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.
What's new?
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub‐Saharan Africa, but there have been few epidemiologic studies. In this multi‐country analysis, the authors used harmonized protocols to investigate infectious, environmental, and other risk factors for eBL. Socioeconomic status and recent malarial fever were associated with reduced eBL risk, while HIV infection, previous malaria, and living in areas targeted for malaria suppression increased eBL risk. These results provide new baseline data regarding eBL epidemiology, indicating that malaria may play a role. They also confirm the feasibility of multi‐site, population‐based enrolment for crucial future eBL studies.
Endemic Burkitt lymphoma (eBL) is an aggressive B cell non-Hodgkin lymphoma associated with antigenic stimulation from Plasmodium falciparum malaria. Whether eBL risk is related to malaria parasite ...density is unknown. To address this issue, children with eBL, asymptomatic and clinical malaria, as a surrogate of malaria parasite density, were assessed.
Malaria-related laboratory results (parasite density, haemoglobin, platelet count, and white cell count WBC) count) were compiled for 4019 eBL cases and 80,532 subjects evaluated for asymptomatic malaria or clinical malaria (severe malaria anaemia, hyperparasitaemia, cerebral malaria, malaria prostration, moderate malaria, and mild malaria) in 21 representative studies published in Africa (mostly East Africa) and 850 eBL cases and 2878 controls with primary data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) case-control study in Uganda, Tanzania, and Kenya. The average values of malaria-related laboratory results were computed by condition and trends across single-year age groups were assessed using regression and spline models.
Overall, malaria infection or malaria was diagnosed in 37,089 of children compiled from the literature. Children with eBL and asymptomatic parasitaemia/antigenaemia, but not those with clinical malaria, were closest in their mean age (age 7.1-7.2 vs. 7.4-9.8 years), haemoglobin level (10.0-10.4 vs. 11.7-12.3 g/dL), malaria parasite density (2800 vs. 1827-7780 parasites/µL), platelet count (347,000-353,000 vs. 244,000-306,000 platelets/µL), and WBC count (8180-8890 vs. 7100-7410 cells/µL). Parasite density in these two groups peaked between four to five years, then decreased steadily thereafter; conversely, haemoglobin showed a corresponding increase with age. Children with clinical malaria were markedly different: all had an average age below 5 years, had dramatically elevated parasite density (13,905-869,000 parasites/µL) and dramatically decreased platelet count (< 159,000 platelets/µL) and haemoglobin (< 7 g/dL).
eBL and asymptomatic parasitaemia/antigenaemia, but not clinical malaria, were the most similar conditions with respect to mean age and malaria-related laboratory results. These results suggest that children with asymptomatic parasitaemia/antigenaemia may be the population at risk of eBL.
Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma that significantly contributes to childhood cancer burden in sub‐Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically ...associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria—such as the sickle cell trait variant, HBB‐rs334(T)—also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome‐scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB‐rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628–0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533–0.885; p = .0037). ABO‐rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379–0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.
The association between Burkitt lymphoma (BL) with malaria resistance was analyzed in a case–control study conducted in children from four countries in Africa. Results indicate that the odds of BL were lower in children with genetic resistance due to the sickle cell trait or a variant linked to blood group O and apparent immunity indicated by low‐ grade asymptomatic infection.
Summary
Platelet counts are decreased in Plasmodium falciparum malaria, which is aetiologically linked with endemic Burkitt lymphoma (eBL). However, the pattern of platelet counts in eBL cases is ...unknown. We studied platelet counts in 582 eBL cases and 2 248 controls enrolled in a case‐control study in Uganda, Tanzania and Kenya (2010–2016). Mean platelet counts in controls or eBL cases with or without malaria‐infection in controls versus eBLcases were compared using Student’s t‐test. Odds ratios (ORs) and two‐sided 95% confidence intervals (95% CIs) were estimated using multiple logistic regression, controlling for age, sex, haemoglobin and white blood cell counts. Platelets were decreased with malaria infection in the controls 263 vs. 339 × 109 platelets/l, P < 0·0001; adjusted OR (aOR) = 3·42, 95% CI: 2·79–4·18 and eBL cases (314 vs. 367 × 109 platelets/l, P‐value = 0·002; aOR = 2·36, 95% CI: 1·49–3·73). Unexpectedly, platelets were elevated in eBL cases versus controls in overall analyses (mean: 353 vs. 307 × 109 platelets/l, P < 0·0001; aOR = 1·41; 95% CI: 1·12–1·77), and when restricted to malaria‐positive (mean 314 vs. 263 × 109 platelets/l, P < 0·0001; OR = 2·26; 95% CI: 1·56–3·27) or malaria‐negative (mean 367 vs. 339 × 109 platelets/l, P < 0·001; OR = 1·46; 95% CI: 1·17–1·83) subjects. Platelets were decreased with malaria infection in controls and eBL cases but elevated with eBL.
Objectives
Northern Tanzania experiences significant malaria‐related morbidity and mortality, but accurate data are scarce. We update the data on patterns of low‐grade Plasmodium falciparum malaria ...infection among children in northern Tanzania.
Methods
Plasmodium falciparum malaria prevalence (pfPR) was assessed in a representative sample of 819 children enrolled in 94 villages in northern Tanzania between October 2015 and August 2016, using a complex survey design. Individual‐ and household‐level risk factors for pfPR were elicited using structured questionnaires. pfPR was assessed using rapid diagnostic tests (RDTs) and thick film microscopy (TFM). Associations with pfPR, based on RDT, were assessed using adjusted odds ratios (aOR) and confidence intervals (CI) from weighted survey logistic regression models.
Results
Plasmodium falciparum malaria prevalence (pfPR) was 39.5% (95% CI: 31.5, 47.5) by RDT and 33.4% (26.0, 40.6) by TFM. pfPR by RDT was inversely associated with higher‐education parents, especially mothers (5–7 years of education: aOR 0.55; 95% CI: 0.31, 0.96, senior secondary education: aOR 0.10; 95% CI: 0.02, 0.55), living in a house near the main road (aOR 0.34; 95% CI: 0.15, 0.76), in a larger household (two rooms: aOR 0.40; 95% CI: 0.21, 0.79, more than two rooms OR 0.35; 95% CI: 0.20, 0.62). Keeping a dog near or inside the house was positively associated with pfPR (aOR 2.01; 95% CI: 1.26, 3.21). pfPR was not associated with bed‐net use or indoor residual spraying.
Conclusions
Nearly 40% of children in northern Tanzania had low‐grade malaria antigenaemia. Higher parental education and household metrics but not mosquito bed‐net use were inversely associated with pfPR.
Objectifs
La Tanzanie connaît une morbidité et une mortalité importantes liées au paludisme, mais les données précises sont rares. Nous mettons à jour les données sur les profils en matière d'infection par le paludisme à Plasmodium falciparum de faible grade chez les enfants dans le nord de la Tanzanie.
Méthodes
La prévalence du paludisme à P. falciparum (pfPR) a été évaluée sur un échantillon représentatif de 819 enfants inscrits dans 94 villages dans le nord de la Tanzanie entre octobre 2015 et août 2016, à l'aide d'un plan d'enquête complexe. Des facteurs de risque de pfPR au niveau individuel et au niveau du ménage ont été déterminés à l'aide de questionnaires structurés. La pfPR a été évaluée à l'aide de tests de diagnostic rapides (TDR) et de microscopie à film épais (TFM). Les associations avec la pfPR, sur la base des TDR, ont été évaluées à l'aide des rapports de cotes ajustés (aOR) et des intervalles de confiance (IC) de modèles de régression logistique de surveillances pondérées.
Résultats
La pfPR était de 39,5% (IC95%: 31,5–47,5) avec les TDR et de 33,4% (26,0–40,6) avec la TFM. La pfPR par les TDR était inversement associée aux parents avec un niveau d’éducation plus élevé, en particulier les mères (5‐7 ans d’études: aOR: 0,55; IC95%: 0,31–0,96, enseignement secondaire supérieur: aOR: 0,10; IC95%: 0,02–0,55), vivre dans une maison proche de la route principale (aOR: 0,34; IC95%: 0,15–0,76), dans un ménage plus grand (2 chambres: aOR: 0,40; IC95%: 0,21–0,79, plus de 2 pièces aOR: 0,35; IC95%: 0,20–0,62). Garder un chien près ou à l'intérieur de la maison était positivement associé à la pfPR (aOR: 2,01; IC95%: 1,26–3,21). La pfPR n’était pas associée à l'utilisation de moustiquaire ou à la pulvérisation de résidus à l'intérieur.
Conclusions
Près de 40% des enfants dans nord de la Tanzanie présentaient une antigénémie paludéenne de faible grade. Un niveau d’éducation parentale plus élevé et les indicateurs du ménage, mais pas l'utilisation de moustiquaires, étaient inversement associés à la pfPR.
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