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ReviewsThe Impact of Human Immunodeficiency Virus Infection on Tuberculosis and Its Control
Section snippets
Methods
A comprehensive search of the English medical literature was made, in September 1990, dating back to 1980, using Medline. Key words used were tuberculosis, AIDS, HIV infection and mycobacterial infection.
Epidemiology
In the United States, there are accumulating data on the impact of HIV infection on TB.7, 8, 9 In 1986, and for the first time in recent decades, there was a slight increase (374 or 1.7 percent) in the number of cases of TB,9 such that by 1989 more than 20,000 excess TB cases have been reported. Overall TB has been found to occur in 4.2 percent of patients with AIDS in the United States.9 In British Columbia, studies have shown a total of 15 cases of TB among 464 AIDS patients in the period
Pathogenesis
Tuberculosis usually is acquired via the respiratory route. Where the immune status is competent this phase usually is asymptomatic and only is manifested by the development of a positive response to tuberculin. Subsequently about 10 percent of subjects develop TB. The maximum period of risk is two years although the diminishing risk remains throughout the subject's lifetime. This endogenous reactivation is responsible for tuberculous disease.19 Cell-mediated immunity plays an important role in
Clinical Features
The symptoms in patients with HIV infection and TB include fever, cough and weight loss.22, 23, 24 These also are common in other nontuberculous opportunistic infections occurring in AIDS patients.11 The presence of unusual extrapulmonary manifestations suggest HIV infection. Table 1 compares the patterns of TB in HIV-positive and HIV-negative patients.
Site of Disease
In the studies reviewed, data on the location of TB were available in 356 HIV-infected patients and are shown on Table 2. One hundred ninety-three (54 percent) had pulmonary disease, 136 (38 percent) had extrapulmonary disease and 27 (8 percent) had both. This relatively high proportion of extrapulmonary disease differs from the pattern of predominantly pulmonary disease seen in approximately 80 percent of immune-competent patients.
Tuberculin Reactivity
Despite the ultimate development of anergy in AIDS patients, at the time of the diagnosis of TB, a significant proportion react to PPD. Table 2 shows the cumulative response rate reported in the literature reviewed. In most instances it was not possible to stratify these patients for CD4 counts or to discriminate between HIV infection and AIDS. In general, patients in the early evolution of their HIV infection may not differ significantly from non-HIV-infected individuals.25 In the 193 cases,
Therapy
When therapy has been instituted the response usually has been good using standard antituberculosis chemotherapy with isoniazid, rifampin and pyrazinamide or ethambutol. Six studies11, 12, 15, 22, 23, 24 specifically investigated response to therapy. Although follow-up in general was short,11 in all cases reported, 100 patients responded clinically and 24 of 43 patients with initial positive bacteriologic studies had evidence of a response. Standard therapy is appropriate,8 though the ultimate
Contact Tracing and Chemoprophylaxis
Contacts of HIV-infected patients with TB should be evaluated according to accepted guidelines for all TB contacts.17, 55, 56 Despite a somewhat lower proportion of smear-positive cases and a relatively high proportion of extrapulmonary TB, contacts of TB-infected AIDS patients have a similar proportion of infected contacts as HIV-negative index cases.11 It is especially important to remember that they belong to groups, eg, homosexuals and drug addicts, having frequent contact with each other,
Chemoprophylaxis in High-Risk Groups
In addition to known infected contacts of patients with TB, it is suggested that groups with high risk of HIV infection and a documented high risk of TB and all who are HIV-positive should be tested for evidence of tuberculous infection. Such groups include intravenous drug abusers,16, 60 prostitutes,61 those attending sexually transmitted disease clinics,62 migrant workers from areas with a high prevalence of both AIDS and TB (eg, Haiti and Africa)63 and prisoners.64, 65 Formerly a cutoff of
Other Issues
Other groups who require special attention include staff treating AIDS patients, particularly those involved in diagnostic tests such as induction of sputum or those administering aerosolized pentamidine. A recent report from New York66 showed that in a 75-bed AIDS unit there were 28 cases of TB in 1985, rising to 155 in 1988. During this period, the PPD skin conversion among staff rose from 5 in 1986 to 12 in 1987 and to 19 during the first half of 1988. Concern has been expressed regarding
HIV Infection and Tuberculosis in Other Developed Countries
The literature on HIV infection and TB in developed countries outside North America until recently has been small, but recent data suggest a similar or even higher prevalence of TB in HIV-infected patients69, 70 than that reported in North America. In 100 successive AIDS patients from Spain, 67 had TB; in 25 patients for whom blood cultures were examined for mycobacteria, 16 were positive.69 These authors report the presence of TB in 30 percent of all patients with AIDS in Spain and suggest
Tuberculosis and HIV Infection in Developing Countries
It is in developing countries such as Haiti and in sub-Saharan Africa73, 74 that HIV infection will have its most dramatic effect on TB. On a continent where the health care system is already fragile,75 HIV infection is increasing the incidence of TB.76 The epidemiology of HIV infection in Africa has been reviewed77 and its spread by the heterosexual route has been emphasized.78 Overall HIV seroprevalence rates in healthy blood donors and women attending prenatal clinics range from 1 to 18
Economic and Demographic Impact
The current HIV epidemic has and will continue to have significant economic and demographic effects. Already the dollar cost of care for a relatively large number of young subjects has been calculated as significant.97 Anderson et al97 reviewed the various estimates of medical care costs in the United States and note that some estimates range as high as 113 billion dollars, during the period 1987-1991, being spent on medical care of patients with HIV infection; TB undoubtedly will add to this.
Conclusion
The primary goal must be to find an effective vaccine against the AIDS virus, but it seems likely that this will be delayed at least for several years. We must continue to seek to limit the spread of the virus and treat those already infected.98 This and other reviews have brought forth sufficient evidence of the relationship between HIV and TB to justify a high awareness of this association and certain practical steps follow. Groups at high risk of HIV infection by virtue of their life-styles
ACKNOWLEDGMENTS
We would like to thank Debbie Thompson, Lois Vandermoor, Heather Costa and Yvonne Camara for secretarial assistance and Dr. M. Yeung for reviewing this manuscript.
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