Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.

Who gets vaccinated in a measles-rubella campaign in Nepal?: results from a post-campaign coverage survey.

BACKGROUND: Following the 2015 earthquake, a measles-rubella (MR) supplementary immunization activity (SIA), in four phases, was implemented in Nepal in 2015-2016. A post-campaign coverage survey (PCCS) was then conducted in 2017 to assess SIA performance and explore factors that were associated with vaccine uptake. METHODS: A household survey using stratified multi-stage probability sampling was conducted to assess coverage for a MR dose in the 2015-2016 SIA in Nepal. Logistic regression was then used to identify factors related to vaccine uptake. RESULTS: Eleven thousand two hundred fifty-three households, with 4870 eligible children provided information on vaccination during the 2015-2016 MR SIA. Overall coverage of measles-rubella vaccine was 84.7% (95% CI: 82.0-87.0), but varied between 77.5% (95% CI: 72.0, 82.2) in phase-3, of 21 districts vaccinated in Feb-Mar 2016, to 97.7% (CI: 95.4, 98.9) in phase-4, of the last seven mountainous districts vaccinated in Mar-Apr 2016. Coverage in rural areas was higher at 85.6% (CI: 81.9, 88.8) than in urban areas at 79.0% (CI: 75.5, 82.1). Of the 4223 children whose caregivers knew about the SIA, 96.5% received the MR dose and of the 647 children whose caregivers had not heard about the campaign, only 1.8% received the MR dose. CONCLUSIONS: The coverage in the 2015-2016 MR SIA in Nepal varied by geographical region with rural areas achieving higher coverage than urban areas. The single most important predictor of vaccination was the caregiver being informed in advance about the vaccination campaign. Enhanced efforts on social mobilization for vaccination have been used in Nepal since this survey, notably for the most recent 2020 MR campaign.

Nepal measles outbreak response immunization during COVID-19: A risk-based intervention strategy.

In 2020, National Immunization Programme (NIP) of Nepal implemented a measles outbreak response immunization (ORI) campaign, which was additional to an ongoing preventive measles-rubella SIA campaign. Both campaigns were implemented during ongoing COVID-19 transmission. By April, 220 measles cases and two deaths were confirmed from eight districts of Nepal. The NIP triangulated information from surveillance (measles and COVID-19), measles immunization performance and immunity profile, programme capacities and community engagement and applied a logical decision-making framework to the collated data to inform 'Go/No-Go' decisions for ORI interventions. This was reviewed by the National Immunization Advisory Committee (NIAC) for endorsement. Outbreak response with non-selective immunization (ORI), vitamin-A administration and case management were implemented in affected municipalities of four districts, while in the remaining districts outbreak response without ORI were undertaken. The structure and iterative application of this logical framework has been described. ORI was implemented without interrupting the ongoing measles-rubella vaccination campaign which had targeted children from 9 to 59 months of age. The age group for ORI was same as SIA in one sub-district area, while for the other three sub-district areas it was from 6 months to 15 years of age. More than 32,000 persons (97% coverage) were vaccinated in ORI response. Overall measles incidence decreased by 98% after ORI. The daily incidence rate of measles was 94 times higher (95% confidence interval: 36.11 - 347.62) before the ORI compared to two weeks after ORI until year end. Close attention to surveillance and other data to inform actions and seamless collaboration between NIP and core immunization partners (WHO, UNICEF), with guidance from NIAC were key elements in successful implementation. This was an example of feasible application of the global framework for implementation of a mass vaccination campaign during COVID-19 through application of a simple decision-making logical framework.