Pneumocystis carinii Pneumonia An Uncommon Cause of Death in African Patients with Acquired Immunodeficiency Syndrome 1 , 2

Y. L. ABOUYA, A. BEAUMEL, S. WCAS, A. DAGO-AKRIBI, G. COULIBALY, M. N'DHATZ, J. B. KONAN, A. YAPI, and K. M. DE COCK

Introduction

The pulmonary manifestations of the acquired immunodeficiency syndrome (AIDS) in adults in developed countries have been welldescribed. The most common opportunistic infection complicating human immunodeficiency virus Type 1 (HIV-l) infection is Pneumocystiscarinii pneumonia, which occurs at presentation in 40070 and during the course of illness in > 80% of patients with AIDS (1). Pulmonary tuberculosis due to Mycobacterium tuberculosis is relativelyuncommon: in the United States, 1.4% of U.S.-born, 4.0% of Africa-born, and 7.3% of Haiti-born AIDS patients present with tuberculosis (2). In Africa, the converse appears to be the case. P. carinii pneumonia is uncommon, the data available indicating prevalences in adult AIDS patients of zero to 22070 (3-10). HIV infection is the strongest of all risk factors for developing tuberculosis in previously infected persons (11). In Africa, the burden of tuberculosis attributable to HIV infection is high (12, 13). Clinical studies of adult patients in Nairobi, Kenya, presenting to acute medical services found that 8.5% of all patients had tuberculosis, 40% of whom were HIV seropositive (14). The available but unsystematic lung biopsy, induced sputum, and autopsy studies of HIV -seropositive patients in Africa show prevalence levels of tuberculosis from 25 to 50% (3-5, 7, 8). The incidence of P. carinii pneumonia can be reduced with specific chemoprophylaxis. It is likely that tuberculosis is underdiagnosed in Africa (13, 14). Thus it is important to establish firmly the frequencies of these and other pulmonary complications of AIDS. The facilities for fully investigating people with pulmonary symptoms are limited in Africa. The most sensitive technique for diagnosing the range of severe pulmonary diseasesin a population is to analyze post

SUMMARY Admissions and deaths In a pulmonary medicine ward In AbidJan, Cote d'ivolre, West Africa, were evaluated over a 6·month period In 1989with systematic autopsies on all petlents who died. Of 473 petlents admitted, 38% were HIY·l seropositive, 4% were HIY·2 seropositive, and 14% reacted to both viruses. A total of 100 patients (21%) died, and deaths were twice as frequent In HIY·seroposltlve compared with HIY·negatlve patients. The pathology of 78 autopsies showed that the predominant cause of death In HIY·seroposltlw patients wes disseminated tuberculosis (40%). Cancer wes the cause of death In 64% of HIY·negatlve patients. Pneumocyatosls wes found In only 9% of HIY·seroposltlve autopsies. Since Pneumocystls carlnllis an uncommon cause of death In this population, prophylaxis for P. carlnll pneumonia Is not werranted for HIY·lnfected patients In Africa. In contrast, research on chemoprophylaxis for tuberculosis Is urgently required. AM REV RESPIR DIS 1992; 145:617-620

mortems. We conducted a systematic . study of lung pathology in patients dying on a pulmonary medicine ward in Abidjan, a city with a high prevalence of HIV-l and HIV-2 infections (15). The aims of the study were (l) to determine the prevalence of HIV-1 and HIV-2 infections among patients hospitalized on the pulmonary diseases service of Abidjan's largest hospital; (2) to examine death rates in relation to HIV -1 and HIV-2 infections; and (3) to examine the pulmonary pathology associated with these infections compared with deaths in HIV -seronegative patients. Methods For 6 months beginning in mid-1989, consecutive adult patients (> 14 yr) admitted to the Pulmonary Medicine Service, University Hospital, Treichville, Abidjan, were studied. They were comprised of black residents of Abidjan. Criteria for admission to this service are symptoms and signs referable to the lungs and heart. Patients wereinvestigatedand managed according to standard hospital procedures. To identify HIV-l and HIV-2 antibodies, serum specimens were tested by whole-virus enzyme-linked immunosorbent assay (ELISA). If repeatedly reactive,they were further tested by virus-specific western blot and synthetic peptide assay as previouslydescribed (16). No facilities were available in Abidjan for culturing mycobacteria. An autopsy was performed on those patients who died. Both lungs were removed,

sectioned, and sampled systematically. Fixed lung and extrapulmonary tissue samples were processed to paraffin. Sections were stained with hematoxylin and eosin, Grocott (for Pneumocystis, Nocardia, and fungi), ZiehlNeelsen and Wade-Fite methods (for acid-fast bacilli and Nocardia), and Gram-1\vort (for gram-positive and gram-negative bacteria). Immunocytochemistry with monoclonal antibodies was used to confirm the presence of cytomegalovirus and Toxoplasma infection. The study was conducted with the approval of the Research and Ethics Subcommittee of the National AIDS Committee.

Results

Over the 6-month study period, there were 495 consecutive adult admissions: 366 (74%) weremale and 129(26%) were female. The mean age of male patients was 41 yr (range 16to 84), and of females was 34 yr (range 15 to 72). (Received in original form March 11, 1991 and in revised form July 29, 1991) 1 From the Service de Pneumophtisiologie and the Service d'Anatomie Pathologique, Centre Hospitalier et Universitaire de 'Ireichville,and Projet RETRO-CI, Abidjan, Cote d'Ivoire, West Africa, the Department of Histopathology, University College and Middlesex School of Medicine, London, England, and the Division of HIVIAIDS, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia. 2 Correspondence and requests for reprints should be addressed to Dr. S. Lucas, Projet RETROCI, 01 BP 1712Abidjan, Cote d'Ivoire, West Africa.

617

618

ABOUVA, BEAUMB., WCAS, ET AL

Males

TABLE 1

TABLE 3

PREVALENCE OF HIV-1 AND HIV-2 INFECTIONS BY SEX AND OUTCOME IN PATIENTS ADMIITED

ASSOCIATED PULMONARY PATHOLOGIES: CONDITIONS DETECTED HISTOLOGICALLY IN LUNG TISSUE BUT NOT CONSIDERED THE PRIME CAUSE OF DEATH ON MORPHOMETRIC CRITERIA

HIV-l

HIV·2

HIV-1/2

Negative

Total

130

14 (4oAl)

58 (17%)

146 (42%)

348

3

9 (7%)

64 (51%)

125

67

473

(37°Al)'

Females Total Died Survived

49 (39%)'

(2%)

179 (38%)*

17 (4%)

(14%)

210 (44%)

29

46 (26%)t

~

6

19

(35%)

(28%)

(14%)

133 (74%)t

11 (65%)

48 (72%)

181 (86%)

HIV Serostatus Pathology

[100] {373]

• Percentages of males. females, and totals.

TABLE 2

HIV Serostatus HIV-2

6 4 1 1

Total HIV* 18 21 4 3

(34%)t (40%) (8%) (6%)

=

25)

Tuberculosis Pyogenic abscess Kaposi's sarcoma CMV infection P. carinii Schistosomal eggs

*

PRIME CAUSES OF DEATH IN 78 AUTOPSIES

HIV-l

HIV· (n

• Old Iibrocaseous tuberculosis in patients with pyogenic pneumonia. t One case of active tuberculosis in association with bronchial carcinoma; one case of old Iibrocaseous tuberculosis in a patient with pyogenic pneumonia. Both Kaposi's sarcoma and scanty cytomegalovirus (CMV) inclusions seen in one patient with confluent pneumocystosis. § SCanty alveoli containing P. carlnii in 8 patient who died of nocardiosis.

t Percentages of patients in each HIV-seroreactive group.

Dual HIV-1I2

All HIV' = 53)

(n

HIV-

Totals

7 (28%) 1 (4%)

25 23 4 3

in relation to that affected by the prime pulmonary pathology. Deaths among HIV-I-seropositive patients. Thberculosis was the cause of 1 1 2 (4%) 16 (64%) 18 death in 13 of 33 (39070) of the HIV-l1 1 seropositive patients. Within the lungs, 1 1 the tuberculosis was nodular and miliary, 2§ 2 2 but not cavitating. In 12cases, the infec111 1 1 15 53 25 78 33 tion showed miliary dissemination to the 5 hilar lymph nodes and outside the tho• Pyogenic pneumonia or bronchopneumonia; stains for acid-fast bacilli, P. carinii, fungi, and Norrax to other organs, such as liver, spleen, ctudia negative. Many cases shOWed gram-positive cocci. t Percentages are per HIV seregroup. and kidney. The histopathology in all 13 *Includes both primary and secondary cancers in lung. cases showed the pattern of nonreactive § One chronic constrictive pericarditis (no tuberculosis evident); one acute pyogenic pericarditis. H Bilateral polycystic kidneys. tuberculosis (18): there was no caseation or granuloma formation, but there was fibrinoid necrosis with abundant karyorevery age group except 60 yr and over. rhectic debris, peripheral hydropic and Serology Data Serum was unavailable for 22 (4070) of Of the HIV-positive deaths, 92070 oc- unactivated macrophages, and large numpatients admitted; these were omitted curred in patients aged < 50 yr compared bers of acid-fast bacilli throughout the from subsequent detailed analysis. The with 48070 of5 HIV-negative deaths (Xl == necrosis. overallprevalence of HIV infection (HIV-I 23; p < 10- ) . The second most frequent pathology, in 12 (36070) of cases, was nonspecific and HIV-2 combined) was 58070 in men pneumonia and bronchopneumonia, ofand 49070 in women (table 1).The highest Pathology Data ten accompanied by abscess formation. rates werein males aged 30 to 39 yr (73070) and in females aged 20 to 29 yr (69070). Of the 99 deaths investigated by autop- These were pyogenic lesions with no Rates for HIV-I infection exceeded those sy, histopathologic material was techni- histologic evidence of acid-fast bacilli, for HIV-2. Of all males, 17070 were cally unsatisfactory or unavailable for 10. Nocardia, or fungal infection. In several seroreactive for both viruses, as were7070 . Of the autopsied cases, 11 lacked HIV cases, gram-positive cocci and gramof females, similar to results previously serologic data. Full data were thus avail- negative rods were identified. , observed in Abidjan (16, 17). able for 78 cases: 53 seropositive patients P. carinii was the cause of death in During the study period, 71 of 263 (75070 of HIV-seropositive deaths during three of 33 (9070) patients and was an as(27070) seropositive patients died com- the study period) and 25 (86070) of the sociated pathology in a further patient (table 3), providing an overall 12070 prevpared with 29 of 210 (14070) seronegative seronegative deaths. The prime causes of death evaluated alence of P. carinii pneumonia in the patients (relative risk = 1.95; 95070 confidence interval 1.3 to 2.9). Each type of from macroscopic and microscopic ex- HIV-l-associated deaths. seroreactivity (HIV-I, HIV-2, and dual- amination of lung and extrapulmonary Widespread pulmonary Kaposi's sarHIV reactivity) was significantly as- tissues are summarized in table 2. Asso- coma was the cause of death in two cases sociated with a fatal outcome (table I). ciated pulmonary pathologies are shown' (6070). Incidental small amounts of pulCase fatality rates, expressed as deaths in table 3: these are diseases not consid- monary Kaposi's sarcoma were seen in per total admissions, were higher in HIV- ered the prime causes of death because a third patient who died of P. carinii positive than in HIV-negativesubjects for the volume of lung affected was small pneumonia; this patient also had infecNonspecific pneumonia' Pulmonary tuberculosis Pneumocystis pneumonia Kaposi's sarcoma Pulmonary nocardiosis Cancer:!: Cor pulmonale Toxoplasma myocarditis Pericarditis Renal failure Totals

12 13 3 2 1 1

4

pcp AS AN UNCOMMON CAUSE OF DEATH IN AFRICANS WITH AIDS

tion with cytomegalovirus with scanty viral inclusions in alveolar cells « 1 per 100 high-power fields at x400 magnification). Nocardia bacteria were identified in one HIV-l-seropositive patient with miliary lung lesions; the bacteria were branching and beaded, Grocott silver positive, and acid fast with Wade-Fite stain but not with Ziehl-Neelsen. This case also showed small quantities of pneumocystosis in adjacent alveoli. One HIV-l-infected patient died of bronchial carcinoma with widespread metastases and another of toxoplasma myocarditis. Deaths among HIV-2-seropositive patients. Of the five patients autopsied, three died of disseminated nonreactive tuberculosis. The fourth had reactive paucibacillary tuberculosis with spread limited to the hilar nodes. The fifth patient had lung adenocarcinoma with extrapulmonary metastases. No HIV-2 patient had P. carinii. Deaths among dual-HIV-reactive patients. The 15 autopsied patients had quantitatively similar pathology to the HIV-l-seropositive group. All four patients dying of tuberculosis (26010) had disseminated nonreactive tuberculosis. . One patient died of P. carinii pneumonia. The two cases of pericarditis comprised one of chronic constrictive pericarditis and one of acute purulent pericarditis; in neither were acid-fast bacilli or granulomas indicative oftuberculosis found histopathologically. The one case of renal failure was due to bilateral polycystic kidneys. Deaths among HIV-seronegative patients. Cancer was the cause of death in the 160f25 (64%) of patients examined, giving a rate ratio of 17.0 (95% CI 4.2 to 68.2) compared with HIV-seropositive patients: nine (36%) had primary lung cancer (four small cell carcinomas, three large cell anaplastic carcinomas, one adenocarcinoma, and one mixed squamous and small cell carcinoma); six patients (24%) had metastatic tumor (one case each with primary tumor in breast, liver, kidney, prostate, stomach, and esophagus); and one patient had disseminated low-grade B cell lymphoma. A total of seven patients (28%) died of nonspecific pneumonia and one of pulmonary hypertension (presumed primary in the absence of a specific etiology). A single patient died of pulmonary nonreactive tuberculosis, giving a rate ratio of deaths from tuberculosis in HIV+ patients of 9.9 (95% CI 1.4 to 70.0) compared with HIV-negative subjects. Deaths amongpatients with unknown

619

fection is becoming widelyrecognized(13, 22). Our study reinforcesthis association. A minimum 44% of all the autopsied patients had evidence of tuberculosis. An estimate was derived of the prevalence of P. carinii pneumonia among HIV-seropositive people in this population: P. carinii pneumonia is not diagnosed clinically here and thus not treated; patients with pulmonary symptoms are referred to the pulmonary medicine service; and whole lungs of those dying Discussion were examined. All five patients with P. In AIDS patients in Africa, death from carinii were HIV seropositive. No pneupulmonary disease is common. This mocystosis was seen in any hilar lymph study is the first in Africa systematically nodes or outside the thorax (and there to investigate the pathologic conditions are no reports of extrapulmonary P. that underlie mortality in HIV-infected carinii from Africa). This 9% prevalence people and to compare them with the of P. cariniipneumonia is consonant with pathologies of non-HIV-infected pa- other studies in Africa that utilized autients. The proportions and causes of topsy, bronchial lavage,or transbronchial death in HIV-seropositivepatients on this biopsy (table 4). These low rates contrast pulmonary medicine service in Abidjan markedly with the ubiquitous P. carinii were quite different from those found in in AIDS patients in North America and HIV-negative patients. Europe. The accumulation of data from For HIV-seropositive people, the rela- Africa, including the present study, tive risk for dying was 1.95 compared strongly contradict the notion that P. with HIV-seronegative people, with simi- carinii pneumonia is common in African lar relative risks for HIV-l-, HIV-2-, and AIDS patients but merely undiagnosed dual-HIV-reactive patients. The age at through lack of investigative facilities. death in HIV-seropositive patients was In Africa before the AIDS epidemic, significantly younger than in HIV- P. carinii pneumonia (PCP) was diagseronegative patients. The prime causes nosed only in malnourished infants (23of death in the 53 patients with the three 25). However,a recent serologicstudy has patterns of HIV seroreactivity were qual- documented a similar 70% prevalence of itatively and quantitatively similar. antibodies to P. carinii in Gambian and Of the HIV-seropositive patients, 40010 in British children by the age of 8 yr (26). died of tuberculosis, a rate nearly 10times Thus the infrequency with which P. higher than in HIV-negativepatients. The carinii infection is identified in Africa pattern of disease was multibacillary, dis- reflects uncommon development of inseminated, and nonreactive, the common fection, not the lack of the infectious pathologic pattern of tuberculosis in the agent in the environment. It is possible terminal stages of HIV infection (5, 18, that HIV-seropositive patients die of 19).Although no mycobacterial cultures more virulent diseases, such as tubercuwere feasible in this study, we are confi- losis, before PCP can develop. It is not dent that all the mycobacterial lesions ob- yet known, in Africa, how the developserved were due to M tuberculosis, not ment of P. carinii pneumonia correlates to an atypical mycobacterial infection, with the degree of immunodepression as such as M avium-intracellulare (MAl). reflected by peripheral blood CD4+lymThe relative histopathologies of the two phocyte counts (27). infections are very distinct in HIV-inIt has been suggested that in the abfected patients (18-20). Furthermore, sence of investigative facilities, pneuparallel studies of HIV-seropositive pa- mocystosis should be suspected in Afritients in Cote d'lvoire and other sub- can HIV-infected patients who have perSaharan African countries have failed to sistent cough or radiologic pulmonary detect atypical mycobacteria in suptum infiltrates in the absence of tuberculosis (21)(projet RETRO-CI, unpublished ob- (28). Empirically, however, in Africa, servations) or blood (14). where diagnostic facilities are generally Thberculosis in HIV-infected people is unavailable, pneumocystosis is unlikely regarded as a reactivation of latent in- to be a relevant diagnosis. . . Only one of the 53 HIV-seropositive fection rather than a new infection (11, 22). In Africa, where prevalence rates of patients had histologic evidence of pultuberculosis and HIV infection are high, monary cytomegalovirus (CMV) infecthe clinical and public health significance tion, and the inclusions werescanty. This of tuberculosis associated with HIV in- infrequency is consonant with the ab-

HIVstatus. Of the 22 patients for whom serologic data wereunavailable, 12(55%) died and were autopsied, with histology available for 11. The pathologic diagnoses weretuberculosis (four), nonspecific pneumonia (four), pericarditis (one), . pulmonary edema (one), and nocardiosis (one). None had P. carinii infection. No cases of infection with Cryptococcus were identified in any patients in this study.

620

ABOUYA, BEAUMEL, WCAS, £T AL.

TABLE 4 PUBLISHED PREVALENCE LEVELS OF Pneumocystis carinii IN HIV-SEROPOSITIVE PATIENTS IN SUB-SAHARAN AFRICA

Country Congo Rwanda Uganda Uganda Uganda zaire Zambia zambia Zimbabwe Cote d'ivoire

BAL and/or TBBx'

Autopsy Diagnosis

No. Studied 45

+ + +

44

+ + + +

+ + +

40 22 57 31 1 27 37 53

No. with PCP (%)

Reference

5 (11%) 3(7%) 0

0 3 (5%) 1 (3%) 1 0

10 3

6 9 5 4

9 7

8 (22%)

8

5 (goAl)

-t

• Techniques of investigation: bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx). This study.

t

sence of CMV in biopsy studies of lung (3, 8) and its rarity at autopsy in Africa (only one of 57 Ugandan AIDS patients had pulmonary CMV) (5). However, the seroprevalence of CMV antibodies in African adults (> 60010) (12, 29) is similar to that found in developed countries in which 60010 of autopsied AIDS patients have widespread CMV infection. Evidently, reactivation of latent CMV infection occurs uncommonly in HIVinfected patients in Africa. The 6010 prevalence of pulmonary Kaposi's sarcoma in Abidjan HIV-seropositive patients contrasts with prevalence levelsof 16to 19010 found by in vivo studies in Rwanda and Zimbabwe (3, 8). The burden of pulmonary Kaposi's sarcoma in AIDS patients across Africa is unstudied, but its distribution is probably as uneven as that of Kaposi's sarcoma in HI V-negative subjects as documented in the pre-AIDS era (30). The lack of pulmonary cryptococcosis in this study population also contrasts with in vivo studies from Rwanda (3)and autopsy observations in Uganda (5), where 14and 19010 of cases, respectively, had cryptococcosis. Again, this suggests geographic variation within the continent. In summary, HIV-seropositivepatients admitted to specialist pulmonary medicine wards in Abidjan had a nearly double risk of dying compared with seronegative subjects. The pathologies in those with HIV-l, HIV-2, and dual-HIV seroreactivity were similar. Thberculosis of the disseminated nonreactive multibacillary pattern was the most common cause of death in HIV-seropositive patients (40010) but was found in only 4010 of seronegative subjects. Similar proportions - 34010 of HIV-seropositive and 28070 of seronegative patients-died of histologically nonspecific acute pneumo-

nias. Of HIV-seropositive patients, 9% had P. carinii infection, but none of the seronegative subjects. In 64% of HIVseronegative subjects, primary or secondary lung cancers werethe cause of death. For the practical management of HIVseropositive patients presenting with pulmonary symptoms in this environment, pneumocystosis is uncommon. There is an urgent need not only for more sensitive means of diagnosis of tuberculosis but also for prophylaxis against the reactivation of this infection in HIV-seropositive people in Africa. References 1. Mills J. Pneumocystis cariniiand Toxoplasma gondii infections in patients with AIDS. Rev Infect Dis 1986; 8:1001-11. 2. Kreiss JK, Castro KG. Special considerations of managing suspected HIV infection and AIDS in patients from developing countries. J Infect Dis 1990; 162:955--60. 3. Batungwanayo J, Taelman H, Bogaerts J, et 01. Pneumopathies et infection a VIH a Kigali, Rwanda, interet du lavage bronchoalveolaire et de la biopsie transbronchique pour le diagnostic etiologique, In: V International Conference on AIDS in Africa. Kinshasa, 1990 (abstract FOD 3). 4. Nelson AM, Longweno C, Tuur S, et 01. Pulmonary pathology of HIV infection in zaire. In: V International Conference on AIDS in Africa. Kinshasa, 1990 (abstract FPB 29). 5. Lucas S, Odida M, Wabinga H. The pathology of severe morbidity and mortality due to HIV infection in Africa. AIDS 1991; 5:S143-8. 6. Lucas S, Goodgame R, Kocian G. Serwadda D. Absence of pneumocystosis in Ugandan AIDS patients. AIDS 1989; 3:47-8. 7. Elvin KM, Lumbwe CM, Luo NP, Bjorkman A, Kallenius G, Linder E. Pneumocystiscariniiis not a major cause of pneumonia in HIV infected patients in Lusaka, zambia. Trans R Soc Trop Moo Hyg 1989; 83:553-5. 8. McLeod Dr, Neil P, Robertson VJ, et al. Pulmonary disease in patients infected with HIV in Zimbabwe, Central Africa. Trans R Soc Trop Med Hyg 1989; 83:694-7. 9. Lucas S, Sewankambo N, Nambuya A, et al. The morbid anatomy of African AIDS. In: Giraldo G, Beth-Giraldo E, Clumeck N, Gharbi Md-R,

Kyalwazi SK, de The G, eds. AIDS and associated cancers in Africa. Basle: Karger, 1988; 124-31. 10. Carme B, Mboussa J, Andzin M, Mbouni E, Mpele P, Datry A. Pneumocystis cariniiis rare in AIDS in Central Africa. Trans R Soc Trop Med Hyg 1991; 85:80. 11. Murray JF. The white plague: down and out, or up and coming? Am Rev Respir Dis 1989; 140:1788-95. 12. Goodgame RW. AIDS in Uganda-clinical and social features. N Engl J Med 1990;323:383-9. 13. Harries AD. Thberculosis and human immunodeficiency virus infection in developing countries. Lancet 1990; 335:387-90. 14. Gilks CF, Brindle RJ, Otieno LS, et 01. Extrapulmonary and disseminated tuberculosis in HIV-l seropositive patients presenting to the acute medical services in Nairobi. AIDS 1990; 4:981-5. 15. De Cock KM, Odehouri K, Moreau J, et 01. Rapid emergence of AIDS in Abidjan, Ivory Coast. Lancet 1989; 2:408-11. 16. De Cock KM, Odehouri K, Colebunders RL, et 01. A comparison of HI V-Iand HIV-2 infections in hospitalized patients in Abidjan, Cote d'Ivoire. AIDS 1990; 4:443-8. 17. De Cock KM, Barrere B, Diaby L, et al. AIDS - the leading cause of adult death in the West African city of Abidjan, Cote d'Ivoire. Science 1990; 249:793-6. 18. Nambuya A, Sewankambo N, Mugerwa J, Goodgame R, Lucas S. Thberculous lymphadenitis associated with HIV infection in Uganda. J Clin Pathol 1988; 41:93-8. 19. YangGCH, Shinella RA. The histopathology of tuberculosis in AIDS: a study of 9 cases. In: Rotterdam H, Racz P, Greco MA, Cockerell CJ, eds. Progress in AIDS pathology, Vol.2. New York:Field & Wood, 1990; 103-10. 20. Zakowski P, Fligiel S, Berlin GW, Johnson L. Disseminated Mycobacterium avium-intracellulare infection in homosexual men dying of acquired immunodeficiency. JAMA 1982; 248:2980-2. 21. Nunn P, Githui W, Gathua S. Thberculosis and HIV infection in Kenya. Ann Intern Med 1991; 114:252-3. 22. Elliott AM, Luo N, Tembo G, et 01. Impact of HIV on tuberculosis in zambia: a cross-sectional study. Br Med J 1990; 301:412-5. 23. Thijs A, Janssens PG. Pneumocystis in Congolese infants. Trop Geog Med 1963; 15:158-72. 24. Abioye AA. Interstitial plasma cell pneumonia iPneumoneystiscarinii) in Ibadan. Report of a case. W Afr Moo J 1967; 16:130-1. 25. Bwibo NO, Owor R. Pneumocystis carinii pneumonia in Ugandan African children. W Afr Med J 1970; 19:184-5. 26. Wakefield AE, Stewart, Moxon ER, Marsh K, Hopkin JM. Infection with Pneumocystis carinii is prevalent in healthy Gambian children. Trans R Soc Trop Med Hyg 1990; 84:800-2. 27. Masur H, Ognibene FP, Yarchoan R, et 01. CD4 counts as predictors of opportunistic pneumonias in HIV infection. Ann Intern Med 1989; 1ll:223-31. 28. Colebunders RL, Perriens J, Kapita B. Clinical manifestations and management of adults with HIV infection. In: Piot P, Mann JM, eds. Balliere's clinical tropical medicine and communicable diseases, Vol. 3, No. 1. AIDS and HIV infection in the tropics. London: Balliere, Tindall, 1988;51-72. 29. Mhalu F, Haukenes G. Prevalence of cytomegalovirus antibody in pregnant women, AIDS patients and STD patients in Dar es Salaam. AIDS 1990; 4:1294-5. 30. Hutt MSR. The epidemiology of Kaposi's sarcoma. Antibiot Chemother 1981; 29:3-8.