44 research outputs found

    Association between malaria exposure and Kaposi's sarcoma-associated herpes virus seropositivity in Uganda.

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    OBJECTIVE: Unlike other herpes viruses, Kaposi's sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. METHODS: Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. RESULTS: Kaposi's sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP-1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti-ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. CONCLUSION: The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation

    Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: a nested case-control study

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    HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p &#60; 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting

    Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohort.

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    Human cytomegalovirus (HCMV) infection has been associated with increased mortality, specifically cardiovascular disease (CVD), in high-income countries (HICs). There is a paucity of data in low- and middle-income countries (LMICs) where HCMV seropositivity is higher. Serum samples from 2,174 Ugandan individuals were investigated for HCMV antibodies and data linked to demographic information, co-infections and a variety of CVD measurements. HCMV seropositivity was 83% by one year of age, increasing to 95% by five years. Female sex, HIV positivity and active pulmonary tuberculosis (TB) were associated with an increase in HCMV IgG levels in adjusted analyses. There was no evidence of any associations with risk factors for CVD after adjusting for age and sex. HCMV infection is ubiquitous in this rural Ugandan cohort from a young age. The association between TB disease and high HCMV IgG levels merits further research. Known CVD risk factors do not appear to be associated with higher HCMV antibody levels in this Ugandan cohort

    Age of Infection with Kaposi Sarcoma-Associated Herpesvirus and Subsequent Antibody Values Among Children in Uganda.

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    We investigated associations between Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion age and KSHV antibody values in Ugandan children. Every annual delay in KSHV seroconversion age was associated with a reduction of 19% (P < 0.0001) in K8.1 and 27% (P < 0.0001) in ORF73 antibody values at 6 years of age. Early infection may be an important risk factor for KSHV pathogenesis and viral shedding in saliva, leading to transmission

    Immune cell phenotype and function patterns across the life course in individuals from rural Uganda

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    BackgroundTo determine the pattern of immune cell subsets across the life span in rural sub-Saharan Africa (SSA), and to set a reference standard for cell subsets amongst Africans, we characterised the major immune cell subsets in peripheral blood including T cells, B cells, monocytes, NK cells, neutrophils and eosinophils, in individuals aged 3 to 89 years from Uganda.MethodsImmune phenotypes were measured using both conventional flow cytometry in 72 individuals, and full spectrum flow cytometry in 80 individuals. Epstein-Barr virus (EBV) IFN-γ T cell responses were quantified in 332 individuals using an ELISpot assay. Full blood counts of all study participants were also obtained.ResultsThe percentages of central memory (TCM) and senescent CD4+ and CD8+ T cell subsets, effector memory (TEM) CD8+ T cells and neutrophils increased with increasing age. On the other hand, the percentages of naïve T (TN) and B (BN) cells, atypical B cells (BA), total lymphocytes, eosinophils and basophils decreased with increasing age. There was no change in CD4+ or CD8+ T effector memory RA (TEMRA) cells, exhausted T cells, NK cells and monocytes with age. Higher eosinophil and basophil percentages were observed in males compared to females. T cell function as measured by IFN-γ responses to EBV increased with increasing age, peaking at 31-55 years.ConclusionThe percentages of cell subsets differ between individuals from SSA compared to those elsewhere, perhaps reflecting a different antigenic milieu. These results serve as a reference for normal values in this population

    Variation in KSHV prevalence between geographically proximate locations in Uganda

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    Kaposi's sarcoma-associated herpesvirus (KSHV) transmission within endemic areas may vary. KSHV seroprevalence has been studied by different groups of researchers using different methods, making it difficult to make direct comparisons. Here we show results on KSHV seroprevalence using the same laboratory method from four different but geographically proximate populations in Uganda. Blood samples from the urban Entebbe Mother and Baby Study (EMaBS), the rural General Population Cohort (GPC), the fishing community Lake Victoria Island Intervention Study on Worms and Allergy related Diseases (LaVIISWA) and the high-risk sexual behaviour Good Health for Women Project (GHWP), were tested for IgG antibody levels to K8.1 and ORF73 recombinant proteins using ELISA. All adult participants of the EMaBS study and the GHWP were women, while the GPC (54% female) and LaVIISWA (52% female) studies had both males and females. EMaBS children were all 5 years of age while their mothers were 14 to 47 years of age. GHWP women were 15 to 45 years old, LaVIISWA participants were 1 to 72 years old while GPC participants were 1 to 103 years old. KSHV seropositivity varied in the different populations. In children aged 5 years, EMaBS had the lowest prevalence of 15% followed by GPC at 35% and LaVIISWA at 54%. In adult women, seropositivity varied from 69% (EMaBS) to 80% (LaVIISWA) to 87% (GPC) to 90% (GHWP). The reasons for the variation in prevalence are unclear but may reflect differences in the prevalence of cofactors between these four geographically proximate populations

    Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: a nested case-control study.

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    HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting

    Comparison of Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus viral load in peripheral blood mononuclear cells and oral fluids of HIV-negative individuals aged 3-89 years from Uganda

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    We previously found that age, sex and malaria were associated with KSHV in individuals from Uganda. In this study, we have evaluated these same factors in relation to EBV in the same specimens. Overall, 74% (oral fluids) and 46% (PBMCs) had detectable EBV. This was significantly higher than observed for KSHV (24% oral fluids and 11% PBMCs). Individuals with EBV in PBMCs were more likely to have KSHV in PBMCs (P = 0.011). The peak age for detection of EBV in oral fluids was 3-5 years while that of KSHV was 6-12 years. In PBMCs, there was a bimodal peak age for detection of EBV (at 3-5 years and 66 + years) while for KSHV there was a single peak at 3-5 years. Individuals with malaria had higher levels of EBV in PBMCs compared to malaria-negative individuals (P = 0.002). In summary, our results show that younger age and malaria are associated with higher levels of EBV and KSHV in PBMCs suggesting malaria impacts immunity to both gamma-herpesviruses

    Risk factors for Kaposi's sarcoma associated herpesvirus (KSHV) DNA in blood and in saliva in rural Uganda

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    INTRODUCTION: Detectable KSHV DNA in blood and increased antibody titres may indicate KSHV reactivation, while transmission of KSHV occurs via viral shedding in saliva. METHODS: We investigated risk factors for KSHV DNA detection by real-time PCR, in blood and viral shedding in saliva, in 878 people aged 3 to 89 years of both sexes in a rural Ugandan population cohort. Helminths were detected using microscopy and malaria parasitaemia was identified using rapid diagnostic tests. Regression modelling was used for statistical analysis. RESULTS: and discussion: KSHV viral load in blood did not correlate with viral load in saliva, suggesting separate immunological control within each compartment. The proportion of individuals with detectable virus in blood was 23% among children aged 3-5 years , 22% among 6-12 years old, thereafter reducing with increasing age. The proportion of individuals with detectable virus in saliva increased from 30% in 3-5 year old children to 45% in those aged 6-12 and decreasing subsequently with increasing age. Overall, 29% of males shed in saliva compared to 19% of females (p = 0.008). Together, these data suggest that young males may be responsible for much of the onward transmission of KSHV. Individuals with a current malaria infection had higher levels of viral DNA in blood (p = 0.031) compared to malaria uninfected individuals. This suggests that malaria may lead to KSHV reactivation, thereby increasing transmission and pathogenicity of the virus

    Profiles of inflammatory markers and their association with cardiometabolic parameters in rural and urban Uganda

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    Background: Inflammation may be one of the pathways explaining differences in cardiometabolic risk between urban and rural residents. We investigated associations of inflammatory markers with rural versus urban residence, and with selected cardiometabolic parameters previously observed to differ between rural and urban residents: homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), blood pressure (BP) and body mass index (BMI). Methods: From two community surveys conducted in Uganda, 313 healthy individuals aged ≥ 10 years were selected by age- and sex-stratified random sampling (rural Lake Victoria island communities, 212; urban Entebbe municipality, 101). Fluorescence intensities of plasma cytokines and chemokines were measured using a bead-based multiplex immunoassay. We used linear regression to examine associations between the analytes and rural-urban residence and principal component analysis (PCA) to further investigate patterns in the relationships. Correlations between analytes and metabolic parameters were assessed using Pearson’s correlation coefficient. Results: The urban setting had higher mean levels of IL-5 (3.27 vs 3.14, adjusted mean difference [95% confidence interval] 0.12[0.01,0.23] p=0.04), IFN-⍺ (26.80 vs 20.52, 6.30[2.18,10.41] p=0.003), EGF (5.67 vs 5.07, 0.60[0.32,0.98] p&lt;0.00001), VEGF (3.68 vs 3.28, 0.40[0.25,0.56] p&lt;0.00001), CD40 Ligand (4.82 vs 4.51, 0.31[0.12, 0.50] p=0.001) and Serpin-E1 (9.57 vs 9.46, 0.11[0.05,0.17] p&lt;0.00001), but lower levels of GMCSF (2.94 vs 3.05, -0.10[-0.19,-0.02] p=0.02), CCL2 (2.82 vs 3.10, -0.45[-0.70,-0.21] p&lt;0.00001) and CXCL10 (5.48 vs 5.96, -0.49[-0.71,-0.27] p&lt;0.00001), compared to the rural setting. In PCA, the urban setting had lower representation of some classical inflammatory mediators but higher representation of various chemoattractants and vasoactive peptides. HOMA-IR, FBG, BP and BMI were positively correlated with several principal components characterised by pro-inflammatory analytes. Conclusions: In developing countries, immunological profiles differ between rural and urban environments. Differential expression of certain pro-inflammatory mediators may have important health consequences including contributing to increased cardiometabolic risk observed in the urban environment
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