Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

BACKGROUND: A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. METHODS: We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. FINDINGS: Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046-0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). INTERPRETATION: PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. FUNDING: The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères.

Diphtheria outbreak with high mortality in northeastern Nigeria.

SUMMARY A diphtheria outbreak occurred from February to November 2011 in the village of Kimba and its surrounding settlements, in Borno State, northeastern Nigeria. We conducted a retrospective outbreak investigation in Kimba village and the surrounding settlements to better describe the extent and clinical characteristics of this outbreak. Ninety-eight cases met the criteria of the case definition of diphtheria, 63 (64.3%) of whom were children aged <10 years; 98% of cases had never been immunized against diphtheria. None of the 98 cases received diphtheria antitoxin, penicillin, or erythromycin during their illness. The overall case-fatality ratio was 21.4%, and was highest in children aged 0-4 years (42.9%). Low rates of immunization, delayed clinical recognition of diphtheria and absence of treatment with antitoxin and appropriate antibiotics contributed to this epidemic and its severity.

[The prevalence of yaws among the Aka in the Congo]. / La prévalence du pian parmi les Aka du Congo.

This study, conducted in 2012 in two districts of the Congo (Bétou and Enyellé), screened for yaws (endemic treponemiasis) that could be treated by a single dose of azithromycin. The screening involved a clinical history, followed by a clinical examination of the children reporting dermatological problems. A rapid diagnostic test for treponema was performed on the children with suspicious lesions. Of 6215 children screened, 485 (7.8%) had such lesions; 480 (99.0%) of them had a rapid diagnostic test, and it was positive for 183 (38.1%). This so-called Morges strategy is aimed at eradicating yaws in endemic areas.

Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20.

The checkpoint protein Mad2 inhibits the activity of the anaphase promoting complex by sequestering Cdc20 until all chromosomes are aligned at the metaphase plate. We report the solution structure of human Mad2 and its interaction with Cdc20. Mad2 possesses a novel three-layered alpha/beta fold with three alpha-helices packed between two beta-sheets. Using deletion mutants we identified the minimal Mad2-binding region of human Cdc20 as a 40-residue segment immediately N-terminal to the WD40 repeats. Mutagenesis and NMR titration experiments show that a C-terminal flexible region of Mad2 is required for binding to Cdc20. Mad2 and Cdc20 form a tight 1:1 heterodimeric complex in which the C-terminal segment of Mad2 becomes folded. These results provide the first structural insight into mechanisms of the spindle assembly checkpoint.