Presentation of life-threatening invasive nontyphoidal Salmonella disease in Malawian children: A prospective observational study

Abstract

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.

Non-typhoidal Salmonella infections among children in a tertiary hospital in Ningbo, Zhejiang, China, 2012–2019

“…However, we did not find a significant difference in the morbidity of respiratory tract infection between iNTS cases and NTS cases. Previous studies have revealed that the risk factors for invasive disease in children included young age and immunosuppression of any cause [7,39,40], which were also revealed in the present study, as infants aged �6 months and children with the underlying medical condition of leukemia were prone to have iNTS infection.…”

“…It was confirmed in our study with the incidence of diarrhea being significantly higher in the non-iNTS infection cases. In addition, some studies have reported that symptoms of pneumonia and respiratory distress occurred frequently in children with iNTS [9,38,39]. https://doi.org/10.1371/journal.pntd.0008732.g004…”

Non-typhoidal Salmonella bloodstream infections in Kisantu, DR Congo: Emergence of O5-negative Salmonella Typhimurium and extensive drug resistance

“…Over the years in DRC, MDR remained widespread in all serotypes, whereas recent data from Mali [47], Malawi [45,60], South-Africa [61], Kenya [62][63][64] and Ghana [65] showed MDR to be less frequent in Salmonella Enteritidis or more variable over time. Since 2013, resistance to ceftriaxone and azithromycin and DCS increased substantially in O5-positive Salmonella Typhimurium in DRC.…”

Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella

“…The effectiveness of antibiotic treatment is hampered by the difficulty in making a diagnosis, the sudden onset of the disease, and the growing frequency of multidrug resistance ( 1 , 2 , 5 ). Higher incidence and increased severity of iNTS disease have been observed in young children below 72 mo of age, in patients with malaria, anemia, malnutrition, HIV, sickle cell disease, and hemolysis ( 6 – 9 ). Moreover, the Global Burden of Disease Study 2015 estimated that NTS is the third commonest cause of diarrheal deaths at 90,300 (95% uncertainty interval, 34,100–183,100) ( 10 ).…”