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

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.

Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome.

BACKGROUND: Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. METHODS: From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. RESULTS: Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. CONCLUSIONS: Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected in children with severe malarial anemia.

Identification and characterization of ceftriaxone resistance and extended-spectrum beta-lactamases in Malawian bacteraemic Enterobacteriaceae.

OBJECTIVES: To enumerate and characterize extended-spectrum beta-lactamases (ESBLs) amongst ceftriaxone-resistant coliforms in Blantyre, Malawi, where third-generation cephalosporin use is currently highly restricted. METHODS: Over the period April 2004-March 2005 all ceftriaxone-resistant isolates from blood cultures were examined for the presence of ESBLs. Isoelectric focusing was performed on enzyme extracts. PCR and DNA sequencing of amplicons were used to identify the underlying genetic determinants responsible for the ESBL phenotypes. Transferability of the ESBL phenotypes was tested by conjugation to a susceptible Escherichia coli J53. RESULTS: Enterobacteriaceae were isolated from 1191 blood cultures, of which 19 (1.6%) were ceftriaxone resistant. Ten isolates (0.7% of all isolates) demonstrated an ESBL phenotype but only eight were characterized as three isolates were from the same patient. Genotypes SHV-11 (n = 1), SHV-12 (n = 3), SHV-27 (n = 1), TEM-63 (n = 2) and CTX-M-15 (n = 1) were detected. Plasmid transfer of the ESBL resistance phenotype was successful for all the isolates. CONCLUSIONS: In a clinical setting of minimal cephalosporin usage there is already a diversity of ESBL genotypes. Increased use of cephalosporins in this setting is likely to result in a rapid expansion of ESBLs and their prevalence will need to be carefully monitored.