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Background Representative data describing serious infections in children aged ≥5 years and adults in Africa are limited. Methods We conducted population-based surveillance for pneumonia, meningitis, and septicemia in a demographic surveillance area in The Gambia between 12 May 2008 and 31 December 2015. We used standardized criteria to identify, diagnose, and investigate patients aged ≥5 years using conventional microbiology and radiology. Results We enrolled 1638 of 1657 eligible patients and investigated 1618. Suspected pneumonia, septicemia, or meningitis was diagnosed in 1392, 135, and 111 patients, respectively. Bacterial pathogens from sterile sites were isolated from 105 (7.5%) patients with suspected pneumonia, 11 (8.1%) with suspected septicemia, and 28 (25.2%) with suspected meningitis. Streptococcus pneumoniae (n = 84), Neisseria meningitidis (n = 16), and Staphylococcus aureus (n = 15) were the most common pathogens. Twenty-eight (1.7%) patients died in hospital and 40 (4.1%) died during the 4 months after discharge. Thirty postdischarge deaths occurred in patients aged ≥10 years with suspected pneumonia. The minimum annual incidence was 133 cases per 100 000 person-years for suspected pneumonia, 13 for meningitis, 11 for septicemia, 14 for culture-positive disease, and 46 for radiological pneumonia. At least 2.7% of all deaths in the surveillance area were due to suspected pneumonia, meningitis, or septicemia. Conclusions Pneumonia, meningitis, and septicemia in children aged ≥5 years and adults in The Gambia are responsible for significant morbidity and mortality. Many deaths occur after hospital discharge and most cases are culture negative. Improvements in prevention, diagnosis, inpatient, and follow-up management are urgently needed. [ABSTRACT FROM AUTHOR]

Background Invasive bacterial diseases (IBD) cause significant mortality in young infants. There are limited population-based data on IBD in young infants in Sub-Saharan Africa. Methods We conducted population-based surveillance for IBD among infants aged 0-90 days in a demographic surveillance area in rural Gambia between 1 March 2011 and 31 December 2017. Infants admitted to health facilities within the study area had standardised clinical evaluation plus conventional microbiological investigation. We defined IBD as isolation of pathogenic bacteria from blood, cerebrospinal fluid, lung, or pleural aspirate. We determined incidence, aetiology and case-fatality of IBD. Results A total of 3794 infants were admitted and 3605 (95%) had at least one sample collected for culture. We detected 254 (8.0%) episodes of IBD (bacteraemia 241; meningitis 14; pneumonia seven). The incidence of IBD in infants aged 0-90 days was 25 episodes/1000 person-years (95% confidence interval (CI) = 22-28), the incidence in neonates was 50 episodes/1000 person-years (95% CI = 43-58) and the incidence in infants aged 29-90 days was 12 episodes/1000 person-years (95% CI = 9-15). The most common pathogens causing IBD were Staphylococcus aureus (n = 102, 40%), Escherichia coli (n = 37, 15%), Streptococcus pneumoniae (n = 24, 9%) and Klebsiella pneumoniae (n = 12, 5%). Case-fatality was 29% (95% CI = 23-37) in neonates and 19% (95% CI = 11-29) in infants aged 29-90 days. A minimum of 7.3% of all young infant deaths in the population were caused by IBD. Conclusions IBD are common in young infants in rural Gambia and have a high case-fatality. Strategies are needed to prevent IBD in young infants. Overcoming barriers to widespread implementation of existing vaccines and developing new vaccines against the most common pathogens causing IBD should be among top priorities for reducing the high mortality rate in young infants. [ABSTRACT FROM AUTHOR]

Background: We investigated the pathogenesis of pneumococcal pneumonia using clinical specimens collected for pneumonia surveillance in The Gambia.Methods: Lung aspirates and nasopharyngeal swabs from 31 patients were examined by culture, quantitative polymerase chain reaction (qPCR), whole genome sequencing, serotyping, and reverse-transcription qPCR.Results: Five lung aspirates cultured pneumococci, with a matching strain identified in the nasopharynx. Three virulence genes including ply (pneumolysin) were upregulated >20-fold in the lung compared with the nasopharynx. Nasopharyngeal pneumococcal density was higher in pediatric pneumonia patients compared with controls (P < .0001).Conclusions: Findings suggest that changes in pneumococcal gene expression occurring in the lung environment may be important in pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence.Methods: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time.Findings: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49).Interpretation: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses.Funding: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]