Rotavirus diarrhea in hospitalized children under 5 years of age in Vientiane, Lao PDR, 2009-2015.

BACKGROUND: Diarrhea is a leading cause of death in children <5 years worldwide, causing an estimated 215,000 deaths in 2013. This evaluation tracks the epidemiologic patterns and most common rotavirus genotypes among hospitalized children in this age group with acute gastroenteritis in Lao PDR. METHODS: Children <5 years in a central tertiary hospital in the capital city were prospectively enrolled into the surveillance platform during January 2009-December 2015. We collected information regarding clinical characteristics of enrolled children. Stool samples were obtained within 24 h of hospital admission and tested for rotavirus using rotavirus antigen detection enzyme immunoassay. Samples were sent to the regional reference laboratories in Australia and South Korea for genotyping. Bivariate analyses compared demographic and clinical characteristics between rotavirus positive and negative children using Chi-square statistical testing. Seasonality of rotavirus and annual genotype distribution are also described. RESULTS: We enrolled 1853 children <5 years with acute gastroenteritis during the surveillance period and collected 1772 fecal specimens, 982 (55%) of which tested positive for rotavirus. A higher proportion of rotavirus acute gastroenteritis was observed among children 12-23 months of age as compared to rotavirus negative children in the same age group, 41% vs 36%. Eighty-six percent of rotavirus positive children experienced vomiting, as compared to 65% of rotavirus negative children. Eighty-five percent (n = 830/982) of rotavirus positive specimens occurred during the dry season (January-April). The most common genotypes identified were G1, G2, G3 and P8 and P4. The most prevalent combined genotype differed annually during the surveillance period. CONCLUSION: Surveillance continues to be important in documenting the burden of rotavirus in children <5 years in Lao PDR as well as providing a baseline for determining the impact of rotavirus vaccine once it is introduced into Lao PDR's national immunization schedule.

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.

A Qualitative Study of Provider Perceptions of Influences on Uptake of Pediatric Hospital Guidelines in Lao PDR.

Strategies to improve the quality of hospital care are needed if ongoing gains in child health and survival are to be made. We previously reported on improvements in the quality of case management in hospitals following a guideline-based intervention in Lao PDR, with variation in the degree of change achieved between clinical conditions. This study aims to understand the factors that influenced the uptake of the guideline-based intervention, and its impact on care. This qualitative study was embedded in a mixed-methods evaluation of guideline implementation in nine hospitals in Lao PDR. Focus groups and individual interviews were conducted with 70 health staff from central, provincial, and district hospitals. The interview guide was based on the Theoretical Domains Framework. Inductive content analysis was performed on interview transcripts to identify themes, supported by field notes from the intervention. Findings were triangulated against previously reported quantitative outcomes using driver diagrams. Key influences on guidelines uptake related to the guideline and intervention (filling a void, physical accessibility, comprehensibility, training in guideline use), health staff (behavior regulation, trust in guidelines, and beliefs about consequences), and the environment (social influences particularly consensus and incorporation into clinical norms). The major barrier was family preference for treatments in conflict with guideline recommendations. This study identifies contextual factors that explain, as well as validate previously identified improvements in care following guideline implementation in Lao PDR. It provides novel understanding of why the same intervention may have a differential impact on different clinical conditions.

APOE Genotype in the Ethnic Majority and Minority Groups of Laos and the Implications for Non-Communicable Diseases.

BACKGROUND: Increasing age is associated with elevated risk of non-communicable diseases, including dementia and Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is a risk factor not only for AD, but also for cognitive decline, depressive symptoms, stroke, hypertension, coronary heart disease, cardiovascular disease, and diabetes. The Lao People's Democratic Republic (Laos) is undergoing development; consequently, life expectancy has risen. To evaluate the future risk of non-communicable diseases, we investigated APOE genotypes and anthropometric characteristics in the Laotian population. METHODOLOGY/PRINCIPAL FINDINGS: Subjects were 455 members of the Lao Loum majority and 354 members of ethnic minorities. APOE genotypes, anthropometric characteristics, blood pressure, and blood glucose were recorded. To compare individual changes, health examination data collected 5 years apart were obtained from a subset of Lao Loum subjects. APOE ε4 allele frequencies were higher among minorities (31.3%) than among Lao Loum (12.6%). In Lao Loum, but not in minorities, mean waist circumference and blood pressure increased significantly across age groups. Comparisons of health conditions between the beginning and end of the 5-year period revealed significant increases in obesity and blood glucose levels in Lao Loum. APOE ε4 carriers exhibited significant increases in resting heart rate in both ethnic groups. CONCLUSIONS/SIGNIFICANCE: A higher ε4 allele frequency was observed in Laotian minorities than in the Laotian majority. Furthermore, higher obesity, blood pressure and blood glucose were observed in the middle-aged ethnic majority. Therefore, given these genetic and non-communicable disease risk factors, it seems likely that as the Laotian population ages, elevated rates of non-communicable aging-related diseases, such as dementia, will also become more prevalent.

Epidemiological study of Japanese encephalitis virus in Vientiane, Lao PDR, in 1990s.

Phylogenetic analysis of Japanese encephalitis virus (JEV) was conducted using core-premembrane and envelope gene sequence data of two strains from Vientiane, Lao People's Democratic Republic, in 1993 and five from Okinawa, Japan, in 2002 and 2003, and previously published strains. The two Vientiane strains designated as LaVS56 and LaVS145 belonged to genotype 1 (G1) and the same subcluster of G1 as Australian strain in 2000, Thai strains in 1982-1985 and 2004-2005, and Vietnamese strain in 2005, but were distinct from the subcluster of recently distributing G1 strains widely in Asia including Okinawan strains and recent Lao strain in 2009. These clusters with own distinct distributions indicated involvements of different mechanisms and routes of spreading viruses and clarified that Australian G1 strain is from Southeast Asia, not from East Asia. Both Vientiane strains were antigenically close to P19-Br (G1, isolate, Thailand), but distinct from Nakayama (G3, prototype strain, Japan), Beijing-1 (G3, laboratory strain, China), and JaGAr#01 (G3, laboratory strain, Japan), demonstrated by cross-neutralization tests using polyclonal antisera. These results together with seroepidemiologic study conducted in Vientiane strongly suggest that diversified JEV cocirculated there in early 1990s.

Implementing WHO hospital guidelines improves quality of paediatric care in central hospitals in Lao PDR.

OBJECTIVES: To evaluate the impact of implementing a multifaceted intervention based on the WHO Pocketbook of Hospital Care for Children on the quality of case management of common childhood illnesses in hospitals in Lao PDR. METHODS: The quality of case management of four sentinel conditions was assessed in three central hospitals before and after the implementation of the WHO Pocketbook as part of a broader mixed-methods study. Data on performance of key steps in case management in more than 600 admissions were collected by medical record abstraction pre- and post-intervention, and change was measured according to the proportion of cases which key steps were performed as well as an overall score of case management for each condition. RESULTS: Improvements in mean case management scores were observed post-intervention for three of the four conditions, with the greatest change in pneumonia (53-91%), followed by diarrhoea and low birthweight. Rational drug prescribing, appropriate use of IV fluids and appropriate monitoring all occurred more frequently post-intervention. Non-recommended practices such as prescription of antitussives became less frequent. CONCLUSIONS: A multifaceted intervention based on the WHO Pocketbook of Hospital Care for children led to better paediatric care in central Lao hospitals. The degree of improvement was dependent on the condition assessed.

Erythrocyte transketolase activity, markers of cardiac dysfunction and the diagnosis of infantile beriberi.

BACKGROUND: Infantile beriberi is a potentially lethal manifestation of thiamin deficiency, associated with traditional post-partum maternal food avoidance, which persists in the Lao PDR (Laos). There are few data on biochemical markers of infantile thiamin deficiency or indices of cardiac dysfunction as potential surrogate markers. METHODOLOGY/PRINCIPAL FINDINGS: A case control study of 47 infants with beriberi and age-matched afebrile and febrile controls was conducted in Vientiane, Laos. Basal and activated erythrocyte transketolase activities (ETK) and activation (α) coefficients were assayed along with plasma brain natriuretic peptide, N-terminal pro-brain natriuretic peptide and troponin T. Basal ETK (and to a lesser extent activated ETK) and plasma troponin T were the only infant biochemical markers that predicted infantile beriberi. A basal ETK ≤ 0.59 micromoles/min/gHb gave a sensitivity (95%CI) of 75.0 (47.6 to 92.7)% and specificity (95%CI) of 85.2 (66.3 to 95.8)% for predicting infantile beriberi (OR (95%CI) 15.9 (2.03-124.2); p = 0.008) (area under ROC curve = 0.80). In contrast, the α coefficient did not discriminate between cases and controls. Maternal basal ETK was linearly correlated with infant basal ETK (Pearson's r = 0.66, p < 0.001). The odds of beriberi in infants with detectable plasma troponin T was 3.4 times higher in comparison to infants without detectable troponin T (OR 3.4, 95%CI 1.22-9.73, p = 0.019). Detectable troponin T had a sensitivity (95%CI) of 78.6 (59.0 to 91.7) % and specificity (95%CI) of 56.1 (39.7 to 71.5) % for predicting infantile beriberi. CONCLUSIONS/SIGNIFICANCE: Basal ETK is a more accurate biochemical marker of infantile beriberi than the activation coefficient. Raised plasma troponin T may be a useful indicator of infantile beriberi in infants at risk and in the absence of other evident causes.

Clinically unapparent infantile thiamin deficiency in Vientiane, Laos.

BACKGROUND: Beriberi occurs in Vientiane, Lao PDR, among breastfed infants. Clinical disease may be the tip of an iceberg with subclinical thiamin deficiency contributing to other illnesses. Thiamin treatment could improve outcome. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 778 sick infants admitted during one year without clinical evidence of beriberi were studied prospectively and erythrocyte transketolase assays (ETK) performed. Biochemical thiamin deficiency was defined both in terms of the activation coefficient (α>31%) and basal ETK activity <0.59 micromoles/min/gHb. Of the 778 infants, median (range) age was 5 (0-12) months, 79.2% were breastfed, 5.1% had α>31% and 13.4 % basal ETK<0.59 micromoles/min/gHb. Infants≥2 months old had a higher frequency of biochemical markers of thiamin deficiency. Mortality was 5.5% but, among infants ≥2 months old, mortality was higher in those with basal ETK<0.59 micromoles/min/gHb (3/47, 6.4%) than in those with basal ETK≥0.59 micromoles/min/gHb (1/146, 0.7%) (P=0.045, relative risk=9.32 (95%CI 0.99 to 87.5)). Multivariate regression analysis indicated that infant age≥2 months and fewer maternal years of schooling were independently associated with infant basal ETK<0.59 micromoles/min/gHb. CONCLUSIONS/SIGNIFICANCE: Clinically unapparent thiamin deficiency is common among sick infants (≥2 months old) admitted to hospital in Vientiane. This may contribute to mortality and a low clinical threshold for providing thiamin to sick infants may be needed.

Provider performance in treating poor patients--factors influencing prescribing practices in lao PDR: a cross-sectional study.

BACKGROUND: Out-of-pocket payments make up about 80% of medical care spending at hospitals in Laos, thereby putting poor households at risk of catastrophic health expenditure. Social security schemes in the form of community-based health insurance and health equity funds have been introduced in some parts of the country. Drug and Therapeutics Committees (DTCs) have been established to ensure rational use of drugs and improve quality of care. The objective was to assess the appropriateness and expenditure for treatment for poor patients by health care providers at hospitals in three selected provinces of Laos and to explore associated factors. METHODS: Cross-sectional study using four tracer conditions. Structured interviews with 828 in-patients at twelve provincial and district hospitals on the subject of insurance protection, income and expenditures for treatment, including informal payment. Evaluation of each patient's medical record for appropriateness of drug use using a checklist of treatment guidelines (maximum score=10). RESULTS: No significant difference in appropriateness of care for patients at different income levels, but higher expenditures for patients with the highest income level. The score for appropriate drug use in insured patients was significantly higher than uninsured patients (5.9 vs. 4.9), and the length of stay in days significantly shorter (2.7 vs. 3.7). Insured patients paid significantly less than uninsured patients, both for medicines (USD 14.8 vs. 43.9) and diagnostic tests (USD 5.9 vs. 9.2). On the contrary the score for appropriateness of drug use in patients making informal payments was significantly lower than patients not making informal payments (3.5 vs. 5.1), and the length of stay significantly longer (6.8 vs. 3.2), while expenditures were significantly higher both for medicines (USD 124.5 vs. 28.8) and diagnostic tests (USD 14.1 vs. 7.7). CONCLUSIONS: The lower expenditure for insured patients can help reduce the number of households experiencing catastrophic health expenditure. The positive effects of insurance schemes on expenditure and appropriate use of medicines may be associated with the long-term effects of promoting rational use of drugs, including support to active DTC work.

Causes of community-acquired bacteremia and patterns of antimicrobial resistance in Vientiane, Laos.

There is no published information on the causes of bacteremia in the Lao PDR (Laos). Between 2000 and 2004, 4512 blood culture pairs were taken from patients admitted to Mahosot Hospital, Vientiane, Laos, with suspected community-acquired bacteremia; 483 (10.7%) cultures grew a clinically significant community-acquired organism, most commonly Salmonella enterica serovar typhi (50.9%), Staphylococcus aureus (19.0%), and Escherichia coli (12.4%). S. aureus bacteremia was common among infants (69.2%), while children 1-5 years had a high frequency of typhoid (44%). Multi-drug-resistant S. Typhi was rare (6%). On multiple logistic regression analysis, typhoid was associated with younger age, longer illness, diarrhea, higher admission temperature, and lower peripheral white blood cell count than non-typhoidal bacteremia. Empirical parenteral ampicillin and gentamicin would have some activity against approximately 88% of clinically significant isolates at a cost of US $1.4/day, an important exception being B. pseudomallei. Bacteremic infants in this setting require an anti-staphylococcal antibiotic.

Dietary and socio-economic factors associated with beriberi in breastfed Lao infants.

A case-control study was conducted to investigate the dietary and socio-economic factors associated with beriberi in infants attending three public hospitals in Vientiane, Lao PDR. Forty-three breast-feeding infants with a median (range) age of 3 (1-9) months were admitted with beriberi. This was defined as the presence of signs of congestive heart failure or shock in the absence of fever or other signs of sepsis, hypovolaemia or cardiac abnormalities, with rapid clinical improvement following parenteral thiamine. Subjects were matched by age and diet to 43 breast-feeding healthy control infants. Compared with control mothers, mothers of infants with beriberi had significantly less diet diversity (p <0.001), soaked glutinous rice for significantly longer or were more likely to pour off excess water from non-glutinous rice (p =0.006), had fewer years of schooling (p <0.05), were more likely to report that income was inadequate for basic needs (p <0.001), to perform hard physical labour (p <0.01) and to be married to farmers (p <0.01). Clinically significant thiamine deficiency in breastfed infants in Lao relates to methods of preparing rice, the food selected by lactating mothers and the family's socio-economic status.