Antibodies reactive to Plasmodium falciparum serine repeat antigen in children with Burkitt lymphoma from Ghana.

The role of protective immunity to Plasmodium falciparum (Pf) malaria in Burkitt lymphoma (BL) is unknown. We investigated the association between BL and antibodies reactive to SE36 antigen, a recombinant protein based on P. falciparum serine repeat antigen 5 gene, targeted by protective malaria immune responses. Cases were children (0-14 years) enrolled at the Korle-Bu Teaching Hospital, Accra, Ghana, during 1965-1994 with BL confirmed by histology or cytology (92% of cases). Controls were apparently healthy children enrolled contemporaneous to the cases from the nearest neighbor house to the case house and were age,- sex-frequency-matched to the cases. Anti-SE36 IgG antibodies were measured using enzyme-linked absorbent immunoassays (ELISAs). SE36 titers were estimated by extrapolating ELISA optical density readings to a standard fitting curve. Anti-SE36 titers were log-transformed for analysis. Odds ratios (ORs) and two-sided 95% confidence intervals (95% CIs) were estimated using unconditional logistic regression. The mean log endpoint dilution titers were 0.63 logs lower in cases than in controls (8.26 [SD 1.68] vs. 8.89 [SD 1.75], Student's t-test, p = 0.019). Lower titers were observed in cases than controls aged 0-4 years (p = 0.05) and in those aged 5-14 years (p = 0.06). Low and medium tertiles of anti-SE36 IgG antibodies were associated with increased OR for BL ([OR 1.67, 95% CI 1.21-2.31] and [OR 1.33, 95% CI 0.96-1.86], respectively, p(trend) = 0.002) in analyses adjusting for age, sex, calendar period and test plate. Our findings suggest that compared to similarly aged children enrolled from the same community, children with BL in Ghana have lower antibodies to SE36 antigen.

HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study.

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.

AIDS-related Burkitt lymphoma in the United States: what do age and CD4 lymphocyte patterns tell us about etiology and/or biology?

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.

Elevated risk for squamous cell carcinoma of the conjunctiva among adults with AIDS in the United States.

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.

Chlamydia pneumoniae, heat shock proteins 60 and risk of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes: a prospective study.

BACKGROUND: There have been suggestions of an association between Chlamydia pneumoniae, chlamydial heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are prone to infections. The objective of this study was to investigate prospectively the role of Chlamydia pneumoniae (CP), chlamydial heat shock protein (Ch-hsp) 60 and a possible intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus. METHODS: Patients aged 30-70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease (International Classification of Disease, 9th Rev. pos. 410-414) between January 1999 and May 2000 in one of two participating rehabilitation clinics in Germany were included in this analysis. Chlamydia pneumoniae (CP), chlamydial heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 status at baseline were measured by serum immunoglobulin G and A antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months (response = 87%). RESULTS: Among the 1052 subjects 37.4% and 39.3% were sero-positive to CP IgA and IgG respectively, 22.2% were sero-positive to Ch-hsp 60 IgG and 8.4% were positive to h-hsp 60 IgG at baseline. During follow-up, secondary CVD events occurred among 71 (6.8%) participants. Occurrence of a secondary CVD event was more common among CP (IgA) and CP (IgG) sero-positive than among sero-negative patients (p-values 0.04 and 0.1, respectively). The risk of secondary CVD events was increased among patients with both a positive CP sero-status and diabetes compared to infection negative, non-diabetic patients and in general, sero-positivity added a hazard to diabetes. The interaction term between infection sero-status and diabetes was not statistically significant. We were not able to show an intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD events in patients with CHD. CONCLUSION: Results from this cohort of 1052 patients with pre-existing CHD cannot exclude a possible moderate increase in risk of secondary CVD events among patients with a positive infection sero-status. However, our study showed no intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD events in patients with CHD. Larger studies or meta-analysis of multiple studies are needed to address the interaction between infection sero-status and diabetes with adequate power.

Role of cytomegalovirus sero-status in the development of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes.

OBJECTIVE: We investigated prospectively the role of cytomegalovirus (CMV) sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus. BACKGROUND: There have been suggestions of an association between cytomegalovirus infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are relatively immunocompromised. METHODS: Patients aged 30-70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease between January 1999 and May 2000 were included in this analysis. CMV status at baseline was measured by serum immunoglobulin G antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months. RESULTS: Among the 1033 subjects with measured IgG antibody for CMV, 56.5% were sero-positive to CMV at baseline. During follow-up, secondary CVD events occurred among 71 (6.9%) participants. Occurrence of a secondary CVD event was more common among sero-positive than among sero-negative patients (adjusted hazard ratio, HR, 1.31, 95% confidence interval (CI) 0.80-2.20), among patients with diabetes HR 2.00 (95% CI 1.20-3.25). The risk of secondary CVD events was strongly increased among patients with both a positive CMV sero-status and diabetes (adjusted HR 2.58, 95% CI 1.32-5.10) compared to CMV negative, non-diabetic patients, whereas either conditions alone was associated with a weak and non-significant increase in risk only. CONCLUSION: Our results are consistent with a possible moderate increase in risk of secondary CVD events among patients with a positive CMV sero-status, and they indicate a strongly increased risk among CMV positive patients with diabetes.