Study populationThe study was part of a larger prospective observational study investigating the genetic susceptibility to invasive pneumococcal disease in Malawian children [32]. This study was conducted at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, between April 2004 and October 2006. We recruited children aged between 2 months and 16 years with a suspected diagnosis of selleck chemicals bacterial meningitis or pneumonia. Details on enrolment criteria, laboratory methods, and management protocols were described elsewhere [33]. We also collected data on the duration of symptoms and on previous antibiotic administration. As our previous data indicated that these factors did not influence outcome in multivariate analysis, we did not include them in the analysis reported here [33].
We recorded the Blantyre Coma Score (BCS) on admission [34]; this has a scale from 0 to 5, with a score of ��2 defining coma. We assessed each child’s nutritional status by using weight-for-height Z scores and height-for-age Z scores. In total, we recruited 377 children to the parent study, but angiogenic factor determination was performed on only the first 293 cases, who constituted the study population of the present investigation. Pneumococcal bacterial loads were determined as previously described [33].We used the following definitions:Cases (n = 293): Children first seen with signs and symptoms of bacterial meningitis or pneumonia in whom growth factors were determined. Healthy controls (n = 15): Healthy afebrile children from the same villages as the cases, who had no malarial parasites on blood film.
Controls were selected by parents or guardians in the neighborhood of the index case as part of a larger study investigating genetic susceptibility in IPD [32]. In a small number of children, parental consent also was given to take venous samples for cytokine and angiogenic factor determination. Invasive pneumococcal disease (IPD) (n = 180): S. pneumoniae was identified (by culture, microscopy, and Gram stain, antigen testing, or PCR) from one or more of the following normally sterile body sites: blood, cerebrospinal fluid, lung aspirate.Serious bacterial infection (SBI) (n = 216): Children with bacterial meningitis or pneumonia, and in whom a bacterial pathogen was identified by culture, polysaccharide antigen test, or PCR in blood, cerebrospinal fluid or lung aspirate fluid (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae b).
No detectable bacterial infection (NBI) (n = 77): AV-951 Children with bacterial meningitis or pneumonia, but who were negative for any bacteria on culture, polysaccharide antigen test, or PCR (S. pneumoniae, N. meningitidis, and H. influenzae b). Pneumonia (n = 82): Confirmed by radiology and positive blood or lung aspirate by culture or PCR. Bacterial meningitis (n = 211): Confirmed by CSF cell count (>10 per microliter) and one of the following tests: CSF culture, Gram stain, polysaccharide antigen, or PCR positive.