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Pathogenic signature of invasive non-typhoidal Salmonella in Africa: implications for vaccine development.

ABSTRACT: Invasive non-typhoidal Salmonella (iNTS) infections are a leading cause of bacteremia in Sub-Saharan Africa (sSA), thereby representing a major public health threat. Salmonella Typhimurium clade ST313 and Salmonella Enteriditis lineages associated with Western and Central/Eastern Africa are among the iNTS serovars which are of the greatest concern due to their case-fatality rate, especially in children and in the immunocompromised population. Identification of pathogen-associated features and host susceptibility factors that increase the risk for invasive non-typhoidal salmonellosis would be instrumental for the design of targeted prevention strategies, which are urgently needed given the increasing spread of multidrug-resistant iNTS in Africa. This review summarizes current knowledge of bacterial traits and host immune responses associated with iNTS infections in sSA, then discusses how this knowledge can guide vaccine development while providing a summary of vaccine candidates in preclinical and early clinical development.

SUBMITTER: Piccini G

PROVIDER: S-EPMC7553687 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Pathogenic signature of invasive non-typhoidal Salmonella in Africa: implications for vaccine development.

Piccini Giulia G Montomoli Emanuele E

Human vaccines & immunotherapeutics 20200721 9

Invasive non-typhoidal Salmonella (iNTS) infections are a leading cause of bacteremia in Sub-Saharan Africa (sSA), thereby representing a major public health threat. Salmonella Typhimurium clade ST313 and Salmonella Enteriditis lineages associated with Western and Central/Eastern Africa are among the iNTS serovars which are of the greatest concern due to their case-fatality rate, especially in children and in the immunocompromised population. Identification of pathogen-assoc ...[more]

PMID: 32692622

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Project description:BackgroundNon-typhoidal Salmonella (NTS) are a frequent cause of invasive infections in sub-Saharan Africa. They are frequently multidrug resistant (co-resistant to ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol), and resistance to third-generation cephalosporin and fluoroquinolone non-susceptibility have been reported. Third-generation cephalosporins and fluoroquinolones are often used to treat invasive NTS infections, but azithromycin might be an alternative. However, data on antibiotic treatment efficacy in invasive NTS infections are lacking. In this study, we aimed to assess the spatiotemporal distribution of antimicrobial resistance in invasive NTS infections in sub-Saharan Africa and to describe the available evidence and recommendations on antimicrobial treatment.MethodsWe conducted a systematic review of all available literature on antimicrobial resistance and treatment in invasive NTS infections. We performed a random effects meta-analysis to assess the temporal distribution of multidrug resistance, third-generation cephalosporin resistance, and fluoroquinolone non-susceptibility. We mapped these data to assess the spatial distribution. We provided a narrative synthesis of the available evidence and recommendations on antimicrobial treatment.ResultsSince 2001, multidrug resistance was observed in 75% of NTS isolates from all sub-Saharan African regions (95% confidence interval, 70-80% and 65-84%). Third-generation cephalosporin resistance emerged in all sub-Saharan African regions and was present in 5% (95% confidence interval, 1-10%) after 2010. Fluoroquinolone non-susceptibility emerged in all sub-Saharan African regions but did not increase over time. Azithromycin resistance was reported in DR Congo. There were no reports on carbapenem resistance. We did not find high-quality evidence on the efficacy of antimicrobial treatment. There were no supranational guidelines. The "Access group" antibiotics ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol and "Watch group" antibiotics ceftriaxone, cefotaxime, and ciprofloxacin were recommended as the first-choice antibiotics in national guidelines or reviews. These also recommended (a switch to) oral fluoroquinolones or azithromycin.ConclusionsIn addition to the widespread multidrug resistance in invasive NTS infections in sub-Saharan Africa, resistance to third-generation cephalosporins and fluoroquinolone non-susceptibility was present in all regions. There was a lack of data on the efficacy of antimicrobial treatment in these infections, and supranational evidence-based guidelines were absent.

Project description:BackgroundInvasive non-typhoidal Salmonella (iNTS) is a growing health-concern in many parts of sub-Saharan Africa. iNTS is associated with fatal diseases such as HIV and malaria. Despite high case fatality rates, the disease has not been given much attention. The limited number of population-based surveillance studies hampers accurate estimation of global disease burden. Given the lack of available evidence on the disease, it is critical to identify high risk areas for future surveillance and to improve our understanding of iNTS endemicity.MethodsConsidering that population-based surveillance data were sparse, a composite index called the iNTS risk factor (iNRF) index was constructed based on risk factors that commonly exist across countries. Four risk factors associated with the prevalence of iNTS were considered: malaria, HIV, malnutrition, and safe water. The iNRF index was first generated based on the four risk factors which were collected within a 50 km radius of existing surveillance sites. Pearson product-moment correlation was used to test statistical associations between the iNRF index and the prevalence of iNTS observed in the surveillance sites. The index was then further estimated at the subnational boundary level across selected countries and used to identify high risk areas for iNTS.ResultsWhile the iNRF index in some countries was generally low (i.e. Rwanda) or high (i.e. Cote d'Ivoire), the risk-level of iNTS was variable not only by country but also within a country. At the provincial-level, the highest risk area was identified in Maniema, the Democratic Republic of Congo, whereas Dakar in Senegal was at the lowest risk.ConclusionsThe iNRF index can be a useful tool to understand the geographically varying risk-level of iNTS. Given that conducting a population-based surveillance study requires extensive human and financial resources, identifying high risk areas for iNTS prior to a study implementation can facilitate an appropriate site-selection process in the future.

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Pathogenic signature of invasive non-typhoidal Salmonella in Africa: implications for vaccine development.

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Pathogenic signature of invasive non-typhoidal <i>Salmonella</i> in Africa: implications for vaccine development.

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