No abstract

Background Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middleincome countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.Methods We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and populationbased childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.Findings In 2018, among children under 5 years globally, there were an estimated 109•5 million influenza virus episodes (uncertainty range [UR] 63•1-190•6), 10•1 million influenza-virus-associated ALRI cases (6•8-15•1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.Interpretation A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middleincome countries.Funding WHO; Bill & Melinda Gates Foundation.

SummaryBackgroundLittle 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.MethodsWe 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.FindingsWe 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.InterpretationThe 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.FundingGAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council.

SummaryBackgroundPneumococcal 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.MethodsWe 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.FindingsWe 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 analy...