Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People's Democratic Republic.
Jocelyn Chan, Jana Y R Lai, Cattram D Nguyen, Keoudomphone Vilivong, Eileen M Dunne, Audrey Dubot-Pérès, Kimberley Fox, Jason Hinds, Kerryn A Moore, Monica L Nation, Casey L Pell, Anonh Xeuatvongsa, Manivanh Vongsouvath, Paul N Newton, Kim Mulholland, Catherine Satzke, David A B Dance, Fiona M Russell, PneuCAPTIVE Lao PDR Research Group
Author Information
Jocelyn Chan: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia jocelyn.chan@mcri.edu.au. ORCID
Jana Y R Lai: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Cattram D Nguyen: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Keoudomphone Vilivong: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Eileen M Dunne: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Audrey Dubot-Pérès: Microbiology Laboratory, Mahosot Hospital, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMHWRU), Vientiane, Vientiane, Lao People's Democratic Republic.
Kimberley Fox: Regional Office for the Western Pacific, World Health Organization (WHO), Manila, Philippines.
Jason Hinds: Institute for Infection and Immunity, St George's University of London, London, UK.
Kerryn A Moore: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Monica L Nation: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Casey L Pell: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Anonh Xeuatvongsa: National Immunization Programme, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Paul N Newton: Microbiology Laboratory, Mahosot Hospital, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMHWRU), Vientiane, Vientiane, Lao People's Democratic Republic.
Kim Mulholland: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
Catherine Satzke: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
David A B Dance: Microbiology Laboratory, Mahosot Hospital, Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMHWRU), Vientiane, Vientiane, Lao People's Democratic Republic.
Fiona M Russell: Infection and Immunity, Murdoch Childrens Research Institute (MCRI), Parkville, Victoria, Australia.
INTRODUCTION: Empiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of PCV, which benefits both vaccinated and non-vaccinated individuals, are mediated by reductions in vaccine-type (VT) carriage (a prerequisite for disease). The aim of this study among hospitalised children in Lao People's Democratic Republic (Lao PDR) is to determine the effectiveness of a 13-valent PCV (PCV13) against VT pneumococcal nasopharyngeal carriage (direct effects) and the association between village-level PCV13 coverage and VT carriage (indirect effects). METHODS: Pneumococcal nasopharyngeal carriage surveillance commenced in December 2013, shortly after PCV13 introduction (October 2013). We recruited and swabbed children aged 2-59 months admitted to hospital with acute respiratory infection. Pneumococci were detected using quantitative real-time PCR and serotyped using microarray. PCV13 status and village-level PCV13 coverage were determined using written immunisation records. Associations between both PCV13 status and village-level PCV13 coverage and VT carriage were calculated using generalised estimating equations, controlling for potential confounders. RESULTS: We enrolled 1423 participants and determined PCV13 coverage for 368 villages (269 863 children aged under 5 years). By 2017, median village-level vaccine coverage reached 37.5%, however, the IQR indicated wide variation among villages (24.1-56.4). Both receipt of PCV13 and the level of PCV13 coverage were independently associated with a reduced odds of VT carriage: adjusted PCV13 effectiveness was 38.1% (95% CI 4.1% to 60.0%; p=0.032); and for each per cent increase in PCV13 coverage, the estimated odds of VT carriage decreased by 1.1% (95% CI 0.0% to 2.2%; p=0.056). After adjustment, VT carriage decreased from 20.0% to 12.8% as PCV13 coverage increased from zero to 60% among under 5. CONCLUSIONS: Despite marked heterogeneity in PCV13 coverage, we found evidence of indirect effects in Lao PDR. Individual vaccination with PCV13 was effective against VT carriage.
