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Context: Burkitt lymphoma (BL) is endemic in Uganda and because of the high incidence, diagnosis is often presumed during clinical care and epidemiologic studies., Objectives: To assess the accuracy of the clinical and the local pathology diagnosis of BL as assessed by an outside pathology review diagnosis and to understand the limitations on histopathology practice in a resource-constrained setting at 1 hospital in Uganda., Design: Clinically presumed pediatric (<15 years) BL cases with biopsies and pathology reports, from 1993 to 2007, were identified at St Mary's Hospital, Lacor (Gulu, Uganda). Local histopathology procedures, hematoxylin-eosin-stained tissue sections, and formalin-fixed paraffin-embedded blocks were reviewed onsite by an outside pathologist, followed by outside study that included tissue microarray immunohistochemistry and in situ hybridization., Results: Local pathology laboratory procedures were inconsistent and suboptimal, especially for tissue fixation. There were 88 clinically presumed BL cases. Sixty-three could be reviewed by outside pathology (25 cases of lost blocks or no remaining tumor) and showed a clinical diagnostic accuracy of 75% (47 confirmed of 63), with a possible range of 62% to 85%, depending on the actual diagnosis of the 25 nonevaluable cases. There were 64 BL cases diagnosed by local pathology. Forty-five could be reviewed by outside pathology (19 cases of lost blocks or no remaining tumor) and showed a local pathology diagnostic accuracy of 82% (37 confirmed of 45), with a possible range of 58% to 88%, depending on the actual diagnosis of the 19 nonevaluable cases. Non-BL diagnoses included other non-Hodgkin lymphomas, Hodgkin lymphoma, and benign infectious lymphadenopathy., Conclusions: Accuracy of clinical diagnosis of BL was reduced by inclusion of other diseases with similar clinical presentations. Local pathology, using morphology alone, only marginally improved clinical accuracy and often could not support outside pathology review due to inadequate laboratory procedures. There is an urgent need to improve pathology services in Uganda before conducting high-quality clinical and epidemiologic studies.

African Burkitt lymphoma is an aggressive B-cell, non-Hodgkin lymphoma linked to Plasmodium falciparum malaria. Malaria biomarkers related to onset of African Burkitt lymphoma are unknown. We correlated age-specific patterns of 2,602 cases of African Burkitt lymphoma (60% male, mean ± SD age = 7.1 ± 2.9 years) from Uganda, Ghana, and Tanzania with malaria biomarkers published from these countries. Age-specific patterns of this disease and mean multiplicity of P. falciparum malaria parasites, defined as the average number of distinct genotypes per positive blood sample based on the merozoite surface protein-2 assessed by polymerase chain reaction, were correlated and both peaked between 5 and 9 years. This pattern, which was strong and consistent across regions, contrasted parasite prevalence, which peaked at 2 years and decreased slightly, and geometric mean parasite density, which peaked between 2 and 3 years and decreased sharply. Our findings suggest that concurrent infection with multiple malaria genotypes may be related to onset of African Burkitt lymphoma.

Introduction: Sexual transmission of human herpesvirus 8 (HHV8) has been implicated among homosexual men, but the evidence for sexual transmission among heterosexual individuals is controversial. We investigated the role of sexual transmission of HHV8 in a nationally representative sample in Uganda, where HHV8 infection is endemic and transmitted mostly during childhood., Materials and Methods: The study population was a subset of participants (n = 2681) from a population-based HIV/AIDS serobehavioral survey of adults aged 15-59 years conducted in 2004/2005. High risk for sexual transmission was assessed by questionnaire and serological testing for HIV and herpes simplex virus 2. Anti-HHV8 antibodies were measured using two enzyme immunoassays targeting synthetic peptides from the K8.1 and orf65 viral genes. The current study was restricted to 2288 sexually active adults. ORs and 95% CIs for HHV8 seropositivity were estimated by fitting logistic regression models with a random intercept using MPLUS and SAS software., Results: The weighted prevalence of HHV8 seropositivity was 56.2%, based on 1302 seropositive individuals, and it increased significantly with age (P(trend)<0.0001). In analyses adjusting for age, sex, geography, education, and HIV status, HHV8 seropositivity was positively associated with reporting two versus one marital union (OR:1.52, 95% CI: 1.17-1.97) and each unit increase in the number of children born (OR: 1.04, 95% CI: 1.00-1.08), and was inversely associated with ever having used a condom (OR: 0.64, 95% CI: 0.45-0.89). HHV8 seropositivity was not associated with HIV (P = 0.660) or with herpes simplex virus 2 (P = 0.732) seropositivity. Other sexual variables, including lifetime number of sexual partners or having had at least one sexually transmitted disease, and socioeconomic variables were unrelated to HHV8 seropositivity., Conclusion: Our findings are compatible with the conclusion that sexual transmission of HHV8 in Uganda, if it occurs, is weak.

Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the United States general population, but the role of immunosuppression could not be excluded. Incidence rates, rate ratios, and 95% confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4 lymphocyte count categories, were estimated using Poisson regression models using data from the United States HIV/AIDS Cancer Match study (1980-2005). BL incidence was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL incidence rate ratio among males was 1.6× that among females and among non-Hispanic blacks, 0.4× that among non-Hispanic whites, but unrelated to HIV-transmission category. Non-BL NHL incidence increased from childhood to adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily with decreasing CD4 lymphocyte counts; in contrast, BL incidence was lowest among people with ≤ 50 CD4 lymphocytes/μL versus those with ≥ 250 CD4 lymphocytes/μL (incidence rate ratio 0.3 [95% confidence interval = 0.2-0.6]). The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of noncumulative risk factors at different ages. Underascertainment or biological reasons may account for BL deficit at low CD4 lymphocyte counts.

Purpose: Human herpesvirus 8 (HHV-8, or Kaposi sarcoma [KS]-associated herpesvirus, KSHV) is a necessary but insufficient cause of KS, as KS develops in few HHV-8-infected persons. In sub-Saharan Africa, marked differences in the geographic distribution of HHV-8 and KS suggest that environmental cofactors influence HHV-8 transmission, control, and progression to KS. However, a direct comparison of HHV-8 prevalence estimates is complicated because studies used different serologic assays and analytic methods. We assessed HHV-8 seropositivity in several African countries with heterogeneous environments and varying KS incidence using a unified approach., Methods: HHV-8 antibodies were measured among 3196 adults (aged 20+ years) and 2404 children (aged <20 years) from five studies in four sub-Saharan countries in Africa. Serum samples were tested by the same laboratory using K8.1 and orf73 enzyme immunoassays., Results: Children's HHV-8-seropositivity ranged from 18.1% in Kampala, Uganda, to 33.8% in North Mara, Tanzania, increasing steeply with age in all populations. Among adults, HHV-8-seropositivity ranged from 23.5% in Nigeria to 70.6% in rural West Nile, Uganda. It was higher in males and rural areas., Conclusions: Our data indicate that geographical exposures, gender, age, and factors correlated with rural residence impact HHV-8 seropositivity in sub-Saharan Africa., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8) is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control.

Background: To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV)., Methods: In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods., Results: Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use) had significantly lower levels of anti-EBNA (P = 0.0001 - 0.07) and anti-VCA (P = 0.0001 - 0.03). Levels of sCD26 were significantly lower for male and non-smoking controls (Padj ≤ 0.03), and they were marginally lower with older age and cortisone use (Padj ≤ 0.09)., Conclusions: Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.

Burkitt lymphoma (BL) is a unique B-cell non-Hodgkin lymphoma with 3 established clinical-epidemiological variants: endemic, sporadic and AIDS-related BL. BL variants show characteristic dysregulation of MYC gene, but the causes of MYC dysregulation or BL arising at different ages are poorly understood. Therefore, we examined population-based BL incidence patterns in the United States to determine age-related risk. BL case and population data were obtained from the NCI's Surveillance, Epidemiology and End Results Databases (1973-2005). Standard cross-sectional age-standardized and age-specific incidence rates were stratified by sex and race and supplemented with age-period-cohort models. We analyzed 3,058 BL cases diagnosed during 1,160,300,297 person-years of observation. Age-standardized incidence rates rose 6.8% per year (95% CI 4.5-9.1) for males and 7.1% (95% CI 3.2-11.1) for females during the study period. The rate among males was 3.2 times that among females, and among Whites 1.3 times that among Blacks. Male-to-female incidence rate ratios did not differ by race, but were 4.2 for pediatric (0-19 years), 4.1 for adult (20-59 years) and 2.0 for geriatric (> or = 60 years) BL. Cross-sectional age-specific rates showed 2 separate peaks among males and females, near ages 10 and 75 years, and a 3rd peak near age 40 years among males. The tri/bimodal incidence pattern was present in sensitivity analyses excluding registries with many HIV/AIDS cases and in period-specific, cohort-specific analyses. To our knowledge, tri/bimodal incidence patterns have not previously been reported for BL. Trimodal/bimodal BL suggests heterogeneity in etiology or biology of BL diagnosed at different ages in males and females., ((c) 2009 UICC.)

Background: The risk factors and co-factors for sporadic childhood BL are unknown. We investigated demographic and age-specific characteristics of childhood BL (0-14 years) in the U.S., Procedure: BL age-standardized incidence rates (2000 U.S. standard population), were calculated using data obtained from 12 registries in the NCI's Surveillance, Epidemiology, and End Results program for cases diagnosed from 1992 to 2005. Incidence rate ratios and 95% confidence intervals (95% CI) were calculated by gender, age-group, race, ethnicity, calendar-year period, and registry., Results: Of 296 cases identified, 56% were diagnosed in lymph nodes, 21% in abdominal organs, not including retroperitoneal lymph nodes, 14% were Burkitt cell leukemia, and 9% on face/head structures. The male-to-female case ratio was highest for facial/head tumors (25:1) and lowest for Burkitt cell leukemia (1.6:1). BL incidence rate was 2.5 (95% CI 2.3-2.8) cases per million person-years and was higher among boys than girls (3.9 vs. 1.1, P < 0.001) and higher among Whites and Asians/Pacific Islanders than among Blacks (2.8 and 2.9 vs. 1.2, respectively, P < 0.001). By ethnicity, BL incidence was higher among non-Hispanic Whites than Hispanic Whites (3.2 vs. 2.0, P = 0.002). Age-specific incidence rate for BL peaked by age 3-5 years (3.4 cases per million), then stabilized or declined with increasing age, but it did not vary with calendar-year or registry area., Conclusions: Our results indicate that early childhood exposures, male-sex, and White race may be risk factors for sporadic childhood BL in the United States., (Published 2009 Wiley-Liss, Inc.)

Epstein-Barr virus (EBV) is a ubiquitous, gamma-1 lymphotrophic virus etiologically linked to nasopharyngeal carcinoma (NPC), endemic to Southern China, and Burkitt lymphoma (BL), endemic to equatorial Africa, both of which are rare elsewhere in the world. Why EBV is associated with different malignancies in different geographic regions remains puzzling and may be related to EBV genotypic variability through specific disease and geographic associations. We review the literature on sequence variation in EBV genes, focusing on LMP-1, EBNA-1, and BZLF-1 and their distribution by geography and disease. Given the limitations of current studies, definitive conclusions regarding the link between EBV genotypes, disease and geography are not possible. We suggest that the true extent of EBV diversity is likely to be greater than is currently recognized. Additional studies conducted in carefully selected populations, that are sufficiently powered to provide robust estimates, and that utilize testing approaches that permit full characterization of viral diversity are needed to further our understanding of patterns of EBV genetic variation and their association with malignancies in different regions.

Background: India has a large and evolving HIV epidemic. Little is known about cancer risk in Indian persons with HIV/AIDS (PHA) but risk is thought to be low., Methods: To describe the state of knowledge about cancer patterns in Indian PHA, we reviewed reports from the international and Indian literature., Results: As elsewhere, non-Hodgkin lymphomas dominate the profile of recognized cancers, with immunoblastic/large cell diffuse lymphoma being the most common type. Hodgkin lymphoma is proportionally increased, perhaps because survival with AIDS is truncated by fatal infections. In contrast, Kaposi sarcoma is rare, in association with an apparently low prevalence of Kaposi sarcoma-associated herpesvirus. If confirmed, the reasons for the low prevalence need to be understood. Cervical, anal, vulva/vaginal and penile cancers all appear to be increased in PHA, based on limited data. The association may be confounded by sexual behaviors that transmit both HIV and human papillomavirus. Head and neck tumor incidence may also be increased, an important concern since these tumors are among the most common in India. Based on limited evidence, the increase is at buccal/palatal sites, which are associated with tobacco and betel nut chewing rather than human papillomavirus., Conclusion: With improving care of HIV and better management of infections, especially tuberculosis, the longer survival of PHA in India will likely increase the importance of cancer as a clinical problem in India. With the population's geographic and social diversity, India presents unique research opportunities that can be embedded in programs targeting HIV/AIDS and other public health priorities.

Helicobacter pylori infection is ubiquitous, infecting close to one-half of the world's population, but its prevalence is declining in developed countries. Chronic H. pylori infection is etiologically linked to gastric adenocarcinoma, especially non-cardia type (63% of all stomach cancer or ~5.5% of the global cancer burden: ~25% of cancers associated with infectious etiology), and to gastric mucosal associated lymphoid tissue (MALT) lymphoma, which accounts for up to 8% of all non-Hodgkin lymphoma. Epidemiological, clinical, and animal studies have established a central role for H. pylori in gastric carcinogenesis and provided insights into the mechanisms and biologic relationships between bacterial infection, host genetics, nutrition, and environmental factors. These discoveries invite strategies to prevent infection to be the logical primary goals in a multi-pronged effort to curtail suffering and death from H. pylori infection-associated cancers.

Endemic Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus and ecologically linked to Plasmodium falciparum malaria. However, these infections imperfectly correlate with BL epidemiology. To obtain recent epidemiological data, we studied district- and county-specific BL incidence and standardized incidence ratios using data collected from 1997 to 2006 at Lacor Hospital in northern Uganda, where studies were last done more than 30 years ago. Among 500 patients, median age was 6 years (interquartile range 5-8) and male-to-female ratio was 1.8:1. Among those known, most presented with abdominal (56%, M:F 1.4:1) vs. only facial tumors (35%, M:F 3.0:1). Abdominal tumors occurred in older (mean age: 7.0 vs. 6.0 years; p < 0.001) and more frequently in female children (68% vs. 50%; OR 2.2, 95% CI 1.5-3.5). The age-standardized incidence was 2.4 per 100,000, being 0.6 in 1-4 year olds, 4.1 in 5-9 year olds and 2.8 in 10-14 year olds and varied 3- to 4-fold across districts. The incidence was lower in districts that were far from Lacor and higher in districts that were close to Lacor. Although districts close to Lacor were also more urbanized, the incidence was higher in the nearby perirural areas. We highlight high-BL incidence and geographic variation in neighboring districts in northern Uganda. Although distance from Lacor clearly influenced the patterns, the incidence was lower in municipal than in surrounding rural areas. Jaw tumors were characterized by young age and male gender, but presentation has shifted away from facial to mostly abdominal., ((c) 2008 Wiley-Liss, Inc.)

Squamous cell carcinoma of the conjunctiva (SCCC) has been associated with HIV infection in equatorial Africa, but the evidence for association with HIV in developed countries, where SCCC is rarer, is controversial. We investigated the risk for SCCC and other eye cancers in the updated U.S. HIV/AIDS Cancer Match Registry Study. We calculated standardized incidence ratios (SIRs) to estimate excess risk for SCCC, primary ocular lymphoma, ocular Kaposi sarcoma (KS) and other eye tumors among 491, 048 adults (aged > 15 years or older) with HIV/AIDS diagnosed from 1980 to 2004. We calculated relative proportions (per 10(5)) to gain insight into risk factors. We identified 73 eye cancers (15 SCCC, 35 primary ocular lymphoma, 17 ocular KS and 6 other). Overall SIRs were elevated for SCCC (SIR, 12.2, 95% CI 6.8-20.2), primary ocular lymphoma (21.7, 95% CI 15.1-30.2) and ocular KS (109, 95% CI 63.5-175). Risk for SCCC was elevated regardless of HIV acquisition category, CD4 lymphocyte count and time relative to AIDS-onset. Relative proportions of SCCC risk were highest with age >or=50 (8/10(5)), Hispanic ethnicity (7/10(5)) and residence in regions with high-solar ultraviolet radiation (10/10(5)). We show significantly increased incidence of SCCC among persons with HIV/AIDS in the U.S. The associations with age and geography are in accord with etiological role for ultraviolet radiation in SCCC., ((c) 2008 Wiley-Liss, Inc.)

Introduction: Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether peripheral blood viral load is a marker of KS burden (total number of KS lesions), KS progression (the rate of eruption of new KS lesions), or both is unclear. We investigated these relationships in persons with AIDS., Methods: Newly diagnosed patients with AIDS-related KS attending Mulago Hospital, in Kampala, Uganda, were assessed for KS burden and progression by questionnaire and medical examination. Venous blood samples were taken for HHV8 load measurements by PCR. Associations were examined with odds ratio (OR) and 95% confidence intervals (CI) from logistic regression models and with t-tests., Results: Among 74 patients (59% men), median age was 34.5 years (interquartile range [IQR], 28.5-41). HHV8 DNA was detected in 93% and quantified in 77% patients. Median virus load was 3.8 logs10/10(6) peripheral blood cells (IQR 3.4-5.0) and was higher in men than women (4.4 vs. 3.8 logs; p=0.04), in patients with faster (>20 lesions per year) than slower rate of KS lesion eruption (4.5 vs. 3.6 logs; p<0.001), and higher, but not significantly, among patients with more (>median 20 KS lesions) than fewer KS lesions (4.4 vs. 4.0 logs; p=0.16). HHV8 load was unrelated to CD4 lymphocyte count (p=0.23)., Conclusions: We show significant association of HHV8 load in peripheral blood with rate of eruption of KS lesions, but not with total lesion count. Our results suggest that viral load increases concurrently with development of new KS lesions.

To determine whether human herpesvirus 8 (HHV-8) is associated with schistosomal and hepatitis C virus infections in Egypt, we surveyed 965 rural household participants who had been tested for HHV-8 and schistosomal infection (seroprevalence 14.2% and 68.6%, respectively, among those <15 years of age, and 24.2% and 72.8%, respectively, among those > or =15 years of age). Among adults, HHV-8 seropositivity was associated with higher age, lower education, dental treatment, tattoos, > or =10 lifetime injections, and hepatitis C virus seropositivity. In adjusted analyses, HHV-8 seropositivity was associated with dental treatment among men (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.1-5.2) and hepatitis C virus seropositivity among women (OR 3.3, 95% CI 1.4-7.9). HHV-8 association with antischistosomal antibodies was not significant for men (OR 2.1, 95% CI 0.3-16.4), but marginal for women (OR 1.5, 95% CI 1.0-2.5). Our findings suggest salivary and possible nosocomial HHV-8 transmission in rural Egypt.

Purpose: Registry-based studies provide valuable data regarding cancer risk among people with HIV/AIDS (PWHA). Such studies utilize the standardized incidence ratio (SIR) to estimate the relative risk (RR), an etiologically relevant measure. However, SIR may underestimate RR when HIV/AIDS prevalence in the general population or RR is high. We quantified the extent of this underestimation for 3 AIDS-related cancers: Kaposi sarcoma (KS), central nervous system non-Hodgkin lymphoma (CNS NHL) and cervical cancer., Methods: We used data on cancer risk among PWHA from the U.S. HIV/AIDS Cancer Match Study. SIRs were compared with RRs estimated using two methods: (1) SIRs calculated using pre-AIDS era (1973-1979) cancer incidence rates (SIRpre-AIDS) and (2) SIRs calculated after subtraction of cancers known to be among PWHA from general population rates (SIRexclusion)., Results: For KS and CNS NHL, SIRs (117.8 and 133.9, respectively) calculated using overall general population rates substantially underestimated both SIRpre-AIDS (19,778 and 3,612, respectively) and SIRexclusion (657.7 and 536.4, respectively). In contrast, the extent of underestimation was negligible for cervical cancer (SIR = 4.9 vs. SIRexclusion = 5.1). For KS and CNS NHL, SIRs were higher in females than in males. However, SIRpre-AIDS and SIRexclusion estimates were more similar, indicating that SIR differences artifactually reflect differences in HIV/AIDS prevalence between males and females. For KS and CNS NHL, trends across calendar time were weaker in SIRs than in SIRpre-AIDS and SIRexclusion., Conclusion: For KS and CNS NHL, SIRs substantially underestimate RRs. This underestimation arises from the exceptionally high relative risk of KS and CNS NHL among PWHA. SIRs must be interpreted cautiously when HIV/AIDS prevalence is high or varies across groups of interest.

Kaposi sarcoma (KS) is endemic in Uganda and shares several risk factors with intestinal parasite infestation, including rural residence, contact with surface water, and walking barefoot, however, the significance of these ecologic relationships is unknown. We investigated these relationships among 1,985 Ugandan patients with cancer. Odds ratios (OR) were calculated using logistic regression. KS patients had higher carriage of Strongyloides stercoralis larvae (OR 2.1, 95% CI 1.2-3.7) and lower carriage of hookworm ova (0.6, 0.4-1.0) and Entamoeba coli cysts (0.7, 0.5-1.0), after adjusting for region of residence, age, gender, and diagnosis. While our findings may be due to confounding, they are compatible with shared risk factors or etiological association between parasites and KS, and warrant well-designed follow up studies.

Kaposi sarcoma (KS) occurs with relatively high frequency in immunosuppressed transplant recipients and in patients with AIDS. Recently, Italian investigators reported transplant-related KS tumors bearing donor-derived antigens, suggesting possible parenteral transmission of KS as whole cells, i.e., chimeric tumors. To investigate the hypothesis that KS whole cells may also be transmitted into immunocompromised persons via heterosexual acts, we tested nodular KS lesions and matched normal tissue obtained from female patients with AIDS for the presence of the Y-chromosome specific sex determining sequence (SRY). Among 25 unique tumors tested, none was positive for SRY sequence. While our results do not exclude sexual cellular transmission of whole KS cells, they suggest that if it occurs, it is rare.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma and is also associated with primary effusion lymphoma, a subset of diffuse large B-cell lymphomas, and multicentric Castleman disease. Because KSHV infection is endemic in sub-Saharan Africa, we sought to identify cases of KSHV-positive non-Hodgkin lymphomas (NHLs) and reactive lymphadenopathy in this region. One hundred forty-four cases (80 NHLs, 64 reactive lymph nodes) from the major pathology laboratory in Uganda were reviewed. One NHL was KSHV-positive, as indicated by staining for the viral latent nuclear antigen. This NHL was a diffuse large B-cell lymphoma in a 5-year-old boy. The tumor was also Epstein-Barr virus-positive. In addition, 2 reactive lymph nodes, both classified histologically as follicular involution, stained KSHV latent nuclear antigen-positive and thus most likely represent multicentric Castleman disease. In all 3 KSHV-positive cases, a minority of cells expressed KSHV viral interleukin 6, a biologically active cytokine homolog. In conclusion, we show that KSHV is rarely associated with lymphoproliferative disorders in sub-Saharan Africa. We describe the first case of a KSHV-positive NHL from this region; this case is also the first reported pediatric lymphoma associated with KSHV infection.

Kaposi's sarcoma (KS) risk is high in immunosuppressed transplant recipients. KS develops in recipients with pre-existing infection with human herpesvirus 8 (HHV-8), the causative agent for KS, but it can also occur in recipients infected by donors. The relative importance of these sources of infection in recipients in the United States is unknown. We report recipient and donor characteristics associated with KS among transplant recipients in the United States. KS risk, after solid organ transplantation during 1993-2003, was analyzed using data from the Organ Procurement and Tissue Network. Associations were determined using proportional hazards regression. Sixtyfive KS cases were identified among 234,127 transplants (incidence 8.8 per 100,000 person-years). Most cases occurred in the first 2 years after transplantation (incidence 12.5 per 100,000 person-years). KS risk increased steadily with recipient age (p(trend) < 0.001) and was associated with the recipient being male (HR 1.8, 95% CI, 1.0-3.2), Hispanic (2.1, 1.1-3.8) and a non-U.S. citizen (3.9, 1.8-8.6). Mismatch at the HLA-B locus, but not at HLA-A or HLA-DR loci, was associated with heightened risk (HR 3.6, 95%CI 1.1-11 for 1-2 vs. 0 HLA-B mismatches). KS was unrelated to donor characteristics and was not significantly related to use of specific antirejection medications. Our study found that KS incidence was low among transplant recipients in the United States, but it was associated with recipient age, sex and citizenship, perhaps reflecting pre-existing HHV-8 infection. The high KS risk immediately posttransplant and in persons with HLA-B mismatch highlights the role of immunosuppression and/or immune stimulation in KS pathogenesis.

Background: Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare., Methods: Sera collected during a household-based survey in rural Tanzania in 1985 were tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models., Results: Of 788 participants, 513 were aged < or = 17 years. H. pylori seropositivity increased from 76% at 0-4 years to 99% by > or = 18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2-31.4 for 10-17 vs. 0-4 years), higher birth-order (11.1; 3.6-34.1 for > or = 3rd vs. 1st born), and having a seropositive next-older sibling (2.7; 0.9-8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7-5.6), consistent with a Th2-dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3-4.4)., Conclusion: H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa.

In Kampala, Uganda, in 2001, hepatitis C virus antibodies were found in 27 (4%) of 603 children and in 62 (12%) of 525 of their mothers. However, only approximately 10% of positive results were confirmed by reverse transcription-PCR, which suggests frequent false-positive results or viral clearance. All sequenced types were genotype 4.

Background: Cigarette smoking has been associated with a decreased risk for AIDS-related and classical KS, but whether it is associated with decreased risk of human herpesvirus 8 (HHV-8) infection is unknown., Study Design: We evaluated factors associated with HHV-8 seropositivity in 2795 participants (132 with KS) in the National Cancer Institute AIDS Cancer Cohort, including 1621 men who have sex with men (MSM), 660 heterosexual men and 514 women. Odds ratios (OR) and 95% confidence intervals were estimated using logistic regression models., Results: Among non-KS subjects, HHV-8 seropositivity was 6%, 13% and 29% among women, heterosexual men and MSM, respectively. HHV-8 seropositivity was decreased in heavier (> or =1/2 pack/day) compared to lighter smokers among women (5% versus 8%; adjusted OR (aOR) 0.4; 95% CI 0.2-0.8) and MSM (27% versus 32%; aOR 0.7; 95% CI 0.6-1.0), but not among heterosexual men (12% versus 16%; aOR 0.7; 95% CI 0.4-1.2). HHV-8 seroprevalence was increased in heavier (> or =1 drink/day) compared to lighter consumers of alcohol among women (16% versus 4%; adjusted OR 5.2; 95% CI 2.3-12), but not among MSM (33% versus 28%; aOR 1.2; 95% CI 0.9-1.6) or heterosexual men (13% versus 13%; aOR 1.1; 95% CI 0.6-2.0). In analyses adjusted for smoking and drinking, HHV-8 seropositivity was positively associated with chlamydia infection (OR=4.3; 95% CI 1.2-13) and with marital status among women p(heterogeneity)=0.03, and with hepatitis (OR=1.6; 95% CI 1.2-2.1), gonorrhea (OR=1.5; 95% CI 1.1-1.9), genital warts (OR=1.5; 95% CI 1.1-2.0) and nitrate inhalant use (OR=1.7; 95% CI 1.3-2.3) among MSM., Conclusions: Inverse association of HHV-8 seropositivity with cigarette smoking may indicate protective effect of tobacco smoke on HHV-8 infection, whereas positive associations with alcohol may reflect either behavioral factors or biological effects modulating susceptibility. Smoking and drinking may influence KS risk, at least in part, by altering the natural history of HHV-8 infection.

Although more than 25 million people in sub-Saharan Africa have human immunodeficiency virus (HIV) infection, little is known regarding their cancer risk. We investigated cancer risk among persons with HIV/AIDS in Uganda using record-linkage. We linked records of 12,607 HIV-infected persons attending The AIDS Support Organization (TASO) in Kyadondo County from October 1988 through December 2002 to the Kampala Cancer Registry. We calculated standardized incidence ratios (SIRs) to identify increased cancer risks in the early (4-27 months after TASO registration), late (28-60 months), or combined (4-60 months) incidence periods. We identified 378 cancers (181 prevalent, 197 incident) among TASO participants. Of incident cancers, 137 (70%) were AIDS-defining cancers. Risk was increased in the early-incident period, compared to the general population, for the AIDS-defining cancers: Kaposi sarcoma (SIR 6.4, 95%CI 4.8-8.4), non-Hodgkin lymphoma (6.7, 1.8-17), and cervical carcinoma (2.4, 1.1-4.4). These three cancers were also increased in the combined periods. Risks of five non-AIDS-defining cancers were increased in the combined periods: Hodgkin lymphoma (5.7, 1.2-17) and cancers of the conjunctiva (SIR 4.0; 1.5-8.7), kidney (16, 1.8-58), thyroid (5.7, 1.1-16), and uterus (5.5, 1.5-14). Cancers of the breast, nasopharynx, and lung were increased either in the early or late incident periods only. Among 407 children, seven cancers were observed, of which five were Kaposi sarcoma. The application of a record-linkage design in Africa broadens the repertoire of epidemiological tools for studying HIV-infected populations. We confirm the increased risks of AIDS-defining cancers and report increased risks of a few non-AIDS-defining cancers.

In Africa, Epstein-Barr virus (EBV) is associated with Burkitt lymphoma. We measured levels of EBV DNA in saliva and buffy coats from 233 asymptomatic Ugandan children with sickle cell disease and their mothers by quantitative real-time polymerase chain reaction. EBV DNA was detected in saliva from 90% of the children (median [interquartile range [IQR]] level, 5.2 [4.2-6.0] log(10) copies/mL of saliva) and 79% of the mothers (median [IQR] level, 4.8 [3.7-5.6] log(10) copies/mL of saliva) (P < .001). EBV DNA was detected in buffy coats from 86% of the children (median [IQR] level, 2.5 [2.2-2.9] log(10) copies/1 x 10(6) peripheral white blood cells [PWBCs]) and 72% of the mothers (median [IQR] level, 2.7 [2.4-3.1] log(10) copies/1 x 10(6) PWBCs) (P = .24). Detection of EBV DNA in saliva was positively correlated with detection in buffy coats. EBV DNA was detected more frequently in saliva and buffy coats than was human herpesvirus 8 DNA. Our results indicate that EBV infection persists, with virus readily detectable in saliva and buffy coats from persons without apparent symptoms in Africa.

Kaposi's sarcoma (KS) is a frequent complication of the acquired immunodeficiency syndrome (AIDS) in homosexual men. Risk factors for developing this malignancy are uncertain, other than immunosuppression and coinfection with human herpesvirus 8 (HHV-8). We therefore examined factors associated with KS in a cross-sectional analysis of 99 cases among 503 HHV-8 seropositive homosexual men with AIDS. Data were collected by computer-assisted personal interviews and medical chart reviews. HHV-8 seroreactivity was determined by enzyme-linked immunosorbent assay for antibodies against HHV-8 K8.1 glycoprotein. KS was significantly less common in blacks compared to whites [risk ratio (RR) = 0.4; 95% CI = 0.2 =0.8] and more common in subjects who had completed college (RR = 1.7; 95% CI = 1.1-2.7) or had annual income greater than dollar 30,000 (RR = 1.5; 95% CI = 1.1-2.2). KS was less common in cigarette smokers (RR = 0.6; 95% CI = 0.5-0.9) and users of crack cocaine (RR = 0.4; 95% CI = 0.1-0.8). KS was less common in bisexual men compared to men who were exclusively homosexual (estimated RR = 0.6; 95% CI = 0.4-0.9) and inversely associated with number of female partners. KS was also less common in men who had received pay for sex (RR = 0.6; 95% CI = 0.4-1.0). These cross-sectional associations could be biased by potential differences in relative timing of HHV-8 and HIV infection, a postulated determinant of KS risk. Alternatively, our findings may reflect factors protective against KS in individuals infected with HHV-8. Future research should focus on identifying practical measures for countering KS that do not increase the risk of other diseases.

Background: Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its distribution is uneven. Transmission occurs during childhood within families by unclear routes., Methods: We evaluated 600 Ugandan children with sickle cell disease and their mothers for factors associated with HHV-8 seropositivity in a cross-sectional study. HHV-8 serostatus was determined using an HHV-8 K8.1 glycoprotein enzyme immunoassay. Odds ratios for seropositivity were estimated using logistic regression, and factor analysis was used to identify clustering among socioeconomic variables., Results: One hundred seventeen (21%) of 561 children and 166 (34%) of 485 mothers with definite HHV-8 serostatus were seropositive. For children, seropositivity was associated with age, mother's HHV-8 serostatus (especially for children aged 6 years or younger), lower maternal education level, mother's income, and low-status father's occupation (P < 0.05 for all). Using communal standpipe or using surface water sources were both associated with seropositivity (OR 2.70, 95% CI 0.80-9.06 and 4.02, 95% CI 1.18-13.7, respectively) as compared to using private tap water. These associations remained, albeit attenuated, after adjusting for maternal education and child's age (P = 0.08). In factor analysis, low scores on environmental and family factors, which captured household and parental characteristics, respectively, were positively associated with seropositivity (P(trend) < 0.05 for both). For mothers, HHV-8 seropositivity was significantly associated with water source and maternal income., Conclusions: HHV-8 infection in Ugandan children was associated with lower socioeconomic status and using surface water. Households with limited access to water may have less hygienic practices that increase risk for HHV-8 infection.

Among 233 children, Kaposi sarcoma-associated herpesvirus (KSHV) DNA was detected in 43% of children seropositive for both K8.1 and orf73, in 29% of children seropositive for K8.1 only, in 14% of children seropositive for orf73 only, and in 7% of children seronegative for both K8.1 and orf73; among 228 mothers, KSHV DNA was detected in 27%, 25%, 4%, and 1%, respectively. KSHV DNA was detected more frequently and at higher levels in saliva than in buffy-coat samples and in children than in mothers. In both children and mothers, detection in saliva was associated with detection in peripheral blood. Detection was associated with K8.1 seropositivity, younger age, and high household density, indicating the importance of in-household person-to-person transmission, likely via saliva., (Copyright 2004 Infectious Diseases Society of America)

Objective: To analyse the contribution of maternal survival and HIV status to child (under-5 years) mortality in a rural population cohort in South-west Uganda., Methods: Approximately 10 000 people residing in 15 neighbouring villages were followed between 1989 and 2000 using annual censuses and serological surveys to collect data on births, deaths, and adult HIV serostatus. Mother-child records were linked, child mortality risks (per 1000 births) and hazard ratios (HRs) for child mortality according to maternal HIV serostatus were computed, allowing for time-varying covariates., Results: A total of 3727 children were born, of whom 415 died during 14 110 child years of follow-up. Mother's HIV status at birth was ascertained unambiguously for 3004 children, of whom 218 were born to HIV-positive mothers. Infant mortality risk was higher for HIV seropositive than seronegative mothers (225 versus 53) as was child mortality risk (313 versus 114). Child mortality risk was also higher for mothers who died (571) than for surviving mothers (128). After controlling for child's age and sex, independent predictors of mortality in children were: mother's terminal illness or death (HR = 3.8); mother being HIV positive (HR = 3.2); child being a twin (HR = 2.0); teenage motherhood (HR = 1.7) and maternal absence (HR = 1.7)., Conclusion: Maternal survival and HIV status are strong predictors of child survival. The higher mortality in HIV-infected women compounds mortality risks for their children, regardless of children's HIV status. Programmes aimed at the welfare of children should take into account the independent effect of mothers' HIV and vital status.

Background: Surveys have been conducted to measure prevalence of eye disease in Africa, but not of incidence, which is needed to forecast trends. The incidence of visual loss is reported in southwest Uganda., Methods: A rural population residing in 15 neighbouring villages was followed between 1994-5 (R1) and 1997-8 (R2). Survey staff screened adult residents (13 years or older) for visual acuity using laminated Snellen's E optotype cards at each survey. Those who failed (VA >6/18) were evaluated by an ophthalmic clinical officer and an ophthalmologist. Incidence of visual loss (per 1000 person years (PY)) was calculated among those who had normal vision at R1., Results: 2124 people were studied at both survey rounds (60.9% of those screened at R1); 48% were male. Participants in R1 were older (34.7 versus 31.5 years at R2, p<0.001). Visual loss in R2 occurred in 56 (2.8%) of 1997, yielding a crude incidence rate of 9.9, and an age standardised incidence rate of 13.2, per 1000 PY. Incidence of visual loss increased with age from 1.21 per 1000 PY among people aged 13-34 to 64.2 per 1000 PY in those aged 65 years or older (p for trend >0.001). The six commonest causes of visual loss were: cataract, refractive error, macular degeneration, chorioretinitis, glaucoma, and corneal opacity. If similar rates are assumed for the whole of Uganda, it is estimated that 30 348 people would develop bilateral blindness or bilateral visual impairment, per year., Conclusions: Cataract and refractive error were the major causes of incident visual loss in south west Uganda. These data are valuable for forecasting and planning eye services.

Patients with HIV infection are at increased risk for developing Kaposi's sarcoma, non-Hodgkin's lymphoma, and several other cancers. The relative risks for the most common epithelial cancers in the general population--lung, breast, colon/rectum, stomach, liver, and prostate--are not increased substantially in people with AIDS, however. Accumulating data suggest that HIV-infected patients also are at increased risk for developing Hodgkin's lymphoma, cervical carcinoma in situ (CIS), other anogenital neoplasms (invasive cancer and CIS), leiomyosarcoma, and conjunctival squamous cell carcinoma. There is inconclusive evidence, however, with regard to HIV infection being associated with invasive cervical cancer, testicular seminoma, or hepatocellular carcinoma. Notably, other viral infections have been implicated in the etiology of many of these conditions. The introduction of highly active antiretroviral therapy (HAART) has decreased the incidence of AIDS-associated cancers in Western countries, but less than 1% of AIDS patients are receiving HAART in the HIV epicenter of sub-Saharan Africa. Further therapeutic advances that extend survival with HIV infection with varying reconstitution of immune competence may lead to additional alterations in cancer risk.

Human herpesvirus 8 (HHV-8) infection is common in Africa. We examined the distribution of HHV-8 within families in rural Tanzania to determine routes of spread. HHV-8 infection was assessed by measuring antibody reactivity with a K8.1 (lytic-phase antigen) immunoassay. The prevalence increased from 3.7% (1/27) among infants to 58.1% (36/62) among children aged 3-4 years and 89.0% (65/73) among adults aged > or =45 years. Women with HHV-8-seropositive husbands had a 7-fold risk for infection (odds ratio [OR], 6.9; 95% confidence interval [CI], 1.9-25.3). HHV-8 seropositivity in children was associated with having at least 1 seropositive first-degree relative (OR, 14.7; 95% CI, 5.9-43.1), a seropositive mother (OR, 7.4; 95% CI, 3.2-16.8), a seropositive father (OR, 4.8; 95% CI, 2.3-10.1), or a seropositive next-older sibling (OR, 4.2; 95% CI, 1.9-9.4). Our data are consistent with the occurrence of HHV-8 transmission within families, from mothers and other relatives to children via nonsexual routes and between spouses via sexual routes.

Background: People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset., Methods: We linked records from AIDS and cancer registries in 11 US regions (1990-1996). We studied 82,217 (86.6%) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the 2 years after AIDS onset. For each cancer, the change in SIRs across CD4 counts (0-49 cells/mm3, 50-99 cells/mm3, 100-199 cells/mm3, and > or =200 cells/mm3) was modeled using Poisson regression., Results: The SIRs for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm3, RRs were 1.36 (95% CI: 1.29-1.43) for KS and 1.48 (95% CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR =1.64, 95% CI: 1.37-1.96, per decline of 100 CD4 cells/mm3) and central nervous system lymphoma (RR = 2.29, 95% CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p =.74). For non-AIDS-defining cancers (overall SIR = 2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts., Conclusion: SKS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors.

Background: Human herpesvirus 8 (HHV-8) infection is common in Africa, but prevalence varies geographically. Studies in Europe and America suggest spread through homosexual contact, but evidence of heterosexual spread is inconsistent. We examined the association between HHV-8 and markers of risky sexual activity in Nigeria., Methods: The study subjects included an adult referent population at relatively low risk of HIV infection, patients attending a sexually transmitted disease (STD) clinic, and female commercial sex workers (CSW). Sera were collected between 1991 and 1994 to study the epidemiology of retroviruses and STD in Lagos, Nigeria. Residual samples were tested for HHV-8 antibodies using a K8.1 enzyme immunoassay and for antibodies to syphilis, chancroid, herpes simplex virus 2, HIV-1/2, and HTLV-1. Associations were sought using chi square tests and logistic regression., Results: Overall, HHV-8 prevalence was 26.5% in 2002 study subjects, being higher among CSW and STD patients (31% in each) than in the referent population (19%). HHV-8 prevalence in women was approximately half that in men in both the referent and the STD populations. Increasing age and STD were each associated with HHV-8-seropositivity in men and women, and among women being a CSW was also a risk factor. HHV-8 antibodies were more frequently detected in those with laboratory evidence of STD in each group. Having at least one STD was associated with having HHV-8 antibodies., Conclusion: The higher prevalence of HHV-8 antibody in groups with multiple sexual partners and the association with STD among individuals both support the sexual transmission of HHV-8 in African adults.

The objective of this study was to examine the epidemic trends of HIV-1 infection in a rural population cohort in Uganda followed for 10 years. The methods used were to assess incidence and prevalence trends in adults in this longitudinal cohort study. The results showed that incidence of infection has fallen significantly in all adults, and separately in males, females, young adults and older adults over the course of the study period. There was also a reduction in prevalence, especially in young men and women. There was some evidence of a cohort effect in women. The conclusions are that this study provides the first evidence of a falling incidence in a rural general population in Africa. This was an observational cohort exposed to national health education messages, giving hope that similar campaigns elsewhere in Africa could be used effectively in efforts to control the HIV epidemic.

Background: Few population-based eye surveys have been conducted in sub-Saharan Africa, limiting the quality of epidemiological information on visual loss from Africa. In the present paper, we describe the prevalence of visual loss in rural Uganda and the screening accuracy of E-optotypes when used by non-medical staff., Methods: Residents of 15 neighbouring villages were screened for visual loss (<6/18 in either eye) using Snellen's E-optotypes. Individuals who failed were initially referred to an ophthalmic clinical officer (OCO), who retested visual acuity and subsequently referred to an ophthalmologist to determine the cause of visual loss. Subjects from two villages (248 individuals) who passed visual acuity screening were re-examined by the OCO to estimate the accuracy of the screening procedure., Results: Of the 4076 adults (aged 13 years and over, 69.3% of the censused population) who participated, 191 (4.7%) failed the vision screening criteria and 648 (15.9%) had non-vision impairing conditions. The prevalence of visual loss was at least 3.9%: 0.4% had bilateral blindness, 1.6% had bilateral visual impairment, 0.7% had unilateral blindness and 1.2% unilateral visual impairment. Cataract was the leading cause for all categories of visual loss except bilateral blindness, for which suspected glaucoma was most frequent. Refractive errors were the second leading cause of bilateral and unilateral visual impairment. Based on one subject (0.4%) in the validation sample who was found to have low vision, we estimated the sensitivity and specificity of E-optotypes for detecting visual loss to be 93% and 99%, respectively., Conclusions: Cataract and refractive errors were responsible for most of the visual loss in rural Uganda. Snellen's E-optotypes provide a suitable cost-saving tool for conducting population-based eye surveys in sub-Saharan Africa.

Background: The incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL) in the general population has markedly increased since the onset of the AIDS epidemic in 1981. However, during the 1990s, the dynamics of the AIDS epidemic changed, as human immunodeficiency virus (HIV) infection rates slowed and effective antiretroviral therapies were introduced. We examined the impact of these changes on the general population incidence of KS and NHL., Methods: Age-standardized incidences for KS and NHL from 1973 through 1998 were obtained from nine population-based cancer registries that participate in the Surveillance, Epidemiology and End Results (SEER) program., Results: During the mid-1990s, KS incidence declined sharply in all nine registries. Decreases in KS incidence were most evident in San Francisco, where KS rates among white men had risen from 0.5 per 100 000 people per year in 1973 to between 31.1 and 33.3 from 1987 through 1991 and then declined to 2.8 in 1998. With background NHL incidence in the general population being much higher than that for KS, changes in incidence related to the AIDS epidemic were most evident in subgroups at high risk of AIDS. In San Francisco, NHL rates among white men rose from 10.7 in 1973 to a peak of 31.4 in 1995 and then declined to 21.6 in 1998. NHL types that were most highly AIDS-associated declined most steeply, whereas the incidence of NHL types not associated with AIDS was either stable or increasing., Conclusion: Changes in KS and NHL incidence since the mid 1990s may reflect declines in the number of individuals with AIDS and improved immune function in such individuals following the introduction of effective antiretroviral therapies in the 1990s. Notably, non-AIDS-associated NHL incidence has continued to increase steadily through 1998.

Objective: To describe the occurrence and characteristics of pleural and peritoneal lymphoma in a large cohort of persons with AIDS in 11 regions in the United States., Methods: We used AIDS and cancer registries to identify cases of non-Hodgkin lymphoma (NHL) among 304,439 adults with AIDS. NHLs were categorized by site codes into pleural/peritoneal lymphoma and other NHLs. Data on age, sex, HIV exposure category, histology, history of Kaposi sarcoma (KS), CD4 counts, and survival were analyzed., Results: Fourteen lymphomas were identified (four within the pleura, 10 in the peritoneum) representing 0.13% (95% confidence interval [CI], 0.05-0.20) of 10,510 cases of NHL. Those with pleural/peritoneal lymphoma were similar to those with other NHLs in age (median, 43 years), race (79% white, 7% black, 14% Hispanic), and HIV transmission category (86% homosexual men), but they tended to have a higher prevalence of prior KS (29% vs. 12%; p =.06). More cases of pleural/peritoneal lymphoma had immunoblastic histology than did other NHLs (43% vs. 22%; p =.06). CD4 counts for pleural/peritoneal lymphomas were also higher than for other NHLs (median 203 vs. 65 cells/mm3; p =.05), but post-NHL survival was similar (median 7.1 vs. 5.1 months, respectively; p =.32)., Conclusions: Pleural and peritoneal lymphomas are a rare subtype of AIDS-associated NHL, occurring with less severe immune deficiency than for other NHLs. The increased frequency among persons with prior KS suggests a common etiology, presumably infection with KS-associated herpesvirus, as found in primary effusion lymphoma.