TY - JOUR
T1 - Inverse association of falciparum positivity with endemic Burkitt lymphoma is robust in analyses adjusting for pre-enrollment malaria in the EMBLEM case-control study
AU - Peprah, Sally
AU - Ogwang, Martin D.
AU - Kerchan, Patrick
AU - Reynolds, Steven J.
AU - Tenge, Constance N.
AU - Were, Pamela A.
AU - Kuremu, Robert T.
AU - Wekesa, Walter N.
AU - Masalu, Nestory
AU - Kawira, Esther
AU - Otim, Isaac
AU - Legason, Ismail D.
AU - Ayers, Leona W.
AU - Bhatia, Kishor
AU - Goedert, James J.
AU - Pfeiffer, Ruth M.
AU - Mbulaiteye, Sam M.
N1 - Funding Information:
This work was supported by funding from the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health’ [Contracts HHSN261201100063C, HHSN261201100007I] plus by the Intramural Research Program, National Institute of Allergy and Infectious Diseases at the National Institutes of Health [support to SJR], Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Open Access funding provided by the National Institutes of Health (NIH).
Funding Information:
We thank the study population and communities for their participation. We thank Ms. Janet Lawler-Heavener at Westat Inc., (Rockville, MD, USA) and Mr. Erisa Sunday at the African Field Epidemiology Network (Kampala, Uganda) for managing the study. We are grateful to the leadership of the collaborating countries and institutions for hosting local field offices and laboratories and supporting the fieldwork. We thank Ms. Laurie Buck, Dr. Carol Giffen, Mr. Greg Rydzak and Mr. Jeremy Lyman at Information Management Services Inc. (Calverton, MD, USA) for coordinating data, and preparing data analysis files.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Falciparum 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. Methods: We 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. Results: The 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). Conclusion: Our 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.
AB - Background: Falciparum 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. Methods: We 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. Results: The 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). Conclusion: Our 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.
KW - Burkitt lymphoma
KW - Epidemiology
KW - Epstein-Barr virus
KW - Plasmodium falciparum
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U2 - 10.1186/s13027-021-00377-0
DO - 10.1186/s13027-021-00377-0
M3 - Article
C2 - 34099001
AN - SCOPUS:85107559366
SN - 1750-9378
VL - 16
JO - Infectious Agents and Cancer
JF - Infectious Agents and Cancer
IS - 1
M1 - 40
ER -