Risk factors for Kaposi's sarcoma in HIV-positive subjects in Uganda.

BACKGROUND: Kaposi's sarcoma (KS) is associated epidemiologically with HIV infection and with human herpesvirus 8 (HHV-8 or KSHV). Both KS and HIV infection are common in Uganda. We conducted a case-control study of 458 HIV-seropositive. Ugandan adults with KS and 568 HIV-seropositive subjects without KS to examine risk factors for HIV-associated KS. METHODS: We recruited newly diagnosed adult KS cases from five hospitals in Kampala, Uganda and controls from a large referral clinic for HIV infection at Mulago Hospital. All cases and controls were counselled and tested for HIV and answered an interviewer-administered questionnaire about their home, socio-economic conditions, lifestyle and sexual behaviour before they became ill. Only HIV-seropositive subjects were included in the analysis. RESULTS: There were 295 males and 163 females with KS and 227 male and 341 female controls. Age distribution was similar but there was a higher proportion of cases (45%) than controls (29%) residing in rural regions of Uganda. KS cases were more likely than controls to have a higher level of education (X2 for trend, 4.8; P = 0.03), to have occupations associated with affluence [chi 2 for heterogeneity, 17.3 on 5 degrees of freedom (df); P = 0.004] and to come from larger settlements [adjusted odds ratio (OR) for settlements of > 1000 versus 10-99 houses, 1.8; 95% confidence interval (CI), 1.1-3.0]. Cases were more likely than controls to have high household income (chi 2 for trend, 32.6; P < 0.001) and other markers of urban or rural wealth such as owning several cows (chi 2 for trend, 9.5; P = 0.002). Cases were more likely to travel away from home (adjusted OR, 1.6; 95% CI, 1.1-2.3) and more likely to have spent increasing time in contact with water (chi 2 for trend, 12.3; P < 0.001). Few indices of sexual behaviour were related to risk of KS, including reported number of sexual partners. Cases were more likely than controls to be married to one rather than several spouses (adjusted OR, 1.6; 95% CI, 1.2-2.2) and to have reported a history of sexually transmitted diseases (STD) (adjusted OR, 1.6; 95% CI, 1.2-2.3). CONCLUSIONS: Among HIV-infected subjects, KS cases are characterized by better education and greater affluence, compared with controls. Urban address, travel away from home, exposure to water, monogamous marriage and self-reported STD were also more frequent among KS cases than controls. The higher socio-economic status of persons with HIV and KS may be a marker for enhanced exposure to a possibly sexually transmitted agent, or for a delayed exposure to a childhood infection. The risk posed by exposure to water among KS cases requires further study.

PIP: The risk factors for Kaposi's sarcoma in HIV-infected persons were investigated in a case-control study conducted in Kampala, Uganda, in 1994-96. Cases included 458 HIV-positive Ugandans with newly diagnosed Kaposi's sarcoma, while the control group was comprised of 568 seropositive subjects without Kaposi's sarcoma. Men and women with Kaposi sarcoma were significantly more likely than controls to have a higher educational level, have prestigious professional or military jobs, to come from large settlements (over 1000 houses), to have a high household income, to travel away from home more than seven nights per year, and to have spent increasing time in contact with water. In addition, cases were more likely than controls to be married to one rather than several spouses and to have a history of a sexually transmitted disease. Indices of sexual behavior, including reported number of sexual partners and condom use, were unrelated to Kaposi's sarcoma risk. The higher socioeconomic status of HIV-infected persons with Kaposi's sarcoma may be a marker for enhanced exposure to a sexually transmitted agent such as human herpes virus-8 or for delayed exposure to a childhood infection. The puzzling association between exposure to water and Kaposi's sarcoma warrants further investigation.

Tuberculous lymphadenitis associated with human immunodeficiency virus (HIV) in Uganda.

Sixteen adults presented with lymphadenopathy which was tuberculous on biopsy; they were all seropositive for human immunodeficiency virus (HIV-1), but none had the clinical criteria of the acquired immunodeficiency syndrome (AIDS). The biopsy specimen showed caseating tuberculosis, with scanty or no visible acid fast bacilli in seven cases; the remaining nine had a poor cellular reactivity with numerous bacilli. Antituberculous chemotherapy for two months reduced the lymphadenopathy. Two patients subsequently developed AIDS. Mycobacterial cultures were not performed, but the infection was almost certainly Mycobacterium tuberculosis. The space-time clustering of tuberculous lymphadenitis now seen in Kampala, and the unusual non-reactive histopathology, are typical of the impairment of cellular immunity induced by HIV infection.

PIP: Tuberculosis is not among the infections currently included in the clinical case description of AIDS. However, tuberculous lymphadenitis is emerging as an increasingly common concomitant infection associated with HIV-1 seropositivity in Africa. 16 HIV-positive patients presenting at Mulago Hospital, Kampala, in 1986, with lymphadenopathy were studied. Lymph node biopsies were done on all 16, but only 7 of the histopathologic specimens showed a normal immune response to tubercle bacilli. The remaining 9 showed numerous bacilli but absent or weak cellular immune response. All patients responded to standard antituberculosis drug therapy; 2 patients developed clinical AIDS. Since HIV seropositivity seems to predispose to nontypical tuberculosis, it is recommended that in future cultures be done on tuberculous tissues from HIV-positive patients in Africa.

Scleroma in Uganda: a review of 85 cases.

Biopsy and autopsy protocols revealed that between 1972 and 1981, 85 cases of scleroma were diagnosed in Uganda. The disease was found to affect females more than males, and was found to be more common in the middle aged. Scleroma occurred in the nose in 96% of cases and presented commonly at a late stage. The disease was found commonly among the tribes of south western Uganda and Itesot in the east. Possible factors associated with the distribution of this disease in Uganda are discussed.

Subcutaneous phycomycosis in Uganda.

This paper reports a further eighty cases of subcutaneous phycomycosis infection in Uganda seen between 1967 and 1974. This brings the number of reported cases from this country to over 140 and indicates an unusual frequency. The infection is more common in certain northern areas but does not appear to be confined to one ecological area. Suggestions are made as to possible factors in the initiation of this unusual infection.

The distribution of non-Burkitt, non-Hodgkin's lymphomas in Uganda in relation to malarial endemicity.

Biopsies of malignant lymphomas collected from all districts of Uganda, filed in the Kampala Cancer Registry for the 8-year period 1966-1973, were reviewed. This review confirmed a relatively low frequency of follicle-centre-cell lymphomas with a follicular growth pattern and the geographical co-distribution between malaria and Burkitt's lymphoma (BL). It also showed a similar, though less marked, association between non-Burkitt, non-Hodgkin's lymphoma (NBNHL) and malarial endemicity, and a correlation in the regional incidence between BL and NBNHL. In both comparisons, these associations were strong for high-grade lymphomas and weak for low-grade neoplasms. BL and other NHL may therefore share, to a varying degree, some common pathogenesis. The excess in frequency of NBNHL of high-grade malignancy in malarial endemic areas appears to be in contrast to Western countries where most non-Hodgkin's lymphomas are of low-grade malignancy.

Cancer in Kampala, Uganda, in 1989-91: changes in incidence in the era of AIDS.

Re-establishment of the cancer registry in Kyadondo County, Uganda, has allowed estimation of incidence rates for the period September 1989 to December 1991. The results are compared with earlier data from the same area, and from other African cancer registries. The most striking feature is the emergence of Kaposi's sarcoma as the leading cancer in males (almost half of all registered cases) and the second most frequent (17.9%) in females. This parallels the evolution of the epidemic of AIDS. There were also marked increases in the incidence of both oesophageal and prostatic carcinoma, while the incidence of cancer of the penis and the urinary bladder declined, possibly as a result of improved standards of hygiene. In females, the incidence of cancer of the cervix has more than doubled since the 1950s, and is now among the highest recorded in the African continent.

PIP: The Kampala Cancer Registry (KCR), in Kyadondo County, Uganda, was established in 1951. During 1972-87, KCR activity was reduced because of the Ugandan political situation. Reactivation of the KCR has provided data on incidence in Kyadondo County residents from September 1989 to December 1991. Kyadondo County had just over 1 million residents (living there at least 1 year) in 1991. Data sources were the records of the Department of Histopathology, which receives KCR registration information along with specimens, and hospital records verified by a cancer registrar from the 4 major county hospitals. (Death certificates are not available at present in Uganda). These data were compared with those reported in 1954-60 and 1968-70 to determine changes in cancer incidence in an era marked by changing lifestyles and the emerging AIDS epidemic. 558 males and 675 females were registered in the 28-month period. Data were tabulated separately for males and females, showing number of cases/site and average annual age-specific incidence rates. Age-standardized incidence rates were compared for 1989-91, 1954-68, 4 other African population-based series, and White and Black US population rates. The most frequent 1981-91 cancers for men were Kaposi's sarcoma, 48.6% esophagus, 6.9%; nonHodgkin's lymphoma (NHL), 6.2%; prostate, 5.5%; and liver, 4.9%. In women, the most frequent cancers were cervical, 32.1% in the highest record in Africa; Kaposi's sarcoma, 17.9%; and breast cancer, 11.4%. A comparison to earlier KCR data revealed that incidence of Kaposi's sarcoma has increased from 2.6 to 30.1/100,000 in men and from 0 to 11/100,000 in women. This finding is clearly related to the AIDS epidemic. However, the rate of NHL, which is an increased risk for US AIDS patients, has shown little change. However, the incidence of NHL (specifically Burkitt's) in KCR children 0-14 years old is relatively high (19/1/million in boys and 12.1/million in girls), and the AIDS epidemic may be responsible, although much remains to be discovered about AIDS-related NHL, particularly Burkitt's. Incidence increases were found in men for esophageal and prostate cancer, whereas cases of cancer of the penis and bladder declined. In women, the incidence of cervical cancer doubled since the 1950s. Breast cancer, while the third most common, shows the typical low, rate of a low-birth population, although the rate has doubled since 1954-60.

Mechanical properties of the colon: comparison of the features of the African and European colon in vitro.

The tensile properties of the colon have been examined using methods which gave repeatable results. They showed little change after storage in salt for up to five weeks. The burst strength remained unchanged along the length of the colon. The tensile strength fell distally, as the thickness of the colonic wall increased. The width at burst decreased distally as did the internal diameter. The visco-elastic property of stress relaxation was constant in all regions. The tensile property of the colon was well developed at birth, but fell with age as did the width at burst and the internal diameter. Stress relaxation was unaffected. Because there may be a mechanical abnormality of the colonic wall in diverticular disease and as Europeans are prone to this condition while Africans are not commonly affected, European and African colons were compared. The tensile strength in a Kampala group was greater than in an Edinburgh one, but fell significantly in both groups with age. The width at burst was greater in the Kampala group, but also declined with age. Stress-relaxation was similar in both groups. In view of the similar properties in childhood of colons from Edinburgh and Kampala, the strength of the adult African compared with European colons may derive later from environmental factors such as diet. There were, however, no differences between the colons with and without diverticular disease in European subjects over the age of 50 years.

Treatment of hepatocellular carcinoma with adriamycin. Preliminary communication.

In a Phase II clinical trial, 14 patients with histologically proven primary hepatocellular carcinoma were treated with adriamycin administered intravenously at a dose of 75 mg/m2 every 3 weeks. All 11 evaluable patients responded with 3 exhibiting complete tumor regression after two, three, and five courses of adriamycin respectively. The remission durations for these 3 were 3, 6, and 7 months, and their survivals were 8, 9, and 13 months, respectively. The median survival of the evaluable patients is 8 months (range 1-13 months). The side effects encountered included myelosuppression, anorexia, nausea, vomiting, and alopecia. Adriamycin seems to be an effective agent in hepatocellular carcinoma. Further trials are underway to test its true efficacy both singly and in combination with other drugs in the management of this tumor.

Further experience in treating patients with hepatocellular carcinoma in Uganda.

One hundred and thirty nine patients with histologically proven hepatocellular carcinoma (HC) were admitted to the Uganda Cancer Institute for treatment. The patients were considerably younger and seemed to have more advanced disease than HC patients in Europe and in North America. Of the 99 evaluable patients, 50 received Adriamycin intravenously; of these, 44% responded, with 10% achieving complete responses. Intraarterial Adriamycin tended to increase the response rate to 75%, but this may be merely a reflection of patient selection. Combination of Adriamycin with other drugs (dichloromethotrexate, 5-azacytidine, Rezoxane and cyclophosphamide) did not enhance its therapeutic effectiveness. The alphafetoprotein response curves observed when Adriamycin was combined with dichloromethotrexate suggested possible antagonisms between the two drugs. Hepatic artery ligation (HAL) is a good and simple palliative procedure with response rates similar to i.v. Adriamycin. However, the administration of Adriamycin after HAL tended to improve on response rates and survival. The toxicities observed were mainly myelosuppression, gastrointestinal disturbance, alopecia, and hyperpigmentation of the skin and mucous membranes.