Seroprotection at Different Levels of the Healthcare System After Routine Vaccination With Diphtheria-Tetanus-Pertussis whole cell-Hepatitis B-Haemophilus influenzae Type B in Lao People's Democratic Republic.

BACKGROUND: The Lao People's Democratic Republic continues to sustain a considerable burden of vaccine-preventable diseases because of incomplete vaccine coverage and weak vaccine responses. We have assessed seroconversion after routine vaccination with the pentavalent vaccine to capture weaknesses of vaccine management at the different levels of the healthcare system. METHODS: A total of 1151 children (aged 8-28 months) with 3 documented doses of the pentavalent vaccine delivered at central hospitals in Vientiane and the provincial hospital, 3 district hospitals, and 10 health centers in Bolikhamxay province were enrolled. Sociodemographic information was collected with a standardized questionnaire. Serum samples were analyzed for antibodies against vaccine components, and bivariate and multivariable analyses were performed to identify risk factors for low vaccine responses. RESULTS: Seroprotection rates at the provincial, district, and health center level were as high as in central hospitals, but seroprotection rates in areas covered by remote health centers were significantly lower. Protective levels also rapidly decreased with age at sampling. Seroprotection rates in Bolikhamxay against the different components reached 70%-77% and were up to 20% higher than in previous studies in the same region; 18.8% more children received the hepatitis B vaccine birth dose and the hepatitis B virus infection rate was 4 times lower. CONCLUSIONS: Vaccine immunogenicity has dramatically improved in a central province, likely due to training and investment in the cold chain. Nevertheless, there remains a need to focus on the "last mile" in remote areas were most children are vaccinated through outreach activities.

Role of pre-existing immunity in driving the dengue virus serotype 2 genotype shift in the Philippines: A retrospective analysis of serological data.

OBJECTIVE: The invasion of dengue virus (DENV)-2 Cosmopolitan genotype into the Philippines, where the Asian II genotype previously circulated challenges the principle of dengue serotype-specific immunity. Assessment of antibodies in this population may provide a mechanistic basis for how new genotypes emerge in dengue-endemic areas. METHODS: We evaluated the neutralizing antibody (nAb) and antibody-dependent enhancement (ADE) responses against the two genotypes using archived serum samples collected from 333 patients with confirmed dengue in Metro Manila, Philippines, before, during, and after the introduction of the Cosmopolitan genotype. We quantified nAb titers in baby hamster kidney (BHK-21) cells with or without the Fcγ receptor IIA (FcγRIIA) to detect the capacity of virus-antibody complexes to neutralize or enhance DENV. RESULTS: The nAb potency of the archived serum samples against the two genotypes was greatly affected by the presence of FcγRIIA. We found significant differences in nAb titers between the two genotypes in BHK-21 cells with FcγRIIA (P <0.0001). The archived serum samples were incapable of fully neutralizing the Cosmopolitan genotype, but instead strongly promoted its ADE compared to the Asian II genotype (P <0.0001). CONCLUSION: These results reinforce the role of pre-existing immunity in driving genotype shifts. Our finding that specific genotypes exhibit differing susceptibilities to ADE by cross-reactive antibodies may have implications for dengue vaccine development.

The Development of New Primer Sets for the Amplification and Sequencing of the Envelope Gene of All Dengue Virus Serotypes.

Dengue virus (DENV) poses a significant threat to global health, infecting approximately 390 million people annually. This virus comprises four serotypes capable of causing severe disease. Genetic analyses are crucial for understanding the epidemiology, evolution, and spread of DENV. Although previous studies have focused on the envelope protein-coding (E) gene, only a few primers can efficiently detect and amplify the viral genes from multiple endemic countries simultaneously. In this study, we designed degenerate primer pairs for each DENV serotype to amplify and sequence the entire E gene, using globally representative sequences for each serotype. These primers were validated using DENV isolates from various Asian countries and demonstrated broad-spectrum detection capabilities and high-quality sequences. The primers provide effective tools for genetic analysis in the regions affected by dengue, aiding strain identification and epidemiological studies during outbreaks.

Seroprevalence of measles and rubella antibodies in vaccinated and unvaccinated infants in the Lao People's Democratic Republic.

BACKGROUND: Even though measles vaccination was introduced in the Lao PDR in 1984, coverage rates remain consistently low and outbreaks continue to occur frequently. This study was performed to investigate the seroprevalence of measles and rubella antibodies in vaccinated and unvaccinated children from Central Lao PDR. METHODS: Antibody titres of 1090 children aged 8-29 months who were vaccinated at different levels of the health care system were assessed by ELISA. Bivariate and multivariable analyses were performed to identify factors affecting seropositivity against measles and rubella. RESULTS: Among the vaccinated children, 67.5% in Vientiane Province and 76.4% in Bolikhamxay Province were double positive/borderline for measles and rubella IgG. A high proportion of unvaccinated children at both study sites (24.4% and 38.4%) were positive/borderline for measles and/or rubella. Time since vaccination <180 days, more than two siblings, and a mother who is a farmer/labourer were negatively associated with seropositivity. CONCLUSIONS: A high prevalence of measles and rubella antibodies was found in unvaccinated children, indicating widespread circulation of both viruses and underreporting of cases. The high proportion of vaccinated children still susceptible to measles suggests problems with vaccine immunogenicity, emphasizing the need for regular evaluations of vaccine efficacy and management.

Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm).

Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.

Timeliness of immunisation with the pentavalent vaccine at different levels of the health care system in the Lao People's Democratic Republic: A cross-sectional study.

BACKGROUND: The timely administration of vaccines is considered to be important for both individual and herd immunity. In this study, we investigated the timeliness of the diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (pentavalent) vaccine, scheduled at 6, 10 and 14 weeks of age in the Lao People's Democratic Republic. We also investigated factors associated with delayed immunization. METHODS: 1162 children aged 8-28 months who had received the full course of the pentavalent vaccine at different levels of the health care system were enrolled. Vaccination dates documented in hospital records and/or immunisation cards were recorded. Age at vaccination and time intervals between doses were calculated. Predictors for timely completion with the pentavalent vaccine at 24 weeks were assessed by bivariate and multivariable analyses. RESULTS: Several discrepancies in dates between vaccination documents were observed. In general, vaccination with the pentavalent vaccine was found to be delayed, especially in health care settings below the provincial hospital level. Compared to the central hospital level, less participants who were vaccinated at the district/health center level received the third dose by 16 (48% at the central hospital level vs. 7.1% at the district and 12.4% at the health center level) and 24 weeks of age (94.4% at the central hospital level vs 64.6% at the district-outreach and 57.4% at the health center level) respectively. In logistic regression analyses, lower education level of the mother as well as vaccination by outreach service, were independently associated with delayed completion of vaccination. CONCLUSION: We observed a general delay of vaccination, especially at lower ranked facilities, which correlated with indicators of poor access to health services. This highlights the need for further improving health equity in rural areas. Age-appropriate vaccination should become a quality indicator for the national immunization programme. In addition, we recommend further training of the health care staff regarding the importance of reliable documentation of dates.

Association between helminth infections and diabetes mellitus in adults from the Lao People's Democratic Republic: a cross-sectional study.

BACKGROUND: As a result of epidemiological transition, the health systems of low- and middle-income countries are increasingly faced with a dual disease burden of infectious diseases and emerging non-communicable diseases. Little is known about the mutual influence of these two disease groups. The aim of this study was to investigate the co-occurrence of helminth infections and diabetes mellitus in adults in Lao People's Democratic Republic (Lao PDR). METHODS: We conducted a cross-sectional study among 1600 randomly selected adults aged 35 and older from four different socio-economical and ecological provinces. Information on socio-demographics, risk factors and health conditions was obtained from personal interviews. Clinical assessments including anthropometry (height, weight, waist and hip circumference) and blood pressure measurements were also conducted. Diabetes was classified based on self-reported diagnoses and a point-of-care glycated haemoglobin (HbA1c) test from finger prick blood samples. Stool samples for helminth diagnosis were examined with formalin-ether concentration technique for intestinal parasitic infections. The independent associations of helminth infections with diabetic status and HbA1c were assessed using multiple regression analyses. RESULTS: The prevalence of pre-diabetes and diabetes was 37.3% and 22.8%, respectively. Fifty-six percent of diabetic cases were undiagnosed and 85% of diagnosed diabetic cases had poor glycemic control. Participants from rural areas and from southern parts of the country had higher infection rates, with Opisthorchis viverrini, being the most common helminth infection (30.5%). We found a positive association between Taenia spp. infections and HbA1c (ß = 0.117; 95% CI: 0.042-0.200) and diabetes mellitus risk (OR = 2.98; 95% CI: 1.10-8.05). No other helminth species was associated with glycated hemoglobin. CONCLUSIONS: Hyperglycaemia and diabetic rates in Lao PDR are alarmingly high, but consistent with other high rates in the region. Given the high rates of under-diagnosis and poorly-controlled glycaemia in diabetes mellitus patients, routine diabetes screening and treatment is essential for the local healthcare system. Large longitudinal cohorts integrating biomarkers are warranted in the search of causal diabetes mellitus risk factors in the region. Common intestinal helminth infections, including O. viverrini, are unlikely to explain the high diabetes mellitus rates observed.