Nobuko Arisue1, George Chagaluka2, Nirianne Marie Q Palacpac3, W Thomas Johnston4, Nora Mutalima4,5, Sally Peprah6, Kishor Bhatia6, Eric Borgstein2, George N Liomba2, Steve Kamiza2, Nyengo Mkandawire2, Collins Mitambo7, James J Goedert6, Elizabeth M Molyneux2, Robert Newton4, Toshihiro Horii3, Sam M Mbulaiteye6. 1. Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. 2. Departments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, Malawi. 3. Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. 4. Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York YO10 5DD, UK. 5. Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK. 6. Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 7. National Health Sciences Research Committee, Research Department, Ministry of Health, P.O. Box 30377, Capital City, Lilongwe 3, 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.
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 Pfinfection 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 PfSERA5infection 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 Pfsera5infection 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 PfSERA5infection 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 Pfinfection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pfinfection in eBL.
Authors: Hsiao-Mei Liao; Hebing Liu; Pei-Ju Chin; Bingjie Li; Guo-Chiuan Hung; Shien Tsai; Isaac Otim; Ismail D Legason; Martin D Ogwang; Steven J Reynolds; Patrick Kerchan; Constance N Tenge; Pamela A Were; Robert T Kuremu; Walter N Wekesa; Nestory Masalu; Esther Kawira; Leona W Ayers; Ruth M Pfeiffer; Kishor Bhatia; James J Goedert; Shyh-Ching Lo; Sam M Mbulaiteye Journal: Front Oncol Date: 2022-03-07 Impact factor: 6.244
Authors: Sally Peprah; Martin D Ogwang; Patrick Kerchan; Steven J Reynolds; Constance N Tenge; Pamela A Were; Robert T Kuremu; Walter N Wekesa; Nestory Masalu; Esther Kawira; Isaac Otim; Ismail D Legason; Leona W Ayers; Kishor Bhatia; James J Goedert; Ruth M Pfeiffer; Sam M Mbulaiteye Journal: Infect Agent Cancer Date: 2021-06-07 Impact factor: 2.965