**Background:** Cholera remains a significant global public health problem despite well-known prevention and control measures. The current seventh pandemic began in South Asia in 1961, reached Africa in 1971, and the Americas in 1991, and is still ongoing. Cholera disproportionately affects the world's poorest people, particularly those lacking access to clean water and adequate sanitation, and those affected by humanitarian crises. Previous estimates reported approximately 95,000 deaths annually from 2008–2012. The disease is considered neglected and underreported, with notification to WHO no longer mandatory since 2005. This study aimed to contribute data on global trends in cholera-related mortality from 1990 to 2019.
**Methods:** This descriptive epidemiological study extracted cholera mortality data from the Global Burden of Disease (GBD) 2019 study, which provides comprehensive mortality estimates for 204 countries and territories. Data sources included WHO country-level death reports, vital registration, verbal autopsy, household surveys, disease registries, and health service use. Cholera death rates were calculated using the Cause of Death Ensemble model and adjusted to GBD standard population estimates. Mortality was analyzed globally and across six WHO regions (Africa, Americas, South-East Asia, Europe, Eastern Mediterranean, Western Pacific). Age-standardized mortality rates (ASRs per 100,000) were used, along with age-specific and sex-specific rates across four age strata (<5, 5–19, 20–54, 55+ years). Joinpoint regression analysis (version 4.9.0.0) was employed to identify statistically significant changes in trends, expressed as Annual Percent Change (APC) and Average Annual Percent Change (AAPC) with 95% confidence intervals. The Monte Carlo permutation method (4499 permutations) assessed significance (p < 0.05). The study was approved by the Ethics Committee of the Faculty of Medical Sciences, University of Kragujevac (Ref. No.: 01-14321).
**Key Results:** Over the 1990–2019 period, approximately 3.0 million deaths due to cholera occurred worldwide. Annual deaths ranged from 83,045 in 1990 to 117,167 in 2019. In 2019, the African Region accounted for 92,790 deaths (79.2% of total), followed by the Eastern Mediterranean Region with 15,247 deaths (13.0%). Less than 1% occurred in the Americas and European Regions. The global age-standardized mortality rate in 2019 was 1.66/100,000 in males and 1.60/100,000 in females. The highest rates were in the African Region (12.29/100,000 males, 10.53/100,000 females), followed by the Eastern Mediterranean Region (2.92/100,000 males, 3.17/100,000 females). Country-level variation was substantial: the highest male mortality rates were in Central African Republic (44.63/100,000) and Nigeria (40.74/100,000); the highest female rates were in Nigeria (37.83/100,000) and Central African Republic (34.64/100,000). Globally, the overall trend for both sexes combined was stable (AAPC −0.2%, 95% CI −0.5 to 0.1). Significantly decreasing trends were observed in the European Region (AAPC −10.7%, 95% CI −11.6 to −9.8), Western Pacific Region (AAPC −8.2%, 95% CI −8.5 to −8.0), and South-East Asia Region (AAPC −7.4%, 95% CI −7.8 to −6.9). The African Region showed a significantly increasing trend (AAPC +1.2%, 95% CI 0.8 to 1.6), with mortality rates rising from 8.7/100,000 in 1990 to 11.3/100,000 in 2019, peaking at 13.7/100,000 in 2009 and 2010. The Eastern Mediterranean Region showed a stable trend (AAPC −0.3%, 95% CI −0.7 to 0.1). By sex, global mortality significantly decreased in males (AAPC −0.4%, 95% CI −0.7 to −0.1) but was stable in females (AAPC −0.1%, 95% CI −0.4 to 0.2). Joinpoint analysis identified five joinpoints (1993, 2000, 2005, 2009, 2014) with six distinct trends for both sexes. Age-specific analysis revealed that mortality rates were nearly five times higher in people under 20 years compared to those 20 years or older. Children under 5 years had the highest rates and showed significantly increasing trends (males: AAPC +0.5%, 95% CI 0.1 to 0.8; females: AAPC +0.6%, 95% CI 0.3 to 0.9). The 5–19 year age group also showed significant increases (males: AAPC +1.4%, 95% CI 0.9 to 1.9; females: AAPC +1.5%, 95% CI 1.0 to 2.1). The 20–54 year group showed stable trends, while the 55+ group showed significant decreases (both sexes: AAPC −1.4%). In the African Region, both age groups (0–19 and ≥20 years) showed significantly increasing trends (AAPC +1.5% and +0.7%, respectively).
**Clinical Implications:** This study demonstrates that despite global progress in reducing cholera mortality in most regions, the disease remains a major public health challenge, particularly in sub-Saharan Africa. The African Region's rising mortality trend, especially among children under 5, is particularly concerning and reflects persistent inadequacies in water and sanitation infrastructure, healthcare access, and vaccination coverage. The finding that children under 5 bear the highest and increasing mortality burden highlights the need for targeted interventions including improved water quality, sanitation, hygiene education, and oral cholera vaccination programs for this vulnerable group. The substantial underreporting (WHO estimates officially reported cases represent only 5–10% of actual cases) suggests the true burden is far greater than documented. The global strategy 'Ending Cholera: The Global Roadmap to 2030' targets a 90% reduction in cholera deaths and elimination of local transmission in up to 20 countries. However, the unfavorable trends in Africa and parts of the Eastern Mediterranean indicate that achieving these targets will require substantially intensified international support, improved surveillance systems, and comprehensive implementation of prevention measures including safe water, sanitation, hygiene, and vaccination, particularly in poverty-stricken and conflict-affected regions.