Mapping anti-diphtheria toxin antibody: a systematic review and meta-analysis with multi-level meta-regression

Diphtheria is a reemerging vaccine-preventable infection of public health concern. Pooled estimates of serum IgG anti-diphtheria antibody levels can assist in estimating the susceptible population. The objective was to estimate pooled estimate of protective IgG anti-diphtheria antibodies in population globally. We searched three databases until May 2023. We included studies reporting serum anti-diphtheria antibody titre > 0.1 IU/ml as seroprotection. NHLBI checklist was used for quality assessment. Heterogeneity was explored and resolved by statistical methods. 1720 articles were retrieved out of which 51 articles were included. The pooled seropositivity rate against diphtheria was 57%. After removal of two influential outlier studies, pooled seropositivity became 51%. The meta-regression results for age depicted that seroprevalence significantly decreased with increasing age. Subgroup analysis done on basis of geographical distribution significantly reduced heterogeneity and revealed that the Western Pacific region and African regions had lower seroprotectivity compared to other regions. Subgrouping done based on year of sample collection revealed seroprotection was lower (55.63%) between 1986 and 2005 which increased to 67.11% between 2006 and 2015 and again dropped to 45.75% between 2016 and 2023. We concluded that after 2015, the disease has reemerged globally, with seroprotection level below 50% (45.75%) and overall only half of the population being seroprotected against diphtheria. So, there is a need for reinforcement of immunity against diphtheria (supplementary vaccination) after screening for antibody titre. PROSPERO registration number CRD42023458131.