NontyphoidalSalmonellaInvasive Disease: Challenges and Solutions

Author:

Crump John A1ORCID,Nyirenda Tonney S2ORCID,Kalonji Lisette Mbuyi34ORCID,Phoba Marie-France34ORCID,Tack Bieke56ORCID,Platts-Mills James A7ORCID,Gordon Melita A89ORCID,Kariuki Samuel M10ORCID

Affiliation:

1. Centre for International Health, University of Otago , Dunedin , New Zealand

2. Department of Pathology, Kamuzu University of Health Sciences , Blantyre , Malawi

3. Department of Medical Biology, University Hospital of Kinshasa , Kinshasa , Democratic Republic of the Congo

4. Department of Microbiology, Institut National de Recherche Biomédicale , Kinshasa , Democratic Republic of the Congo

5. Department of Clinical Science, Institute of Tropical Medicine , Antwerp , Belgium

6. Department of Microbiology, Immunology and Transplantation, KU Leuven , Leuven , Belgium

7. Division of Infectious Diseases and International Health, School of Medicine, University of Virginia , Charlottesville, Virginia , USA

8. Malawi Liverpool Wellcome Trust Programme , Blantyre , Malawi

9. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool , Liverpool , United Kingdom

10. Centre for Microbiology Research, Kenya Medical Research Institute , Nairobi , Kenya

Abstract

AbstractNontyphoidal Salmonella are a leading cause of community-onset bacteremia and other serious infections in sub-Saharan African countries where large studies indicate that they are an uncommon cause of moderate-to-severe diarrhea. Approximately 535 000 nontyphoidal Salmonella invasive disease illnesses and 77 500 deaths were estimated to occur in 2017; 422 000 (78.9%) illnesses and 66 500 (85.9%) deaths in countries in sub-Saharan Africa. Lineages of Salmonella enterica serovar Typhimurium sequence type (ST) 313 and lineages of Salmonella enterica serovar Enteritidis ST11 dominate as causes of invasive disease. A major reservoir for these specific strains outside of humans has not been identified to date. Human fecal shedding of such strains is common in areas where nontyphoidal Salmonella invasive disease incidence is high. The case-fatality ratio of nontyphoidal Salmonella invasive disease is approximately 15%. Early diagnosis and treatment are needed to avert fatal outcomes. Antimicrobial resistance, including multiple drug resistance, decreased fluoroquinolone susceptibility, and resistance to third-generation cephalosporins, is increasing in prevalence and is likely to further compromise patient outcomes. Naturally acquired immunity against invasive disease develops in children aged >3 years in endemic areas, likely mediated in part by the sequential acquisition of T-cell immunity, followed by antigen-specific immunoglobulin G antibodies. Vaccines in preclinical or clinical development include live-attenuated S. enterica serovar Typhimurium, nontyphoidal S. enterica core and O-polysaccharide glycoconjugates, multiple antigen-presenting system complexes, and generalized modules for membrane antigens vaccines. The latter are in phase I trials in Europe and Africa. Both vaccine use, and other effective, evidence-based nonvaccine interventions, are needed to prevent and control nontyphoidal Salmonella invasive disease.

Funder

Bill & Melinda Gates Foundation

US National Institutes of Health

Research Foundation—Flanders

FWO

European Society of Clinical Microbiology and Infectious Diseases

EU Horizon 2020 Research and Innovation Programme

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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