article · Open Forum Infectious Diseases
Nontyphoidal Salmonella causes substantial community-onset bacteremia and severe infections in sub-Saharan Africa, where it rarely manifests as moderate-to-severe diarrhoea. In 2017, an estimated 535,000 invasive cases and 77,500 deaths occurred globally, with sub-Saharan Africa accounting for roughly 79 percent of illnesses and 86 percent of deaths. Strains of Salmonella Typhimurium sequence type 313 and Salmonella Enteritidis sequence type 11 dominate these infections, accompanied by widespread human faecal shedding but no identified animal reservoir. With an estimated case-fatality ratio of 15 percent, clinical management relies on prompt diagnosis and therapy. However, rising antimicrobial resistance, including multidrug resistance and resistance to third-generation cephalosporins, complicates treatment. Natural immunity develops in children over three years old, offering a path for prevention. Vaccine candidates, such as live-attenuated formulations, glycoconjugates, and generalized modules for membrane antigens, are in preclinical and phase 1 clinical development alongside non-vaccine control measures.
Invasive nontyphoidal Salmonella presents an acute public health challenge, causing high fatality rates in sub-Saharan Africa. As bacterial resistance to standard and advanced antibiotics continues to rise, existing treatments become less reliable. Tracking circulating strains and developing effective preventative vaccines are critical priorities to reduce fatal outcomes in vulnerable populations, particularly young children.
The findings point to direct opportunities in vaccine and diagnostics development for global health manufacturers and clinical research organisations. Current development pipelines include live-attenuated strains, glycoconjugates, multiple antigen-presenting system complexes, and generalized modules for membrane antigens, with the latter evaluated in phase 1 human trials in Europe and Africa. Diagnostic tools enabling early detection are also required to guide effective therapy against increasingly resistant bacterial strains.
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Nontyphoidal <i>Salmonella</i> 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 <i>Salmonella</i> 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 <i>Salmonella enterica</i> serovar Typhimurium sequence type (ST) 313 and lineages of <i>Salmonella enterica</i> 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 <i>Salmonella</i> invasive disease incidence is high. The case-fatality ratio of nontyphoidal <i>Salmonella</i> 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 <i>S. enterica</i> serovar Typhimurium, nontyphoidal <i>S. enterica</i> 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 <i>Salmonella</i> invasive disease.
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DOI: 10.1093/ofid/ofad020
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