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

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

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

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

MOESM1 of Cost-effectiveness analysis of the national decentralization policy of antiretroviral treatment programme in Zambia

Additional file 1. Markov Model

Acquisition of monosomy 7 and a RUNX1 mutation in Pearson syndrome

Pearson syndrome (PS) is a very rare and often fatal multisystem disease caused by deletions in mitochondrial DNA that result in sideroblastic anemia, vacuolization of marrow precursors, and pancreatic dysfunction. Spontaneous recovery from anemia is often observed within several years of diagnosis. We present the case of a 4-month-old male diagnosed with PS who experienced prolonged severe pancytopenia preceding the emergence of monosomy 7. Whole-exome sequencing identified two somatic mutations, including RUNX1 p.S100F that was previously reported as associated with myeloid malignancies. The molecular defects associated with PS may have the potential to progress to advanced myelodysplastic syndrome

Health outcomes and cost impact of the new WHO 2013 guidelines on prevention of mother-to-child transmission of HIV in Zambia.

BackgroundCountries are currently progressing towards the elimination of new paediatric HIV infections by 2015. WHO published new consolidated guidelines in June 2013, which now recommend either 'Antiretroviral drugs (ARVs) for women living with HIV during pregnancy and breastfeeding (Option B)' or 'Lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV (Option B+)', while de facto phasing out Option A. This study examined health outcomes and cost impact of the shift to WHO 2013 recommendations in Zambia.MethodsA decision analytic model was developed based on the national health system perspective. Estimated risk and number of cases of HIV transmission to infants and to serodiscordant partners, and proportions of HIV-infected pregnant women with CD4 count of ≤350 cells/mm3 to initiate ART were compared between 2010 Option A and the 2013 recommendations. Total costs of prevention of mother-to-child transmission of HIV (PMTCT) services per annual cohort of pregnant women, incremental cost-effectiveness ratio (ICER) per infection averted and quality-adjusted life-year (QALY) gained were examined.ResultsOur analysis suggested that the shift from 2010 Option A to the 2013 guidelines would result in a 33% reduction of the risk of HIV transmission among exposed infants. The risk of transmission to serodiscordant partners for a period of 24 months would be reduced by 72% with 'ARVs during pregnancy and breastfeeding' and further reduced by 15% with 'Lifelong ART'. The probability of HIV-infected pregnant women to initiate ART would increase by 80%. It was also suggested that while the shift would generate higher PMTCT costs, it would be cost-saving in the long term as it spares future treatment costs by preventing infections in infants and partners.ConclusionThe shift to the WHO 2013 guidelines in Zambia would positively impact health of family and save future costs related to care and treatment

Estimates of the global burden of Congenital Rubella Syndrome, 1996-2019

Objectives: Many countries introduced rubella-containing vaccination (RCV) after 2011, following changes in recommended World Health Organization (WHO) vaccination strategies and external support. We evaluated the impact of these introductions. Methods: We estimated the country-specific, region-specific, and global Congenital Rubella Syndrome (CRS) incidence during 1996-2019 using mathematical modeling, including routine and campaign vaccination coverage and seroprevalence data. Results: In 2019, WHO African and Eastern Mediterranean regions had the highest estimated CRS incidence (64 [95% confidence intervals (CI): 24-123] and 27 [95% CI: 4-67] per 100,000 live births respectively), where nearly half of births occur in countries that have introduced RCV. Other regions, where >95% of births occurred in countries that had introduced RCV, had a low estimated CRS incidence (<1 [95% CI: <1 to 8] and <1 [95% CI: <1 to 12] per 100,000 live births in South-East Asia [SEAR] and the Western Pacific [WPR] respectively, and similarly in Europe and the Americas). The estimated number of CRS births globally declined by approximately two-thirds during 2010-2019, from 100,000 (95% CI: 54,000-166,000) to 32,000 (95% CI: 13,000-60,000), representing a 73% reduction since 1996, largely following RCV introductions in WPR and SEAR, where the greatest reductions occurred. Conclusions: Further reductions can occur by introducing RCV in remaining countries and maintaining high RCV coverage

Sensitivity analysis.

a<p>Total costs = PMTCT programme costs+future treatment costs of infected children and partners for 10 years.</p>b<p>QALYs gained by averting infant and partner infections.</p