Professional Documents
Culture Documents
doi:10.1016/j.prrv.2004.04.006
Worldwide, tuberculosis (TB) is the most frequent coinfection 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 tuberculous infection, this increases to 78%/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 susceptible to both HIV infection and TB.
EPIDEMIOLOGY
TB is the most common opportunistic infection in HIVinfected individuals and it is estimated that about 6070% of
HIV-infected adults in India eventually develop TB.6 Unlike
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S. SWAMINATHAN
PATHOGENESIS OF TB
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THERAPY
It is generally accepted that HIV-positive people with TB
respond as well to short-course chemotherapy as HIVnegative 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 (1012 mg/kg/day), pyrazinamide
(30 mg/kg/day) and ethambutol (1520 mg/kg/day) for the
first 2 months followed by isoniazid and rifampicin for the
next 4 months is recommended.33 Drugs may be administered daily or thrice weekly and directly observed treatment is recommended wherever possible. For meningitis
and bone and joint TB, a minimum of 9 months of treatment 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 therapy.16 Palme et al. found that although adherence to
treatment was high (96%), the cure rate was 58% for
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S. SWAMINATHAN
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 7083% 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 isoniazid 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
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 HIVpositive children.
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