Complement 5a Receptor Polymorphisms Are Associated With Panton-Valentine Leukocidin-positive Staphylococcus aureus Colonization in African Pygmies.

Panton-Valentine leukocidin (PVL) is common in African Staphylococcus aureus and can be associated with skin and soft tissue infection. PVL-positive S. aureus colonization is associated with a variant of complement receptor 5a, the cellular target of the lukS PVL subunit.

Molecular evidence of Wolbachia endosymbiosis in Mansonella perstans in Gabon, Central Africa.

The discovery of obligatory intracellular bacteria of the genus Wolbachia in filariae infecting humans led to the use of antibiotics as a potent treatment option. Mansonella perstans is the cause of the second most prevalent filariasis in Gabon, but so far reports on the presence of Wolbachia in this nematode have been inconsistent. We report on the presence of Wolbachia in M. perstans in patients from Gabon, which we identified using polymerase chain reaction (PCR) with primer sets specific for 16S rDNA and ftsZ. Sequence analysis revealed a single consensus sequence, which could be phylogenetically assigned to Wolbachia of the supergroup F. Wolbachia could only be identified in 5 of 14 or 7 of 14 cases, depending on the investigated gene; detection of Wolbachia was associated with higher-level filaremia. Before generalizing the use of antibiotics for mansonellosis, further clarification of the obligatory nature of the endosymbiosis in this nematode is needed.

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.

BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).

Methaemoglobin and COHb in patients with malaria.

BACKGROUND: Haemolytic conditions may contribute to disease pathogenesis and severe clinical manifestations through the liberation of free haemoglobin (Hb) and production of toxic free haem. Thus, free Hb and haem should be associated with altered MetHb and COHb levels in malaria as in other conditions. METHODS: This study comprises data collected at three different sites: (i) a retrospective analysis of the first arterial blood gas result (ABGS) of any patient during 2010 at the University Hospital in Lisbon; (ii) a retrospective analysis of ABGS from patients with severe malaria admitted to the intensive care unit in Berlin, Germany; and (iii) a prospective study of non-invasive MetHb measurements in children with and without malaria in Lambaréné, Gabon. RESULTS: In Lisbon, the mean MetHb level was 1.4% (SD: 0.5) in a total of 17,834 ABGS. Only 11 of 98 samples with a MetHb level of >3.0 referred to infections. COHb levels showed no particular association with clinical conditions, including sepsis. In 13 patients with severe malaria in Berlin, the mean MetHb levels on admission was 1.29%, with 1.36% for cerebral malaria and 1.14% for non-cerebral malaria (P > 0.05). All COHb measurements were below 2.3%. In Lambaréné, Gabon, 132 healthy children had a mean MetHb level of 1.57%, as compared to 150 children with malaria, with a value of 1.77% and 2.05% in uncomplicated and complicated cases, respectively (P < 0.01). CONCLUSIONS: The data appears consistent with the methaemoglobin/haem hypothesis in malaria and sepsis pathogenesis. However, although MetHb was significantly different between healthy controls and children with malaria in Africa, the difference was rather small, also when compared to previous studies. Still, non-invasive bedside MetHb testing may warrant further evaluation as it could be a simple adjuvant tool for prognosis in resource poor settings.

Colonization dynamics of Streptococcus pneumoniae in a remote African population: A prospective cohort study.

The aim of this study was to analyze the population dynamics of Streptococcus pneumoniae in a remotely living African Pygmy population. The same pygmy population (Gabon) was prospectively screened for nasopharyngeal S. pneumoniae colonization in 2011 (n = 103), 2013 (n = 104) and 2017 (n = 107). Non-duplicate isolates (n = 126) were serotyped and tested for antimicrobial resistance (broth microdilution). At the three sampling time points, resistance rates were highest for tetracycline (36-58%), followed by penicillin (parenteral, meningitis-breakpoints, 6-39%) and chloramphenicol (3-15%). The majority of isolates was non-typeable (NT, n = 18/126, 14.3%) followed by serotype 6B (n = 17/126, 13.5%), 21 and 15A (n = 9/126, 7.1%, each). The distribution of serotypes was highly dynamic as only three serotypes (14, 17F, NT) were detected during all three visits. Resistance rates and serotypes of nasopharyngeal S. pneumoniae markedly changed in the remote Babongo population. This rapid change in serotypes could challenge the selection of pneumococcal vaccine.

Tuberculosis Treatment Outcome and Drug Resistance in Lambaréné, Gabon: A Prospective Cohort Study.

Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action.

Streptococcus pneumoniae colonization in remote African Pygmies.

BACKGROUND: African Pygmies have many risk factors for invasive pneumococcal disease (IPD), such as low socioeconomic status and low quality of health care. We characterized Streptococcus pneumoniae from Gabonese Pygmies and analyzed risk factors for S. pneumoniae carriage to improve prophylaxis and therapy of IPD in this neglected, remotely living African community. METHODS: Nasopharyngeal carriage of S. pneumoniae, susceptibility, serotypes and risk factors for IPD were assessed in 103 Pygmies in a cross-sectional study. RESULTS: The carriage rate was 37% (n = 38), with the highest proportion (79%, n = 11) in children between two and four years (n = 14). The predominant serotypes were 15A (24%, n = 9), 11A (16%, n = 6) and 6A (13%, n = 5). Non-susceptibility was detected against penicillin (Clinical and Laboratory Standards Institute; CLSI) meningitis breakpoints; (18%, n = 7), trimethoprim/sulfamethoxazole (61%, n = 23), tetracycline (55%, n = 21) and chloramphenicol (3%, n = 1). Among adult participants (n = 51), 69% (n = 35) regularly consumed alcohol and 75% (n = 38) reported to smoke cigarettes. CONCLUSION: The high proportion of nicotine and drug abuse might increase the risk of IPD. The unusual serotypes challenge a broad coverage by currently marketed vaccines; the broad antibiotic resistance limits the choice of therapy for S. pneumoniae infection.