In 2023, approximately 108 million infants worldwide received three doses of the diphtheria-tetanus-pertussis (DTP) vaccine, yet significant disparities persist, particularly in low-resource settings like West Africa. Despite the DPT vaccine's proven efficacy against diphtheria, the region continues to experience high rates of outbreaks for diphtheria, tetanus, and typhoid in 2024. This review aims to highlight the recent diphtheria crisis and analyze the trends and challenges of DTP vaccine coverage in West Africa by shedding light on socio-economic conditions, healthcare facilities and genetic factors. The review seeks to provide insights into improving vaccination rates and public health outcomes in the region, emphasizing the critical role of the DPT vaccine in combating life-threatening diseases. Enhanced surveillance and effective response strategies and development of region specific theraputics by the analysis of genomic variability in Africans, specifically within the human leukocyte antigen (HLA) locus are essential to address the ongoing public health challenges posed by diphtheria and related infections in West Africa.