# Environmental determinants of KSHV transmission in rural Uganda

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $493,570

## Abstract

PROJECT SUMMARY/ABSTRACT
 Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma (KS), is
unique among human herpesviruses in that it is not ubiquitous in human populations, but rather shows marked
geographic hotspots in prevalence, being particularly common in sub-Saharan Africa (SSA). Moreover, there is
variation in prevalence even between geographically proximate locations within the same population in SSA.
This strongly suggests the presence of modifiable environmental factors that facilitate and maintain high levels
of transmission in SSA and we posit that malaria infection is a key underlying factor. We provide extensive
published and preliminary data supporting an interaction between malaria infection in children and KSHV
seroprevalence. We hypothesize that malaria infection in children increases their susceptibility to KSHV
through alterations in immune function or expansion of KSHV cellular targets or both. For children that are
already KSHV infected, malaria infection could lead to viral reactivation resulting in higher viral loads in
peripheral blood, higher frequency of shedding or both. The General Population Cohort (GPC) in rural Uganda
is a longitudinal study investigating the trends and determinants of the HIV epidemic, as well as non-
communicable disease risk factors. We found that KSHV seroprevalence in the GPC is among the highest ever
reported (>90%) and children are infected at an early age (~30% by 3 years). The early age of KSHV infection,
the endemic malaria transmission and the high levels of KSHV seroprevalence in the Ugandan GPC provides
us with a unique opportunity to directly test our hypothesis. We will do this by enrolling a prospective infant
cohort within the GPC determining the effect of P. falciparum on the establishment of KSHV infection;
characterizing immune phenotype in children prior to KSHV infection and evaluate effects of P. falciparum on
KSHV reactivation. In this proposal, we will capitalise on an ongoing substantive research program on KSHV
and will embed the proposed work within a long-standing population-based cohort in rural Uganda, with a
substantial body of existing data. The proposed work will address the profound knowledge gap regarding
factors that influence KSHV transmission. This may, in the future, lead to the development of interventions to
reduce transmission and thereby reduce the burden of KS.

## Key facts

- **NIH application ID:** 10169385
- **Project number:** 5R01CA239588-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** ROSEMARY ROCHFORD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $493,570
- **Award type:** 5
- **Project period:** 2019-06-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169385

## Citation

> US National Institutes of Health, RePORTER application 10169385, Environmental determinants of KSHV transmission in rural Uganda (5R01CA239588-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169385. Licensed CC0.

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