Seroprevalence of pertussis in Madagascar and implications for vaccination

Abstract

Pertussis is a highly contagious infectious disease and remains an important cause of mortality and morbidity worldwide. Over the last decade, vaccination has greatly reduced the burden of pertussis. Yet, uncertainty in individual vaccination coverage and ineffective case surveillance systems make it difficult to estimate burden and the related quantity of populationlevel susceptibility, which determines population risk. These issues are more pronounced in low-income settings where coverage is often overestimated, and case numbers are underreported. Serological data provide a direct characterisation of the landscape of susceptibility to infection; and can be combined with vaccination coverage and basic theory to estimate rates of exposure to natural infection. Here, we analysed cross-sectional data on seropositivity against pertussis to identify spatial and age patterns of susceptibility in children in Madagascar. A large proportion of individuals surveyed were seronegative; however, there were patterns suggestive of natural infection in all the regions analysed. Improvements in vaccination coverage are needed to help prevent additional burden of pertussis in the country.

Leveraging serology to titrate immunisation programme functionality for diphtheria in Madagascar

“…The latter observations are harder to interpret as both natural infection and waning of immunity might have occurred within this age group, which also experienced variable levels of vaccination coverage (Figure 1A, Figure 2). Among the older age group, the highest proportion of diphtheria antibody seronegative children is found in Antananarivo, where vaccination coverage is expected to be the most elevated [19]. This suggests that natural infection may have contributed to seroconversion in the other regions, although differential antibody waning may also have played a role.…”

“…Consequently, the high proportion of diphtheria only seropositive individuals shown in our study either suggests high levels of circulating diphtheria, incomplete/missing vaccination or suboptimal immune response to the pertussis component of the vaccine. Selection bias may be present since only individuals with available health center registries were included excluding those not in the registries who are likely under-vaccinated [18,19]. Our analysis is also limited by the small number of districts and samples reducing the generalizability of our results.…”

“…A total of 593 sera of children aged 6 to 11 months from three districts and 8 to 15 years from five districts ( Fig. 1b ) collected May to September 2016 and analysed in the previous poliomyelitis and pertussis serology study [ 18 , 19 ] were selected. With 12 sera depleted, and 34 lost, 547 were available for analysis ( Table 1 ).…”

“…We used antibody titre levels at ≥0.01 IU/ml as the seropositivity threshold (sensitivity and specificity of ~94% [ 27 ]). For pertussis, the concentration of anti-PT IgG was determined using a commercially available ELISA kit (EUROIMMUN, Lübeck, Germany), see [ 19 ] for details; we set the lower limit of detection, 5 IU/ml, as the threshold for seropositivity. We opted to set a lower threshold to increase sensitivity and provide conservative bounds on vaccination.…”

“…Since the pertussis and diphtheria vaccines were combined in the mid-1940s [ 17 ], and are in use in combined form in Madagascar, interpretation of diphtheria serology titres can be strengthened by also considering serological status to pertussis. Here, we tested available Madagascar sera collected during a serology study on poliomyelitis in 2016 [ 18 ] and analysed in a pertussis serology study in 2020 [ 19 ] for anti-diphtheria IgG antibody levels to evaluate the immune profiles of children aged 6–11 months old and 8–15 years old, DTP vaccination coverage and diphtheria footprint in selected districts in Madagascar ( Fig. 1b ).…”