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Epidemiology of AIDS and Tuberculosis1 MAMMADE LOURDESGARCIA GARC~A,~ Josh LUIS VALDESPINO G~MEz,~ MAMMACECILIA GARCIA SANCHO,~ REY ARTURO SALCEDOALVAREZ,~FERNANDO ZACA~~AS,~ & JAIME SEP~JLVEDAAMOR~ 444 This article reviews literature on the epidemiology, pafhogenicify, and control of HIV and Mycobacterium tuberculosis coinfecfion. Regarding pafkogenicify, immune sysfem de- feriorafion makes HIV-infected people more likely to develop active tuberculosis on prima y or secondary exposure to the bacillus or to suffer reactivation of lafenf infections, and fo experience considerably higher rates of exfrapulmona y manifesfafions, relapses, and deafk. Regarding epidemiology, as of 1990 there were an esfimafed 3 million people coinfecfed with HIV and M. tuberculosis, with some 300 000 active tuberculosis cases and 120 OOO- 150 000 tuberculosis deaths occurring annually among fkose coinfecfed. Over 500 000 coin- fecfed people are thought to reside in the Americas, over 400 000 of them in Latin America. In general, the impacf of coinfecfion is evident. Relafively kigk and increasing prevalences of HIV infection have been defected among tuberculosis patients around fke world, and tuberculosis has become a frequent complication of AIDS cases. Moreover, there is no longer any doubt fkaf coinfecfion obsfrucfs tuberculosis prevenfion and control. Among other things, it affecfs BCG vaccination policies, suggesfs fke need to administer preventive ckemopro- pkylaxis fo HIV-infected individuals at higk risk of harboring or contracting tuberculosis infections, and complicates both defection and freafment of acfive tuberculosis cases. The recent proliferafion of M. tuberculosis strains resisfanf to multiple drugs, most notably in fke United States, compounds the problem. Tuberculosis prevention and control are still technically and economically feasible. How- ever, more must be done to establish surveillance programs with laborafo y support. More research is needed to determine what case prevention measures are best-suited to current circumstances and the HIV/AIDS presence. More efiecfive preventive freafmenf regimens tkaf are well tolerated, well complied with, and do not pose the risk of mulfiresistance need to be devised. More health workers need fo be trained to suspect tuberculosis and to conduct timely and appropriate testsconfirming fkis diagnosis. And finally, more must be done fo sfandardize the types and durations of fke various curative freafmenf regimens employed. he HIV/AIDS epidemic has had a ‘Revised translation of an article entitled “Epide- rniologfa de1 SIDA y la tuberculosis” that was pub- T major impact on the epidemiology of lished in Spanish in the Bolefin de la Oj?cinaSanitaria tuberculosis around the world-includ- Panamericana, Vol. 116, No. 6, 1994, pp. 546-565. ing the Americas, where its conse- Reprint requests and other correspondence should quences have been observed in both in- be addressed to Dra. Maria de Lourdes Garcia Gar- dustrialized and developing countries. da, Carpio 470-3er piso, Col. Santo Tom&, Deleg. Miguel Hidalgo, 11340, Mexico, DF, Mexico. This article reviews certain pathogenic ‘National Institute of Epidemiologic Diagnosis and aspects of the interrelationship between Reference (Instituto National de Diagkstico y Re- infections caused by the human immu- ferencia Epidemiologicos), Mexico City, Mexico. nodeficiency virus (HIV) and Mycobacfe- 3Regional Program on AIDS and Sexually Trans- rium tuberculosis. It then analyzes the mitted Diseases, Pan American Health Organiza- tion, Washington, D.C., U.S.A. epidemioIogic status of coinfection ‘Undersecretariat for Coordination and Develop- worldwide, particularly in the Americas, ment, Mexico City, Mexico. and examines the problems confronting Bulletin of PAHO 29(I), 2995 37 efforts to control tuberculosis following tracted, the presence of an HIV infection the appearance of coinfection. increases the subject’s chances of devel- oping active tuberculosis (9,20). Along these HIV AND M. TUBEXCULOSIS lines, a study conducted by Daley et al. COINFECTION: PATHOGENIC (9) found that at least 50% of a group of CONSIDERATIONS HIV-positive patients exposed to M. tuber- culosiscontracted tuberculosis infection and The progression from infection with 111. 37% developed active tuberculosis. These tuberculosis through tuberculous disease frequencies are higher than those that has been described thoroughly. In coun- would normally be expected among un- tries where the tuberculosis prevalence is infected individuals. high, infection generally occurs in early Molecular biology techniques have infancy. Less than 10% of the individuals made it possible to demonstrate exoge- infected with M. tubercuIosis subse- nous reinfection and development of ac- quently develop active tuberculosis after tive tuberculosis among individuals who an interval ranging from 1 to 50 years (1 - have had the disease previously. Small 3). Activation of the infection is contin- et al. (ZZ), by using a “DNA fingerprint- gent upon the integrity of the host’s im- ing” technique-restriction fragment mune system. Advanced age (4), preg- length polymorphism (RFLP) analysis- nancy, associated diseases such as diabetes demonstrated the existence of reinfec- mellitus (5), and treatment with cortico- tions caused by multiresistant strains in steroids (6) have all been associated with HIV-positive patients who had already development of active tuberculosis. The been treated for a prior episode of tu- ensuing lethality of the disease, how- berculosis caused by sensitive strains. ever, depends primarily on access to These studies indicate that such patients health services. In a pattern strongly re- do not develop immunity and accord- flecting the presence or absence of such ingly become reinfected upon reexposure access, it is typical for between 10% and to the tuberculosis bacillus. 50% of those with active cases to die after A relationship between HIV and M. an interval ranging from 1 to 10 years (7). tuberculosis infections is also evident in Knowledge of the natural history of HIV cases where the bacillus is reactivated fol- infection has progressed considerably in lowing deterioration of an HIV-positive recent years. At present, it is believed host’s immune system. M. tuberculosishad that some 44% of those infected with HIV been identified as a potential opportun- as a result of sexual transmission develop istic agent even before the advent of the AIDS within a 13-year period. Over 90% AIDS era. In connection with HIV, its of those with AIDS then die after an in- high pathogenicity reflects the fact that terval generally ranging from 6 months it becomes active before other opportun- to 2 years, though intervals exceeding istic agents such as Pneumocystiscminii or 2 years have been reported (8). Toxoplasma gondii. In this regard, it is The natural history of M. tuberculosis noteworthy that the CD4 lymphocyte and HIV infection changes when both counts in coinfected patients are higher infections coexist in the same individual. (between 300 and 400/mm3) following de- Some studies have pointed out that the velopment of active tuberculosis (12). likelihood of an HIV-infected individual At present, HIV infection constitutes contracting tuberculosis upon exposure to one of the most important risk factors the bacillus is greater than that of an in- determining whether an individual with dividual uninfected with HIV. Similarly, signs of tuberculous infection, such as once tuberculosis infection has been con- cutaneous reactivity to PPD, will develop 38 Bullefin of PAHO 29(l), 1995 active tuberculosis. Selwyn et al. (23) have ary manifestations (16, 27). Morais et al. demonstrated the risk that HIV infection found that 18.3% of 420 HIV-infected pa- represents for the development of tuber- tients in Rio de Janeiro had extrapul- culosis in coinfected subjects. These au- monary tuberculosis (18). Casiro et al. (29) thors studied a group of intravenous drug estimated that 40% of the AIDS patients users. Among other things, they found in Argentina in 1982-1990 had dissemi- that HIV-infected individuals’ risk of de- nated tuberculosis, and that in the year veloping tuberculosis was 26 times higher 1991 this percentage reached 60.6%. On if they had positive PPD skin test results the other hand, the frequencies of pul- than if they had negative results. Again monary tuberculosis found for these two studying intravenous drug users, Selwyn periods were 25.7% and 21.2%, respec- and colleagues (14) found that when an tively, and those for tuberculous lymphad- HIV-infected individual’s negative re- enitis were 17.1% and 9%, respectively. sponse to PPD was associated with anergy The percentage of tuberculosis relapses to other cutaneous immunogens, that in HIV-positive individuals is also higher. person’s risk of developing tuberculosis As Table 1 indicates, it has been esti- was relatively high. Moreover, when these mated that such patients suffer relapses coinfected patients developed tubercu- between 3.7 and 16 times more fre- losis, the clinical characteristics of the dis- quently than those who are not HIV-pos- ease were found to differ from those ob- itive. Specifically, Hawken et al., study- served in individuals who were not ing subjects in Kenya, found that relapses coinfected. Notably, extrapulmonary lo- were 16 times more frequent in HIV- calizations (including miliary tuberculo- positive patients with tuberculosis (20). sis and infections involving the lym- Idigbe et al., studying the frequency of phatic system,