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

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

Impact of the change in WHO's severe pneumonia case definition on hospitalized pneumonia epidemiology: case studies from six countries

Objective: To quantify the impact of the change in definition of severe pneumonia on documented pneumonia burden. Methods: We reviewed existing data acquired during observational hospitalized pneumonia studies, before the introduction of the pneumococcal conjugate vaccine, in infants aged 2-23 months from Fiji, Gambia, Lao People's Democratic Republic, Malawi, Mongolia and Viet Nam. We used clinical data to calculate the percentage of all-cause pneumonia hospitalizations with severe pneumonia, and with primary end-point consolidation, according to both the 2005 or 2013 World Health Organization (WHO) definitions. Where population data were available, we also calculated the incidence of severe pneumonia hospitalizations according to the different definitions. Findings: At six of the seven sites, the percentages of all-cause pneumonia hospitalizations due to severe pneumonia were significantly less (P < 0.001) according to the 2013 WHO definition compared with the 2005 definition. However, the percentage of severe pneumonia hospitalizations, according to the two definitions of severe pneumonia, with primary end-point consolidation varied little within each site. The annual incidences of severe pneumonia hospitalizations per 100 000 infants were significantly less (all P < 0.001) according to the 2013 definition compared with the 2005 definition, ranging from a difference of -301.0 (95% confidence interval, CI: -405.2 to -196.8) in Fiji to -3242.6 (95% CI: -3695.2 to -2789.9) in the Gambia. Conclusion: The revision of WHO's definition of severe pneumonia affects pneumonia epidemiology, and hence the interpretation of any pneumonia intervention impact evaluation

Evaluation strategies for measuring pneumococcal conjugate vaccine impact in low-resource settings

Objectives: Pneumococcal conjugate vaccines (PCVs) are effective in reducing pneumococcal disease. We measured 13-valent PCV (PCV13) effect on different pneumococcal outcomes using diverse studies in Lao People’s Democratic Republic. Methods: Studies included: pre-PCV13 population-based record review of hospitalized childhood pneumonia cases; acute respiratory infection (ARI) study post-PCV13 to demonstrate effectiveness (VE) against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance in all ages (2004–2018); carriage studies in children hospitalized with ARI (2013–2019); community carriage surveys pre- and post-PCV13. Results: Annual pneumonia incidence rate in children pre-PCV13 was 1,530 (95% confidence interval [CI] 1,477–1,584) per 100,000. Adjusted VE against hypoxic pneumonia was 37% (95% CI 6–57%). For IPD, 85% (11/13) of cases were due to vaccine-types pre-PCV13, and 43% (3/7) post-PCV13 in children aged <5 years; for ≥5 years, 61% (27/44) and 42% (17/40), respectively. For ARI cases, adjusted VE for vaccine-type carriage was 39% (95% CI 4–60) in <5 year olds; slightly higher than community surveys (23% [95% CI 4–39%] in 12–23 month olds). Conclusions: Despite limited baseline data, we found evidence of PCV13 impact on disease and carriage. Our approach could be used in similar settings to augment existing WHO PCV evaluation guidelines