Nasopharyngeal Pneumococcal Colonization Density Is Associated With Severe Pneumonia in Young Children in the Lao People's Democratic Republic.

BACKGROUND: No studies have explored the association between pneumococcal nasopharyngeal density and severe pneumonia using the World Health Organization (WHO) 2013 definition. In Lao People's Democratic Republic (Lao PDR), we determine the association between nasopharyngeal pneumococcal density and severe pneumonia in children. METHODS: A prospective observational study was undertaken at Mahosot Hospital, Vientiane, from 2014 to mid-2018. Children <5 years admitted with acute respiratory infections (ARIs) were included. Clinical and demographic data were collected alongside nasopharyngeal swabs for pneumococcal quantification by lytA real-time quantitative polymerase chain reaction. Severe pneumonia was defined using the 2013 WHO definition. For pneumococcal carriers, a logistic regression model examined the association between pneumococcal density and severe pneumonia, after adjusting for potential confounders including demographic and household factors, 13-valent pneumococcal conjugate vaccine status, respiratory syncytial virus co-detection, and preadmission antibiotics. RESULTS: Of 1268 participants with ARI, 32.3% (n = 410) had severe pneumonia and 36.9% (n = 468) had pneumococcal carriage. For pneumococcal carriers, pneumococcal density was positively associated with severe pneumonia (adjusted odds ratio, 1.4 [95% confidence interval, 1.1-1.8]; P = .020). CONCLUSIONS: Among children with ARIs and pneumococcal carriage, pneumococcal carriage density was positively associated with severe pneumonia in Lao PDR. Further studies may determine if pneumococcal density is a useful marker for pneumococcal conjugate vaccine impact on childhood pneumonia.

Epidemiology of acute respiratory viral infections in children in Vientiane, Lao People's Democratic Republic.

Respiratory infections are one of the most frequent reasons for medical consultations in children. In low resource settings such as in Lao People's Democratic Republic, knowledge gaps and the dearth of laboratory capacity to support differential diagnosis may contribute to antibiotic overuse. We studied the etiology, temporal trends, and genetic diversity of viral respiratory infections in children to provide evidence for prevention and treatment guidelines. From September 2014 to October 2015, throat swabs and nasopharyngeal aspirates from 445 children under 10 years old with symptoms of acute respiratory infection were collected at the Children Hospital in Vientiane. Rapid antigen tests were performed for influenza A and B and respiratory syncytial virus. Real-time reverse-transcription polymerase chain reactions (RT-PCRs) were performed to detect 16 viruses. Influenza infections were detected with a higher sensitivity using PCR than with the rapid antigen test. By RT-PCR screening, at least one pathogen could be identified for 71.7% of cases. Human rhinoviruses were most frequently detected (29.9%), followed by influenza A and B viruses combined (15.9%). We identify and discuss the seasonality of some of the infections. Altogether these data provide a detailed characterization of respiratory pathogens in Lao children and we provide recommendations for vaccination and further studies.

Nasal or throat sampling is adequate for the detection of the human respiratory syncytial virus in children with acute respiratory infections.

Human respiratory syncytial virus (HRSV) is one of the most important causes of acute respiratory infections (ARI) in young children. HRSV diagnosis is based on the detection of the virus in respiratory specimens. Nasopharyngeal swabbing is considered the preferred method of sampling, although there is limited evidence of the superiority of nasopharyngeal swabs (NPS) over the less invasive nasal (NS) and throat (TS) swabs for virus detection by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR). In the current study, we compared the three swabbing methods for the detection of HRSV by RT-qPCR in children hospitalized with ARI at Mahosot Hospital, Vientiane, Laos. In 2014, NS, NPS, and TS were collected from 288 children. All three samples were tested for HRSV by RT-qPCR; 141 patients were found positive for at least one sample. Almost perfect agreements (κ > 0.8) between the swabs, compared two by two, were observed. Detection rates for the three swabs (between 93% and 95%) were not significantly different, regardless of the clinical presentation. Our findings suggest that the uncomfortable and technically more demanding NPS method is not mandatory for HRSV detection by RT-qPCR.

Haemophilus influenzae serotype b seroprevalence in central Lao PDR before and after vaccine introduction.

INTRODUCTION: Vaccination has dramatically reduced invasive Haemophilus influenzae type b (Hib) disease worldwide. Hib vaccination was introduced in the Lao PDR in 2009, as part of the pentavalent vaccine. To contribute to the understanding of the epidemiology of Hib in Lao PDR and the protection levels before and after the introduction of the vaccination, we tested serum samples from existing cohorts of vaccine age-eligible children and unvaccinated adolescents for antibodies against Hib. METHODS: Serum samples from 296 adolescents born before vaccine introduction and from 1017 children under 5 years (vaccinated and unvaccinated) were tested for anti-Hib antibodies by ELISA. Bivariate analyses were performed to investigate factors associated with long-term protection. RESULTS: The vast majority of all participants showed evidence of short- (42.7%) or long-term (56.1%) protection against Hib. Almost all of the unvaccinated adolescents had antibody titers indicating short-term protection and almost half (45.6%) were long-term protected. Nearly all children (>99.0%) were at least short-term protected, even those that were unvaccinated or whose vaccination status was unknown. Among vaccinated children, participants vaccinated more than 1 or 2 years ago and with a mid-upper arm circumference z-score < -2 were less likely to be long-term protected. DISCUSSION: Nearly all adolescents born before the introduction of Hib vaccination in the Lao PDR had antibody titers corresponding to at least short-term protection, indicating a high burden of Hib disease at that time. After vaccine introduction, all but four children (>99%) showed at least short-term protection. Possible explanations for the proportion of protected, yet apparently unvaccinated children, may be past infections, cross-reacting antibodies or faulty vaccination documentation. Our results highlight the need for robust surveillance and reporting of invasive Hib disease to determine the burden of disease despite vaccination.

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.

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.

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.

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 <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 <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.