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Bangladesh introduced the ten-valent pneumococcal conjugate vaccine (PCV10) into its national immunization program in March 2015 creating an opportunity to assess the real-world impact of PCV on invasive pneumococcal disease (IPD). Between January 2014 and June 2018, children aged 3–35 months in three rural sub-districts of Sylhet district of Bangladesh were visited every two months to collect morbidity and care-seeking data. Children attending sub-district hospitals with pneumonia, meningitis, or sepsis were assessed for IPD after obtaining informed consent. Blood and cerebrospinal fluid were collected from enrolled children to isolate pneumococcus using culture and molecular test. Children who were age-eligible to receive the PCV and had pneumococcus isolated were enrolled as cases. Four age and sex-matched clinic and community controls were selected for each case within one to two weeks of case identification. Data on immunization status and confounders were collected. PCV coverage was estimated using vaccine coverage surveys. Case-control and incidence trend analyses were conducted to assess the impact of PCV on IPD. The community cohort yielded 217,605 child years of observations and 154,773 sick child-visits to study hospitals. Pneumococcus was isolated from 44 children who were age-eligible to receive PCV; these children were enrolled as cases. The cases were matched with 166 community- and 150 clinic-controls. The matched case-control analyses using community-controls showed 83% effectiveness (95% CI: 1.57–97.1%) and clinic controls showed 90% effectiveness (95% CI: −26.0% to 99.1%) of PCV in preventing IPD. Incidence trend analysis estimated vaccine effectiveness at 80.1% (95% CI: 38.4, 93.6). PCV in this pediatric population in Bangladesh was highly effective in preventing IPD. [ABSTRACT FROM AUTHOR]

Pneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh. We conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3–35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression. We matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, −0.2%, 38.4%) for ≥2 PCV10 doses and among 3–11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, −22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls. Clinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment – compared to clinic controls – was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs. [ABSTRACT FROM AUTHOR]