Edward Mbidde

A case-control study of human immunodeficiency virus infection and cancer in adults and children residing in Kampala, Uganda.

Uganda offers a unique setting in which to study the effect of human immunodeficiency virus‐1 (HIV‐1) on cancer. HIV‐1 is prevalent there, and cancers which are known to be HIV‐associated, such as Kaposis sarcoma and Burkitts lymphoma, are endemic. Adults residing in Kampala, Uganda, presenting with cancer in city hospitals were interviewed and had an HIV test. Of the 302 adults recruited, 190 had cancers with a potentially infectious aetiology (cases). The remaining 112 adults with tumours not known to have an infectious aetiology formed the control group. In addition, 318 children who were also Kampala residents were recruited and tested for HIV: 128 with cancer (cases) and 190 with non‐malignant conditions (controls). HIV seroprevalence was 24% in adult controls and 6% in childhood controls. The odds of HIV seropositivity among cases with specific cancers (other than Kaposis sarcoma in adults) were compared with that among controls, using odds ratios (ORs), estimated with unconditional logistic regression. All ORs were adjusted for age (<5, 5–14, 15–19, 30–44, 45+) and sex and, in adults, also for the number of lifetime sexual partners (1 or 2, 3–9, 10+). In adults, HIV infection was associated with a significantly (p < 0.05) increased risk of non‐Hodgkins lymphoma [OR = 6.2, 95% confidence interval (CI) 1.9–19.9, based on 21 cases] and conjunctival squamous‐cell carcinoma (OR = 10.9, 95% CI 3.1–37.7, based on 22 cases) but not with cancer at other common sites, including liver and uterine cervix. In children, HIV infection was associated with a significantly increased risk of Kaposis sarcoma (OR = 94.9, 95% CI 28.5–315.3, based on 36 cases) and Burkitts lymphoma (OR = 7.5, 95% CI 2.8–20.1, based on 33 cases) but not with other cancers. The pattern of HIV‐associated cancers in Uganda is broadly similar to that described elsewhere, but the relative frequency of specific cancers, such as conjunctival carcinoma, in HIV‐infected people differs.

The epidemiology of conjunctival squamous cell carcinoma in Uganda

As part of a larger investigation of cancer in Uganda, we conducted a case–control study of conjunctival squamous cell carcinoma in adults presenting at hospitals in Kampala. Participants were interviewed about social and lifestyle factors and had blood tested for antibodies to HIV, KSHV and HPV-16, -18 and -45. The odds of each factor among 60 people with conjunctival cancer was compared to that among 1214 controls with other cancer sites or types, using odds ratios, estimated with unconditional logistic regression. Conjunctival cancer was associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2–19.4; P<0.001), and was less common in those with a higher personal income (OR 0.4, 95% CI 0.3–1.2; P<0.001). The risk of conjunctival cancer increased with increasing time spent in cultivation and therefore in direct sunlight (χ2 trend=3.9, P=0.05), but decreased with decreasing age at leaving home (χ2 trend=3.9, P=0.05), perhaps reflecting less exposure to sunlight consequent to working in towns, although both results were of borderline statistical significance. To reduce confounding, sexual and reproductive variables were examined among HIV seropositive individuals only. Cases were more likely than controls to report that they had given or received gifts for sex (OR 3.5, 95% CI 1.2–10.4; P=0.03), but this may have been a chance finding as no other sexual or reproductive variable was associated with conjunctival cancer, including the number of self-reported lifetime sexual partners (P=0.4). The seroprevalence of antibodies against HPV-18 and -45 was too low to make reliable conclusions. The presence of anti-HPV-16 antibodies was not significantly associated with squamous cell carcinoma of the conjunctiva (OR 1.5, 95% CI 0.5–4.3; P=0.5) and nor were anti-KSHV antibodies (OR 0.9, 95% CI 0.4–2.1; P=0.8). The 10-fold increased risk of conjunctival cancer in HIV infected individuals is similar to results from other studies. The role of other oncogenic viral infections is unclear.

Immunogenicity of a Recombinant Human Immunodeficiency Virus (HIV)–Canarypox Vaccine in HIV-Seronegative Ugandan Volunteers: Results of the HIV Network for Prevention Trials 007 Vaccine Study

In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.

Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda.

Burkitt lymphoma, a childhood tumor common in parts of sub‐Saharan Africa, has been directly associated with Epstein‐Barr virus (EBV) and indirectly with prevalence of malaria. We studied antibodies to both EBV and malaria in children diagnosed with this cancer in Uganda. We performed a case‐control study of HIV‐seronegative children (≤15 years) admitted to hospital. Cases were diagnosed with Burkitt lymphoma and controls with non‐malignant conditions or non‐lymphatic cancers. Interviews were conducted and serological samples collected and, when possible, tested for both EBV and malaria. Adjusted odds ratios (ORs) for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, residential district, household income and tribe. The mean age of cases was 7 years and 61% were male. Compared to controls, cases were more likely to be reported having received more frequent treatment for malaria in the past year (OR = 2.0; p = 0.001) and less likely to be living in a home where insecticides were used (OR = 0.2; p < 0.0001). Odds ratios for Burkitt lymphoma in children increased with increasing antibody levels against EBV (p < 0.0001) and malaria (p = 0.05). Findings were similar for children residing in districts close to the capital city and in remote areas. Cases were 5 times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 5.0; p = 0.003). Our findings suggest that EBV and malaria may act synergistically in the pathogenesis of childhood Burkitt lymphoma. Malaria prevention measures may also prevent this childhood cancer.

The sero-epidemiology of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) in adults with cancer in Uganda.

The association between the prevalence of antibodies against Kaposis sarcoma‐associated herpesvirus (KSHV or human herpesvirus 8 [HHV‐8]) and sociodemographic, sexual, reproductive and lifestyle factors was investigated in a study of adults presenting with cancer at hospitals in Kampala, Uganda. Patients were interviewed and tested for antibodies against KSHV (using an indirect immunofluorescent assay). Data are presented for 607 patients who were not infected with the human immunodeficiency virus‐1 (HIV) and who did not have Kaposis sarcoma (these included people with cancers of the uterine cervix [140], breast [58], liver [41], oesophagus [36], lymphoma [47], other cancers [285] and benign tumours [63]). The prevalence of anti‐KSHV antibodies was 50% overall (302/607) and did not differ significantly by cancer site (p = 0.4) or sex (p = 0.2), but increased linearly with age from 35% in those under 25 years to 55% in those 45 years and over (χ2 trend [1 df] = 9.1; p < 0.001). After adjusting for age and sex, anti‐KSHV antibodies were more common in tribal groups other than the Baganda tribe (54% vs. 45% among Baganda; p = 0.02), but there was no significant (p > 0.05) variation in seroprevalence by district of birth, region of residence prior to becoming ill or various measures of wealth. The prevalence of anti‐KSHV antibodies decreased with increasing number of older siblings, although this may be due to chance (p = 0.05) and was higher among people who had ever been married (p = 0.03). There was no significant association (p > 0.05) between the presence of antibodies against KSHV and other sexual and reproductive factors. Among the 302 patients with anti‐KSHV antibodies, the proportion with high titres increased linearly with increasing age (p = 0.03) and was higher among those reporting having had a blood transfusion (p = 0.03). In conclusion, in this population in Uganda, where KSHV is relatively common, the prevalence of anti‐KSHV antibodies increased with age but showed little association with nearly 50 other factors studied.

Clearance of Circulating Epstein-Barr Virus DNA in Children with Acute Malaria after Antimalaria Treatment

Children living in malaria-endemic regions have a high incidence of Burkitt lymphoma (BL), the etiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. In the present study, we compared EBV DNA loads in plasma and saliva samples from Ugandan children with acute malaria (M+) at the time of diagnosis and 14 days after antimalaria treatment, children without malaria (M-), and children with BL. EBV DNA was detected, by real-time polymerase chain reaction, in 31% of the plasma and in 79% of the saliva samples from children in the M+ group. Antimalaria treatment led to clearance of plasma viral load in 85% of the cases but did not affect the levels in saliva. There was a significant difference in plasma EBV loads across the groups. The lowest levels were detected in samples from the M- group, increased levels were detected in samples from the M+ group, and levels reached the highest values in samples from children with BL. The same trend was evident in the frequency and levels of anti-BZLF1 antibodies, which is indicative of viral reactivation. In the M+ group, the positive plasma samples clustered around 7-9 years of age, the peak incidence of BL. The clearance of circulating EBV after antimalaria treatment suggests a direct relationship between active malaria infection and viral reactivation.

Reemerging Sudan Ebola Virus Disease in Uganda, 2011

Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities.

Infection with human papillomavirus and HIV among young women in Kampala, Uganda

BACKGROUND Information on the prevalence of cervical infection with different human papillomavirus (HPV) types among young women is essential to support the introduction of HPV vaccine in Uganda. METHODS Cross-sectional findings are presented from a cohort study of 1,275 sexually active women aged 12-24 years seeking health services at a clinic for teenagers in Kampala, Uganda. We assessed the presence of 39 HPV types by use of highly sensitive polymerase chain reaction assays. RESULTS The prevalence of HPV infection was 74.6%, and the prevalence of human immunodeficiency virus infection was 8.6%. High-risk HPV types were found in 51.4% of women, and the most frequently detected high-risk types were, in decreasing order, HPV 52, 51, 18, and 16. A total of 71.8% of the women who were positive for HPV 16 and/or 18 were also infected with other high-risk HPV types. HIV-positive women had a higher prevalence of HPV infection (87.8% vs 73.2%) and of multiple-type infections (64.6% vs 37.3%), compared with HIV-negative women. Employment in the tertiary sector, lifetime number of sexual partners, concurrent pregnancy, and the presence of genital warts were significantly associated with HPV positivity. CONCLUSIONS The prevalence of HPV infection is high among young women in Kampala, Uganda. Clinics for teenagers provide an opportunity to monitor the impact of HPV vaccines and, possibly, to catch up unvaccinated young women who have recently become sexually active.

Risk factors for Kaposi's sarcoma: a case-control study of HIV-seronegative people in Uganda.

As part of a larger investigation of cancer in Uganda, we conducted a case‐control study of Kaposis sarcoma in human immunodeficiency virus‐1 (HIV)‐seronegative adults presenting at hospitals in Kampala. Cases comprised 117 HIV‐seronegative patients with Kaposis sarcoma and controls comprised 1,282 HIV‐seronegative patients with a provisional diagnosis of cancer other than Kaposis sarcoma. Study participants were interviewed about social and lifestyle factors, tested for HIV and, if there was sufficient sera, for antibodies against Kaposis sarcoma‐associated herpesvirus (KSHV or human herpesvirus 8 [HHV8]), using an immunofluorescent assay. Independent effects of these factors were identified using unconditional logistic regression, after adjusting for age group (<30, 30–44, 45+) and sex. Antibody status for KSHV was available for 68% (80) of cases and for 45% (607) of controls. Among cases, 78% (91) were male and 57% (66) were over the age of 35. Cases were more likely than controls to be from tribal groups other than the Baganda (p = 0.05), to have higher household incomes (p = 0.003), to have left their home region at younger ages (p < 0.001), to own goats or pigs (p = 0.02) and to rarely or never use shoes (p < 0.001). Similar results were obtained when analyses were restricted to cases and controls with anti‐KSHV antibodies. The seroprevalence of KSHV was 79% (63/80) in those with Kaposis sarcoma as compared to 50% (302/607) in those without (χ2 heterogeneity (1 df) = 21.0; p < 0.001) and the risk of the tumour increased with increasing anti‐KSHV antibody titres (χ2 trend (1 df) = 29.7; p < 0.001). The risk of Kaposis sarcoma is clearly linked to antibody status for KSHV, but it would seem that in Uganda other factors are also important in the development of the tumour.

Clinical characteristics and outcome of children with Burkitt lymphoma in Uganda according to HIV infection.

Characteristics of children with Burkitt lymphoma (BL) and HIV infection have not been described in Uganda before.