Trends in the global and Chinese burden of rabies from 1990 to 2021 and forecasted to 2040: evidence from the Global Burden of Disease study 2021

Abstract

Background

This study analyzed global rabies burden and trends from 1990 to 2021, offering epidemiological insights worldwide by using the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2021 database.

Methods

We obtained all relevant data on rabies worldwide from the GBD database from 1990 to 2021, including incidence, mortality, and disability-adjusted life years (DALYs), were analyzed by gender, age, sociodemographic index (SDI), and region using the GBD 2021 data. Trends were assessed with average annual percentage change (AAPC), and future trends were predicted using a Bayesian age-period-cohort (BAPC) model.

Results

From 1990 to 2021, global rabies incidence and age-standardised incidence rates (ASIR) decreased by 53.8% and 69.4%, respectively. Mortality and DALYs also declined by 50.2% and 54.5%. The most significant declines were observed between 2007 and 2010, particularly in low SDI regions, with AAPC for incidence, mortality, and DALYs ASRs at − 3.983%, − 3.929%, and − 3.97%, respectively. South Asia had the highest incidence in 2021, while Central Latin America saw a 99.9% decrease in ASIR. Nepal had the highest ASIR in both 1990 and 2021, though it significantly declined over time. In China, significant reductions in rabies burden occurred post-2005, with consistently higher rates in men.

Conclusions

The study emphasizes the importance of targeted interventions and addressing regional disparities to reduce the global rabies burden.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-025-12425-w.

Introduction

Rabies is a vaccine-preventable zoonosis with a significant mortality burden worldwide, causing approximately 60,000 mortalities and severe dysfunction of the central nervous system annually, and children living in the poorest countries are the most vulnerable group [1, 2]. Nevertheless, rabies remains a neglected disease [3]. Rabies is reported in more than 150 countries, excluding Antarctica [4]. Approximately 99% of human cases occur in developing countries, mainly in Asia and Africa [5]. Some regions and countries suffered the heaviest burden of rabies, such as India [6] and Nepal [7]. However, due to the inadequate rabies prevention and reporting systems in some regions and countries, the actual situation regarding rabies incidence and mortality may have been severely underestimated [8]. Notably, the World Health Organization constructed a rabies reporting database named Rabnet that handles the disadvantages of rabies’ reporting information [9]. Therefore, a comprehensive analysis of the current global burden of rabies incidence and mortality will provide a valuable reference for rabies prevention and control. This is particularly important for offering strong support in policy-making for regions with poor rabies control capabilities.

Rabies is a fatal disease that is relatively completely vaccine-preventable, with effective vaccines being available for > 100 years [10]. However, significant regional disparities in effective vaccination globally remain, both for humans and animals. In high-income countries, rabies has been effectively eliminated through mass dog vaccination and timely postexposure prophylaxis for humans [11]. During the COVID-19 pandemic, substantial funds were directed toward combating the virus, which resulted in insufficient human and financial resources for rabies prevention and control [12, 13]. International public health organizations, such as Gavi, have historically contributed to narrowing the gap between high- and low-income countries in rabies prevention by increasing vaccine accessibility and reducing costs [14]. Before the COVID-19 outbreak, global burden and trends in rabies have been reported from 2010 to 2015 and from 1990 to 2019 [15, 16]. Therefore, investigating the global burden of rabies post-pandemic and calling for increased global attention and investment in rabies control are crucial to achieve eradication goals and improve public health systems.

Our study provides updated global rabies estimates and includes data from previously unassessed or data-scarce regions, relying on predictive covariates and global trends adjusted for the sociodemographic index (SDI) level. Thus, we aimed to highlight the scope and intricacies of rabies implications worldwide, informing healthcare decisions and contributing substantially to the existing body of knowledge.

Methods

Data source

We used data from the 2021 Global Burden of Disease (GBD) study, currently coordinated by the Institute for Health Metrics and Evaluation (IHME). The GBD 2021 study was published in 2024 with epidemiologic assessments of 371 diseases and injuries, 87 risk factors, and 256 causes of mortality from 204 countries and territories [17]. Detailed information about rabies incidence, mortality, and disability-adjusted life years (DALYs) was freely gathered at the GBD 2021 website (http://ghdx.healthdata.org/gbd-results-tool). All measures were presented as all ages and age-standardised rates (ASRs) per 100,000 individuals, with uncertain interval (UI) of 95% for clarity. Ethical approval and informed consent were waived because the GBD is publicly available, and the analysis did not include identifiable information.

Estimation of incidence, mortality, and dalys

Based on the GBD database, the DisMod-MR 2.1 method, a Bayesian meta-regression analysis was used for model construction. This technique uses disparate and limited epidemiological data to establish nonfatal outcomes and adjusts data from different sources to account for variation in study methodologies, which enforced consistent epidemiological parameters [18]. The International Classification of Diseases (ICD) code was used to describe rabies defined from recorded registration sources for ICD-10 (A82-A82.9) and ICD-9 (071-071.9, V01.5, V04.5) [19]. GBD researchers developed SDI, a composite measure to assess a region’s social and economic status. By integrating per capita income, educational attainment, and fertility rates, SDI creates a single indicator from 0 to 1, reflecting the social and economic status of a region or country [18]. The SDI was subdivided into five quantiles, high, high-middle, middle, low-middle, and low SDI.

Descriptive analysis

Initially, we conducted a descriptive analysis of the incidence, mortality, and DALYs of rabies from 1990 to 2021, including raw numbers and standardised rates. Subsequently, a systematic overview of the rabies burden was conducted in 1990 and 2021, categorized by gender, SDI regions, GBD regions, and 204 countries. Subsequently, we provided a preliminary description of the temporal trends for each indicator over from 1990 to 2021.

Data analysis

We used the Joinpoint regression (JPR) model developed by the National Cancer Institute [20], a tool frequently utilized to analyze temporal trends and pinpoint statistically significant inflection points. Additionally, the model also calculates the annual percent change (APC) and average annual percent change (AAPC) [21, 22]. We constructed the JPR model using the age-standardised annual rates of rabies in globe and China. An APC > 0 and < 0 indicate a yearly increase and a yearly decrease in ASRs, respectively. The trend is considered monotonic with no inflection points when APC equals AAPC. Our analysis leveraged JPR to discern significant changes in data trends over time, effectively distinguishing real shifts from random variability. We performed decomposition analysis to identify factors contributing to changes in rabies incidence, mortalities, and DALYs from 1990 to 2021, focusing on demographic influences, such as population growth and aging [23]. Subsequently, we analyzed the relationship between the rabies burden and the SDI by using smoothing splines models across five SDI levels, 21 GBD regions, and 204 countries [24]. The Pearson's correlation coefficient was used to assess linear associations between variables [25, 26]. The SDI, a composite index of per capita income, years of schooling, and fertility rate, ranges from 0 (least developed) to 1 (most developed), reflecting the impact of socioeconomic development on rabies. Slope inequality index (SII) and concentration index were used to evaluate disparities [27, 28], where positive SII values indicate better health outcomes in higher SDI regions, and CI values range from − 1 to 1 [29]. Moreover, we benchmarked regional burdens against top-performing regions using frontier analysis, highlighting areas for improvement and guiding policy interventions. For future projections, we utilized Bayesian age-period-cohort (BAPC) analysis with data from the UN World Population Prospects 2019 Revision and World Health Organization (WHO) World Population Data [30, 31]. This approach, implemented using the BAPC package in R (version 4.3.2) which builds on the traditional generalized linear model (GLM) framework. This Bayesian framework is general utilized the Integrated Nested Laplace Approximation (INLA) package, which was chosen for the precision in estimating marginal posterior distributions.

Results

Global pattern and trends in rabies from 1990 to 2021

Between 1990 and 2021, the global rabies incidence decreased by 53.8%, from 22,035 cases to 10,181 cases. The age-standardised incidence rate (ASIR) dropped by 69.4%, from 0.422 to 0.129 cases per 100,000 individuals. Similarly, global rabies mortality decreased by 50.2%, with cases declining from 21,806 to 10,084, whereas the age-standardised mortality rate (ASMR) also decreased by 69.4%, from 0.417 to 0.128 cases per 100,000 individuals. DALYs reduced by 54.4%, from approximately 1,368,780 to 569,550 cases, with the age-standardised DALY rate (ASDR) decreasing by 69.4%, from 24.485 to 7.496 cases per 100,000 individuals (Fig. 1, S1, and Table 1, S1, S2). Varied trends were shown using APC and AAPC in a detailed analysis. The steepest decline in ASIR occurred from 2007 to 2010, with an APC of − 7.74%. The overall AAPC for ASIR was − 3.811% (95% CI: −4.143%–−3.478%), indicating a significant decrease from 1990 to 2021. ASMR significantly declined between 2006 and 2013, with an APC of − 6.58% and an AAPC of − 3.759% (95% CI: −3.928%–−3.59%). ASDR also significantly decreased during 2006–2013, with an APC of − 6.5% and an AAPC of − 3.753% (95% CI: −3.975%–−3.531%) (Fig. 2; Table 1, S1, and S2).

Fig. 1.

The age-standardised incidence, mortality, and DALY rate (per 100,000 persons) of rabies among global and SDI quintiles between 1990 and 2021. SDI = sociodemographic index; DALY = disability-adjusted life years

Fig. 3.

Choropleth maps showing geographic variation in ASIR, ASMR, ASDR and associated AAPCs of rabies. (A) ASIR per 100,000 persons in 1990; (B) ASIR per 100,000 persons in 2021; (C) AAPC in ASIR; (D) ASMR per 100,000 persons in 1990; (E) ASMR per 100,000 persons in 2021; (F) AAPC in ASMR; (F) ASDR per 100,000 persons in 1990; (G) ASDR per 100,000 persons in 2021; (H) AAPC in ASDR. ASIR age-standardised incidence rate; ASMR age-standardised mortality rate; ASDR age-standardised DALY rate; AAPC average annual percentage change

Table 1.

Incidence numbers and ASR per 100,000 cases of rabies in 1990 and 2021, with percent changes and AAPC in ASIR from 1990 to 2021, categorized by global, SDI quantiles, and GBD regions.an be an exemplary model for the r

Location	Incidence						AAPC	p value
	No of people with rabies in 1990	No of people with rabies in 2021	Age standardised rate in 1990 (per 100, 000)	Age standardised rate in 2021 (per 100, 000)	Relative change of numbers from 1990 to 2021 (%)	Relative change of age-standardized rate from 1990 to 2021 (%)
Global	22035(15732 to 28729)	10181(6080 to 14293)	0(0 to 1)	0.129(0.076 to 0.182)	-53.8(-66.5 to -40.4)	-69.4(-77.6 to -61)	-3.811(-4.143 to -3.478)	<0.001
Sex：
Female	9208(6416 to 13382)	3800(2202 to 6184)	0(0 to 1)	0.096(0.055 to 0.159)	-58.7(-73.1 to -40.2)	-72.9(-82.1 to -61)	-4.21(-4.619 to -3.799)	<0.001
Male	12827(8777 to 16297)	6381(3528 to 8964)	0(0 to 1)	0.162(0.089 to 0.228)	-50.3(-66 to -31.1)	-67(-77.2 to -54.8)	-3.638(-4.138 to -3.135)	<0.001
SDI quantile：
High	11(7 to 14)	17(12 to 23)	0(0 to 0)	0.001(0.001 to 0.002)	60(25.3 to 107)	10(-13 to 37.6)	0.272(-1.028 to 1.59)	0.683
High-middle	354(218 to 479)	244(136 to 365)	0(0 to 0)	0.016(0.009 to 0.024)	-31(-52.6 to -5.4)	-53.9(-68.3 to -37.3)	-2.847(-3.837 to -1.846)	<0.001
Middle	3592(2636 to 4418)	1904(1134 to 2795)	0(0 to 0)	0.075(0.044 to 0.111)	-47(-61.6 to -26.9)	-67.5(-76.5 to -55.6)	-3.586(-4.066 to -3.105)	<0.001
Low-middle	11414(8211 to 14550)	3817(2453 to 5399)	1(1 to 1)	0.217(0.139 to 0.305)	-66.6(-74.1 to -54.7)	-80.3(-84.5 to -73.7)	-5.184(-5.642 to -4.725)	<0.001
Low-middle	6660(4227 to 10637)	4196(2074 to 7177)	1(1 to 2)	0.415(0.22 to 0.711)	-37(-61.4 to -12.9)	-70.9(-79.9 to -61.4)	-3.983(-4.246 to -3.719)	<0.001
GBD regions：
Andean Latin America	17(13 to 20)	0(0 to 0)	0(0 to 0)	0(0 to 0)	-99.5(-99.8 to -99)	-99.7(-99.9 to -99.4)	-23.414(-26.232 to -20.489)	<0.001
Australasia	0(0 to 0)	0(0 to 0)	0(0 to 0)	0(0 to 0)	113.9(45.8 to 212.6)	37.6(-10.3 to 118.4)	4.825(0.596 to 9.231)	0.025
Caribbean	0(0 to 1)	1(0 to 1)	0(0 to 0)	0.001(0.001 to 0.002)	49.9(-5 to 164.6)	-24.9(-54.2 to 33)	-1.358(-2.726 to 0.028)	0.055
Central Asia	13(7 to 25)	9(6 to 14)	0(0 to 0)	0.01(0.006 to 0.015)	-31.6(-63.2 to 24.2)	-49.3(-71 to -14.5)	-3.277(-4.08 to -2.467)	<0.001
Central Europe	4(4 to 5)	0(0 to 0)	0(0 to 0)	0(0 to 0)	-96.4(-97.3 to -95.2)	-98.1(-98.5 to -97.5)	-13.81(-15.867 to -11.702)	<0.001
Central Latin America	65(60 to 71)	0(0 to 0)	0(0 to 0)	0(0 to 0)	-99.8(-99.9 to -99.8)	-99.9(-99.9 to -99.9)	-19.092(-19.871 to -18.305)	<0.001
Central Sub-Saharan Africa	17(3 to 51)	22(4 to 60)	0(0 to 0)	0.02(0.004 to 0.045)	30.4(-32.9 to 133.4)	-41.7(-62.3 to -6.9)	-1.858(-2.02 to -1.697)	<0.001
East Asia	1103(647 to 1526)	627(335 to 950)	0(0 to 0)	0.036(0.02 to 0.054)	-43.2(-61.5 to -18.5)	-63.3(-75.1 to -48.1)	-1.258(-4.149 to 1.721)	0.404
Eastern Europe	12(11 to 13)	5(4 to 7)	0(0 to 0)	0.002(0.002 to 0.002)	-56.1(-64.2 to -43.9)	-63.4(-69.6 to -54.4)	-2.687(-3.713 to -1.65)	<0.001
Eastern Sub-Saharan Africa	2478(1162 to 5344)	1916(740 to 4224)	1(1 to 3)	0.496(0.197 to 1.132)	-22.7(-59.2 to 30.1)	-65.2(-79.1 to -43.6)	-3.476(-3.588 to -3.365)	<0.001
High-income Asia Pacific	1(1 to 1)	0(0 to 0)	0(0 to 0)	0(0 to 0)	-62.7(-71.3 to -55.7)	-92.3(-93.1 to -91.3)	-7.451(-9.025 to -5.851)	<0.001
High-income North America	2(2 to 2)	7(6 to 7)	0(0 to 0)	0.002(0.002 to 0.002)	300.7(255.4 to 343.7)	181.4(151.1 to 212.7)	3.144(1.721 to 4.588)	<0.001
North Africa and Middle East	94(48 to 140)	15(7 to 23)	0.028(0.015 to 0.039)	0.003(0.001 to 0.004)	-83.7(-89.6 to -72.7)	-90(-93.3 to -84.8)	-6.884(-7.508 to -6.255)	<0.001
Oceania	1(0 to 2)	2(0 to 4)	0(0 to 0)	0.028(0.008 to 0.084)	126.6(17 to 333.3)	-28.1(-62.6 to 35.5)	-1.037(-1.086 to -0.989)	<0.001
South Asia	15417(11334 to 19205)	5189(3452 to 7083)	2(1 to 2)	0.305(0.203 to 0.417)	-66.3(-73.8 to -55.5)	-80.8(-84.8 to -75)	-5.449(-5.75 to -5.148)	<0.001
Southeast Asia	1469(1095 to 1968)	663(393 to 972)	0(0 to 0)	0.098(0.058 to 0.147)	-54.9(-70.7 to -34.2)	-70.1(-79.4 to -58.3)	-4.221(-4.533 to -3.908)	<0.001
Southern Latin America	0(0 to 0)	0(0 to 0)	0(0 to 0)	0(0 to 0)	71.4(35.4 to 114.9)	-9.2(-27.6 to 12.6)	-1.301(-3.055 to 0.484)	0.146
Southern Sub-Saharan Africa	29(16 to 44)	29(17 to 47)	0(0 to 0)	0.038(0.022 to 0.059)	2(-34.7 to 65.9)	-31.2(-55.6 to 10.7)	-1.246(-1.63 to -0.861)	<0.001
Tropical Latin America	78(55 to 105)	0(0 to 0)	0(0 to 0)	0(0 to 0)	-99.5(-99.6 to -99.3)	-99.6(-99.7 to -99.5)	-16.788(-18.938 to -14.58)	<0.001
Western Europe	1(0 to 1)	2(2 to 2)	0(0 to 0)	0(0 to 0)	280.4(224.8 to 348.7)	101.2(79.3 to 126.6)	2.414(1.517 to 3.318)	<0.001
Western Sub-Saharan Africa	1235(567 to 2162)	1693(674 to 2705)	1(0 to 1)	0.333(0.136 to 0.526)	37.2(-26.1 to 121)	-45.3(-66.6 to -16.8)	-1.847(-1.964 to -1.731)	<0.001

Fig. 2.

Joinpoint analysis of the trends of incidence, mortality, and DALYs of rabies from 1990 to 2021. (A) AAPC and APC of incidence; (B) AAPC and APC of mortality; (C) AAPC and APC of DALYs. DALYs = disability-adjusted life years; AAPC = average annual percentage change; APC = annual percentage change

Global trends by sex in rabies from 1990 to 2021

From 1990 to 2021, ASRs for both sexes declined. Although both sexes experienced similar downward trends, men consistently had higher rates across all categories. In absolute numbers, incidence and mortality significantly decreased over time. Sex-specific analysis of rabies incidence revealed that ASRs markedly decreased, with the most significant reductions occurring between 2007 and 2010 for both men (APC: −7.72%) and women (APC: −8.85%). Male incidence rate declined faster (AAPC: −3.638%, P < 0.001) than females (AAPC: −4.21%, P < 0.001) (Fig. 2A; Table 1). Mortality rates also decreased, particularly for men between 2006 and 2013 (APC: −6.35%) and women from 2006 to 2012 (APC: −7.27%). Across both incidence and mortality, ASRs were consistently higher in men than in women. However, female mortality declined more rapidly (AAPC: −4.14%, P < 0.001) than males (AAPC: −3.55%, P < 0.001) (Fig. 2B and Table S1). In terms of ASDR, both sexes showed clear trends. DALY trends substantially reduced in men between 2006 and 2013 and women from 2006 to 2012, with APCs of − 6.19% and − 7.35%, respectively. The overall decline in DALYs was reflected in AAPCs of − 3.49% for men and − 4.19% for women (Fig. 2C and Table S2).

Pattern and trends in rabies of 5 SDI quantiles and 21 GBD regions from 1990 to 2021.

Initially, we detected the burden and trends of five SDI quantiles. Data showed that low SDI regions had the most declining trends. In low SDI, the ASIR, ASMR, and ASDR were observed from 1990 at 1.412 (95% UI: 0.897–2.305), 1.427 (95% UI: 0.9–2.34), and 76.193 (95% UI: 48.327–122.197), respectively, to 2021 at 0.411 (95% UI: 0.217–0.708), 0.415 (95% UI: 0.22–0.711), and 21.906 (95% UI: 10.818–37.738), respectively. With an AAPC of − 3.983% (95% CI: −4.246%–−3.719%) for ASIR, − 3.929% (95% CI: −4.181% to − 3.676%) for ASMR, and − 3.97% (95% CI: −4.17%–−3.77%) for ASDR, respectively (Figure S2 and Table 1, S1, S2).

From 1990 to 2021, rabies incidence varied significantly across 21 regions. In 2021, South Asia recorded the highest number of cases at 5188.671 (95% UI: 3452.192–7083.061). Andean Latin America and Australasia had the lowest ASIR. ASIR significantly declined in Central Latin America, with a 99.9% relative reduction and an AAPC of − 19.092% (95% CI: −19.871%–−18.305%) (Figure S3, S4 and Table 1, S1, S2). Although ASIR statistically increased in high-income regions, such as North America, Western Europe, and Australia, this is of little practical significance. In terms of mortality, South Asia had the highest incidence in 2021 at 5139.399 (95% UI: 3417.339–7013.769), with an ASIR of − 66.3 (95% UI: −73.8–−55.6) per 100,000 cases and an AAPC of − 5.416% (95% CI: −5.756%–−5.075%, P < 0.001) (Figure S3, S4 and Table 1, S1, S2). Regarding DALYs, South Asia and Eastern Sub-Saharan Africa had the highest numbers at 257,449.304 (95% UI: 166,294.779–365,123.332) and 124,148.263 (95% UI: 46,424.88–272,056.142), respectively. The highest ASDRs were 26.671 (95% UI: 10.273–59.735) and 19.752 (95% UI: 7.864–31.374) in Eastern and Western Sub-Saharan Africa, respectively. Notably, ASDR declined most significantly in South Asia from 79.862 (95% UI: 59.158–99.394) in 1990 to 14.188 (95% UI: 9.128–20.181) in 2021, with an AAPC of − 5.618% (95% CI: −5.884% to − 5.351%, P < 0.001) (Figure S3, S4 and Table 1, S1, S2).

National trends in rabies from 1990 to 2021

From 1990 to 2021, rabies numbers varied significantly across 204 countries and territories. In terms of incidence, India and Ethiopia had the greatest burden in 1990, with 12,701 (95% UI: 9,400–15,819) and 1769 (95% UI: 534–4353) cases, respectively. By 2021, these countries still had the highest incidences, with India at 4061 (95% UI: 2552–5721) and Ethiopia at 1050 (95% UI: 316–2821), reflecting decreases of 68% and 40.6%, respectively. In 1990 and 2021, Nepal had the highest ASIR at 6.239 (95% UI: 3.014–10.708) and 1.711 (95% UI: 0.922–2.647), respectively, with an AAPC of − 4.339% (95% CI: −4.485% to − 4.192%, P < 0.001). Regarding mortality, India and Ethiopia also had the highest numbers in 1990, with 12,567 (95% UI: 9298–15,681) and 1749 (95% UI: 531 − 4,308) mortalities, respectively. In 2021, India and Ethiopia recorded 4023 (95% UI: 2,530 − 5,677) and 1,043 mortalities (95% UI: 313 − 2,905), marking reductions of 68% and 40.4%, respectively. Additionally, Nepal had the highest ASMR in 1990 and 2021 at 6.184 (95% UI: 2.96–10.525) and 1.694 (95% UI: 0.91–2.62), respectively, with an AAPC of − 4.284% (95% CI: −4.474% to − 4.093%, P < 0.001). In terms of DALYs, India and Ethiopia were the most affected in 1990, with 760,115 (95% UI: 566,591–973,214) and 117,132 (95% UI: 35,428–279,678) DALYs, respectively. By 2021, these figures had decreased to 195,116 (95% UI: 118,441–280,802) in India and 68,521 (95% UI: 20,502–183,503) in Ethiopia, with reductions of 74.3% and 71.8%. Additionally, Nepal had the highest ASDR in 1990 and 2021 at 313.289 (95% UI: 152.12–527.491) and 81.658 (95% UI: 45.498–129.558ss), respectively, with an AAPC of − 4.527% (95% CI: −4.694% to − 4.359%, P < 0.001) (Fig. 3, S5 and Table S3, S4, S5).

Fig. 8.

Frontier analysis, represented by the solid black lines, explores the relationship between SDI and ASR for incidence, mortality, and DALYs in the context of rabies. (A, B) Frontiers analysis with ASIR; (C, D) Frontiers analysis with ASMR; (E, F) Frontiers analysis with ASDR. SDI sociodemographic index; DALY disability-adjusted life years; ASR age-standardised rate; ASIR age-standardised incidence rate; ASMR age-standardised mortality rate; ASDR age-standardised DALY rate

Global trends by age in rabies from 1990 to 2021

The incidence rates and numbers increase in younger age groups, with a significant peak in the 5–9-year-old bracket, where males consistently outnumber females in 1990 (Fig. 4A). The mortality rates followed a similar pattern, also peaking at ages 5–9 years, with males showing higher rates than females in 1990 (Fig. 4B). DALYs are the highest in the 5–9-year-old age group for both sexes, with males having a slightly higher rate in 1990 (Fig. 4C). These patterns persisted in 2021, wherein males continued to bear a greater burden of rabies across incidence, mortality, and DALYs (Fig. 4D, E, F).

Fig. 4.

The time trends of rabies burden from 1990 to 2021 by 20 age groups every 5 years worldwide

Correlations of ASR with SDI

Investigating rabies metrics across 5 SDI quantiles, 21 regions, and 204 countries revealed a subtle correlation with SDI. In 1990, ASRs for incidence, mortality, and DALYs showed a slight but statistically significant negative correlation with SDI (R = − 0.398, P < 0.001; R = − 0.398, P < 0.001; R = − 0.415, P < 0.001). By 2021, these correlations remained slightly negative, with incidence, mortality, and DALYs showing similar patterns (R = − 0.576, P < 0.001; R = − 0.576, P < 0.001; R = − 0.597, P < 0.001), (Fig. 5). Across the 21 GBD regions from 1990 to 2021, incidence, mortality, and DALYs ASRs also displayed a slight negative correlation with SDI, with statistical significance (R = − 0.618, P < 0.001; R = − 0.62, P < 0.001; R = − 0.627, P < 0.001) (Figure S6). A broader analysis across countries and territories confirmed these trends, showing negative correlations between SDI and incidence, mortality, and DALYs ASRs (R = − 0.58, P < 0.001; R = − 0.58, P < 0.001; R = − 0.6, P < 0.001), (Figure S7).

Fig. 5.

Pearson's correlation analysis between the SDI and ASR of incidence, mortality, and DALYs for rabies across 5 SDI quantiles, 1990 vs. 2021. (A) Incidence in 1990; (B) Mortality in 1990; (C) DALYs in 1990; (D) Incidence in 2021; (E) Mortality in 2021; (F) DALYs in 2021. SDI = sociodemographic index; ASR = age-standardised rate; DALYs = disability-adjusted life years

Health inequality analysis

The concentration index for rabies indicated an uneven burden, whereas the slope index suggested a slight decrease in inequality over time. The SII showed a narrowing of the incidence rate gap, decreasing from − 0.385 (95% CI: −0.427–−0.344) in 1990–−0.175 (95% CI: −0.2–−0.15) in 2021. The concentration index was − 0.585 (95% CI: −0.692–−0.478) in 1990 and − 0.519 (95% CI: −0.612–−0.427) in 2021, with no significant changes observed (Fig. 6A, B and Table S6). Similarly, the mortality rate gap decreased from − 0.38 (95% CI: −0.422–−0.339) in 1990–−0.173 (95% CI: −0.199–−0.148) in 2021, whereas the concentration index dropped from − 0.585 (95% CI: −0.692–−0.478) in 1990–−0.519 (95% CI: −0.612–−0.427) in 2021, again with no significant changes noted (Fig. 6C, D and Table S6). The DALY rate gap also reduced from − 26.726 (95% CI: −29.73–−23.721) in 1990–−10.226 (95% CI: −11.715–−8.737) in 2021. The concentration index slightly declined from − 0.588 (95% CI: −0.694–−0.482) in 1990–−0.565 (95% CI: −0.663–−0.467) in 2021, with no significant changes observed (Fig. 6E, F and Table S6). Additional details on health inequalities in SDI and GBD regions can be found in Table S6.

Fig. 6.

Health inequality regression and concentration curves for the incidence, mortality, and DALYs, 1990 vs. 2021. (A) SII of incidence; (B) CI of incidence; (C) SII of mortality; (D) CI of mortality; (E) SII of DALYs; (F) CI of DALYs. DALYs = disability-adjusted life years; SII = slope inequality index; CI = concentration index

Trends of rabies from 1990 to 2040

From 1990 to 2040, data on rabies shows clear trends in incidence, mortality and DALYs. The total incidence numbers for both sexes have steadily declined, with consistent decreases observed in both males and females. The ASR of incidence for both sexes has continuously decreased since 1990 (Fig. 7A, B). Mortality numbers also show a significant decline for both genders combined. The ASR of mortality for both sexes follows a similar downward trend (Fig. 7C, D). The number and ASR of DALYs from 1990 consistently declined in both sexes, with this trend expected to continue until 2040. Males reflect this decline, whereas females consistently show a slightly lower ASR (Fig. 7E, F). Since 1990, males have consistently had higher numbers and ASR than females, which is expected to continue from 2022 to 2040.

Fig. 7.

Projected numbers and ASR of incidence, mortality, and DALYs for rabies by sex (both, male and female) from 1990 to 2040 based on the BAPC model. (A, B) Number and ASR of incidence; (C, D) Number and ASR of mortality; (E, F) Number and ASR of DALYs. ASR = age-standardised rate; DALYs = disability-adjusted life years; BAPC = Bayesian age-period-cohort

Frontiers analysis

In a comprehensive frontier analysis of rabies incidence and mortality across 204 countries and territories from 1990 to 2021, distinct trends were observed with the SDI and ASRs. ASRs declined as SDI values increased from 0.0 to 1.0, marked by a shift from lighter to darker density shades, reflecting a general reduction in incidence over time. Similarly, mortality rates and DALYs due to rabies decreased with increasing SDI, indicating that the burden of rabies diminishes as countries develop (Fig. 8A, C, E and Table S7). The 2021 frontier analysis highlighted notable differences among countries. Nepal, Ethiopia, and Malawi had significantly higher incidence rates, placing them far from the frontier, whereas Afghanistan, Yemen, and Haiti were closer, indicating that they achieved better outcomes relative to their SDI. In terms of mortality, Nepal, Ethiopia, and Malawi again showed considerable gaps from the frontier. Interestingly, high SDI countries, such as the United Kingdom and the United States, exhibited larger deviations from optimal outcomes than expected for their developmental level. For DALYs, Nepal and Ethiopia showed rates closer to the aspirational benchmark set by the frontier (Fig. 8B, D, F and Table S7).

Rabies in China

By contrast, rabies incidence, mortality, and DALYs significantly peaked in the 5 − 9 and 50–69-year-old groups in 2021, with males consistently showing higher numbers than females (Figure S8). The incidence and mortality rates also increased overall across all age groups. DALYs were highest in the 5–9-year-old age group for both sexes, with males slightly surpassing females in 2021. From 1990 to 2021, China experienced similar patterns in incidence, mortality, and DALYs, with peaks around 2005 (Figure S9). The AAPC for incidence, mortality, and DALYs were − 3.481 (95% CI: −4.802–−2.141), − 3.787 (95% CI: −4.648–−2.918), and − 4.423 (95% CI: −5.312–−3.527), respectively. Throughout this period, males consistently had higher numbers and ASRs compared with females (Figure S10 and Table S8, S9, S10).

Discussion

Rabies is a globally widespread infectious disease, which is primarily transmitted by dogs, and is closely linked to the level of economic development. Generally, the more economically developed a region is, the lower the incidence and prevalence of rabies. Few zoonotic diseases incite as much fear and anxiety as rabies. Effective therapeutic measures remain unavailable based on current reports on global advances in rabies postexposure treatment. Therefore, the focus on rabies must be on prevention and control. The global incidence of rabies is generally declining based on surveillance and prevention measures by the WHO and the Centers for Disease Control across various countries, as well as campaigns for oral rabies vaccination [32] and postexposure prophylaxis (PEP) for humans [33]. Data from the 2021 GBD Study demonstrated a decreasing trend in the rabies burden from 1990 to 2021. Compared with the previously rabies GBD analysis [16], we introduced health inequality and frontiers analysis to explore the deep burden status or rabies. We observed that the burden is heaviest in countries with low SDI levels, with incidence rates significantly higher in low SDI regions. The incidence gradually decreases as the SDI level increases. In low SDI regions, the incidence rate among males is usually higher than that of females, particularly in sub-Saharan Africa and South Asia. Additionally, the incidence rates among the 5–9- and 9–14-year-old age groups are higher than in other age groups, consistent with the 2019 data. Compared with 2019, the incidence rate among middle-aged individuals has decreased possibly due to improved prevention and awareness efforts regarding rabies.

For the European Union (EU), according to the standards of the World Organization for Animal Health (OIE), 12 European countries declared themselves rabies-free [34]. In 2016, 3,982 rabies cases were reported in the European Rabies Surveillance Database, indicating that rabies incidence decreased by 4.3 times over the past 38 years. The United States has also targeted the variant [35]. Consequently, for global rabies control, the focus must be on low SDI regions. The EU has achieved significant success in eradicating rabies by combating rabies in wildlife through oral rabies vaccination [36], coupled with financing within EU member states and bilateral agreements with neighboring countries. Beyond political boundaries, in 1977, the WHO established the European Rabies Bulletin (www.who-rabies-bulletin.org) [37], which became the cornerstone of the European rabies strategic plan and epidemiological assessments. The EU guidelines recommend a comprehensive monitoring approach to rabies, including areas where vaccination needs to be repeated, timing of vaccination campaigns, bait distribution methods and densities, duration of vaccination campaigns, and monitoring and supervision. Due to these measures crossing political borders, significant achievements have been made, particularly in establishing permanent vaccination zones in non-EU neighboring countries. Current data showed that low SDI regions, such as sub-Saharan Africa and South Asia, had the highest incidence rates globally, particularly among the male population. South and Southeast Asia also had high incidence rates, with gender differences remaining, with males generally having higher DALY rates than females, possibly related to higher outdoor activity levels among males. Due to economic underdevelopment, insufficient government investment in rabies control, and lack of cross-political regional alliances in low SDI regions, widespread medical knowledge on postexposure prevention or insufficient immunoglobulin availability is lacking, leading to the current situation. Postexposure treatment management should be strengthened while ensuring the efficacy of cell culture vaccines, particularly adhering to WHO guidelines for a complete postexposure treatment protocol when thoroughly treating wounds. Human or equine rabies immunoglobulin (HRIG, ERIG) must be used alongside rabies vaccines in severe exposure situations (WHO Geneva, WHO Expert Committee on Rabies. WHO Technical Report Series 824). Globally, the supply of these immunoglobulins is lacking currently. For example, India produces 120 L of ERIG locally annually and imports an additional 50–100 L, but it still requires 1,500 L annually to treat these severe cases [38]. Therefore, from a global perspective, humanitarian efforts should be fully mobilized to aid low SDI regions, including financial and medical assistance. Regional economic financing and international charitable financial support should be included for financial assistance. Moreover, medical assistance should include aiding these regions with annual or multiyear oral vaccination programs, compiling detailed rabies epidemiological information, and assisting high incidence regions, such as sub-Saharan Africa, South Asia, and Southeast Asia in building strong rabies prevention and control partnerships across political borders, with permanent vaccination zones established in neighboring countries. The COVID-19 pandemic has negatively impacted rabies post-exposure prophylaxis services in Asia, including service disruptions and supply issues with vaccines and immunoglobulins. It is recommended that PEP be classified as an emergency medical service in the future and that mass dog vaccination be accelerated to prevent the disease at its source [12, 39].

Globally, the incidence, mortality, and DALY rates have been generally decreasing across various regions, particularly in Southeast Asia, South Asia, and sub-Saharan Africa. Compared with other regions, the burden in Eastern and Western sub-Saharan Africa remains significantly higher, although it is gradually decreasing. North America, East Asia, and Eastern Europe have lighter burdens and show a significant downward trend. Over time, the global public health burden of rabies has been steadily decreasing, particularly in high SDI and some middle-income regions. However, rabies burden remains high in low and lower-middle SDI regions, particularly in sub-Saharan Africa and South Asia, indicating the effectiveness of global health interventions and emphasizing the importance of strengthening prevention and control efforts in high-burden areas. Nonetheless, high SDI regions should be vigilant against cross-species rabies transmission. Although many regions globally have decreased incidence, mortality, and DALY rates of rabies, North America, South America (e.g., Argentina, Brazil), and Australia showed increased incidence rates. Rabies prevention and control is a long-term battle. Although dogs are the primary hosts, the disease can spread to other animals, making them the main sources of infection in certain areas, such as the red fox in Croatia [40], bats in Brazil [41], and raccoon dogs and foxes in the EU, with badgers in southeastern China and raccoon dogs and foxes in the north now becoming major local sources of infection [42]. In the first half of the 20th century, rabies in foxes emerged in Europe, which may have originated from interspecies transmission from domestic dogs to other species at an unknown location in the east [43]. Subsequently, the disease rapidly spread across the continent at an estimated speed of approximately 60 km annually [44]. Initially, it was an epidemic confined to unaffected fox populations that soon became endemic. The rabies virus variants were preserved within fox populations and frequently transmitted to other wildlife, domestic animals, and even humans. After the European Union developed and supported oral rabies vaccination for 10 years, the successful implementation of oral rabies vaccination campaigns for foxes and raccoon dogs provided a blueprint for eliminating rabies transmission in wildlife. Therefore, rabies prevention and control efforts must remain robust, regardless of the SDI.

In the 2021 analysis of global rabies, ASIR, ASMR, ASDR, and AAPC of these indicators across regions, the highest incidence regions were primarily concentrated in Western and Eastern sub-Saharan Africa, South Asia (e.g., India), and Southeast Asia. The incidence per 100,000 people reached or exceeded 1.6 in some sub-Saharan African countries and India. The geographical distribution of mortality mirrored that of the incidence, which was still mainly concentrated in sub-Saharan Africa and South Asia. The distribution of DALY rates indicates that the disease burden is most significant in sub-Saharan Africa, West Africa, East Africa, and South Asia, with DALY rates reaching or exceeding 80, reflecting the significant impact of rabies on public health. China should be vigilant against cross-border, cross-species rabies transmission in India, Nepal, Pakistan, Laos, and Vietnam, which geographically border China. Permanent vaccination zones should be established, border surveillance strengthened, foreign species controlled, and regular sampling of susceptible wild mammals conducted. Apart from the natural migration of infected animals, the greatest threat to rabies-free countries is the risk posed by companion animals entering with the disease [32]. Noncommercial pets entering the country must be vaccinated against rabies and undergo serological testing, depending on the status of origin country of origin. In most cases, these infected animals are unvaccinated puppies or young dogs illegally transported from rabies-endemic areas through illegal channels [45]. Although imported rabid animals imported into the country have not yet resulted in any human rabies cases, their presence poses a serious potential consequence. Therefore, traveler awareness should be raised, customs inspection vigilance enhanced, and thorough rabies surveillance conducted on any companion animals exhibiting clinical signs that may indicate rabies. Overall, the progress and challenges in rabies prevention and control in specific regions highlight the necessity of continuing to strengthen global rabies prevention and control measures.

For instance, rabies has begun to circulate independently among wild animals in some areas, such as ferret badgers, making rabies control more challenging. In 2007, the number of human rabies mortalities peaked at 3,300, the reduction in human rabies mortalities is primarily due to widespread PEP and increased public awareness [46]. Approximately 40 million people are bitten by dogs each year in China. However, medical professionals in China rarely conduct rabies risk assessments. Although approximately 40 million people are bitten by dogs annually, medical professionals often do not conduct detailed rabies risk assessments, resulting in a large number of suspected cases receiving PEP. Consequently, approximately 12–15 million doses of human rabies vaccine are administered annually to individuals bitten by suspected or unknown rabid animals [47, 48].

Therefore, rabies control in China currently relies primarily on PEP rather than source control, a costly approach that is limited in its effectiveness at preventing rabies transmission from dogs to humans and other susceptible animals. Furthermore, these regulations are not effectively enforced despite implementing dog registration and rabies vaccination systems in China. The vast number of dogs, uneven distribution, and varying coverage of dog vaccination all exacerbate the difficulties in rabies control. Moreover, the Chinese government mistakenly labeled the decrease in human mortality as “progress,” leading to a subsequent relaxation of control measures [47]. Since 1949, several large-scale rabies outbreaks in China’s history have shown that dog-mediated rabies is the main source of infection for humans and other animals. Due to the absence of public education, strict management, and mandatory vaccination, canine rabies has spread to the yellow-throated marten (Melogale moschata, FBs) in southern China, where the virus is circulating independently within this animal group [49, 50]. Finally, unregistered and stray dogs are difficult to capture and vaccinate with inactivated vaccines. In China, oral vaccines for free-roaming dogs and wild animals are still in the laboratory research stage, which was hindered by technical and official reasons. Therefore, immediate action is necessary for China to eliminate dog-mediated human rabies by 2030 and prevent the increasingly complex transmission dynamics among wildlife.

Conclusions

The global rabies burden is decreasing annually, with ASIR, ASMR, and ASDR in many regions, particularly in sub-Saharan Africa, East Asia, and Southeast Asia, showing a downward trend. Some high-income regions and Andean Latin American regions show a slight upward trend in ASIR and ASMR, which may be related to vaccination rates, public health measures, and disease management in different regions. Rabies prevention and control are of global importance, particularly in countries with low and lower-middle SDI levels. Interventions should focus on sub-Saharan Africa, East Asia, and Southeast Asia. In response to the WHO’s call to eliminate dog-transmitted rabies by 2030, countries must rise to the challenge of firm political commitment and feasible planning and must act immediately to prevent rabies transmission dynamics from becoming increasingly complex due to cross-species transmission. With the world’s largest population, China did a profound contribution in reducing the rabies incidence and mortalities which can be an exemplary model for the rest low SDI quintiles.

Electronic supplementary material

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Abbreviations

GBD

Global Burden of Disease

AAPC

Average annual percentage change

DALYs

Disability-adjusted life years

ASR

Age-standardised rate

ASIR

Age-standardised incidence rate

ASMR

Age-standardised mortality rate

ASDR

Age-standardised DALYs rate

ICD

International Classification of Diseases

AAPC

Average annual percent change

JPR

Joinpoint regression

BAPC

Bayesian age-period-cohort

SII

Slope inequality index

UI

Uncertainty interval

CI

Confidence interval

SDI

Sociodemographic index

WHO

World Health Organization

INLA

Integrated Nested Laplace Approximation

Author contributions

Qingsong Chen and Sizhe Huang: Conceptualization, Methodology, Writing – original draft, Writing – review & editing, Formal analysis, Validation, Visualization. Li Shi and Ping Zhang: Data curation, Visualization. Fabao Yang: Data curation. Dekun Ming: Supervision. Jinchuan Zhao: Supervision and Writing – review & editing.

Funding

Not applicable.

Data availability

The datasets generated during the current study are available in the Global Health Data Exchange query tool (https://vizhub.healthdata.org/gbd-results/).

Declarations

Ethics approval and consent to participate

No ethical approval was required for this study.

Consent for publication

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.