Pneumococcal carriage in vaccine-eligible children and unvaccinated infants in Lao PDR two years following the introduction of the 13-valent pneumococcal conjugate vaccine.

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3 + 0 schedule (doses at 6, 10 and 14 weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5-8 week old infants (n = 1000) and 12-23 month old children (n = 1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12-23 months (adjusted prevalence ratio [aPR] 0.77 [0.61-0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89-1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43-1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85-1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p < 0.001). In 12-23 month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p = 0.004 and p < 0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR

Determining the pneumococcal conjugate vaccine coverage required for indirect protection against vaccine-type pneumococcal carriage in low and middle-income countries: a protocol for a prospective observational study.

INTRODUCTION: Pneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific. METHODS AND ANALYSIS: We are recruiting cases, defined as children aged 2-59 months admitted to participating hospitals with acute respiratory infection in Lao People's Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened using lytA qPCR and serotyped by microarray. Village-level vaccination coverage, for the resident communities of the recruited cases, is determined using administrative data or community survey. Our analysis will investigate the relationship between VT carriage among undervaccinated cases (indirect effects) and vaccine coverage using generalised estimating equations. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant ethics committees at participating sites. The results are intended for publication in open-access peer-reviewed journals and will demonstrate methods suitable for low- and middle-income countries to monitor vaccine impact and inform vaccine policy makers about the PCV coverage required to achieve indirect protection

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.

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 lytA 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

Influences on maternal and child nutrition in the highlands of the northern Lao PDR

In two remote northern provinces of the Lao People's Democratic Republic, provincial and district teams were trained and subsequently conducted a qualitative study using a participatory approach to investigate people's knowledge, attitudes, beliefs and practices in relation to women's and children's nutrition. Using focus group discussions, key informant interviews, and structured observation, the teams found that certain nutrition behaviours, including food taboos, may contribute to the high prevalence of child malnutrition and micronutrient deficiencies in these northern provinces. Ethnic groups gave details of nutrition-related beliefs and practices; the teams found that many of these are likely to be amenable to change through relatively low cost nutrition promotion informed by these findings. In particular, barriers to exclusive breastfeeding, food taboos and hygiene behaviour could be addressed. The study also demonstrated that with appropriate training, supervision and support, local teams are able to plan and conduct a large scale qualitative study. (author abstract

Health policy processes in Asian transitional economies

This paper draws on studies of current knowledge on health policy processes in Cambodia, China and Lao PDR by a number of researchers in the POVILL Consortium. They are based on reviews of international and national literature and of policy documents, interviews with key informants and preliminary findings of small studies in a selection of rural localities. It explores why policy makers have become increasingly interested in strategies for helping household cope when a family member develop serious illness and the reason for their preference for demand-side approaches. It looks at, amongst other things, the influence of policy networks and stakeholder interests on policy formulation. It then explores factors that affect implementation. It concludes with a discussion of the questions that ongoing field studies are addressing

Factors associated with pneumococcal carriage and density in infants and young children in Laos PDR

Nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus) is a precursor to pneumococcal disease. Several host and environmental factors have been associated with pneumococcal carriage, however few studies have examined the relationship between host factors and pneumococcal carriage density. We sought to identify risk factors for pneumococcal carriage and density using data from cross-sectional pneumococcal carriage surveys conducted in the Lao People's Democratic Republic before and after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Nasopharyngeal swabs were collected infants from aged 5-8 weeks old (n = 999) and children aged 12-23 months (n = 1,010), pneumococci detected by quantitative PCR, and a risk factor questionnaire completed. Logistic and linear regression models were used to evaluate associations between participant characteristics and pneumococcal carriage and density. In infants aged 5-8 weeks, living in a household with two or more children under the age of five years (aOR 1.97; 95% CI 1.39-2.79) and low family income (aOR 1.64; 95% CI 0.99-2.72) were positively associated with pneumococcal carriage. For children aged 12-23 months, upper respiratory tract infection (URTI) symptoms (aOR 2.64; 95% CI 1.97-3.53), two or more children under five in the household (aOR 2.40; 95% CI 1.80-3.20), and rural residence (aOR 1.84, 95% CI 1.35-2.50) were positively associated with pneumococcal carriage. PCV13 vaccination was negatively associated with carriage of PCV13 serotypes (aOR 0.60; 95% CI 0.44-0.83). URTI symptoms (p < 0.001), current breastfeeding (p = 0.005), rural residence (p = 0.012), and delivery by Caesarean section (p = 0.035) were associated with higher mean pneumococcal density in pneumococcal carriers (both age groups combined). This study provides new data on pneumococcal carriage and density in a high disease burden setting in southeast Asia