It is now widely appreciated that the epidemiology , clinical manifestations,management and prognosis of tuberculosis are radically altered in patients with human immunodecficiency virus(HIV) infectin.It is estimated that a third of the world population has been infected with Mycobacterium tuberculosis The prevalence of HIV infection is highly variable and changing in different regions of the world.10 million persons worldwide are infected with HIV,with 60% of this latter number resident in subSaharan Africa.
Indian figures for prevalence of HIV infection
Output Using 1998 Sentinel data the current estimate is
The frequency with which HIV and M tuberculosis occur together is determined by the epidemiology of each disease in a given population.
Approximately 2 billion people (one-third of the world's population) are infected with Mycobacterium tuberculosis, the cause of TB.
TB is the cause of death for one out of every three people with AIDS worldwide.
The spread of the HIV epidemic has significantly impacted the TB epidemic. One-third of the increase in TB cases over the last five years can be attributed to the HIV epidemic (Source: UNAIDS).
Sources: **CDC Update: The Deadly Intersection Between TB and HIV
Pathogenesis:The immune response to Mycobacterium Tuberculosis in HIV infected patients
When tubercle bacilli are inhaled , mechanical barriers of the upper airways and mucociliary system of the bronchial mucosa eliminate large particles. Only particles less than 5 microns in diameter reach the alveoli,where the bacilli are ingested by the macrophages. Establishment of TB infection probably depends on the number of and viability of the bacilli versus the microbicidal activity of the macrophages.Because most alveolar macrophages are not activated ,their microbicidal activity is low, viable bacilli multiply both within the macrophages and extracellularly, and are transported by lymphatic vessels to the mediastinal lymph nodes and the blood stream, where they seed other parts of the body. Some macrophages that ingest tubercle bacilli process mycobacterial antigens and present them to T lymphocytes., which in turn release lymphokines that are chemotactants and growth factors for additional lymphocytes and macrophages. Interferon gamma is an important lymphokine that activates macrophages to more effectively ingest and kill mycobacteria. At this point, the host has mounted a cell mediated immune response and delayed type hypersensitivity response to M.tuberculosis antigens is manifested clinically by development of a positive tuberculin skin test. In approximately 90% of immunocompetent persons infected with M.tuberculosis ,immune defenses are effective and tuberculosis disease does not develop. Cell mediated immunity is ineffective in 5% of infected persons resulting in disease within 1 year of infection. In an additional 5% ,TB develops later in life when cell mediated immune defenses wane with age or from other immuno suppressive processes.
Cd4+cells(T4 cells) and macrophages play a central role in immune defenses against M.tuberculosis
. HIV specifically infects CD4+ cells and macrophages ,resulting in progressive depletion and dysfunction of CD+ T cells. Macrophage function is also abnormal because of direct infection with HIV, coupled with lack of macrophage-activating factors produced by CD4+ cells. These factors facilitate development of progressive primary pulmonary TB (Fig 2), haematogenous dissemination of M.Tuberculosis
to extrapulmonary sites,and increased likelihood of reactivation of prior tuberculosis infection. Thirty seven per cent of HIV infected close contacts of TB patients develop disease within 5 months.
Fig2-Primary type of TB in an adult with HIV infection.
The risk of reactivation of TB in HIV infected patients previously infected with M.Tuberculosis
is 8% to 10% per year (Table 1) and one may therefore speculate that the lifetime TB risk of such patients approaches 100%.
Table 1.RISK OF CLINICAL TUBERCULOSIS IN INDIVIDUALS INFECTED WITH TB AND HIV IN THE UNITED STATES AND AFRICA.
Country
Year of report
Study methods
% Annual risk of TB
HIV+/TB+ HIV-/TB+
United States
1989
Prospective study ,intravenous drug users
7.9
0
Zaire
1991
Retrospective study, women of child bearing age
6.2
0.2
Zaire
1991
Prospective study, factory workers and spouses
5.6
0.8
Rwanda
1991
Prospective study women attending prenatal clinics
5.5
0.2
Clinical featuresThere are two distinct clinical patterns of tuberculosis in HIV infected patients that depend on when in the course of evolving HIV infection the tuberculosis develops.Of the two the one that has received the greater attention develops when tuberculosis complicates the late stages of HIV disease;in other words , just before or even after the onset of AIDS.In this circumstance , the clinical and radiographic features are likely to differ substantially from those in non HIV infected patients with "ordinary" tuberculosis. Among the important differences that have been observed are:
that patients with tuberculosis and HIV infection often have a negative tuberculin reaction
that more than half will have extrapulmonary (especially lymph node involvement) and
that upper lobe cavitary disease is infrequent and the chest radiographs are usually atypical.
The late stage of HIV infection is recognised clinically by the presence of other markers of AIDS eg (Herpes etc Fig 3) and or low CD4 cells.
Fig 3:Patient with TB and Herpes Zoster ( advanced HIV infection)
Patients with advanced HIV infection and virtual absence of cellular immunity cannot develop or maintain hypersensitivity to tuberculoprotein;this explains many of the unususal features of tuberculosis in this setting,including dissemination.In contrast ,patients with less advanced HIV infection have relatively well preserved cellular immunity,and the usual clinico radiographic features are observed.
Reported Indian experience
Centre
Number of cases screened
Number Positive
Elisa WB
Reference
Sivaraman et al Pondicherry
225
6 6
Ind J Tub 1992,39,35-39
NIV Pune
359
4 4
Quoted by Banavalikar et al 1997
Anuradha et al Chennai
392
3 -
Ind J Tub 1993,40,13-15
Chennai and Vellore
3071
12 -
Quoted by Banavalikar
Mumbai
5024
296 -
Mohanty .K.C. and Basheer PM.m.95-119
Banavalikar et al Delhi
1002
13 5
Banavalikar et al 1997 44,17-20
The radiolgical presentations of TB in HIV seropositives
Authors
Cavitary
Hilar adenopathy
Diffuse/miliary
Pleural effusion
Sivaraman et al 1992
3
2
2
0
Anuradha et al 1993
3
-
-
-
Mohanty and Basheer(1995)
144
-
6
12
Banavalikar et al (1995)
-
-
2
1
Treatment of HIV infection with TB
Treatment guidelines for HIV-infected patients are identical to the
standard regimens recommended for those without HIV . All therapeutic
combinations should include rifampicin, and
patients should be monitored for drug interactions with protease
inhibitors. Treatment duration is also the same unless therapeutic
response is slow. Directly observed therapy is the standard of care.
The response to treatment if given adequately and regularly is reported to be the same in Hiv and non HIV patients.However the significant difference in the TB patient coinfected with HIV are
Median survival of about 18 months after diagnosis
High frequency of adverse reactions that occur(in below 20% of cases)
Recent recommendations of WHO state that one course of immunoglobulins could prolong the life expectancy and delay the development of full blown AIDS.
Patients with risk factors for drug-resistant M tuberculosis
infection may need treatment with four or more drugs. There are many reports in western literature on multi drug resistant TB in HIV infected patients.Where facilities are available,it would be ideal to have drug sensitivty tests done and chemotherapy started accordingly. Recently, an
increasing prevalence of tuberculosislike disease due to infection with
other mycobacteria (eg, M kansasii, M bovis) has been observed in
HIV-infected populations in USA and some western countries.
Patients with HIV infection should undergo a tuberculin skin test
yearly, and those with an induration of 5 mm or more who lack
manifestations of active tuberculosis should receive prophylactic
treatment with isoniazid for 1 year . Many
HIV-infected patients have anergy, which recent investigations have shown
may wax and wane. Past recommendations that anergic patients in
environments highly endemic for tuberculosis should also undergo
prophylaxis are controversial , because recent studies have failed to
show benefit from this practice .
