Extra-Pulmonary Tuberculosis: a High Frequency in the absence of HIV infection

Item

Title
Extra-Pulmonary Tuberculosis: a High Frequency
in the absence of HIV infection
extracted text
158

INT J TUBERC LUNG DIS 1(2):159-162
© 1997 IUATLD

The International Journal of Tuberculosis and Lung Disease

miotherapie ; 4 patients out etc exclus pour diverses rai­
sons, ce qui laisse 29 cas pour I’analyse. Aucune reclmte

necessitant un retraiteinent n'a etc observec.
CONCLUSION: La combinaison de la chirurgie (quand
elle esl indiquee) et d'une chimiotherapie courte de 9
niois est efficace dans le traitement de la paraplegic de

Pott. Une recuperation neurologique a etc observec chez

tous les patients a la fin de 9 mois ; 8 ont recuperc par
la seule chimiotherapie ; une recuperation motrice
complete a etc obtenue chez 62% d'entre eux au troisieme mois et chez 90% au sixieme mois.

Extra-pulmonary tuberculosis: a high frequency
in the absence of HIV infection
R. L. Cowie, J. W. Sharpe

RESUMEN

Tuberculosis Services for Southern Alberta, Calgary, Alberta, Canada

SUMMARY
OBJETIVOS: Evaluar la eficacia de una quimioterapia
de corta duracion de 9 meses y estudiar el tipo de recupcracion neurologica en los pacientes con paraplegia de

Pott.
METODO : Pacientes que prescniaban una paraplegia
espastica rcciente debida a una tuberculosis vertebral
clinica y radiologicamente activa, que comprometia los
cuerpos vertebrales D4-LI, fueron tratados con estreptomicina, rifampicina, isoniacida y etambutol diariamente
durante los dos primeros meses. y luego. con rifampi­
cina e isoniacida dos veces por semana durante los side
meses siguientes. Este estudio fue conducido en dos
faxes. En la primera fase se incluyeron 10 pacientes en
un estudio abierto, en el que todos los pacientes habian
sido sometidos a una intervencion quirurgica de tipo

Hong Kong modificada, ademas de la quimioterapia ;
en la fase siguiente, 23 pacientes incluidos en el estudio
fueron distribuidos de manera aleatoria en dos grupos
de tratamiento : quimioterapia sola y quimioterapia mas
cirugia. Todos los pacientes fueron seguidos durante

5 arms a partir del comienzo del tratamiento. Para predecir la recuperacidn neurologica se elaboro un sislema

de score.
RESULTADOS : En total 33 pacientes fueron induidos y
tratados con quimioterapia : 13 pacientes fueron atribuidos al tratamiento con quimioterapia sola, de los cuales
3 debieron ser operados en razon de un deterioro clinico ;
los otros 20 recibieron la quimioterapia mas la intervencion quirurgica ; 4 pacientes fueron excluidos por diversas razones. Io que deja 29 casos para el analisis.
No se observd ninguna recaida que necesitara un rctratamiento.
CONCLUSION: La combinacion de la cirugia (cuando
esta indicada) y de una quimioterapia de corta duracion
de 9 meses cs eficaz en el tratamiento de la paraplegia

de Pott. Todos los pacientes presentaron una recuperacion neurologica al final de los 9 meses ; 8 sc recuperaron con quimioterapia sola. Se obtuvo una recuperacion moiora completa en el 62% de los casos a los 3

SETTING: A tuberculosis centre for the diagnosis, man­
agement and control of all tuberculosis in a region in
Western Canada with a population of approximately

1.2 million.
OBJECTIVE: To measure the proportion of cases of
extra pulmonary tuberculosis in relation to country of
birth, age and gender of the subject.
DESIGN: A prospective study of all patients with tuber­
culosis diagnosed during a five-year period. 1990-1994.
Information relating to age. country of birth and details
relating to their tuberculosis were all gathered and
stored on a computerised tuberculosis register.
RESULTS: A total of 351 patients with tuberculosis
were diagnosed during the five-year period. Jixlrapulmon.irv tuberculosis, defined as disease which, with
tlieexception of miliary tuberculosis, was not associated

with lung involvement, was diagnosed in 160 (46%) of
the patients. I he incidence of extra-pulmonary tuber-

cidosis, especially lymph node disease, tended to be
higher in younger patients but was significantly higher
in immigrants from Asia in whom the majority (61%)
presented with extra-pulmonary disease. Less than 2%
of the subjects in this study were infected w ith the human
immunodeficiency virus (HIV).
CONCLUSION: Extra-pulmonary tuberculosis ac­
counted for approximately half of the cases of tuber­
culosis in a western Canadian tuberculosis centre. Hus
high frequency of extra-pulmonary disease was not at­
tributable to HIV infection.
key words: tuberculosis;extra-pulmonary; non-HIV;
immigrant; age

meses y en el 90% a los 6 meses.
U THOIKIH PRE VIOUS STUDIES have show n that
extra-pulmonary tuberculosis is more frequent in young
adults and in those of Asian origin,1 '' a high inci­

dence of extra-pulmonary disease has become sy nony
■nous with the human immunodeficiency virus HIV
infection,’ ’ which is more prevalent in those with
extra-pulmonary than with pulmonary tuberculosis/

Previous studies in Canada9 anti the USA1" have sug­
gested that 16 to 18% of all cases of tuberculosis will
be extra-pulmonary. The present study of patients
presenting to the tuberculosis service for the southern
hall ol the Province of Alberta. Canada, was set up
when an initial review of the tuberculosis register
showed a higher than expected proportion of patients
with extra-pulmonary disease. The completed study

has confirmed the initial impression that approxi­
mately half of the patients with tuberculosis had
extra-pulmonary disease without associated pulmo

ern part of the Province of Alberta. All relevant in­
formation concerning these patients is collected and
entered into the Provincial tuberculosis register. All
patients with tuberculosis diagnosed during the fiveyear period from January 1 1990 to December 31 1994
were included in this study. Information gathered and
examined for this study included the site or sites in­
volved bv tuberculosis, and the age, gender and coun­
try of birth of the patient. During the period of the
study, an unlinked anonymous study of HIV infec­
tion in the patients with tuberculosis who were not
known to have HIV infection was conducted to deter­
mine the prevalence of HIV infection in patients with
tuberculosis.
I he data were analyzed with x’ analy sis of contin­
gency tables. Student’s t test and ANOVA or by the
Kruskal-Wallis one-way ANOV.A when the data were
not normally distributed.11

nary involvement.

RESULTS

POPULATION AND METHODS

The facility managed 351 patients with tuberculosis

The tuberculosis facility in Calgary, Alberta, manages
all cases of tuberculosis in the population of thesouth-

in the five-year period, a rate of approximately 6 cases
per 100 HOI) inhabitants per year. Fifty-two percent ol

Correspondence to: Dr. R. I . Cow.e, Foothills Hospital. 1403-29 Street NW. ( algary, Alberta, Canada T2N 2T9

Frequent eirtra-pulmonary TB without HIV infection
160

161

The International Journal of Tuberculosis and lung Disease

the patients were immigrants from Asia: one third

=

dll

14.6. /’ < O.OOOOI) and female gender (x2 dfl

of Asian-born subjects with extra-pulmonary tuber­

hours of sunlight per annum, but it is possible that

culosis has been noted in other studies of immigrant

the seasonal imbalance might be associated with re­

populations in industrialised countries.1*4

duced vitamin 1) levels compared with those preva­

each from China and from Vietnam, 15% from the

= 14.2. P < ().0()02) were the strongest determinants

Indian subcontinent and 12% from Philippines; 182

for extra-pulmonary tuberculosis. Patients with extra-

It is not clear why so many Asian-born immigrants

Tuberculosis of superficial lymph nodes is recog­

lent in Asian immigrants' countries of origin.

pulmonary tuberculosis and in particular those with

develop extra-pulmonary tuberculosis. In most in­

The diagnosis of tuberculosis was established by

h mph node disease were younger than those with pul­

stances. immigrants to Canada are screened and usu­

nised to occur in a younger group than those with tu­

culture of Al v< obuctertuiu tuberculosis in 267 patients

monary tuberculosis; these differences were signifi­

ally treated for pulmonary tuberculosis before immi­

berculosis elsewhere. In the present study the relation­

163 with pulmonary. 104 with extra-pulmonary dis­

cant m general and within the Asian and the non-

gration. Such screening and treatment would have no

ship w ith age was dominated by the country of birth

ease ; by histology combined with characteristic clin­

aboriginal ( anadian born groups (see Table).

impact on the risk of pulmonary tuberculosis after

ami gender of the subjects. The subjects with lymph

immigration in those immigrants who have been in­

node disease were the youngest within each group,

fected with Al. tuberculosis but have normal pre­

but the Asian-born group with lymph node disease

52%) were female.

ical or radiologic features and response to treatment

in 46 patients (6 with pulmonary, 40 with extra-

DISCUSSION

pulmonary disease); and in the remaining 38 patients

immigration radiographs. However, it has been shown

were older than those with node disease from the

that one third of cases of tuberculosis develop in sub­

other groups (see Table). Immigration from an Asian

pulmonary tuberculosis been found to account for

jects who were known to have lung ‘scars' suggesting

countrv was thus the major risk factor for lymph node

as much as 46% of the cases of tuberculosis. An ear-

previous post-pnmary

tuberculosis.1"’211

tuberculosis in the present and other studies.l-’-," ls

ical primary pulmonary complex in ,i recent contact.

lier North American study reported 37% of extra-

Thus the pre-immigration screening and treatment, if

I he diagnosis of tuberculosis in the industrialised

Three patients with pulmonary tuberculosis were

pulmonary tuberculosis but the total number of cases

completely effective, could account for a 33% reduc­

world isTiften delayed because the disease is not com­

known to be infected with HIV. An additional two

with tuberculosis in the ll-year study was III. all pa­

tion in new cases of pulmonary tuberculosis, and the

mon. 1 he increase in extra-pulmonary tuberculous

subjects with HIV' infection were detected amongst

tients had been admitted to hospital and the sample

absence of such a policy might thus result in an in­

disease is likely to further delay the diagnosis.9-,“ In

those with tuberculosis in the province-wide anony­

was thus small and probably not representative of .ill

crease in the total number of cases of tuberculosis and

the present study, five deaths occurred in subjects w ho

mous unlinked study. Thus, the maximum prevalence

ol the tuberculosis in the community.12

.1 decrease in the proportion of subjects of Asian origin

presented for investigation w ith symptoms and signs

In an earlier study of extra-pulmonary tubercu­

with extra-pulmonary tuberculosis. Using our data,

of extra-pulmonary tuberculosis 3 to <8 months before

(if both of these unidentified subjects were from the

losis m (.anada. Enarson et al.** reported that 17%

the percentage of Asian-born with extra-pulmonary

their death revealed the diagnosis. Specimens are often

southern part of the province:. Pulmonary tubercu­

of their cases hail extra-pulmonary tuberculosis. hiiT

tuberculosis would decrease from 61% to 51%: (no.

not submitted for mycobacterial cuhureH>ccause of

losis, primary (six patients) or post-primary, occurred

excluded patients with pleural and miliary

with extra-pulmonary

laiturcTo consider a diagnosis of extra-pulmonary tu-

in 189 (.54%) patients; in 13 of these there was addi­

from their definition. Using their definition, we would

tuberculosis: new total = [no. with pulmonary tuber­

bercuiosis. With the rising prevalence of resistant AT

tional involvement of extra-pulmonary sites. In 162

reclassify 31 (17 miliary and 14 pleural) of our pa­

culosis

0.66] + no. with extra-pulmonary tubercu­

tuberculosis, especially in Asian countries, it is diffi­
cult to provide appropriate treatment for tuberculosis

(14 pulmonary. 24 extra-pulmonary) the diagnosis

In no previous population-based study

was based on the same features without histological
support or on characteristic syndromes such as a typ­

of HIV infection in those with tuberculosis was 1.4%

has extra-

disease

pulmonary

tuberculosis/new total with

46%) patients only extra-pulmonary sites were in­

tients but still have double the proportion w ith extra-

losis = ([71/0.66] + 111) = 219 and percentage with

volved. Intra-thoracic, extra-pulmonary disease oc­

pulmonary disease (36% versus 17%) recorded from

extra-pulmonary

curred in 16 patients (pleural 14, pericardial 2) and

their 1970-1974 study. Much of that change in the

2I9| x 100 = 51%). It would appear, therefore, that

present study, drug susceptibility

17 additional patients had miliary disease. T he major­

pattern of tuberculosis might reflect an increase in the

even w ithout the pre-immigration screening and treat­

not available for 34% of the patients with lymph

tuberculosis would thus be [III

ity (79 patients) of those with extra-pulmonary tuber­

number of foreign born, notably Asian-born, in the

ment programme, a still very

culosis had disease involving superficial lymph nodes.

(Canadian population in the intervening 20 years. I low -

immigrants would present with extra-pulmonary tu­

high 51% of Asian

when mvcobacteri.il cultures are not available. In the
information was

node disease because specnncns had been placed in
jormalm.

Extra-pulmonary tuberculosis accounted for 61"/.,

ever, no data concerning the country of birth of the

berculosis. There are few reports concerning the pro­

In conclusion, this population based study of tuber­

of the cases of tuberculosis in patients born in Asia.

( anadian population arc available, although current

portion of patients with tuberculosis who have extra

culosis in Western (. anada has demonstrated a high

Asian patients were specially prone to lymph node dis­

immigration data suggest that approximately

17.%

pulmonary tuberculosis in the countries where our

proportion of cases of extra-pulmonary tuberculosis

ease: 82"/.i of the 79 patients with lymph node tuber­

arc foreign born. Similar population changes have oc­

immigrant population were born. Cine report from

not attributable to HIV infection. In the Asian-born

culosis were born m Asia. Icmale patients accounted

curred in most ol the industrialised world and the

Taiwan indicates that 20% of tuberculosis patients

members of the population, extra-pulmonary tubercu­

for 71% of the superficial Is mph node disease and

findings of the present study are thus likely to be gen­

have extra-pulmonary‘disease wTfh or w ithout puTino-

losis is more common than pulmonary tuberculosis.

52'’/., of .ill cases of tuberculosis. Origin m Asia (x2

eralisable to other centres. I he very high proportion

n^rTdiscase.1' A Malaysian study reports" irXCextEk.
pulmonary tuberculosis, 14% of whom also hail pul­

monary tuberculosis.1'- The data from Malaysia and

Table

Taiwan suggest that the high proportion of extra-

Age by area of origin and sue of tuberculosis

pulmonary disease in Asians in our study is associ­

Asian
|n = 182|
age ISO)

Other immigrant
|n » 64|
age (SO)

Canada
|n
60|
age (SO)

Aboriginal
Canadian
|n = 39|
age (SO)

P

common in immigrants from Asia,11" but no expla­

Pulmonary
(post primary)|n - 183|

57 4
(22 10)
PH

52 1
(22 52)
|44|

53 9
(19 60)
|4()|

39 0
(22 49)
|28|

0 008

nation for this finding is apparent. Any explanation

Extra pulmonary
(not lymph node)
|n = 83|

50 9
(22 10)
|46|

43 6
(19 63)
|I4|

45 9
(22 61)
|15|

57 6
(27 27)
|8|

05

Lymph node
|n = 79|

40 2
(16 47i
|65|

31 0
(25 30)
I6|

26 0
(32 16)
|5|

30 0
(4 00)
131

02

P

<00001

0 07

0 02

0 1

Birth place

ated with their having immigrated. Lymph node tuber­
culosis, in particular, has been noted by others tobe

would need to account for the apparent difference in
the proportions of lymph node and other forms of
extra-pulmonary tuberculosis in Asian countries as

compared with those in Asians who emigrate. One ex­

■ the SIX patients with primary tubetcuksus were not included in
in this analysis as they weie all young children, mean age 4 years
The P values tn lhe table represent analysts of vanj'ito ’'
The Asian born pattents with lymph node disease .tn I pulmonary disease wore significantly older than all other patients with disease in those sites (lymph node
P - 0 03. pulmonary P - 0 0041

planation. proposed for Asian immigrants to Britain,

is that their propensity to develop extra-pulmonary tu­
berculosis is associated with reduced immunocompe­

tence against tuberculosis from vitamin 1) deficiency

induced by reduced exposure to sunlight.IS Weather
records from Southern Alberta suggest above average

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INT J TUBERC LUNG DIS 1(2):163-169
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A retrospective comparison of clarithromycin versus rifampin
in combination treatment for disseminated Mycobacterium
avium complex disease in AIDS: clarithromycin decreases
transfusion requirements.
W. J. Burman,*1 R. R. Reves,*1* C. A. Rietmeijer,*’ D. L. Cohn*1
•Denver Disease Control Service, Denver Health and Hospitals, and ’the Departments of Medicine (Division of
Infectious Diseases) and ‘Preventive Medicine and Biostatistics, University of Colorado Health Sciences Center,
Denver, Colorado, USA

SUMMARY

SETTING: Urban county medical center.

agents were used less often (28% vs. 44%. P = 0.04).

OBJECTIVE: To compare clinical outcomes associated

In

RESUME

with two treatment regimens for AIDS-associated dis­

anemia at the time of DMAC diagnosis was associated

CADRE : Un centre de tuberculosc pour le diagnostic, le

qui. a I'exception d'une tuberculosc miliaire, nest pas as-

seminated Mycobacterium ai’ium complex (DMAC).

with transfusion-dependence (relative risk |RR] 5.6,

traiiement ct le contrble de toutes les formes de tuberculosc

socicc a line atteinte parenchymateuse, a etc diagnostiquec

Erom

1989 to mid-1992, patients were treated wiih

95% confidence interval [Cl] 2.2, 13.8, P < 0.001) and

dans une region du Canada occidental dont la popula­

dans 160 cas (46%). ^incidence de la tuberculosc extra-

rifampin, cthambutol, and clofazimine; in mid-1992

clarithromycin treatment was inversely associated with

tion est d'environ 1.2 million.

pulinonaire et en particulicr des maladies ganglionnaircs,

clarithromycin replaced rifampin.

OBJECTlf : Mcsurer la proportion descas de tuberculosc

a tendance a etre plus elevee chez les sujets jeunes mais

DESIGN:

extrapulmonairc rappories au pays d'origine, a Lage et

an sexe des patients.

retrospective

a

multivariate

logistic

regression

model,

severe

transfusion dependence (RR 0.4, 95% Cl 0.1, 0.98, P =

of

with

0.04). In a multivariate Cox regression model including

est significativement plus elevee chez les immigrants pro­

DM/\C; the main outcome measures assessed were toxic­

other factors affecting survival, clarithromycin treat­

venant d'Asie, dont la majorite (61%) sc presentent avcc

ity associated with DMAC treatment, transfusions after

ment did not confer a survival advantage (P = 0.74).

SCHEMA : Elude prospective de tons les patients atteints

tine affection extrapulmonairc. Moins de 2% des sujets

the diagnosis of DMAC. and survival.

CONCLUSIONS:

de tuberculosc, diagnostiques pendant une pcriode de cinq

de cettc etude etaient infectes par le virus de I'immuno-

RESULTS: 88 patients received the rifampin-based regi­

men was better tolerated and was associated with sub

ans (1990-1994). Les informations relatives a Cage ct au

deficience humaine (VIH).

men and 86 were treated w ith the clarithromycin-based

stantially

pay s d’origine, ci les details en rapport avec la tuberculosc

CONCLUSION : La tuberculosc extrapulmonairc repre-

regimen. Drug-related adverse events were recorded less

rifampin-based regimen; survival was not affected.

out etc rassembles ct saisis dans un registre informatise

sente approximativement la moitie des cas de tuberculosc

frequently

de tuberculosc.

dans un centre de tuberculosc du Canada occidental. Cette

42%, P

RESULTATS : Pendant la pcriode de cinq ans, le diagnos­

haute frequence de la tuberculosc extrapulmonairc n'est

tic de tuberculosc a etc portc chez 351 patients. La tu-

pas attribuable a I'infcction par le VIH.

bcrculose extrapulmonairc. definie cominc une affection

A

with

=

clarithromycin

forma en la cual. fuera de la tuberculosis miliar, no sc

diagnostico. tratamiento y control de todas las formas

constata un compromiso pulmonar. El 46% (160) de los

de tuberculosis en una region de Canada occidental cuva

pacientes presentaban esta forma de la enfermedad. La

poblacidn es de alrededor de 1.2 millones de habitantes.

incidencia de la tuberculosis extrapulmonar y en parti­

OBJETIVOS : Mcdir la proporcidn de tuberculosis exlra-

cular la afeccibn ganglionar presentaba una tendencia a

pulmonar en funcidn del pais de origen, edad y sexo de

ser mas alia en los sujetos jovenes, pero era significati-

los pacientes.

vamente mas elevada en los immigrantes de proveniencia

ME TO DO : F.studio prospectivo de todos los pacientes de

asiatica, en los cuales el 61% de los pacientes presenta­

tuberculosis diagnosticados durante un periodo de cinco

ban una tuberculosis extrapulmonar. Menus del 2% de

anos (1990-1994). Las informaciones con rcspecto a la

los sujetos de este estudio estaban infcctados pur cl virus

edad, pais de origen y los detalles relativos a la tuberculosis

de la inmunodeficiencia humana (VIH).

fueron recolectadas y entradas en un registro computa-

CONCLUSION : La tuberculosis extrapulmonar representa

rizado de tuberculosis.

aproximadamente la mitad de los casus de tuberculosis

RESULTADOS : Durante el periodo de cinco anos sc di-

en un centro de tuberculosis de Canada occidental. Esta

agnostied un total de 351 pacientes con tuberculosis. La

alta frecuencia de tuberculosis extrapulmonar no es atri-

tuberculosis extrapulmonar fue definida como aquella

buible a la infeccidn por VIH.

treatment

(21%

vs.

lower

I he

clarithromycin-containing

transfusion

requirements

than

regi­
the

KEY WORDS: Alv. i>hj, teriuxi avntnt complex; AIDS;

clarithromycin; rifampin; transfusion

Mvcohactcnum avium complex

mens th.it were used for DMAC treatment among

disease (DMAC.) is one of the most common oppor­

AIDS patients in a municipal health care system. The

tunistic infections in patients with advanced acquired

immune deficiency

MARCO DE REFERENCIA : Centro de tuberculosis para el

patients

0.005), and additional antimycobacterial

DISSEMINATED

RESUMEN

review

syndrome (AIDS).1

initial treatment regimen consisted of rifampin in

Retrospec­

combination w uh cthambutol and clofazimine; rifam­

tive- and prospective observational studies’-4 suggest

pin was replaced by clarithromycin w hen the latter be­

that multidrug treatment of DMAC is associated with

came available in early 1992.

improvements in symptoms and survival.

I he new

macrolide antibiotic clarithromycin has impressive actisity against AL avium complex, both in vitro and

METHODS

in animal models.' Human studies using quantita­

I he records of the Mycobacteriology Laboratory of

tive mycobactereniia as an endpoint have confirmed

Ik-nver 1 Icalth and I lospitals were used to identify pa­

the preclinical studies6-

suggesting that clarithromy­

tients with AL avium complex isolated from speci­

cin has more activity than previous multidrug regi-

mens ol blood, liver, or bone marrow between I |an-

inens.”-'1 These results have led to the recommenda­

u.iry

tion that clarithromycin or azithromycin be included

performs all mycobacterial cultures for Denver Gen­

in all initial treatment regimens for DMAC,"1-11 but

eral I lospital and the .AIDS clinic. We did not include

there is limited information regarding the effects ol this

patients with Al. avium complex isolated solely from

enhanced bacteriologic activity on clinical outcomes.

non-stenie sites (i.c., sputum or stool), nor were such

We conducted a retrospective study to compare the
clinical outcomes associated with two standard regi-

1989 and 31 December 1993. This laboratory

patients generally irealed presumptively lor DMAC in
our clinic.

After an initial positive blood culture.

Correspondence to: William |. Burman MD. 605 Bannock St.. Denver. ( () XO2O4, USA. Tel: (.303) 4 36-7200. E.ix:
4 36-7211.

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RF-TB-1.17.pdf

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