Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma: A case-control study in Malawi

Nobuko Arisue; George Chagaluka; Nirianne Marie Q. Palacpac; W. Thomas Johnston; Nora Mutalima; Sally Peprah; Kishor Bhatia; Eric Borgstein; George N. Liomba; Steve Kamiza; Nyengo Mkandawire; Collins Mitambo; James J. Goedert; Elizabeth M. Molyneux; Robert Newton; Toshihiro Horii; Sam M. Mbulaiteye

doi:10.3390/cancers13071692

Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma: A case-control study in Malawi

Nobuko Arisue, George Chagaluka, Nirianne Marie Q. Palacpac, W. Thomas Johnston, Nora Mutalima, Sally Peprah, Kishor Bhatia, Eric Borgstein, George N. Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, James J. Goedert, Elizabeth M. Molyneux, Robert Newton, Toshihiro Horii, Sam M. Mbulaiteye^*

^*Corresponding author for this work

Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to Plasmodium falciparum (Pf) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of Pf genetic diversity is unclear. A potential role of Pf genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of Pf infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher Pf genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in Pf-serine repeat antigen-5 (Pfsera5), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all Pf polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed Pfsera5 PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed PfSERA5 infection status. The patterns of Pfsera5 PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed Pfsera5 infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured Pf genetic diversity. Results: Pfsera5 PCR was positive in 108 eBL cases and 70 controls. Mixed PfSERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12–4.26, which remained significant in adjusted results (adjusted odds ratio [aOR] of 2.40, 95% CI of 1.11–5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL. Conclusions: Our results increase the evidence supporting the hypothesis that infection with mixed Pf infection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pf infection in eBL.

Original language	English
Article number	1692
Journal	Cancers
Volume	13
Issue number	7
DOIs	https://doi.org/10.3390/cancers13071692
Publication status	Published - 2 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

Africa
Burkitt lymphoma
Complexity of infection
Epidemiology
Epstein Barr virus
Plasmodium falciparum

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Arisue, N., Chagaluka, G., Palacpac, N. M. Q., Thomas Johnston, W., Mutalima, N., Peprah, S., Bhatia, K., Borgstein, E., Liomba, G. N., Kamiza, S., Mkandawire, N., Mitambo, C., Goedert, J. J., Molyneux, E. M., Newton, R., Horii, T., & Mbulaiteye, S. M. (2021). Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma: A case-control study in Malawi. Cancers, 13(7), Article 1692. https://doi.org/10.3390/cancers13071692

@article{a023d2e3698141dc8e6db23976c225a0,

title = "Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma: A case-control study in Malawi",

abstract = "Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to Plasmodium falciparum (Pf) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of Pf genetic diversity is unclear. A potential role of Pf genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of Pf infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher Pf genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in Pf-serine repeat antigen-5 (Pfsera5), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all Pf polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed Pfsera5 PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed PfSERA5 infection status. The patterns of Pfsera5 PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed Pfsera5 infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured Pf genetic diversity. Results: Pfsera5 PCR was positive in 108 eBL cases and 70 controls. Mixed PfSERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12–4.26, which remained significant in adjusted results (adjusted odds ratio [aOR] of 2.40, 95% CI of 1.11–5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL. Conclusions: Our results increase the evidence supporting the hypothesis that infection with mixed Pf infection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pf infection in eBL.",

keywords = "Africa, Burkitt lymphoma, Complexity of infection, Epidemiology, Epstein Barr virus, Plasmodium falciparum",

author = "Nobuko Arisue and George Chagaluka and Palacpac, {Nirianne Marie Q.} and {Thomas Johnston}, W. and Nora Mutalima and Sally Peprah and Kishor Bhatia and Eric Borgstein and Liomba, {George N.} and Steve Kamiza and Nyengo Mkandawire and Collins Mitambo and Goedert, {James J.} and Molyneux, {Elizabeth M.} and Robert Newton and Toshihiro Horii and Mbulaiteye, {Sam M.}",

year = "2021",

month = apr,

day = "2",

doi = "10.3390/cancers13071692",

language = "English",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute",

number = "7",

}

Arisue, N, Chagaluka, G, Palacpac, NMQ, Thomas Johnston, W , Mutalima, N, Peprah, S, Bhatia, K, Borgstein, E, Liomba, GN, Kamiza, S, Mkandawire, N, Mitambo, C, Goedert, JJ, Molyneux, EM, Newton, R, Horii, T & Mbulaiteye, SM 2021, 'Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma: A case-control study in Malawi', Cancers, vol. 13, no. 7, 1692. https://doi.org/10.3390/cancers13071692

TY - JOUR

T1 - Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma

T2 - A case-control study in Malawi

AU - Arisue, Nobuko

AU - Chagaluka, George

AU - Palacpac, Nirianne Marie Q.

AU - Thomas Johnston, W.

AU - Mutalima, Nora

AU - Peprah, Sally

AU - Bhatia, Kishor

AU - Borgstein, Eric

AU - Liomba, George N.

AU - Kamiza, Steve

AU - Mkandawire, Nyengo

AU - Mitambo, Collins

AU - Goedert, James J.

AU - Molyneux, Elizabeth M.

AU - Newton, Robert

AU - Horii, Toshihiro

AU - Mbulaiteye, Sam M.

PY - 2021/4/2

Y1 - 2021/4/2

N2 - Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to Plasmodium falciparum (Pf) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of Pf genetic diversity is unclear. A potential role of Pf genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of Pf infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher Pf genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in Pf-serine repeat antigen-5 (Pfsera5), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all Pf polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed Pfsera5 PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed PfSERA5 infection status. The patterns of Pfsera5 PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed Pfsera5 infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured Pf genetic diversity. Results: Pfsera5 PCR was positive in 108 eBL cases and 70 controls. Mixed PfSERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12–4.26, which remained significant in adjusted results (adjusted odds ratio [aOR] of 2.40, 95% CI of 1.11–5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL. Conclusions: Our results increase the evidence supporting the hypothesis that infection with mixed Pf infection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pf infection in eBL.

AB - Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to Plasmodium falciparum (Pf) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of Pf genetic diversity is unclear. A potential role of Pf genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of Pf infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher Pf genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in Pf-serine repeat antigen-5 (Pfsera5), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all Pf polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed Pfsera5 PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed PfSERA5 infection status. The patterns of Pfsera5 PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed Pfsera5 infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured Pf genetic diversity. Results: Pfsera5 PCR was positive in 108 eBL cases and 70 controls. Mixed PfSERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12–4.26, which remained significant in adjusted results (adjusted odds ratio [aOR] of 2.40, 95% CI of 1.11–5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL. Conclusions: Our results increase the evidence supporting the hypothesis that infection with mixed Pf infection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pf infection in eBL.

KW - Africa

KW - Burkitt lymphoma

KW - Complexity of infection

KW - Epidemiology

KW - Epstein Barr virus

KW - Plasmodium falciparum

UR - http://www.scopus.com/inward/record.url?scp=85103485178&partnerID=8YFLogxK

U2 - 10.3390/cancers13071692

DO - 10.3390/cancers13071692

M3 - Article

AN - SCOPUS:85103485178

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 7

M1 - 1692

ER -

Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma: A case-control study in Malawi

Abstract

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Keywords

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