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

Low and disparate seroprotection after pentavalent childhood vaccination in the Lao People's Democratic Republic: a cross-sectional study

Objective In Lao People's Democratic Republic, the high burden of vaccine-preventable diseases is thought to be mainly due to low vaccine coverage. We investigated the seroprotective response against diphtheria–tetanus–whole cell pertussis–hepatitis B–Haemophilus influenzae type b (DTPw-HepB-Hib) vaccine in children. Methods Serum was collected from 1131 children aged 9 to 50 months and their mothers in a cross-sectional study between December 2013 and July 2014. All children had records of three injections of the DTPw-HepB-Hib vaccine. Serum was analysed for hepatitis B surface antigen (HBsAg), anti-HBsAg (anti-HBs), anti–hepatitis B virus core antigen (anti-HBc), anti-diphtheria and anti-tetanus antibodies. Stool samples were collected for detection of parasites. Demographic and nutritional information were also obtained. Results Protective levels of anti-HBs antibodies were found in 394 (37.9%) of 1039 children; 529 (55.7%) of 950 and 809 (85.2%) of 950 children were seroprotected against diphtheria and tetanus. Time since vaccination, age, home birth and malnutrition only partially explained the poor vaccine responses. Overall, 81 (7.8%) of 1039 children and 445 (40.3%) of 1105 of mothers were anti-HBc positive. Ten (1.0%) of 1039 of the children and 77 (7.0%) of 1105 of the mothers were HBsAg carriers. Conclusions After a full documented course of vaccination, seroprotective rates were unusually low and disparate against components of the pentavalent vaccine. These can only partially be explained by the negative predictors identified. Although many children had been infected, only few were chronic carriers of HBsAg. Our study demonstrates an urgent need to monitor the serologic response to vaccination, particularly in resource-poor countries

Some sustained improvements in pneumonia case management four and five years following implementation of paediatric hospital guidelines in Lao PDR

In 2010, WHO paediatric hospital guidelines were implemented in Lao PDR, along with training workshops and feedback audits, achieving significant improvements in pneumonia case management when assessed one-year post-intervention. The sustainability of these improvements is hereby assessed, four and five years post-intervention. Medical records of children aged 1-59 months, diagnosed with pneumonia in 2010, 2011, 2014 and 2015 from a central Lao hospital were reviewed. Information relating to clinical steps in pneumonia case management was extracted and a scoring system applied based on the documentation of each clinical step, producing a pneumonia assessment score for each case. Comparisons of clinical steps and mean assessment score across study years were performed using Pearson's chi-squared and t-tests, respectively. Of 231 pneumonia cases, the mean assessment scores in 2010, 2011, 2014 and 2015 were 57%, 96%, 69% and 69% respectively, showing a significant reduction from the immediate post-intervention period (2011) to 2015 (p < 0.01). Mean assessment score in 2014/2015 was significantly higher than in 2010 (p < 0.01). The high standards of pneumonia case management in 2011 were not observed in 2014/2015 in the absence of ongoing intervention but overall quality of care remained higher than pre-intervention levels, suggesting some degree of sustainability in the long-term

The effectiveness of the 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia in children in Lao People's Democratic Republic: An observational hospital-based test-negative study

Background Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. Methods A prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. Findings There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. Interpretation PCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings

The effectiveness of the 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia in children in Lao People's Democratic Republic: An observational hospital-based test-negative study

Background: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. Methods: A prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. Findings: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. Interpretation: PCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings. Funding: Funded by the Bill & Melinda Gates Foundation

High prevalence of mumps in Lao People's Democratic Republic

In the Lao People’s Democratic Republic (PDR), mumps is not a notifiable disease and mumps vaccine is currently not included in the routine childhood immunization programme. In order to assess the burden of disease, we investigated the seroprevalence of mumps-specific IgG antibodies across four provinces. In addition, we genetically characterized mumps viruses from the past 3 years from several outbreaks and single cases. Blood and/or throat swabs from suspected cases were investigated for specific IgM antibodies or viral RNA. Mumps cases occurred between March and November in 2011-2013 and 5- to 15-year-olds were most affected. Four sequences from an outbreak in the north of Lao PDR in 2011 were identical and belonged to genotype G. Eight sequences from two outbreaks and two individual cases from 2012 and 2013 belonged to genotype J. In addition, sera collected from 2379 healthy infants and school pupils aged between 9 months and 19 years and from pregnant women aged between 16 and 46 years were investigated for mumps-specific IgG. Overall, 58.2% were positive, 39.5% were negative and the remaining 2.3% were equivocal. The seropositivity increased with age, with the lowest percentage found in <1-year-old infants (9.1%) and the highest in the cohort of pregnant women (69.2%). More female subjects than male subjects were seropositive (60.4 vs. 54.9%). There were some differences between the locations. Mumps should be a notifiable disease in Lao PDR in order to get more accurate case numbers and cost estimates for public health-care, and vaccination of children and high-risk groups should be considered

Acute respiratory infections in hospitalized children in Vientiane, Lao PDR - the importance of Respiratory Syncytial Virus

The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children &lt;5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD® kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children &lt;3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time