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cal examination, antimicrobial susceptibility test and molphological and serological characteristics. J. olin. Mterobiol., 21, t68-1"13. Kochi, A. (1991), The global tuberctdosis situation and the new control strategy of the World Health Organization. Tnbercle, 72, 1-6. Masur, H., Ognihene, F.P. & Yarehoan, R. (1989), CD4 counts as predictors of opportunistic pneumonias in HIV infection. Arch. Intern. Med., I l l , 223-231. O'Brien, R.J.. Getter, L.J. & Snider, D.E, (1987), The ¢pidemiology of non-tuberculous mycobacterial disease in the United States. Artier. Rev. Resp. Dis., 135, 1007-1014. Pinching, A.S. (1987L Acquired immune deficiency syndrome: with special reference to tuberculosis. Tubercle, 68, 65-69. Pitchenik, A.E., Cole, C., Russell, B.W., Fischl, M.A., Spira, T.J. & Snider, D.E. 0984), Tuberculosis, atypical mycobacteriosis and the acquired immunodeficiency syndrome among Haitian and non-Haitian patients in south florida. Ann. ln!ern. Med., 101, 641-645. Pitchenik, A.E., FerteL D. &Bloch, A.B. (1988), Mycobaeterial disease: epidemiology, diagnosis, treatment and prevention. Clin. Chest Med., 9, 425-441. Pitchenik, A.E., Russell, B.W., Cleary, T., Pejovie, 1., Cole, C. & Snider, D.E. (1982), The prevalence of tuberculosis and drug resistance among Haitians. New EngL J. Med., 307, 162-165.

Portaels, F., Larsson, L. & Smccts, P. (1988), Isolation of mycobacteria from healthy person's stools. Int. J. Leprosy, 56, 468-471. Quinn, T.C. (1989), Interactions of the human immunodefictency virus and tubereulosts and implications for BCG vaccination. Rev. infect. Dis., It, $375-384. Rotterdam, H. & Sommers, S.C. (1985), Alimentary tract biopsy lesions in the acquired immune deficiency syndrome. Pathology, 17, 181-192. Selwyn, P.A., Hartel, D., Lewis, V.A.. Schoenbaum, E.E., Vermund, S.H., Klein, R.S., Walker, A.T. & Friedland, G.H. (1989), A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. New EngL J. Med., 320, 545-550. Slutkin, G.. Leowski. J. & Mann. J. (1988), The effects of the AIDS epidemic on the tuberculosis problem and tuberculosis programmes, in "The Global Impact of AIDS" (A.F. Fleming, M. Carhelo, D.W. Fitzsimmons, M.R. Bailey & J. Mann) (pp. 21-25). Alan R. Liss, N~:w York. Styblo, K. (1990), The global aspects of tuberculosis and HIV infection. Bull. Int. L'n. Tuberc., 65, 2g-32. Yakrus, M.A. & Good, R.C. (1990), Geographic distribulion, frequency and specimen source of ?4, aviumcomplex serotypes isolated from patients with acquired immunodeficiency syndrome. J. elin. MicrobioL, 28, 926-929.

Epidemiology of mycobacteriai diseases in AIDS C.R. H o r s b u r g h , J r . Division o f HIV/AIDS, National Center for Infectious Diseases, Centers f o r Disease Control, Public Health Service, US Department o f Health and Human Services; arid the Division o f Infectious Diseases, Emor.v University and Grady Memorial Hospital, Atlanta, GA (USA)

Introduction Because a cell-mediated immune response is needed to control infection with mycobaeteria, conditions that impair the cellular immune system predispose patients to mycobaeterial disease (Horsburgh, 1989). Acquired immunodeficiency syndrome (AIDS) has rapidly become the most common cause of impaired

cell-medimed immunity, arid increased frequency and severity of a number of mycubacterial diseases have been reported in persons with this disorder. Increases in tuberculosis and Myeobaeterium avium complex disease (MAC) have both been documented to be associated with A I D S (Barnes et aL, 1991 ; Horsburgh, 1991). More recently, an outbreak of infections with ~4ycobacterium haemophihon in A I D S patients has

Address correspondence and reprint requests to: C. Robert Horsburgh, Jr.. M.D.. Mailstop E 45, Centers for DiseaseControl, Atlanta, GA 30333.

MYCOBACTERIA AND AIDS been reported (CDC, 1991b). Other mycobacterial diseases, such as those caused by hi. marinum, M . kansasii, M. simiae, M. xenopi, M . scrofulaeeurn, M. fortuitum, and M. gordonae, have been reported in AIDS patients, but it is not clear whether they are any more c o m m o n in patients with AIDS than in the general population. Leprosy, a mycobacteriosis that occurs in many of the same geographic areas as AIDS, has somewhat surprisingly been shown to have neither increased incidence nor increased severity in patients with A I D S (Leonard et aL, 1990; Tekle-Haimot et al., 1991 ; Ponnighaus el aL, 1991). Other mycobacterial infectious, such as those eaused by M. chelonae, M. szulgai, and ~',L uleerans, have yet to be reported in patients with AIDS. This review will therefore focus on tuberculosis and M A C infection, the two most important mycobactedal causes of morbidity in AIDS.

Tuberculosis Tuberculosis is the most c o m m o n mycobacteriosis of m a n and is being seen with increasing frequency in patients with H I V infection (Rieder et al., 1989; Barnes et al., 1991). (It should be noted that a diagnosis o f pulmonary tuberculosis does not establish a diagnosis o f AIDS unless extrapulmonary spread is documented; however, persons with H I V infection without A I D S also have an increased risk of tuberculosis.) In this review, I will consider tuberculosis in persons with A I D S or H I V infection. Cases of tuberculosis in such patients may be due either to reactivation of a previously contained focus of M. tuberculosis infection or to a decreased ability of HIV-infected persons to control primary tuberculous infection, resulting in a higher fraction of exposed HlV-infected persons developing disease. Several studies have documented a high rate of reactivation o f tuberculous infection in H1V-infected persons (Selwyn et al., 1989; Braun et aL, 1991). Moreover, the fraction of HIV-infected persons who develop active disease after exposure to tuberculosis is much higher that~ that of exposed HlV-uninfected persons (Di Perri, 1989; CDC, 1991b). In the developing world, where over 50 percent of the adult population may he tuberculous-infected, it is not surprising that active tuberculosis may occur in 25-43 percent of AIDS patients (Lucas et al., 1991 ; Nelson el aL, 1991). Countries in Africa, Asia and South America had reported over 100,1300 AIDS oases to the World Health Organization by June 1991. Since many more are HIV-infected without AIDS, as many as 2.4 million persons coinfected with H I V and M. tuberculosis may exist in subsaharan Africa alone (Stanford et aL, 1991). In the United States, despite the fact that tuberculous infection is less common, the increase in tuberculosis cases since 1984 has been attributed to the H1V epidemic (Reider

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et al., 1989). This seems highly likely, since the increases in tuberculosis have occurred in the same geographic areas and demographic groups that have been most affected by the AIDS epidemic. In a survey of HIV seroprevalence i:a patients with tuberculosis, the highest rates of HIV infection were seen in New York, Newark, Boston and Miami, areas that also have high rates of AIDS (Onorato et eL, 1992). Not only is tuberculosis more likely to progress to active disease in the HIV-infeeted person, it is also likely to be more widespread. Disseminated disease, with or without a pulmonary focus, has been seen to be more c o m m o n in HIV-infected persons than in the HIV-uninfected (Chaisson et al., 1987; Pitchenik et aL, 1987). This is presumably due to the inability of the host immune response to contain the initial focus of infection. Among HIV-infected persons seen at outpatient facilities in the US, pulmonary tuberculosis rates were significantly increased both in blacks (3.1 070vs 1.2 0"/0 ill whites) and in intravci~ous drug users (4.2 ~'G versus 1.4 qr0 in men who reported sex with men) (Farizo et al., 1991). Among US A I D S patients, disseminated tuberculosis was more common among those born outside the U S ; in persons born in the US, blacks, h!spanics and intravenous drug users had the highest rates of disseminated tuberculosis (Braun et al., 1990). This presumably reflects higher rates of previously contained tuberculous infection in those gronps. The contribution of primary tuberculosis in HIVinfected persons to the rise in incidence o~ tuberculosis in the US is difficult to define. HIV-infected persons with ruherculosis do ndt appear more likely than HIV-uninfected persons to spread tuberculous infection to household contacts (Pitchenik et aL, 1987; Manoff el al., 1988). Indeed, as H1V-infected persons may be more likely than HlV-uninfected persons to have extrapulmonary disease and equally or less likely to be smear-positive if they do have pulmonary disease (Theuer et aL, 1990; Long et aL, 1991 ; Klein et aL, 1989; Elliott et aL, 1990), a given person with H I V and tuberculosis may be less likely to spread the infection. However, because HIVinfected persons, once expose'a, are more likely than the HIV-uninfected to develop active disease, there is a potential for a multiplication effect; despite a similar infectivity of each HIV-infected person with active tuberculosis, more exposed HlV-infeeted persons will have active disease. This can lead to rapid spread of tuberculosis, as has been demonstrated by outbreaks of the disease on AIDS wards (Di Perri et aL, 1989; CDC, 1991a; CDC, 1991c; Pitchenik et eL, 1990). If a drug-resistant strain of M. tuberculosis is involved, standard therapeutic and prophylactic regimens may not be effective, and delayed recognition of the drug resistance may result in premature discontinuation of isolation, thus in-

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creasing the potential ft~r transmission (CDC, 1990). In general, HIV-infected patients with drugsusceptible M . tuberculosis respond as well to therapy as HIV-uninfected patients, although a longer duration of treatment is recommended (Barnes et al., 1991). Reports from Africa have shown decreased response to therapy and increased mortality for HIVinfected patients with active tuberculosis (Braun et al., 1991 ; Perriens et aL, 1991 ; Abouya el al., 1991). However, these studies used different therapeutic regimens than those recommended for use in the U S ; moreover, since initial susceptibility testing of isolates was not reported, it is difficult to know that the findings did not result from use of inadequate therapeutic regimens. The absence o f antiretroviral therapy in the African patients with H I V infection and tuberculosis may have also contributed to the decreased survival o f this group, especially in view of theoretical concerns that tuberculosis may exacerbate HIV infection (Valone el al., 1988 ; Moreno et aL, 1989). M A C disease M A C disease is the most common bacterial infection of AIDS patients in the U S and Europe, where prevalence studies indicate that 17-24 percent of A I D S patients are affected (Horsburgh, 1991). Countries in Europe, North America and Australia had reported over 245,000 A I D S cases to the World Health Organization by June 1991. suggesting that there may have been 40-58,0'00 cases of MAC. It is important to note that, while M A C disease is common in Europe, North America and Australia. it is extremely rare in Africa, South Amerl.ca and Asia (Okello et al., 1990). The reasom for this are unclear, but may include absence of virulent M A C isolates in the environment, protection by BCG or tuberculous infection and rare survival of A I D S patients to low CD4 levels. Studies have identified environmental M A C isolates in Africa, but the pathogenicity of these isolates is unknown. In view of the low rates of M A C disease in U S AIDS patients born outside the U S (3.7 'go vs. 6.3 "go in all others; Horsburgh and Selik, 1989 and unpublished observations), it would appear that host factors, rather than environmental factors, are primary. CD4 cell counts have been performed in a number of African sites, and a l t h o u g h survival to low C D 4 c o u n t s ( < 25 cells/cublc millimeter) is uncommon, it can occur. While BCG vaccinaiion has been proposed as an explanation for differing rates of M A C disease in AIDS (KaBenius et al., 1989), no data are presently available to confirm this hypothesis; a study is currently in progress (Von Reyn et aL, 1991). The most logical explmlation. 1 believe, for the rarity of M A C in AIDS patients in the developing world is the

Y

widespread prevalence of tuberculous infection. The reason for the "protective effect" is not, however, true protection, but rather the fact that these persons reactivate their tuberculosis and die long before they reach the low levels of immunosuppression that cause them to be susceptible to MAC. If antiretroviral therapy were to become as widespread in Africa as it presently is in Europe and North America, we might see an increase in the incidence of M A C in African A I D S patients. M A C disease has been increasingly reported in recent years, although it is not clear if these increases are the result of increased availability of diagnostic tests, an increase in surveillance for M A C related to the availability of treatment options, or true increases in incidence (Horsburgh, 1991). Recent information from our clinic in Atlanta suggests that all three o f these factors are occurring. Increased clinical awareness of the signs and symptoms associated with M A C disease was temporally associated with an increase in the incidence of eases, from 5.7 percent in 1985-8 to 23.3 percent in 1989-90 (Havlik et aL, 1992). However, it was also noted that the patients diagnosed in 1989-90 had had A I D S longer before a diagnosis of M A C (8 months versus 4.5 months), suggesting that patients were surviving longer. Since M A C incidence increases as CD4 cell counts decrease, it is apparent that the prolonged survival o f A I D S patients resulting from the administration o f zidovudine has resulted in the population o f A I D S patients who are now being followed having lower CD4 cell counts than those being followed previously. Therefore, part of the increases seen m a y represent true increases in incidence. Reports of disseminated non-tuberculous ntycobaeterial infection (DNTM) in A I D S (96 percent of which is M A C infection) collected in 1981-7 showed no differences in rates by sex or mode of acquisition of HIV, and small differences by race and age (Horsburgh and Selik, 1989). More recent reports show that homosexual/bisexual men now have higher rates of D N T M than intravenous drug users (8.8 percent versus 6.0 percent, manuscript in preparation), suggesting that this group may have increased access to diagn~x~.L facilities or may have lower CD4 cell levels as a group, resulting in increased susceptibility to MAC. The earlier occurrence of the H I V epidemic in homosexual/bisexual men and increased use of zidovudine may have resulted in a greater proportion of this population surviving to very low CD4 cell levels. Early reports suggested that M A C disease did not adversely affect survival of AIDS patients; however, several more recent studies have documented that AIDS patients with M A C disease have a significantly shorter survival than comparable A I D S patients without M A C (Jaeobson et al.. 1991 ; Horsburgh et al., 1991 ; Chaisson et aL, 1991). While antimycobac-

MYCOBACTER1A AND AIDS

terial regimens are now available that can ameliorate symptoms and decrease levels of mycobacteraemia, their effect on survival remains to be conclusiviely demonstrated, lr. a retrospective study, we showed that A I D S patients with M A C who received at least 3 antimycobacterial agents for at least 3 months had a survival similar to controls (median I 1 months for each group), and significantly longer survival than A I D S patients with M A C who did not receive antimyeobacterial therapy (median 4 months; Hatsburgh et al., 1991). However, the study was retrospective, and it is possible that physicians preferentially gave antimycobacterial agents to patients who were " n o t as sick", despite similar laboratory and clinical parameters. Thus the outcomes of current prospective trials are eagerly awaited. M A C disease, unlike tuberculosis, does not appear to be transmitted from person to person, but rather appears to be acquired from the environment (Horsburgh and Selik, 1989). Since the disease can be either pulmonary or gastrointestinal (both leading promptly to dissemination), the route of spread is presumed to be both inhalation and ingestion. Possible sources o f acquisition ino!ude water, food and soil. While the serotypes causing disseminated infection vary geographically (Ruf et al., 1989; Yakrus and Good, 1990; Hoffner et al., 1990), no correlation has been shown between the prevalence of serotypes in the environment and those recovered from patients. A study is currently underway to attempt to identify the reservoir(s) and activity(los) of risk for acquisition of this organism.

Conclusions Both tuberculosis and M A C disease are il,¢reased in frequency and severity in persons with H I V infection. These increases pose serious challenges for public health and patient care. The increased incidence of tuberculosis is taxing prevention and control efforts; the critical situation in Africa has recently been highlighted (Stanford el aL, 1990. Tbese efforts have been compounded by the unreliability of skin testing in HIV-infected per.~ons. New methods for diagnosis of both tuberculous infection and disease ~n HIVqnfected persons are needed. In the case of M A C disease, the reservoirs and mode of acquisition of this pathogen must be identified so that primary prevention o f M A C disease can be accomplished. Prophylactic antibiotic regimens for those at highest risk of M A C are currently being evaluated. Tuberculosis in HIV-infected persons has been reported to respond well to antituberculous therapy. However, the ominous appearance of multiply drug resistant strains in the HIV-infected population suggests that a prompt response to therapy cannot be counted on. This may result in a decrease in our abil-

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ity to limit the spread of this infection and will surely be an important force in the epidemiology of tuberculosis in the future. Therapeutic regimens for M A C are also suboptimal, despite apparent inoreased survival with therapy, New developments in the area of therapeutics will be needed to control both of these mycobacterial epidemics.

References Abouya, L., Kassim, S,, Ackah, A., Digheu, H,, Gnaore, E., gassan-Morakro, M., Coulibaly, I.-M., Coulibaly, D., Doorly, R. & De Cock. K.M. (1991), Prospective cohort study of pulmonary tuberculosis patients with HIV infections in Abidjan, Cote D'lvoire. Abstracts of the Vlth International Conference on AIDS in Africa, Dakar, 290. Barnes, P.F., Block, A.B., Davidsaa, P.T. & Snider, D.E. (1991), Tuberculosis in patients with human immunodeficiency virus infection. New Engl. J. AIed., 324, 1644-1650. Braun, M,M,, Bali, N,, Ryder, R.W., Ekungola, B.. Mukadi, Y., Nsuami, M., Matela, B., Williame. L-C., Kaboto, M. & Heyward, W, (1991), A retrospective cohort study of the risk of tuberculosis among women of childbearing age with HIV infection in Zaire. Amer. Rev. Resp. Dis., 143, 501-504. Braun, M.M., Byers, R.H., Heyward, W.L., Ciesielski, C,A,, Bloch, A,B., Berkelman, R.L. & Snider, D.E. (1990), Acquired irmnunode ficicncy syndrome and extrapulmonary tuberculosis in the United States. Arch. Intern. Med., 150, 1913-1916. CDC (1990), Nosocomial transmission of multidrugresistant tuberculosis among HlV-infeeted patients in an urban hospital - - Flodda. Mortal. Morbid. Weekly Rep., 39, 718-722. CDC (1991a), Nosocomial transmission of muhidrug resistant tuberculosis among HIV-infected persons - Florida and New York. 1988-1991. Mortal. Morbid. Weekly Rep., 40, 585-591. CDC (1991b), Mycobocterium haemophilum infections - New York City metropolitan area, 1990-1991, Morlel, Morbid. Weekly Rep., 40, 636-637 & 643. CDC (1991c1. Tuberculosis outbreak amt, ng persons in a residential facility for HIV-infected persons -- San Francisco. MorlaL Morbid. Weekly Rep., 40, 649-652. Chaisson, R.E., Keruly, J., Richman. D.D.. Creagh-Kirk, T., Moore, R.D. & the ZDV Epidemiology Group (1991), Incidence and natural history of AIycoba,~erium avium-complex infection in advanced HIV disease treated with zidovudine, Amer. Roy, Resp. Dis., 143, A278. Chaisson, R.E., Schecter, G.F., Theuer. C.P., Rutherford. G.W., Echenberg, D.F. & Hopewell, P.C. (1987), Tuberculosis in patients with the acquired immunodeficiency syndrome. Amer. Rev. Resp. Dis.. 136, 570-574. Di Perri, G., Crueiani, M , Danzi. MC,, Luzzati, R., De Checcili, G., Ma[eila, M., Pizzlghc]la, S., Mazzi, R., SolbiatL M., Concia, E. & Bassetti, D. (1989), Nosocomial epidemic of active tuberculosis among HIV-infected patients. Lancet, IL 1502-1504.

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Ellimt, A.M., Luo, N., Tembo, G., Halwiindi, B., Steenbergen, G., Machiels, L , Pobee, J., Nunn, P., Hayes, R.J. & McAdam, K. 41990),Impact of I-IIV on tuberculosis in Zambia: a cross-sectional study. Brit. &led. J., 301,415-417. Farizo, K.M., Buehler, J.W. & the adult/adolescent spectrum of HIV disease study group 41991), Pulmonary mycobacterial infections in persons wi;h l-llV infection. Abstracts of the 31st lntcrscience Confer*.nee on Aatimicrobial Agents and Chemotherapy, 139. Havlik, J.A., Horsburgh, C.R., Metehock, B., Williams, P.P., Farm, S.A. & Thompson, S.E. 11992), Disseminated Mycobaeterium avium complex infection : clinical identification and epidemiologie trends. J. infect. Dis. (in press). Hoffncr, S.E., kallenius, G., Petrini, B., Brennan, P.J. & Tsang, A.Y. 41990), Serovars of Mycobacteriunl avium complex isolated from patients in Sweden. J. clin. MicrobioL, 28, 1105-1107. Hnrsburgh. C.R. (1989), Mycobacterial infections in the immunocompromised host. Sere. Respir. Med., 10, 61-67. Horsburgh, C.R. (1991), Mycobactertum avium complex infection in the acquired immunodefieieney syndrome. New EngL J. Med., 324, 1332-1338. Horsburgh, C.R., Havlik, J.A., Ellis, D.A., Kennedy, E., Farm, S.A., Dubois, R.E, & Thompson, S.E. (1991), Survival of patients with acquired immune deficiency syndrome and disseminated Mycobacterium avium complex infection with and without antimyeobaeterial chemotherapy. Amer. Rev. Resp. Db., 144, 557-559. Horsburgh, C.R. & Selik, R.M. {19891,The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS). Amer. Rev. Resp. Dis., 139, 4-7. Jacobsen, M.A., Hopewell, P.C., Yajko, D.M,, Hadley, W.K., Lazarus, E., Mohanty, P.K., Modin, G.W., Feigal, D.W., Cusick, P.S. & Sande, M.A. (1991}, Natural history of disseminated Mycobacterium avium complex infection in AIDS..L infect. Dis., 164, 994-998. Kallenius, G., Hoffner, S.E. & Svenson, S.B. (1989), Does vaccination with bacille Calmette-Guerin protect against AIDS? Rev. infect. Dis., If, 349-351. Klein, N.C., Duncaason, F.P. & Lenox, T.H. (1989), Use of myeobacterial smears in the diagnosis of pulmonary tuberculosis in AIDS/ARC patients. Chest, 95, 1190-1192. Leonard, G., Sang,are, A.. Verdier, M., et al. (1991), Prevalence of HIV infection among patients with leprosy in African countries and Yemen. ,L AIDS, 3, 1109-1113. Long, R., Scalcini, M.. Manfreda, J.. Carte, G., Philippe, E., Hershfield, E., Sekla, L. & Stackiw, W. (1991), hnpact of human immunodeficieney virus type l on tuberculosls in rural Haiti. Amer. Rev. Resp. Dis., 143, 69-73. Luca% S., Hounnou, A., Diomede, M., Beaumel, A., Kadio, A., Giordzno, C., Ezaui, N., Honde, M., Peacock, C. & De Cock, K.M. (1991), The Pathology of terminal HIV-2 infection in Abidjan, Cote D'lvoire. Abstracts of the Vlth International Conference on AIDS in Africa, Dakar, 84.

Manoff, S,B., Caut hen, G.M., Stonehurner, R.L.. BIoch, A.B., Schultz, S. & Snider, D,E. 0988), TB patients with AIDS: Are tbey more likely to spread TB ? Abstracts of the IVth International Conference on AIDS, Stockholm, 2, 216. Meeran, K. 41989),Prevalence of HIV infection among patients with leprosy and tuberculosis in rural Zambia. Brit, Med. J., 298, 364-365. Moreno, C., Taverne, J., Mehlert, A., et aL (19891, Lipoarabinamannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and marine maerophages. Clin. exp. lmmunol,, 76, 240-245. Okonda, L., Nelson, A.M., Mukadi, Y., Mbuyamba, L. & Angritt, P. (1991), HIV associated tuberculosis: an underdiagnosed condition? Abstracts of the Vlth International Conference on AIDS in Africa, Dakar, 292. Onorato, I.M., McCray, E. & Field Services Branch (1992). Prevalence of human immunodeficiency virus Infection among patients attending tuberculosis clinics in the United States. J. infect. Dis., 165, 87-92. Perriens, J.H., Colebunder~, R.L.. Karahunga, C., Williame, J.-C., Jeugmans. J., Kaboto, M., Mukadi, Y., Pauwels. P., Ryder, R.W., Prignot, J. & Pier. P. 0991). Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with "standard" chemotherapy in Kinshasa, Zaire. Amer. Rev. Resp. Dis., 144, 750-755. Pitchenik, A.E., Burr, J., Suarez, M., Fertel, D., Gonzalez, G. & Moas, C. (t987), Human T-cell lymphotropic virus-Ill (HTLV-III) seropositivity and related disease among 71 consecutive padents in whom tuberculosis was diagnosed. Amer. Rev. Resp. Dis., 135, 875-879. Pilchenik, A.E., et aL (1990), Outbreaks of drug-resistant tuberculosi~ at AIDS centre. Lancet, 11, 440-441. Ponnighaus, J.M., Mwanjasi, L.J., Fine, P.E.M., Shaw, M.-A., Turner, A.C.. O×borrow, S.M., Lucas, S.B., Jenkins, P.A., Sterne, J.A.C. & Bliss, L. (1991), Is HIV infection a risk factor for leprosy? Intern. J. Leprosy, 59, 221-228. Rieder, H.L., Cauthen, G.M., Kelly, G.D., Bloch, A.B. & Snider, D.E. ll989), Tuberculosis in the United States. J. Amed, reed. Ass., 262, 385-389. Ruf, B., Peters, M., Schroder, H.-I. & Pohle, H.D. (1989), Mycobacterium avium-intracellulare serovars in German AIDS patients. Lancet, 11, 110l. Selwyn, P.A., Hat tel, D., Lewis, V.A., Sehoenbaum, E.E., Vermund, S.H., Klein, R.S., Walker, A.T. & Friedland, G.H. {19891,A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeflciency virus infection. New EngL J. Med., 320, 545-550. Shattock, R., Friedland, J.S. & Griffin, G.E. (1991), Phagocytosis of Mycobacterium tuberculosis stimulates transcription of human immunodeficieney virus (HIV) types 1 and 2 in macrophages. Abstracts of the Vllth International Conference on AIDS, Florence l, 147. Small, P.M., Sehecter, G.F., Godman, P.C., Sonde, M.A., Chaisson, R.E. & l-lopeweli, P.C. (1991), Treatment of tuberculosis in patients with advanced human im-

MYCOBACTERIA AND AIDS munodefieieney virus infection. New EngL J. Med., 324, 289-294. Stanford, J.L., Grange, J.M. & Pozniak, A. (1991), Is Africa lost? Lancet, II, 557-558. Tckle-Haimanot, R., Frommel, D., Tadesse, T., et el. (1991), A survey of HTLV-I and HIVs in Ethiopian leprosy patients. AIDS, 5, 10g-ll0. Theuer, C.P., Hopewell, P.C., Elias, D., Schecter, G.F,, Rutherford, (3.W. & Chaisson, R.E. (1990), Human immunodeficiency virus infection in tuberculosis patients. ,/. infect. Dis., 162, 8-12. Valone, S,E., Rich, E., Wallis, R.S. & EIIner, J.J. (1988), Expression of tumor necrosis factor in vitro by hu-

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man monuclear phagocytes stimulated with whole Mycobacterium boris BCG and mycobactcrial antigens. Infect. Immun., 56, 3313-3315. Von Reyn, C.F., Falkinham, J.O., Brindle, R., Ranki, A., St. Louis, M., Arhelt, R. & O'Connor, G. (1991), The international epiderniology ofM. avium in AIDS. Abstracts of the Vllth International Conference on AIDS, Florence 2, 262. Yakrus, M.A. & Good, R.C. (1990), Geographic distribution, frequency, and specimen source of Myeobacterium avium complex serntypes isolated from patients with acquired immunodeficiency syndrome..L clin. MicrobioL, 28, 926-929.

Clinical aspects of ..-a,-,-.-,---~-h""~'*~l---,.'nfections in HIV infection R . J . C o k e r ¢n, T . J . H e l l y e r t2), I , N , B r o w n t21 i*l a n d J . N . W e b e r (1) (I) Department o f Genitourinuly Medicine end Comm!mie,~bl~ Di~eetsa% ond t21 Department o f Medieul Microbiology, St. Mary's Hospital Medical School, London W2 I N Y

Introduction Mycobacterial infection has long been associated with defective cell-mediated immunity. In the current A I D S epidemic, infection with ,~Iycobacterium tuberct*losis and Mycobacterium avium-intracellulare complex (MAC) look certain to remain dominant features. Other atypical mycobacteria are involved to a lesser extent. Effects of H I V infection on incident leprosy seem largely speculative. We shall consider the mycobaeteria in patients with H1V infection in four groups: M. tuberculosis, MAC, the other atypical rnycobacteria and M. leprae. The purpose of this article is to provide a brief overview and to highlight the experience at a major British AIDS referral hospital.

Mycobacterium tuberculosis infection Tuberculosis probably affects about one third of the world's population and the number of people dually infected with M. tuberculosis and H1V is increas-

t*) To whom coz,~demce should he addressed.

ing rapidly, particularly in countries in subsaharan Africa. It is estimated that lnor~: than 3 million people are dually infected. There are three distinct cpidemiological patterns of tuberculosis associated with H I V : 1) Reactivation of past M. tuberculosis infection in subjects subsequently infected with HIV; 2) fresh infection of H I V antibody positive individuals ; and 3) cases within the general population arising from direct contact with infectious individuals from categories (l) and (2). Evidence for an interaenon between tuberculosis and AIDS is provided by the increased number of reported cases when HIV encroaches on areas endemic for tuberculosis and the often high rates of HIV posifivity in patients admitted for tuberculosis in such areas. This evidence is well documented elsewhere and there appears to be great variation according to locality with up to 60 % patients HIV-seropositlve, e.g. in Zambia (Elliott et al., 1990). A compounding factor in developing countries may be fhe breakdown of the tuberculosis control infrastructure,