Recent outbreaks of monkeypox (Mpox) have occurred in countries outside of Africa, with large numbers of cases spreading rapidly to almost every continent. We aimed to analyze the correlation between the Global Health Security (GHS) Index (categories and indicators) and the Mpox case rate in different regions and globally. In this cross-sectional study, we used data from Mpox cases from the WHO, and the GHS categories and indicators for detection, prevention, reporting, health system, rapid response, international norms compliance, and risk environment. Outcome measures were the relationship between GHS index (categories and indicators) and Mpox case rate using crude and adjusted non-linear regression models. After performing adjusted analyses, only risk environment and detection and reporting index were associated with Mpox case rates in the 99 countries and the Region of the Americas, respectively. Antimicrobial resistance (AMR) indicators of the prevention category, risk communication of the rapid response category, the joint external evaluation and performance veterinary services of the norms category, and the infrastructure adequacy of the risk environment category were associated with Mpox case rates in the 99 countries (p<0.05). Laboratory systems strength and quality indicator of the detection and reporting category, and emergency response operation indicator of the response rapid category were associated with Mpox case rates in the countries of the region of the Americas (p<0.05). AMR indicator of the prevention of the emergence category, and the infrastructure adequacy of the risk environment category were associated with Mpox case rates in the countries of the European Region (p<0.05). In the countries of the other regions, only the trade and travel restrictions indicator of the rapid response category was associated with Mpox case rates (p<0.05). Countries, particularly in the Americas region, with high levels of infrastructure adequacy and laboratory system strength and quality as measured by the GHS index are better equipped to detect more Mpox cases. Therefore, they have higher Mpox case detection rates and can successfully respond to Mpox outbreaks.
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