Se Eun Park1, Gi Deok Pak1, Peter Aaby2, Yaw Adu-Sarkodie3, Mohammad Ali4, Abraham Aseffa5, Holly M Biggs6, Morten Bjerregaard-Andersen2, Robert F Breiman7, John A Crump8, Ligia Maria Cruz Espinoza1, Muna Ahmed Eltayeb9, Nagla Gasmelseed9, Julian T Hertz6, Justin Im1, Anna Jaeger10, Leon Parfait Kabore11, Vera von Kalckreuth1, Karen H Keddy12, Frank Konings1, Ralf Krumkamp10, Calman A MacLennan13, Christian G Meyer14, Joel M Montgomery15, Aissatou Ahmet Niang16, Chelsea Nichols1, Beatrice Olack17, Ursula Panzner1, Jin Kyung Park1, Henintsoa Rabezanahary18, Raphaël Rakotozandrindrainy18, Emmanuel Sampo19, Nimako Sarpong20, Heidi Schütt-Gerowitt21, Arvinda Sooka22, Abdramane Bassiahi Soura23, Amy Gassama Sow24, Adama Tall16, Mekonnen Teferi5, Biruk Yeshitela5, Jürgen May10, Thomas F Wierzba1, John D Clemens25, Stephen Baker26, Florian Marks1. 1. International Vaccine Institute, Seoul, Republic of Korea. 2. Bandim Health Project, Bissau, Guinea-Bissau Research Center for Vitamins and Vaccines, Copenhagen, Denmark. 3. Kumasi Centre for Collaborative Research in Tropical Medicine School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. 4. International Vaccine Institute, Seoul, Republic of Korea Johns Hopkins University, Baltimore, Maryland. 5. Armauer Hansen Research Institute, Addis Ababa, Ethiopia. 6. Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina Kilimanjaro Christian Medical Centre, Moshi, Tanzania. 7. Centers for Disease Control and Prevention, Nairobi, Kenya Emory Global Health Institute, Emory University, Atlanta, Georgia. 8. Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina Kilimanjaro Christian Medical Centre, Moshi, Tanzania Duke Global Health Institute, Duke University, Durham, North Carolina Centre for International Health, University of Otago, Dunedin, New Zealand. 9. University of Gezira, Wad Medani, Sudan. 10. Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. 11. Schiphra Hospital, Ouagadougou, Burkina Faso. 12. National Institute for Communicable Diseases Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 13. Jenner Institute, Nuffield Department of Medicine, University of Oxford Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom. 14. Institute of Tropical Medicine, Eberhard-Karls University Tübingen, Germany. 15. Centers for Disease Control and Prevention, Nairobi, Kenya. 16. Institute Pasteur Senegal, Dakar. 17. Kenya Medical Research Institute (KEMRI), Nairobi. 18. University of Antananarivo, Madagascar. 19. Schiphra Hospital, Ouagadougou, Burkina Faso Institut Supérieur des Sciences de la Population, University of Ouagadougou, Burkina Faso. 20. Kumasi Centre for Collaborative Research in Tropical Medicine. 21. International Vaccine Institute, Seoul, Republic of Korea Institute of Medical Microbiology, University of Cologne, Germany. 22. National Institute for Communicable Diseases. 23. Institut Supérieur des Sciences de la Population, University of Ouagadougou, Burkina Faso. 24. Institute Pasteur Senegal, Dakar Université Cheikh Anta Diop de Dakar, Senegal. 25. International Vaccine Institute, Seoul, Republic of Korea International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka Fielding School of Public Health, University of California, Los Angeles. 26. Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Abstract
BACKGROUND: Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. METHODS: Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. RESULTS: A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2.44; P = .031) and gram-positive bacteremias, particularly Staphylococcus aureus, exhibited a high proportion of coinfection with Plasmodium malaria. Salmonella Typhimurium and Salmonella Enteritidis were the predominant NTS serovars (53/73; 73%). Both moderate (OR, 6.05; P = .0001) and severe (OR, 14.62; P < .0001) anemia were associated with iNTS disease. CONCLUSIONS: A positive correlation between iNTS disease and malaria endemicity, and the association between Plasmodium parasite positivity and iNTS disease across sub-Saharan Africa, indicates the necessity to consider iNTS as a major cause of febrile illness in malaria-holoendemic areas. Prevention of iNTS disease through iNTS vaccines for areas of high malaria endemicity, targeting high-risk groups for Plasmodium parasitic infection, should be considered.
BACKGROUND: Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria. METHODS: Febrile patients received a blood culture and a malaria test. Isolated bacteria underwent antimicrobial susceptibility testing, and the association between iNTS disease and malaria was assessed. RESULTS: A positive correlation between frequency proportions of malaria and iNTS was observed (P = .01; r = 0.70). Areas with higher burden of malaria exhibited higher odds of iNTS disease compared to other bacterial infections (odds ratio [OR], 4.89; 95% CI, 1.61-14.90; P = .005) than areas with lower malaria burden. Malaria parasite positivity was associated with iNTS disease (OR, 2.44; P = .031) and gram-positive bacteremias, particularly Staphylococcus aureus, exhibited a high proportion of coinfection with Plasmodiummalaria. Salmonella Typhimurium and Salmonella Enteritidis were the predominant NTS serovars (53/73; 73%). Both moderate (OR, 6.05; P = .0001) and severe (OR, 14.62; P < .0001) anemia were associated with iNTS disease. CONCLUSIONS: A positive correlation between iNTS disease and malaria endemicity, and the association between Plasmodium parasite positivity and iNTS disease across sub-Saharan Africa, indicates the necessity to consider iNTS as a major cause of febrile illness in malaria-holoendemic areas. Prevention of iNTS disease through iNTS vaccines for areas of high malaria endemicity, targeting high-risk groups for Plasmodiumparasitic infection, should be considered.
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