Summary Background Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive ...pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011. Methods We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008–May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013–Dec 31, 2014), adjusting for changes in case ascertainment over time. Findings We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30–71) in the 2–23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64–91) reduction in serotypes covered by the PCV13 vaccine. In the 2–4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25–75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39–83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2–59 months increased by 47% (−21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time. Interpretation The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2–59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2–4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. Funding GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP) , Bill & Melinda Gates Foundation , and the UK Medical Research Council.
Summary Background Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, ...and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence. Methods We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2–59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia. Findings We investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2–11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7–36) in 2014–15. In the 12–23 month age group, radiological pneumonia decreased from 15·3 to 10·9 cases per 1000 person-years (29% decline, 12–42). In children aged 2–4 years, incidence fell from 5·2 to 4·1 cases per 1000 person-years (22% decline, 1–39). Incidence of all clinical pneumonia increased by 4% (–1 to 8), but hospitalised cases declined by 8% (3–13). Pneumococcal pneumonia declined from 2·9 to 1·2 cases per 1000 person-years (58% decline, 22–77) in children aged 2–11 months and from 2·6 to 0·7 cases per 1000 person-years (75% decline, 47–88) in children aged 12–23 months. Hypoxic pneumonia fell from 13·1 to 5·7 cases per 1000 person-years (57% decline, 42–67) in children aged 2–11 months and from 6·8 to 1·9 cases per 1000 person-years (72% decline, 58–82) in children aged 12–23 months. In the case-control study, the best estimate of the effectiveness of three doses of PCV13 against radiological pneumonia was an adjusted odds ratio of 0·57 (0·30–1·08) in children aged 3–11 months and vaccine effectiveness increased with greater numbers of doses (p=0·026). The analysis in children aged 12 months and older was underpowered because there were few unvaccinated cases and controls. Interpretation The introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia. Funding GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council.
Summary Background The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV ...given alongside the measles–rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. Methods We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9–10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles–rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4–6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2 -transformed antibody titres. This trial is registered with ClinicalTrials.gov , number NCT01847872. Findings Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, −4·5% 95% CI −9·5 to −0·1; yellow fever, 1·2% –2·9 to 5·5). Measles and poliovirus responses were unaffected (measles, 6·8% 95% CI −1·4 to 14·9; poliovirus serotype 1, 1·6% –6·7 to 4·7; serotype 2, 0·0% –2·1 to 2·1; serotype 3, 0·0% –3·8 to 3·9). Poliovirus seroprevalence was universally high (>97%) after vaccination, but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose. The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route. There were no safety concerns. Interpretation The data support the future co-administration of IPV, measles–rubella, and yellow fever vaccines within the Expanded Programme on Immunization schedule at 9 months. The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated, although it results in a high post-vaccination poliovirus seroprevalence. Funding Bill & Melinda Gates Foundation.
Pooled estimates from across the African diaspora show that black men who have sex with men (MSM) are 15 times more likely to be HIV positive compared with general populations and 8·5 times more ...likely compared with black populations. Disparities in the prevalence of HIV infection are greater in African and Caribbean countries that criminalise homosexual activity than in those that do not criminalise such behaviour. With the exception of US and African epidemiological studies, most studies of black MSM mainly focus on outcomes associated with HIV behavioural risk rather than on prevalence, incidence, or undiagnosed infection. Nevertheless, black MSM across the African diaspora share common experiences such as discrimination, cultural norms valuing masculinity, concerns about confidentiality during HIV testing or treatment, low access to HIV drugs, threats of violence or incarceration, and few targeted HIV prevention resources.
The treatment of tarsometatarsal joint fracture-dislocations generally consists of realignment followed by stabilization with rigid internal fixation. The purpose of this study was to determine the ...strongest orientation for the “Lisfranc's screw” for repair of disruption of the articulation between the first and second metatarsals and the medial and intermediate cuneiforms. To this end, Lisfranc's ligament was sectioned in 6 pairs of fresh-frozen, human cadaver feet, after which a 3.5-mm partially threaded, cannulated screw was placed across the Lisfranc joint in 1 of 2 opposing directions. In one group, the screw was oriented in the more traditional medial cuneiform to second metatarsal base direction. In the other group, the screw was oriented from the second metatarsal base to the medial cuneiform. After fixation, each construct was pulled to transverse plane failure at the tarsometatarsal joint with a servohydraulic mechanical testing system. The overall force to failure was 157.04 ± 54.79 N (range, 96.8-249.2 N). For the traditional medial cuneiform to second metatarsal base screw orientation group, the mean force to failure was 148.97 ± 54.93 N, whereas for the second metatarsal base to medial cuneiform group the mean force to failure was 165.12 ± 58.57 N, and this difference was not statistically significant (P = .2475). Although not statistically significantly different in regard to force to failure strength, the authors describe an alternative approach to the orientation of “Lisfranc's screw” for stabilization of the relationship of the medial cuneiform to the second metatarsal. Level of Clinical Evidence: 5
Summary Background Although many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets (LLINs), the two studies assessing the benefit of ...the combination of these two interventions gave conflicting results. We aimed to assess whether the addition of indoor residual spraying to LLINs provided a significantly different level of protection against clinical malaria in children or against house entry by vector mosquitoes. Methods In this two-arm cluster, randomised, controlled efficacy trial we randomly allocated clusters of Gambian villages using a computerised algorithm to LLINs alone (n=35) or indoor residual spraying with dichlorodiphenyltrichloroethane plus LLINs (n=35). In each cluster, 65–213 children, aged 6 months to 14 years, were surveyed at the start of the 2010 transmission season and followed in 2010 and 2011 by passive case detection for clinical malaria. Exposure to parasite transmission was assessed by collection of vector mosquitoes with both light and exit traps indoors. Primary endpoints were the incidence of clinical malaria assessed by passive case detection and number of Anopheles gambiae sensu lato mosquitoes collected per light trap per night. Intervention teams had no role in data collection and the data collection teams were not informed of the spray status of villages. The trial is registered at the ISRCTN registry, number ISRCTN01738840. Findings LLIN coverage in 2011 was 3510 (93%) of 3777 children in the indoor residual spraying plus LLIN group and 3622 (95·5%) of 3791 in the LLIN group. In 2010, 7845 children were enrolled, 7829 completed passive case detection, and 7697 (98%) had complete clinical and covariate data. In 2011, 7009 children remained in the study, 648 more were enrolled, 7657 completed passive case detection, and 7545 (98·5%) had complete data. Indoor residual spraying coverage per cluster was more than 80% for both years in the indoor residual spraying plus LLIN group. Incidence of clinical malaria was 0·047 per child-month at risk in the LLIN group and 0·044 per child-month at risk in the indoor residual spraying plus LLIN group in 2010, and 0·032 per child-month at risk in the LLIN group and 0·034 per child-month at risk in the indoor residual spraying plus LLIN group in 2011. The incident rate ratio was 1·08 (95% CI 0·80–1·46) controlling for confounders and cluster by mixed-effect negative binomial regression on all malaria attacks for both years. No significant difference was recorded in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons; the mean number of A gambiae sensu lato mosquitoes per trap per night was 6·7 (4·0–10·1) in the LLIN group and 4·5 (2·4–7·4) in the indoor residual spraying plus LLIN group (p=0·281 in the random-effects linear regression model). Interpretation We identified no significant difference in clinical malaria or vector density between study groups. In this area with high LLIN coverage, moderate seasonal transmission, and susceptible vectors, indoor residual spraying did not provide additional benefit. Funding UK Medical Research Council.
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