Mean platelet counts are relatively decreased with malaria but relatively increased with endemic Burkitt Lymphoma in Uganda, Tanzania, and Kenya

Abstract

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.

Inverse association of falciparum positivity with endemic Burkitt lymphoma is robust in analyses adjusting for pre-enrollment malaria in the EMBLEM case-control study

“…The results were significant in stratified analyses by age (< 5 years versus ≥10 years or older), which is a surrogate for age-related acquired immunity against malaria. These results are similar to those reported in two studies that did not control for pre-enrollment anti-malaria treatment [ 23 , 34 ] and those in our previous analyses that included a limited adjustment for a few variables about pre-enrollment anti-malaria treatment [ 24 , 33 ]. Our findings, based on the most comprehensive adjustment of pre-enrollment exposures and for other risk factors of eBL and stratified analyses, reduce support for the null hypothesis that pre-enrollment anti-malaria treatment is the major explanation for the observed low falciparum positivity among eBL patients, on one hand, and increase support for exploring alternative hypotheses, on the other hand.…”

“…The associations did not change when we included the aforementioned factors in the logistic regression model to control for pre-enrollment anti-malaria treatment (aOR = 0.46, 95% CI: 0.37, 0.56). The inverse association remained robust (aOR = 0.45, 95% CI 0.35, 0.59, P < 0.0001) when we further adjusted for mean platelet count, hemoglobin, and WBC count as confounders [ 33 ] and in stratified analysis for children < 5 years (aOR = 0.46; 95% CI: 0.29, 0.75) and those ≥10 years (aOR = 0.47; 95% CI: 0.32, 0.71), and was significant in country-specific analyses (aOR = 0.54 in Uganda, aOR = 0.48 in Tanzania and aOR = 0.30 in Kenya; Supplementary Table 4 ).…”

“…Our study found significantly lower prevalence of falciparum positivity, defined as any, recent, or current falciparum infection, in eBL patients than controls in crude and adjusted analyses. The ORs did not change when we adjusted for Inpatient malaria and Outpatient malaria factors as surrogates of pre-enrollment anti-malaria treatment, for the other four factors obtained from EFA, for platelets, low hemoglobin, and elevated white cell counts, which are risk factors for eBL [ 33 ]. The results were significant in stratified analyses by age (< 5 years versus ≥10 years or older), which is a surrogate for age-related acquired immunity against malaria.…”

Functional changes in hemostasis during asexual and sexual parasitemia in a controlled human malaria infection

“…Overall, our findings confirm previous observations by our group that platelets are not or only mildly activated during early asexual parasitemia in CHMI and that platelet activation is unlikely to explain the early drop in platelet count [27]. Our findings also do not provide evidence that activation of coagulation, and more specific thrombin, underlies the decrease in platelet count [28][29][30]. We assessed activation of the coagulation by measuring plasma concentrations of different plasma pro-and anticoagulation markers, as well as assays of TG and thrombin dynamics [31,32].…”

Platelets beyond their count, as a key element of the innate immune system in the fight against malaria

“…But what happens to platelet count in those subjects that develop eBL? The case control study conducted from 2010 to 2016 in Uganda, Tanzania and Kenya, and published in this issue of the Journal, 7 reveals for the first time the differences in terms of platelet count between patients with eBL and controls, with or without active malaria infection. And, above all, it strives to make sense of platelet counts themselves, providing interesting insights for clinical and preclinical research.…”