PAEDIATRIC RESPIRATORY REVIEWS (2004) 5, 225–230

doi:10.1016/j.prrv.2004.04.006

SERIES: HIV-ASSOCIATED LUNG DISEASE

Tuberculosis in HIV-infected children

Soumya Swaminathan

Tuberculosis Research Centre, Mayor VR Ramanathan Road, Chetpet, Chennai 600 031, India

KEYWORDS Summary Tuberculosis (TB) is the most common opportunistic infection in human
tuberculosis; immunodeficiency virus (HIV)-infected people worldwide. HIV-positive children are at
HIV infection; risk of diagnostic error as well as delayed diagnosis of TB because of overlapping clinical
children and radiographic features with other lung diseases. Acute pneumonias and chronic lung
diseases such as bronchiectasis and lymphocytic interstitial pneumonitis are difficult to
distinguish from TB. TB manifestations are more severe in HIV-positive children and
progression to death is more rapid than in HIV-negative children. The response to
standard short-course therapy in HIV-positive children is not as good as in HIV-negative
children due to lower cure rates and higher mortality. TB hastens the progression of HIV
disease by increasing viral replication and reducing CD4 counts further. Although Bacille
Calmette-Guerin vaccination could lead to disseminated Mycobacterium bovis disease in
the presence of immunosuppression, this has been rarely reported. More studies are
required to assess the role of newer diagnostic tests, TB preventive therapy and co-
administration of anti-retroviral therapy in the control of TB among HIV-infected children.
ß 2004 Elsevier Ltd. All rights reserved.

Nearly 5 million people (4.2 million adults and 700 000
children) are newly infected with human immunodeficiency
virus (HIV) each year; more than 95% of them belong to
developing countries. It is estimated that there are 40
million people living with HIV/acquired immunodeficiency
syndrome (AIDS) worldwide and of these, 2.5 million are
children less than 15 years of age.1 HIV is lowering life
expectancy and reversing gains in child survival in some
parts of Africa.2 Paediatric HIV infection is acquired mainly
by transmission from mother to child during pregnancy,
labour or breast feeding. Perinatal transmission accounts for
>90% of infections in children and is a major concern in
most developing countries.3 Antenatal HIV prevalence
rates vary widely by region and range from 1% in India
to 25–30% in some countries in south and east Africa.
Although effective interventions in the form of anti-retro-
viral drugs during pregnancy, elective Caesarean section
and avoidance of breast feeding reduce transmission to
<2%, these are not widely available to most mothers in the
developing world. Until inequalities in health care are
addressed and resolved, it is likely that the number of
HIV-infected children in the world will continue to increase.
Correspondence to: S. Swaminathan. Tel.: þ91 44 28362442;
fax: 91-44-28362528; E-mail: doctorsoumya@yahoo.com
Worldwide, tuberculosis (TB) is the most frequent co-
infection in subjects with HIV-1 infection.4 TB and HIV have
adverse effects on each other. TB worsens the course of
HIV-related immunodeficiency through a variety of
mechanisms, whereas HIV infection is the strongest known
risk factor for the development of active TB. This occurs
due to re-activation of latent infection as well as increased
susceptibility to new infections.5 While the lifetime risk of
developing disease is 10% in individuals with latent tuber-
culous infection, this increases to 7–8%/year in those who
acquire HIV infection.6 The incidence of TB in patients with
AIDS is almost 500 times the incidence in the general
population and TB is thought to account for about 30% of
AIDS deaths.7 TB rates have increased by 35% in some
countries due to the impact of the HIV epidemic. A study
from Zaire showed that the risk of TB in HIV-positive
mothers was three times more than in HIV-negative
mothers.8 Infants born to HIV-infected mothers are sus-
ceptible to both HIV infection and TB.
EPIDEMIOLOGY
TB is the most common opportunistic infection in HIV-
infected individuals and it is estimated that about 60–70% of
HIV-infected adults in India eventually develop TB.6 Unlike

1526–0542/$ – see front matter ß 2004 Elsevier Ltd. All rights reserved.
226
other opportunistic infections, it occurs throughout the
course of HIV-1 infection. Children acquire TB infection
through contact with infected adults. Children with HIV
infection are at increased risk of progression from asymp-
tomatic tuberculous infection to TB disease. Although the
proportion of HIV-infected children with TB is lower than
HIV-infected adults, the number with HIV-attributable TB is
increasing rapidly. Several studies have demonstrated
increased rates of childhood TB associated with increasing
rates of disease in HIV-infected adults in the community.9,10
In Kenya, the annual risk of TB in school children increased
sharply between 1986 and 1996 in districts with a 50% HIV
prevalence among TB patients, but this was not seen in
other districts.11
In various studies in India, 14–67.5% of children with HIV
infection have been diagnosed with TB.12–14 These figures
vary widely, partly because of difficulties in the definitive
diagnosis of TB as some symptoms produced by HIV/AIDS
are similar to TB. There are few studies of HIV seropreva-
lence among children with TB from different parts of the
world. A study from Zambia showed an HIV seroprevalence
rate of 37%15 while Madhi et al. reported HIV seropreva-
lence of 42% among children with TB in South Africa.16 In
most parts of India, HIV seroprevalence among children with
TB is low (<2%); however, it was 18% among children with
central nervous system or miliary TB in Mumbai.13 Another
study from Mumbai on the utility of clinically directed
selective screening among hospitalised children found that
HIV seropositivity was highest among children with oral
candidiasis (41%), followed by chronic diarrhoea (18%),
disseminated TB (16%), severe malnutrition (14%) and
serious pyogenic infections (11%). While the presence of
oral thrush was the only significant independent predictor, as
the number of risk factors increased, the chances of the child
being infected with HIV also increased.17
PATHOGENESIS OF TB
Cell-mediated immune responses, specifically those
mediated by CD4þ T cells, are important for the control
of both HIV and TB. Thus, individuals with HIV infection,
whose CD4þ T cells are depleted, are less capable of
controlling replication of Mycobacterium tuberculosis. They
are more likely to acquire infection from the environment,
progress rapidly from primary infection to TB disease and
develop re-activation of latent TB infection. Infection with
M. tuberculosis most often occurs via the respiratory tract.
After infection, alveolar macrophages present mycobacter-
ial antigens to CD4þ T cells. This results in the release of
interferon-g and other cytokines, which in turn activates
macrophages to control the mycobacterial infection. With-
out the recruitment and activation of macrophages by the
CD4þ T-cell secreted cytokines in HIV-positive individuals,
there is poor granuloma formation, little or absent caseous
necrosis, poor containment of mycobacteria with large
organism loads and haematogenous dissemination.2
S. SWAMINATHAN
IMPACT OF TB ON HIV DISEASE
The course of HIV infection is accelerated subsequent to
the development of TB. Mycobacteria enhance HIV repli-
cation in tissues by inducing nuclear factor kappa-B, the
cellular factor that binds to the promoter region of HIV.18,19
The development of TB is associated with increased
HIV-1 replication and increased viral loads.5,20 Increased
systemic immune activation as well as altered local cytokine
milieu at sites of M. tuberculosis infection have been impli-
cated in enhanced HIV-1 activity in patients with HIV and
TB. While the in-vitro IFN-g response of mononuclear cells
to mycobacterial antigens is impaired, there are high cir-
culating plasma levels of this cytokine.21 Similar changes
have been observed with the other Th1 cytokines IL-12
and IL-18. This paradoxical response with a mismatch
between in-vitro and in-vivo cytokine responses under-
scores the need for assays that reflect the real situation in
blood/tissues. Mononuclear cell activation is a feature of
active TB both systemically and at sites of M. tuberculosis
infection. Mononuclear cells that express HLA-DR are the
most productive source of HIV replication. Dysregulation in
b chemokines (e.g. MIP-1a and RANTES) and their recep-
tors has been described during TB; this may contribute to
enhanced viral dissemination.22 The programmed cell
death of T cells is increased at the time of diagnosis of
pulmonary TB in HIV-infected patients; this may be partly
responsible for further loss of immune responses directed
to HIV-1.23 TB provides a milieu of continuous cellular
activation and irregularities in cytokine and chemokine
circuits that are permissive of viral replication and expan-
sion in situ.5 While most studies have been conducted in
adults, it is likely that the co-pathogenesis of these two
infections is similar in children.
CLINICAL FEATURES AND
DIAGNOSIS
As most childhood TB is paucibacillary, the diagnosis is
usually based on the history of contact with an adult smear-
positive patient, symptoms and signs of TB, a positive
tuberculin skin test and an abnormal chest radiograph.
While children <2 years old are likely to be infected in
the household by their parents or caregivers, others are
more likely to be infected in the community. For children
living in high burden countries, the absence of household
contact certainly does not exclude TB. While many HIV-
positive adults have the typical clinical and radiological
manifestations of TB, atypical presentations frequently
occur, especially in those with low CD4 counts. Data from
children co-infected with HIV and TB suggest that the
clinical and radiological manifestations do not vary signifi-
cantly from those who are seronegative, although the
disease tends to progress more rapidly.24,25 There may
be an increased tendency for extrapulmonary disease and
dissemination. Extrapulmonary involvement occurs in more
TUBERCULOSIS IN HIV-INFECTED CHILDREN
than 70% of patients with TB and pre-existing AIDS but
only in 24–45% of patients with less advanced HIV dis-
ease.26 In the Ivory Coast, 29% of HIV-positive children had
extrapulmonary disease which was similar to 26% in HIV-
negative children. The common extrapulmonary manifes-
tations were lymphadenopathy, pleural effusion and miliary
TB.27 Chronic weight loss, malnutrition and absence of
Bacille Calmette-Guerin (BCG) scarring are more common
in HIV-infected children with TB. They are also more likely
to show cavitation and miliary TB on chest x ray while
tuberculin reactivity is significantly lower.16
In the author’s experience, of 22 HIV-infected children
diagnosed with TB, the common presenting symptoms were
persistent cough or fever with failure to thrive. The most
common clinical sign was protein energy malnutrition. Only
two children had a positive tuberculin reaction. In most
children, diagnosis was based on a combination of clinical
features and radiological abnormalities (unpublished obser-
vations). The most common radiographic abnormality was
the presence of parenchymal infiltrates/opacities followed by
hilar/mediastinal lymph node enlargement. A miliary-like
picture was seen in four children; however, in three children,
the lesions persisted despite anti-TB therapy, suggesting
other diagnoses. A study from Zimbabwe showed that
lobar infiltrates, especially in the lower lobes, were more
common in HIV-positive children.28
The diagnosis of TB in children with HIV infection poses a
number of challenges. Symptoms and signs are non-specific
and mimic many infections and bacteriologic diagnosis is
uncommon. Sputum induction has been suggested as a
diagnostic method for infants and children hospitalised with
community-acquired pneumonia. Induced sputum gave
higher yields than gastric lavage or nasopharyngeal aspirate
for M. tuberculosis and Pneumocystis carinii, respectively.29
Tuberculin skin testing is of limited value as it is only positive
in a minority of children with HIV infection. A final diagnosis
of confirmed or probable TB is less common than in HIV-
negative children (36% vs 63%), mainly due to the over-
lapping clinical features of these two infections.30
Many children with HIV-1 infection have features of
chronic lung disease with abnormal chest radiographs, thus
making the diagnosis of pulmonary TB even more difficult.31
Furthermore, radiographic manifestations of TB overlap
Table 1 Features helping to differentiate between miliary tuberculosis and lymphocytic
interstitial pneumonitis.
Miliary tuberculosis
Occurs in younger children
Finger clubbing uncommon
Parotid enlargement rare
Child is acutely ill
Widespread distribution of small,
evenly-sized nodules (<2 mm)
Responds to anti-TB treatment
227
with other conditions like P. carinii pneumonia (PCP),
bacterial pneumonia and lymphocytic interstitial pneumo-
nitis (LIP). In the author’s series, the diagnosis of LIP was
made after children had been given a therapeutic trial of
anti-TB therapy for presumed miliary TB but did not show
clinical improvement. LIP is more likely than TB if: recurrent
respiratory infections improve slightly with antibiotics and
steroids; finger clubbing is present; and there is no response
to anti-TB therapy (Table 1). In an autopsy study in African
children dying of respiratory illnesses, Chintu et al. found
that the three most frequent findings in the HIV-positive
group were acute pyogenic pneumonia (41%), PCP (29%)
and cytomegalovirus (22%), whilst TB was seen in all age
groups irrespective of HIV status.32 Such data underscore
the urgent need for improved diagnostic tests for bacterial
pathogens, TB and PCP in resource-limited settings.
THERAPY
It is generally accepted that HIV-positive people with TB
respond as well to short-course chemotherapy as HIV-
negative people. Alhough there have been no clinical trials
in children, studies in HIV-positive adults have shown similar
sputum smear conversion and cure rates as HIV-negative
adults. For pulmonary and most forms of extrapulmonary
TB, standard 6-month chemotherapy with isoniazid (5–
10 mg/kg/day), rifampicin (10–12 mg/kg/day), pyrazinamide
(30 mg/kg/day) and ethambutol (15–20 mg/kg/day) for the
first 2 months followed by isoniazid and rifampicin for the
next 4 months is recommended.33 Drugs may be adminis-
tered daily or thrice weekly and directly observed treat-
ment is recommended wherever possible. For meningitis
and bone and joint TB, a minimum of 9 months of treat-
ment is recommended. Thiacetazone should not be used
since its use is associated with life-threatening Stevens–
Johnson syndrome. Pyridoxine 10 mg daily may be given to
prevent peripheral neuropathy due to isoniazid.
Mortality rates have been reported to be higher among
HIV-infected children with TB than in those without HIV; in
one study, the mortality was 13.4% in HIV-positive and
1.5% in HIV-negative children during the course of ther-
apy.16 Palme et al. found that although adherence to
treatment was high (96%), the cure rate was 58% for
Lymphocytic interstitial pneumonitis
Usually starts in second year, uncommon in infancy
Finger clubbing common
Parotid enlargement may be present
Child is relatively well
Nodules larger, not uniform in size, with
accompanying reticular pattern
No response to anti-TB treatment
228
HIV-positive and 89% for HIV-negative TB patients while
mortality was six-fold higher.34 Deaths are due directly to
TB as well as other AIDS-related opportunistic infections.
Paradoxical reactions may occur during the course of anti-
TB therapy when anti-retroviral treatment restores
immune function. This reaction, also known as immune
reconstitution syndrome, occurs a few weeks after treat-
ment is begun and can manifest as high fever, enlargement
of existing lymph nodes or appearance of new ones with
worsening parenchymal lesions on chest x ray. The reaction
is self-limiting and can be managed conservatively but needs
to be distinguished from a new opportunistic infection.
These reactions can occur in patients on anti-TB treatment
alone but are most common when both TB and HIV
treatment are started together.
The treatment of HIV-infected children with multi-drug-
resistant TB (MDRTB) is likely to require the use of second-
line medications and should be undertaken by an expert.
MDRTB can occur when HIV-positive children are in contact
with adult patients with drug-resistant TB, a phenomenon not
uncommon where HIV is prevalent.35 Second-line drugs
commonly employed are a combination of kanamycin with
a fluoroquinolone, e.g. ofloxacin or ciprofloxacin, ethiona-
mide, cycloserine and pyrazinamide/ethambutol. The choice
of regimen would usually depend on the drug susceptibility
pattern of the adult contact, if available.
Drug interactions can occur between HIV and TB
medications. Rifampicin induces hepatic cytochrome P-
450, resulting in lower serum concentrations of medica-
tions metabolised through this pathway. Rifampicin should
not be administered with protease inhibitors and there is
conflicting evidence of its interaction with nevripaine.
Rifampicin may be substituted by rifabutin but this is not
widely available. In general, the drug combinations pre-
ferred with anti-TB therapy are a combination of two
nucleoside reverse transcriptase inhibitors (ZDV plus lami-
vudine or stavudine plus lamivudine) with efavirenz or
abacavir. More data are needed on the use of these
combinations in children.
Mycobacterium avium complex
Disseminated infection with Mycobacterium avium complex
(MAC) occurs almost exclusively in children and adults with
advanced HIV disease. MAC includes two closely related
species, M. avium and M. intracellulare. They are intracellular
parasites that proliferate within macrophages; in children
with defective cell-mediated immunity, uncontrolled bac-
terial replication occurs. M. avium are environmental sapro-
phytes and can be found in soil, water, food and animals.
The gut may be the portal of entry for the organism.
Clinical presentation can be indolent and slowly pro-
gressive. Most children are severely immunosuppressed
and present with fever, weight loss, abdominal pain and
anaemia. Night sweats, diarrhoea, malaise, neutropenia and
hepatomegaly have been described. Without treatment,
S. SWAMINATHAN
survival ranges from 9 to 11 months. The diagnosis of M.
avium infection requires cultivation from blood or tissue;
blood cultures are usually done using the BACTEC radio-
metric system. Characteristic histological findings of acid-
fast bacilli within macrophages are highly suggestive of MAC
infection but cultures are necessary to distinguish species.
Treatment is with a combination of two or more drugs:
clarithromycin 15 mg/kg daily in two divided doses or
azithromycin 10 mg/kg once daily with ethambutol 15–
20 mg/kg once daily and/or rifabutin 5–10 mg/kg once daily.
Children treated for disseminated MAC must remain on
lifelong prophylaxis with at least two drugs.
PREVENTIVE THERAPY
Preventive therapy (chemoprophylaxis) with isoniazid is
effective in preventing progression of TB infection to disease.
Several studies have documented that 6 or 12 months of
isoniazid (INH) given to tuberculin-skin-test-positive patients
resulted in a 70–83% reduction in the incidence of TB. Based
on these studies, the Centres for Disease Control currently
recommend prophylaxis for all HIV-infected individuals with
a tuberculin skin reaction >5 mm.36 It is important to
exclude active TB before preventive therapy is instituted.
There are several alternative shorter regimens such as 2
months of rifampicin and pyrazinamide, 3 months of iso-
niazid and rifampicin etc., but none have been found to be
superior to 12 months of isoniazid.
BCG vaccination
BCG is one of the most widely used vaccinations in the
world and is part of the Expanded Program of Immunization
(EPI) schedule, often being administered in the weeks after
birth. Although it is a live attenuated vaccine, the World
Health Organisation recommends that BCG should be given
to children with suspected HIV infection unless they have
symptomatic disease, because the risks of TB far outweigh
the complications of immunisation.3 While there have been
no population-based controlled studies of BCG-related
complications, there are reports of regional or disseminated
BCG disease in HIV-infected children. Hesseling et al.
reported six cases of BCG disease among mycobacterial
isolates from 49 HIV-infected children (four with regional
axillary adenitis and two with pulmonary BCG disease). All
patients were asymptomatic at birth, <12 months of age and
severely immunodeficient at presentation.37 Children with
HIV-related or other causes of immunodeficiency are at risk
of disseminated BCG disease and this has to be considered
when evaluating a sick infant for TB.
CONCLUSIONS
TB is one of the most common infections seen in children in
areas of the world where HIV is prevalent. Clinical features
overlap with HIV disease and radiographic findings may be
TUBERCULOSIS IN HIV-INFECTED CHILDREN
non-specific. Although treatment using standard anti-TB
regimens is effective, outcome is poor due to high mortality
rates. Wider access to anti-retroviral therapy is likely to
reduce mortality and morbidity due to TB in HIV-infected
children and adults. Research is required to identify better
diagnostic tests and treatment strategies that include both
anti-TB and anti-retroviral drugs.
PRACTICE POINTS
 HIV is the strongest known risk factor for the
development of TB
 TB accelerates the course of HIV disease
 Symptoms and signs are non-specific; differential
diagnosis includes PCP, bacterial pneumonia and LIP
 Tuberculin test is usually negative
 Standard short-course anti-TB regimens are
recommended for treatment but mortality is
higher in HIV-positive children than HIV-negative
children with TB
 Paradoxical reactions may occur, especially when
anti-TB and anti-retroviral therapy are started
together
RESEARCH DIRECTIONS
 Better diagnostic tests for TB, PCP, pyogenic
pneumonia.
 Clinical trials of anti-retroviral with anti-TB therapy.
 Clinical trials of preventive therapy for TB in HIV-
positive children.
REFERENCES
1. World Health Organisation. Fight Stigma and Discrimination. New
Delhi: WHO SEARO, 2003.
2. Pilheu JA. Tuberculosis 2000: problems and solutions. Int J Tuberc
Lung Dis 1998; 2: 696–703.
3. Seth V, Narain S, Simpson L. HIV and tuberculosis. In: Seth V, Kabra
SK (eds). Essentials of Tuberculosis in Children. New Delhi: Jaypee
Brothers, 2001; pp. 199–208.
4. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus
statement. Global burden of tuberculosis: estimated incidence,
prevalence and mortality by country. WHO Global Surveillance
and Monitoring Project. JAMA 1999; 282: 677–686.
5. Toossi Z. Virological and immunological impact of tuberculosis on
human immunodeficiency virus type 1 disease. J Infect Dis 2003; 188:
1146–1155.
6. Swaminathan S, Ramachandran R, Baskaran G et al. Risk of
development of tuberculosis of HIV infected patients. Int J Tuberc
Lung Dis 2000; 4: 839–844.
7. Zumla A, Squire SB, Chintu C, Grange JM. The tuberculosis
pandemic: implications for health in tropics. Trans R Soc Trop Med
Hyg 1999; 93: 113–117.
8. Braun MM, Badi N, Ryder RW et al. A retrospective cohort study of
the risk of tuberculosis among women of child bearing age with HIV
infection in Zaire. Am Rev Respir Dis 1991; 143: 501–504.
229
9. Harries AD. Tuberculosis and human immunodeficiency virus
infection in developing countries. Lancet 1990; 335: 387–390.
10. Jones D, Malecki J, Bigler W et al. Pediatric tuberculosis and human
immunodeficiency virus infection in Palm Beach County, Florida. Am J
Dis Child 1999; 46: 1166–1170.
11. Odhiambo J, Borgdoff MW, Kiambih FM et al. Tuberculosis and HIV
epidemic: increasing annual risk of TB infection in Kenya 1986–1996.
Am J Public Health 1999; 89: 1078–1082.
12. Cherian T, Verghese VP. Tuberculosis with human immunodeficiency
virus infection. Ind J Pediatr 2000; 67: 47–52.
13. Merchant RH, Shroff RC. HIV seroprevalence in disseminated
tuberculosis and chronic diarrhea. Ind Pediatr 1998; 35: 883–887.
14. Daga SR, Verma N, Gosavi DV. HIV infection in children: Indian
experience. Ind Pediatrics 1999; 36: 1250–1253.
15. Luo C, Chintu C, Bhat S et al. HIV infection in Zambian children with
tuberculosis: changing seroprevalence and evaluation of a TCZ free
region. Tuberc Lung Dis 1994; 75: 110–115.
16. Madhi SA, Huebner RE, Deodens L, Aduc T, Wesley D, Cooper PA.
HIV-1 co-infection in children hospitalized with tuberculosis in South
Africa. Int J Tuberc Lung Dis 2000; 4: 448–454.
17. Karande S, Balke S, Kelkar A, Ahuja S, Kulkarni M, Mathur M. Utility of
clinically-directed selective screening to diagnose HIV infection in
hospitalized children in Bombay, India. J Trop Pediatr 2002; 48: 149–155.
18. Lederman MM, Georges DL, Kunsner DJ, Mudido P, Giam CZ,
Toossi Z. Mycobacterium tuberculosis and its purified protein
derivative activate expression of human immunodeficiency virus. J
Acquir Immune Defic Syndr 1994; 7: 727–733.
19. Zhang Y, Nakata K, Weiden M, Rom WN. Mycobacterium
tuberculosis enhances human immunodeficiency virus-1 replication
by transcriptional activation at the long terminal repeat. J Clin Invest
1995; 95: 2324–2331.
20. Goletti D, Weissman D, Jackson RW et al. Effect of Mycobacterium
tuberculosis on HIV replication: role of immune activation. J Immunol
1996; 157: 1271–1278.
21. Subramanyam S, Hanna LE, Sankaran K et al. HIV alters plasma and
M. tuberculosis – induced cytokine production in patients with
tuberculosis. J Interferon Cytokine Res 2004; 20: 101–106.
22. Frasiamo M, Capelli G, Santucci M et al. Expression of CCR5 is
increased in human monocytes-derived macrophages and alveolar
macrophages in the course of in vivo and in vitro Mycobacterium
tuberculosis infection. AIDS Res Human Retroviruses 1999; 15: 869–
874.
23. Hirsh CS, Toossi Z, Vanham G et al. Apoptosis and T cell
hyporesponsiveness in pulmonary tuberculosis. J Infect Dis 1999;
179: 945–953.
24. Khouri Y, Mastrucci M, Hutto C et al. M. tuberculosis in children with
HIV type1 infection. Pediatr Infect Dis J 1992; 11: 950–955.
25. Moss WJ, Dedyo I, Suarez M et al. Tuberculosis in children infected
with human immunodeficiency virus. A report of 5 cases. Pediatr
Infect Dis J 1992; 11: 114–120.
26. Chan SP, Bimbaum J, Rao M. Clinical manifestation and outcome of
tuberculosis in children with AIDS. Pediat Infect Dis J 1996; 15: 443–
447.
27. Garay JE. Clinical presentation of pulmonary tuberculosis in under
10s and differences in AIDS-related cases: a cohort study of 115
patients. Trop Doctor 1997; 27: 139–142.
28. Mukadi YD, Witkor SZ, Coulibaly M et al. Impact of HIV infection on
the development, clinical presentation and outcome of tuberculosis
among children in Abidjan, Cote d’ Ivoire. AIDS 1997; 11: 1151–
1158.
29. Zar HJ, Tannenbaum E, Hanslo D, Hussey G. Sputum induction as a
diagnostic tool for community acquired pneumonia in infants and
young children from a high HIV prevalence area. Pediatr Pulmonol
2003; 36: 58–62.
30. Kiwanuka J, Graham SM, Coulter JB et al. Diagnosis of pulmonary
tuberculosis in children in an HIV-endemic area, Malawi. Ann Trop
Paediatr 2001; 21: 2–14.
230
31. Jeena PM, Coovadia HM, Thula SA et al. Persistent and chronic lung
disease in HIV-1 infected and uninfected African children. AIDS 1998;
12: 1185–1193.
32. Chintu C, Mudenda V, Lucas S et al. UNZA-UCLMS Project
Paediatric Post-mortem Study Group. Lung diseases at necropsy in
African children dying from respiratory illness: a descriptive necropsy
study. Lancet 2002; 360: 985–990.
33. Abrams EJ. Opportunistic infections and other clinical manifestations
of HIV disease in children. Pediatr Clin North Am 2000; 47: 79–108.
34. Palme IB, Gudetta B, Bruchfeld J, Muhe L, Giesecke J. Impact of
S. SWAMINATHAN
human immunodeficiency virus 1 infection on clinical presentation,
treatment outcome and survival in a cohort of Ethiopian children
with tuberculosis. Pediatr Infect Dis J 2002; 21: 1053–1061.
35. Third Report on WHO/IUATLD Global Project on Anti-Tubercu-
losis Drug Resistance Surveillance, 2004. www.iuatld.org.
36. Preventive therapy against tuberculosis in people living with HIV.
Policy statement. Wkly Epidemiol Record 1999; 74: 385–398.
37. Hesseling AC, Schaaf HS, Hanekom WA et al. Danish bacilli
Calmette-Guerin vaccine-induced disease in human immunodefi-
ciency virus-infected children. Clin Infect Dis 2003; 37: 1226–1233.