Abstract
Diphtheria is a potentially devastating disease whose epidemiology remains poorly described in many settings, including Madagascar. Diphtheria vaccination is delivered in combination with pertussis and tetanus antigens and coverage of this vaccine is often used as a core measure of health system functioning. However, coverage is challenging to estimate due to the difficulty in translating numbers of doses delivered into numbers of children effectively immunised. Serology provides an alternative lens onto immunisation, but is complicated by challenges in discriminating between natural and vaccine-derived seropositivity. Here, we leverage known features of the serological profile of diphtheria to bound expectations for vaccine coverage for diphtheria, and further refine these using serology for pertussis. We measured diphtheria antibody titres in 185 children aged 6-11 months and 362 children aged 8-15 years and analysed them with pertussis antibody titres previously measured for each individual. Levels of diphtheria seronegativity varied among age groups (18.9% of children aged 6-11 months old and 11.3% of children aged 8-15 years old were seronegative) and also among the districts. We also find surprisingly elevated levels of individuals seropositive to diphtheria but not pertussis in the 6-11 month old age group suggesting that vaccination coverage or efficacy of the pertussis component of the DTP vaccine remains low or that natural infection of diphtheria may be playing a significant role in seropositivity in Madagascar.
Highlights
In the pre-vaccine era, diphtheria was a leading cause of childhood mortality [1]
Summary Diphtheria is a potentially devastating disease whose epidemiology remains poorly described in many settings, including Madagascar
Diphtheria vaccination is delivered in combination with pertussis and tetanus antigens and coverage of this vaccine is often used as a core measure of health system functioning
Summary
In the pre-vaccine era, diphtheria was a leading cause of childhood mortality [1]. The etiological agent Corynebacterium diphtheriae (or, more rarely, Corynebacterium ulcerans) causes either respiratory or cutaneous disease, with the former associated with higher risk of mortality, and reportable to the World Health Organization (WHO). The case fatality rate (CFR) may be around 29%, but health care improvements have driven this number close to zero if patients are properly diagnosed [2]. This progress has occurred alongside notable reductions in case numbers as a result of expansion of immunization by vaccination beginning after World War II [1]. Even in highly vaccinated populations where the level of indirect protection should be high, unvaccinated individuals may be vulnerable following introduction of the pathogen [6,7,8]
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