Risk factors for Burkitt lymphoma in East African children and minors: A case–control study in malaria‐endemic regions in Uganda, Tanzania and Kenya

Abstract

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub‐Saharan African countries, however, few epidemiologic studies have been undertaken and none attempted enrolling cases from multiple countries. We therefore conducted a population‐based case–control study of eBL in children aged 0–15 years old in six regions in Northern Uganda, Northern Tanzania and Western Kenya, enrolling 862 suspected cases and 2,934 population controls (response rates 98.5–100%), and processing ~40,000 vials of samples using standardized protocols. Risk factor questionnaires were administered, and malaria period prevalence was measured using rapid diagnostic tests (RDTs). A total of 80.9% of the recruited cases were diagnosed as eBL; 61.4% confirmed by histology. Associations with eBL risk were computed using logistic regression models adjusted for relevant confounders. Associations common in at least two countries were emphasized. eBL risk was decreased with higher maternal income and paternal education and elevated with history of inpatient malaria treatment >12 months before enrollment. Reporting malaria‐attributed fever up to 6 months before enrollment and malaria‐RDT positivity at enrollment were associated with decreased eBL risk. Conversely, reporting exposure to mass malaria suppression programs (e.g., indoor residual insecticide) was associated with elevated risk. HIV seropositivity was associated with elevated eBL risk, but the relative impact was small. The study shows that it is feasible to conduct networked, multisite population‐based studies of eBL in Africa. eBL was inversely associated with socioeconomic status, positively associated with inpatient malaria treatment 12 months ago and with living in areas targeted for malaria suppression, which support a role of malaria in eBL.

Endemic Burkitt lymphoma: a complication of asymptomatic malaria in sub-Saharan Africa based on published literature and primary data from Uganda, Tanzania, and Kenya

“…The analysis utilized primary data compiled from children enrolled in the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) Study conducted in Uganda, Tanzania, and Kenya during 2010–2016 [ 19 ]. The EMBLEM study enrolled children aged 0–15 years old with eBL (histologically or cytologically confirmed in 61.4% of cases) at six local district or regional hospitals in Uganda, Tanzania, and Kenya [ 19 ]. EMBLEM also enrolled healthy children from 300 random villages in the same regions as the cases [ 19 ].…”

“…The EMBLEM study enrolled children aged 0–15 years old with eBL (histologically or cytologically confirmed in 61.4% of cases) at six local district or regional hospitals in Uganda, Tanzania, and Kenya [ 19 ]. EMBLEM also enrolled healthy children from 300 random villages in the same regions as the cases [ 19 ]. To ensure the comparability of malaria exposure before enrolment for the controls and eBL cases, eligibility was restricted to usual residents (≥ 4 months prior to enrollment) of the study area.…”

Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda

“…Briefly, the eBL cases were enrolled at St. Mary’s Hospital, Lacor, in Gulu district and at Kuluva Hospital in Arua district. These hospitals have the capacity to diagnose and treat eBL and are responsible for virtually all the cases in North‐Central and Northwest Uganda (Peprah et al , ). The controls were enrolled from 100 local‐area villages randomly selected from the region as previously described (Maziarz et al , ).…”

“…The controls were enrolled from 100 local‐area villages randomly selected from the region as previously described (Maziarz et al , ). Participant eligibility was restricted to children aged 1–15 years who had been residing in the geographically defined study area for at least four months (Peprah et al , ). To capture microgeographical factors that may correlate with unmeasured factors that influence malaria transmission risk (Ogwang et al , ), villages in the study area were categorized as rural or urban and as near or far from surface water (defined as a swamp, river, or lake).…”

“…To investigate these hypotheses, we leveraged data from the Epidemiology of Burkitt lymphoma in East African children and minors (EMBLEM) study (Legason et al , ; Peprah et al , ) to assess HLA associations with eBL risk in northern Uganda based on high‐resolution HLA sequencing.…”