CI/CIDSE Conference On Tuberculosis and HIV The Challenge of Cure and Care
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CI/CIDSE Conference
On
Tuberculosis and HIV
The Challenge of Cure and Care
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Missionsarztliches Institut Wurzburg
Medical Mission Institute
□ Managing Director/Secretariat
J
Salvatorstr. 7, D-97074 Wurzburg, Germany
Tel.: ++49-931 -791 -2900, Fax.: ++49-931-791-2801
e-mail: mi.gf@mail.uni-wueizburg.de
Units:
□ Tropical Medicine and Control of Epidemics
Salvatorstr. 7, D-97074 Wurzburg, Germany
Tel.: ++49-931-791-2900, Fax.: ++49-931-791-2801
e-mail: mi.trop-med@mail.uni-wuerzburg.de
□ Health Services and HIV/AIDS
Salvatorstr. 22; D-97074 Wurzburg, Germany
Tel.: ++49-931-80485-0, Fax.:++49-931-80485-25
e-mail: mi.heatth@mail.uni-wuerzburg.de
□ Appropriate Technology in the Health Sector
Herrmann-Schell - Str. 7, D-97074 Wurzburg, Germany
Tel.: ++49-931 -80485-15, Fax.: ++49-931/80485-20
e-mail: mi.appro@mail.uni-wuerzburg.de
I
□ Co-operation in Need and Disaster
Salvatorstr. 22; D-97074 Wurzburg, Germany
Tel.: ++49-931-80485-17, Fax.:++49-/7841-441
e-mail: mi.cinad@mail.uni-wuerzburg.de
CI/CIDSE Conference
On
Tuberculosis and HIV
8
The Challenge of Cure and Care
Wuerzburg, Germany
8th - 11th March 1999
E APR
02.03.9017 11
Bankers: Postgirokonto Niirnberg (BLZ760 100 85) Nr. 13898-853
Dresdner Bank AG, Wurzburg (BLZ 790 800 52) Nr. 30 11 574 - Liga eG, Wurzburg (BLZ 750 902 00) Mr. 300 6565
%|sW
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TB and HIV - Facts, Basic Issues and Background
Tuberculosis and HIV/AIDS in Women
Approaches to address Tuberculosis in Prisons of
Low Income Countries
Measures to prevent Tuberculosis Transmission
in Health Care Fact ties
Tuberculosis in Childhood: Diagnosis, Prevention
and Thera
©
Tb during complex
Disasters
References
M
I
A compilation of background papers worked out by
staff of the different units of
the Medical Mission Institute
Editorial
r-
8
Although the term ’’institute" in the name of the Medical Mission Institute may suggest a strong focus
on academic research, its primary mission is to share practical solutions and provide rather basic
advise for partners in developing and fast developing countries who work at peripheral levels close to
the communities they serve.
In fulfilment of this commitment members of the Institute have elaborated background papers on some
topics of outstanding interest in respect to tuberculosis and HIV/AIDS. They address issues such as
"women", "children", "prisons" “refuges” or measures how to protect health workers from infection
with tuberculosis during their work. We are aware that the complex issues of the conference could
suggest other topics as well. Yet, we have chosen these topics because of the working experience we
have.
It is a great pleasure to present these papers to the participants of the CI/CIDSE Conference on TB and
HIV/AIDS for their kind consideration. As with other ‘policy documents’ we have edited we welcome
your critical comments.
Klemens Ochel
Head of the Unit Health Services and HIV/AIDS
Medical Mission Institute
Wuerzburg. March 99
TB - HIV: Facts, Basic Issues and Background
Klemens Ochel, MD, MPH
Unitfor Health Services and HIV/AIDS
Medical Mission Institute
Introduction
I
The growing epidemic of human immune de
ficiency virus (HIV) has breathed new life into
an old enemy - Tuberculosis (TB). In both
developing and industrialised countries, Tu
berculosis has re-emerged as a serious health
problem. From 30 to 70 percent of young
adults in developing countries are infected
with Mycobacterium Tuberculosis. They carry
a risk of developing the disease, although this
risk is relatively small. Tuberculosis kills more
youth and adults than any other infectious
disease in the world today. It is a big killer
comparable to malaria. More than 100,000
children die of Tuberculosis each year. The
above mentioned increase can be attributed to
at least four factors:
• the growing migration from countries or
settings where TB is common,
• the transmission of TB in congregate set
tings (e.g. health care facilities, correc
tional facilities or shelters for the home
less),
• a deterioration of the health care infra
structure and
• the HIV/AIDS pandemic.
As more specific causes of the world-wide
increase in Tuberculosis which are mainly
related to the health sector, experts identified
non-compliance with control programmes,
inadequate diagnosis and treatment, ambula
tory and self-administered treatment. This may
lead to situations where Tuberculosis becomes
incurable, in particular when multi-drug resis
tant species of the TB germ are causing the
infection.
Tuberculosis and HIV/AIDS are problems
which are not just additive, but augment each
other in regard to their negative effects on the
existence of humans. The HIV epidemic spurs
the spread of TB and increases the Tuberculo
sis risk for the whole population. One third of
E:\PR-Arbeit\TB-Konferenz\TB - HIV Basic Issues2.doc
the increase in the incidence of TB in the last
five years can be attributed to HTV. By the end
of the century, an estimated 15 percent of TB
cases will be attributed to HIV. HIV weakens
the immune system. Someone who is HIV
positive and infected with TB is 30 times more
likely to become sick than someone infected
with TB who is HIV-negative. WHO estimates
that by the end of the century HIV infection
will annually cause nearly 1.5 million cases of
TB disease that otherwise would not have oc
curred! TB is the leading cause of death
among people who are living with HIV. It
accounts for almost one-third of AIDS deaths
world-wide, 40 percent of AIDS deaths in
Africa and in Asia. In Africa, HIV is the single
most important factor determining the in
creased incidence of TB in the last ten years.
Of nearly 31 million people world-wide who
were HIV-positive in 1997, around one-third
were believed to be infected with TB? In 1993,
the World Health Organisation (WHO) took an
unprecedented step and declared Tuberculosis
a global emergency, so great was the concern
about the modem TB epidemic.
The health sector reform, which is currently
taking place in low or middle income countries
following the implementation of structural
adjustment programmes, advocates the use of
rational measures aimed at increasing effi
ciency of health services. However the nega
tive effects on national TB control pro
grammes in many countries underlines, that
cuts in governments’ social budgets have had
the effect of favouring the development of the
private medical and pharmaceutical sector,
rather than rationalising the choice of priori
ties. The emphasis on cost recovery in basic
health services is penalising the poorest
groups, most vulnerable also for TB and HIV.
Due to the rapid implementation of the health
sector reform TB control programmes were
disintegrated in several ways:
02.03.99 16:06
TB - HIV: Facts, Basic Issues and Background
Issues related to TB and HIV
•
•
•
•
the central programme unit very often was
diluted and its own specific budget disap
peared,
antituberculosis drug supply systems were
‘integrated’ into pharmaceutical supply
systems that were defective, inefficient
and run by irresponsible people,
bureaucratic conflicts happened with those
in charge of general health information
systems, or
arbitrary cuts in hospital beds available for
Tuberculosis patients have taken place,
with no redistribution of human and finan
cial resources, and no previous or parallel
improvements in the conditions for am
bulatory treatment of patients.
History of Tuberculosis
Tuberculosis probably occurred as a sporadic
and unimportant disease of humans in their
early history. Epidemic spread began slowly
with increasing population density. Experts
estimate that a social network of 180 to 440
persons is required to achieve the stable host
pathogen relationship necessary to become
endemic in a community. From the 17^ cen
tury onwards the epidemic slowly spread
world-wide as a result of infected Europeans
travelling to and colonising distant sites. At
first it was brought to the American continent.
As late as 1880s, Tuberculosis was not com
monly seen in Russia and it was relatively
uncommon in India and at the same time it
was almost unknown within the interior of
sub-Saharan Africa.
Decentralisation has been decided upon in a
bureaucratic fashion and has been applied
inadequately. The provincial and regional lev
els have not always received the supplemen
tary resources they needed and at the periph
eral level Tuberculosis control is still consid
ered a ‘vertical’ programme. Presently, TBcontrol programmes are still managed as verti
cal programmes. In this manner, integration
into primary health care services is made diffi-
Neither the vaccination against TB, nor the use
of antibiotics have been decisive for the de
cline of Tuberculosis in industrial countries
since 1850. History has taught public health
science that multi-sectoral and integrated de
velopmental approaches may lead to success.
Figure 1:
Historical development of number of deaths due to TB
Annual TB Death
The Magnitude of the Problem
and Epidemiological Facts
(Key Issues: Incidence, Prevalence, Morbid
ity, Mortality, Demographic Changes)
5 million
4 million
The world-over 2 billion of people, this
means one third of the population, are in
fected with TB bacilli". More than four mil
lion persons are estimated to get infected with
both TB and HIV per year, of whom 80% live
in developing countries. Three countries,
India, China, and Indonesia, account for half
of the annual world total of new TB cases.
3 million
2 million
Sanalona
Movement
1 million
1850
1900
Discovery
of TB Bacillus
WHO
TB Global Emergency
1950
Discovery
of First TB Drug
2000
2050
rikMijt
NT > mtac LUNO DIS
1991
cult. This raises the question what can be a
solution in the future, a promotion of TBprogrammes within the health sector, or the
strengthening of primary health care through
integration of TB and HIV work? What is the
position and the role of church related socio
medical services and in which way should they
develop in the future?
Annually, 9 million people fall ill with active
tuberculosis, 2 million in Africa alone. Nearly
3 million TB cases per year occur in south-east
Asia. Over a quarter of a million TB cases per
year occur in Eastern Europe. It is estimated
that at least 8% of all TB cases world-wide
show a connection to HIV infection. Of the
15.3 million people estimated to be infected
-2-
I
TB - HIV: Facts, Basic Issues and Background
I
Africa where 91-100 per 100,000 die of TB.
That means that every twentieth death is
caused by TB. TB is the cause of 7% of all
deaths in developing countries. It is assumed
that 26% of TB deaths in adults could be pre
vented.
15.3 million people estimated to be infected
with HIV and M. Tuberculosis at the end of
1997, 11.7 million (76 percent) live in subSaharan Africa. There are reports from some
African countries that this proportion has risen
to 60% already1'*,iv. HIV infection accelerates
the development of active Tuberculosis and its
course. Active Tuberculosis increases the
morbidity and fatality of HIV infected per
sons7/*. The incidence of Tuberculosis is ex
pected to rise from 10.2 million cases by the
year 2000 to 12 million by 2005.
Trends in Industrial Countries
The annual incidence of TB cases in the
United States of America and in the Nether
lands decreased from about 50 per 100,000
people to about 10 per 100,000 during the
period 1953 to 1984. Since 1985 the rate has
now increased to 35 per 100,000, the largest
increase being observed in the age group 25 to
45 years. The results of a Swiss epidemiologi
cal study published in 1993 (using the method
"DNA fingerprinting") are: a) there is at pres
ent in Europe an active spread of TB bacteria
in the same social environment as in the
United States of America, b) there is proof of a
spill-over to the general population, c) the
spread of strains of resistant bacteria could be
documented, and d) public health measures are
not coping adequately with the extent of the
spread as they concentrate on traditional
groups at risk like immigrants, the homeless,
etc., and not the general population^. In in
dustrial countries it is unlikely that TB as a
problem of public health undergoes an essen
tial increase as the rate for TB infection is low
for the age group who is vulnerable for
HIV/AIDSviii.
The TB germ, Mycobacterium Tuberculosis^ is
highly prevalent in much of the developing
world and in poor urban parts of industrialised
countries. In these communities, people typi
cally become infected in childhood. But a
healthy immune system usually keeps the in
fection in check. In the past, before the era of
HIV, only 5 to 15% ’’carriers” ever developed
active tuberculosis. TB germs are spread
through the air from patients with active pul
monary tuberculosis. For people living with
HIV and TB, the risk of developing active
Tuberculosis is 30 to 50 fold higher than for
people infected with TB alone. World-wide,
over the next four years, the spread of HIV
will result in more than 3 million new TB
cases among both HIV-positive and HIV
negative people.
The world over 3 million people die of TB
annually, one third of them in Asia. The high
est fatality rates have been documented in
Box 1:
Epidemiological Features of other frequent
diseases in developing countries:
In the following some particular medical facts
are outlined. The risk of TB reactivation in an
HIV infected person is said to be 7.9 cases for
100 person years1X. HIV infected persons
without prior TB infection develop primary
TB in 37% of cases after expositionx. Dis-,
seminated and extrapulmonary forms of TB
are more frequent in immunodeficient adults
(factor two to five). 24-42% of HIV infected
persons who do not suffer from AIDS show
extrapulmonary diseases. Of those with AIDS
70% do.xl There is no increased risk as re
gards probability for other persons to become
TB infected when in contact with an HIV in
fected person than from contact with a not
HIV infected one. The explanation for that is
the low rate of sputum positive pulmonary TB
measles:
100 million cases per year
3 million deaths per year
malaria:
300 million infections world wide,
110 million cases,
2 million deaths per year
diarrhoea:
death of 3 million children (<5ys.) per year,
STIs/ STDs:
10-20% of the adult population in develop
ing countries; causing a decline of 10-17%
by disability and suffering
-3-
TB - HIV: Facts, Basic Issues and Background
the HIV infected are sputum negative, and in
Asia it is said to be one quarter of all cases.
in HIV infected persons. Epidemic incidence
of TB disease caused by highly resistant bacte
ria poses a special problem. These bacteria are
MDR-TB (multi drug resistant TB). The fatal
ity rate is said to be 70-90% within 4-16 weeks
after the onset of MDR-TB diseasex**. It
seems that hospices, AIDS wards or other
institutions exclusively specialised for the
treatment and care of AIDS patients promote
this incidence. In addition, the increase in TB
disease is a growing burden on health budgets.
TB treatment costs have risen 50 times in the
large cities of the USA during the past five
yearsx***.
An undiagnosed or untreated sputum positive
TB patient is likely to infect on average 10-14
other contact persons in the course of one
yearxvik Of the latter 0.5 to 1.2 persons will
develop TB disease during the following 1-3
years. According to a calculation made in
Uganda and based on a model which considers
the presently valid figures for HIV prevalence
20% and annual infection risk 2%, the fre
quency of cases suffering from active TB will
rise 12% by the year 2000 to an incidence of
4218 per 100,000 inhabitants^**. This means
that 2% of the age group 15-49 will fall ill
with active TB.
Trends in Developing Countries
In many countries, the Figure 2:
AIDS virus is the major Incidence trends in industrial and developing countries from 1950 to 2000
cause of huge increases
in TB incidence over the
i
1 developping countries
last ten years. For exam
-r 60
1600
♦
industr. countries
ple, in Malawi the num
o 1400
--50
£®
ber of TB cases increased
A
—
E 1200
j-40 "
from 5300 in 1985 to just
O
©
o 1000
over 20 000 in 1996, of
o 800
-■30 s
which about 60% are
"-20 |
8. 600
attributable to HIV.
Cfi
400
®
w
ro
200
o
The average prevalence
0
4o
+
+
+
+
of TB infection in coun
1970
1990
1995
1950
2000
tries of sub-Saharan Af
rica in the age group 15
to 49 years is reported to
be 40-50%. Relevant studies in Uganda,
Rwanda and Ex-Zaire revealed an infection
Factors Determining Health
rate in adults of 60 to 100% in the mentioned
Seeking Behaviour
age groups.xlv Incidence as well as prevalence
of TB show a five to ten times higher figure in
(Key Issues: health cultures, stigma, discrimi
developing countries compared to industrial
nation;)
ones and are rising further. A doubling of fig
ures was found in Uganda within a period of 4
Social issues leading to greater vulnerability
are relatively well researched. But insufficient
years. Although factors like war, poverty,
attention is given to determinants of health
malnutrition, overpopulation and alcoholism
seeking behaviour. A difference has to be
are important in the promotion of TB, the
spread of HIV infection is the most important
made between factors lying in the person and
risk factor in developing countries.xv It is said
external factors related to the social, cultural
that HIV infection resulted in an additional
but also political environment.
150,000 TB deaths in Africa alone during
It sometimes seems completely forgotten by
199O.XV1 The number of sputum negative
programme managers that that the health cul
cases is rising. In Africa, 20% of TB cases in
ture of the population at risk is contributing
enormously to the complexity of TB control.
-4-
u
TB - HIV: Facts, Basic Issues and Background
to Tuberculosis treatment. Three specific top
ics need to be assessed according to the set
ting:
• the perception and interpretation of Tuber
culosis symptoms that trigger the search
for medical care
• the influence of social stigma on help
seeking adherence to therapy, and
• the adherence to treatment recommenda
tions
Anyhow, as a matter of fact, the retention of
patients’ in treatment is particularly difficult in
nations, regions or neighbourhoods where the
level of formal education is low, difficulties
and cost of transportation to clinic settings are
enormous, patients lack fund with which to
access clinical care while experiencing loss of
income producing labour during clinic visits,
and the organisation and administration of
health care is problematic. These effects need
to be assessed and to be addressed in a multi
ple interacting treatment and care model, if
really cure of the patient is being aimed at.
Problems arise from the fact that it very often
defers from that of clinical professionals. On
the other hand the professional language used
in programmes aggravates the stigma. Af
fected people feel offended by terms like "case
load”, "active case finding", "sputum positive
patient", etc.
Social scientists call the health culture the
information and understanding that people
have learned from family, friends and neigh
bours as to the nature of a health problem, its
cause, and its implications. Sick people use
their health culture to interpret their symp
toms, give their meaning, assign them sever
ity, organise them into a named symptom,
decide with whom to consult, and for how
long to remain in treatment. Astonishing
enough is the fact, that in research of health
seeking behaviour, very little attention has
been given to the question how people who are
symptomatic actively cope with Tuberculosis.
It may be helpful for deeper analysis to use a
health belief model. The health belief model
predicts that the response of people to a threat
ening illness depends on four factors:
• the believe to be susceptible to the condi
tion,
• the appreciation how severe they think the
illness is,
• the assumption what benefits they think
can be obtained by taking preventive ac
tion, and
• the perception how costly the barriers to
obtaining that assistance might be.
Medical Aspects
TB is a contagious disease. Like the common
cold, it spreads through the air. Only people
who are sick with pulmonary TB are infec
tious. Tubercle Bacilli can only be made visi
ble under the microscope by acid fast staining
and are found in sputum smears. Therefore,
other names are used like acid fast bacilli
(AFB) for Mycobacterium Tuberculosis or
smear positive or sputum positive cases for
patients. When infectious people cough,
sneeze, talk or spit, they propel TB germs
known as bacilli into the air. A person needs
only to inhale one of these to be infected. The
probability that Tuberculosis will be transmit
ted depends on infectiousness of the person
with tuberculosis, environment in which expo
sure occurred and the duration of the exposure.
Persons of the highest risk of becoming in
fected with Mycobacterium Tuberculosis are
close contacts. Infection rates usually range
from 21 % to 23 % for the contacts of infec
tious TB-patients. HIV infected persons with
Tuberculosis disease are not considered more
infectious than non-HIV-infected persons with
Tuberculosis disease. Left untreated, each
person with active TB will infect on average
Research has found that rather than the symp
toms themselves, it is the varying interpreta
tion of their meaning and what they imply for
a functioning social life that motivates group
members to seek care. Patients interpretation
of symptoms, decisions on when and from
whom to seek help, and the response to medi
cal regimens conform to their own explanatory
model of what is wrong, influence help seek
ing pathways. It is a pity that health care pro
viders often do not recognise this. Patients
efforts to cope are often construed by provid
ers as ignorance, lack of concern, vacillation
or non-adherence. It has to be recommended
that in any programme, the doctor-patient re
lationship has to be analysed in respect to the
impact of socio-cultural factors and adherence
-5-
TB - HIV: Facts, Basic Issues and Background
/
resistant strain. Drug-resistant TB is more
difficult and more expensive to treat, and more
likely to be fatal. In industrialised countries
TB treatment costs around US $2,000 per pa
tient, but rises more than 100-fold to up to US
$250,000 per patient with MDR-TB. Up to 50
million people may actually be infected with
drug-resistant TB. There is no cure affordable
to developing countries for some multidrug
resistant (MDR) strains, defined as resistant to
the two most important drugs, isoniazid and
rifampicin.
between 10 and 15 people in each year. But
people infected with TB will not necessarily
develop the disease. The immune system
'walls off the TB bacilli which, protected by a
thick waxy coat, can lie dormant for years and
years. If someone's immune system is weak
ened, the chances of getting sick are greater.
Some medical conditions increase the risk that
TB-infection will progress to disease. The risk
is approximately three times greater (e.g.
among diabetics) up to more than one hundred
times greater (e.g. among people with FHVinfection) for persons who have medical con
ditions than for those who do not. Such condi
tions include substance and drug use (esp.
drug injection), recent infection with M. Tu
berculosis (within the past two years), findings
suggestive of previous TB (in a person who
received inadequate or no treatment), prolong
corticosteroid therapy, cancer of the head and
neck, renal diseases, chronic malabsorption
syndromes and low body weight.
The emergence of strains of Mycobacterium
Tuberculosis that are resistant to antimycobacterial agents is a world-wide problem.
The World Health Organisation -WHO- and
the International Union Against Tuberculosis
and Lung Diseases -IUATLD- have estab
lished a global project of drug resistance sur
veillance that is based on standard epidemiol
ogical methods and quality control through an
extensive network of reference laboratories.
The highest rates of multi-drug-resistant Tu
berculosis have been reported in Nepal (48%),
Gujarat State, India (33,8%), New York City
(30,1%), Bolivia (15,3%) and Korea (14,5%).
MDR-TB is caused by inconsistent or partial
treatment, when patients do not take all their
medicines regularly for the required period
because they start to feel better, when doctors
and health workers prescribe the wrong drugs
or the wrong combination of drugs, or the drug
supply is unreliable.
Although patients with HIV-associated TB
mostly have typical clinical patterns, their
frequency of atypical manifestations is in
creased, making diagnosis more difficult. Re
currence rates may be higher than in HIV
negative persons through relapse or reinfec
tion. Drug resistant TB has been associated
with HIV, particularly in the U.S.A., where
HIV-associated TB may occur in the context
of other factors that decrease access to health
care such as intravenous drug use and migra
tion. Drug reactions, particularly skin erup
tions, are more common in People Living
With HIV/AIDS (PLWHA), notably to thiacetazone, which may lead to life threatening
reactions. M. Tuberculosis also enhances the
replication of HIV, leading to higher viral
levels and possibly to more rapid progression
of HIV disease in PLWH who develop TB
compared to those who do not.
Figure 3:
Descriptive Model of the outcome Tuberculis infection
Natural history of tuberculosis disease
' Infection
I
Infection Controlled
From a public health perspective, poorly su
pervised and incomplete treatment of TB is
worse than no treatment at all. When people
fail to complete standard treatment regimens
or are given the wrong treatment, they may
remain infectious. The bacilli in their lungs
may develop resistance to anti-TB drugs. Peo
ple infected by them will have the same drug-
I
Defence Weakening
! Sometimes
| ill with
; primary
i infection
Jr
CroftMiMd. 1996
-6-
TB - HIV: Facts, Basic Issues and Background
cilities through fear of being diagnosed with
TB and by association with HIV. Misconcep
tions about TB and HIV also lead to some
health care workers worrying about the risk of
acquiring HIV from their patients. Other staff
may discriminate against TB patients, per
ceiving them to be less deserving of care on
account of the association with HIV infection.
The risk of nosocomial and institutional
transmission has a negative impact on staff
motivation: The high HIV seroprevalence
among patients facilitates the spread of TB. As
the HIV prevalence rises in the general popu
lation, institutional transmission also becomes
a serious concern for those working in health
care facilities or living in crowded surround
ings in other institutions such as prisons,
mines or barracks.
Interactions Between TB and
HIV PROGRAMMES
Impact of HIV on TB control pro
grammes
According to experiences made in TB control
programmes the impact of HIV on the pro
grammes are manifold. First of all pro
grammes have to deal with an increased num
ber of patients. From 5 up to 10 percent of
dually infected adults develop TB each year. If
HIV seroprevalence rises as high as 10 percent
of the adult population, 100 to 200 new cases
of HIV-related TB can be expected per
100,000 total population. In most countries,
this will represent at least a twofold increase in
numbers of cases, with the most heavy impact
on urban areas.
Problems arise in respect to diagnosis: In ad
dition to the effect of an increased burden of
Tuberculosis on establishing the diagnosis, it
is also more difficult to diagnose individual
cases. Furthermore, HIV causes several other
pulmonary problems that may be misdiag
nosed as TB.
Treatment becomes more complicated: The
advent of highly active anti-retroviral therapy
(HAART) in the industrialised countries may
cause problems of drug interactions in the few
who are able to afford this treatment; the pro
tease inhibitors are contra-indicated while
taking rifampicin. TB programmes are in
creasingly facing patients with other medical
problems associated with HIV in addition to
TB.
Despite all efforts morbidity and mortality will
increase: Even in programmes that use the
DOTS strategy, mortality in HIV-positive
patients is high, mostly from other manifesta
tions of HIV disease. This leads both to loss of
the community’s confidence in the programme
as well as to deterioration in staff morale. Ad
herence to therapy and follow-up may be
threatened by other medical and social prob
lems affecting HIV-infected patients.
The stigma affects a wider group of people:
The association of TB with HIV is widely
recognised in communities bearing the brunt
of the dual epidemic. HIV remains nearly eve
rywhere a highly stigmatising infection. Some
patients may choose not to attend health fa-
Box 2:
Public Health Model of HIV and Tuberculo
sis
• in a low HIV prevalent area, less than one per
1,000 of the potential population suffers from
Tuberculosis (100 per 100,000 prevalence of the
disease)
• in a low HIV prevalent area, one per 1,000 of the
total population will develop Tuberculosis dis
ease (incidents of disease)
• in a high HIV prevalent area, three to four per
1,000 of the total population will develop Tuber
culosis annually (incidents of disease). About to
40 to 60 % of all TB-patients in sub-Saharan Af
rica are infected with HIV
• about 10 % of HIV-negative persons infected
with Tuberculosis will develop in their lifetime
• almost 8 % of HIV-positive persons infected with
Tuberculosis will develop Tuberculosis per year
or have a lifetime risk of 30 % or greater
• HIV infection appears to be the highest risk fac
tor for reactivation of Tuberculosis infection into
active disease, however, more and more data
suggests that a substantial proportion of TB in
fections in HIV-positive patients is the result of
newly enquired infection.
• in the early stages of HIV-infection, the clinical
presentation of Tuberculosis is similar to that in
any immuno-competent host; in the advanced
stages of HIV infection, about 1/3 will present as
pulmonary form only, 1/3 as extra-pulmonary
form 1/3 as a combination of both
-7-
TB - HIV: Facts, Basic Issues and Background
In summary, TB diagnosis and treatment
are vital components of any HIV care pro
gram. There exist considerable opportuni
ties for synergy between TB and HIV pro
grammes. The decentralisation and in
creasing autonomy for districts that health
sector reform is bringing to many countries
should be used as an opportunity to enhance
the concerted management of the dual epi
demics. Possible actions include: training;
community care; IEC manuals and guide
lines; advocacy; surveillance; collaboration
with NGOs; and social mobilisation.
In summary, HIV has adversely affected TB
control programmes both directly through
increases in caseloads and more difficult
diagnosis, but also indirectly through its
effect on health-seeking behaviour and the
interaction between patient and provider at
the health services. The control of TB in
areas with a high prevalence of HIV infec
tion is therefore, to a considerable degree,
dependant on the success of the HIV control
programme.
Impact of TB on HIV control
Programmes
The potential synergy of TB and
HIV programmes
Since TB is one of the most common compli
cations of HIV infection and is treatable, accu
rate diagnosis and effective treatment of TB
should be two of the most important compo
nents of any HIV care program. As prophy
laxis against opportunistic infections becomes
more widely sought by HIV-infected persons
in developing countries, preventive therapy for
Tuberculosis in HIV-infected persons will
become increasingly discussed. Although pre
venting TB in people living with HIV/AIDS
(PLWA), who have not yet developed active
TB, has been demonstrated in clinical trials,
there are operational challenges to ensure that
patients with active TB are not given preven
tive therapy whilst they need full treatment.
Failure to exclude active disease will result in
inappropriate monotherapy and lead to the
development of drug resistance.
The following statements refer mostly to the
national level. Non-governmental organisa
tions and church institutions have to develop
their role in relation to the concepts outlined
below. From case studies in five developing
countries, WHO and UNAIDS have identified
the following basic obstacles to the creation of
greater awareness and commitment:
• lack of good epidemiological data on each
of the dual epidemics
• lack of professional consensus about costeffective approaches to TB control, STD
control and HIV containment and
• reluctance to monitor effectiveness (cov
erage and outcome) of ongoing TB and
HIV/AIDS programs
According to experts, real progress in control
ling TB and providing care for HIV can only
be made with a dual strategy targeting both
epidemics: TB control and HIV prevention.
This will require overcoming myths and mis
conceptions - and gathering the resources
needed for action.
TB programmes and some countries have a
well-developed strategy that is integrated into
provincial and district hospitals and urban and
rural health centres, and which ensures deliv
ery of care to TB patients and monitors out
come. In contrast, strategies for care of pa
tients with HIV-related illnesses are at an ear
lier stage of development in most affected
countries. TB patients are also an easily identi
fied group that has a higher prevalence of HIV
infection than the general population. They
are, therefore, a suitable target for interven
tions to reduce further transmission of HIV
and, if possible, biomedical interventions to
prevent or treat other HIV-associated prob
lems.
In respect to TB, their is consensus that con
tinuing expansion of the DOTS strategy is
needed to control the global burden of TB. In
areas of high HIV prevalence, the control of
TB is, to a considerable degree, dependant on
the success of HIV control programmes. TB
diagnosis and treatment should be vital com
ponents of the HIV care program, and HIV
care must be included in TB programmes. It is
also possible to prevent some cases of TB in
PLWHA who have not yet developed active
-8-
TB - HIV: Facts, Basic Issues and Background
•
•
•
•
I
nity health workers, a combination of patient
education and incentive, and intensive staff
supervision. (Note: the use of the term compli
ance with treatment is more and more dis
couraged, because it has the unfortunate con
notation that the patient is docile and subser
vient to the provider. To complete treatment is
usually an independent choice of the patient
and best described as adherence. Recently, the
term concordance has been suggested, to re
flect the active exchange of information, nego
tiation, and spirit of co-operation). A system
atic review of randomised trials found that all
the strategies tested seem to improve adher
ence. Independent effects of health education
could not be assessed, and there are no trials
available yet to test the effectiveness of di
rectly observed treatment. DOTS has usually
been introduced as part of a comprehensive
effort to improve Tuberculosis services. The
most accompanying interventions are im
proved accessibility of services, increased
availability of drugs, changes in drug regi
mens, patient incentives, tracing of patients
who default, and outreach efforts. Directly
observed treatment may, therefore, simply be a
marker for a serious commitment to Tubercu
losis control. Health providers should draw on
what is known to be effective when designing
strategies appropriate to the local circum
stances. Further innovations, especially those
that are feasible in developing countries,
should be evaluated in randomised control
trials, before introduced into a routine practice.
if additional resources are available, estab
lishment culture and drug susceptibility
testing
the establishment of treatment services
within the health infrastructure where su
pervised short course chemotherapy is
given and patient education is provided
the assurance of a regular supply of drugs
and diagnostic material
the design of a plan of supervision and
the formulation of a project development
plan
The performance of TB Control Programmes
in different countries has been assessed in
1998 by WHO and the IUATLD. Excellent
progress against a global TB epidemic in
nearly one-hundred countries is being over
shadowed by the stalled or slow progress in
many of the twenty-two countries which ac
count for the vast majority of the world’s TB
cases. Table 1 (Annex) provides information
on the level of performance according to dif
ferent countries.
Constraints which were identified relate to
financial shortages in programmes, poorly
qualified staff and lack of capacity to develop
and sustain effective TB programmes. During
assessments and evaluations of programmes
different insufficiencies can be noted. Very
often there is an insufficient participation of
patients and communities. Other problems are
insufficiencies in respect of diagnostic serv
ices of the health sector and difficulties to
achieve the necessary cure rates because of
problems of adherence to treatment, effective
ness of drugs or follow-up by the health sector.
Again and again it is shown that in many proj
ects the conclusion has to be drawn that far too
few people are entering the system of treat
ment and too many are not properly diag
nosed! Experiences, how TB activities on a
district level can be improved, are summed up
in table 2 (Annex).
DOTS
In recent years WHO has refined and pro
moted a specific strategy for TB control.
DOTS is the name for a comprehensive strat
egy which primary health services around the
world are using to detect and cure TB patients.
The strategy depends on five elements for its
success. If any of these elements are missing,
the ability to consistently cure TB patients is
jeopardised. The difference to other ap
proaches is the fact that DOTS makes the
health system, and not the patient, responsible
for achieving a cure. There is a lively debate,
if this is always positive. The five elements of
DOTS:
'r
Despite adequate delivery systems, some pa
tients with Tuberculosis do not complete
treatment. Six specific interventions have been
tested in randomised trials to improve adher
ence. Interventions examined were reminder
cards, patient education and incentive for pa
tients, help from peer group through commu-
ys
-11 -
05639
y*/
j
TB - HIV: Facts, Basic Issues and Background
/
adopted the DOTS strategy. Of those, 63 have
implemented DOTS countrywide. If WHO
targets to detect 70 percent and to cure 85
percent of new infectious TB cases are met by
2010, one-quarter of TB cases and one-quarter
of TB deaths could be prevented in the next
two decades.
• directly: resources should be directed to
ward identifying sputum smear positive
cases for treatment. Until high cure rates
are achieved, programmes should not ac
tively search for other people in the com
munity who might have TB
• observed: patients must be observed
swallowing each dose of their medicine.
This is especially critical during the first
two months
• treatment: TB patients must be provided
with complete treatment. Sputum must be
examined under microscope after two
months and at the end of the treatment. A
recording and reporting system is needed to
rigorously monitor and evaluate the prog
ress made.
• short course: correct combination and
dosage of a TB drugs must be used for the
right length of time. The drug regimen in
cludes isoniazid, rifampicin, pyrazinamide,
streptomyzine and ethambutol.
The Centre for Epidemiological Research
South Africa (HLABISA) published a study
about the cost-effectiveness of directly ob
served treatment (DOTS) and conventionally
developed treatment for tuberculosis. The es
sential results of that experience from rural
South Africa can be summed up as follows.
Directly observed treatment was 2.8 times
cheaper overall, than conventional treatment to
deliver. Directly observed treatment worked
out 2.4 to 4.2 times more effective, costing
US$900 per patient cured compared with ei
ther US$2,100 or US$3,700 for conventional
treatment. Because directly observed treatment
can considerably reduce a hospital stay, its
implementation will increase the capacity of
hospitals to cope with a rising Tuberculosis
caseload, wherever the conventional approach
is currently used.
Once infectious patients have been detected
using microscopy services, health and com
munity workers as well as trained volunteers
observe and record patients swallowing the
correct dosage of anti-TB medicines for six to
eight months. After two months sputum smear
testing is repeated, to check progress, and
again at the end of treatment. A recording and
reporting system documents patients' progress
throughout. DOTS produces cure rates of up to
95 percent even in the poorest countries.
DOTS prevents new infections and the devel
opment of MDR-TB.
The impact of the success of DOTS is limited
in many developing countries by the low
health coverage of the population, the alloca
tion of insufficient sums to specific activities
of the national Tuberculosis programme, par
ticularly training and supervision and by the
priority given to non infectious TB cases. It is
important to note that there is no need for
compulsory HIV testing, if DOTS is applied.
TB patients can be cured with DOTS regard
less of where they live and whether they are
also infected with HIV. Hence there is no need
to insist on testing for HIV. However, it makes
sense to offer TB patients voluntary counsel
ling and HIV testing which may be beneficial
for planning their future.
A six-months' supply of drugs for DOTS costs
US $11 per patient in some parts of the world.
The World Bank has ranked the DOTS strat
egy as one of the "most cost-effective of all
health interventions." In the few years since
DOTS was introduced on a global scale, more
than 1.7 million infectious patients have re
ceived effective DOTS treatment. In half of
China, cure rates among new cases are 96 per
cent. In Peru, widespread use of DOTS for
more than five years has led to the successful
treatment of 91 percent of cases and a decline
in the overall number of cases. In spite of this
rapid progress, only 12 percent of estimated
TB patients received DOTS in 1996. At the
beginning of 1997, 95 out of 212 countries had
Research
It is crucial, that the DOTS strategy should not
be pursued in a way that excludes the possi
bility of developing other forms of TB control.
It is crucial to devote resources for research
- 12-
TB - HIV: Facts, Basic Issues and Background
for new diagnostic tools, new drugs and effec
tive vaccines for TB
Another aspect of research is MDR-TB.
WHO’s Global Tuberculosis Programme
joined forces with the International Union
Against Tuberculosis and Lung Disease and
started the Global Project on Anti
Tuberculosis Drug Resistance Surveillance. In
December 1997, a first report was published.
Resistance of M. Tuberculosis to antibiotics is
a man-made amplification of spontaneous
mutations in the genes of the tubercle bacilli.
Treatment with an inappropriate drug regimen,
due to irregular drug supply, inappropriate
prescription or poor adherence to treatment,
suppresses the growth of strains susceptible to
that drug, but permits the multiplication of
drug resistant strains. This phenomenon is
called “quiet resistance”. Subsequent trans
mission of such resistant strains from an in
fectious case to other persons leads to disease
which is drug resistant from the outset, a phe
nomenon known as primary resistance. In the
report, the following important conclusions
were drawn:
• Drug resistance is ubiquitous. Failure to
improve TB control will lessen multi-drug
resistance.
• There are several hot spots around the
world where MDR-TB prevalence is high
and could threaten control programmes.
These are Latvia, Estonia and Russia, the
Dominican Republic and Argentina and the
Ivory Coast in Africa.
• There is a strong correlation between both
the overall quality of TB control and use of
standardised short course chemotherapy as
well as low levels of drug resistance.
• The MDR-TB Level is a useful indicator of
national TB control programmes perform
ance.
lem of Tuberculosis. The most important fac
tors responsible for the increase are man made
like changes in the social context and growing
poverty leading to migration. This goes to
gether with the deterioration of the health care
infrastructure in many countries and the fact
that sometimes TB control programmes are
poorly managed or under funded.
Of the 15.3 million people estimated to be co
infected with HIV and Mycobaterium Tuber
culosis at the end of 1997, 11.7 million live in
sub-Saharan Africa. The annual rate of new
diseases of Tuberculosis is expected to rise up
to 12 million by the year 2005. More than
three million people will die of the disease
every year. It is assumed that 26% of these TB
deaths in adults can be prevented.
Real progress in controlling Tuberculosis and
providing care for HIV can only be made with
a dual strategy targeting both epidemics. Con
trol of TB means curing patients, and HIV
prevention means not only health education,
capacity building, legal and spiritual support,
but also assurance of blood safety, cure for
opportunistic infections and sexually trans
mitted diseases. Lessons of capacity building
which have been learned in the AIDS work
may overcome blockages in TB control pro
grammes in respect to help seeking behaviour
and adherence to treatment. Church institu
tions have a specific experience to share in this
respect. It is important that new alliances be
tween public services and non-governmental
services assure that the challenges of cure and
care are met in the future.
Figure 4:
TB Epidemic in Zambia
Tuberculosis in Zambia:
__________________ new cases, 1985 - 2010
Expectations in respect to classic science go
into the improvement of diagnostic tests, the
rapid detection of drug resistance, the devel
opment of new vaccines and the development
of immuno-therapeutic agents.
Thousands of Cases
■ due to HIV
■ not due to HIV
20 'XZ~—I 15
II
10o 1^
' ---------I —1 II
1985
Conclusion
1990
1995
2000
| I
2005
j I
II
2010
♦— Projections ——
In the last decade, the HIV pandemic has con
tributed to the already worsening health prob-
- 13-
MawtryoTHMlth
ZmInk 1977
TB - mV: Facts, Basic Issues and Background
Annexes
Table 1: State of performance of national TB control programmes
Countries
which Countries with successful
made important pro- TB Control Programs
gress in TB Control
Countries with
Very poor performance of TB Control
Low income countries
• Ethiopia
• Afghanistan
• India
• Myanmar (Burma)
• Nigeria
• Pakistan
• Sudan
• Uganda
Middle income countries
• Brazil
• Indonesia
• Iran
• Mexico
• Philippines
• Russian Confederation
• South African Republic
• Thailand
Bangladesh
Peru
Vietnam
Armenia
Cambodia
Cuba
Malawi
Morocco
Mongolia
Nicaragua
Oman
Slowenia
Table 2: Measures to improve the outcome of a TB control programme
Measures
to improve participation
Strengthen contact tracing
Reduce the
stigmatisation
through health education
Demystification of TB as an
ordinary disease
Improvement of co-operation
between health services and
traditional healers
Promotion of voluntary testing
and counselling services
Offer of tuberculin testing (or
chemoprophylaxis) to all HIV
positive patients
\\RECHNER0\RECHNER4\PR-Arbeit\TB-Konferenz\TB
HIV Basic Issues2.doc
Measures
diagnostic to improve the therapeutic
sensitivity, sub-system
(effectiveness of drug regimen
and adherence)
Make sputum collection more • In short course regimens re
efficient
placements of drugs is of minor
Quality
control
of labimportance
technician: inter-reader vari • Direct supervision of treatment
ability, comparison with refer
of non-complicated cases at a
ence lab
peripheral level
Introduction of presumptive • Food or other incentives can be
PTB treatment
given to improve adherence
Isolation of TB suspects; • Monitor and evaluate cost
wearing masks obligatory for
effectiveness of decentralisa
suspects (not for staff)
tion and involvement of com
munity
Measures
to
improve
(examination,
reliability)
the
02.03.99 15:19
TB - HIV: Facts, Basic Issues and Background
Epidemiologic Tables
Tuberculosis Control and Surveillance
Characteristics of the countries and regions in the Global Project on Anti-Tuberculosis
Drug Resistance Surveillance, 1995
d^dntry
£
Benin
Country/region
population
5,409,000
7,414,000
Botswana
1,487,000
161,79000
China (Henan Prov.) 91,000,000
i@ia.:r'■■■;.
11,005,866
Dominican Republic 7,823,000
Oia (Delhi state)
10,000,000
Ivory Coast
14,253,000
28,261,000
2,557,000
Latvia
21,918,000
■^fepaf_'_
23,780,000
Peru
j^ssifeffvanovo)
I, 271,100
Thailand
58,791,000
74,545,000
g^jgSam:
Zimbabwe
II, 261,000
TB cases notified
in country/ region
2,400
9,614
5,655
88,109
39,078
I, 579
4,053
48,600
II, 988
28,142
1,541
19,804
46,787
662
45,428
55,739
30,831
Notification rate
7100,00
44
130
380
54
43
14
52
486
84
100
60
90
197
52
77
75
274
Estimated spu
tum + cases
3,286
11,177
2,677
58,244
35,865
991
3,872
41,600
12,571
17,804
805
16,471
26,753
566
45,769
55,685
10,490
Characteristics and treatment outcomes of Tuberculosis patients
in the countries and regions surveyed, 1995
Estimated
HIV Treatment success Cases for
Country
(co-infection %)
ment (%)
(%)
Benin
13.0
75
10
3.1
64
25
Bolivia
50.0
72
10
Botswana
10.0
54
8
30
China (Henan province)
0.0
91
Cnba
91
7
1.3
10.0
71
16
Dominican Republic
pddiai(Delhi state)
1.0
83
27
Ivory Coast
45.0
67
6
30.0
20
73
Latvia
0.0
55
19
Nepal
8
0.7
73
Peru
0.4
81
15
14
Russia (Ivanovo Oblast)
0.0
70
3
Thailand
20.0
58
Vietnam
1.2
88
11
Zimbabwe
60.0
67
7
. -
J-iiu. J.
......
-■
- 15-
retrea-
TB - HIV: Facts, Basic Issues and Background
Tuberculosis Control and Surveillance
Characteristics of the countries and regions
in the Global Project
on Anti-Tuberculosis Drug Resistance Surveillance,1995
Country/region
Population
5,409,000
7,414,000
^puntiy
Benin
-g&livia
Botswana
China (Henan)
IjSiS
'...
Dominican Rep.
Ivory Coast
Kenya ;
Latvia
Peru
t^^sia (Ivanovo)
Thailand
Vjiet Nam
Zimbabwe
I, 487,000
161,79000
91,000,000
II, 005,866
7,823,000
10,000,000
14,253,000
28,261,000
2,557,000
21,918,000
23,780,000
I, 271,100
58,791,000
74,545,000
II, 261,000
TB cases notified Notification rate
in country/ region Z100,00
44
2,400
9,614
130
380
5,655
54
88,109
43
39,078
I, 579
4,053
48,600
II, 988
28,142
1,541
19,804
46,787
662
45,428
55,739
30,831
14
52
486
84
100
60
90
197
52
77
75
274
Estimated sputum+ cases
3,286
11,177
2,677
58,244
35,865
991
3,872
41,600
12,571
17,804
805
16,471
26,753
566
45,769
55,685
10,490
Reference
1 WHO, Tuberculosis control as an integral part of primary health care; 1988; ISBN 92 4 154244 6
“ C. Robert Horsburgh, Jr and Anton Pozniak; Epidemiology of tuberculosis in the era of HIV; AIDS 1993,
7(suppl 1): S109-S114
Kochi A; The global tuberculosis situation and the new control strategy of the World Health Organisation.
Tubercle 1991,72:1-6
IV De Cock KM, Gnaore E, Adjorlolo G et al: Risk of tuberculosis in patients with HIV-1 and HIV-2 infections
in Abidjan, Ivory Coast, BMJ 1991, 302:496-499
v Pozniak A, Neill P, Ndemera B: Is Tuberculosis a cofactor in HIV immune suppression? VIII International
Conference on AIDS/ III STD World Congrss, Amsterdam, July 1992, abstract PoA2121,
V1 Ledermann M, Georges D, Zeichner S: Mycobacterium tuberculosis activates HIV-1 expression, VIII Inter
national Conference on AIDS/ III STD World Congrss, Amsterdam, July 1992, abstract PoA2154,
V1' Agnes Genewein, Amalio Telenti et al.: Molecular approach to identifying route of transmission of tubercu
losis in teh community; Lancet, Vol. 342 October 2, 1993
vni Murray C.J.L., Styblo K and Rouillon A; Tuberculosis in developing countries burden, intervention and
cost; Bulletin of the international union against tubercuslosis and lung disease; March 1990, Vol:65, N°1
1X Selwyn P, Hartel D., Lewis V, et al.; A prospective study of the risk of tuberculosis among intravenous durg
users with human immunodeficiency virus infection; N.EnglJ. Med. 1989, 320:545-550
x Daley C, Small P, Schter G, et al.; An outbreak of tuberculosis with accelerated progression among persons
infected with the HIV; N.Engl.J. Med. 1992, 326:231-235
Xl Barnes P, Bloch A, Davidson P, Snider D; Tuberculosis in patients with human immunodeficiency virus
infection; N.Engl.J.Med. 1991, 324:1644-1650
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TB - HIV: Facts, Basic Issues and Background
x" Dooley SW, Jarris WR, Martore WJ, Sinder Jr DE: Mulitdrug-resistant tuberculosis; Ann Intern Med
1992, 117:257-259,
xm Geen J, Arno P: AIDS and Tuberculosis in New York Hosptitals, VIII International Conference on AIDS &
STD World Congress, Amsterdam, July 1992, abstract PuC8095
x,v Lowell, AM: Tuberculosis in the World, Trends in Tuberculosis Incidence, Prevalence and Mortality at the
Beginning of the Third Decade of the Chemotherapeutic Era, US Department of Health, Education and Welfare,
CDC, 1976 (HEW Publication No. CDC 76-8317)
xv Styblo, op cit
XVI Lucas S, Hounnou A, Beaumel A et al.: The pathology of adult HIV infection in Abidjan, Cote d' Ivoire,
VIII International Conference on AIDS/III STD World Congrss, Amsterdam, July 1992, abstract PoB3751,
xv“ Styblo K: Recent advances in epidemiological research in tuberculosis. Adv Tuberc Res 1980, 20:1-63
xv,,, Schulzer M, Fitzgerald J M, Enarson D A, Grzybowski S: An estimate of the future size of the tuberculo
sis problem in sub-Saharan Africa resulting from HIV infection. Tubercle Lung Dis 1992, 73:52-58
- 17-
Tuberculosis and HIV/AIDS in Women
Luitgard Fleischer, Mphil
Medical Mission Institute
Introduction
Tuberculosis is the leading infectious cause of
death in women world-wide. The disease poses a
major threat to women's health. Population
growth, the HIV epidemic, increasing poverty and
rising levels of drug resistance will inevitably
increase the burden of this disease in women. Tu
berculosis kills over one million women each year
(1). The greatest burden of disease is in the age
group 15-49 years. 80 % of deaths in this age
group is due to tuberculosis (3, 4). It is widely not
appreciated that this major cause of suffering and
death in women is preventable.
Women and the epidemiology of
TUBERCULOSIS
Globally, the prevalence of infections with Myco
bacterium tuberculosis is similar in males and
females until adolescence, after which it is higher
in males (6). Reasons for higher rates of infections
among men may be due to:
• biological mechanisms placing men at higher
risk of developing tuberculosis;
• greater number of social contacts experienced
by men who tend to work outside the home
more than women;
• undemotification in women as active case
finding does not take place: suspected cases
must present themselves to health services in
order to get diagnosed; this puts women at a
disadvantage.
• socio-economic and cultural factors (16, 17).
While the rate of infections after adolescence is
higher in men than in women, more females prog
ress to tuberculosis in their reproductive years than
men of the same age. This may be due to:
• rapid hormonal changes during pregnancy;
• postpartum descent of the diaphragm;
• expansion of the lung;
• nutritional strain of lactation;
• stress and insufficient sleep due to the de
mands of child rearing (11, 12).
E:\PR-Arbeit\TB-Konferenz\Tb_women.doc
Women of reproductive age have higher mortality
and case fatality rates from tuberculosis than men
of the same age (18):
• increased biological susceptibility to tubercu
losis related to child bearing;
• lower awareness of tuberculosis among
women leading to delays in diagnosis and
treatment;
• less access to health care for women;
• less income to be spent on health.
Late presentation which leads to worse prognosis
is caused by fear and stigma (20-25): fear of young
women not to find a husband if diagnosed; fear
that the husband may take another wife; fear to get
a divorce. The lower education of women may
also delay presentation as signs and symptoms
may not be recognized because they are unknown.
Consequences of tuberculosis in
WOMEN
Child survival and the welfare of households and
communities are affected (28 - 30).
• There is a high risk of infection, disease and
death for their children.
• If the woman dies, lack of care for children especially daughters - becomes evident.
• The economic productivity of women is af
fected: reduced farming for subsistence as well
as reduced production of export crops cause
loss of income leading to poverty of house
holds and communities.
Tuberculosis control
DOTS (detection of infectious cases, documenta
tion, treatment and supervision) in women is there
fore vital. TB control programmes should, how
ever, be sensitive to constraints for women:
• socio-economic factors: poverty is dispropor
tionately high in women
• low social status and barriers in access to
health care
02.03.99 15:28
Tuberculosis and HTV/AIDS in Women
•
•
Conclusions and
the reproductive role of women
passive case-finding puts women at disadvan
tage
RECOMMENDATIONS
Tuberculosis control should be given global health
priority. It is cost-effective and can prevent an
enormous lot of suffering and death. The DOTSstrategy needs to be gender-sensitive in its imple
mentation in order to ensure that women may be
come aware of their special risks and have access
to treatment. This needs political will of the coun
tries affected and adequate financial resources
given to TB control programmes both by govern
ments, donor agencies and NGOs.
The minimum of 6 months of supervised treatment
is often in conflict with womens’ other duties.
Women may face greater difficulties maintaining
compliance:
• restrictions on women travelling alone;
• restrictions regarding being treated by male
health providers;
• cultural values attached to women's health;
• lack of decision making power for women;
• fear of miscarriage due to drug taking (34);
• fear of reduced ability to breastfeed;
• fear of young women to have reduced chances
to get married if diagnosis becomes known
makes them discontinue visits to TB clinics.
Tuberculosis and HIV/AIDS in
References
women
HIV negative individuals infected with TB have a
10 % lifetime risk of developing tuberculosis. HIV
positive individuals have an annual risk of be
tween 3 and 13 % regarding progression to disease
(35, 36). In one study in Africa up to 54 % of
AIDS patients developed clinical TB in the course
of HIV infection. While women during their re
productive years are most at risk of progressing
from TB infection to disease, they are also at
greatest risk of HIV infection. Women with HIV
and tuberculosis are younger than men: 24:37
years (41). Thus, the HIV epidemic is increasing
the incidence of TB in women in low income
countries especially.
2
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119
Approaches to address tuberculosis in prisons of low
INCOME COUNTRIES
Gesine Ruppert-Mann, MD, MPH
Unitfor Health Services and HIV/AIDS
Medical Mission Institute
Data from several countries reveal that tuberculo
sis is a problem in prisons. 1’2,3 This is due to the
fact that the majority of prisoners come from the
poor sectors of society sharing a background of
unhealthy living conditions. In addition, TB is
frequently transmitted among prisoners who, in
turn, become a source of infection for the general
public, e.g. on the occasion of family visits or after
discharge when tuberculosis was not cured during
stay in prisonAS
Because of the adverse implications of high tuber
culosis prevalence in jails for prisoners, staff and
the outside community, control programs have
been started in prisons. The comparatively "closed
setting" of a prison appeared to offer advantages
for running a tuberculosis control program suc
cessfully.^ However, a closer look reveals a num
ber of problems which need to be tackled before
positive results can be expected.
•
•
•
Environmental factors and
ASPECTS OF INTERNAL ORGANISATION
AFFECTING THE OCCURRENCE OF TB
AND ITS TREATMENT
• Overcrowding is a common feature of prisons
often accompanied by poor ventilation. The
latter is a special problem in countries with a
cool climate where insufficient heating during
periods of low temperature urges prisoners to
keep windows closed for fear of freezing.
Problems with ventilation get worse, if also
laundry is dried in the cells/rooms because it
otherwise may get stolen.
• In countries of a generally high unemployment
rate, products manufactured by inmates cannot
•
find a market leading to unemployment of pris
oners. This automatically increases the time
which they spend in their badly ventilated
rooms.
Where revenue from prisoners' production
originally had been used for buying essential
supplies including medicines, sudden economic
decline, as experienced by many poorer coun
tries, has a direct impact on food and drug pro
vision as well as maintenance and repair of
buildings, further worsening the unhygienic
conditions.
Diet is often insufficient,- either because of
economic reasons or because nutritional re
strictions are regarded as an adequate kind of
punishment. Even if a sufficient diet is pro
vided, repressive relationships among inmates
may prevent its just distribution.
The official power structure represented by the
prison administration is accompanied by an un
official power structure governing culture and
affairs among inmates. This unofficial structure
comprises of at least three levels: (1) the bosses
- professional criminals often with outside con
nections, (2) the silent majority - those who just
serve their term, and (3) the despised ones who
may have offended this internal system, may be
known as homosexuals (and/or rape victims
within the prison) or may be outcasts from
other groups.
Communication and a certain degree of co
operation between the official prison admini
stration and bosses is essential for any inter
vention which requires direct participation
from the side of prisoners. Yet, the hierarchy
among prisoners automatically reduces chances
for any inmate of the lower categories to be
come involved and benefit from any program.
*The following insights are based on my own experiences during occasional visits in Philippine and Thai prisons and during
an assessment of the TB situation in Moldovan prisons.7 They match well with observations in countries of the former Soviet
Union reported by Reyes and Coninx.8
E:\PR-Arbeit\TB-Konferenz\Tb_Prtson.doc
02.03.99 16:04
Approaches to address tuberculosis in prisons of low income countries
• Regarding the official administration, low sala
ries, inadequate training and lack of career per
spectives easily result in collusion between
staff and bosses in criminal activities. This is
another reason for a limited access to benefits
for certain sectors of the prison population.
• Referrals from one prison to the other happen
not only during the period of investigation, but
also while serving a long-term sentence. They
may be ordered because of
(1) issues of internal security and/or over
crowding,
(2) lack of food, medical facilities or staff or
(3) even promotional reasons on grounds of
prisoners’ good behaviour. Such referrals ham
per attempts for active case finding and lead
frequently to interruption or even a complete
halt of treatment for chronic conditions, be
cause quality of health services differ between
prisons. Respective decisions are often taken
without consideration of a prisoner's health or
treatment requirements.
Roles and responsibilities in
SERVICE PROVISION AFFECTING TB
OCCURRENCE AND ITS TREATMENT
Mutual trust between health service providers
and prisoners cannot easily develop in such a
situation.
• While tuberculosis is a widely dreaded disease
also among prisoners, there is an abundance of
even more immediate concerns for them. These
are in the forefront, often so much so that in
fection with tuberculosis may be actively
sought in order to get the benefits of treatment.
The diagnosis of tuberculosis may permit to re
ceive more nutritious meals or stay in the hos
pital for a few weeks. It will also entitle to re
ceive drugs. Even if these are provided under
strict observation, prisoners know techniques to
avoid swallowing them. After return to their
rooms, they may be kept for "sale" to guards in
exchange for goods or some floor space to
sleep on.
• On the other hand, there may be also an occa
sional influx of tuberculosis drugs organised by
the bosses through their outside connections.
These drugs are considered more effective than
those offered by the prison health services. This
leads to inconsistent treatment with its known
consequences for development of MDR-TB.
Open questions
• Prison health services function under the
authority of the correctional department, a unit
usually attached to the Ministry of Justice.
Thus, they are cut off from monitoring and/or
support through the Ministry of Health for as
pects of surveillance, diagnostic equipment and
drug supply, control of standards of care provi
sion, professional promotion and, last but not
least, remuneration.
• Normally, the high social status attached to
health personnel fuels staff motivation. How
ever, working in a prison environment may
carry with it a certain stigma. The compara
tively low social reputation experienced by
prison health care providers impedes their mo
tivation to offer quality services.
• Prison health services have an ambiguous role
to play: on the one hand, they are regarded by
prisoners as representative of the system which
is responsible for their detention; on the other,
they are the first port of call for health prob
lems and the gate keepers for access to certain
benefits on account of a medical condition.
-2-
An understanding of the above mentioned factors,
which are typical for a prison situation, asks for
tuberculosis control measures which address is
sues well beyond the medical realm and/or con
sistent implementation of the DOTS strategy. The
following are important issues to be addressed:
1. It is essential that certain restrictive measures
necessary for TB control are adopted and con
sistently implemented. This will be the case
only if interests between providers and patients
concur well enough to override concerns about
personal autonomy of patients.
Will it be possible to agree on a TB control
program in prisons looking at the differing
interests of people who would need to co
operate in such a program?
What ethical implications has it if such a
program is carried out in an environment of
coercion?
2. It is essential for all tuberculosis programs to
fuel and maintain motivation for high quality
performance of providers and patients alike.
Approaches to address tuberculosis in prisons of low income countries
What can be done to improve the situation
regarding training and supportive supervi
sion?
What immediate priorities need to be met
before a true concern regarding TB control
can be expected?
Whose message will/can prisoners trust?
3. It is essential to secure a continuous, adequate
supply of anti-tuberculosis drugs as well as
necessary laboratory equipment.
What needs to be done, if responsibility for
the control program lies with a govern
mental department usually not involved in
dealing with issues of health service or
ganisation?
Is the suggestion to integrate prison health
care with the health priorities of the Minis
try of Health really a valid option in view
of the notorious difficulties with inter
departmental co-operation? Which depart
ment, for example, will make the final de
cision in regard to referral of prisoners
when referral is likely to result in incom
plete treatment?
It is essential to provide the required TB drugs
consistently.
Will it ever be possible to interrupt the
"black market for TB drugs" which is or
ganised through the unofficial system with
collusion of guards?
Who within the materially disadvantaged
population of prisoners and guards can be
expected to understand the negative impact
of such practices on (public) health and
make it a personal priority, if even well-off
members of the mainstream society are not
ready to adhere to DOTS on grounds that
this would mean to sacrifice immediate
material gains from their well paying pa
tients who ask for new, more potent drugs?
ships, which may gain from more flexible ap
proaches. Even a review of legal codes and prac
tices may be necessary, e.g. in regard to the ade
quacy of punishment in view of its risky implica
tions. In many countries Church related organisa
tions enjoy already established contacts with pris
oners and official administration through their
prison apostolates. Some of them are even in
volved in prison health education. They are espe
cially well placed to address these burning issues
and should be encouraged to reconsider the poten
tial role they could play by co-operating with the
public administration in this difficult field.
References
i.
2.
3.
4.
5.
6.
Conclusion
TB control requires an assessment of priorities of
different stakeholders and adaptation of messages
and measures to meet immediate needs. Providing
enough buildings or a balanced diet may be part of
it. In addition, an adequate answer could also re
quire a review of responsibilities in respect of
areas of conflict in administrative interrelation-
-3-
7.
8.
Meyer FJ, Konietzko N. Tuberkulose in
Deutschland - eine sozial ungleich verteilte Last.
Deutsches Arzteblatt 93, 19. Januar 1996; 93(3):
C83-85
Coninx R. Tuberculosis in Bakou’s prisons. The
experience of the International Red Cross.
TB&HIV, December-January-February 1997; 13:
18-19.
Coninx R, Pfyffer GE, Mathieu C, Savina D,
Debacker M, Jafarov F et al.. Drug resistant
tuberculosis in prisons in Azerbaijan: case study.
BMJ 1998;316:1423-1425
Beilin EY, Fletcher DD, Safyer SM. Association
of tuberculosis infection with increased time in or
admission to the New York City jail system. JAMA
1993 May 5;269(17):2228-31
Chaves F, Donda F, Cave MD, Alonso-Sanz M,
Gonzalez-Lopes A, Eisenach KD, et al.. A
longitudinal study of transmission of tuberculosis in
a large prison population. Am J Respir Crit Care
Med 1997 Feb; 155(2):719-25
Maher D, Grzemska M, Coninx R, Reyes H,
Crofton J, Sommaruga C. Guidelines for the
control of tuberculosis in prisons. World Health
Organisation, International Committee of the Red
Cross. Geneva, 1998
Krumme B, Ruppert-Mann G. The situation of
tuberculosis and nutrition in Moldovan prisons. An
assessment mission to Moldova from 9 to 27 July,
1997. Missionsarztliches Institut Wuerzburg, 1997.
Unpublished
Reyes H, Coninx R. Pitfalls of tuberculosis pro
grammes in prison. BMJ 1997;315:1447-1450 (29
November)
Measures to prevent TB Transmission in
Health Care Facilities
Klemens Ochel, MD, MPH
Unit for Health Services and HIV/AIDS
Medical Mission Institute
Practical and affordable measures for the protec
tion of health care workers from tuberculosis in
developing andfast developing countries.
Risk of TB infection among
HEALTH CARE WORKERS
It is well known to health workers that they have
an increased risk of getting into contact with in
fectious diseases during their work. Any kind of
pathogenic bacteria, protozoa, viruses and fungi
can be transmitted to them via the usual ways of
transmission like contact with blood, through
droplets in the air (aerogen) or contact with infec
tive tissues. The majority of infections are harm
less. This means, that they can easily be prevented,
diagnosed or treated. It is important to make sure
that they do not cause permanent damage (sequalae) and that effective preventive or curative
measures are accessible also in developing coun
tries like vaccination or antibiotic treatment. But
the resurgence of tuberculosis has caused a lot of
reluctance in health workers to work in TB wards
or to deal with patients suspect for TB. They con
sider TB not only to be possibly fatal, but they
know that TB may have both disabling effects
requiring long term treatment and socially stigma
tising properties. Furthermore this problem of
nosocomial infections is aggravated by the risk of
acquiring multi-drug resistant forms of TB or even
HIV which is completely incurable.
An increase of TB infections and diseases in
health workers are confirmed in any health care
setting in the world where TB prevalence is rising.
There are several reasons for the increase of TB
transmission in health care settings:
• Global resurgence of TB
• Poor hospital infection control practices
• The problem of multi-drug resistant tuberculo
sis and
• HIV-infection
\\RECHNER0\RECHNER4\PR-Arbeit\TBKonferenz\Tb_noso.doc
From public health institutions in industrialised
countries, TB was reported to be the sixth most
common occupationally acquired infection among
laboratory workers. It has been estimated that
health professionals are two to nine times more
likely to contract Mycobacterium Tuberculosis
than the general public.
Information is limited about the risk of TB trans
mission to health care workers in countries with a
high HIV prevalence, in particular in Sub-Saharan
Africa. A study carried out in Malawi found that
the rate of TB infections among nurses working in
medical and TB wards was 6,600 per 100,000 nearly 40 times higher than the case notification
rate among the general population in Malawi in
1994 (180 per 100,000). This underlines that the
relative risk of health workers acquiring Tubercle
Bacilli in specific settings can be up to 40 times
greater than that of the general population.
Figure 1: A medical assistant in Thai
land is examining a TB patient (by
Farmer, BMJ, 1997)
Prevention of nosocomial infections is not only a
major concern for managers of health care facili
ties, but it is also an ethical obligation. Rates of
02.03.99 15:40
Measures to prevent TB Transmission in Health Care Facilities
• isolation of infectious TB patients: patients
with suspected pulmonary tuberculosis can be
kept together in one area of the ward, that is
screened of from other sections, particularly
those occupied by patients with known and
suspected HIV/AIDS infection; it is particu
larly important that infectious patients are iso
lated from those most susceptible to tuberculo
sis, e.g. immuno-suppressed patients and in
fants; after treatment, immuno-competent pa
tients with drug-sensitive tubercle bacilli fol
lowing a shortcourse chemotherapy rapidly be
come non-infectious (this occurs in about two
weeks); to increase safety, it is preferable to
continue to isolate all smear-positive patients
until they have become sputum smear-negative;
• use of short course chemotherapy for smear
positive, pulmonary tuberculosis: short course
chemotherapy is much more effective and after
two months of therapy, 90 % of patients be
come smear-negative, irrespective of HIV-sero
status; short course chemotherapy should be
used wherever possible for all smear-positive
pulmonary TB cases.
transmission in health services appear to be higher,
if the diagnosis of tuberculosis in hospitalised
patients is delayed, when patients do not receive
adequate therapy or where there is unrecognised
drug-resistance. In the following, practical advice
is given that is reasonably effective and can be
implemented in low income countries. Further
more measures are discussed in respect to diagno
sis and treatment of infectious TB patients and
environmental control in order to protect health
workers.
Diagnosis and treatment of
INFECTIOUS TB PATIENTS
The most cost-effective method of interrupting the
chain of TB transmission is the rapid diagnosis
and treatment of infectious patients. There are
several ways of insuring as early a diagnosis as
possible with the least possible risk of transmis
sion of infection to others.
• adherence to criteria for suspected pulmonary
tuberculosis (suggested by the national TB
control programme or respective TB authori
ties);
• investigating TB suspects as outpatients, i.e.
that all suspects are screened by one office;
helpful is the use of an outpatient card register
and a laboratory sputum register;
• decreasing delays in sputum collection and
delivery of results to hospital wards: one possi
ble solution to these delays is to appoint a ward
officer, who follows an explicit list of duties;
• decreasing delays in laboratory smear micros
copy; most hospital laboratories stain sputum
smear using the Ziehl-Neelsen method and ex
amine for acid-fast bacilli using light micros
copy; central hospitals can speed up the diag
nosis of pulmonary TB by investing in a fluo
rescent microscope;
• improving the safety of sputum smear micros
copy for laboratory workers: the exterior of
sputum containers may be contaminated; labo
ratory workers should therefore clean the out
side of such containers with a suitable disin
fectant before opening and processing them; a
matter to improve the sensitivity of sputum
smear diagnosis has been successfully tested in
Ethiopia, putting household bleach in the spu
tum and concentrating the bacteria by centrifu
gation;
Environmental Control
One of the most effective measures to reduce TB
transmission in health care settings is the im
provement of ventilation.
• TB wards and other high risk areas in the hos
pital: the wards should have plenty of light,
many windows that open to the outside and
doors to the other parts of the hospital that are
kept closed most of the time; exhaust vents that
move air from wards to the outside are useful,
but may be too costly for many health care in
stitutions; the same principles apply to outpa
tient clinics and to rooms in which sputum in
duction procedures are carried out; ultraviolet
light has a germicidal effect on tubercle bacilli,
its effectiveness in reducing TB transmission
has not been confirmed in practice. UV-lights
are also expensive, require proper maintenance
and are potentially harmful if not installed
properly;
• for working conditions in laboratories: clear
guidelines are suggested by WHO and the
IUATLD which should strictly be followed.
-2-
Measures to prevent TB Transmission in Health Care Facilities
prevented is high; therefore surveillance of
health care staff in areas of high TB prevalence
by regular tuberculin testing is probably of lit
tle value, because many health care workers
will already have a positive skin test; regular
screening using chest radiographs every six to
twelve months is also probably not costeffective; the most cost-effective way of
screening therefore is to follow rigorously the
guidelines for screening TB suspects recom
mended by IUATLD and WHO, and to treat
health care workers as soon as active tuberculo
sis is confirmed;
• use of BCG-vaccine: in low income countries,
the majority of health care workers will have
received BCG-vaccine at birth; the questions
then arise whether re-vaccination with BCG
confers additional protection against tuberculo
sis, and whether BCG vaccination of adult,
HIV-positive individuals is safe. WHO dis
courages the use of BCG re-vaccination on the
basis of lack of evidence for additional protec
tion and concerns for safety; BCG-vaccine can
safely be given to children without sympto
matic HIV-infection, but it should be withheld
from children with clinical AIDS or with
symptomatic HIV-infection; at present, BCGre-vaccination as a means of preventing TB in
health care workers cannot be recommended;
• use of Anti-TB drugs like Isoniacid for preven
tive therapy: trials have shown that Isoniacid
given to HIV-infected persons, significantly re
duces the annual rate of TB; Isoniacid preven
tive therapy may rarely be associated with
hepatitis; the risk of complication is generally
low, although it is greater for persons over 50
years of age, and for those who are heavy
drinkers; at present, WHO and the IUATLD
hold that there is insufficient information to
recommend implementation of Isoniacid pre
ventive therapy for co-infected persons, as one
of the components of TB-control strategies in
programme settings world-wide. Research is on
the way to evaluate feasibility and cost
effectiveness.
Protecting the Health Care
Worker
First of all, it is important that health care workers
must know about tuberculosis and about the risk of
transmission in health care settings. It can be pre
sumed that knowledge about TB is generally very
low. Training and continuous education are a first
priority. The measures outlined below should then
be considered for personal protection.
• HIV-infected staff should avoid working with
TB-patients and TB-specimens: if a health care
worker is known to be HIV-seropositive, he or
she should be removed to other, safer areas
within the hospital; due to stigma and discrimi
nation, voluntary testing may be difficult; an
other approach is to advise health care workers
who exhibit some of the clinical features of
symptomatic HIV-infection, to request transfer
from high risk environments;
• face masks: special face masks, called HEPA
masks, ensure protection against TB by filter
ing out droplet nuclei of diameter one to five
micrometer; however since each mask costs
USS 5 to USS 7, no low income country could
afford to use them for widespread TB control in
health care settings; standard surgical masks
have been developed to prevent the exhalation
of particles; while they are effective in doing
so, their efficacy in preventing the inhalation of
droplet nuclei containing tubercle bacilli of di
ameter one to five micrometer is less than 50
%; the use of such masks by TB-patients with a
productive cough who are being transferred to
other parts of the hospital for investigation such
as chest radiograms, may help to reduce trans
mission of the disease; routine use of such
masks by staff or ward visitors is not generally
recommended, although they may be of some
help for staff supervising coughing procedures;
• patient cough hygiene: educating patients to
place a hand in front of their mouth when
coughing and ensuring that coughing patients
are examined with their heads turned away
from the health worker, are hygienic measures
of unproved benefit, but which are simple to
implement;
• screening of health care staff for infection and
disease: tuberculin skin testing at regular inter
vals is controversial because many workers do
not comply with screening requirements, the
prevalence of true positive tests is low, and in
consequence, the cost per case of tuberculosis
i.
-3-
References
Harries, A.D., Maher, D., Nunn, P. Practical and
affordable measures for the protection of health
care workers from tuberculosis in low-income
countries. Bulletin of the World Health Organiza
tion 1997; 75 (5): 477-489.
Tuberculosis in childhood: diagnosis, prevention and
THERAPY
Gisela Sperling, MD
Unit for Co-operation in Need and Disaster
Medical Mission Institute
Introduction
Course of infection
WHO estimates that there are 8 million new cases
of tuberculosis worldwide each year (AHRTAG
Child Health, special supplement 1996). However,
this statistic is based primarily on the number of
new confirmed cases of smear-positive, infectious
pulmonary tuberculosis (TB) in adults. There are
no comparable global epidemiological statistics on
the occurence of TB in childhood, only some na
tional studies were conducted in industrialised
societies.
Paediatricians distinguish between three phases in
the development of tuberculosis:
• Exposure means that a child is living in close
and continuous contact with a member of the
household or neighbour who is suffering from
infectious pulmonary tuberculosis.
• Infection is usually aerogen by inhalation of
droplets infected with tubercle bacteria con
tained in the sputum of the sick person the
child gets in contact with.
• Outbreak of the disease: depending on the
quantity and virulence of the tubercle bacteria
that are inhaled as well as the efficiency or in
efficiency of the child’s immune system, either
the infection can be overcome or it leads to a
manifest outbreak of the disease. Young chil
dren and people with a weakened immune sys
tems are at particular risk of the disease break
ing out.
Another aspect is the fact that the disease presents
with a different clinical picture in children. Myco
bacterium tuberculosis can rarely be identified in
their sputum or gastric secretion. This complicates
the diagnosis of primary pulmonary tuberculosis in
childhood. Of the 3 million people who die each
year as a result of tuberculosis, 170,000 are chil
dren. The primary cause of death in this age group
is the so-called dissemination of the disease lead
ing to meningitis and miliary tuberculosis. Chil
dren up to the age of 2 years are especially at risk.
The following factors further the spread of tuber
culosis:
• high rates of prevalence, especially in the
southern hemisphere, with a large reservoir of
tubercle bacteria carriers;
• increasing poverty with attendant consequences
(confined living space, poor standard of hy
giene, malnutrition, etc.);
• absence or inadequacy of TB control pro
grammes;
• spread of HIV infection.
Tuberculosis is primarily caused by the Mycobac
terium Tuberculosis. Another species of the bacte
ria, mycobacterium bovis, may also cause the dis
ease in countries where herds of cattle are in
fected. In some tropical countries mycobacterium
africanum may be the cause. Every age group is
susceptible to mycobacterial infections. However,
pregnant women, children under the age of 6 years
and adolescents are at a particularly high risk. In
children already infected with HIV an outbreak of
TB can lead to a serious ‘dissemination’ of the
disease - which is nearly always fatal.
In the fight against tuberculous in childhood the
first phase (exposition) and the second phase (in
fection) are especially important. Studies have
shown that up to 40% of exposed, untreated in
fants living in close contact with a person who is
suffering from infectious pulmonary tuberculosis
develop manifest tuberculosis themselves within
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KonferenzVTb child.doc
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02.03.99 15:45
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05639
Tuberculosis in childhood: diagnosis, prevention and therapy
1-2 years (cf. Pedriatr. Infect. Dis. J. 1995,
14:445-70).
assess and requires specific criteria. In a highincidence region an induration measuring more
than 10 mm in diameter indicates a concurrent or
previous infection or TB disease. Prior BCG vac
cination may lead only to indurations smaller than
10 mm in diameter. However, in children infected
with HIV an induration of 5 mm or more is evi
dence of TB infection or disease.
Preventive measures
The following preventive measures can be taken to
control tuberculosis in childhood:
The BCG vaccination (Bacillus Calmette-Guerlin)
is included in the WHO expanded immunization
programme ( EPI ). It should be administered to
new-born infants as soon as possible in highincidence regions. However, the vaccination can
not prevent infection with Mycobacterium Tuber
culosis. It only stops the ‘dissemination’ of the
disease. Nevertheless, this saves some 50% of
infants from the dissemination of tuberculosis
disease, especially meningitis tuberculosis. The
protection by BCG - vaccination is estimated to be
effective for 5-6 years.
A negative reaction to the tuberculine test (no
visible reaction) does not exclude the possibility of
infection with Mycobacterium Tuberculosis or
even an outbreak of the disease. Apart from pre
mature testing in the pre-allergic phase, diseases
that weaken the immune system, such as measles,
whooping cough, miliary tuberculosis, meningitis
tuberculosa, malnutrition, HIV-AIDS, or a previ
ous cortico-steroid therapy can all be causes of a
failure to react.
Tuberculine testing should have the following
consequences:
A positive reaction in exposed children who do not
show clinical symptoms indicates a probable in
fection. Such children should be given a controlled
course of prophylactic treatment with INH (Isoniacid) for 6-9 months.
Children with clinical symptoms who show a
positive reaction should be examined by a doctor
in order to confirm or exclude the diagnosis of TB.
This is done according to clinical criteria, includ
ing an X-ray of the lungs (thorax) if at all possible.
The results of these examinations indicate whether
prophylactic or curative treatment is necessary. A
presumed outbreak of tuberculosis in a child can
be confirmed by the following clinical criteria:
1. positive tuberculine test (A negative test result
does not exclude the possibility of an outbreak
ofTB.);
2. stunted growth, arrested weight or weight loss;
3. two or more bouts of fever, when other diseases
have been ruled out;
4. coughing or asthma-like symptoms for longer
than 2 weeks;
5. swelling of the lymphnodes without accompa
nying pain;
6. swelling of the joints and/or deformation of the
spine;
7. swollen belly;
8. malnutrition, no marked improvement within 4
weeks of proper nutrition.
There is a small risk that in children co-infected
with HIV, BCG vaccination can lead to a progres
sion of HIV infection. Fatal consequences are pos
sible. According to WHO however, this causes no
change in the recommendation to administer BCG
to all newborns in settings where the prevalence of
tuberculosis is high. In the control of childhood
tuberculosis, the emphasis should be placed on
finding exposed and infected children. Such chil
dren can be saved from an outbreak of the disease
by a 6 to 9 months’ prophylactic treatment with
INH (Isoniazid). The option of INH prophylactic
treatment (3 months only) applies also to neonates
exposed to tuberculosis through the mother suf
fering from infectious pulmonary tuberculosis.
Diagnosis and clinical
PRESENTATION
Usually, there are no clinical symptoms during the
phases of exposition and infection. Therefore the
Mendel-Mantoux tuberculine test (an intracutaneous injection of 5 Units highly purified tuberculine
- PPD) is especially valuable in identifying in
fected children. A positive reaction to the tubercu
line test consists of an erythema and induration
(hardening) of the skin at the area of injection. The
reaction is assessed by measuring the diameter of
the induration. After prior BCG vaccination the
reaction to a tuberculine test is more difficult to
-2-
Tuberculosis in childhood: diagnosis, prevention and therapy
Children should be treated during the Initial Phase
in hospital, if possible. Depending on local cir
cumstances, the Continuation Phase consists of
providing the drugs daily or intermittently (i.e. 2 to
3 times per week, provided correct intake can be
controlled and monitored). Pulmonary and extrapulmonary cases are treated the same way.
The clinical criteria 2-5 as well as 8 may also indi
cate HIV infection. The question arises whether
laboratory examinations are necessary to diagnose
tuberculosis. The adult patient with an infectious
pulmonary tuberculosis hosts a quantity of tuber
cle bacteria in his/her sputum which can be identi
fied by microscopy as acid-fast rods. However, in
the case of children the microscopic examination
of sputum or gastric secretion rarely produces
results. Primary pulmonary tuberculosis emerges
rarely as infectious tuberculosis in childhood. And
when it does, there is a very small quantity of
bacteria.
In treating tuberculosis in children, at least 3 syn
ergistic effective antituberculotics are usually nec
essary. In the case of meningitis tuberculosa,
streptomycin is also administered as a fourth drug
for the first four weeks in the initial phase of
treatment. In treating tuberculosis in adults, the
most important target is to eliminate the bacteria
as quickly as possible. This can usually be done
with four drugs. Thiacetazone, which in some
regimens is administered in combination with
isoniazid ( INH ), should not be given to patients
infected with HIV as it has serious dermatological
side-effects (dermatitis bullosa).
Treatment of Tuberculosis
IN CHILDHOOD
DOTS - the Short Course Directly Observed
Treatment - is the key to successful treatment.
(Tab 1)
The duration of treatment has been considerably
shortened and patient compliance improved
through the introduction of various antituberculotic drugs killing tubercle bacteria or preventing
their growth. These get to both the extracellular
and intracellular bacteria populations. The most
effective drug in reaching the extracellular and
intracellular bacteria is rifampicin. Pyrazinamide
is especially effective against intracellular myco
bacteria, which have a weaker metabolism but are
crucial in the way the disease develops over a long
period. INH (isoniazid), streptomycin and ethambutol are also particularly effective against the
intracellular bacteria. All antituberculotics have
side-effects. These are partly dependent on the
dose administered, which is not always calculated
carefully for children (Tab. 2). Ethambutol, which
is often used to treat adults, should not be given to
children under the age of eight, for it is difficult to
diagnose nervus opticus neuritis, a possible toxic
side effect.
1
The direct costs of ‘short course treatment’ for a
child are between US $17 and $30 for the initial
phase, depending on what drugs are used. The
follow-up phase costs lie, on average, between US
$30 and $40, depending on the length of treatment.
With intermittent therapy the costs of treatment
can be reduced by almost half. The prophylactic
treatment of young children with INH (isoniacid)
for 9 months costs about US $6.
(These figures are based on the UNICEF price list
of 1994.)
Future outlook
The most important aspect of any successful tu
berculosis treatment or prevention programme is
observation by a responsible medical practitioner
or health worker. It also demands a well organised
and continuously monitored control system. Under
such optimal conditions, conversion rates of 95%
with a relapse quota ofjust 5% can be achieved.
Such management could prevent development of
multiple-drug-resistant TB and, thus, increase the
cure rate in childhood TB. In addition, it would
help to save financial ressources as well as drugs
for TB treatment which are known to be insuffi
ciently supplied already.
Curative treatment consists of an Initial Phase of
2 months, followed by a Continuation Phase of
4-6 (at most 9-12) months, depending on the se
verity of the disease. Meningitis tuberculosa, mili
ary tuberculosis and tuberculosis of the bones and
joints require a 9 - 12 months of treatment. This is
also the case with children suffering from tuber
culosis who are also infected with HIV. The length
of treatment is the same for adults and children.
But the number and choice of drugs are different.
-3-
Tuberculosis in childhood: diagnosis, prevention and therapy
Table 1
Short-Course Chemotherapy for Drug-Susceptible
Tuberculosis - Pulmonary and Extrapulmonary In Infants and Children
INITIAL PHASE
Isoniazid (INH)
Rifampicin
Pyrazinamid
Streptomyin
DURATION
2 MONTHS
5-10 mg/KG body weight/day
ii
H
lOmg/KG "
25 - 30mg/KG ”
20 - 30 mg/KG ”
ti
tt
it
maximum dosis 300 mg
”
600 mg
1500 mg
750 mg
H
II
CONTINUATION PHASE DURATION 4 - 6 ( 9 - 12 ) MONTHS
A:
Daily under directly observed therapy
Isoniazid (INH)
Rifampicin
5 - lOmg/KG bodyweight/day
lOmg/KG ”
B: Intermittend treatment = 2 or 3 times weekly
under directly observed therapy
Isoniazid (INH)
Rifampicin
15 mg/KG body weight 2 or 3 times/week
lOmg/KG ”
Table 2
ADVERSE REACTIONS of ANTITUBERCULOUS DRUGS
ISONIAZID
INH - HEPATOPATHY
PERIPHERAL NEURITIS
(by inhibition of pyridoxin utilization)
Prevention: Vit.B 6 10-15 mg/day
RIFAMPICIN
HEPATOPATHY
Orange coloration of urine and secretions
Gastro-intestinal irritations
PYRAZINAMID
HEPATOPATHY
Increase of urine-acid >7 mmol/1
Treatment:Allopurinol 100 mg/kg /day
ETHAMBUTOL
OPTIC NEURITIS
( early diagnosis :red-green color
discrimination)
STREPTOMYCIN
DEAFNESS (N. acusticus, N.vestibularis)
-4-
TB DURING COMPLEX DISASTERS
Barbara Krumme, MD, DTM&H, MSc
Unitfor Co-operation in Need and Disaster
Medical Mission Institute
While public health professionals were very
restrictive in the past to encourage TB
treatment in ongoing emergencies and in
unstable refugee settings because of their
awareness of increasing drug resistance in
such situations, two factors had somehow
forced them to change their general rejec
tion : the growing number of unqualified
and uncoordinated TB-treatment centers of
all sorts of NGOs in emergencies in the
absence of integrated control aspects and
the growing prevalence of HIV-infected
people with a high susceptibility to TB dis
ease after infection.
Mission hospitals often carry a special bur
den, when dealing with TB in disaster ar
eas.
Health consequences of
DISASTERS
The socioeconomic situation continues to
worsen in many countries in the South and
in Eastern Europe, most severely in coun
tries with frequent natural disasters, fol
lowed by migration and unorganized reset
tlement of large numbers of people and in
countries affected by long lasting wars and
civil wars accompanied by a vicious circle
of general poverty and human destitution.
Most people in such situations either share
their homes and their food with migrants or
refugees from other regions or are migrants
and refugees themselves, in more or less
organized camps or community shelters or
scattered in private houses or temporary
shelters, either in the countryside or in
overcrowded towns.
E:\PR-Arbeit\TB-Konferenz\Zink TB-Konferenz.doc
TB, A SPECIAL THREAT IN LONGLASTING DISASTER SITUATIONS
ESPECIALLY IF LINKED TO HIGH
HIV-PREVALENCE
In these conditions many essential factors
for a healthy environment are missing, like
enough water of acceptable quality, appro
priate sanitation, shelter that protects from
adverse climatic conditions, appropriate and
accessible nutrition for people in need, es
sential health care provision, to name but
the most urgent ones. As a result communi
cable diseases may spread rapidly, first of
all kind of diarrhea, respiratory infections
and other droplet infections like measles
and parasitic infections, especially when
refugees come into contact with malaria
without efficient immune response from
past infections. Combined with malnutrition
these infections can considerably reduce the
immune competency and susceptibility to
further diseases when coming into contact,
especially where contact is facilitated by
crowded living conditions. This is most
relevant in high prevalence migrant or refu
gee populations. HIV-infected people have
a 25% chance to develop TB after infec
tion 1, while non-HIV-infected people have
only a 10% chance.
Therefore we must assume that with longer
stays in the circumstances described above
the spread of TB may increase dramatically
in many of the worlds actual major disaster
areas.
TB in such situations is also a threat for the
hosting community, if they live in close
1 Kessler, C.; Tuberculosis control in refugees. A
focus on developing countries. Diss. University
of London 1995.
World Health Organization: The HIV/AIDS and
tuberculosis epidemic. Implications of TB con
trol. 1994. WHO/TB/97.221.
02.03.99 15:59
TB DURING COMPLEX DISASTERS
contact with refugees or migrants, under
poor conditions and especially if the preva
lence of HIV-infection is high among them.
tion worse. As a consequence WHO docu
ments report for 1996 word-wide TB infec
tion in every third person and around 3 mil
lion deaths due to TB, more than from any
other disease.
Only rarely do refugees enter a well organ
ized and wealthy country like those from
Indochina to the USA2 or asylum seekers
from Eastern Europe in the West. The
prevalence of open TB is significantly
higher in refugees from Indochina and from
Eastern Europe compared to their host
countries, because they represent the
prevalence of TB of their country of Ori
gin.2 However, our higher-quality living
conditions, nutritional standards and health
systems have continuously reduced TBprevalence in our communities in spite of
the influx of TB infected and diseased refu
gees.
(This fact may change in future with further
development of MDR-TB^ and HIVprevalence in communities (e.g. New York,
Bronx.)
Especially in situations of temporary reset
tlement and lack of political commitment
and security, treatment of TB, which has a
duration of 6-8 months, is a risky endeavor.
Qualified, supervised and appropriately
equipped laboratories are rare with low
coverage.
In many countries drugs of any kind are not
prescribed but freely available in stores or
on market places, also those for TBtreatment. TB patients often buy their drugs
as long as their money lasts and they feel
very sick. Therefore, poor people are espe
cially at risk to interrupt treatment. This
situation not only poses the threat of relapse
and drug resistance for the individual, but
he/she might also spread the resistant bacilli
to others. Then, this is a real threat for the
community as a whole.
Poor people might even sell their drugs if
DOTS56 is not strictly applied as soon as
their health condition improves in the pres
ence of other felt priority needs. Even
health personnel might feel tempted to earn
money by selling drugs if their salaries ar
rive irregularly and are widely insufficient
to cover daily requirements.
The same might happen where relief agen
cies are not sufficiently well organized be
fore they start a TB control program, not
familiar with professional health and public
health standards and not aware of the dan
ger of MDR-TB. Many only see the indi
vidual patient, wish to help as soon as pos
sible in a curative manner in order to reduce
individual suffering, and start treatment
without considering the consequences and
Most migrants and refugees from complex,
long lasting emergencies, on the other hand,
enter neighboring countries with economic
problems and people's health status similar
to their own and where TB and HIV might
be on an increase. The movement of people
and their weak health status make the situa-
2 International Organization for Migration
(IOM) Tuberculosis Working Group: Outcome
of second-line tuberculosis treatment in migrants
from Vietnam. Tropical Medicine and Interna
tional Health 1998;3:975-980.
Sutherland, J.E. et al.: Indochinese refugee
health assessment and treatment. The Journal of
Family Practice 1983; 16 (1): 61-67.
Sutter, R.W., Haeflinger,E.: Tuberculosis mor
bidity and infection in Vietnamese in Southeast
Asian refugee camps. American Review of Res
piratory Diseases 1990; 141: 1483-1486.
3 Deutsches Zentralkomitee zur Bekampfung der
Tuberkulose. 22.1nformationsbericht. 1996.
Khomenko, A.: Tuberculosis in Eastern Europe
and the countries of the CIS. TB & HIV 1997;
13:7-14
4 Multiple Drug Resistant TB
5 Directly Observed Therapy Short-term
6 Kumaresan, J.A. et al.: Tuberculosis control in
Bangladesh: success of DOTs strategy. Interna
tional Journal of Tuberculosis and Lung Disease
1998; 2 (12): 992-998
-2-
TB DURING COMPLEX DISASTERS
planning the months ahead. In disasters
people tend to think more of today than of
tomorrow. Thus while caring for the sick
patient they easily forget about their re
sponsibility towards the community and the
still healthy people at risk of infection and
disease.
and frequently also still at a later stage (like
in Sierra Leone, DRCongo or Angola). Ex
tremely carefully informed decisions have
to be made in every special circumstance
before a program is started which should
never be led by sentimentality alone. Too
dangerous are the consequences of inter
rupted and failed treatments.
The aims of TB-control
Secondly the reduction of TB transmis
sion is a goal. This means early detection of
open TB cases through information of the
community, anti-discrimination campaigns
and appropriate diagnostic (laboratory) and
treatment capabilities (DOTS). Both have to
be organized and in place before the start of
TB control activities, otherwise the help
might reach an individual patient but the
disease continues to spread rapidly in the
community.
WHICH SHOULD NOT BE
COMPROMISED
I
The aim of every TB intervention has to be
first of all the complete cure of all pa
tients under treatment. This is difficult to
be achieved if the onset of such program is
done in a hurry. Only when the first emer
gency measures are already effectively ap
plied, the refugee community is registered
and organized, essential health services are
provided and acute communicable diseases
under control (estimated or known death
rate less than 1 in 10 000 people per day7 )
the time has come to consider TB interven
tion. A TB control program has to be re
gional oriented and best integrated into
other health activities. The amount of drugs
needed for the whole treatment of a certain,
estimated number of patients ( this number
afterwards is limiting the acceptance of
more new patients and has to be kept in
mind) have to be available, the staff at the
site and the funding secured for at least one
to two years ahead.
The burden of TB for Mission
HOSPITALS IN DISASTER AREAS
In church related health activities we often
find one typical scenario in war areas:
Mission hospitals, in former times only part
of the overall health system in a region,
have to serve for a waste area, as the coun
try suffers severe destruction during war
and civil war. National resources are used
for other priorities and as people flee from
danger, structures break down. National
health centers are closed when staff no
longer receive their pay or medical supplies
run out. Control programs are usually the
first to come to an end. The only centers
which continue to function in such situa
tions are often only those belonging to
church, run by high motivated religious
congregations and funded by foreign do
nors. As they were engaged in TB-diagnosis
and -treatment in the past they continue
usually without questioning.
TB-patients bear down on these few re
maining centers from far and wide. Many of
them walk through the countryside for sev-
It has always be considered that in case of
security problems, evacuation of staff and
new movements of people are likely to hap
pen. This will most probably interrupt
treatment and increase the danger of drug
resistance for the individual patient and for
the community. Often, security is difficult
to judge at the beginning of an emergency
7 World Health Organization: Tuberculosis con
trol in refugee situation. An inter-agency field
manual. 1997. WHO/TB/97.221.
-3-
TB DURING COMPLEX DISASTERS
nario may also occur when humanitarian aid
agencies are forced by local political
authorities to restrict their activities to the
towns (Ethiopia under the regime of Meguisto Haile Miriam) or if the towns are
relatively more secure due to external mili
tary presence (Sierra Leone, Liberia with
ECOMOG forces).
eral days. The consequence is that the
church health institution has more work
than it can cope with. More TB-patients
than usually have to remain for treatment as
their homes are too far away for them to
return to the center every day or to continue
treatment elsewhere near-by. Thus they
have to find or have to be given accommo
dation. In these circumstances, the result of
becoming such a “draw-factor”, is: provi
sion of water and sanitation are generally
inadequate, the accommodations quickly
become overcrowded, and food supplies are
insufficient. These factors in turn create a
general health threat and can lead to the
outbreak of acute communicable diseases in
addition. (In these situations donor agencies
are requested for more funding, so that TBbuildings, hospital beds for TB-patients and
the overall TB curative capacity can be
increased. In future and as soon as the secu
rity situation allows, this can hinder a flexi
ble and quick adaptation and a more appro
priate public health response because hos
pital beds will be left empty, which is often
embarrassing for the staff and perhaps
misinterpreted as a decrease in service
quality by donors. This will result in a long
lasting high dependency from external
funding with all the difficulties implied.)
A POSSIBLE INTERVENTION
STRATEGY (AN EXAMPLE FROM
THE NORTH OF UGANDA)
In complex disasters the reduction of health
services and long distances often means that
patients seek help too late^. Many of them
will have infected already many of their
contacts and the number of those who die
when they eventually reach the remaining
church center will be high. This creates
even more stress for the staff and more fear
of TB, more denial, less early intervention
and more discrimination towards TB pa
tients in the population.
While mission institutions are predomi
nantly located in rural areas a similar see-
Besides meanwhile well documented and
advocated rules and recommendations for
the running of TB-control programs by
WHO and other authors the quite often
found situation described above needs spe
cial attention.
In Uganda, Lwala Hospital^, Soroti district,
with a still insecure and uncertain situation
between 1987 and 1990 with a totally de
stroyed district health system a “centrifu
gal approach” was successfully applied: In
3 different health centers, deserted by inse
curity, situated in different directions on a
circle of around 20 km and more around the
mission hospital were made “satellite”
health centers of the mission hospital espe
cially qualified to diagnose and treat TB. In
addition TB-diagnosis and TB-treatment
was supported and supervised by the mis
sion hospital in the district state hospital
after negotiations with the national authori
ties. In all centers microscopically discov
ered TB (which means highly infectious
open TB) was given priority in the absence
of radiology and culture. Treatment was
only given under strict observation of health
workers and after counseling the patient and
his /her family in the presence of the health
worker in charge, responsible for the fol-
8 Krumme, B.: Tuberkulose. In: Bekampfung
von Infektionskrankheiten in der Humanitaren
Hilfe, Missionsarztliches Institut / Caritas inter
national, Wurzburg 1997
9 Financed mainly by “German Emergency
Doctors” and partly by “TB - Association Wurz
burg”
-4-
TB DURING COMPLEX DISASTERS
ological surveillance and investigation.
American Journal of Public Health
1990; 80 (7): 824-828.
7. Farmer, R., et al.: Epidemiology and
Public Health Medicine.p.179.
8. Fleten, M.K., Forte, G.B.: Pre-packed
kits for diagnosis and treatment of tu
berculosis in former Yugoslavia. Tu
bercle and Lung Disease 1995; 76: 360366.
9. Fordor, T., Vadasz, L, Lorinczi, L:
Drug-resistant tuberculosis in Budapest.
International Journal of Tuberculosis
and Lung Disease 1998; 2(9):732-735.
10. Gibson, N., Boillot, F., Jalloh, H.: The
cost of tuberculosis to patients in Sierra
Leone’s war zone. International Journal
of Tuberculosis and Lung Disease
1998; 2 (9): 726-731.
11. Jackson, C.: Linguistic and cultural
aspects of tuberculosis screening and
management for refugees and immi
grants. IUATLD Conference on March
1-2, 1996, Chicago.
12. Kessler, C., Conolloy, M., Levy, M.,
et al.: Tuberculosis control in refugees
and displaced persons. 1995. WHO/
TB/95.
13. Kessler, C.; Conolly, M., Levy, M., et
al.: Tuberculosis control in refugee
populations: a challenge to both relief
agencies and National Programs. Inter
national Journal of Tuberculosis and
Lung Disease 1998; 2(2): 105-110.
14. Krumme, B.: Control of communicable
diseases in the context of humanitarian
aid. In: European Commission and
NOHA: Medicine and public health in
humanitarian assistance. European
Communities, 1998: 28-55.
15. Malilay, J., Flanders, W.D., Brogan,
D.: A modified cluster-sampling
method for post-disaster rapid assess
ment of needs. Bulletin of the World
Health Organization 1996; 74 84): 399405.
16. Medecins sans frontieres: Refugee
health. An approach to emergency
low-up of the patient as well as in the pres
ence of a community leader.
Health promotion in the community and
creating awareness for early TB-symptoms
were effectively undertaken by cured pa
tients after training during treatment, pref
erably by teachers. Attractiveness of pre
senting in one of the centers in case of
symptoms was increased by food aid to
patients and by supporting small-scale in
come generating activities (mat making).
In a situation were the funding of the TB
program was secured by foreign donors this
methodology helped effectively to improve
early treatment and the compliance of pa
tients and their cure.
This example might stimulate early aware
ness and the initiative of adapted interven
tion strategies in similar situation like in
actual Angola and in many other complex
disaster areas.
Further Reading:
i. Beaglehole, R., Bonita, R., Kjellstrom, R: Basic epidemiology. WHO,
Geneva 1993: 71-81
2. Bevan, E.: Tuberculosis treatment is
expensive for patients in developing
countries. British Medical Journal 1997;
315: 187-188.
3. Centers for Disease Control (CDC):
Essential components of a tuberculosis
prevention and control program.
MMWR. 1995; 44 (RR-1 l):l-34.
4. Centers for Disease Control (CDC):
Health status of Indochinese refugees.
MMWR 1979; 28 (33) 385-399.
5. Cruickshank, et al.: Warm climate
countries. Churchill Livingstone, 1996:
p.197
6. Elias, C.J., Alexander, B.H., Sokly,
T.: Infectious disease control in a long
term refugee camp: the role of epidemi
- 5-
TB DURING COMPLEX DISASTERS
25. Soffer, A.D.: Medicine in Cambodian
refugee camps. Annals of Internal
Medicine 1996; 105: 618-621.
26. Sukrakanchana-Ttrikham, P., Puechal, X., Rigal, J., et al.: 10-year as
sessment of treatment outcome among
Cambodian refugees with sputum
smear-positive tuberculosis in Kaho-IDang, Thailand. Tubercle and Lung
Disease 1992; 73: 384-387.
27. The John K'Hopkins University: Epi
demiologic, Natural History, Classifi
cation, Diagnosis, Treatment and Pro
phylaxis ofTB. 1998.
28. Trkanjec, Z., Tekavec, J., Pulji'c, I.:
Tuberculosis in refugees. The Lancet
1994; 343: 1640.
29. UNAIDS: Tuberculosis and AIDS.
UNAIDS Best Practice Collection.
1997.
30. Wilkinson, D., Davies, G.R.: Pediatric
tuberculosis in rural South Africa value of directly observed therapy.
Journal of Tropical Pediatrics 1998; 44:
266-269.
31. World Health Organization: TB ad
vocacy. Geneva, 1998.
32. Zuber, P.L.F., Binkin, N.J., A.C.
Ignacio, et al.: Tuberculosis screening
for immigrants and refugees. Diagnostic
outcomes in the State of Hawaii.
American Journal of Respiratory and
Critical Care Medicine 1996; 154: 151155.
situations. MacMillan Ltd., London
1997.
17. Miles, S.H., Maat, R.B.: A successful
supervised out-patient short-course tu
berculosis treatment program in an open
refugee camp on the Thai.-Cambodian
border. American Journal of Respira
tory Diseases 1984; 130: 827-830.
18. Miles, S.H.: Follow-up on tuberculosis
treatment in a Cambodian refugee
camp. American Review of Respiratory
Diseases 1987; 135:512.
19. Mushtaque, A., Chowdhura, R..,
Chowdhury, S., et al.: Control of tu
berculosis by community health work
ers in Bangladesh. The Lancet 1997;
350: 169-172.
20. Pilheu, J.A.: Tuberculosis 2000: prob
lems and solutions. International Jour
nal of Tuberculosis and Lung Disease
1998; 2 (9): 696-703.
21. Porter, J., Kessler, C.: Tuberculosis in
refugees: a neglected dimension of the
“global epidemic of tuberculosis”.
Transactions of the Royal Society of
Tropical Medicine and Hygiene 1995;
89: 241-242.
22. Powell, K.E., Brown, D., Farer, L.S.:
Tuberculosis among Indo-chinese refu
gees in the United States. JAMA 1983;
249(U):1455-1460.
23. Rieder, H.L., Snider, D.E: Tuberculo
sis control in refugee settlements. Tu
bercle 1989; 70: 127-134.
24. Shears, P., Berry, A.M., Murphy, R.,
et al.: Epidemiological assessment of
the health and nutrition of Ethiopian
refugees in emergency camps in Sudan,
1985. British Medical Journal 1987;
295:314-318.
-6-
References
CI/CIDSE Conference on TB and HIV; March 1999; MMI Wuerzburg
1. GENERAL ARTICLES
Centers for Disease Control (CDC). The deadly intersection between TB and HIV. 1998.
Becx-Bleumink, M., Broekmans, J.F.. Tuberculosis: where do we stand? Tropical Medicine and International
Health 1998; 1: 423-424.
UNAIDS.Tuberculosis and AIDS. UNAIDS Best Practice Collection. 1997.
Msamanga, G.I., Fawzi, W.W. The double burden of HIV infection and tuberculosis in Sub-Saharan Africa.
New England Journal of Medicine 1997, 337 (12) 849-851.
AHRTAG, Enda. Combattre la tuberculose et le VIH. Action centre le SID A 1996; 30-31.
World Health Organization (WHO). A deadly partnership. Tuberculosis in the era of HIV. 1996.
WHO/TB/96.204.
Hausler, H.P., Raviglione, M.C. Prise en charge de la tuberculose au niveau communautaire en Afrique
Subsaharienne. SIDAlerte 1996;56: 8-15.
SidAlerte Internationale. Tuberculose & SEDA, meme combat.. 1996.
Bloom B. R. (ed.), Tuberculosis - Pathogenesis, protection and control; ASM Press, Washington DC, 1994,
2. EPIDEMIOLOGY
Holmes, C.B., Hausler, H., P. Nunn. A review of sex differences in the epidemiology of tuberculosis.
International Journal of Tuberculosis and Lung Disease 1998; 2 (2): 96-104.
World Health Organization (WHO). Epidemiological Forecast. The Observer 1998.
MAP. The status and trends of the HIV/AIDS epidemics in the world. 1998.
Cohn, D.L., Bustreo, F., Raviglione, M.C. Drug-resistant tuberculosis: review of the worldwide situation
and the WHO/IUATLD -global surveillance project Clinical Infectious Diseases 1997; 24 (suppl 1):
S121-130.
Conooly, M., Nunn, P. Women and tuberculosis. World Health Statistics Quarterly 1996; 45: 115-119.
Robert-Koch-Institut. Zur Tuberkulose-Situation in der Welt 1995. Epidemiologisches Bulletin 1996; 34:1
Raviglione, M.C., Nunn, P., Kochi, A., et al.. The pandemic of HIV-associated tuberculosis.
3. FACTORS CAUSING VULNERABILITY
Rubel, A.J., Garro, L.C. Social and cultural factors in the successful control of tuberculosis. Public Health
Reports 1992; 107: 626-636.
Floyd, K., Wilkinson, D. Tuberculosis in the HIV/AIDS era: interactions, impacts and solutions. AIDS
Analysis Africa 1997; 7: (5) 5-7
Farmer, P. Social scientists and the new tuberculosis. Social Science & Medicine 1997; 44: (3) 347-358.
Kessler, C., Connolly, M., Levy, M., etal. Tuberculosis control in refugees and displaced persons. 1996.
WHO/TB/96.209
Kessler, C., Connolly, M., Levy, M., et al. Tuberculosis control in refugee populations: a challenge to both
relief agencies and National Programs. International Journal of Tuberuclosis and Lung Disease 1998;
2(2): 105-110.
Rangan, S.: Making TB care and cure a reality for women. The Observer 1998; Sept. 15: 2
TB2biblio.rtf
25.02.99 13:29
4. MEDICAL ASPECTS
UNAIDS Policy statement on preventive therapy against tuberculosis in people living with HIV. Report of
a meeting in Geneva, Febr. 18-20, 1998. WHO/TB/98.225: 3-6.
Zumla, A., Grange, J. Tuberculosis. British Medical Journal 1998; 316: 1962-1964.
12th World AIDS Conference, Geneva, June 28- July 3,1998. Abstracts.
Jaramillo, E. Pulmonary tuberculosis and health-seeking behaviour: how to get a delayed diagnosis in Cali,
Colombia. Tropical Medicine and International Health 1998; 3: 138-144.
Halsey, N.A., Coberly, J.S., Desormeaux, J., et al. Randomised trial of isoniazid versus rifampicin and
pyrazinamide for prevention of tuberculosis in HIV-1 infection. The Lancet 1998; 351: 786-792.
lUATLD; Treatment regimens in HIV-infected tuberculosis patients - An official statement. International
Journal of Tuberculosis and Lung Disease 1998; 2(2): 175-178
Whalen, C.C., Johnson, J.L., Okwera, A., et al. A trial of three regimens to prevent tuberculosis in Ugandan
adults infected with the human immunodeficiency virus. New England Journal of Medicine 1997;
337: 801-808.
Bevan, E. Tuberculosis treatment is expensive for patients in developing countries. British Medical Journal
1997; 315: 187-188.
World Health Organization (WHO). Anti-tuberculosis drug-resistance in the world. 1997. WHO/TB/97.229.
Perlman, D.C., Hanvanich, M. Prophylaxis and treatment of HIV-related tuberculosis. AIDS 1997,11
(Suppl.A): S173-S179.
World Health Organization (WHO). Tuberculosis. The WHO/IUATLD global project on antituberculosis
drug-resistance surveillance. Weekly Epidemiological Record 1996; 71.281-285
5. PUBLIC HEALTH
5.1. Promotion
Dick, I, van der Walt, H. Hoogendoom, L. et al. Development of a health education booklet to enhance to
tuberculosis treatment. Tubercle and Lung Disease 1996; 77: 173-177.
Wallace, D. The resurgence of tuberculosis. The Lancet 1996; 347: 1115-1116.
De Cock, K.M., Binkin. N.J., Zuber, P.L., et al. Research issues involving HIV-associated tuberculosis in
resource-poor countries. JAMA 1996; 276: 1502-1507.
Chaulet, P. After health sector reform, whither lung health? International Journal of Tuberculosis and Lung
Disease 1998; 2(5): 340-359.
Liefooghe, R., Baliddawa, J.B., Kipruto, E.M., et al. From their own perspective. A Kenyan community's
perception of tuberculosis. Tropical Medicine and International Health 1997; 2: 809-821.
The Kasango Project Team and The Unit for Research and Training in Public Health. The impact of primary
and secondary health care levels on tuberculosis control activities in Kasongo (Zaire). Bulletin of
the International Union Against Tuberculosis 1982; 57:150-155.
5.2. Prevention
Dick, J., Lombard, C. Shared vision- a health education project designed to enhance adherence to anti
tuberculosis treatment International Journal of Tuberculosis and Lung Disease 1997; 1 (2): 181-186.
Wilkinson, D., Squire, S B., Gamer, P. Effect of preventive treatment for tuberculosis in adults infected with
HIV: systematic review of randomised placebo controlled trials. British Medical Journal 1998, 317:
625-629.
-2-
Reyes, H., Coninx, R. Pitfalls of tuberculosis programmes in prisons. British Medical Journal 1997, 315:
1447-1450.
Squire, S B., Wilkinson, D. Strengthening „DOTS“ through community care for tuberculosis. British
Medical Journal 1997; 315: 1395-1396.
Kochi, A. Is DOTS the health breakthrough of the 1990s? World Health Forum 1997; 18:225-247.
Wilkinson, D., Davies, G.R. Coping with Africa’s increasing tuberculosis burden: are community
supervisors an essential component of the DOT strategy? Tropical Medicine and International
Health 1997; 2: 700-704.
5.3.2. Research
Wouters, P. Genome sequence TB unravelled. 1998.
World Health Organization (WHO). Tuberculosis and HIV Research: Working Towards Solutions - Results
of a WHO Workshop on the Formulation of a New TB/HIV Research Strategy. 1995.
WHO/TB//95.193.
Douglas B. Young; New tools for tuberculosis control: do we really need them? International Journal of
Tuberculosis and Lung Disease 1997; 1(3): 193-195.
Grange, J.M., Festenstein, F. The human dimension of tuberculosis control. Tubercle and Lung Disease 1993;
74: 219-222.
5.3.3. Structures
UNAIDS. HIV threatens progress against worsening global tuberculosis epidemic. UNAIDS Press Release
1998.
World Health Organization (WHO). TB Advocacy. A practical guide. 1998. WHO/TB/98.239.
International Union Against Tuberculosis and Lung Disease (IUATLD). Official policies of the IUATLD.
IUATLD Newsletter; January 1998.
6. ISSUES OF ETHICS AND HUMAN RIGHTS
World Council of Churches. Consultative Group on AIDS. Final Report. 1996.
Shuster, E. The Nuremberg Code: Hippocratic ethics and human rights. The Lancet 1998; 351: 974-977.
Harvey, J.C. The ethics of the AIDS care. Journal of the International Association of Physicians in AIDS Care
1997;3:14-24.
Grange, J.M. DOTS and beyond: towards a holistic approach to the conquest of tuberculosis. International
Journal of Tuberculosis and Lung Disease 1997; 1(4): 293-296.
Zumla, A., Grange, J.M. Establishing a united front against the injustice of tuberculosis. International
Journal of Tuberculosis and Lung Disease 1998; 2(3): 179-181.
7. Resolution
McAdam, K.P.W.J. Back to the future: ‘the ten commitments’. In: Porter, J.D.H., McAdam, K.P.W.J.:
Tuberculosis: Back to the future. Wiley, London. 1994, pp.267-276.
Medical Co-ordination Secretariat (MCS). Policy considerations and recommendations. In: AIDS policy paper
1998; 26-30.
-4-
References
CI/CIDSE Conference on TB and HIV; March 1999; MMI Wuerzburg
12th World AIDS Conference, Geneva, June 28- July 3,1998. Abstracts.
AHRTAG, Enda. Combattre la tuberculose et le VIH.Action contre le SIDA 1996; 30-31.
Becx-Bleumink, M., Broekmans, J.F.. Tuberculosis: where do we stand? Tropical Medicine and International
Health 1998; 1: 423-424.
Bevan, E. Tuberculosis treatment is expensive for patients in developing countries. British Medical Journal
1997; 315: 187-188.
' Bloom B. R. (ed.), Tuberculosis — Pathogenesis, protection and control; ASM Press, Washington DC, 1994,
Centers for Disease Control (CDC). The deadly intersection between TB and HIV. 1998.
Chaulet, P. After health sector reform, whither lung health? International Journal of Tuberculosis and Lung
Disease 1998; 2(5): 340-359.
Cohn, D.L., Bustreo, F., Raviglione, M.C. Drug-resistant tuberculosis: review of the worldwide situation
and the WHO/IUATLD -global surveillance project Clinical Infectious Diseases 1997; 24 (suppl 1):
S121-130.
Coleman, R.L., Wilkinson, D., McAdam, K.P.W.J. Voluntary lay supervisors of directly observed therapy
for tuberculosis in Africa. Tropical Doctor 1998; 28: 78-80.
Conooly, M., Nunn, P. Women and tuberculosis. World Health Statistics Quarterly 1996; 45: 115-119.
De Cock, K.M., Binkin, N.J., Zuber, P.L., et al. Research issues involving HIV-associated tuberculosis in
resource-poor countries. JAMA 1996; 276: 1502-1507.
Dick, J., Lombard, C. Shared vision- a health education project designed to enhance adherence to anti
tuberculosis treatment International Journal of Tuberculosis and Lung Disease 1997; 1 (2): 181-186.
Dick, J., van der Walt, H. Hoogendoom, L. et al. Development of a health education booklet to enhance to
tuberculosis treatment. Tubercle and Lung Disease 1996; 77: 173-177.
Douglas B. Young; New tools for tuberculosis control: do we really need them? International Journal of
Tuberculosis and Lung Disease 1997; 1(3): 193-195.
Dujardin, B., Kegels, G., Buve, A., et al. Tuberculosis control: did the programme fail or did we fail the
programme? Tropical Medicine and International Health 1997; 2: 715-718.
Farmer, P. Social scientists and the new tuberculosis. Social Science & Medicine 1997; 44: (3) 347-358.
Farmer, P., Robin, S., Ramilus, S.L., et al.: Tuberculosis, poverty, and „compliance“: lessons from rural
Haiti. Seminars in Respiratory Infections 1991; 6(4): 254-260.
Floyd, K., Wilkinson, D. Tuberculosis in the HIV/AIDS era: interactions, impacts and solutions. AIDS
Analysis Africa 1997; 7: (5) 5-7
Floyd, K., Wilkinson, D., Gilks, C. Comparison of cost effectiveness of directly observed treatment (DOT)
and conventionally delivered treatment for tuberculosis: experience from rural South Africa.
British Medical Journal 1997, 315: 1407-1411.
Grange, J.M. DOTS and beyond: towards a holistic approach to the conquest of tuberculosis. International
Journal of Tuberculosis and Lung Disease 1997; 1(4): 293-296.
Grange, J.M., Festenstein, F. The human dimension of tuberculosis control. Tubercle and Lung Disease 1993;
74: 219-222.
Halsey, N.A., Coberly, J.S., Desormeaux, J., et al. Randomised trial of isoniazid versus rifampicin and
pyrazinamide for prevention of tuberculosis in HIV-1 infection. The Lancet 1998; 351: 786-792.
Harries, A.D., Maher, D., Nunn, P. Practical and afforadable measures for th eprotection of health-care
workers from tuberculosis in low-income countries. Bulletin of the World Health Organization 1997;
75 (5): 477-489.
Harvey, J.C. The ethics of the AIDS care. Journal of the International Association of Physicians in AIDS Care
1997;3:14-24.
TBbiblio.rtf
25.02.99 13:29
Hausler, H P., Raviglione, M.C. Prise en charge de la tuberculose au niveau communautaire en Afrique
Subsaharienne. SIDAlerte 1996;56: 8-15.
Holmes, C.B., Hausler, H., P. Nunn. A review of sex differences in the epidemiology of tuberculosis.
International Journal of Tuberculosis and Lung Disease 1998; 2 (2): 96-104.
International Union Against Tuberculosis and Lung Disease (IUATLD). Official policies of the IUATLD.
IUATLD Newsletter; January 1998.
IUATLD; Treatment regimens in HIV-infected tuberculosis patients - An official statement International
Journal of Tuberculosis and Lung Disease 1998; 2(2): 175-178
Jaramillo, E. Pulmonary tuberculosis and health-seeking behaviour: how to get a delayed diagnosis in Cali,
Colombia. Tropical Medicine and International Health 1998; 3: 138-144.
Kessler, C., Connolly, M., Levy, M., etal. Tuberculosis control in refugees and displaced persons. 1996.
WHO/TB/96.209
Kessler, C., Connolly, M., Levy, M., et al. Tuberculosis control in refugee populations: a challenge to both
relief agencies and National Programs. International Journal of Tuberuclosis and Lung Disease 1998;
2(2): 105-110.
Kochi, A. Is DOTS the health breakthrough of the 1990s? World Health Forum 1997; 18:225-247.
Liefooghe, R., Baliddawa, J.B., Kipruto, E.M., et al. From their own perspective. A Kenyan community’s
perception of tuberculosis. Tropical Medicine and International Health 1997; 2: 809-821.
Maher D., P. Chaulet, Sergio Spinaci, A. Harries, Le traitement de la Tuberculose: Principes a I’intention des
programmes nationaux. Organisation Mondiale de la Sante, 1997; WHO/TB/97.220
Maher, D., Rhausler, P., Raviglione, C., et al. Tuberculosis care in community care organizations in subSaharan Africa: practice and potential. International Journal of Tuberculosis and Lung Disease 1997;
1(§): 276-283.
MAP. The status and trends of the HIV/AIDS epidemics in the world. 1998.
McAdam, K.P.W.J. Back to the future: ‘the ten commitments’. In: Porter, J.D.H., McAdam, K.P.W.J.:
Tuberculosis: Back to the future. Wiley, London. 1994, pp.267-276.
Medical Coordination Secretariat (MCS). Policy considerations and recommendations. In: AIDS policy paper
1998; 26-30.
Msamanga, G.I., Fawzi, W.W. The double burden of HIV infection and tuberculosis in Sub-Saharan Africa.
New England Journal of Medicine 1997, 337 (12) 849-851.
Napolitano, L. Gulf states launch TB elimination initiative. The TB Treatment Observer 1997; 3:1
Perlman, D C., Hanvanich, M. Prophylaxis and treatment of HIV-related tuberculosis. AIDS 1997;! 1
(Suppl.A): S173-S179.
Rangan, S.: Making TB care and cure a reality for women. The Observer 1998, Sept. 15: 2
Raviglione, M.C., Dye, C., Schmidt, S.. etal. Assessment of worldwide tuberculosis control. The Lancet 1997;
350: 624-629.
Raviglione, M.C., Nunn, P., Kochi, A., et al.. The pandemic of HIV-associated tuberculosis.
Reyes, H., Coninx, R. Pitfalls of tuberculosis programmes in prisons. British Medical Journal 1997, 315:
1447-1450.
Rieder, H.L., Dixie, E., Snider, J. Tuberculosis control in refugee settlements. Tubercle 1989; 70: 127-134.
Rieder, H.L., Enarson, D. A. A computer-based ordering system for supplies in national Tuberculosis
Programs. Tubercle and Lung Disease 1995; 76: 450-454.
Robert-Koch-Institut. Zur Tuberkulose-Situation in der Welt 1995. Epidemiologisches Bulletin 1996; 34:1
Rubel, A. J., Garro, L.C. Social and cultural factors in the successful control of tuberculosis. Public Health
Reports 1992; 107: 626-636.
Shoaib, I.M. DOTS only good on paper. Africa Health 1998; 20:(3)
Shuster, E. The Nuremberg Code: Hippocratic ethics and human rights. The Lancet 1998; 351: 974-977.
SidAlerte Internationale. Tuberculose & SEDA, meme combat.. 1996.
-2-
Squire, S B., Wilkinson, D. Strengthening „DOTS“ through community care for tuberculosis. British
Medical Journal 1997; 315: 1395-1396.
TB & Leprosy Control Services, Daka, Bangladesh. National guidelines for tuberculosis control. 1993.
The Kasango Project Team and The Unit for Research and Training in Public Health. The impact of primary
and secondary health care levels on tuberculosis control activities in Kasongo (Zaire). Bulletin of
the International Union Against Tuberculosis 1982; 57:150-155.
UNAIDS. HIV threatens progress against worsening global tuberculosis epidemic. UNAIDS Press Release
1998.
UNAIDS. Policy statement on preventive therapy against tuberculosis in people living with HIV. Report of
a meeting in Geneva, Febr. 18-20, 1998. WHO/TB/98.225: 3-6.
UNAIDS.Tuberculosis and AIDS. UNAIDS Best Practice Collection. 1997.
Volmink, I, Gamer, P. Systematic review of randomised trials of strategies to promote adherence to tuberculosis
treatment. British Medical Journal, 1997, 315: 1403-1406.
Wallace, D. The resurgence of tuberculosis. The Lancet 1996; 347: 1115-1116.
Whalen, C.C., Johnson, J.L., Okwera, A., et al. A trial of three regimens to prevent tuberculosis in Ugandan
adults infected with the human immunodeficiency virus. New England Journal of Medicine 1997;
337: 801-808.
Wijnen, A. van. Practical Guidelines for the implementation of a tuberculosis control programme. 1993.
Wilkinson, D., Davies, G.R. Coping with Africa’s increasing tuberculosis burden: are community
supervisors an essential component of the DOT strategy? Tropical Medicine and International
Health 1997; 2: 700-704.
Wilkinson, D., Squire, S B., Gamer, P. Effect of preventive treatment for tuberculosis in adults infected with
HIV: systematic review of randomised placebo controlled trials. British Medical Journal 1998, 317:
625-629.
World Council of Churches. Consultative Group on AIDS. Final Report. 1996.
World Health Organization (WHO). A deadly partnership. Tuberculosis in the era of HIV. 1996.
WHO/TB/96.204.
World Health Organization (WHO). Annual Tuberculosis Case Notification. WHO. Health Indicators. 1997:
101-108.
World Health Organization (WHO). Anti-tuberculosis drug-resistance in the world. 1997. WHO/TB/97.229.
World Health Organization (WHO). Epidemiological Forecast. The Observer 1998.
World Health Organization (WHO). Framework for effective tuberculosis control. 1993.
World Health Organization (WHO). Global Tuberculosis Control - WHO Report 1998; WHO/TB/98.237
World Health Organization (WHO). Guidelines for conducting a review of a national tuberculosis
tuberculosis programme; WHO/TB/98.240
World Health Organization (WHO). Managing the dual epidemics of tuberculosis and HFV/AIDS - A review
of challenge and response in Brazil, India, Indonesia, Kenya and Thailand. 1998. WHO/TB/98.243
World Health Organization (WHO). TB Advocacy. A practical guide. 1998. WHO/TB/98.239.
World Health Organization (WHO). The HIV/AIDS and tuberculosis epidemics. Implications for TB
control. 1994. WHO/TB/CARG(4)/94.4.
World Health Organization (WHO). Treatment of tuberculosis: guidelines for national programmes. 1997.
WHO/TB/97.220
World Health Organization (WHO). Tuberculosis and HIV Research: Working Towards Solutions - Results
of a WHO Workshop on the Formulation of a New TB/HIV Research Strategy. 1995.
WHO/TB//95.193.
World Health Organization (WHO). Tuberculosis control as an integral part of primary health care. 1988.
World Health Organization (WHO). Tuberculosis. The WHO/IUATLD global project on antituberculosis
drug-resistance surveillance. Weekly Epidemiological Record 1996; 71:281-285
-3-
World Health Organization. Tuberculosis control in refugee situations. An inter-agency field manual. 1997.
WHO/TB/97.221
Wouters, P. Genome sequence TB unravelled. 1998.
Zumla, A., Grange, J. Tuberculosis. British Medical Journal 1998; 316: 1962-1964.
Zumla, A., Grange, J.M. Establishing a united front against the injustice of tuberculosis. International
Journal of Tuberculosis and Lung Disease 1998; 2(3): 179-181.
-4-
- Media
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