Dataset Information

Malaria parasite-mediated alteration of macrophage function and increased iron availability predispose to disseminated non-typhoidal Salmonella infection.

ABSTRACT: Disseminated infections with non-typhoidal Salmonella (NTS) are a significant cause of child mortality in sub-Saharan Africa. NTS infection in children is clinically associated with malaria, suggesting that malaria compromises control of disseminated NTS infection. To study the mechanistic basis for increased NTS susceptibility, we utilized a model of concurrent infection with Salmonella enterica serotype Typhimurium and Plasmodium yoelii Underlying malaria blunted monocyte expression of Ly6C, a marker for inflammatory activation, and impaired recruitment of inflammatory cells to the liver. Hepatic mononuclear phagocytes expressed lower levels of iNOS, TNFα and GM-CSF and increased production of IL-10 and heme oxygenase-1, indicating that that underlying malaria modifies the activation state and inflammatory response of mononuclear phagocytes to NTS. P. yoelii infection also increased intracellular iron levels in liver mononuclear cells, as evidenced by elevated levels of ferritin and by rescue of a S. Typhimurium tonBfeoB mutant defective for iron uptake. In addition, concurrent P. yoelii infection partially rescued the systemic colonization defect of a S Typhimurium spiB mutant defective for type III secretion system-2 (T3SS-2), indicating that the ability of phagocytic cells to limit spread of S. Typhimurium is impaired during concurrent P. yoelii infection. These results show that concurrent malaria increases susceptibility to disseminated NTS infection by blunting macrophage bactericidal mechanisms and providing an essential nutrient that enhances bacterial growth.

SUBMITTER: Lokken KL

PROVIDER: S-EPMC6105891 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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Malaria Parasite-Mediated Alteration of Macrophage Function and Increased Iron Availability Predispose to Disseminated Nontyphoidal Salmonella Infection.

Lokken Kristen L KL Stull-Lane Annica R AR Poels Kikkie K Tsolis Renée M RM

Infection and immunity 20180822 9

Disseminated infections with nontyphoidal Salmonella (NTS) are a significant cause of child mortality in sub-Saharan Africa. NTS infection in children is clinically associated with malaria, suggesting that malaria compromises the control of disseminated NTS infection. To study the mechanistic basis for increased NTS susceptibility, we utilized a model of concurrent infection with Salmonella enterica serotype Typhimurium and Plasmodium yoelii nigeriensis (P. yoelii). U ...[more]

PMID: 29986892

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Project description:The geographical overlaps of malaria parasites and Salmonella spp. can lead to co-infection of these two pathogens, especially in the tropics where malaria is endemic. Moreover, few literatures suggested that malaria infection was associated with Salmonella bacteremia. Therefore, this study quantified pooled prevalence of typhoidal/non-typhoidal Salmonella (NTS) and probability of typhoidal/NTS and malaria co-infection among febrile patients. The systematic review protocol was registered at PROSPERO (CRD42021252322). Studies on co-infection of typhoidal/NTS and malaria were searched in PubMed, Scopus, and Web of Science. The risk of bias of the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. Meta-analyses on the following criteria were performed: (1) pooled prevalence of typhoidal/NTS and malaria co-infection among febrile patients, (2) pooled prevalence of typhoidal/NTS among malaria patients, (3) pooled prevalence of malaria infections among patients with Salmonella spp. infection, and (4) probability of typhoidal/NTS and malaria co-infection among febrile patients. Additionally, the case fatality rate and mean difference of malarial parasitemia between typhoidal/NTS and malaria co-infection and Plasmodium monoinfection were also determined. The subgroup analyses of typhoidal/NTS, regions (Africa and Asia), countries, time (publication year), characteristics of participants, and diagnostic tests for identifying Salmonella spp. were also conducted. A sensitivity test was performed to determine the robustness of the study outcomes. Publication bias among the included studies was evaluated using the funnel plot and Egger's test. All analyses were performed using Stata version 15 (StataCorp LLC, Texas, USA) with a p-value < 0.05 indicating statistical significance. Eighty-one studies that met the eligibility criteria were included in the analyses. Of the 73,775 study participants, 4523 had typhoidal/NTS and malaria co-infections. The pooled prevalence rates of typhoidal/NTS and malaria co-infection among febrile patients were 14% (95% confidence interval [CI], 9-19%; I2, 99.4%; 2971/17,720 cases) and 1% (95% CI 1-1%; I2, 89.9%; 252/29,081 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of typhoidal/NTS infection among patients with malaria were 31% (95% CI 23-39%; I2, 99.5%; 3202/19,208 cases) and 3% (95% CI 2-3%; I2, 86.8%; 407/40,426 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of malaria infection among patients with typhoidal/NTS were 17% (95% CI 6-29%; I2, 33.3%; 13/75 cases) and 43% (95% CI 32-53%; I2, 89.1%; 287/736 cases), respectively. Malaria infection was associated with typhoidal/NTS in children aged < 15 years (p < 0.0001; odds ratio, 0.36; 95% CI 0.23-0.58; I2, 73.9%; 3188/43,212 cases). The case fatality rate in patients with malaria and NTS co-infections was 16% (95% CI 9-24%; I2, 89.1%; 18/103 cases). From the view of the present study, the inappropriate use of the Widal test for Salmonella spp. diagnosis can overestimate the prevalence of typhoidal/NTS and malaria co-infections. Malaria infection associated with typhoidal/NTS in children and the high case fatality rates among few patients with co-infections were highlighted. Future prospective longitudinal studies using the appropriate and confirmatory dsiagnosis for Salmonella spp. infections are highly recommended to ensure the real prevalence of co-infection and highlight the outcome of co-infection for providing adequate treatment in febrile patients who live in areas where malaria is endemic, such as tropical Africa and India.

Dataset Information

Malaria parasite-mediated alteration of macrophage function and increased iron availability predispose to disseminated non-typhoidal Salmonella infection.

Publications

Malaria Parasite-Mediated Alteration of Macrophage Function and Increased Iron Availability Predispose to Disseminated Nontyphoidal Salmonella Infection.

Similar Datasets

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