clinically indicated.
NUTRITION OF THE HIV POSITIVE CHILD
Nutritional support in the HIV-positive child include:
•
Monitoring weight and height at each visit to identify growth failure
•
Diet providing 150 -200 Kcalories/kg/day, and 2-3 gm protein/kg /day
•
Caloric density may be increased by the addition of fats such as coconut
oil that are easily digested
•
Lactose-free formula in the infant with lactose intolerance secondary to
chronic diarrhoea.
•
Predigested milk formula (Pregestemil) in the infant with chronic
diarrhoea and no lactose intolerance
7
•
Micronutrient supplementation with Vitamin A, iron and zinc
•
Antioxidants such as Vitamin E, seleniun^glutathione and beta-carotene .
•
Nasogastric tube feeding may be used in the child with odynophagia or
anorexia
•
Appetite stimulants such as cyproheptadine may be tried
•
Gastrostomy feeds/total partenteral nutrition may be tried in specialized
centers for children who do not respond to all other interventions.
45
MODULE 3
__________ RESPIRATORY PROBLEMS
CLINICAL CRITERIA
TREATMENT_____________________
Persistent cough/ dyspnoea Trimethoprim-sulfamethoxazole (15 minimal findings
20 mg/kg per day TMP) in four daily
Diffuse bilateral interstitial doses for 2 to 3 weeks T. prednisolone
infiltrates (CXR)
2 mg/kg/day for 2 weeks
Hypoxemia (pulse oximetry) tapered and stopped by 3rdweek
7 -—-Serum LDH level > 2 to 3
times normal
Response to co-trimoxazole
therapy
INFECTION
Pneumocystis
carinii
Bacterial
pneumonia
Pulmonary TB
Lymphoid
interstitial
pneumonia
a
Acute onset high fever
leukocytosis with shift to the
left
Lobar consolidation (CXR)
Positive blood cultures______
Fever>l month
Weight loss
Cough
Close contact with TB
Positive PPD > 5 mm
AFB positive
Histology of TB
Radiology suggestive of TB
Response to ATT
Conventional antibiotics
INAH/Rifampicin/Pyrazinamide/Eth
ambutol 2 months
Isoniazid /Rifampicin 4 months
Extended upto 7 months in slow
responders (sputum positivity or
persistence of signs or symptoms after
the initial 2 months).
Extrapulmonary disease:
Continuation phase for 7 months (total
therapy 9 months)__________________
Bilateral
reticulonodular Bronchodilator therapy
infiltrates (CXR)
In case of hypoxia treat with steroids
Serum LDH elevated to
within 2 to 3 times normal
Elevated
immunoglobulin
levels
No response to therapy with
antibiotics/ATT
46
MODULE 3
INDICATIONS FOR ANTI-VIRAL TREATMENT
CRITERIA
INDICATION
CLINICAL:
Category C
LABORATORY:
Any clinical category (N,A,B,CZ) with
CD4 count < 15%
(See page 49 for age-specific counts)
As many of the symptoms of HIV disease overlap with symptoms seen in
children without HIV disease in resource-limited settings, initiation of ART in
children < 18 months of age should not be considered in the absence of viral
load assays and CD4 counts.
ANTI-RETROVIRAL REGIMENS
REGIMEN
FIRST-LINE
NRTIs
NNRTI / PI
ZDV + 3TC
NVP or EFZ
ZDV + 3TC + ABC
SECOND-LINE
d4T + ddl
IDV
d4T + ddl
NVP/EFZ(if
first
3
NRTIs)
&
47
MODULE 3
OPPORTUNISTIC INFECTION PROPHYLAXIS
PCP prophylaxis beyond 1 year of age is also given to all children with a
J
previous
episode
of
PCP
and
those
with
evidence
of
severe
immunosuppression (CD4 count < 500 between 1-5 years age or < 200
between 6-12 years age). In the absence of CD4 testing all children with a
history of Clinical Category B or C illness may be considered candidates for
PCP prophylaxis.
APPENDIX: ANTIRETROVIRAL DRUGS
Nucleoside analogues inhibiting HIV-1 reverse transcriptase (NRTIs):
Major toxicity
Dosage
Drug
bd;
Bone
Zidovudine
180
(ZDV/AZT)
4mg/kg bd in neonates
suppression
Didanosine (ddl)
90 - 150 mg/ M2 bd;
Pancreatitis,
50
mg/M2
mg/M2
bd
marrow
hepatitis
in Peripheral neuropathy
neonates
Lamivudine (3TC)
Stavudine
(d4T)
bd;
Pancreatitis,
2 mg/kg bd in neonates
Neutropenia
1 mg/kg bd
Pancreatitis,
4
mg/kg
hepatitis
hepatitis
Peripheral neuropathy
Zalcitabine (ddC)
0.005 to 0.01 mg/kg tid
Mucocutaneous
eruptions
Abacavir
(ABC)
8
mg/
kg
(in > 3 mo. age)
Ml
bd
Life-threatening
hypersensitivity
48
MODULE 3
Non-nudeoside analogues inhibiting HIV-1 RT (NNRTIs)
Drug
Nevirapine
(NVP)
Delavirdine
(DLV)
Efavirenz
(EFV)*
Dosage
Major toxicity
120 mg/M2 od x 2
wks then 200 mg/M2
bd
Dose unknown
200 -600 mg
in > 3 yrs age
od
Severe
skin
rash Hepatitis
Mild skin rash
GI symptoms
Skin
rash
CNS symptoms
*Efavirenz pediatric dose: No data for children younger than 3 years.
By body weight, once-a-day dosing as follows:
10 to <15 kg: 200 mg, 15 to <20 kg: 250 mg
20 to <25 kg: 300 mg, 25 to <32.5 kg: 350 mg
32.5 to <40 kg: 400 mg, >/= 40 kg: 600 mg.
Inhibitors of HIV-1 protease (Pls):
Drug
Dosage
Indinavir
(IDV)
500 mg/M2 tid
Ritonavir
(RTV)
350 - 450 mg/ M2 bd
Saquinavir
(SQV)
Nelfinavir
(NFV)
Dose unknown
Amprenavir
(VZX 478)
55
nig/kg
bd;
40 - 50 mg/kg tid < 1 yr
age___________
bd
20
mg/kg
in > 4 yrs age
Major toxicity
Indirect
hyperbilirubinemia;
kidney
stones,
GI
symptoms,
GI
symptoms,
hyperlipemia
Hepatitis,
pancreatitis
GI
symptoms.
Hyperglycemia
GI
symptoms,
rash
I lyperglycemia
GI
symptoms,
hyperlipemia, rash, mood
disorders
49
MODULE 3
1994 Revised Pediatric HIV Classification System: Immunologic Categories
Based on Age-Specific CD4+ Lymphocyte Count and Percentage
| Age of Child~
Immune Category
</= 12 months
Cells/mm3 (%)
1-5 years
6-12 years
Cells/mm3 (%) Cells/mm3 (%)
Category 1:
No suppression
>/= 1,500 (>25) >/= 1,000 (>25) >/= 500 (>25)
Category 2:
Moderate
suppression
750-1,499 (15 24)
500- 999 (1524)
200-499 (15 24)
750 (<15)
500 (< 15)
200 (< 15)
Category 3:
Severe suppression
REFERENCES
1.
WHO/UNAIDS/UNICEF Statement on Policy Guidelines of HIV and
infant feeding, (available at www.unaids.org).
2.
Cherian T, Verghese V.P. (2000).Tuberculosis with human
immunodeficiency virus infection. Indian f Pediatr 67: S47-S52.4
3.
Verghese VP, Cherian T, Cherian A.J., Babu P.G., John TJ, Kirubakaran
C, Raghupathy P. (2002) Clinical manifestations of HIV-1 infection. Indian
Pediatr 39: 57-63.
4.
WHO (2001) Use of antiretroviral drugs for MTCT prevention,
(available at www.unaids.org).
FURTHER READING
1.
HIV/AIDS in infants, children and adolescents. Pediatric Clinics of
North America February 2000; 47 (1). WB Saunders Company, Philadelphia.
2.
Yogev R, Connor E (eds) Management of HIV infection in infants and
children. (1992), Mosby-Year Book Inc., St.Louis
3.
Pizzo P.A., Wilfert CM (eds) Pediatric AIDS (1998). Williams and
Wilkins, Baltimore.
sc
WHO, UNICEF, UNAIDS Statement
on Current Status of
WHO/UNAIDS/UNICEF Policy Guidelines
CTV1
A recent early report of evidence that HIV is less likely to be transmitted through exclusive breastfeeding does not
warrant a change in existing WHO/UNICEF/UNAIDS policy.
In the last ten years, evidence has accumulated that HIV can be transmitted through breast-milk. WHO and
UNAIDS currently estimate that a child breastfeeding from a mother who is HIV positive has a 15% risk of
infection by this route. Every year 200,000 infants may acquire HIV in this way. Where resources permit, many
HIV-positive mothers now choose to feed their babies artificially, and to avoid breastfeeding altogether. In resource
poor settings,where the risks of artificial feeding may be particularly high, the decision for both individual mothers
and policy-makers is more difficult. The situation has led in some settings to a loss of support for initiatives to
promote breastfeeding, and to some women avoiding breastfeeding even if they do not know their HIV status.
In 1997, UNAIDS, WHO and UNICEF issued a joint policy statement on HIV and infant feeding, which stated that
- "As a general principle, in all populations, irrespective of HIV infection rates, breastfeeding should continue to be
protected, promoted and supported" and - "Counselling for women who are aware of their HIV status should include
the best available information on the benefits of breastfeeding, on the risk of HIV transmission through
breastfeeding, and on the risks and possible advantages associated with other methods of infant feeding" and - "It is
therefore important that women be empowered to make fully informed decisions about infant feeding, and that they
be suitably supported in carrying them out."
In 1998, WHO, UNICEF and UNAIDS held a technical consultation on HIV and Infant Feeding, and issued
guidelines with a human rights perspective, based on the joint policy statement (1). These guidelines call for a
strengthening of initiatives to protect, promote and support breastfeeding among mothers who are HIV negative or
of unknown HIV status, and they describe several infant feeding options for consideration by HIV-positive mothers
These include:
- replacement feeding with commercial formula or home prepared formula
- breastfeeding in the way generally recommended
- breastfeeding exclusively and stopping early
7
—-= z use of heat treated expressed breast-milk
- wet-nursing,
in all cases with timely and adequate complementary feeding. There is no attempt to favour any one of these options
over the others, as the principle recommendation is for mothers to receive counselling that will enable them to make
a fully informed decision appropriate to their situation and resources. The responsibility of the policy-maker and
health care manager is to provide the necessary support to enable mothers to make and carry out their choice
whether to breastfeed or to use replacement feeds.
The studies on which existing estimates of transmission are based do not distinguish between infants who are
exclusively breastfed and those, usually the majority, who are both breastfed and receive other foods or drinks. A
recently published early report (2) suggests that exclusive breastfeeding, that is, when an infant is aiven no other
food or drink of any sort, may be less likely to transmit infection than mixed feeding, possibly because other foods
can damage the infants gut, and make it easier for the virus to cross the intestinal mucosa. This report has raised the
hopes of many health workers, who are concerned about the adverse effects on child health of decreasing rates of
breastfeeding. The question has been raised as to whether or not WHO should revise its infant feeding
recommendation.
&
The information contained in this early report is interesting and important. However, because of limitations of the
study size and design, firm conclusions cannot be drawn without further research. That such research should be
conducted as a matter of urgency is clear, and has been identified by WHO as a priority.
5|
hre^t’^d10 ' h06
nSk °f maStitis and niPP'e damaSe which could increase transmission of HIV Stoonma
ZZXthe Z
S.SSSSSSSS?
uuurmaiion
as
n
becomes
available.
^eSd^tSS’. GuideHneS f°r decision-®akers. WHO/FRH/NUT/CHD/98.1; UNAIDS/98.3;
Care managerS and SUperViSOrS' WHO/FRH/NUT/CHD/98.2;
2. Coutsoudis A, Pillary K, Spooner L,
’ L,
Z
E, ”
Kuhn
L, Coovadia
HM. Influence of infant-feeding patterns on early motherto-child transmission of HIV-1 in Durban, South Africa:
' —
—: a prospective cohort study. Lancet 1999; 354:471-76
5 2.
Supplement-Indian J Pediatr 2000; 67: S47-S52
Tuberculosis in Children
Tuberculosis with Human Immunodeficiency Virus Infection
Thomas Cherian and Valsan P Verghese
I
I
Department of Child Health, Christian Medical College & Hospital, Vellore, Tamilnadu
Abstract. Tuberculosis is the commonest opportunistic infection in HIV-infected patients in developing countries including
India. The seroprevalence of HIV among tuberculosis patients in various parts of India has been increasing steadily.
Children who are HIV-infected have a higher risk of progression after primary infection. Children born to HIV positive
parents who are not infected themselves are also at higher risk of acquiring tuberculosis because of exposure. The
clinical and radiological manifestations of tuberculosis are similar to those seen in HIV-uninfected individuals, except in
those with advanced immunodeficiency. Most patients respond well to standard chemotherapy but mortality remains
high because of other opportunistic infections. Preventive treatment with isoniazid for 6-12 months is effective in reducing
those with latent infection.
Key words : HIV infected; Latent infection.
'II
The HIV epidemic started a new era in the history of tuberculosis patients throughout India has increased
mycobacterial disease in humans, both in developed and significantly in the past few years. In Pune, the prevalence
developing countries. There has been a resurgence in the of HIV infection among tuberculosis patients increased
number of cases of active tuberculosis worldwide. More from 3.2% in 1991 to 20.1% in 19967.
Most available data on HIV and tuberculosis is from
ominous has been the emergence of multi-drug resistant
tuberculosis. The significance of tuberculosis in the natural adults. It is not surprising that tuberculosis is more
history and progression of HIV infection is now well common among HIV-infected adults than children since
recognized. Extrapulmonary tuberculosis was classified there is a cumulative increase in the risk of tuberculosis
as an AIDS defining illness in children in 1987*. In the with age. Adults may develop disease from progression
most recent classification system for HIV infection in of a primary infection as well as reactivation of latent
children, extrapulmonary tuberculosis is included as a infection. Disease in children, on the other hand, usually
category C condition, i.e. defining severe symptomatic follows progression of primary infection. Though the
proportion of HIV-infected children with tuberculosis is
HIV infection2.
lower than HIV-infected adults, the number of children
Epidemiology of HIV and Tuberculosis
with HIV-attributable tuberculosis is rapidly increasing.
Using estimates of prevalence of tuberculosis and HIV in It is estimated that worldwide there will be over 56,000
various regions, it has been observed that by mid-1994 cases of HIV-attributable tuberculosis annually in children
there were 5.6 million persons co-infected with HIV and by the year 2000H. A study from Mumbai showed a
tuberculosis worldwide; more than 1.15 million of these prevalence of HIV of 18% among children with CNS
live in Southeast Asia (including India3). It is estimated
tuberculosis or miliary tuberculosis; the prevalence of HIV
that deaths from tuberculosis will increase from 2.5 million seropositivity among children with chronic diarrhea in
annually in 1990 to 3.5 million annually in 2000. The the same study was 24%9. In our cohort of 49 children
proportion of HIV -attributable tuberculosis deaths will with HIV infection, seven (14%) were diagnosed to have
increase from 4.6% to 14.2%. In the developed countries, tuberculosis (unpublished data).
the increasing rates of tuberculosis have been reversed
with effective tuberculosis control programs. In India, the Copathogenicity of Tuberculosis and HIV Disease
rates of HIV-luberculosis co-infection are steadily The association between HIV and tuberculosis is not
increasing. Here tuberculosis is the commonest surprising because of the overlap in the populations at
opportunistic infection in HIV infected. Close to 60% of greatest risk for infection with both these organisms and
adults with symptomatic HIV infection have the importance of cell mediated immunity in controlling
tuberculosis16. The seroprevalence of HIV antibody among tuberculosis. Thus, those with HIV infection arc more likely
------------------------------------------------------------------------- to develop active disease when infected with Mycobacterium
Correspondence :Tliom;..1 Cherian, Department of Child tuberculosis and, consequently, more likely to spread the
Health, Christian Medical College & Hospital, Vellore infection to their close contacts. Areas of the world with
632004, Tamilnadu
Supplement-Indian J Pediatr 2000; 67: SS2
S47
THOMAS CHERIAN & V P VERGHESE
the highest rates of tuberculosis (>100 cases per 100,000 upper lobe tuberculosis is more common in those with CD4
population) are the same regions where HIV is rapidly counts> 200/mm1, whereas hilar/mediastinal adenopathy
increasing. In these areas transmission of HIV is and diffuse pulmonary infiltrates (withoutcavitation) are
predominantly heterosexual and HIV infection in children more common in those with CD4 counts<200/mm3 |g.
puts them at high risk for co-infection with M. tuberculosis,
Data from children co-infected with HIV and
following which they also have a higher risk of progression tuberculosis also suggest that the clinical and radiological
to active disease; the risk of active disease in children with manifestations do not vary significantly from those who
HIV is 5-10 times higher than those without HIV9.
are HIV seronegative19. However, one study from Zimbabwe
Children born to HIV-infected mothers, but who are showed that lobar infiltrates, especially those involving
not themselves infected, are also at higher risk for acquiring the lower lobes were more common in the HIV seropositive
tuberculosis because of the increased risk of exposure to children20. In the cohort of 31 HIV seropositive children
tuberculosis from their parents. It is estimated that with tuberculosis in Cote d'Ivoire, nine (29%) had
tuberculosis rate in the first four years of life among children extrapulmonary disease19. This was not significantly higher
born to HIV-infected mothers is 10 times higher than in than in HIV seronegative children, 26% of whom had
non-HIV-infected and 30 times higher in HIV-infected extrapulmonary disease19. The common extrapulmonary
children, respectively, as compared to other children1’1.
manifestations were lymphadenopathy, pleural effusion
While it is clear that HIV infection increases the risk and miliary tuberculosis, the latter seen more frequently in
of tuberculosis, it is now becoming increasingly clear that the I IlV-infecled cohort19.
the reverse is also true. Immunologic and virologic
In our own experience, all seven children co-infected
evidence indicates that the immune response to with HlV and tuberculosis had pulmonary disease. All of
tuberculosis enhances HIV replication, accelerating the them presented with prolonged fever, weight loss and
progression of the infection11. Therefore, prevention and failure of the pulmonary signs and symptoms to subside
early treatment of tuberculosis is very important in HIV- despite adequate antibiotic therapy. Chest radiographs
infected patients.
showed only hilar adenopathy in one, lobar infiltrates with
Infection with M. luberculosis most often occurs via or without hilar adenopathy in four (fig. 1) and diffuse
the respiratory tract. After infection, alveolar macrophages infiltrates in two children, respectively.
present the mycobacterial antigens to CD 4 positive TThe clinical features of tuberculous meningitis in
cells. This results in the release of interferon gamma (ll;NY), children who are seropositive for 111V are also not
which in turn activates macrophages to control the significantly different from those in seronegative children,
mycobacterial infection. However, the activated I lowever, venlriculomegaly, gyral enhancement and
macrophages also release interleukin-1, which enhances cortical atrophy on CT scan are more common in HIV
HIV replication1211. Mycobacteria also enhance HIV seropositive children21. Also, mortality and the incidence
replication by inducing nuclear factor Kappa-B, the cellular of severe neurological sequelae are more common in HIV
factor that binds to the promoter region of HIV14,15.
seropositive children. Co-existing HIV encephalopathy and
Clinical Manifestations of Tuberculosis in Patients with diminished immune function may account for the poorer
HIV Co-infection
piognosis21.
In majority of the adults (> 15 years) with HIV infection, the Laboratory Diagnosis
clinical and radiological manifestations of tuberculosis are In children the majority of tuberculosis cases are diagnosed
similar to those seen in non-HIV infected adults16,17. Studies clinically without microbiological confirmation. The
in Kenya and Tanzania have shown that 88-92% of HIV diagnosis is based mainly on clinical suspicion and
seropositive adults with tuberculosis had only pulmonary radiological manifestations.
involvement whereas 0.6 to 3% had both pulmonary and
The tuberculin skin test is often negative, especially
extrapulmonary involvement and 8-12% had only in those with more advanced HI V disease. Only one-third
extrapulmonary involvement16. Of those with to less than half of children co-infected with tuberculosis
extrapulmonary involvement, 85% had lymphadenopathy and HIV have a positive tuberculin test19-20-22. Because of
(mainly cervical)16. Miliary tuberculosis was uncommon the higher risk of tuberculosis in children living in
and found in only 1.7% of 1722 tuberculosis patients with households with HIV-infected adults and because of
HIV in Kenya16. Though many HIV-infected adults have diminished immune responses in children with HIV
typical clinical and radiological manifestations of infection, the American Academy of Pediatrics recommends
tuberculosis, atypical presentations do occur frequently, using induration > 5 mm as the criterion for diagnosis of
especially in those with low CD4 counts. Thus, cavitatory tuberculous infection23. These criteria have not been
S48
Supplement-Indian J Pediatr 2000; 67: SS2
3
TUBERCULOSIS WITH HIV INFECTION
J
lit
Figurel: Chest radiograph of a child with tuberculosis and HIV co-infection showing mediastinal
lymphadenopathy and lobar infiltrates.
’ " ' document for the latest treatment recommendations.
adequately evaluated in developing countries, especially
in those where BCG vaccination is part of routine childhood Pulmonary tuberculosis/For drug-susceptible pulmonary
tuberculosis, standard 6-month therapy with isoniazid
immunization.
’
t
one
would
expect,
smears
and
(INH), rifampicin (RIF), pyrazinamide (PZA) and
Contrary to what
often
negative
in
HIV-infected
adult
ethambutol (EMB) daily for the initial two months followed
cultures are more <
patients with tuberculosis24. Similar findings are reported by INH and RIF, daily or twice weekly, for at least 4
among children with co-infection19,20. Despite this, it is additional months, is recommended. Conversion from
recommended that aggressive attempts be made to obtain sputum positive to sputum negative with this regimen is
a positive culture to differentiate between M. tuberculosis similar in HIV seropositive and seronegative patients with
and other mycobacteria, as well as to determine the tuberculosis. However, it is not known if relapse rates are
antimicrobial susceptibility.
higher in HIV-infected patients. Hence, some experts
Smears from needle aspiration and Ziehl-Neelson recommend extending the treatment to9 months.The CDC
staining are often negative in HIV patients who have recommends a minimum of 6 months therapy, with
tuberculous lymphadenitis25. Hence, biopsy with extension to 9 months in those who show slow response,
histopathological examination and culture of the lymph Slow response is defined as sputum positivity or persistence
node tissue are recommended to establish the diagnosis, of signs and symptoms of disease after 2 months of
Newer diagnostic modalities including molecular therapy26. Directly observed therapy is recommended,
methods of diagnosis of tuberculosis may yield better wherever possible.
results than routine smear and culture in the HIV-infected
Extrapulnionary tuberculosis /The drug regimen
population, but these methods need further evaluation, and duration of treatment used for pulmonary
Moreover, these methods for diagnosis are seldom available tuberculosis are generally adequate to treat most forms
in regions where the two infections most frequently co of extra pulmonary tuberculosis. However, for certain forms
of tuberculosis, such as meningitis and bone and joint
exist.
tuberculosis, a 9-month regimen of a rifamycin-containing
Treatment
regimen is recommended2'*.
The treatment of tuberculosis in HIV-infected individuals
Dini; ivsist.mt (ubvtvulafis .'Hie risk of drug resislanl
has been extensively reviewed in a recent public.dion h orn lubi’ivulosis is higher among those co-inlccled with I II Vz/.
the Centres for Disease Control and Prevention (CDC), The reasons for this arc not clear, but this might relied the
Atlanta, USA2". Readers are advised to consult this
e <n
THOMAS CHERIAN & V P VERGHESE
*
fact that a higher proportion of tuberculous disease in HIV- in the treatment of tuberculosis in patients receiving Pls;
infected individuals follows recently acquired infection. the
” PI ritonavir should not, however, be used in treatment
In recent years there had been an increasing number regimes containing rifabutin.
of reports of rifampicin monoresistance in HIV co-infected
Outcome oft/jempy.^hen tuberculosis develops
patients. The reasons for this are also not fully understood, in HIV-infected individuals, the prognosis is poor, despite
Possible reasons3 include (1) increased rates of bacterial treatment. The 1-year mortality for treated HIV-related
of suppressed
cell mediated tuberculosis is 20-35% both in developed and developing
replication in an cenvironment
----- ---- -------rt
alabsorption and (3) countries26. The observed mortality in co-infection with
immunity, (2) selective drug malabsorption
inadequate tissue penetration of the drug.
HIV and tuberculosis is four times higher than in
For isoniazid-resistant tuberculosis, a regime tuberculosis without HIV29. Although death may be due to
containing RIF, PZA and EMB may be used for the full tuberculosis, more often it is due to other HIV-related
duration of treatment (6-9 months). Intermittent therapy complications3’5.
may be used after daily therapy for the initial 8 weeks.
Prevention
For tuberculosis resistant only to rifampicin a 9- Chemoprophylaxis/Prevention of tuberculosis in the HIVmonth regime consisting of INH, EMB, PZA and infected population not only prevents progression of HIV
streptomycin for the initial two months, followed by INH, disease but also limits the spread of tuberculosis among
PZA and streptomycin for the next 7 months is
susceptible contacts.
recommended.
Several studies have documented that six or 12
In multidrug resistant tuberculosis (i.e. resistant to
that months of INH given to tuberculin test positive patients
INH and RIF), aggressive treatment with a regime
i J
contains an aminoglycoside or capreomycin and a resulted in a 70-83% reduction in incidence of tuberculosis,
fluoroquinolone is recommended. The duration of therapy A multicentric trial in the United States, Brazil, Mexico and
must be at least 24 months after culture conversion.
Haiti showed that 2 months of RIF and PZA was equivalent
Paradoxical reactions to treatment: Pa tients who to 12 months of INH alone. There is no comparison between
receive antituberculosis treatment along with anti-retroviral a 6-month and 12-month regime of INH, but treatment
therapy may manifest a paradoxical worsening of beyond 12 months does not seem to provide additional
symptoms, which are attributable to a recovery of tuberculin benefit. The duration of the protective effect of prophylaxis
hypersensitivity as a result of therapy28. Such patients is not known and the effect on mortality and progression
manifest with hectic fevers, lymphadenopathy, worsening of HIV appears to be limited.
chest radiographic findings (e.g. miliary infiltrates and
Based on these studies, the CDC currently
pleural effusion) and worsening of original tuberculosis recommends prophylaxis for all HIV-infected individuals
lesions. Discontinuation or changes in tuberculosis or with a tuberculin skin reaction >5 mm26. INH prophylaxis
antiretroviral therapy is rarely required in most situations, has not been found beneficial in anergic HIV-infected
A short course of steroids to suppress the immune response patients. However, some experts recommend prophylaxis
may ameliorate some of the signs and symptoms, such as for anergic or tuberculin negative I UV-infecled individuals
lymphadenopathy.
with high risk for exposure to tuberculosis. These
Interaction between rifamycins and anti-retroviral recommendations hold true for children as well. Yearly
dropsof the newer anti-retroviral drugs interact with tuberculin testing and prophylaxis is recommended for all
the rifamycin group of anti-tuberculosis drugs, further HIV-infectcd children.
complicating treatment. Rifampicin induces the enzyme
Non-I HV-infected children of parents with
CPY 450 that increases the metabolism of protease tuberculosis arc also at high risk for developing
inhibitors (I’ls) resulting in lower serum levels of these tuberculosis. Once a year tuberculin testing and
drugs. Since 1’1 resistant mutants of HIV may emerge if prophylaxis if they become tuberculin sensitive is
optimal levels of the drug are not maintained during recommended23.
therapy, concomitant therapy with rifampicin and I’ls is
As has been staled earlier, mortality in treated
not recommended ’". On the other hand the protease tuberculosis patients co-inlcc.led with I IIV is largely due to
inhibitor ritonavir inhibits CPY 450, which results in other opportunistic infections rather than leaclivation of
increased concentration of rifabutin and resultant toxicity, tuberculosis. This is especially true in patients in
Since current evidence indicates that the anti tuberculosis developing countries who are not receiving antiretroviral
activity of rifabutin is equal to that of rifampicin, it is therapy. A recent study from Cote d'Ivoire has shown that
recommended that this drug be used instead of rifampicin cotrimoxazole prophylaxis, started after completion of a 6-
S50
*
Supplement-Indian J Pediatr 2000; 67: SS2
TUBERCULOSIS WITH HIV INFECTION
Public Henltli 1998; 29:37-6.
month course of antituberculosis treatment in patients co
infected with HIV, resulted insignificantly lower mortality 5. Kumaraswamy N, Solomon S, Jayaker Paul SA, Vemlla R,
Amalraj RE. Spectrum of opportunistic infections among
and hospital admissions during a 10-month follow up
AIDS patients in Tamilnadu. Ini J STD AIDS 1995; 6: 447-9.
ffCG vaccination /There are a few case reports of 6. Kaur A, Babu PG, Jacob M ct nl. Clinical and laboratory profile
of AIDS in India. / Acquir Innniine Def. Syndr 1992; 5: 883-9.
disseminated BCG infection in individuals with HIV.
However, several studies in developing countries have 7. Paranjape RS, Tripathy SP, Menon PA cl al. Increasing trend
of HIV seroprevalence among pulmonary tuberculosis
documented that adverse reactions following BCG
patients in Pune. Indian ] Med Res 1997: 106: 207-11.
vaccination in HIV-infected infants are no higher than in
non-infected infants’2. Therefore, BCG vaccination is 8. Merchant RH, Shroff RC. Hiy_seroprev.Vleno, in
disseminated tuberculosis and chronic diarrhea. Indian
recommended for infants of HIV-infected mothers m
Pediatr 1998; 35: 883-7.
countries where it is part of the routine immunization
schedule, provided the children do not have evidence 0 9.
. -Husson RN. Tuberculosis. In : Pizzo PA, Wilfert CM (cds).
Pediatric AIDS. 3'u edn. Baltimore, Wiliams and Wilkins. 1998;
advanced immunodeficiency. However, the efficacy of
139-56.
BCG in HIV-infccled children is not known. One small
10
Bornschlugcl
K, Thomas P, Channing K, Salelan S, Kaye K.
case-control study showed no el'ficacy in I IIV-infecled
Tuberculosis
in
children born to 1 IIV inlecled women in New
children compared to 59% efficacy in uninfected children
York City (Abstract). XI International Conference on AIDS,
of HIV seropositive mothers”.
Vancouver, Canada. 1996.
Conclusion
U. Whalen C. Copathogenicity of tuberculosis and human
immunodeficiency virus disease. Clin Infect Dis (In Piess).
Tuberculosis is the commonest opportunistic infection in
the HIV-infected population in developing countries, 12. Folks TM, Justement J, Kinter A, Dinarello CA, Fauci AS.
including India. There has been an increase in the
Cytokine-induced expression of HIV-1 in a chronically
infected promonocyte cell line. Science 1987; 238: 800-2.
incidence of tuberculosis following the HIV epidemic. ’T he
clinical and radiological manifestations of tuberculosis are 13 Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor alpha
similar to those seen in I II V-uninfected individuals, except
and interleukin I stimulate the human immunodehciency
virus enhancer by activation of the nuclear factor kp. Proc
in those with advanced immunodeficiency, where atypical
presentations may be seen. Most patients respond well to
Natl Acad Sci USA 1989; 86: 2336-40.
standard chemotherapy, but mortality remains high 14. Lederman MM, Georges DL, Kusner DJ, Mudido P, Ciam
CZ, Toossi Z. Mycobacterium luberciilosi^ and its purified
primarily because of other opportunistic infections.
protein derivative activate expression of human
Prophylactic chemotherapy is effective in reducing the
immunodeficiency virus. / Acquir Immune I bf ic Syndr 1991;
incidence of tuberculosis in those with latent infection.
7: 727-33.
BC(vaccination is recommended in inlanls born to 111V
seropositive mothers unless they have evidence ol 15. Zhang Y, Nakata K, Weiden M, Rom WN. Mycobaclcrium
tuberculosis enhances human immunodeficiency virus - I
advanced immunodeficiency. However, the efficacy of
replication by transcriptional activation at the long terminal
BCG in preventing tuberculosis in these children in not
repeat. J Clin luucsl 1995; 95: 2324-31.
known.
16. I larries AD. Tuberculosis and human immunodeficiency virus
REEERENCES
infection in developing countries. Liiicct 1990; 335: 387-90.
Centers for Disease Control and Prevention. Revision of the l7. , |iirries AD, Nyangulu DS, Kangombe C el ill. 1 he scourge
CDC surveillance ease definition for acquired ol | HV-related tuberculosis : a cohort.study "' •'
l'
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21. TopleyJM, Bamber S, Coovadia HM, Corr PD. Tuberculous 28. Narita M, Ashkin D, Hollender ES, Pitchenick AE. Paradoxical
worsening of tuberculosis following anti-retroviral therapy
mcniny.ilis and co-infeclion with I 11V. /\iiii Tmp Pticdinlr 1998;
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22. Jeena PM, Mitha T, Bamber S, Wesley A, Coutsoudis A,
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Perriens JH, Colebunders RL, Karahunga C et al. Increased
Coovadia HM. Effects of the human immunodeficiency virus
mortality and tuberculosis treatment failure rate among
on tuberculosis in children. Tuberc l.ung Dis 1996; 77: 437-43.
human immunodeficiency virus (HIV) seropositive
23. American Academy of Pediatrics, Committee on Pediatric
compared with HIV seronegative patients with tuberculosis
AIDS. Evaluation and medical treatment of the HIV-exposed
treated with "standard" chemotherapy in Kinshasa, Zaire.
infant. Pediatrics 1997; 99: 909-17.
Am Rev Respir Dis 1991; 144: 750-5.
24. Johnson JL, Vjecha MJ, Okwera A et al. Impact of human
30. Small PM, Schccter GF, Goodman PC, Sande MA, Chaisson
immunodeficiency virus type-1 infection on the initial
RE, Hopewell PC. Treatment of tuberculosis in patients with
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tuberculosis in Uganda. Makereie University-Case Western
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Witkor SZ, Sassan-Moroko M, Grant AD et al. Efficacy of
Dis 1998; 2: 397-404.
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25. Bekcdam HJ, Boeree M, Kamenya A el al. Tuberculous
morbidity and mortality in HIV-1 infected patients with
lymphadenitis, a diagnostic problem in areas of high
tuberculosis in Abidjan, Cote d'Ivoire: a randomized
prevalence of HIV and tuberculosis. Trans Roy Soc Trop Med
controlled trial. Lancet 199; 353: 1469-75.
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32. O'Brien KL, Ruff AJ, Lous MA et al. Bacillus Calmette-Guerin
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Bhat G, Diwan V, Chintu C, Kabika M, Masona J. HIV, BCG
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Mathew S, Perakath B, Nair A, Sheshadn MS,
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249-250.
manifestations and outcome of HIV/AIDS
among children diagnosed at our hospital, to
add to the emerging description of clinical
manifestation of HIV infection among
children in India.
Subjects-and Methods
Valsan Philip Verghese
Thomas Cherian
Anil J. Cherian
P. George Babu*
T. Jacob John*
Chellam Kirubakaran
P. Raghupathy
The
The global
global pandemic of acquired
immunodeficiency syndrome (AIDS) has
already claimed an estimated five million
lives(l). Pediatric AIDS threatens much of
the progress made in child survival in
developing countries over the past ten to
fifteen years. The earliest reports of AIDS in
Indian children have come from multi
transfused thalassemic children(2). More
recent reports have described the clinical
manifestations in children with perinatally
acquired infection(3,4). This report describes
the
mode
of
transmission,
clinical
INDIAN PEDIATRICS
The clinical case records of children
diagnosed to have HIV infection at our
hospital from January 1988 to March 2001
were reviewed. All children had .a detailed
history and clinical examination performed at
the first visit. Serological testing was
performed in 45 children because of
symptoms suggestive of HIV infection, in 35
children because their parents had positive
HIV ELISA tests, and in 8 children as part of
preoperative screening. HIV infection was
defined using the revised surveillance case
From the Departments of Child Health and Clinical
Virology*, Christian Medical College Hospital,
Vellore 632 004, India.
Correspondence to: Dr. Thomas Cherian, Department
of Child Health, Christian Medical College
Hospital, Vellore 632 004, India.
E-mail: cheri@cmcvellore.ac.in
Manuscript received: June 26, 2000;
Initial review completed: July 27, 2000,
Revision accepted: June 14, 2001.
57
VOLUME 39—JANUARY 17, 2002
BRIEF REPORTS
definition for HIV infection(5), and children
were classified into clinical categories using
the revised CDC classification of 1994(6).
Children younger than 18 months were
considered HIV-infected if they tested posi
tive on HIV RNA-PCR assay, or, in addition
to positive serology (repeatedly reactive
ELISA and confirmatory Western Blot), they
had increased serum immunoglobulins,
depressed CD4 lymphocyte count and mani
fested evidence of symptomatic HIV infec
tion (AIDS-indicator conditions diagnosed
definitively or presumptively, or recurrent
bacterial infections) that met criteria included
in the 1987 pediatric AIDS surveillance case
definition(7).
monitoring,
elevated
serum
lactate
dehydrogenase (LDH), presence of diffuse
infiltrates on the chest radiograph and
response to co-trimoxazole(7,8); in one child
who failed to respond to co-trimoxazole,
diagnosis was confirmed by post-morterm
lung biopsy. Lymphoid interstitial pneumonia
(LIP) was diagnosed on the basis of chronic
cough and presence of reticulonodular
opacities on the chest radiograph, with or
without hilar lymphadenopathy, persisting for
more than 2 months and unresponsive to
antimicrobial or antituberculous therapy(7).
Esophageal candidiasis was diagnosed in the
presence of recent onset of retrosternal pain
on swallowing and oral candidiasis(7) and
resolution of symptoms with fluconazole
therapy; diagnosis was confirmed with a
barium swallow in one of the 4 patients.
Tuberculosis was diagnosed on the basis of
chronic cough and fever, failure to thrive and
weight loss, persistent radiographic findings
despite adequate antibiotic therapy; and
clinical and radiological improvement with
antituberculous therapy(9). Encephalopathy
was diagnosed using CDC criteria(6).
Serological diagnosis of HIV infection
was made on repeatedly reactive ELISA
testing (UBI HIV 1/2 EIA, Beijing United
Biomedical Ltd., China; DETECT HIV,
Biochem Immunosystems Inc., Canada;
ABBOTT EIA PLUS, Abbott, USA) and
confirmed by Western blot (HIV Blot 2.2
Gene Labs, Singapore; IMMUNOBLOT
INNOLIA, Immunogenetics, Belgium). HIV
RNA testing was done using an RT-PCR
assay (AmplicorHIV 1 Monitor Test Version
1.5, Roche Diagnostics, NJ, U.S.A.). CD4
lymphocyte subset testing was done using a
flowcytometer (Becton Dickinson Facscan,
USA) or using an ELISA test (Capcellia CD4/
8, Sanofi Diagnostics Pasteur, France).
Addtional investigations were done as
clinically indicated.
Only 7 children were started on anti
retroviral therapy owing to cost constraints.
Coexisting infections were treated using
appropriate antimicrobial drugs. All severely
immunosuppressed children and, after 1995,
all HIV-exposed infants aged 6 weeks to
12 months received prophylaxis against
Pneumocystis carinii (10). Data from the
questionnaires and clinical case records was
entered and analyzed using the software SPSS
for Windows (Version 7.5).
Microbiological confirmation of diag
nosis of tuberculosis and Pneumocystis
carinii pneumonia (PCP) was not always
possible. In such cases guidelines from the
1987 CDC surveillance case definition were
used. PCP was diagnosed based on findings of
persistent cough and/or tachypnea with
minimal findings on auscultation, hypoxemia
on pulse oximetry or arterial blood gas
INDIAN PEDIATRICS
Results
Eighty-eight children, 50 boys and 38
girls, were included in the study. Seventy
seven (87%) of the .88 had acquired infection
by perinatal transmission. Nine children
58
VOLUME 3 9-J ANUARY 17,2002
GO
BRIEF REPORTS
Table I enumerates the various clinical
manifestations seen in these children.
Organisms isolated from pus culture from
abscesses and suppurative foci were Group A
beta-hemolytic streptococci, enterococci,
coagulase-negative
staphylococci
and
Staphylococcus aureus, and from ear pus in
children with recurrent otitis media were
Pseudomonas aeruginosa, E. coli and Proteus
mirabilis.
(10%) acquired infection following blood
transfusion. Three children with thalassemia,
one with Fanconi anemia and one with
classical hemophilia developed infection
following multiple blood transfusions that
started between 1986 to 1993; of these, one
child acquired the infection as late as 1998.
Three children were transfused with their
fathers’ blood in the neonatal period in 1989,
1990 and 1994, respectively; the fathers were
later found to be HIV positive and the mothers
HIV negative. The ninth child was transfused
with an unrelated donor’s blood in 1994
following a road traffic accident; both parents
were HIV negative. In two children the mode
of transmission could not be ascertained. In a
15 month old child infection was proved by
HIV RNA testing but both parents were
negative on repeated testing using both
ELISA and Western Blot and there was no
definite history of blood or blood product
transfusion. In another 10-year-old asympto
matic girl whose mother was HIV negative
sexual abuse was considered. Her father had
died a year previously reportedly with
tuberculosis and genital ulcers.
Of the 23 children with recurrent diarrhea,
enteric pathogens were isolated in only five
(Salmonella typhimurium, enteropathogenic
E.coli, Vibrio cholerae (2 children) and
Shigella sonnet). The organisms isolated in
blood culture from the six children with
documented septicemia were Staphylococcus
aureus (2 children), coagulase-negative
staphylococci, Enterococcus faecalis (2
children), Salmonella typhimurium, and
Pseudomonas aeruginosa. In all three
children with meningitis no organisms were
isolated on CSF culture, and antigen detection
for H. influenzae type b, pneumococcus and
cryptococcus were negative.
All 12 children diagnosed to have
tuberculosis (11 pulmonary and 1 miliary)
had parents with pulmonary tuberculosis. The
Mantoux test was positive (10 x IO mm) in
only two; induration was less than 5 mm in the
remaining children. Acid fast bacilli (AFB)
were seen in smear and isolated in culture
from fasting gastric juice in only 4 children
though at least three specimens were
collected from each child with suspected
tuberculosis. Radiographic findings in the 11
children with pulmonary tuberculosis
revealed only a right hilar node in 1 child,
diffuse infiltrates in 4 children, and segmental
or lobar lesions in 6 (of whom 2 had pleural
effusions and 2 had hilar adenopathy in
addition). Of the 12 children, 3 have
completed therapy, 4 are-still on treatment and
The median duration of follow up was 8
months (range 1 to 156 months). Twenty
seven children are still on regular follow up.
Ten children died, and 51 children were lost to
follow up at varying periods following
diagnosis of HIV infection.
Twelve children were asymptomatic
(category N). Seventy-six children were
symptomatic, with 18 children in category A,
27 in category B and 31 in category C. The
age at onset of symptoms ranged from 1
month to . 10 years. Thirty six of the 76 (47%)
became symptomatic before 12 months of
age; all but 3. were infected perinatally. The
remaining 40 became symptomatic at 20 to
120 months of age; 35 were infected
perinatally.
INDIAN PEDIATRICS
59
VOLUME 39—JANUARY 17, 2002
11
BRIEF REPORTS
TABLE 1-Frequency of Clinical Manifestations oj
HIV Infection
regular follow up and are responding, 4
children were lost to follow up and one child
died due to fulminant hepatitis 2 weeks after
initiating anti-tuberculous therapy.
Number
Percentage
55#
46
33*
23
19
19+
16
12
72
60
43
30
25
25
21
16
Six
children
were
presumptively
diagnosed to have PCP; CD4 counts done in 4
of these children showed evidence of severe
immunosuppression in 3. All six had oral
candidiasis. Two died in hospital; one was 41/z
months old and the other 21/z years old; post
mortem lung biopsy done in one showed
presence of P. carinii cysts in the alveolar
spaces.
Category B Symptoms
44
Failure to thrive
23
Recurrent diarrhea
20
Candidiasis (oral)
13
Pneumonia (single episode)
11
Pulmonary tuberculosis
6
Septicemia
3
Meningitis
3
Giant molluscum contagiosum
Lymphoid interstitial pneumonia 2
2
Hepatitis
1
Cardiomyopathy
58
30
26
17
14
8
4
4
2.6
2.6
1.3
Of the 21 children with evidence of
encephalopathy by CDC criteria, 11 had
progressive encephalopathy, with regression
of milestones, spasticity and hyperreflexia;
one had dysarthric speech, two had ataxia,
two had hemiplegia and two . had wellcontrolled seizures in addition. We were able
to obtain CT scans in only two children; both
showed evidence of cortical atrophy and one
child had basal ganglia calcifications in
addition.
Category A Symptoms
Hepatomegaly
Lymphadenopathy
Splenomegaly
Papular urticaria
Pyoderma (recurrent)
Dermatoses (other)
Otitis (recurrent)
Parotitis (recurrent)
Category C Symptoms
Encephalopathy
Pneumonia (recurrent)
21
(Progressive 11)
14
Pneumocystis carinii pneumonia
Esophageal candidiasis
Pyopericardium
Septic arthritis
Miliary tuberculosis
CMV pneumonia
6
4
1
1
1
1
Ten children died. Six of the ten were
younger than 12 months, and the oldest was
50 months old at death. Documented (by post
mortem biopsy) causes of death in 4 of the 6
children who died in hospital were
Pneumocystis carinii pneumonia in one,
cytomegaloviral (CMV) pneumonia in one,
dilated cardiomyopathy in one, and fulminant
hepatitis in one. The fifth child died in
hospital following an attack of cholera with
persistent acidosis and hypokalemia, and in
the sixth a clinical diagnosis of PCP was
made, but we were unable to confirm the
diagnosis as the parents refused permission
for post-mortem lung biopsy. Four children
died at home; one had acute watery diarrhea,
two died of bronchopneumonia that did not
respond to oral antibiotics, and the fourth died
28
18
8
5
1.3
1.3
1.3
1.3
# includes 3 children with hepatomegaly due to
thalassemia.
* includes 2 children with splenomegaly due to
thalassemia.
+ seborrheic dermatitis, yiral warts, varicella zoster,
oral herpes simplex, pediculosis, icthyosis: 1 pa
tient each; 2 patients with herpes zoster and tinea
infection, 1.1 patients with scabies.
INDIAN PEDIATRICS
60
VOLUME 39—JANUARY. 17, 2002
^"2BRIEF REPORTS
at home with severe progressive ence
phalopathy.
Discussion
Though our data show that the mode of
acquisition and clinical manifestations of
pediatric HIV/AIDS in India are not
substantially different from that reported in
other countries, there are several important
aspects of the disease that we would like to
highlight.
Transfusion-associated transmission of
HIV continues to occur in India despite
regulations requiring screening of donors,
either because screening procedures are not
being followed or because transmission may
occur despite screening. The former is likely
in the case of the children infected from
transfusions from their fathers. Many small
hospitals without access to blood banks may
transfuse patients with blood from a close
relative without screening in the mistaken
belief that the blood would be safe. Our data
shows that this is not necessarily true and that
unscreened blood must not be used,
irrespective of the donor.
Our data also shows that a bimodal
progression occurs in Indian children, as
described in other countries(l 1). A significant
proportion of patients present in infancy and
have severe disease and early death, while
children surviving beyond 5 years of age tend
to have only moderate signs and symptoms
and have longer survival.
urticaria, thought to be due to a hyper
sensitivity reaction to environmental factors
or allergens such as insect saliva or mosquito
bites, was commonly seen in our patients.
This condition has been described as one of
the initial manifestations of HIV infection in
Haitian adults and children(l3,14).
Respiratory infections were a common
problem in our series. Microbiological
confirmation of tuberculosis and Pneumo
cystis carinii penumonia was not always
possible, and diagnosis was often pres
umptive, based on clinical criteria and
response to therapy. As in other studies from
India and other tropical countries(4,13),
bacterial pneumonia occurred more fre
quently than PCP and LIP. This may reflect
the greater importance of bacterial infections
in tropical countries as well as limited
diagnostic options for the diagnosis of PCP
and LIP. A recent Indian study has shown a
4% incidence of PCP when confirmed with
bronchoalveolar lavage(4). In India, where
definitive diagnosis using bronchoalveolar
lavage or lung biopsy are seldom feasible,
using presumptive criteria for early diagnosis
of Pneumocystis carinii pneumonia and PCP
prophylaxis in infants of HIV-positive mother
may prevent one of the major causes of death
in infancy.
Our experience is similar to other studies
showing that HIV-infected children with
tuberculosis often have a negative tuberculin
test(3,15), the proportion of children with
positive smears or cultures is low(16), and
that clinical and radiological features do not
differ from children without HIV infection.
The common clinical manifestations of
HIV infection such as hepatomegaly,
generalized lymphadenopathy and spleno
megaly, and skin infections, recurrent
diarrhea, and failure to thrive are the same as
in studies of HIV-infected children in both
Western(12) and tropical countries(13), and
in recent reports from India(3,4). Papular
INDIAN PEDIATRICS
The high incidence of encephalopathy in
this series of children is comparable to other
studies in both developed(17) and developing
countries(4,18), and highlights the need for
developmental and neurological assessment
of the HIV-infected child at each visit.
61
VOLUME 39—JANUARY 17, 2002
BRIEF REPORTS
Key Messages
• Though the predominant route of transmission of HIV infection is vertical, transmission
via blood transfusion still takes place.
• There was evidence of a bimodal progression of disease due to HIV infection.
• Clinical manifestations of HIV infection were similar to those described in developed
countries, except that bacterial infections were commoner than opportunistic infections.
•
In the absence of easily affordabie antiretroviral therapy, prompt diagnosis and treatment
of bacterial infections, and PCP prophylaxis may be the keys to prolonging life and ensuring
optimal health in children with HIV infection.
Among the 10 children who died, the
predominant causes of death were respiratory.
Since a proportion of these could be due to
PCP, prophylaxis for all HIV-exposed infants
from 6 weeks to 12 months of age may be
important in reducing mortality.
Contributors: VPV and TC designed the study,
enrolled the patients, carried out follow up, analyzed
the data and prepared the manuscript. AJC helped
with patient enrolment and follow up. PGB
performed the serology. TJJ, CK and PR assisted in
patient enrollment, data analysis and manuscript
preparation.
Funding: None.
5.
Centers for Disease Control and Prevention.
Revised surveillance case definition for HIV
Infection. Mor Mortal Wkly Rep 1999;
48(RR13): 29-31.
6.
Centers for Disease Control and Prevention.
Revised classification system for human
immunodeficiency virus infection in children
less than 13 years of age. Mor Mortal Wkly
Rep 1994;43(RR 12): 1-10.
7.
Centers for Disease Control and Prevention.
Revision of the CDC surveillance case
definition for Acquired Immunodeficiency
Syndrome. Mor Mortal Wkly Rep 1987;
36(Suppl): 1S-15S.
8.
O’Brien RF. In search of shortcuts: Definitive
and indirect tests in the diagnosis of
Pneumocystis carinii pneumonia in AIDS.
Am Rev Resp Dis 1989; 139: 1324-1327.
9.
Chintu C, Bhat G, Luo C, Raviglione M,
Diwan V, Dupont HL, et al. Seroprevalence
of human immunodeficiency virus type 1
infection in Zambian
children
with
tuberculosis. Pediatr Infect Dis J 1993; 12:
499-504.
10.
Centers for Disease Control and Prevention
1995 Revised guidelines for prophylaxis
against Pneumocystis carinii pneumonia for
children infected with or perinatally exposed
to human immunodeficiency virus. Mor
Mortal Wkly Rep 1995; 44(RR 4): 1-10.
11.
Italian Register for HIV infections in
Children. Features of children perinatally
Competing interests: None stated.
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Merchant RH, Oswal JS, Bhagwat RV,
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62
volume 39-january 17, 2002
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clinical presentation and outcome of
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D’Ivoire. AIDS 1997; 11: 1151-1158.
infected with HIV-1 surviving longer than 5
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Galli L, deMartino M, Tovo P-A, Gabiano C,
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Garay JE. Clinical presentation of pulmonary
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17.
Cooper ER, Hanson C, Diaz C, Mendez H,
Abboud R, Nugent R, et al. Encephalopathy
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18.
Mukadi YD, Wiktor SZ, Coulibaly I-M,
Coulibaly D, Mbengue A, Folquet AM, et al.
Impact of HIV infection on the development,
Drotar D, Olness K, Wiznitzer M, Guay L,
Marum L, Svilar G, et al. Neurodevelopmental outcomes of Ugandan infants
with human immunodeficiency virus type 1
infection. Pediatrics 1997; 100: e5.
Evaluation of Chronic Cough in
Children: Clinical and Diagnostic
Spectrum and Outcome of
Specific Therapy
tracheobronchial tree from potentially
injurious substances and by removal of
endogenous secretions and other materials,
such as pus, necrotic tissue and foreign
bodies(l).
V.S. Dani
Sandeep S. Mogre
Rajendra Saoji
Chronic cough needs to be evaluated for
the underlying disease in a systematic manner
regarding the nature of cough, timing of
cough, onset of cough, site of pathology,
associated clinical features, response to
13.
!
14.
15.
*
Jean SS, Reed GW, Verdier R-l, Pape JW,
Johnson WD, Wright PF. Clinical
manifestations of human immunodeficiency
virus infection in Haitian children. Pediatr
Infect Dis J 1997; 16: 600-606.
Liautaud B, Pape JW, DeHovitz JA, Thomas
F, LaRoche AC, Verdier RI, et al. Pruritic
skin lesions: A common initial presentation
of Acquired Immunodeficiency Syndrome.
Arch-Dermatol 1989; 125: 629-632.
<
From the Department of Pediatrics, Indira Gandhi
Medical College and Hospital, Nagpur, Maha
rashtra, India.
Correspondence to: Dr. Mrs. V.S. Dani, Gandhi Sagar
Cough may be voluntary or involuntary,
infrequent and hardly noticeable or painful,
disruptive and debilitating. Cough may be
viewed as a continuum of health through
disease and is a useful host defense
mechanism. Cough gives protection to the
INDIAN’ PEDIATRICS
(East), Mahal, Nagpur 440 002, Maharashtra,
India.
Manuscript received: January 29, 2001;
Initial review completed: March 13, 2001;
Revision accepted: June 13, 2001.
63
VOLUME 39—JANUARY 17, 2002
WORLD HE >MTH OR'^ANIZATlQN ■ FAMiLY AND COMMUNITY HEALTH CLUSTER •DEPARTMENT OP
Contents
2. Use of antiretroviral drugs for MTCTprevention
3
I
Primary prevention of HIV infection among future parents and
l avoidance of unwanted pregnancies among women infected with
i HIV are fundamental long term strategies in the prevention of
; transmission of HIV to infants. However, many HIV-infected
; women become pregnant and others may acquire HIV infection
j during pregnancy. The use of antiretroviral drugs during pregnancy and delivery has been shown to be i
| effective in reducing the transmission of HIV from mothers to infants. These regimens reduce the risk
|
I of MTCT by decreasing viral replication in the mother and through prophylaxis of the infant during and
I after exposure to the virus.
! This section reviews the evidence available to date on efficacy and safety of antiretroviral regimens,
| including those based on nevirapine, for MTCT-prevention.
I
I
Remarkable reductions in paediatric HIV infection rates have been observed in industrialized countries
■ since 1994 when the Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 showed that
j administration of zidovudine to women from the fourteenth week of pregnancy and during labour, and
i to the newborn decreased the risk of MTCT by nearly 70% in the absence of breastfeeding? When
________ ______
I combined with elective caesarean section this regimen resulted in <a transmission rate of 2% or less, in
non-breastfeeding populations/'0 The use of combination antiretroviral regimens, known as highly
; active antiretroviral therapy or HAART, for the treatment of HIV-infected individuals has resulted in
i similar low vertical transmission rates when used by pregnant women.9
I
I The cost and complexity of these regimens have restricted their use in resource-poor settings.
I
i
I
i
I
I
i
However, from 1998, a shorter zidovudine alone regimen starting from 36th week of pregnancy was
!
I shown to reduce the risk of transmission of HIV at 6 months by 50% in a non-breastfeeding
population12 and by 37% in breastfeeding populations.^12 Other clinical trials have shown that short
course antiretroviral regimens using the combination zidovudine and lamivudine,12 or nevirapine alone1^
i
also substantially decrease the risk of HIV transmission (Table 3).
I
I
I
I
1
i
i
Ii
■
|
Ij
I
1
|
t
I
*
Table 3. Use of antiretroviral regimens for MTCT-prevention
Reference):
Schedule^
PraaicaHty
Effica^*/Trahsmission Rates/Comments
NON-BREASTFEEDING POPULATIONS
ACTG076/
ANRS0246
ZDV
Pregnancy: from wk 14
lOOmg 5 times dly.
Intrapartum:
2mg/kg intravenous (IV)
infusion over 1 h,
continuous hly IV infusion
of 1 rng/kg
Postpartum Infant:
2 mg/kg orally 6 hly for 6
wks
Thai short
course'13
ZDV
Pregnancy: from wk 36
300mg twice dly
Intrapa rtum:
300mg 3 hly
PH PT,
Thailand12
ZDV
Long-Short,
Long-Long
Pregnancy: from wk 28
300mg twice dly
Intrapartum: 300mg 3
hly
Postpartum Infant:
2mg/kg 6 hly for 3 days or
6 wks
Short-Long
Pregnancy: from wk 35
300mg twice dly
Intra partum:
300mg 3 hly
Postpartum Infant.
2mg/kg 6 hly for 6 wks
+++
4- + 4- +
18-mth efficacy 68%
18-mths transmission rate 8%
Original regimen.
Requires extensive resources.
+++
++
+++
+++
++
6-mth efficacy 50%
6-mths transmission rate 9%
7
I
6-mths transmission rate 6%
May be slightly better than 'Thai short course'
++ +
+++
6-mths transmission rate 8%
Similar to 'Thai short course'
I
BREASTFEEDING POPULATIONS
i
I
i
BREASTFEEDING POPULATIONS
CDC, W
Africa12
ZDV
Pregnancy:
from wk 36
300mg twice dly
Intrapartum:
300mg 3 hly
DITRAME/
ANRS 049a
W Africali
ZDV
Pregnancy:
from wk 36
300mg twice dly
Intrapartum: 600mg
Postpartum mother:
300mg twice dly for 1
week
PETRA Arm
A13
ZbV+3TC
Pregnancy: from wk 36
ZDV+3TC twice dly
intrapartum: ZDV 3hly/
3TC twice dly
Postpartum mother:
ZDV+3TC
twice dly for 1 wk
Postpartum Infant:
ZDV+3TC
twice dly for 1 wk
PETRA Arm
Intrapartum: ZDV 3hly/
3TC twice dly
Postpartum mother:
ZDV/3TC twice dly for 1
wk
Postpartum Infant:
ZDV+3TC twice daily for 1
wk
& SAINT18
ZDV+3TC
HIVNET 012h
& SAINT18
NVP
Intrapartum: 200mg at
start of labour (HIVNET) or
at hospital intrapartum
(SAINT)
Postpartum mother:
200mg stat (SAINT only)
Postpartum Infant:
2mg/kg stat within 48 hrs
(SAINT) or
72 hrs (HIVNET 012)
z
V'
+++
++
6-mth efficacy 37%
3-mths transmission rate 17%
++
++
6*-mth efficacy 38%;
6 mths transmission rate 18%
Pooled 24-mth W African data
CDC/DITRAME: 28% efficacy and transmission
rate 22%
+++
6-wk efficacy 54%
6-wks transmission rate 7%
+
+++
PETRA: 6-wk efficacy 39%
6-wk transmission rate 10%
SAINT: 6-wk transmission rate 10%
Programmatically attractive because of
simplicity and relatively low cost.
++++
HIVNET 012: 14-16-wk efficacy 47%;
6-wks transmission rate 12%
12-mth efficacy 42%;
12-mths transmission rate 16%
SAINT: 8-wks transmission rate 13%
Programmatically very attractive because of
simplicity and very low cost. Concerns over
drug resistance in women who have access to
ARV therapy.
Efficacy: Percentage reduction in HIV transmission rate in active arm compared with placebo, except for NVP which was
compared in HIVNET012 with a probably ineffective regimen consisting of intrapartum ZDV for the mother and 1 week post
partum for the infant
ZDV: Zidovudine 3TC: Lamivudine NVP: Nevirapine ARV: Antiretroviral
Adapted from: Efficacy of Antiretroviral Regimens for the Prevention of Mother to Child Transmission of HIV and Some
Programmatic Issues : Farley T, Buyse D, Gaillard P, Perriens J. Background documents for WHO Technical Consultation
October 2000.4
o
Short term efficacy as determined by infant's infection status at 6-8 weeks of life has been
demonstrated for the short course prophylactic regimens comprising zidovudine alone, zidovudine plus
lamivudine, or nevirapine alone. Long term efficacy as determined by the child's infection status at 24
months of age has been evaluated for the short course zidovudine regimen, and at 18 months of age
for the nevirapine regimen, in breastfeeding populations.^ Available data indicate that the proportion
of children acquiring HIV through breastfeeding was comparable in both these regimens and the early
difference in reduction of HIV transmission persisted despite continued exposure to HIV through
breastfeeding. Assessment of the long-term efficacy of the zidovudine plus lamivudine regimen in such
populations is still in progress.
All regimens include an intrapartum component, with varying duration of antepartum and/or
postpartum prophylaxis. While the efficacy of the more complex regimens which include antepartum,
intrapartum and postpartum components is somewhat higher^the single dose nevirapine regimen
provided during labour to the mother and postpartum to the infant has also been shown to be
efficacious and is more practical.
——
2,2 g
For women and infants who are offered antiretroviral prophylaxis of MTCT, the risk associated with
exposure to one or more drugs must be weighed against the benefit of reducing the risk of transmission
to infants of a fatal infection. Short-term safety and tolerance of the antiretroviral prophylactic
regimens has been demonstrated in all the controlled clinical trials on MTCT-prevention. Collection of
data on long-term safety and on patterns of resistance to the antiretroviral drugs is ongoing.
2.3 choice ot antiretroviral reyimenfs)
The choice of regimen(s) to be included in a MTCT-prevention programme should be detecmined by
assessment of feasibility, efficacy, acceptability and cost. However, it should be noted that drug costs
may represent only a fraction of the costs of the services that are required for an effective MTCTprevention programme.
Practical considerations in choosing antiretroviral regimens for MTCT-prevention
I
nr
1
.
5... i'
-------.............................. -........
Baa
'• - - ? < ■ •} .■'
......... - — ....................... .......... . .............. ——...
Proportion.erf;births .occurring in±ealiK.rarefe
......----------
. /
r:.. • _
r.-. • -. -
. - /
:. ■ ..'r:.-.
2=4 Use of nevirapine for MTCT-prevention
In recent years, the use of nevirapine has attracted considerable attention because of its demonstrated
efficacy in clinical trials in reducing MTCT, low cost and ease of use in MTCT-prevention programmes.
Further information about its use for this purpose is provided below.
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to HIV-1
reverse transcriptase, slowing the rate of viral DNA synthesis and thereby inhibiting viral replication.
Nevirapine is rapidly absorbed when given orally to adults, and has a long elimination half-life ti/2 of
approximately 40 hours. Nevirapine crosses the placenta efficiently after a single oral 200 mg dose to
the mother at the onset of labour. In infants, median ti/2 ranges from 45 to 72 hours for elimination of
the maternal nevirapine, and from 37 to 46 hours for the elimination of a single 2mg/kg neonatal
dose.12
Short-term safety and tolerance of single dose nevirapine has been demonstrated in clinical trials. Data
from 38 women and infant pairs enrolled in the initial phase I trials, PACTG 250 and HIVNET 006,
showed no rash or serious adverse events detected either through laboratory tests of through
observation of clinical symptoms in women or infants, attributable to nevirapine. In the HIVNET 01214
and SAINT studies,15 960 women and infant pairs were exposed to the intrapartum/newborn nevirapine
regimen, there were no significant differences in serious toxicity, occurrence of rash, anaemia, liver
abnormalities or death between nevirapine and short course regimens of zidovudine or
zidovudine/lamivudine in women or infants. In the PACTG 316 study, 1506 women receiving
antiretroviral treatment (usually combination therapy) were randomized to receive extra dose of
nevirapine or placebo at the time of delivery. There was no difference in maternal or infant toxicity
between the two study arms.22 Collection of long-term safety data following administration of single
dose nevirapine is ongoing.
Selection of resistant virus has been observed among some women and infants who received single
dose nevirapine21'22 or lamivudine.22'23 for preventing MTCT. The resistant virus will revert to wild type
susceptible strains within 12 to 24 months after stopping the treatment with nevirapine. The clinical
1
-I I
significance of the emergence of resistance in the context of MTCT prevention programmes is as yet
unknown, particularly with regard to future treatment options for the mother or the child, or to the
outcome of prophylaxis during a subsequent pregnancy if the same drug is used. The WHO Technical
Consultation in October 2000 carefully reviewed the available information and concluded that the
benefit of decreasing mother-to-child HIV transmission with these antiretroviral drug prophylaxis
regimens greatly outweighed concerns related to development of drug resistance.1
Nevirapine and zidovudine were included in the WHO Model List of Essential Drugs in 1999, solely for
the indication of MTCT prevention of HIV.24 The HIVNET 012 regimen of nevirapine used for MTCT-
prevention is a single 200 mg oral tablet to be taken by the mother at the onset of labour and a single
oral dose of nevirapine in suspension (2 mg/kg) to be given to the newborn within 72 hours of birth.
Experience in the field suggests that the oral tablet for the mother can be taken at home at onset of
labour. However, it is essential that the child should be brought to a health facility within 72 hours of
birth for the oral dose of nevirapine in suspension.
Previous section I Contents I Next section
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I
Organization (WHO), and all rights are reserved by the Organization. The document may, however, be freely
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I
;
f
I
HIV Physician Training Course 2002,
Christian Medical College, Vellore
DISTANCE LEARNING COURSE
SAFE BLOOD BANKING
Author: JoyMammen
Course Organiser : Anand Zachariah
Distance Learning Expert: Janet Grant, Open University, UK
This course is supported by the European Commission through grant number
IND/B76211/1B/1999/0379 provided to the HIV/STI Prevention and Care Research
Programme of the Population Council India.
MODULE 4
‘J
1
MODULE 4
OVERVIEW
This module will help you examine blood safety procedures in your
institution's blood bank or that in your locality and to consider what
improvements are needed in blood banking in your own situation.
Millions of lives are saved by blood transfusion. However people who receive
blood that has not been properly collected or tested are at risk of developing
transfusion transmissible infections (TTI) including HIV, Hepatitis B,
Hepatitis C and malaria. In India it is estimated that 0.8 % of all HIV infection
is transfusion-related (24,000 cases of estimated 3,000,000 HIV positive
individuals). The problem of transfusion-related hepatitis C is even greater.
A safe blood supply can be achieved only if:
(a) Blood donors are volunteers and not paid to donate blood and a large
pool of such volunteers is maintained.
(b) Potential donors are interviewed by trained staff to exclude those who
are at high risk of harboring TTIs.
(c) All blood is screened appropriately for TTIs including HIV, Hepatitis B
and C and malaria.
(d) Unnecessary blood transfusions are
i
avoided by educating medical
staff on the transfusion guidelines.
All blood banks should aim to achieve these standards of blood safety.
OBJECTIVES
After completion of this module you should be able to:
1. Understand the advantages of voluntary donation and consider ways of
increasing your local volunteer donor pool.
2
MODULE 4
2. Outline the procedure for donor evaluation and to exclude individuals at
high risk of TTIs.
3. Enumerate the appropriate tests for screening for transfusion transmissible
infections (TTIs) and their standards.
4. List indications for use of blood and blood components.
5. Examine your set-up with regard to blood safety and consider ways in
which existing safety standards can be improved.
CONTENTS
No.
4.1
4.2
4.3
Title
Activity
Voluntary Blood Donation
15
3
Readings
Types of Blood Donors-lndia
5
31
Prevalence of TTIs
5
32
Professional blood donors
5
32
Activity
Creating a volunteer pool
10
5
Reading
Safe blood starts with me
Activity
Finding out about
4.5
4.6
7-9
20
10
of blood donors
10
38
Activity
Blood Screening for TTIs
30
13
Reading
Risk of TTIs
10
39
Activity
Clinical transfusion guidelines
30
16
Readings
Definition of blood and blood
5
40
Clinical transfusion guidelines
15
41
Activity
Staff education in transfusion
15
19
Readings
Clinical transfusion guidelines
15
41-42
Tutor Marked Assignment
60
27-29
Total estimated study time
275
Activity
Donor Evaluation
Reading
Criteria for exclusion
components
4.7
34
60
local blood bank
4.4
Time (min) Page
3
Before
you
Activity
start
4.3
Activity
yy Finding out
MODULE 4
we
4.1
about
would.
like
you
perform
Xour local blood bank.
will need to visit your local blood bank for this.
You
Only after
completing this should you come back to Activity 4.1.
The aim of the first activity is
different
types
of
blood
to help you think about
donors
and
the
advantages
voluntary donation.
To do
the next activity you
s t udy
"Types
of
the
"Prevalence
tablesr
of
TTIs
-Type
^Professional Blood Donors"
blood
of
Page
31) f
32)
and
(page
(page 32)in the readings.
have finished reading these tables you can
of
will need to
donors-India"
donor"
the
Once you
undertake the next
activi ty.
ACTIVITY 4.1
VOLUNTARY BLOOD DONATION (15 min)
What
are the advantages of using voluntary donors as the
main source of blood compared to
donors?
1.
2.
3.
family and replacement
4
MODULE 4
FEEDBACK 4.1
What are the advantages of using voluntary donors as the
main source of blood?
1. Voluntary donors have a lower incidence and prevalence of TTIs
than family/replacement donors or paid donors.
2. Voluntary donors are more likely to be willing to donate blood regularly
and in case of emergency.
3. Voluntary donors are not likely to be prone to anemia due to
frequent donations.
5
MODULE 4
The aim of the next activity is to help you consider ways of
increasing your local
volunteer donor pool.
activity you will need to study,
To do
the next
"Safe blood starts with me"
(page 34) in the readings. Once you have finished reading this
section you can undertake the next activity.
AGTIVITY4.2
CREATING A VOLUNTEER POOL (15 min)
The
authorities
encourage
the
in
your
local
volunteer blood donors
hospital
NCC
in
to
been
trying
to
their
cadets
as
have
enrol
your blood bank.
Your blood
bank has requested you to give a talk to the NCC cadets
on the topic,
"Why should I be a voluntary blood donor?".
List the points that you would present in your talk:
1.
)
2.
3.
4.
5.
6.
7.
/KrvH
6
MODULE 4
"FEEDBACK 4.2
List the points that you would present in your talk.
1. One unit of blood can save more than one life.
2. Blood is a drug for which there is no other substitute.
3. Voluntary blood donors have been found to have healthy lifestyles and
hence lower rates of transfusion transmissible infections.
4. Blood volume regenerates in 2 hours, blood cells in 2 weeks and iron
stores in 2 months. Therefore donating blood does not result in adverse
health problems.
5. If you have any condition which makes the blood that you donate
unsafe, then you need to inform the doctor who is screening you.
6. You have no risk of acquiring HIV infection by donating blood.
7. A qualified doctor will examine you before blood donation and check
you for any condition that may make blood donation unsafe for you.
8. Donating blood is a good will gesture, a way of sharing your life with
another person.
The
next
activi ty
information
about
is
aimed
at
helping
your blood bank
or
you
find
out
any nearby blood
€
bank.
For this activity you will need to make a
15-30 minute
visit to the blood bank of your hospital.
If you do not
have
a
blood
bank
then phone
or
visi t
the person
in
charge of the nearest blood bank which your institution
uses.
The information obtained in this activity will be
essential
to
this module.
the completion of subsequent
activi ties in
After completing this activity you will be
required to tear out
the 2 sheets of this activity and
send it with your tutor marked assignment to Vellore.
7
MODULE 4
ACTIVITY 4.3
FINDING OUT ABOUT YOUR LOCAL BLOOD BANK
(60 min)
For this
exercise you need to go to your institution's
blood bank or alternately, speak on the telephone to the
person in charge of the blood bank nearest to your place.
Find out the following information from the bank:
l.What is the volume of blood supplied by your bank?
No. of units/year
2. Which of the following does your bank transfuse:
(tick against those items that are applicable)
Whole blood
Packed cells
Platelet-rich concentrate
Cryoprecipitate
Plasma
3. What is the proportion of different donors?
♦
8
MODULE 4
Proportion
(%)
Voluntary
non-remunerated
donations
Family/Replacement
donations
Paid donations
4. Does your blood bank have an officer?
Yes / No
5. Identify:
a. Which of the following screening tests are used
in your blood bank.
b. Which kits are used.
c. Look at the literature on the pamphlet of the
kit to determine the sensitivity of the tests.
d. Find out the rate of infection by these tests
in the donor population
(during a recent
period).
♦
♦
9
MODULE 4
Sensitivity of Rate
Test
Kit used
the test
of
infection
in donors
HIV ELISA
9
?
HbsAg
Ant-HCV
Malarial
smear
6. Does your bank conduct education campaigns to encourage
volunteer donation?
Yes / No
7. Does your bank have a register of volunteer donors who
can be contacted?
Yes /No
8. Does your blood bank have written guidelines regarding
indications for blood and component transfusion?
Yes/ No
'^FEEDBACK 4.3
This information will be needed as you do the subsequent
exercises and we will come back to these shortly. After
completing this activity you will need to tear out the 2
sheets of activity 4.3 and send it along with your tutor
marked assignment in the addressed envelop.
10
MODULE 4
This activity aims to improve your knowledge in relation
to
donor
evaluation
and
develop
a
protocol
for
donor
evaluation. Before doing the activity, read yyCriteria for
exclusion of blood donors"
(page 38)in the reader,
Once
you have finished reading the criteria you can undertake
the next activity.
Activity 4.4
DONOR EVALUATION (20 min)
Prepare a donor evaluation form for your blood bank using
the format given below. Use the history and examination
sub-headings to list your points.
HISTORY * Recent * Past * Personal * Family * Treatment *
Systems review
)KiV■
/
./
)
11
EXAMINATION
Respiratory
*
General
MODULE 4
*
Abdomen
★
Cardiac
*
12
MODULE 4
FEEDBACK 4.4
Prepare a donor evaluation form for your blood bank using
the format given below.
HISTORY
Recent - Fever, infections, weight loss, genital ulcer, genital discharge,
gland enlargement, jaundice.
Past - Jaundice, TB, major illness, anaemia, cancer, STDs, cardiac or lung
condition , recurrent diarrhoea.
Personal - number of sex partners, IV drug use, MSM (men who have sex
with men) behaviour, alcohol abuse.
Treatment - Drugs being received, history of blood donation, received
blood
transfusion,
frequent
injections, surgeries,
previous
medical
diagnosis.
Systems review - Hepatic or haematological problems.
EXAMINATION
General: Pallor, skin lesions, jaundice, oral Candida, tattoo marks, IV drug
use marks, high and low blood pressure
Abdomen: Liver, spleen enlargement.
Cardiac: Evidence of cardiac disease.
Respiratory. Evidence of respiratory disease.
13
The
next
exercise
helps
blood
MODULE 4
you
examine
screening
the
risk
of
TTI
how
this
may
be
despite
adequate
reduced.
Tn order to do this exercise read "Risk of TTI
from
adequately
reader.
screened
and
blood"
Once you have read
(page
this you
can
from
the
undertake
the
39)
activity.
ACTIVITY 4.5
BLOOD SCREENING FOR TTIs (30 min)
1. Calculation
of risk of
infection
from transfusion of
adequately screened blood in your blood bank:
Use the data from the above reading and the total volume
of
blood
transfused
in
your
blood
bank
in
a
year
to
calculate the risk of infection from transfusion.
Eg. Risk of transfusion for HIV 1/ 493,000
If total number of units transfused = N,
Risk of HIV from adequately screened blood in your
blood bank =
N x 1/493,000
Risk of infection from transfusion in 1 year:
HIV-
Hepatitis C -
Hepatitis B -
2. What is the ideal sensitivity of a test to be used for
screening in blood bank?
14
3. Give
the
reasons
why
MODULE 4
there
are
small
risks
of
risks
of
transfusion despite properly screened blood.
1.
G>aT
c/
2.
3.
4. What
are
ways
of
further
reducing
the
transfusion?
\
1.
2.
1^. C-AA'<.O-
3.
7^.
4.
7
c
’V'sQ <• C^Li
15
MODULE 4
FEEDBACK 4.5
1. Calculation of risk of infection from transfusion of
adequately screened blood in your blood bank:
Risk of infection from transfusion in 1 year -
HIV - N/493,000
Hepatitis C-N/103,000
Hepatitis B-N/63,000
(N = Number of transfusions in a year)
figures may not
These
because
they
are
be
derived
accurate
for your blood bank
from
results
the
of
another
study.
2 . What is the ideal sensitivity of a test to be used
for screening in blood bank?
> 99%
3. The reasons why there are small risks of transfusion
despite properly screened blood.
1. Donation during window period
2. Errors in the test
3. Clerical errors
4 . What are ways of reducing the risk of transfusion
further?
16
MODULE 4
1. Using higher sensitivity tests which further reduce the window period
2. Rejection of donors who may be at high risk of infections
3. Ensure that kits are in good condition
4. Maintain a quality control system for the tests and also check that
Drug Controller of India has approved the tests.
5. Better systems to reduce clerical errors.
This
activity
aims
to
improve
your
knowledge
regarding
the
clinical guidelines for blood and blood component transfusion.
Before
doing
the
activity,
read
^Definition
of
blood
components" (page 41-42)
and ^Clinical transfusion guidelines"
in the reader.
Once you have finished reading these
(page 41)
you can undertake the next activity.
ACTIVITY 4.6
CLINICAL TRANSFUSION GUIDELINES (30 min)
Study the following clinical scenarios.
(a)
Indicate
in
column
indicated
(b)
Indicate
2
would use in your set up.
whether
which
transfusion
blood
product
is
you
17
MODULE 4
Case Scenario
transfu
Type
sion
blood
Indicat
product
of
ed
1 A 45 year old woman presents with tiredness
0/E koilonychias.
failure.
pallor,
Haemoglobin
6
no signs of cardiac
■
Microcytosis
g%
OZ/j
Hypochromia ++
2 A patient following a road traffic accident has
external
haemorrhage
and
is
found
be
to
in
shock
3 A patient with chronic liver disease comes to
the OPD with ascites.
Prothombin time
(PT) :
seconds,
-14
Partial
control
thromboplastin
time
seconds.
(PTT):
30
Patient
50
4 A patient presents with snake bite and
massive
seconds, control
haematemesis.
^0 p
30 seconds.
Prothombin time
(PT) :
Patient 2
min, control-14 seconds. Partial thromboplastin
time
(PTT):
Patient
3 minutes,
control
30
seconds.
5 A
patient
with
Idiopathic
thrombocytopenic
•
__---- --- |
thrombocytopenias
(ITP)
c/o
evidence of clinical bleeding.
Purpura.
Platelet
No
count
25, 000/cmm .
6 A patient with aplastic anaemia presents with
echymoses
and nose bleeds.
count 10,000/cmm.
Hb
3 g%,
Platelet
<
18
MODULE 4
FEEDBACK 4.6
1
Indic
Type
ated
product
of
blood
No
Explanation
There is no evidence of haemodynamic
instability and the anemia can be treated
haemateni cs.
2
Yes
Whole blood
Acute blood loss with hypovolemia is a
definite
indication
for
whole
blood
transfusion.
3
No
Coagulopathy without bleeding does not
require FFP transfusion.
4
Yes
Fresh
blood
or
FFP with packed
Coagulopathy with bleeding is a definite
indication for FFP therapy.
cells
5
No
Thrombocytopenia without life threatening
bleeding
does
not
require
platelet
transfusion.
6
Yes
rich
Use specific components in this situation:
concentrate and
packed red cells for anemia and platelet
as
rich concentrate for thrombocytopenia. In
Platelet
packed
cells
needed.
case the components are not available then
Or Fresh blood
fresh blood may be used.
MODULE 4
19
The next activity aims at helping you
think about
ways
that you can educate your staff regarding rational drug
use.
Refer back once again to the
^Clinical transfusion
guidelines" (Page 41-42) before you start this activity.
ACTIVITY 4.7
STAFF EDUCATION IN TRANSFUSION GUIDELINES
(15 min)
You have been concerned regarding the
inappropriate use
of blood products in your hospital. Your department has
asked you to prepare a pamphlet for doctors working in
your hospital to encourage the rational use of available
blood and blood components.
Use the template on the next page to guide you.
20
MODULE 4
PAMPHLET ON RATIONAL BLOOD USE
Introduction
Component
Composition
Appropriate
Inappropriate
Use
use
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21
MODULE 4
-^FEEDBACK 4.7
Introduction
Avoid unnecessary transfusions because of transfusion-associated risks.
Blood is a scarce commodity and should be used sparingly.
Components are preferred to whole blood where possible.
If components are used, many patients can benefit from a single donation.
Check details on blood bag before transfusing to prevent transfusionassociated mishaps.
Appropriate Use
Inappropriate use
Red cells
Acute blood loss
Chronic anemia without
Plasma
Exchange transfusions
symptoms
Compone
Composit
nt
ion
Whole
blood
Small
Platelets
volume
intra
operative blood loss
Packed
cell
Red cells
Acute blood loss
Chronic anemia without
Symptomatic anaemia
symptoms
Severe
pre-operative
operative blood loss
volume
intra-
operative blood loss
anaemia
Significant
Small
Intra
22
Platelet
Platelets
MODULE 4
Thrombocytopenia
with
rich
bleeding
concent
Functional
rate
disorders with bleeding
Thrombocytopenia
without bleeding
platelet
(eg. ITP with purpura)
Fresh
Protein
Replacement
of
frozen
Coagulati
coagulation
factors
Eg.
Protein source
plasma
on
Snake
DIG,
liver
Routine
pre-operative
factors
disease with bleeding
and
post-operative
bite,
multiple
Volume expansion
Treatment of bleeding in a cover
Haemophiliac
when
specific
factor
concentrates
available
are
not
23
NOTES
MODULE 4
31
MODULE 4
READINGS
TYPES OF BLOOD DQNORS-INDIA
The cornerstone of a safe and adequate supply of blood and blood products is
the recruitment, selection and retention of voluntary, non-remunerated blood
donors from low risk populations.
There are three types of blood donors:
1. Voluntary non-remunerated donor:
A donor who gives blood freely and voluntarily without receiving money or any
other form of payment.
2. Family or replacement donor A donor who gives blood when it is required
by a member of the patient's family or community. This may involve a hidden
paid donation system in which the patienfs family pays the donor.
3. Commercial or professional donor:
A donor who gives blood for money or other form of payment
The following table provides the proportion of different donors based on a
national survey of blood banks in India.
Proportion
Voluntary
non-
remunerated
39.3
donations
Family/Replacement
58.0
donations
The below tables shows the rates of TTIs in different donor groups.
32
MODULE 4
'
X
I I
PREVALENCE OF TTIs-TYPE OF DONOR
Prevalence (per 1000 units screened)
Voluntary
Hepatitis B
Hepatitis C
HIV
157
0~
0.279
0.328
0.461
donations
Family/Replacement 3.52
donations
PROFESSIONAL BLOOD DONORS
Professional blood donation is currently illegal. Therefore blood bank
statistics do not show the extent of the problem of professional donation.
However professional donors may masquerade as relative replacement
donors.
Paid donors present a major risk to the safety of the blood supply for the
following reasons.
1. Paying donors to give blood undermines the voluntary non
remunerated system of blood donation which is the foundation of a safe
blood supply.
2. The highest incidence and prevalence of transfusion-transmissible
infections are generally found among commercial or paid donors.
3. They are often undernourished, in poor health and may donate their
blood more frequently than is recommended. This may have harmful
effects on their own health as well as presenting either a risk to the
recipients of their blood or providing them little or no benefit.
4. If donors are paid, it is usually necessary to charge patients for the blood
they receive. Poor families may not be able to afford to pay for blood when
they need it.
33
MODULE 4
5. The ethical basis of paying individuals to provide blood (or any tissue or
organ) is a cause of concern in many countries. The commercial
procurement of blood, plasma and organs often leads to serious abuses
and may result in adverse consequences. These include the transmission of
serious infections both to patients and to the donors themselves through
improper collection methods.
34
MODULE 4
SAFE BLOOD STARTS WITH MF.
Donation of blood is a gesture of goodwill and care for the fellow
human beings. There is no gift more valuable than a Gift of Blood, as it
is actually a Gift of Life for the person who receives it.
A safe blood is the one that does not harm the donor, is free from
infection or other harmful agents, that does no harm to the recipient
and that is used for the benefit of the patients health and well being.
The slogan Safe Blood Starts With Me denotes that it is me who is the
donor of safe blood. This unit of your blood will save life of more than
one patient. As a member of the society it is your responsibility to
donate blood.
You can go to the nearest government approved blood centre, which is
based on voluntary non-remunerated blood donation and make your
significant contribution to saving life of a patient by donating blood.
Your contribution is extremely valuable to us.
One unit of donated blood can help save lives of more than one
person. One unit of blood can be separated into several components
(such as red cells, platelets and plasma) which can meet the needs of
many patients. For example, red cells can be given to patients with
severe anaemia and platelets can be given to cancer patients.
Trauma victims, cancer patients and patients with inherited blood
disorders require most of the blood.
There is no substitute of blood available. Human blood cannot be
manufactured and human beings are the only source of blood, which
can be used for humans.
Animal blood cannot be used in place of human blood.
Although the requirement of blood is alike throughout the year, there
is usually a seasonal shortage of blood during summer and winter
35
MODULE 4
months as schools and colleges are closed, people go on vacations and
there are fewer available donors. There is an increased need for blood
donation during these times to maintain an adequate blood supply for
all patients needing life-saving blood transfusions.
Blood cannot be stored indefinitely, for example red blood cells can
only be stored for about 5 weeks at a temperature of 4-60C and platelets
survive only for 5 days at 22-24°C. The need for a regular blood
donahon becomes important in view of the limited shelf-life of blood
and blood components.
People who are anaemic cannot donate blood. However, they should
undergo treatment for anaemia and can donate blood once the
haemoglobin is within normal range.
Whole blood donation can be made safely at an interval of 3 months
if the donor has no anaemia risk particularly iron deficiency.
Repeated blood donation at this interval does not cause any sort of
weakness. As pre-menopausal women are more prone to iron
deficiency their donation interval is usually longer.
There is absolutely no risk of getting AIDS or any other disease (such
as hepatitis B and hepatitis C) from donating blood. The blood is
collected using sterile equipment. A new blood bag with attached
sterile disposable needle is used for each blood donor and the needle is
destroyed immediately after the donation.
You can give blood from the age of 18 years to 60 years safely without
any risks at all to your health. It may be a little earlier or later
according to national standards.
You are examined before giving blood about your suitability to give
blood. If there is any risk to your health due to blood donation or there
is any risk to the recipient on receiving the blood, your blood will not
be collected.
36
MODULE 4
You must know that many tests need to be done before blood can be
transfused. It may take about 3 days to do all these tests. If you only
want to donate blood for your family members or friends in need, there
may be no time in emergency situations to collect, test and issue your
blood for a particular patient. Therefore, there is a need to have
sufficient blood available to tackle any emergencies. This is only
possible if healthy volunteers donate blood on a regular basis.
Donating blood does not take a long time. The actual blood collection
procedure takes about 8-10 minutes. Donors are however, encouraged
to spare about one hour for the whole process. The safety of blood
actually depends on answering the donor selection questionnaire
sincerely and honestly. After the donation you must take rest for 10
minutes at least and have a drink to replenish the fluids.
Individuals who have ever suffered from hepatitis B, hepatitis C or
AIDS at any time in their life should not donate blood. Those who
practice high-risk sexual behaviour or abuse intravenous drugs should
also not donate blood. Please remember a little of your time can save
someone's life.
Give blood voluntarily As a blood donor, it is your moral
responsibility to make sure that the blood, which you donate, is safe
and it not likely to transmit any infection, which you may be carrying.
To ensure good donor selection, you will be asked few questions in
confidence about your life style and your sexual history. The purpose
of asking these questions is to select healthy and safe donor for the
needy and sick patients, and collect blood, which is safe and unlikely to
transmit any infection. You must listen to these questions and answer
them as correctly as possible, because we know that you too want to
help a patient who is in real need rather than harming a patient.
37
MODULE 4
Please go and enrol yourself as a voluntary donor. You can either donate
blood at a blood centre or at any of the mobile donor sessions organised by
the blood service.
38
MODULE 4
CRITERIA FOR EXCLUSION OF BLOOD DONORS
1) Age <17, > 60 years.
2) 16 weeks between donations < 3 donations/year.
3) Significant cardiovascular, respiratory, renal disease and neurological
disease requiring treatment, insulin dependent diabetes mellitus,
cancer and pregnancy.
4) Donors taking potentially teratogenic drugs or drugs that accumulate
over a long time. Avoid donors taking any drug except Eltroxin and
oral contraceptive pills.
5) Acute bacterial infections and short duration fevers.
6) HIV, Hepatitis B and Hepatitis C.
Risk groups:
7) Those who have received a transfusion of blood or blood products
8) Those who have had acupuncture
9) Those who have had tattooing
10) Men who have sex with men
11) Those who have multiple sex partners
12) IV drug abusers
13) Those who have a history of alcohol abuse
14) Anemia
(The above is not a comprehensive list of exclusion criteria.)
39
MODULE 4
RISK OF TTI FROM ADEQUATELY SCREENED
BLOOD
HIV-1 in 493,000 units transfused
Hepatitis C -1 in 103,000 units transfused
Hepatitis B-1 in 63,000 units transfused
(The risk of transfusion associated hepatitis. From: New England Journal of
Medicine June 27,1996)
40
DEFINITION
OF
BLOOD
MODULE 4
AND
BLOOD
COMPONENTS
Blood product: Any therapeutic substance prepared from human blood
Whole blood: Unseparated blood collected into an approved container
containing an anticoagulant-preservative solution
Blood component
1 A constituent of blood, separated from whole blood,
such as:
Red cell concentrate
•
Red cell suspension
•
Plasma
Platelet concentrates
2 Plasma or platelets collected by apheresis*
3 Cryoprecipitate, prepared from fresh frozen plasma,
which is rich in Factor VIII and fibrinogen
4 Plasma derivative Human plasma proteins prepared under
pharmaceutical manufacturing conditions, such as:
•
Albumin
•
Coagulation factor concentrates
•
Immunoglobulins
* Apheresis: a method of collecting plasma or platelets directly from
the donor, usually by a mechanical method
41
MODULE 4
CLINICAL TRANSFUSION GUIDELINES
Component
Indications
Contraindications
_ Red cell replacement in acute blood Risk of volume overload in patients
loss with hypovolemia
with:
_ Exchange transfusion
- Chronic anaemia
Patients
needing
red
cell - Incipient cardiac failure
transfusions
where
red
cell
concentrates or
suspensions are not available_______
Red
Cell _ Replacement of red cells in anaemic Same as red cell concentrate
patients
Concentrate
_ Use with crystalloid replacement
fluids or colloid solution in acute
blood loss________________________
Red
cell Same as red cell concentrate
Red cells suspended in additive
solution are not advised for
suspensions
exchange transfusion
of neonates.______________________
Minimizes white cell immunization Will not prevent graft-vs-host
Leucocyte
in patients receiving repeated disease, although it can improve: for
reduced blood
transfusions but, to achieve this, all this purpose,
blood components given to the blood__ components should _ be
patient must be leucocyte-depleted
irradiated where facility is available
_ Reduces risk of CMV transmission (radiation dose:
in special situations
25-30 Gy)
_ Patients who have experienced two
or more previous febrile reactions to
red cell transfusion________________
Treatment of bleeding due to:
Platelet
_ Not generally indicated for
—
Thrombocytopenia
prophylaxis of bleeding in surgical
concentrates
— Platelet function defects
patients, unless
_ Prevention of bleeding due to known to have significant pre
thrombocytopenia, such as in bone operative platelet deficiency
marrow failure
_Not indicated in:
— Idiopathic
autoimmune
thrombocytopenic purpura (ITP)
— Thrombotic
thrombocytopenic
purpura (TTP)
— Untreated
disseminated
intravascular coagulation (DIG)
— Thrombocytopenia
associated
with septicaemia, until treatment
has
commenced
or
in
cases
of
hypersplenism
Fresh
Replacement
of
Frozen
multiple * Volume expansion
Whole blood
9
42
Plasma
Liquid plasma
(Bank plasma)
Cryoprecipitate
coagulation factor deficiencies, e.g.:
— Liver disease
— Warfarin anticoagulant overdose
— Depletion of coagulation factors in
patients receiving large volume
transfusions.
Disseminated
intravascular
coagulation (DIC)
Thrombotic thrombocytopenic
purpura (TTP)
Deficiencies of liver dependent
(stable) coagulation factors
_ As an alternative to Factor VIII
concentrate in the treatment of
inherited
deficiencies of:
—Von Willebrand Factor (von
Willebrand's disease)
— Factor VIII (haemophilia A)
-Factor XIII
_ As a source of fibrinogen in
acquired
coagulopathies: e.g.
disseminated
intravascular coagulation (DIC)
MODULE 4
* Protein source
* To improve wound healing
* Volume expansion
* Protein source
* To improve wound healing
43
MODULE 4
CHARACTERISTICS OF SELECTED BLOOD PRODUCTS
1. WHOLE BLOOD (CPD-Adenine-1)
Data for a 450 ml (10%) donation volume. Whole blood may contain an
alternative anticoagulant/ additive solution.
Description
•
•
•
•
•
•
•
•
Up to 510 ml total volume (this volume may vary in accordance
with local policies)
450 ml donor blood
63 ml anticoagulant
Haemoglobin approximately 12 g/ml
Haematocrit 35 (45 %)
No functional platelets
No labile coagulation factors (V and VIII)
Unit of issue 1 donation, also referred to as a 'unif or 'pack'
Infection risk
• Not sterilized, so is capable of transmitting any agent present in
cells or plasma which has not been detected by routine
screening for transfusion-transmissible infections, including:
_ HIV-1 and HIV-2
_ Hepatitis B and C
_ Other hepatitis viruses
_ Syphilis
_ Malaria
_ Chagas disease
Storage
•
•
Between +2°C and +6°C in an approved blood bank refrigerator,
ideally fitted with a temperature chart and alarm
May be stored up to 35 days if collected in a suitable
anticoagulant such as citrate phosphate dextrose with added
adenine (CPDA-1) During storage at +2°C to +6°C, changes in
composition occur resulting from red cell metabolism
Indications
•
•
•
Red cell replacement in acute blood loss with hypovolaemia
Exchange transfusion
Patients needing red cell transfusions where red cell
concentrates or suspensions are not available
Contraindications
44
•
MODULE 4
Risk of volume overload in patients with:
Chronic anaemia
Incipient cardiac failure
Administration
• Must be ABO and Rh compatible with the recipient
• Complete transfusion within 4 hours of commencement
• Never add medication to a unit of blood
45
MODULE 4
BLOOD COMPONENTS
2. RED CELL CONCENTRATE
May also be called 'packed red cells', 'concentrated red cells' or 'plasmareduced blood'.
Description
•
•
•
•
•
•
150-200 ml red cells from which most of the plasma has been
removed
Haemoglobin approximately 20 g/100 ml (not less than 45 g per
unit)
Haematocrit 55-75%
Unit of issue 1 donation
Infection risk same as whole blood
Storage same as whole blood
Indications
•
•
Replacement of red cells in anaemic patients
Use with crystalloid replacement fluids or colloid solution in
acute blood loss
Administration
• Same as whole blood
• To improve transfusion flow, normal saline (50-100 ml) may be
added using a Y-pattern infusion set
3. RED CELL SUSPENSION
Description
•
•
•
•
•
•
•
150-200 ml red cells with minimal residual plasma to which
approximately
110 ml normal saline, adenine, glucose, mannitol solution (SAGM) or an equivalent red cell nutrient solution has been added
Haemoglobin approximately 15 g/100 ml (not less than 45 g per
unit)
Haematocrit 50-70 %
Unit of issue 1 donation
Infection risk same as whole blood
Storage same as whole blood
46
MODULE 4
Indications
•
Same as red cell concentrate
Contraindications
• Red cells suspended in additive solution are not advised for
exchange transfusion of neonates. The additive solution may be
replaced with plasma, 45% albumin or an isotonic crystalloid
solution, such as normal saline
Administration
• Same as whole blood
• Better flow rates are achieved than with red cell concentrate or
whole blood
4. LEUCOCYTE-DEPLETED RED CELLS
Description
•
•
•
•
•
•
A red cell suspension or concentrate containing <5 x 10 6 white
cells per pack, prepared by filtration through a leucocyte
depleting filter
Haemoglobin concentration and haematocrit depend on
whether the product is whole blood, red cell concentrate or red
cell suspension
Leucocyte depletion removes the risk of transmission of
cytomegalovirus (CMV)
Unit of issue 1 donation
Infection risk same as whole blood
Storage depends on production method: consult blood bank
Indications
•
•
•
Minimizes white cell immunization in patients receiving
repeated transfusion but, to achieve this, all blood components
given to the patient must be leucocyte-depleted
Reduces risk of CMV transmission in special situations
Patients who have experienced two or more previous febrile
reactions to red cell transfusion
Contraindications
• Will not prevent graft-vs-host disease, although it can improve:
for this purpose, blood components should be irradiated where
facility is available (radiation dose: 25-30 Gy)
Administration
• Same as whole blood
47
•
MODULE 4
A leucocyte filter may also be used at time of transfusion if
leucocyte-depleted red cells or whole blood are not available
Alternative: Buffy coat-removed whole blood or red cell suspension is
usually effective in avoiding febrile non-haemolytic transfusion
reactions. The blood bank should express the buffy coat in a sterile
environment immediately before transporting the blood to the bedside.
Transfusion should start within 30 minutes of delivery with the use,
where possible, of a leucocyte filter. Transfusion should be completed
within 4 hours of commencement.
5. PLATELET CONCENTRATES (prepared from whole blood donations)
Description
•
•
•
•
Single donor unit in a volume of 50-60 ml of plasma should
contain:
At least 55 x 109 platelets
<1.2 x 109 red cells
<0.12 x 109 leucocytes
Unit of issue may be supplied as either:
• Single donor unit: platelets prepared from one donation
• Pooled unit: platelets prepared from 4 to 6 donor units 'pooled'
into one pack to contain an adult dose of at least 240 x 109
platelets
Infection risk
Same as whole blood, but a normal adult dose involves between
4 and 6 donor exposures
Bacterial contamination affects about 1% of pooled units
Storage
20oC-24°C (with agitation) for up to 5 days in specialized
platelet packs, although some centres use ordinary plastic packs
which restrict storage to 72 hours
Longer storage increases the risk of bacterial proliferation and
septicaemia in the recipient
Indications
Treatment of bleeding due to:
— Thrombocytopenia
— Platelet function defects
—^Prevention of bleeding due to thrombocytopenia, such
as in bone marrow failure
48
MODULE 4
Contraindications
• Not generally indicated for prophylaxis of bleeding in surgical
patients, unless known to have significant pre-operative platelet
deficiency
• Not indicated in:
— Idiopathic autoimmune thrombocytopenic purpura
(FTP)
— Thrombotic thrombocytopenic purpura (TTP)
— Untreated disseminated intravascular coagulation
(DIC)
— Thrombocytopenia associated with septicaemia, until
treatment has commenced or in cases of hypersplenism
Dosage
•
•
1 unit of platelet concentrate/10 kg body weight: in a 60 or 70 kg
adult, 4-6 single donor units containing at least 240 x 109
platelets should raise the platelet count by 20-40 x 109 /L
Increment will be less if there is:
— Splenomegaly
— Disseminated intravascular coagulation
— Septicaemia
Administration
• After pooling, platelet concentrates should be infused as soon as
possible, generally within 4 hours, because of the risk of
bacterial proliferation
• Must not be refrigerated before infusion as this reduces platelet
function
• 4-6 units of platelet concentrates (which may be supplied
pooled) should be infused through a fresh standard blood
administration set
• Special platelet infusion sets are not required, Platelet
concentrates should be infused over about 30 minutes
• Platelet concentrates prepared from Rh D positive donors
should not be given to a Rh D negative potential child-bearing
female
• Platelet concentrates that are ABO compatible should be given
whenever possible
Complications
• Febrile non-haemolytic and allergic urticarial reactions are not
uncommon, especially in patients receiving multiple
transfusions.
49
MODULE 4
6.FRESH FROZEN PLASMA
Description
•
•
•
Pack containing the plasma separated from one whole blood
donation within 6 hours of collection and then rapidly frozen to
-25°C or colder temperature.
Contains normal plasma levels of stable clotting factors, albumin
and Immunoglobulin
Factor VIII level at least 70% of normal fresh plasma level
Unit of issue
• Usual volume of pack is 200-300 ml
• Smaller volume packs may be available for children
Infection risk
• If untreated, same as whole blood
• Very low risk if treated with methylene blue/ultraviolet light
inactivation (see virus 'inactivated' plasma)
Storage
•
At -25°C or colder for up to 1 year
•
Replacement of multiple coagulation factor deficiencies, e.g.:
— Liver disease
-Warfarin anticoagulant overdose
- Depletion of coagulation factors in patients receiving large
volume transfusions.
_ Disseminated intravascular coagulation (DIC)
_ Thrombotic thrombocytopenic purpura (TTP)
•
Initial dose of 15 ml/kg
Indications
Dosage
Administration
• Must normally be ABO compatible to avoid risk of haemolysis
in recipient
• No crossmatching needed
• Before use, should be thawed in water which is between 30°C
and 37°C. Higher temperatures will destroy clotting factors and
proteins
• Once thawed, should be stored in a refrigerator at 2OC-6°C
50
•
•
Precautions
•
MODULE 4
Infuse using a standard blood infusion set as soon as possible
after thawing
Labile coagulation factors rapidly degrade; use within 6 hours of
thawing
Acute allergic reactions are not uncommon, especially with
rapid infusions
• Severe life-threatening anaphylactic reactions occasionally occur
• Hypovolaemia alone is not an indication for use
51
MODULE 4
7. LIQUID (Bank) PLASMA
Plasma separated from a whole blood unit and is stored at +4°C. No labile
coagulation factors: i.e. Factors V and VIII.
8. CRYOPRECIPITATE
Description
Prepared from fresh frozen plasma by collecting the precipitate
formed during controlled thawing and resuspending it in 10-20
ml plasma
Contains about half of the Factor VIII and fibrinogen in the
donated whole blood: e.g. Factor VIII: 80-100 i.u./pack;
fibrinogen: 150-300 mg/pack
Unit of issue
Usually supplied as a single donor pack or a pack of 6 or more
single donor units that have been pooled
Infection risk
As for plasma, but a normal adult dose involves at least 6 donor
exposures
Storage
At -25°C or colder for up to 1 year
Indications
As an alternative to Factor VIII concentrate in the treatment of
inherited deficiencies of:
—Von Willebrand Factor (von Willebrand's disease)
— Factor VIII (haemophilia A) [where factor concentrates
are not available]
— Factor XIII
—As a source of fibrinogen in acquired coagulopathies:
e.g. disseminated intravascular coagulation (DIC)
Administration
• If possible, use ABO-compatible product
• No compatibility testing is needed
• After thawing, infuse as soon as possible through a standard
blood administration set
• Must be infused within 6 hours of thawing
52
MODULE 4
REFERENCES
1. Sudarsanam A. (1998) Increasing prevalence of HIV antibody among blood
donors monitored over 9 years in one blood bank. Ind. JI. Med. Research 1998
2. Harris VK, SC Nair, PK Das, U Sitaram, YN Bose, A Sudarsanam, E Mathai
(1999). Prevalence of syphilis and parasitic infections among blood donors in
a tertiary care centre in Southern India.
Annals of Tropical Medicine and
Parasitology 93:163-65.
3. Das PK, Harris VK, Shoma B, Bose YN, Annie S. (1999) Trend of hepatitis
B virus infection in southern Indian blood donors. Indian ] Gastoenterol. 18:
182
4. Hazra SC, Chatterjee S, Das Gupta S, Chaudhuri U, Jana CK, Neogi DK
(2002). Changing scenario of transfusion-related viral infections.
J Assoc
Physicians India, 50:879-81.
Kapur S, Mittal A. Incidence of HIV infection & its predictors in blood donors
in Delhi. Indian J Med Res, 108:45-50.
Position: 468 (5 views)