Global burden of leishmaniasis, 1990–2021: systematic analysis of the global burden of disease study

Abstract

Background

Leishmaniasis is a neglected tropical disease with significant global public health implications, leading to diverse clinical manifestations. It disproportionately affects impoverished populations in over 90 countries, making it a major health concern worldwide.

Methods

This study provides a comprehensive analysis of the global burden of leishmaniasis from 1990 to 2021 across 204 countries and territories, using data from the Global Burden of Disease Study 2021. It estimates the disability-adjusted life years (DALYs) associated with leishmaniasis, assessing its impact across different age groups, sexes, and sociodemographic index (SDI) categories.

Results

The findings show a decline in the global age-standardized DALY rate for visceral leishmaniasis, from 75.73 to 5.39 per 100,000 population (a reduction of 92.9%). However, the DALY rate for cutaneous and mucocutaneous leishmaniasis has increased from 3.86 to 4.88 per 100,000 (a 26.4% rise), particularly in low- and middle-SDI countries. The study also reveals significant sex disparities in occupational risk factors, with men being more vulnerable to environmental and industrial exposures. Additionally, nutritional deficiencies, particularly calcium and zinc deficiencies, are identified as significant global risk factors.

Conclusion

The results underscore the need for targeted public health interventions, particularly those addressing nutritional deficiencies and occupational exposures. Region-specific health strategies should be developed to account for local risk factors, sex differences, and the varying impacts of environmental and industrial exposures, especially in less developed regions.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12939-025-02691-0.

Introduction

Leishmaniasis, a vector-borne disease caused by protozoan parasites of the genus Leishmania, represents one of the most significant yet neglected tropical diseases (NTDs) impacting global public health [1, 2]. Transmitted primarily through the bite of infected female phlebotomine sandflies, leishmaniasis manifests in various clinical forms, ranging from cutaneous lesions to life-threatening visceral infections [3, 4]. The disease predominantly affects impoverished populations in over 90 countries, particularly in regions across Asia, Africa, the Middle East, and Central and South America [5]. Despite its extensive geographic distribution, leishmaniasis remains underreported and inadequately addressed, contributing to its persistence as a major public health challenge.

The global burden of leishmaniasis remains significant. The World Health Organization (WHO) estimates that approximately 700,000 to 1 million new leishmaniasis cases occur annually, with over 350 million people at risk of infection [6]. The disease is responsible for significant morbidity and mortality, particularly in low- and middle-income countries where access to healthcare is limited [7]. Visceral leishmaniasis (VL), also known as kala-azar, is the most severe form of the disease, with a high fatality rate if left untreated [8, 9]. It is estimated that VL alone causes 50,000 to 90,000 deaths each year, primarily affecting populations in East Africa, India, and Brazil [6]. Cutaneous leishmaniasis (CL), while less fatal, results in severe disfigurement and disability, affecting social and economic well-being in endemic regions [10]. Mucocutaneous leishmaniasis (MCL), though less common, can lead to devastating facial disfigurement and significant morbidity [11].

Over the past three decades, the Global Burden of Disease (GBD) study has provided invaluable insights into the trends and impacts of various diseases, including leishmaniasis [12]. The GBD 1990–2021 study offers a comprehensive analysis of the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) associated with leishmaniasis, highlighting the persistent and evolving burden of the disease. Understanding the global burden of leishmaniasis is essential for shaping public health strategies and effectively allocating resources for disease control and prevention. However, the lack of clarity regarding the attributable risk factors for leishmaniasis in different countries hampers the development of effective strategies to address the disease at global and regional levels.

In this study, we analyze trends of leishmaniasis in DALYs over time to illuminate the persistent challenges in leishmaniasis control and provide insights to guide future research and policy efforts. Additionally, we seek to identify global risk factors associated with the disease, underscoring the need for targeted public health interventions. This analysis reinforces the critical need to strengthen healthcare systems in endemic regions, enhance disease surveillance, and address the social determinants of health contributing to the ongoing persistence and spread of leishmaniasis. Building upon previous GBD analyses, this study utilizes the most recent GBD 2021 data and provides a more detailed examination of occupational, nutritional, and sociodemographic risk factors, offering new perspectives on the drivers of global and regional disparities in disease burden.

Methods

Data source

The GBD 2021 project estimated the DALYs linked to 371 diseases and injuries across 204 countries and territories from 1990 to 2021 [12, 13]. This extensive dataset was compiled through a rigorous evaluation of various sources, including censuses, household surveys, civil registration and vital statistics, disease registries, health service utilization records, air pollution monitors, satellite imaging, and more. The comprehensive findings of the GBD 2021 study have been documented in prior publications [14, 15]. For our analysis, we retrieved data from the Global Health Data Exchange specifically on leishmaniasis DALYs, broken down by age, sex, and region, as well as DALYs attributable to different risk factors, each accompanied by corresponding 95% uncertainty intervals [16].

Estimation of disease burden of leishmaniasis in Global Burden of Disease Study 2021

In the GBD Study 2021, data from systematic reviews of published literature, survey data, longitudinal studies, and other sources were incorporated into DisMod MR-2.1, a Bayesian meta-regression model, to estimate the non-fatal burden of leishmaniasis, including its various types. For leishmaniasis, crude years lived with disability (YLDs) were calculated by multiplying the disease prevalence by the disability weights associated with the specific health state. These YLD estimates were further refined using a micro-simulation model that accounted for comorbidities. Years of life lost (YLLs) were determined by multiplying the estimated number of deaths from leishmaniasis by the standard life expectancy at the age of death [17]. The total DALYs were then calculated using the YLDs and YLLs [18]. Briefly, the calculation of YLDs requires estimates of disease and incidence, average duration of associated disability, and disability weight. Disability weights are expressed on a scale from 0 to 1, with 0 representing ideal health and 1 representing death. The calculation methods for YLLs and YLDs are provided in Supplementary Material 1. All estimates are presented with 95% uncertainty intervals (UIs), derived from 500 Monte Carlo draws from the Bayesian posterior distributions generated in DisMod-MR 2.1 [13]. The UIs correspond to the 2.5th and 97.5th percentile values across these draws, reflecting uncertainty propagated through all stages of the estimation process.

Estimation of attributable risk factors for leishmaniasis in Global Burden of Disease Study 2021

The GBD Study 2021 evaluated the disease burden attributable to 88 risk factors and their combinations across global, regional, and national levels [15]. Attributable DALYs represent the potential reduction in disease burden that could have been realized if population-level exposure to these risk factors had shifted to an alternative or counterfactual distribution [19]. This reduction was estimated by multiplying the total DALYs for a specific outcome by the population attributable fraction, reflecting the proportion of outcomes that would decrease within a population over a given period if exposure were reduced to the theoretical minimum risk level [15]. Detailed definitions of risk factors and the specific estimation methods employed in the study are provided in the other published literature [14, 15]. Additionally, a generalized linear mixed model was used to analyze the association between each risk factor and leishmaniasis. The unstandardized data from GBD was used for the analysis to preserve the original scale of the variables and facilitate the interpretation of the coefficients in their natural units. No transformations or standardizations were applied to the predictor variables before fitting the generalized linear mixed model. The model was controlled for region-fixed effect and time random effect. The generalized linear mixed model (GLMM) was chosen because it accounts for both fixed and random effects, enabling the analysis of hierarchical data structures and accommodating unobserved heterogeneity across regions and time. Potential collinearity among risk factors was examined using pairwise correlation analysis and variance inflation factors (VIFs). Variables with VIF values greater than 5 were considered highly collinear; however, no variables exceeded this threshold. To assess whether sex differences persisted after adjusting for occupational exposure, we fitted sex-specific panel regressions using age-standardized DALY rates (1990–2021) by sex. The outcome was log-transformed DALY rate. Models included fixed effects for SDI and calendar year. Occupational pollution exposures were derived from the GBD by selecting risk factors beginning with “Occupational …”; exposures were standardized and summarized as (i) a mean z-score index and (ii) the first principal component (PCA-1) as a robustness check. Heteroskedasticity-robust (HC3) standard errors were used. We also tested sex-by-exposure interaction analyses.

Statistical analysis

We calculated age-standardized rates and their corresponding 95% confidence intervals by standardizing against the world standard population, as reported in the GBD Study 2021 [15]. These estimates are expressed per 100,000 population. To assess the magnitude and direction of temporal trends in DALYs for leishmaniasis, we calculated the average annual percent change (AAPC) with 95% confidence intervals using joinpoint regression. The analysis was conducted using the Joinpoint Regression Program (version 5.2.0, National Cancer Institute, USA), which fitted the simplest joinpoint model that data would support. The process began with the minimum number of joinpoints (e.g., a straight line with no joinpoints) and tested whether additional joinpoints were statistically significant and warranted inclusion in the model. Significance was determined using a Monte Carlo permutation method. The AAPC was calculated by weighting the annual percent change (APC) of each segment in the final significant model. Comparisons were made across sex, age groups (< 5, 5–14, 15–24, 25–34, 35–44, 45–54, and >55 years), and sociodemographic index (SDI) categories (five levels). Least squares regression and generalized additive models were applied to examine potential linear or non-linear relationships between SDI and age-standardized rates or corresponding AAPC. All statistical analyses were performed using Python (version 3.8.1), with a P-value of < 0.05 considered statistically significant.

Patient and public involvement

The GBD Study is a large-scale collaborative effort with contributions from over 7,500 experts across nearly 150 countries [12]. We did not involve patients in the design phase of this study, as we utilized secondary data from the GBD Study 2021. The research question was not directly focused on leishmaniasis management at the individual patient level. As such, patients were not involved in developing the research question, collecting or analyzing data, interpreting the findings, or writing the manuscript.

Results

Global distribution of leishmaniasis in 2021

In 2021, the global age-standardized DALYs rate for leishmaniasis was 10.27 per 100,000 population (95% confidence interval (95% CI): 5.99 to 21.96). When broken down by category, the age-standardized DALYs rate for VL was 5.39 per 100,000 population (95% CI: 1.70 to 17.12), while for cutaneous and mucocutaneous leishmaniasis (CML), it was 4.88 per 100,000 population (95% CI: 3.29 to 6.85). Analysis by SDI revealed that countries with a low SDI had the highest age-standardized DALYs rate, at 25.20 per 100,000 population (95% CI: 15.06 to 47.50) (Supplementary Tables 1–3).

The association between the age-standardized DALYs rates for leishmaniasis, VL, and CML and the SDI displayed a declining trend, with higher DALYs rates observed in countries with lower SDI (all models, P < 0.001) (Fig S1). Regionally, the greatest burden of leishmaniasis, including both visceral and cutaneous/mucocutaneous forms, was concentrated in parts of South Asia, Central America, South America, East Africa, and North Africa (Fig S2-S4 and Supplementary Tables 1–3). At the national level, the 10 countries with the highest age-standardized DALY rates in 2021 were Afghanistan, Suriname, Sudan, Djibouti, Nicaragua, Panama, Turkmenistan, Tunisia, Iraq, and Brazil.

Globally, the age-standardized DALY rates for leishmaniasis and VL were higher in men (12.60 and 7.31, respectively) compared to women (7.87 and 3.36, respectively). In contrast, the age-standardized DALYs rate for CML was similar between men and women (5.29 and 4.51, respectively) (Supplementary Tables 1–3).

Temporal trend of leishmaniasis from 1990 to 2021

The age-standardized DALY rates for leishmaniasis and VL decreased globally and across all five SDI categories for both sexes from 1990 to 2021 (Fig. 1 and Supplementary Tables 1–3). In contrast, the age-standardized DALYs rate for CML increased globally and in countries with Low- and Middle-SDI during the same period. The VL-to-CML DALY rate ratio declined steadily across all SDI categories, with a faster reduction in VL than in CML (Fig S5A). By 2021, this ratio had dropped below 1 across nearly all SDI categories, with the sole exception of low SDI (Fig S5B). This finding indicates that CML had overtaken VL as the primary contributor to the total leishmaniasis burden—especially in high SDI regions.

Fig. 1.

Temporal trend of DALYs rate for the burden of leishmaniasis. The burden of leishmaniasis, VL, and CML globally and by sociodemographic index (five categories; countries with a high, high-middle, middle, low-middle, or low sociodemographic index) from 1990 to 2021 (A). Average annual percent change, globally and by sociodemographic index category, from 1990 to 2021, is also shown (B)

Globally, the age-standardized DALYs rate for leishmaniasis decreased from 79.59 (95% CI: 29.90 to 246.55) in 1990 to 10.27 (95% CI: 5.99 to 21.96) in 2021. Similarly, the age-standardized DALYs rate for VL declined from 75.73 (95% CI: 25.98 to 242.77) in 1990 to 5.39 (95% CI: 1.70 to 17.12) in 2021. However, the age-standardized DALYs rate for CML increased from 3.86 (95% CI: 2.51 to 5.63) in 1990 to 4.88 (95% CI: 3.29 to 6.85) in 2021 (Fig. 1 and Supplementary Tables 1–3). Notably, compared to countries with a Low-middle SDI, those with Low- and Middle-SDI experienced a faster increase in the age-standardized DALYs rate for CML, with an average annual percent change of 2.07% (95% CI: 1.85% to 2.29%) and 0.88% (95% CI: 0.78% to 0.98%), respectively.

When analyzed by region, Western Sub-Saharan Africa exhibited the most rapid increases in age-standardized DALYs rates for both leishmaniasis and VL from 2.94 (95% CI: 1.77 to 4.63) and 0.69 (95% CI: 0.38 to 1.12) in 1990 to 5.54 (95% CI: 3.74 to 7.81) and 2.89 (95% CI: 1.50 to 4.78) in 2021, respectively. In contrast, South Asia classified by the World Bank recorded the fastest rise in age-standardized DALYs rates for CML during the same period from 1.98 (95% CI: 1.08 to 3.41) in 1990 to 4.39 (95% CI: 2.91 to 6.24) in 2021. At the country level, Niger experienced the steepest increase in age-standardized DALYs rates for leishmaniasis overall from 5.56 (95% CI: 3.15 to 8.64) in 1990 to 29.38 (95% CI: 16.25 to 46.89) in 2021, Chad for VL from 2.82 (95% CI: 1.49 to 4.52) in 1990 to 18.96 (95% CI: 9.69 to 30.73) in 2021, and Morocco for CML from 3.52 (95% CI: 1.19 to 7.81) in 1990 to 12.51 (95% CI: 7.84 to 17.84) in 2021 (Supplementary Tables 1–3). Additionally, Figure S1 demonstrates a negative association between SDI levels and the age-standardized DALY rates for leishmaniasis, VL, and CML (P < 0.001).

The age-specific DALYs rate for VL decreased with age, while the DALYs rate for CML increased with age (Supplementary Tables 4–6). An analysis of age distribution revealed that the differences in DALY rates for VL between men and women were primarily due to disparities in the 35–44 years age group (Figs. 2 and 3). Although the overall age-standardized DALYs rate for CML was similar between sexes, in the > 55 years age group, the DALYs rate was higher in men (7.03) than in women (4.49) (Fig. 4).

Fig. 2.

Difference and ratio in age-specific DALYs of leishmaniasis between men and women by sociodemographic index (five categories; countries with a high, high- middle, middle, low-middle, or low sociodemographic index), from 1990 to 2021. The difference is equal to the age-specific rate in men minus that in women (A), and the ratio is equal to the age-specific rate in men divided that in women (B), with a difference > 0 and a ratio > 1 meaning men have higher rates

Fig. 3.

Difference and ratio in age-specific DALYs of VL between men and women by sociodemographic index (five categories; countries with a high, high- middle, middle, low-middle, or low sociodemographic index), from 1990 to 2021. The difference is equal to the age-specific rate in men minus that in women (A), and the ratio is equal to the age-specific rate in men divided that in women (B), with a difference > 0 and a ratio > 1 meaning men have higher rates

Fig. 4.

Difference and ratio in age-specific DALYs of CML between men and women by sociodemographic index (five categories; countries with a high, high- middle, middle, low-middle, or low sociodemographic index), from 1990 to 2021. The difference is equal to the age-specific rate in men minus that in women (A), and the ratio is equal to the age-specific rate in men divided that in women (B), with a difference > 0 and a ratio > 1 meaning men have higher rates

Attributable risk factors for DALYs in leishmaniasis Globally

For VL, both males and females are impacted by various occupational and environmental exposures, with notable differences in magnitude between the sexes. Among males, occupational exposure to beryllium stands out as a significant risk factor (P < 0.05). Other occupational exposures for males, such as sulfuric acid, benzene, formaldehyde, and arsenic, also contribute substantially to VL risk (P < 0.05). Environmental pollutants like nitrogen dioxide and lifestyle factors such as low milk and calcium intake are additional risk factors for males (P < 0.05), though with lower coefficients. Males are also at risk from lifestyle choices such as chewing tobacco and low physical activity (P < 0.05) (Fig. 5 and Supplementary Table 7). In females, occupational exposure to sulfuric acid presents the highest risk among the listed factors (P < 0.05), though it is less impactful than beryllium exposure in males. Other occupational hazards like formaldehyde, asbestos, and asthmagens also contribute to VL risk in females (P < 0.05), albeit at lower levels compared to males. Environmental pollutants like nitrogen dioxide and nutritional deficiencies such as low calcium and zinc intake are notable risk factors for females (P < 0.05), with the latter showing a significant association with VL. Interestingly, both sexes share some common risk factors, such as residential radon exposure and childhood sexual abuse (P < 0.05), but these appear to have a relatively minor impact compared to occupational hazards (Fig. 5 and Supplementary Table 7).

Fig. 5.

Association of DALYs of leishmaniasis with risk factors globally. The risk was stratified by type and sex, as illustrated in the Sankey diagram (A). The Venn diagram illustrates the overlap of risk factors across sexes in VL (B) and CML (C)

For CML, the data highlights trichloroethylene as a significant occupational risk for both sexes (P < 0.05), but with a higher impact on females than males. Similarly, beryllium, cadmium, and chromium exposure are relevant for females (P < 0.05), while in males, the risks are lower but still present. For both sexes, polycyclic aromatic hydrocarbons and nickel exposure are consistent occupational hazards (P < 0.05), though more pronounced in females. Additionally, females show some risk from arsenic exposure (P < 0.05), whereas males face a more moderate risk from diesel engine exhaust (P < 0.05) (Fig. 5 and Supplementary Table 7).

Attributable risk factors for dalys in leishmaniasis regionally

For VL, in low-SDI regions, the most significant risk factors are occupational exposures, particularly for males. Exposure to beryllium and cadmium emerges as an overwhelming risk (P < 0.05) with extremely high coefficients. Other important exposures include formaldehyde, arsenic, and sulfuric acid (P < 0.05), which, although less severe than beryllium and cadmium, still contribute substantially to the disease burden. Environmental pollutants like nitrogen dioxide also play a notable role in these regions (P < 0.05), particularly in males. Additionally, poor nutrition, exemplified by low intake of milk and calcium, further exacerbates VL risk in low-SDI populations (P < 0.05) (Supplementary Table 7). In middle-SDI regions, the risk from occupational exposures declines, although beryllium exposure remains a key factor for males (P < 0.05). Exposures to formaldehyde and sulfuric acid are still present but with less intensity compared to low-SDI regions (P < 0.05). Environmental factors like nitrogen dioxide pollution continue contributing to VL risk (P < 0.05), though the impact is smaller. Lifestyle factors, including chewing tobacco and low physical activity, emerge as relevant risks, suggesting a shift like health challenges as development improves (P < 0.05) (Supplementary Table 7). In high-SDI regions, the overall burden from occupational exposure is significantly reduced (P < 0.05). However, formaldehyde, sulfuric acid, and chromium remain relevant (P < 0.05), though their impact is lower than in less developed regions. Lifestyle risks, such as tobacco use and zinc deficiency, persist as key contributors to VL (P < 0.05) (Supplementary Table 7).

For CML, in low-SDI regions, trichloroethylene exposure is a major risk factor (P < 0.05), particularly for females, along with significant risks from beryllium and cadmium exposure (P < 0.05). In addition, arsenic and polycyclic aromatic hydrocarbons are also important contributors to disease risk (P < 0.05), affecting both males and females (Supplementary Table 7). In middle-SDI regions, the risk from trichloroethylene exposure remains significant (P < 0.05), though at a lower level, and is accompanied by exposure to chromium and polycyclic aromatic hydrocarbons (P < 0.05). While occupational exposures still contribute to CML, the impact is less severe compared to low-SDI regions (P < 0.05) (Supplementary Table 7). In high-SDI regions, occupational risks for CML are further reduced, though trichloroethylene and beryllium exposure still pose risks (P < 0.05), albeit to a lesser degree (Supplementary Table 7).

Discussion

Principal findings

This study offers an extensive analysis of the global burden of leishmaniasis from 1990 to 2021, revealing several significant trends and disparities. The global age-standardized DALYs rate for VL has shown a marked decline over the past three decades, reflecting advancements in control measures and interventions, particularly in regions with higher socio-demographic development. However, this positive trend contrasts with the increasing age-standardized DALYs rate for CML, which has risen, especially in countries with low- and middle-SDI, indicating an ongoing public health challenge in less-developed regions.

The study also identifies substantial sex disparities in the burden of leishmaniasis. Globally, males and females share many risk factors for VL and CML, with males more affected by industrial exposures and females by chemicals like trichloroethylene and cadmium. Environmental pollutants and nutritional deficiencies impact both sexes, while lifestyle risks like tobacco use and inactivity are more prominent in males. Tailored, sex-specific interventions are essential to reduce the disease burden.

Regional variations in the impact of risk factors are clearly observed, with occupational exposures being more prominent in certain areas, while nutritional deficiencies are more critical in less developed regions. Low-SDI regions face the highest risk from occupational exposures and nutritional deficiencies. As regions develop, risks shift towards lifestyle factors and residual industrial hazards, requiring adaptive public health strategies.

Difference in the burden of leishmaniasis

The findings of this study demonstrate a significant decline in the global burden of VL from 1990 to 2021, as measured by age-standardized DALY rates, consistent with findings from other studies [1, 20, 21]. The primary reasons for this decline are public health interventions and medical infrastructure improvements globally. This trend is consistent with the findings of previous studies, such as those by Alvar et al. and Burza et al., which reported a decreasing burden of VL in certain endemic regions (such as the Indian subcontinent, including India, Bangladesh, and Nepal) during earlier decades [5, 22]. The observed decline in our study is particularly pronounced in low-SDI and low-middle-SDI regions, where targeted interventions, such as the introduction of rapid diagnostic tests and effective vector control measures, have been widely implemented [23–25]. This suggests that the global health community’s efforts to combat VL have been partially successful, at least in areas with better healthcare infrastructure.

However, unlike VL, whose disease burden has declined in many endemic regions due to optimized control programs and improved access to treatment, the burden of CML has shown an upward trend — particularly in countries with low-to-middle SDI. This difference in disease burden is likely attributed to the varying distribution ranges and prevalence intensity of their pathogens and vectors: VL is primarily caused by the Leishmania donovani complex, transmitted by specific sandfly vectors (e.g., Phlebotomus genus in the Old World), and is more responsive to targeted control measures. In contrast, CML is mainly caused by species of the subgenus Viannia (such as Leishmania braziliensis), with vectors predominantly from the Lutzomyia genus in the New World, and its transmission also involves animal hosts like forest rodents. Additionally, the upward trend of CML reflects distinct epidemiological differences from VL: a broader geographic distribution and reliance on zoonotic transmission cycles. These characteristics stand in stark contrast to VL’s transmission patterns and the effectiveness of control responses targeting it, making CML difficult to control effectively through conventional measures designed for VL [1, 5, 20, 22]. This study shows that in low-SDI countries, the DALYs rate for CML has been increasing since 1990, with similar trends observed in other studies conducted in Brazil’s northeastern and northern regions [26, 27]. This disparity may stem from the ongoing impact of environmental changes, such as deforestation and urbanization, which increase human contact with sandflies carrying Leishmania parasites. In high-burden countries such as Afghanistan, Suriname, Sudan, Djibouti, Nicaragua, Panama, Turkmenistan, Tunisia, and Iraq, persistent transmission is largely driven by poverty, weak health infrastructure, limited access to diagnosis and treatment, and challenges in vector control [22, 28]. Political instability and population displacement in conflict-affected regions further hinder surveillance and control efforts, contributing to sustained endemicity. Reflecting our findings, Moran analyses in northeastern Brazil indicate that high incidences of leishmaniasis in these high-risk areas are closely associated with socioeconomic factors such as poverty and inadequate infrastructure [29]. Comparable patterns have also been documented in East African settings, where fragile health systems and large-scale population movements continue to sustain transmission [22, 28]. Moreover, migrants and displaced populations often experience barriers to diagnosis and treatment, especially in resource-limited or non-endemic contexts, further complicating control strategies [30]. Together, these factors highlight persistent inequities that maintain high leishmaniasis burdens across endemic regions.

Risk factors for leishmaniasis burden

The analysis of risk factors in this study revealed that nutritional deficiencies, deficient milk, calcium intake, and zinc deficiency, play a significant role in the burden of VL, a finding consistent with the work of Oryan and Akbari, who highlighted the importance of micronutrients in modulating immune responses to Leishmania infection [31]. Brazil’s research has also identified malnutrition and lack of physical exercise as significant factors influencing VL, highlighting the importance of nutritional interventions and promoting healthy lifestyles in these areas [26, 32, 33]. However, our study further quantifies the global impact of low milk, calcium intake, and zinc deficiency on DALY rates, providing a more comprehensive view of its role as a risk factor across different regions. This underscores the necessity for nutritional interventions, especially in low-SDI regions, where access to a balanced diet is often limited. These interventions may reduce the pathogen load of Leishmania in the bloodstream, thereby decreasing the likelihood of transmission through vector bites.

In contrast, our findings on the role of occupational exposures in CL and MCL diverge somewhat from earlier studies, such as those by Valero et al., which primarily focused on environmental factors without considering the sex-specific impacts of occupational risks [34]. Our study reveals that men in VL, particularly those engaged in jobs involving heavy metals like chromium, are disproportionately affected. This sex disparity in risk exposure is crucial for designing targeted public health interventions. The discrepancy between our findings and earlier studies may stem from differences in study design, as our analysis utilized a more granular, region-specific approach, allowing us to identify subtler patterns of risk [1, 20, 21].

After adjusting for the composite occupational exposure index, males continued to have significantly higher DALY rates than females for both visceral leishmaniasis (VL) and cutaneous/mucocutaneous leishmaniasis (CML). For VL, the adjusted male–female difference was β = 0.834 (SE = 0.109, P < 0.001), corresponding to + 130.2% on the original scale; for CML, β = 0.268 (SE = 0.055, P < 0.001), + 30.8%. Results were consistent using the PCA-based exposure index, and sex-by-exposure interactions were not significant (VL P = 0.506; CML P = 0.847), indicating that occupational exposure did not materially modify the sex effect (Supplementary Table 8).

However, it is essential to note that the environmental characteristics of the study areas and the living habits of the populations may act as confounding variables. In areas with hot and humid climates and poor sanitation, the incidence of CL and CML may be higher, even when the exposure levels to these risk factors are similar [35]. For example, in some tropical regions, the close proximity of human settlements to natural water bodies or forests may increase the likelihood of contact with pathogen - carrying insects, thereby confounding the relationship between occupational exposure and the diseases. Occupational activities such as mining and forestry often place individuals in close proximity to sandfly habitats. For instance, in mining areas, environmental disruptions can lead to an increase in sandfly breeding sites. Miners are thus more likely to come into contact with infected sandflies, which significantly elevates their risk of VL and MCL infection [36–38]. In regions with a low SDI, where mining and agricultural activities are prevalent, the population’s exposure to infected sandflies due to work - related environmental factors is higher. This situation contributes to the relatively high prevalence of VL in these occupational groups [35]. These regional and sex differences suggest that future public health strategies need to target specific at-risk groups, particularly in low-SDI regions, by focusing on improving workplace safety, reducing exposure to harmful substances, and strengthening nutritional interventions.

Strengths and limitations of this study

This study benefits from the comprehensive nature of the GBD dataset, which provides detailed estimates of the burden of leishmaniasis across a wide range of countries and demographic groups. The use of advanced statistical methods, including joinpoint regression and generalized linear mixed model, strengthens the reliability of the findings by accounting for temporal trends and regional variations.

However, there are limitations inherent in the study. The accuracy of the GBD estimates is contingent on the quality of the underlying data, which can vary significantly between regions. For example, in low-SDI regions, underreporting and misclassification of leishmaniasis cases may lead to underestimation of the true disease burden. Additionally, the focus on DALYs as the primary measure of disease burden may not fully capture leishmaniasis’s broader social and economic impacts, particularly in regions where the disease is endemic. Moreover, while the study provides valuable insights into risk factors, the potential for confounding variables, such as unmeasured environmental factors or genetic predispositions, cannot be entirely ruled out. Furthermore, as this study is based on observational data from the GBD 2021 framework, the identified associations between occupational or nutritional exposures and leishmaniasis DALYs should be interpreted as correlations rather than causal relationships. Future longitudinal or interventional studies are warranted to validate these findings.

Public health and policy implications

The findings of this study offer important evidence to inform the implementation of the WHO Roadmap for Neglected Tropical Diseases 2021–2030, which emphasizes integrated vector control, equitable access to diagnosis and treatment, and enhanced surveillance for leishmaniasis. The pronounced disparities observed across SDI levels and sexes highlight the need for equity-oriented resource allocation and context-specific interventions. Moreover, by identifying nutritional and occupational risk factors associated with leishmaniasis burden, our results reinforce the importance of coordinated actions across health, labor, and social sectors to reduce exposure risks and strengthen population resilience in endemic settings.

Conclusions

The study highlights the persistent global burden of leishmaniasis, with notable disparities across regions, sexes, and socio-demographic categories. While significant progress has been made in reducing the burden of VL, the rising trend in CML calls for renewed public health efforts, particularly in low- and middle-SDI regions. The identified sex differences and regional variations in risk factors suggest that future interventions must be tailored to address specific vulnerabilities, emphasizing the need for a multifaceted approach to combat leishmaniasis globally. In particular, integrated nutritional interventions and occupational safety measures should be prioritized as central components of leishmaniasis prevention and control programs, complemented by strengthened surveillance systems and equitable access to healthcare in endemic settings.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

S.L. wrote the main manuscript text and prepared the figures. T.Q. contributed to data analysis and interpretation. N.Z., M.L., and X.H. contributed to the literature review and revised the manuscript. X.W. assisted with data collection and analysis. S.J., M.L., and S.W. contributed to the study design and methodology. L.Z. and X.W. supervised the study, reviewed and edited the manuscript, and provided overall guidance. All authors reviewed and approved the final manuscript.

Funding

This study was supported by the institutional foundation of the First Affiliated Hospital of Xi’an Jiaotong University (2024-QN-39).

Data availability

All relevant data are within the manuscript. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Ethical approval

Not applicable.

Competing interests

The authors declare no competing interests.