Kaposi Sarcoma-Associated Herpesvirus Infection and Endemic Burkitt Lymphoma

J Infect Dis. 2020 Jun 16;222(1):111-120. doi: 10.1093/infdis/jiaa060.

Abstract

Background: Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria coinfections. However, the role of Kaposi sarcoma-associated herpesvirus (KSHV), also endemic in Africa, has not been evaluated as a cofactor in eBL pathogenesis.

Methods: Multiplexed seroprofiles for EBV, malaria, and KSHV were generated for 266 eBL patients, 78 non-eBL cancers, and 202 healthy children. KSHV and EBV loads were quantified by PCR.

Results: KSHV seroprevalence did not differ by study group but was associated with age. Seropositivity, defined by K8.1/LANA or in combination with 5 other KSHV antigens (ORF59, ORF65, ORF61, ORF38, and K5) was associated with antimalarial antibody levels to AMA1 (odds ratio [OR], 2.41, P < .001; OR, 2.07, P < .001) and MSP1 (OR, 2.41, P = .0006; OR, 5.78, P < .001), respectively. KSHV loads did not correlate with antibody levels nor differ across groups but were significantly lower in children with detectable EBV viremia (P = .014).

Conclusions: Although KSHV-EBV dual infection does not increase eBL risk, EBV appears to suppress reactivation of KSHV while malaria exposure is associated with KSHV infection and/or reactivation. Both EBV and malaria should, therefore, be considered as potential effect modifiers for KSHV-associated cancers in sub-Saharan Africa.

Keywords: Plasmodium falciparum malaria; Epstein-Barr virus; Kaposi sarcoma-associated herpesvirus; Kenya; endemic Burkitt lymphoma.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Burkitt Lymphoma / epidemiology
  • Burkitt Lymphoma / etiology*
  • Burkitt Lymphoma / genetics*
  • Burkitt Lymphoma / physiopathology
  • Child
  • Child, Preschool
  • Coinfection
  • Female
  • Herpesviridae / genetics*
  • Herpesviridae Infections / epidemiology
  • Herpesviridae Infections / etiology*
  • Herpesviridae Infections / genetics*
  • Herpesviridae Infections / physiopathology
  • Humans
  • Infant
  • Kenya / epidemiology
  • Male
  • Sarcoma, Kaposi / complications*
  • Sarcoma, Kaposi / epidemiology
  • Sarcoma, Kaposi / genetics*
  • Sarcoma, Kaposi / physiopathology
  • Seroepidemiologic Studies