The Relationship Between Invasive Nontyphoidal Salmonella Disease, Other Bacterial Bloodstream Infections, and Malaria in Sub-Saharan Africa


Se Eun Park, Gi Deok Pak, Peter Aaby, Yaw Adu-Sarkodie, Mohammad Ali, Abraham Aseffa, Holly M. Biggs, Morten Bjerregaard-Andersen, Robert F. Breiman, John A. Crump, Ligia Maria Cruz Espinoza, Muna Ahmed Eltayeb, Nagla Gasmelseed, Julian T. Hertz, Justin Im, Anna Jaeger, Leon Parfait Kabore, Vera von Kalckreuth, Karen H. Keddy, Frank Konings, Ralf Krumkamp, Calman A. MacLennan, Christian G. Meyer, Joel M. Montgomery, Aissatou Ahmet Niang, Chelsea Nichols, Beatrice Olack, Ursula Panzner, Jin Kyung Park, Henintsoa Rabezanahary, Raphaël Rakotozandrindrainy, Emmanuel Sampo, Nimako Sarpong, Heidi Schütt-Gerowitt, Arvinda Sooka, Abdramane Bassiahi Soura, Amy Gassama Sow, Adama Tall, Mekonnen Teferi, Biruk Yeshitela, Jürgen May, Thomas F. Wierzba, John D. Clemens, Stephen Baker, and Florian Marks


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.


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