Promotion of oral fluid methods for evaluation and surveillance of the measles immunization programme in Ethiopia
This work aims to demonstrate the use of oral-fluid methods in evaluating the effectiveness of a vaccination programme at the individual (vaccine conversion) and population levels (herd immunity and virus transmission and origin) within a developing country context. The setting for this work was Ethiopia- a country beset with huge economic, social and logistical difficulties in vaccine programme implementation. The study comprises the following: First, the development and evaluation of highly sensitive measles specific IgG/IgM ELISAs using oral-fluid, second, the application of these assays to evaluate routine and campaign measles vaccination programmes, and third genotyping of measles virus strains circulating in the country, again using oral-fluid samples. Paired blood and oral fluid samples were obtained from787 individuals of all ages from rural Ethiopia for evaluation of the measles enhanced IgG antibody capture (GAC) enzyme linked immunosorbent assay (ELISA). Relative to serum, oral fluid assay sensitivity and specificity were: 97.4% and 91.1% for measles IgG. This work is the development and evaluation of a new method that has contributed scientifically to vaccination programme evaluation and refinement. Pre- and post-vaccine antibody determined in 296 children attending for routine measles immunization in Addis Ababa suggested the average vaccination age at which 92.6% (200/216) seroconversion rate attained was about nine and half months. Oral-fluid based testing show 87.3% (185/212) seroconversion rate for IgM antibody compared to the 92.6% serconversion rate for serum. This work included the development and use of an oral-fluid enhanced MACELISA as a useful substitute to serum in evaluating vaccine seroconversion. RT-PCR was performed for oral-fluid and serum samples collected from outbreaks and sporadic measles cases across the country to study the molecular genotype characteristics of the strains. Sequence analysis of outbreaks and sporadic case samples revealed that the viruses of the D4, D8 and B3 genotypes were found in the country. This study also demonstrates the practicality of integrating oral-fluid based genotyping into measles surveillance efforts. Pre-campaign survey work carried out in Assella town by collecting oral-fluid samples from 1928 children aged 9-59 months visiting vaccination stations, and post-campaign survey work undertaken by cluster-based random sampling of 750 oral fluid samples from eligible individuals aged between 9 months to <20 years clearly show (i) a shortfall in measles 'immunity 'in the target age group (9-59 months), and (ii) a significant deficit in 'immunity' in those too old to have received the vaccine. This work demonstrates for the first time the merit of oral-fluid sampling in evaluating a measles vaccine campaign. The main achievements summarized above, give weight towards the practicality of using oral fluid in evaluating and refining immunization programmes in the developing country setting. It waits to be seen if the non-invasive technology will gain wider support in the measles control activities.