Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi
Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to <i>Plasmodium falciparum</i> (<i>Pf</i>) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of <i>Pf</i> g...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/7/1692 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nobuko Arisue |
| collection | DOAJ |
| description | Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to <i>Plasmodium falciparum</i> (<i>Pf</i>) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of <i>Pf</i> genetic diversity is unclear. A potential role of <i>Pf</i> genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of <i>Pf</i> infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher <i>Pf</i> 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 <i>Pf-</i>serine repeat antigen-5 (<i>Pfsera5</i>), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all <i>Pf</i> polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed <i>Pfsera5</i> PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed <i>Pf</i>SERA5 infection status. The patterns of <i>Pfsera5</i> PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed <i>Pfsera5</i> infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured <i>Pf</i> genetic diversity. Results: <i>Pfsera5</i> PCR was positive in 108 eBL cases and 70 controls. Mixed <i>Pf</i>SERA5 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 <i>Pf</i> infection is increased with eBL and suggest that measuring <i>Pf</i> genetic diversity may provide new insights into the role of <i>Pf</i> infection in eBL. |
| first_indexed | 2024-03-10T12:38:27Z |
| format | Article |
| id | doaj.art-34034d5a678f4ac9b39bb8d179d3e281 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:38:27Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-34034d5a678f4ac9b39bb8d179d3e2812023-11-21T14:04:29ZengMDPI AGCancers2072-66942021-04-01137169210.3390/cancers13071692Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in MalawiNobuko Arisue0George Chagaluka1Nirianne Marie Q. Palacpac2W. Thomas Johnston3Nora Mutalima4Sally Peprah5Kishor Bhatia6Eric Borgstein7George N. Liomba8Steve Kamiza9Nyengo Mkandawire10Collins Mitambo11James J. Goedert12Elizabeth M. Molyneux13Robert Newton14Toshihiro Horii15Sam M. Mbulaiteye16Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanDepartments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, MalawiDepartment of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanEpidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York YO10 5DD, UKEpidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York YO10 5DD, UKInfections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAInfections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, MalawiDepartments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, MalawiDepartments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, MalawiDepartments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, MalawiNational Health Sciences Research Committee, Research Department, Ministry of Health, P.O. Box 30377, Capital City, Lilongwe 3, MalawiInfections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartments of Pediatrics and Surgery, College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, MalawiEpidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, York YO10 5DD, UKDepartment of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanInfections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USABackground: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to <i>Plasmodium falciparum</i> (<i>Pf</i>) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of <i>Pf</i> genetic diversity is unclear. A potential role of <i>Pf</i> genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of <i>Pf</i> infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher <i>Pf</i> 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 <i>Pf-</i>serine repeat antigen-5 (<i>Pfsera5</i>), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all <i>Pf</i> polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed <i>Pfsera5</i> PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed <i>Pf</i>SERA5 infection status. The patterns of <i>Pfsera5</i> PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed <i>Pfsera5</i> infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured <i>Pf</i> genetic diversity. Results: <i>Pfsera5</i> PCR was positive in 108 eBL cases and 70 controls. Mixed <i>Pf</i>SERA5 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 <i>Pf</i> infection is increased with eBL and suggest that measuring <i>Pf</i> genetic diversity may provide new insights into the role of <i>Pf</i> infection in eBL.https://www.mdpi.com/2072-6694/13/7/1692<i>Plasmodium falciparum</i>Burkitt lymphomaEpstein Barr virusepidemiologyAfricacomplexity of infection |
| spellingShingle | 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 Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi Cancers <i>Plasmodium falciparum</i> Burkitt lymphoma Epstein Barr virus epidemiology Africa complexity of infection |
| title | Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi |
| title_full | Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi |
| title_fullStr | Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi |
| title_full_unstemmed | Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi |
| title_short | Assessment of Mixed <i>Plasmodium falciparum</i> <i>sera5</i> Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi |
| title_sort | assessment of mixed i plasmodium falciparum i i sera5 i infection in endemic burkitt lymphoma a case control study in malawi |
| topic | <i>Plasmodium falciparum</i> Burkitt lymphoma Epstein Barr virus epidemiology Africa complexity of infection |
| url | https://www.mdpi.com/2072-6694/13/7/1692 |
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