Exposure to Holoendemic Malaria Results in Elevated Epstein‐Barr Virus Loads in Children

Moormann, Ann M.; Chelimo, Kiprotich; Sumba, Odada P.; Lutzke, Mary L.; Ploutz‐Snyder, Robert; Newton, Duane W.; Kazura, James W.; Rochford, Rosemary

doi:10.1086/428910

Cited by 190 publications

(224 citation statements)

References 31 publications

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“…One important eBL co-factor, Epstein-Barr virus infection, is evenly distributed in the population and infection occurs early in childhood. 21,22 Our consistent findings, therefore, may imply clustering of other environmental or socio-cultural eBL co-factors, although potential reporting bias must also be assessed. Neither high-risk cluster included administrative units in Siaya District, as initially hypothesized.…”

Section: Spatial Clusteringmentioning

confidence: 82%

Spatial clustering of endemic Burkitt's lymphoma in high‐risk regions of Kenya

Rainey

Omenah

Sumba

et al. 2006

Intl Journal of Cancer

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103

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Endemic Burkitt's lymphoma (eBL), the most common childhood cancer in sub‐Saharan Africa, occurs at a high incidence in western Kenya, a region that also experiences holoendemic malaria. Holoendemic malaria has been identified as a co‐factor in the etiology of this cancer. We hypothesized that eBL may cluster spatially within this region. Medical records for all eBL cases diagnosed from 1999 through 2004 at Nyanza Provincial General Hospital were reviewed for case residential information to examine this hypothesis. Two cluster detection methods, Anselin's Local Moran test for spatial autocorrelation and a spatial scan test statistic, were applied to this residential data to determine whether statistically significant high‐ and low‐risk areas were present in the Province. During the 6‐year study period, 272 children were diagnosed with eBL, with an average annual incidence of 2.15 cases per 100,000 children. Using Empirical Bayes smoothed rates, the Local Moran test identified 1 large multi‐centered area of low eBL risk (p‐values < 0.01) and 2 significant multi‐centered clusters of high eBL risk (p‐values < 0.001). The spatial scan detected 3 small independent low‐risk areas (p‐values < 0.02) and 2 high‐risk clusters (p‐values = 0.001), both similar in location to those identified from the Local Moran analysis. Significant spatial clustering of elevated eBL risk in high‐malaria transmission regions and of reduced incidence where malaria is infrequent suggests that malaria plays a role in the complex eBL etiology, but that additional factors are also likely involved. © 2006 Wiley‐Liss, Inc.

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Section: Spatial Clusteringmentioning

confidence: 82%

Spatial clustering of endemic Burkitt's lymphoma in high‐risk regions of Kenya

Rainey

Omenah

Sumba

et al. 2006

Intl Journal of Cancer

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103

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“…Although age differed between the groups, with the controls being slightly older than the cases, both groups were within the age range of children at risk of developing eBL (i.e., 5-9 years of age). 32 There were several limitations to this study. Because of this study being conducted in a limited-resource setting, diagnosis was not confirmed by immunohistochemistry; therefore, it is possible but highly improbable that BL patients may have been misclassified.…”

Section: Discussionmentioning

confidence: 94%

“…A distinct possibility exists for genetic variation that alters the balance between antiinflammatory and proinflammatory cytokines to contribute to the immunologic dysregulation over EBV observed in eBL. [32][33][34] IL-6 and IL-10 are two cytokines that have been implicated in the pathogenesis and progression of other lymphoproliferative disorders. 14,35,36 We hypothesized that these cytokines could potentially provide a permissive milieu for eBL oncogenesis, and therefore, patients with eBL might be more likely to possess genotypes that predispose them to higher levels of inducible IL-6 and IL-10.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 and Interleukin-10 Gene Promoter Polymorphisms and Risk of Endemic Burkitt Lymphoma

Oduor¹,

Chelimo²,

Ouma³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Overexpression of interleukin-6 (IL-6) and IL-10 in endemic Burkitt lymphoma (eBL) may facilitate tumorigenesis by providing a permissive cytokine milieu. Promoter polymorphisms influence interindividual differences in cytokine production. We hypothesized that children genetically predisposed for elevated cytokine levels may be more susceptible to eBL. Using case-control samples from western Kenya consisting of 117 eBL cases and 88 ethnically matched healthy controls, we tested for the association between eBL risk and IL-10 (rs1800896, rs1800871, and rs1800872) and IL-6 (rs1800795) promoter single nucleotide polymorphisms (SNPs) as well as IL-10 promoter haplotypes. In addition, the association between these variants and Epstein Barr Virus (EBV) load was examined. Results showed that selected IL-10 and IL-6 promoter SNPs and IL-10 promoter haplotypes were not associated with risk eBL or EBV levels in EBV-seropositive children. Findings from this study reveal that common variants within the IL-10 and IL-6 promoters do not independently increase eBL risk in this vulnerable population.

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“…Our observation that long-term persistence of a murine gammaherpesvirus is age-dependent, as is the development of an IM-like syndrome, suggests that a greater understanding of persistence of gammaherpesviruses in children is needed. Indeed, we have reported the ready detection of EBV DNA and high viral loads in peripheral blood in children under the age of four living in Kenya (Moormann et al, 2005). Whether early age of infection leads to higher viral persistence in mucosal sites in children remains to be determined, but it is relevant to note that endemic Burkitt's lymphoma only affects children and that the presentation of tumours is primarily in the jaw (de-The, 1977).…”

Section: Discussionmentioning

confidence: 99%

Infection of neonates with murine gammaherpesvirus 68 results in enhanced viral persistence in lungs and absence of infectious mononucleosis syndrome

Ptaschinski

Rochford

2008

Journal of General Virology

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We used the murine gammaherpesvirus 68 (γHV-68), which serves as a model for human gammaherpesvirus infection, to determine whether age at infection altered the pattern of gammaherpesvirus pathogenesis. We infected mice intranasally at 8 days old (pups) and 6 weeks old (adults) to investigate differences in γHV-68 pathogenesis. There was no difference between adults or pups in acute infection in the lungs at 6 days post-infection (p.i.). However, mice infected as pups exhibited a more disseminated viral infection with viral DNA detected in the spleen, liver and heart as measured by quantitative PCR (Q-PCR). In addition, viral DNA was detected in the lungs of mice infected as pups until 60 days p.i. Three viral transcripts (M2, M3 and M9) were expressed at both 30 and 60 days p.i. In contrast, no viral DNA or mRNA expression was detected in lungs of mice infected as adults at 30 or 60 days p.i. Mice infected as adults experienced a peak in latent infection in the spleen at 16 days p.i., corresponding with an increase in splenic weight and expansion of the Vβ4+ CD8+ T-cell population, similar to infectious mononucleosis observed following infection of young adults with Epstein–Barr virus. However, the increase in splenic weight of infected pups was not as pronounced and no significant increase in Vβ4+ CD8+ T-cell expansion was observed in infected pups. Together, these data suggest that the pathogenesis of murine gammaherpesvirus γHV-68 is age-dependent.

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Exposure to Holoendemic Malaria Results in Elevated Epstein‐Barr Virus Loads in Children

Cited by 190 publications

References 31 publications

Spatial clustering of endemic Burkitt's lymphoma in high‐risk regions of Kenya

Spatial clustering of endemic Burkitt's lymphoma in high‐risk regions of Kenya

Interleukin-6 and Interleukin-10 Gene Promoter Polymorphisms and Risk of Endemic Burkitt Lymphoma

Infection of neonates with murine gammaherpesvirus 68 results in enhanced viral persistence in lungs and absence of infectious mononucleosis syndrome

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