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Sequential acquisition of T cells and antibodies to nontyphoidal Salmonella in Malawian children.

ABSTRACT: Salmonella Typhimurium (STm) remain a prominent cause of bacteremia in sub-Saharan Africa. Complement-fixing antibodies to STm develop by 2 years of age. We hypothesized that STm-specific CD4? T cells develop alongside this process.Eighty healthy Malawian children aged 0-60 months were recruited. STm-specific CD4? T cells producing interferon ?, tumor necrosis factor ?, and interleukin 2 were quantified using intracellular cytokine staining. Antibodies to STm were measured by serum bactericidal activity (SBA) assay, and anti-STm immunoglobulin G antibodies by enzyme-linked immunosorbent assay.Between 2006 and 2011, STm bacteremias were detected in 449 children <5 years old. STm-specific CD4? T cells were acquired in infancy, peaked at 14 months, and then declined. STm-specific SBA was detectable in newborns, declined in the first 8 months, and then increased to a peak at age 35 months. Acquisition of SBA correlated with acquisition of anti-STm-lipopolysaccharide (LPS) immunoglobulin G (r = 0.329 [95% confidence interval, .552-.062]; P = .01) but not anti-STm-outer membrane protein or anti-STm-flagellar protein (FliC).Acquisition of STm-specific CD4? T cells in early childhood is consistent with early exposure to STm or cross-reactive protein antigens priming this T-cell development. STm-specific CD4? T cells seem insufficient to protect against invasive nontyphoidal Salmonella disease, but sequential acquisition of SBA to STm LPS is associated with a decline in its incidence.

SUBMITTER: Nyirenda TS

PROVIDER: S-EPMC4054899 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Sequential acquisition of T cells and antibodies to nontyphoidal Salmonella in Malawian children.

Nyirenda Tonney S TS Gilchrist James J JJ Feasey Nicholas A NA Glennie Sarah J SJ Bar-Zeev Naor N Gordon Melita A MA MacLennan Calman A CA Mandala Wilson L WL Heyderman Robert S RS

The Journal of infectious diseases 20140116 1

<h4>Background</h4>Salmonella Typhimurium (STm) remain a prominent cause of bacteremia in sub-Saharan Africa. Complement-fixing antibodies to STm develop by 2 years of age. We hypothesized that STm-specific CD4⁺ T cells develop alongside this process.<h4>Methods</h4>Eighty healthy Malawian children aged 0-60 months were recruited. STm-specific CD4⁺ T cells producing interferon γ, tumor necrosis factor α, and interleukin 2 were quantified using intracellular cytokine staining. Antibodies to STm w ...[more]

PMID: 24443544

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Project description:Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0-15 years) and 52/256 children (20%; 95%CI 15-25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71-82%), 123/240 (51%; 95%CI 45-58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36-49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8-35.1), dyspnea (OR 4.2; 95%CI 1.5-12.0) and HIV infection (OR 3.3; 95%CI 1.1-10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children.

Dataset Information

Sequential acquisition of T cells and antibodies to nontyphoidal Salmonella in Malawian children.

Publications

Sequential acquisition of T cells and antibodies to nontyphoidal Salmonella in Malawian children.

Similar Datasets

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