Nontyphoidal strains of Salmonella (NTS) are a common cause of bacteremia among African children. Cellmediated immune responses control intracellular infection, but they do not protect against extracellular growth of NTS in the blood. We investigated whether antibody protects against NTS bacteremia in Malawian children, because we found this condition mainly occurs before 2 years of age, with relative sparing of infants younger than 4 months old. Sera from all healthy Malawian children tested aged more than 16 months contained anti-Salmonella antibody and successfully killed NTS. Killing was mediated by complement membrane attack complex and not augmented in the presence of blood leukocytes. Sera from most healthy children less than 16 months old lacked NTS-specific antibody, and sera lacking antibody did not kill NTS despite normal complement function. Addition of Salmonella-specific antibody, but not mannose-binding lectin, enabled NTS killing. All NTS strains tested had long-chain lipopolysaccharide and the rck gene, features that resist direct complement-mediated killing. Disruption of lipopolysaccharide biosynthesis enabled killing of NTS by serum lacking Salmonella-specific antibody. We conclude that Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children. This finding and the age-incidence of NTS bacteremia suggest that antibody protects against NTS bacteremia and support the development of vaccines against NTS that induce protective antibody.

Background Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. MethodsIn this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. Results From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P = 0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P = 0.003). ConclusionsThe 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.)

Background-In bacteremia owing to Streptococcus pneumoniae, high bacterial counts at

Alveolar macrophages (AM) are the first professional phagocytes encountered by aerosols containing infections in the lungs, and their phagocytic capacity may be affected by these infections or environmental particles. The aim of this study was to evaluate the innate endocytic and phagocytic properties of human AM obtained from patients with pulmonary tuberculosis and to characterize the vacuoles in which Mycobacterium tuberculosis bacilli reside in vivo. AM were obtained by bronchoalveolar lavage from patients with suspected tuberculosis and from asymptomatic volunteers (controls). Clinical case definitions were based on mycobacterial culture of respiratory specimens and HIV serology. To assess phagocytosis, endocytosis, and acidification of the endosomal system, AM were cultured with IgG-coated polystyrene beads, dextran, and a pH-sensitive reporter (3-(2,4-dinitroanilino)-3-amino-N-methyldipropylamine) and were evaluated by light and immunoelectron microscopy. Cells from 89 patients and 10 controls were studied. We found no significant difference between the two groups in the ability of AM either to ingest beads and dextran or to deliver them to acidified lysosomes. In AM from patients with tuberculosis, the bacilli were located in vacuoles that failed to accumulate endocytosed material and were not acidified. We concluded that AM from patients with tuberculosis and HIV infections were competent to endocytose and phagocytose material and to deliver the material to functional, acidified lysosomes. M. tuberculosis residing in these AM arrests the progression of their phagosomes, which fail to fuse with acidified lysosomes. This confirms, for the first time in humans with tuberculosis and HIV, the conclusions from previous animal and in vitro studies.

BackgroundWe sought to determine the impact of the Ebola virus epidemic on the availability, uptake and outcome of routine maternity services in Sierra Leone.MethodsThe number of antenatal and postnatal visits, institutional births, availability of emergency obstetric care (EmOC), maternal deaths and stillbirths were assessed by month, by districts and by level of healthcare for 10 months during, and 12 months prior to, the Ebola virus disease (EVD) epidemic. All healthcare facilities designated to provide comprehensive (n=13) or basic (n=67) EmOC across the 13 districts of Sierra Leone were included.ResultsPreservice students were not deployed during the EVD epidemic. The number of healthcare providers in facilities remained constant (incidence rate ratio (IRR) 1.03, 95% CI 1.00 to 1.07). Availability of antibiotics, oxytocics, anticonvulsants, manual removal of placenta, removal of retained products of conception, blood transfusion and caesarean section were not affected by the EVD epidemic. Across Sierra Leone, following the onset of the EVD epidemic, there was a 18% decrease in the number of women attending for antenatal (IRR 0.82, 95% CI 0.79 to 0.84); 22% decrease in postnatal attendance (IRR 0.78, 95% CI 0.75 to 0.80) visits and 11% decrease in the number of women attending for birth at a healthcare facility (IRR 0.89, 95% CI 0.87 to 0.91). There was a corresponding 34% increase in the facility maternal mortality ratio (IRR 1.34, 95% CI 1.07 to 1.69) and 24% increase in the stillbirth rate (IRR 1.24, 95% CI 1.14 to 1.35).ConclusionsDuring the EVD epidemic, fewer pregnant women accessed healthcare. For those who did, an increase in maternal mortality and stillbirth was observed. In the post-Ebola phase, ‘readiness’ (or not) of the global partners for large-scale epidemics has been the focus of debate. The level of functioning of the health system with regard to ability to continue to provide high-quality effective routine care needs more attention.