Estimating the immunogenicity of measles-rubella vaccination administered during a mass campaign in Lao People's Democratic Republic using multi-valent seroprevalence data.

Measles and rubella are important causes of morbidity and mortality globally. Despite high coverage reported for measles vaccination, outbreaks continue to occur in some countries. The reasons for these outbreaks are poorly understood. We apply Bayesian methods to multi-valent seroprevalence data for measles and rubella, collected 2 years and 3 months after a mass measles-rubella vaccination campaign in Lao PDR to estimate the immunogenicity and vaccination coverage. When the vaccination coverage was constrained to exceed 95% or 90%, consistent with officially-reported values, the immunogenicity of the measles vaccine component was unexpectedly low (75% (95% CR: 63-82%) and 79% (CR: 70-87%) respectively. The estimated immunogenicity increased after relaxing constraints on the vaccination coverage, with best-fitting values of 83% (95% CR: 73-91%) and 97% (95% CR: 90-100%) for the measles and rubella components respectively, with an estimated coverage of 83% (95% CR: 80-88%). The findings suggest that, if the vaccine coverage was as high as that reported, continuing measles outbreaks in Lao PDR, and potentially elsewhere, may be attributable to suboptimal immunogenicity attained in mass campaigns. Vaccine management in countries with high reported levels of coverage and ongoing measles outbreaks needs to be reviewed if measles elimination targets are to be achieved

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

Evaluation of nationwide supplementary immunization in Lao People's Democratic Republic: Population-based seroprevalence survey of anti-measles and anti-rubella IgG in children and adults, mathematical modelling and a stability testing of the vaccine.

BACKGROUND: Measles outbreaks have occurred in some countries despite supplementary immunization activities (SIA) using measles-containing vaccine with high vaccination coverage. We conducted a cross-sectional seroprevalence survey to estimate population immunity in Lao People's Democratic Republic where repeated mass immunization has failed to eliminate measles. METHODS AND FINDINGS: In this nationwide multistage cluster sampling survey conducted in 2014 based on probability proportionate to size sampling, blood samples were collected from 2,135 children and adults living in 52 randomly selected villages. Anti-measles and anti-rubella IgG were measured, and IgG prevalence was calculated. We applied mathematical modelling to estimate the number of cases of congenital rubella syndrome (CRS) in 2013 that were averted by the 2011 SIA. A stability testing was applied to the MR vaccine at 4°C, 25°C, and 35°C to examine stability differences between measles and rubella vaccine components. Measles IgG prevalence was significantly lower in the target age groups (5-21 years) of the 2011 SIA using a combination vaccine for measles and rubella vaccine (MR vaccine) than in young adults (22-39 years) (86.8% [95% CI: 83.0-90.6] vs. 99.0% [98.3-99.8]; p<0.001), whereas rubella IgG prevalence was significantly higher (88.2% [84.5-91.8] vs. 74.6% [70.7-78.5]; p<0.001). In the SIA target age groups, prevalence of measles IgG, but not rubella IgG, increased with age. CRS cases prevented in 2013 ranged from 16 [0-50] to 92 [32-180] if the force of infection had remained unchanged or had been reduced by 75%, respectively. In freeze-dried conditions, the measles vaccine component was more heat sensitive than the rubella component. CONCLUSIONS: Inconsistent IgG prevalence between measles and rubella in Lao PDR can be partly explained by different stability of the measles and rubella vaccine components under heat exposure. Suboptimal vaccine handling may cause insufficient immunogenicity for measles, which subsequently leads to an outbreak despite high SIA coverage, while direct evidence is lacking. Temperature monitoring of the vaccine should be conducted

Determination of factors affecting the vaccination status of children aged 12–35 months in Lao People’s Democratic Republic

Vaccines are one of the most important achievements in public health, and a major contributor to this success is the Expanded Programme on Immunization. The utilisation of vaccination services and completion of the recommended schedule are determined by numerous factors. In Lao People’s Democratic Republic (Lao PDR), the overall immunisation coverage has been improving. However, notwithstanding the improvement in immunisation coverage and the supplementary immunisation activities, there have been measles, diphtheria, and polio outbreaks in the country. The recent multicounty study of household health surveys revealed that the within-country economic-related inequality in the delivery of a vaccine was still high in Lao PDR. Our previous work evaluated the factors associated with vaccination status among the children aged 5–9 years old, which was older age group for this type of study. This study evaluated factors that affect vaccination status among children aged between 12 and 35 months. It is a nationwide population-based cross-sectional study that used data obtained through multistage cluster sampling. We found that the proportion of infants who were fully immunised was lower than the national target and that “maternal ethnicity” (odds ratio (OR) 0.34, 95% confidence interval [CI]: 0.20–0.60), “paternal education” (OR 1.87, 95% CI: 1.12–3.10), and “source of information about vaccination date by medical staff” (OR 1.65, 95% CI: 1.01–2.71) were significantly associated with the children’s vaccination status. Numerous factors are associated with the completion of the recommended vaccine schedule, and some factors are location-specific. Identification of these factors should lead to actions for facilitating the optimal use of vaccination services by all the children in Lao PDR

Assessment of temperatures in the vaccine cold chain in two provinces in Lao People’s Democratic Republic: a cross-sectional pilot study

Abstract Objective All childhood vaccines, except the oral polio vaccine, should be kept at 2–8 °C, since the vaccine potency can be damaged by heat or freezing temperature. A temperature monitoring study conducted in 2008–2009 reported challenges in cold chain management from the provincial level downwards. The present cross-sectional pilot study aimed to assess the current status of the cold chain in two provinces (Saravan and Xayabouly) of Lao People’s Democratic Republic between March–April 2016. Two types of temperature data loggers recorded the temperatures and the proportions of time exposed to  8 °C were calculated. Results The temperature remained within the appropriate range in the central and provincial storages. However, the vaccines were frequently exposed to > 8 °C in Saravan and  8 °C during the transportation in Saravan and to both > 8 and < 0 °C in Xayabouly. Thus, challenges in managing the cold chain in the district storage and during transportation remain, despite improvements at the provincial storage. A detailed up-to-date nationwide analysis of the current situation of the cold chain is warranted to identify the most appropriate intervention to tackle the remaining challenges

Seroprevalence of chronic hepatitis B, as determined from dried blood spots, among children and their mothers in central Lao People's Democratic Republic: a multistage, stratified cluster sampling survey

Background: There is limited information regarding the prevalence of hepatitis B in Lao PDR, where the hepatitis disease burden is substantial. Thus, reliable seroprevalence data is needed for the disease, based on probability sampling. Methods: A stratified, multistage, cluster sampling survey of hepatitis B surface antigen (HBsAg) positivity among children aged 5–9 years and their mothers aged 15–45 years was conducted. Participants were selected randomly from the central region of Lao PDR via probability-proportional-to-size sampling. Blood samples were collected onto filter paper and subsequently analyzed using a chemiluminescent microparticle immunoassay. Results: A total of 911 mother-and-child pairs were collected; the seroprevalence of HBsAg was estimated to be 2.1% (95% confidence interval 0.8–3.4%) among children and 4.1% (95% confidence interval 2.6–5.5%) in their mothers after taking into account the sampling design and the weight of each sample. The children's HBsAg positivity was positively associated with maternal infection and being born in a non-health facility, while the maternal infection status was not associated with any background characteristic. Conclusions: Lao PDR has a relatively lower HBsAg prevalence in the general population compared to surrounding countries. To ensure comparability to other countries and to future data, rapid field tests are recommended for a nationwide prevalence survey

Analysing the characteristics of a measles outbreak in Houaphanh province to guide measles elimination in the Lao People’s Democratic Republic

Introduction: In recent years, the incidence of measles has declined in the Lao People’s Democratic Republic. However, an outbreak was reported in August 2014 in Houaphanh province, which was the biggest outbreak in the country since 2008. We describe the characteristics of this outbreak and outline critical interventions for the Lao People’s Democratic Republic to achieve measles elimination. Methods: Fever and rash cases in the Khouan and Samtai districts with an onset date from 1 September to 25 October 2014 were investigated. Active case finding and health facility record reviews were carried out. Appropriate samples from the individuals with suspected measles were tested to confirm the diagnosis. Results: A total of 265 suspected cases including 12 deaths were reported from eight villages in the Khouan and Samtai districts. Forty-five individuals tested positive for measles IgM. Most of the confirmed patients were male (n = 28, 62%), less than 5 years old (n = 23, 51%) and from the Hmong ethnic community (n = 44, 98%). The majority of the people with suspected measles (n = 213, 80%) and all the confirmed ones were unvaccinated. A measles vaccination campaign conducted in the eight affected villages resulted in 76% coverage of the targeted population. Discussion: Low routine coverage and measles occurrence among unvaccinated individuals indicate underimmunized areas. The geographical and sociodemographic characteristics of this outbreak highlight the need for tailored vaccination strategies to close the immunity gap. A sensitive surveillance system that is able to detect, notify, investigate and guide response measures, including a second measles dose in the routine immunization schedule, will be essential for the Lao People’s Democratic Republic to attain its measles elimination status

Immunity levels to poliovirus in Lao children and adults before the vaccine-derived poliovirus outbreak: A retrospective study

In 2015, several provinces in Lao People's Democratic Republic (Lao PDR) experienced a vaccine-derived poliovirus outbreak. This survey was conducted (i) to evaluate the vaccination coverage in different settings and cohorts using the seroprevalence of anti-poliovirus (PV) antibodies as a surrogate measure, and (ii) to explore the usefulness of an ELISA in a country with limited resources and a specific epidemiological setting. IgG antibodies were assessed by ELISA in Lao children (n = 1216) and adults (n = 1228), including blood donors and health care workers. Protective antibody titers against the 3 vaccine serotypes were determined by microneutralization (VNT) in a subset of participants. More than 92% of the children had anti-poliovirus antibodies, regardless of nutritional status or access to health care, highlighting the success of the vaccination outreach activities in the country. In contrast, anti-poliovirus seroprevalence reached only 81.7% in blood donors and 71.9% in health care workers. Participants born before the introduction of poliovirus vaccination in Lao PDR were considerably less likely to be seropositive. These findings align with the epidemiology of the outbreak. Neutralizing antibodies against at least one of the 3 poliovirus serotypes were detected in all children (99/99) and 93/99 had antibodies against all serotypes. Similarly, all health care workers had neutralizing antibodies against at least one and 92/99 against all serotypes. The comparison of both assays shows an acceptable underestimation of vaccine coverage in children by ELISA, but a low sensitivity of the ELISA in the adults. We show that the ELISA is a reasonable alternative to the VNT in particular in vaccinated children, that an improved version should be serotype specific, and that negativity thresholds should be revisited for optimal sensitivity and specificity. Thus, polio-free countries with an uncertain vaccination coverage and limited laboratory capacity, that are at risk of vaccine-derived poliovirus outbreaks or of re-importation of wild poliovirus may benefit from an improved ELISA for cohort studies to evaluate their immunization program in children.Peer Reviewe

Immunity levels to poliovirus in Lao children and adults before the vaccine-derived poliovirus outbreak: A retrospective study

In 2015, several provinces in Lao People's Democratic Republic (Lao PDR) experienced a vaccine-derived poliovirus outbreak. This survey was conducted (i) to evaluate the vaccination coverage in different settings and cohorts using the seroprevalence of anti-poliovirus (PV) antibodies as a surrogate measure, and (ii) to explore the usefulness of an ELISA in a country with limited resources and a specific epidemiological setting. IgG antibodies were assessed by ELISA in Lao children (n = 1216) and adults (n = 1228), including blood donors and health care workers. Protective antibody titers against the 3 vaccine serotypes were determined by microneutralization (VNT) in a subset of participants. More than 92% of the children had anti-poliovirus antibodies, regardless of nutritional status or access to health care, highlighting the success of the vaccination outreach activities in the country. In contrast, anti-poliovirus seroprevalence reached only 81.7% in blood donors and 71.9% in health care workers. Participants born before the introduction of poliovirus vaccination in Lao PDR were considerably less likely to be seropositive. These findings align with the epidemiology of the outbreak. Neutralizing antibodies against at least one of the 3 poliovirus serotypes were detected in all children (99/99) and 93/99 had antibodies against all serotypes. Similarly, all health care workers had neutralizing antibodies against at least one and 92/99 against all serotypes. The comparison of both assays shows an acceptable underestimation of vaccine coverage in children by ELISA, but a low sensitivity of the ELISA in the adults. We show that the ELISA is a reasonable alternative to the VNT in particular in vaccinated children, that an improved version should be serotype specific, and that negativity thresholds should be revisited for optimal sensitivity and specificity. Thus, polio-free countries with an uncertain vaccination coverage and limited laboratory capacity, that are at risk of vaccine-derived poliovirus outbreaks or of re-importation of wild poliovirus may benefit from an improved ELISA for cohort studies to evaluate their immunization program in children