Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda

Abstract

BackgroundFalciparum malaria is an important risk factor for African Burkitt lymphoma (BL), but few studies have evaluated malaria patterns in healthy BL-age children in populations where both diseases are endemic. To obtain accurate current data, patterns of asymptomatic malaria were investigated in northern Uganda, where BL is endemic.MethodsBetween 2011 and 2015, 1150 apparently healthy children under 15 years old were sampled from 100 villages in northern Uganda using a stratified, multi-stage, cluster survey design. Falciparum malaria prevalence (pfPR) was assessed by questionnaire, rapid diagnostic test (RDT) and thick film microscopy (TFM). Weighted pfPR and unadjusted and adjusted associations of prevalence with covariates were calculated using logistic models and survey methods.ResultsBased on 1143 children successfully tested, weighted pfPR was 54.8% by RDT and 43.4% by TFM. RDT sensitivity and specificity were 97.5 and 77.8%, respectively, as compared to TFM, because RDT detect malaria antigens, which persist in peripheral blood after clinical malaria, thus results based on RDT are reported. Weighted pfPR increased from 40% in children aged under 2 years to 61.8% in children aged 6–8 years (odds ratio 2.42, 95% confidence interval (CI) 1.26–4.65), then fell slightly to 49% in those aged 12–15 years. Geometric mean parasite density was 1805.5 parasites/µL (95% CI 1344.6–2424.3) among TFM-positive participants, and it was higher in children aged <5 years at 5092.9/µL (95% CI 2892.7–8966.8) and lower in those aged ≥10 years at 983.8/µL (95% CI 472.7–2047.4; P = 0.001). Weighted pfPR was lower in children residing in sub-regions employing indoor residual spraying (IRS) than in those residing in non-IRS sub-regions (32.8 versus 65.7%; OR 0.26, 95% CI 0.14, 0.46). However, pfPR varied both within IRS (3.2–55.3%) and non-IRS sub-regions (29.8–75.8%; Pheterogeneity <0.001). pfPR was inversely correlated with a child’s mother’s income (P = 0.011) and positively correlated with being enrolled in the wet season (P = 0.076), but sex was irrelevant.ConclusionsThe study observed high but geographically and demographically heterogenous patterns of asymptomatic malaria prevalence among children living in northern Uganda. These results provide important baseline data that will enable precise evaluation of associations between malaria and BL.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1778-z) contains supplementary material, which is available to authorized users.

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

“…The ecosystem in the geographic area was characterized by lakes, rivers and swamps, and supports perennial but variable holoendemic malaria transmission for >6 months in the year, except in parts of Kenya where malaria is seasonal and lasts for shorter durations . The selected geographic areas have historically had notable BL endemicity . We considered several choices of controls, including health‐facility, school or neighborhood controls.…”

“…Neighborhood controls were considered but rejected because of logistical challenges required to maintain consistent quality of work (a control can only be enrolled after a case has been encountered) across multiple sites in different countries and concerns about low response rates . Therefore, we enrolled population‐based controls of a similar age distribution as the cases sampled from 300 random villages (100 villages per country) selected from national census roster according to urban/rural status and proximity to water, as previously described . The key assumption of this approach was that children residing in the same area as the cases would be exposed to similar exposures when broadly matched for age, geography and sex .…”

“…The key assumption of this approach was that children residing in the same area as the cases would be exposed to similar exposures when broadly matched for age, geography and sex . Before sampling, villages in the census roster were categorized as “rural” based on having a census enumeration area (EA) population count of children below 15 years being less than the EA mean population count, otherwise as “urban.” Villages were further classified as near water (swamp, river or lake) based on the EA boundary being within 500 m of surface water, otherwise as far from water based on geographical information maps.…”

“…All subjects provided venous blood specimens (collected pretreatment in the cases) for research (10 ml) and for clinical tests (4 ml) in EDTA tubes. Clinical specimens were immediately examined by light microscopy for asexual malaria parasite forms and for malaria antigens (HRP‐2 and pan‐LDH) using commercial malaria rapid diagnostic tests (malaria‐RDTs) . Malaria antigens remain detectable by RDTs for 35–42 days after treatment of symptomatic malaria .…”

“…Therefore, we enrolled suspected eBL cases and population‐based controls in six rural malaria‐endemic areas in Northern Uganda, Northeastern Tanzania and Western Kenya (Fig. ) in the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study during 2010–2016 …”