Data is sourced from GBD database (2021), which is a global health research platform supported by Institute for Health Metrics and Evaluation (IHME) at the University of Washington, and jointly maintained by World Health Organization (WHO), the World Bank, and other institutions. It covers the health data of 204 nations and territories worldwide since 1990, quantifies 87 risk factors and 371 diseases, meanwhile providing standardized indicators such as age standardized rate (ASR) multi-dimensionally classified such as age, gender, and year. The GBD 2021 study applies complex statistical models such as MR-BRT, DisMod MR 2.1, CODEm, etc. to adjust the collected data from around the world to reduce its heterogeneity. We obtained processed data (prevalence, incidence, deaths, and DALYs) for all regions and countries from the GBD 2021 study for secondary analysis.

SDI serves as a composite metric for assessing regional socioeconomic development status. This index, ranging from 0 (minimal development) to 1 (optimal development), is derived from three weighted components: gross domestic product per capita, educational attainment (measured by average schooling years), and fertility rates. Based on their SDI scores, geographical units were stratified into five distinct development tiers (high, high-middle, middle, low-middle, low). The focus of this study is on relation between SDI values and various disease burden indicators.

Disease burden metrics selected for this study comprise four principal indicators: “Prevalence,” “Incidence,” “Deaths” and “DALYs.” ASR adjusts crude rate (including incidence rate and mortality) by applying a standardized population distribution. This methodological approach effectively eliminates potential biases arising from differences in population age distributions between regions or across time periods. The ASR per 100,000 individual is computed according to equation below: ASR=∑i=1Aaiwi∑i=1Awi×100,000 (a_i: the i^th age category’s rate in specific age range; w: corresponding i^th age group’s population size within reference population; A: total count of group). From GBD database, age-standardized death rate (ASDR), age-standardized prevalence rate (ASPR), age-standardized DALYs rate, and age-standardized incidence rate (ASIR).

The temporal trends of ASR were quantified with estimated annual percentage change (EAPC). The computational approach involves fitting the model: ln(y_t) = α + βt + ϵ (y_t is the natural logarithm of ASR; α is the intercept; β captures the temporal slope coefficient; ϵ accounts for random variation). The EAPC value is subsequently calculated as 100 × [exp(β)−1]. Linear regression model is applied for calculation on 95% confidence interval (CI) of EAPC. If the lower bounds of EAPC with its entire 95%CI are both positive, it indicates a significant upward trend in ASR. On the contrary, if the upper bounds of EAPC and its 95%CI are both negative, it reflects a significant downward trend in ASR. If both conditions are not met, the ASR is defined as stable.

We conducted correlation analysis on the disease burden (ASPR, ASIR, age-standardized DALYs rate, ASDR) and SDI values of all regions and countries, which were performed in R version 4.4.2. We use “cor.test” function from “stats” R package to carry out Pearson correlation analysis. All tests were two-sided with a significance level set at p < 0.05. In addition, we conducted statistical analysis on the disease burden of different genders worldwide using “tbl_summary” function from “gtsummary” R package.

The Bayesian age–period–cohort (BAPC) model is an analysis tool based on the Bayesian statistical framework, mainly used to decompose the age, period, and queue effects of disease burden over time, and predict future trends. The statistical principle is based on Bayesian inference, using Markov Chain Monte Carlo (MCMC) or Integrated Nested Laplace Approximation (INLA) algorithms to handle data loss and uncertainty, while introducing prior knowledge to enhance the robustness of small sample data. Compared to traditional models, its advantages lie in the comprehensive analytical ability of multidimensional time effects, robust handling of data sparsity and measurement errors, and flexible integration of multidimensional data. In this study, we applied disease burden data from GBD 2021 and demographic forecast data from the IHME, using the “BAPC” R package to predict the trend of disease burden changes at the global level.

Global prevalence of OFCs reached 4,124,006.8 cases (95%UI: 3,318,692.5–5,026,199.6) in 2021, representing a 40.3% increase from 1990 (2,937,706.5 cases, 95% UI: 2,389,357.8–3,535,593.7). Despite this substantial growth in case number, ASPR in 2021 remained nearly unchanged at 53.4 per 100,000 (95% UI: 43–65), comparable to the 1990 ASPR of 53.5 (95% UI: 43.4–64.5). EAPC of ASPR was −0.04 (95% CI: −0.05 to −0.02) (Table 1; Figure 1). Global incidence of OFCs in 2021 was 183,302.4 cases (95%UI: 135,255.4–241,690.8), marking a 24.79% decrease from 1990. ASIR declined from 3.8 per 100,000 (95% UI: 2.8–4.8) in 1990 to 3.0 per 100,000 (95% UI: 2.2–3.9) in 2021. EAPC for ASIR was −0.89 (95% CI: −0.94 to −0.83), suggesting a persisting downward trend in incidence (Table 1; Figure 1). OFCs-related deaths were estimated at 1,718.6 cases (95% UI: 484.8–4,409.5) in 2021, reflecting an 86.09% reduction compared to 1990, with an EAPC of −6.17 (95% CI: −6.24 to −6.11) (Table 1; Figure 1). Global DALYs attributed to OFCs reached 408,775.3 (95% UI: 252,320.1–671,119.9) in 2021, showing a 68.32% decrease from 1990. The age-standardized DALYs rate stood at 5.8 per 100,000 (95% UI: 3.5–9.8), with an EAPC of −4.13 (95% CI: −4.28 to −3.98) (Table 1; Figure 1).

From the perspective of social development level, OFCs burden worldwide shows notable regional differences, and the disease burden indicators vary greatly among different SDI regions. The ASPR in low-middle SDI regions represented to be the highest, of 76.3 per 100,000 (95% UI: 60.7–93.6), and regions with high SDI reported the lowest, of 33.6 per 100,000 (95% UI: 27–40.6). The EAPC of the two regions is similar, with the former being −0.23 (95% CI: −0.29 to −0.16) and the latter being −0.23 (95% CI: −0.25 to −0.22). ASPR dropped in all regions, with the middle-high SDI region showing the most notable drop, showing EAPC of −0.46 (95% CI: −0.52 to −0.39). ASPR has decreased from 40.4 per 100,000 (95% UI: 32.9–48.3) in 1990 to 36.2 per 100,000 (95% UI: 29.6–43.5) in 2021, indicating more significant progress in the prevention and treatment of OFCs in these regions compared to other areas. The EAPC of the low SDI region is −0.29 (95% CI: −0.32 to −0.26), and its ASPR has decreased from 68.9 per 100,000 (95% UI: 55–83.8) in 1990 to 62.8 per 100,000 (95% UI: 50.5–76.8). The EAPC within middle-SDI region is −0.07 (95% CI: −0.1 to 0.04), which is almost the same as the ASPR in 1990 and 2021 (Table 1; Figure 1).

ASIR also shows regional differences. High SDI regions exhibited the lowest ASIR at 2.5 per 100,000 (95% UI: 1.8–3.2), and middle-low SDI regions showed the highest at 3.3 per 100,000 (95% UI: 2.5–4.4). The analysis of the ASIR reveals notable trends. The EAPC in the high-middle SDI regions is the highest, reaching −1.53 (95% CI: −1.59 to −1.47), while other regions exhibit a more uniform EAPC of around −0.85 (Table 1; Figure 1). The ASDR in low SDI areas is the highest, reaching 0.1 per 100,000 (95% UI: 0–0.2), whereas other regions are nearly at zero. Similarly, the EAPC for high-middle SDI areas is the highest, at −11.62 (95% CI: −12.12 to −11.11) (Table 1; Figure 1). The age-standardized DALYs rate further revealed regional differences. Low SDI regions have the highest DALYs rate at 8.6 per 100,000 (95% UI: 3.9–21.7), while high SDI regions have the lowest at 2.2 per 100,000 (95% UI: 1.4–3.4). Notably, high-middle SDI regions show the most significant decrease in age-standardized DALYs rate, with an EAPC of −8.17 (95% CI: −8.57 to −7.76) (Table 1; Figure 1).

Global data demonstrate a substantial 31-year decline (1990–2021) in OFCs disease burden, primarily attributable to advancements in medical technology and socioeconomic development. High-middle SDI regions exhibited particularly notable progress, reflecting accelerated improvement in therapeutic and preventive capability once society reaches this developmental threshold. Indicators of disease burden in high-SDI regions maintained the lowest level over three decades, due to their well-established superior healthcare infrastructure and social conditions since 1990. Conversely, the paradoxically lower prevalence and incidence rates observed in low-SDI regions are likely attributable to severe underreporting primarily driven by neonatal mortality among untreated cases and systemic gaps in health surveillance systems (20). Despite incremental advancements in low- and low-middle SDI regions, OFCs continues to impose disproportionately heavy health burden in these areas.

From the perspective of geography, the top three regions with the highest ASPR in 2021 are South Asia, North Africa and Middle East, Central Asia, the values are, respectively, 89.1 per 100,000 (95% UI: 70.7–110.1), 85.2 per 100,000 (95% UI: 68.2–103.5), and 80 per 100,000 (95% UI: 64.6–96.4). In contrast, high-income North America had the lowest ASPR at 19.7 per 100,000 (95% UI: 15.1–24.9). ASPR in the Australasia and Europe are significantly lower than those in Asia and Africa. Almost all regions experience a decline in prevalence between 1990 and 2021, except for the four regions: Andean Latin America, East Asia, Caribbean, Southeast Asia, with EAPCs of 1.63 (95% CI: 1.54 to 1.72), 1.32 (95% CI: 1.24 to 1.4), 0.82 (95% CI: 0.78 to 0.86), and 0.6 (95% CI: 0.54 to 0.65), respectively (Table 1). Additionally, we conducted a correlation analysis between ASPR and SDI across varying areas, incorporating changes in SDI from 1990 to 2021. The results are shown in Figure 2. We used distinct shapes and colors to represent different regions and plotted 21 lines based on their SDI changes over this period. The computation outputted negative relation between ASPR and SDI, with a correlation coefficient of −0.34 (95% CI: −0.41 to −0.28) and p-value < 0.001 (Figure 2).

Despite the most significant decline in ASIR in Central Asia over the past 32 years, with an EAPC of −1.75 (95% CI: −1.83 to −1.67), its ASIR still ranks highest at 5.1 per 100,000 (95% UI: 3.6–6.9). South Asia and high-income Asia Pacific follows closely, with rates of 3.8 per 100,000 (95% UI: 2.7–5.1) and 3.8 per 100,000 (95% UI: 2.5–5.2), respectively. The region with the lowest ASIR is Oceania, at 1.5 per 100,000 (95% UI: 1.0–2.1). The regions with positive EAPC values include Southeast Asia Oceania, Caribbean, high-income North America, with values of 0.67 (95% CI: 0.62 to 0.73), 0.38 (95% CI: 0.3 to 0.46), 0.28 (95% CI: 0.16 to 0.41), and 0.01 (95% CI: −0.09 to 0.12), respectively (Table 1). The correlation coefficient between SDI values and ASIR across different regions is −0.04 (95% CI: −0.12 to 0.03), with a p-value of 0.25, indicating no significant correlation (Figure 2).

Oceania has the highest ASDR at 0.2 per 100,000 (95% UI: 0–0.4), while in other regions the value is around zero. During the 32 years, ASDR has significantly decreased in all regions (Table 1). The correlation coefficient between SDI values and ASDR is −0.51 (95% CI: −0.57 to −0.45), with a p-value of<0.001, indicating a significant correlation (Figure 2).

The top three rates of age-standardized DALYs in 2021 are Oceania, North Africa and Middle East, Southern Sub-Saharan Africa, at 17.5 per 100,000 (95% UI: 4.8–42.2), 9.7 per 100,000 (95% UI: 5.7–21.2), and 7.7 per 100,000 (95% UI: 4.9–11.4), respectively. High-income North America has the lowest rate at 1.3 per 100,000 (95% UI: 0.8–2.0). Rates of age-standardized DALYs have dropped within all regions, with East Asia showing the most notable decline, at an EAPC of −9.41 (95% CI: −9.93 to −8.88) (Table 1). The SDI value of each region shows negative relation with rate of age-standardized DALYs, with a correlation coefficient of −0.55 (95% CI: −0.60 to −0.50), p-value < 0.001 (Figure 2).

In 2021, countries with the top three high ASPR were Palestine (147.15 per 100,000, 95% UI: 119.61–176.54), State of Qatar (140.47 per 100,000, 95% UI: 111.24–173.15), and Islamic Republic of Pakistan (136.06 per 100,000, 95% UI: 107.62–169.11), all of which are in Asia. The country with the lowest ASPR is Canada (9.07 per 100,000, 95% UI: 7.15–11.05). Puerto Rico is the country with the most notable elevation in ASPR (EAPC: 2.05, 95% CI: 1.93 to 2.18), while Italy has the most notable decline in ASPR (EAPC: −1.36, 95% CI: −1.55 to −1.17) (Supplementary Table S1; Figure 3A). The fastest elevation in case number is in Qatar, with a 534.2% elevation in case number in 2021, compared to 1990 (Figure 4A). We conducted several correlation analyses between these disease burden indicators and SDI values across different countries. Correlation coefficient between SDI and ASPR is −0.23, showing a negative correlation, with a 95% CI of −0.36 to −0.10 and a p-value < 0.05 (Figure 5).

In terms of ASIR, the top-ranked countries are Kazakhstan (6.34 per 100,000, 95% UI: 4.33–8.64), Mongolia (6.21 per 100,000, 95% UI: 4.00–9.25), and Turkey (5.81 per 100,000, 95% UI: 4.09–7.76), all situated in Central Asia. Conversely, Canada has the lowest ASIR at 0.83 per 100,000 (95% UI: 0.58–1.13). The ASIR of Taiwan (Province of China) has seen the most significant increase (EAPC: 2.95% CI: 1.73 to 2.28) (Supplementary Table S2; Figure 3B). Countries experiencing a rapid surge in the number of cases include Qatar, Papua New Guinea, Chad, Niger, Mali, and Somalia, with their incidence rates in 2021 more than doubling compared to 1990 (Figure 4B). The correlation coefficient between SDI values and ASIR is −0.06 (95% CI: −0.20 to 0.08), with a p-value of 0.376, indicating no clear correlation between the two (Figure 5).

Papua New Guinea has the highest ASDR (0.19 per 100,000, 95% UI: 0.04–0.52) (Supplementary Table S3; Figure 3C). Except for a few regions and countries with an increase in ASDR globally (e.g., Afghanistan, Trinidad, and Tobago), there has been significant decreases in ASDR in all others. It can be observed that countries with increased deaths, such as Afghanistan, Chad, Somalia, etc., are mainly located in Sub Saharan Africa and Central Asia (Figure 4C). The correlation coefficient between the SDI values and ASDR is −0.62 (95% CI: −0.70 to −0.53), with p-value <0.05, indicating a significant correlation (Figure 5).

The age-standardized DALYs rate is highest in Afghanistan (22.53 per 100,000, 95% UI: 5.8–104). The fastest decline is in China, with an EAPC of −9.59 and a 95% CI: −10.13 to −9.03 (Supplementary Table S4; Figure 3D). Likewise, the nations experiencing the most substantial increases are predominantly in Sub Saharan Africa and Central Asia (Figure 4D). The correlation coefficient between the SDI values and ASDR is −0.64 (95% CI: −0.71 to −0.55), p-value <0.05(Figure 5).

Between 1990 and 2021, trends of OFCs disease burden showed nearly identical patterns between two genders. Male population exhibited higher ASDR, age-standardized DALYs rate, ASPR compared to females, while females exhibited higher ASIR. The disparity in ASPR between genders remained stable, with males maintaining higher ASPR values by 2021. In contrast, ASDR, age-standardized DALYs rate, and ASIR reached comparable levels between males and females by 2021 (Figure 6). Among the four disease burden indicators, only ASPR showed statistically significant gender differences (p < 0.001).

We predict the trajectory of OFCs burden from 2022 to 2050. The combined ASPR for both sexes is anticipated to decline globally, falling from roughly 53.4 per 100,000 in 2021 to about 51.4 per 100,000 by 2050, which equates to a nearly 3.7% reduction over 30 years. Expected prevalence in male population is fairly constant, with minor rise from around 54.7 per 100,000 to 51.5 per 100,000, from 2021 to 2050. For females, a comparable decline is anticipated, with the prevalence rate falling from around 52.0 per 100,000 in 2021 to 51.5 per 100,000 by 2050. The global incidence of OFCs is also expected to experience a slight downward trend for both genders combined. ASIR is projected to decrease from approximately 2.81 per 100,000 in 2021 to about 1.78 per 100,000 by 2050. Additionally, ASDR for OFCs is expected to decline for both sexes combined, from roughly 0.026 per 100,000 in 2021 to around 0.003 per 100,000 by 2050. Moreover, rate of age-standardized DALYs for OFCs is expected to see a significant decline for the sum of both gender groups, falling from 5.8 per 100,000 to approximately 2.0 per 100,000, 2021 to 2050. In all, the decrease in the ASPR is relatively modest, and the data differences between males and females are minimal (Figure 7).

The GBD data rely on model estimates, which may introduce information bias due to variations in disease definitions, diagnostic criteria, and data collection methods (e.g., inconsistent reporting standards across national health departments). These factors can lead to overestimation or underestimation of disease burdens in specific regions, particularly in countries/regions with underdeveloped healthcare systems or weak data reporting mechanisms. Additionally, the database lacks detailed granular data (e.g., race/ethnicity, disease subtypes), limiting in-depth analyses for specific populations.