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

Abstract

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.

Fig 1. Measles IgG seroprevalence measured by ELISA in different age groups from representative populations of Lao PDR, 2014.

*An ELISA value of 120 mIU/mL was considered positive. †Individuals 5–14 years old and 15–21 years old were among the targeted age groups of supplementary immunization activities conducted in 2011 using the MR combination vaccine with coverage of 97%. Their IgG prevalence was estimated to be 86.8% (95% CI: 83.0–90.6).

Fig 2. Rubella IgG seroprevalence measured by ELISA in different age groups from representative populations in Lao PDR, 2014.

*An ELISA value of 10 IU/ml was considered positive. †Individuals 5 to 14 years old and 15 to 21 years old were among the targeted age groups of supplementary immunization activities conducted in 2011 using the MR combination vaccine with coverage of 97%. Their IgG prevalence was estimated to be 88.2% (95%CI: 84.5–91.8).

Fig 3. Comparison between the predictions of age-specific percentage seronegative, obtained using the best-fitting catalytic model and the observed data.

Bars reflect 95% confidence intervals of the observed data. Lines reflect predictions from the best-fitting model.

Fig 4. Stability testing of freeze-dried measles and rubella combination vaccines.

After incubation of freeze-dried vaccines at 4°C (A), 25°C (B), or 35°C (C), titres of measles and rubella viruses in the vaccines were measured by plaque assays. Filled squares and open circles indicate titres of measles and rubella viruses, respectively. Means of three vials are shown. Error bars indicate standard deviations.

Fig 5. Stability testing of reconstituted measles and rubella combination vaccines.

After incubation of reconstituted vaccines at 4°C (A), 25°C (B), or 35°C (C), titres of measles and rubella viruses in the vaccines were measured by plaque assays. Filled squares and open circles indicate titres of measles and rubella viruses, respectively. Means of three vials are shown. Error bars indicate standard deviations.