Abstract
BackgroundFalciparum and endemic Burkitt lymphoma (eBL) are co-endemic in Africa, but the malaria experience in eBL patients is unknown. A lower prevalence of falciparum has been reported in eBL patients, but those results are anecdotally attributed to pre-enrollment anti-malaria treatment.MethodsWe studied 677 eBL patients and 2920 community controls aged 0–15 years enrolled in six regions in Uganda, Tanzania, and Kenya during 2010–2016. Falciparum was diagnosed using thick blood film microscopy (TFM) and antigen-capture rapid diagnostic tests (RDTs). Guardians of the children answered a 40-item structured questionnaire about their child’s pre-enrollment lifetime malaria history and treatment, demographics, socioeconomics, animal exposures, fevers, and hospitalizations. We utilized exploratory factor analysis to reduce the 40 questionnaire variables into six factors, including Inpatient malaria and Outpatient malaria factors that were surrogates of pre-enrollment anti-malaria treatment. The six factors accounted for 83–90% of the variance in the questionnaire data. We calculated odds ratios and 95% confidence intervals (OR 95% CI) of association of eBL with falciparum positivity, defined as positive both on TFM or RDTs, or only RDTs (indicative of recent infection) or TFM (indicative of current falciparum infection) versus no infection, using multivariable logistic regression, controlling for group of age (0–2, 3–5, 6–8, 9–11 and 12–15 years), sex, and study site and the afore-mentioned pre-enrollment factors.ResultsThe prevalence of falciparum infection was 25.6% in the eBL cases and 45.7% in community controls (aOR = 0.43, 95% CI: 0.40, 0.47; P < 0.0001). The results were similar for recent falciparum infection (6.9% versus 13.5%, aOR = 0.44, 95% CI: 0.38, 0.50; P < 0.0001) and current falciparum infection (18.7% versus 32.1%, aOR = 0.47, 95% CI: 0.43, 0.51; P < 0.0001). These aORs for any, recent and current falciparum infection did not change when we adjusted for pre-enrollment factors (aORs = 0.46, =0.44, and = 0.51, respectively) were significantly lower in stratified analysis for any infection in children < 5 years (aOR = 0.46; 95% CI: 0.29, 0.75) or ≥ 10 years (aOR = 0.47; 95% CI: 0.32, 0.71).ConclusionOur study results reduce support for pre-enrollment antimalaria treatment as a sole explanation for the observed lower falciparum prevalence in eBL cases and open a space to consider alternative immunology-based hypotheses.
Highlights
Endemic Burkitt lymphoma is an aggressive germinal-center (GC) B-cell non-Hodgkin lymphoma [1] first described in African children by Denis Burkitt in 1958 [2]
This hypothesis has been supported by findings that endemic Burkitt lymphoma (eBL) patients are more likely than controls to have evidence of prior malaria, as measured by higher anti-malaria antibody titers in plasma [4,5,6], and less likely to be protected from malaria, as measured by carriage of genetic variants that protect against malaria [7, 8]
Both eBL cases and controls were tested for falciparum infection using thick blood film microscopy (TFM) and commercial antigen rapid diagnostic tests
Summary
Endemic Burkitt lymphoma (eBL) is an aggressive germinal-center (GC) B-cell non-Hodgkin lymphoma [1] first described in African children by Denis Burkitt in 1958 [2]. Epidemiological studies noted a geographical correlation of Plasmodium falciparum with eBL, which opened the hypothesis about whether this correlation was evidence of causation [3]. This hypothesis has been supported by findings that eBL patients are more likely than controls to have evidence of prior malaria, as measured by higher anti-malaria antibody titers in plasma [4,5,6], and less likely to be protected from malaria, as measured by carriage of genetic variants that protect against malaria [7, 8]. A lower prevalence of falciparum has been reported in eBL patients, but those results are anecdotally attributed to pre-enrollment anti-malaria treatment
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