Lasting benefit of infant hepatitis B vaccination in adolescents in the Lao People’s Democratic Republic

Objectives Hepatitis B is endemic in Lao PDR with 8–10% of the adult population being chronically infected. We investigated the impact of hepatitis B vaccination on infection in adolescents born shortly before and after the introduction of the vaccine in 2001. Methods 779 students from Vientiane Capital and Bolikhamxay province were tested for HBV markers by ELISA. Socio-demographic information was collected with a standardized questionnaire. Predictors/risk factors for seroprotection or exposure to hepatitis B infection were assessed by bivariate and multivariable analyses. Results The prevalence of a serological vaccination profile increased significantly after the introduction of the vaccine (13.2%–21.9%, p < 0.05, in Vientiane; 3.0%–19.7%, p < 0.001, in Bolikhamxay), which translated into at least a 2-times lower prevalence of past infection. In logistic regression, older students in Bolikhamxay were less likely to be vaccinated and more likely to have been infected by HBV in the past. Conclusion Even though this study documented a sizable and lasting reduction in past hepatitis B infections in adolescents born after the introduction of infant hepatitis B vaccination, the overall levels of protective anti-HBs were low and warrant at least the introduction of a booster for adolescents. Furthermore, we suggest improving the coverage of the hepatitis B birth dose

Diphtheria in Lao PDR: insufficient coverage or ineffective vaccine?

Background During late 2012 and early 2013 several outbreaks of diphthe-ria were notified in the North of the Lao People’s Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions. Methods A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12–59 months. Serum samples, socio-demographic data, nutri-tional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA. Results Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4–28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74–85, 4], p = 0.01) and the lack of advice on vac-cination given at birth (OR: 9.8 [95% CI: 1.5–63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008–0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status. Conclusions Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical defi-ciencies in the methods of storage and distribution of vaccines as well as unreliability of vac-cination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against diphtheria and recommendations are provided to prevent future outbreaks

Pertussis in Lao PDR: Seroprevalence and disease

Objectives Pertussis is a debilitating vaccine-preventable infection. The aim of this study was to determine susceptibility and exposure to pertussis in Lao PDR in different age groups and subpopulations. Methods A total 3072 serum samples were obtained from different cohorts: children with documented vaccination, pre-schoolers, schoolchildren, blood donors, healthcare workers (HCWs), and pregnant women and paired cord blood. Samples were tested for anti-pertussis toxin IgG antibodies. A history of Bordetella pertussis exposure was defined according to antibody titres. Four hundred and seventy-five throat swabs and nasopharyngeal aspirates were analysed by PCR for the presence of B. pertussis in symptomatic children at the Children's Hospital in Vientiane. Results Overall pertussis seroprevalence was 57.5%. The prevalence of titres indicating acute infection or recent vaccination or infection/vaccination within the last 12 months ranged from 7.4% (100/1356) in adults to 21.4% (25/117) in pre-schoolers (age 1–5 years). B. pertussis was detected in 1.05% (5/475) of children with respiratory symptoms in Vientiane Capital. Conclusions It is suggested that routine childhood vaccination, in particular outreach, as well as vaccination of HCWs should be strengthened. A childhood booster and vaccination of pregnant mothers should be considered. There is also a need to improve reporting and to introduce pertussis testing in at least one central facility

Varicella zoster and fever rash surveillance in Lao People’s Democratic Republic

Background In Lao PDR, the epidemiology of varicella infection is uncertain, since it is not a notifiable disease and VZV outbreaks are rarely reported as fever/rash (F/R) diseases. Methods We estimated the seroprevalence of VZV (IgG ELISA) in different age cohorts (9 months to 46 years; N = 3139) and investigated VZV and 6 other viruses in patients during F/R outbreaks and in an ad hoc sentinel site in the context of the national reporting system (IgM ELISA, PCR). Results At least 80% of the sampled population had evidence of VZV infection before the age of 15. The largest increase in seroprevalence occurred between the age groups 1 to 5 and 6 to 7 year-olds. A VZV outbreak (clade 2) also occurred in this age group mostly during the first year of primary school (median age 6 years, interquartile range 4.0–7.5). During a dengue outbreak, 6% had varicella. At our F/R sentinel site, 14% of children with viral etiology were laboratory diagnosed as varicella and among others, a sizeable number of measles (N = 12) and rubella cases (N = 25) was detected compared to those reported for the whole country (N = 56 and 45), highlighting nationwide a large challenge of underreporting or misdiagnosis of these notifiable diseases because of lack of diagnostic laboratory capacity. Conclusion We recommend strengthening the clinical and laboratory diagnosis of VZV, measles and rubella, the surveillance and reporting of notifiable F/R diseases by retraining of healthcare workers and by setting up sentinel sites and enhancing laboratory capacity

Hepatitis B virus in the Lao People’s Democratic Republic: a cross sectional serosurvey in different cohorts

Background Despite hepatitis B vaccination at birth and at 6, 10 and 14 weeks of age, hepatitis B virus (HBV) infection continues to be endemic in the Lao People’s Democratic Republic (PDR). We carried out a cross-sectional serological study in infants, pre-school children, school pupils and pregnant women to determine their burden of disease, risk of infection and vaccination status. Methods A total of 2471 participants between 9 months and 46 years old were recruited from urban (Vientiane Capital, Luang Prabang), semi-urban (Boulhikhamxai and Savannakhet) and remote rural areas (Huaphan). All sera were tested for anti-HBs and anti-HBc. Sera testing positive for anti-HBc alone were further tested for the presence of HBsAg. Results A low prevalence of HBsAg (0.5%) was detected among infants from Vientiane and Luang Prabang, indicating some success of the vaccination policy. However, only 65.6% had protective anti-HBs antibodies, suggesting that vaccination coverage or responses remain sub-optimal, even in these urban populations. In pre-school children from remote areas in Huaphan, 21.2% were positive for anti-HBc antibodies, and 4.6% were for HBsAg positive, showing that a significant proportion of children in these rural regions have early exposure to HBV. In pre-school children with 3 documented HBV vaccinations, only 17.0% (15/55) were serologically protected. Among school-children from semi-urban regions of Luang Prabang, Boulhikhamxai and Savannakhet provinces, those below the age of 9 who were born after HBV vaccine introduction had anti-HBc and HBsAg prevalence of 11.7% and 4.1%, respectively. The prevalence increased to 19.4% and 7.8% of 10–14 year olds and to 27% and 10.2% of 15–19 year olds. Pregnant women from Luang Prabang and Vientiane had very high anti-HBc and HBsAg prevalence (49.5% and 8.2%), indicating high exposure and risk of onward vertical transmission to the unborn infant. Conclusions Overall, the results demonstrate a dramatic deficiency in vaccination coverage and vaccine responses and/or documentation within the regions of Lao PDR studied, which included urbanized areas with better health care access. Timely and effective hepatitis B vaccination coverage is needed in Lao PDR

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

Comparison of population-based measles-rubella immunoglobulin G antibody prevalence between 2014 and 2019 in Lao People's Democratic Republic: Impacts of the national immunization program.

OBJECTIVES: We evaluated the effectiveness of the Lao People's Democratic Republic's measles-rubella immunization program using the seroprevalence from two cross-sectional surveys. METHODS: The nationwide surveys occurred in 2014 and 2019 using a multistage cluster sampling, both requiring samples from 2184 individuals from 52 randomly selected villages. Immunoglobulin G titers, measured using enzyme-linked immunosorbent assay, were considered positive at ≥120 mIU/ml (measles) and ≥10 IU/ml (rubella). We calculated the vaccination-related reduction in the force of rubella infection and the number of congenital rubella syndrome cases averted in 2019. RESULTS: We collected 2135 (women: 55.2%, mean age: 23.2 years) and 2001 (52.7%, 23.1 years) samples in 2014 and 2019, respectively. During 2014-2019, immunoglobulin G prevalence increased from 83.9% (95% confidence interval [CI]: 83.8-84.0) to 98.3% (97.7-98.8) for measles and from 75.4% (75.3-75.5) to 87.8% (86.4-89.2) for rubella. The most plausible reduction in the average force of rubella infection was 100% (95% CI: 28-100) since vaccination started, averting 78 (95% CI: 42-128) congenital rubella syndrome cases in 2019. CONCLUSION: This is the first population-based study for measles and rubella at two different time points in developing countries. Measles and rubella seroprevalence increased significantly during 2014-2019, greatly exceeding the immunity thresholds for their elimination

A Simple Manual Rosetting Method for Absolute CD4(+) Lymphocyte Counting in Resource-Limited Countries

A CD4 monoclonal antibody which reacts with CD4(+) lymphocytes but does not react significantly with monocytes was generated and used to develop a simple method for CD4 count. In a comparison with standard flow cytometry, high correlation was obtained. The developed method can be an alternative to flow cytometry for resource-limited countries

Preprint: Hepatitis B virus infection in the Lao PDR: A systematic review

Introduction Even though hepatitis B is endemic in the Lao PDR, the understanding of the epidemiology of hepatitis B infection is incomplete. This article reviews the available literature about hepatitis B seroprevalence, risk factors and genotypes in the Lao population in order to provide an up- to date summary of the HBV epidemiology in the Lao PDR, identify knowledge gaps and provide public health recommendations. Methods Using PubMed/Medline and ScienceDirect, all studies reporting the prevalence of hepatitis B markers or genotype distribution in the Lao PDR published were systematically reviewed. Results The 21 studies included focused on the general population, blood donors, women, children, health care workers and garment factory workers. The studies varied extensively in sample size, target population, methods, study location and time periods. The prevalence of the hepatitis B surface antigen (HBsAg) in blood donors was reported to be 8.7%-9.6% in 2003-2006. In the years 2011-2012, the reported HBsAg prevalence among women (including pregnant women) ranged from 0%-9.5% and among children aged 5-9 years from 1.7%-8.7%, depending on study location and age. The majority of strains characterized in Lao PDR belonged to genotypes B and C. Conclusion Studies displayed considerable heterogeneity in populations, design and laboratory methods. A high HBsAg prevalence was reported in adults including pregnant women. Low infant vaccination coverage and compromised vaccine immunogenicity were found. Only two studies focused on HBV in risk populations, emphasizing the need for further studies to characterize hepatitis B epidemiology in potentially vulnerable groups. Hepatitis B infection continues to represent a substantial public health threat in the Lao PDR and needs to be monitored to inform health authorities and to counteract over-burdening of the health care system. In order to end mother to child transmission, vaccination coverage with the hepatitis B birth dose should be increased