Plasmodium falciparum malaria is associated with increased KSHV seropositivity and higher KSHV antibody breadth and magnitude: results of a case-control study from rural Uganda

Previously, we showed that children with asymptomatic Plasmodium falciparum (Pf) malaria infection had higher Kaposi sarcoma-associated herpesvirus (KSHV) viral load, increased risk of KSHV seropositivity and higher KSHV antibody levels. We hypothesise that clinical malaria has an even larger association with KSHV seropositivity. Therefore in the current study, we investigated the association between clinical malaria and KSHV seropositivity and antibody levels. Between 12/2020 to 03/2022, sick children (aged 5-10 years) presenting at a clinic in Uganda were enrolled in a case-control study. Pf was detected using malaria rapid diagnostic tests (RDT) and subsequently with quantitative real-time polymerase chain reaction (qPCR). Children with malaria were categorized into two groups; RDT+/PfPCR+ and RDT-/PfPCR+. The seropositivity of KSHV was 60% (47/78) among Pf uninfected children, 79% (61/77); among children who were RDT-/PfPCR+ (Odds Ratio [OR] 2.41, 95% CI 1.15-5.02) and 95% (141/149) in children who were RDT+/Pf PCR+ (OR 10.52, 95% CI: 4.17-26.58; P (trend)< 0.001). Furthermore, RDT+/PfPCR+ children followed by RDT-/PfPCR+ children had higher KSHV IgG and IgM antibody levels and reacted to more KSHV antigens compared to uninfected children. Clinical malaria is associated with both increased KSHV seropositivity and antibody magnitude suggesting that Pf is affecting KSHV immunity. © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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