Global patterns and trends of carbon monoxide poisoning: A comprehensive spatiotemporal analysis using joinpoint regression and ARIMA modeling, 1990–2021

Weiguang Wang; Yongai Ling; Xianwei Xiong; Jiajie Zhou

doi:10.1371/journal.pone.0330778

. 2025 Aug 22;20(8):e0330778. doi: 10.1371/journal.pone.0330778

Global patterns and trends of carbon monoxide poisoning: A comprehensive spatiotemporal analysis using joinpoint regression and ARIMA modeling, 1990–2021

Weiguang Wang ^1,^*,^‡, Yongai Ling ¹, Xianwei Xiong ¹, Jiajie Zhou ²

Editor: Antonio Peña-Fernández³

PMCID: PMC12373207 PMID: 40844973

Abstract

Background

Carbon monoxide (CO) poisoning causes approximately 41,000 deaths annually worldwide despite being preventable. Previous studies focused primarily on mortality alone, lacked systematic socio-demographic analysis, and provided no predictive models. This study comprehensively analyzes global CO poisoning patterns using spatiotemporal methods to inform evidence-based prevention strategies.

Methods

We analyzed Global Burden of Disease Study 2021 data from 204 countries (1990–2021) for age-standardized incidence, mortality, and disability-adjusted life years (DALYs). Joinpoint regression identified temporal trends with statistical precision, spatial statistics quantified geographic clustering, and ARIMA modeling projected trends through 2050. We examined associations with socio-demographic index (SDI) across regions and countries.

Results

Global age-standardized incidence rates decreased significantly by 35.1% from 12.13 (95% UI: 8.30–17.00) to 7.87 (95% UI: 5.54–10.81) per 100,000 population (annual percentage change: −1.16%, 95% UI: −1.35% to −0.96%, p < 0.001). Mortality rates declined more dramatically by 53.9% from 0.76 (95% UI: 0.66–0.91) to 0.35 (95% UI: 0.24–0.40) per 100,000 (annual change: −2.79%, 95% UI: −3.14% to −2.44%, p < 0.001). DALY rates showed the steepest reduction of 59.5% from 37.59 (95% UI: 31.75–44.76) to 15.22 (95% UI: 10.67–17.57) per 100,000 (annual change: −3.18%, 95% UI: −3.51% to −2.84%, p < 0.001). Eastern Europe demonstrated the highest burden (37.98 per 100,000 in 2021). Males experienced significantly higher mortality than females (0.50 vs 0.20 per 100,000, p < 0.001). SDI analysis revealed an inverted U-shaped relationship (Spearman’s r = 0.76, p < 0.001), with peak burden at moderate development levels (SDI: 0.6–0.7).

Conclusions

These findings directly address previous research gaps by demonstrating: (1) faster mortality decline than incidence decline indicates improved global treatment capabilities; (2) the SDI-burden relationship identifies moderate-development countries as priority intervention targets; (3) significant male predominance (2.5-fold higher mortality) supports gender-specific prevention programs; and (4) persistent Eastern European hotspots require targeted infrastructure improvements. Predictive models forecast continued decline through 2050 and enable evidence-based healthcare planning. This comprehensive analysis provides the first multi-dimensional global assessment, offering crucial evidence for differentiated prevention strategies worldwide.

Introduction

Carbon monoxide (CO) poisoning is one of the most common causes of fatal poisoning worldwide [1]. The burden of CO poisoning remains significant despite its preventable nature. Previous research has estimated that approximately 970,000 poisoning incidents occur annually worldwide, resulting in around 41,000 deaths [2]. CO is a colorless, odorless, and tasteless toxic gas produced by the incomplete combustion of carbon-containing fuels. Common sources include faulty heating systems, poorly ventilated cooking appliances, vehicle exhaust, and the burning of charcoal or other fuels in enclosed spaces [3].

Carbon monoxide exposure occurs through multiple pathways. Common sources include faulty heating systems, poorly ventilated cooking appliances, vehicle exhaust in enclosed spaces, and fuel-burning equipment such as generators [4]. Motor vehicle exhaust represents a significant source of CO exposure, particularly from stationary vehicles in enclosed spaces [5]. The health impacts range from acute symptoms including headache, dizziness, and nausea at concentrations of 50–100 ppm to severe neurological damage, cardiac arrhythmias, and death at concentrations exceeding 400 ppm [6]. Long-term sequelae among survivors include persistent neurological deficits, cognitive impairment, and increased risk of delayed neurological sequelae affecting 10–32% of patients [6].

The health impacts of CO poisoning can be severe and far-reaching. Acute exposure can lead to symptoms ranging from mild (headache, dizziness, nausea) to severe (loss of consciousness, heart damage, and death) [7]. Long-term sequelae among survivors may include neurological deficits, cognitive impairment, and cardiovascular complications. The economic burden is also substantial, encompassing direct medical costs, lost productivity, and long-term care expenses [8].

Several studies [9–11] have attempted to characterize the burden of CO poisoning at various levels. Long [9] et al. examined global mortality trends from 1990–2017, while Cui [10] et al. focused specifically on China’s burden from 1990–2019. The Lancet Public Health [11] provided insights into mortality patterns from 2000–2021. However, existing research has several important limitations.

First, previous studies [9–11] primarily focused on mortality rates alone or were limited to specific regions like China. There is a lack of comprehensive analysis incorporating incidence, mortality, and disability-adjusted life years (DALYs) at the global level. This multi-dimensional understanding is crucial for fully grasping the public health impact of CO poisoning.

Second, although some studies [9–11] have examined regional variations in CO poisoning burden, they failed to systematically analyze the relationship between socio-demographic index (SDI) and CO poisoning burden at both regional and national levels. Understanding this relationship is crucial for policy-making and resource allocation, particularly in identifying vulnerable populations and regions.

Third, while existing studies [9–11] have described historical trends, there is no long-term prediction model for CO poisoning burden. Such predictions are essential for future healthcare planning and prevention strategies, especially given changing global patterns of energy use and climate.

Fourth, although gender disparities in CO poisoning have been noted in previous studies [9–11], systematic analysis of sex-specific patterns in incidence, mortality and DALYs across different regions and time periods is lacking. Understanding these patterns is vital for developing targeted prevention strategies.

Additionally, most existing studies [9–11] are descriptive in nature and do not provide in-depth analysis of geographical gradients or explore the complex factors contributing to regional variations in CO poisoning burden. Such detailed geographical analysis could reveal important patterns in disease burden distribution and help identify region-specific risk factors.

To address these significant gaps in knowledge, we conducted a comprehensive global analysis of CO poisoning burden using data from the Global Burden of Disease (GBD) Study 1990–2021. Our study aims were to: (1) quantify the global burden of CO poisoning across multiple dimensions including incidence, mortality, and disability-adjusted life years (DALYs); (2) analyze the relationship between socio-demographic development and CO poisoning burden at global, regional, and national levels; (3) develop predictive models estimating the future CO poisoning burden through 2050; (4) examine detailed geographical and sex-specific patterns in disease burden distribution; (5) explore the implications of these patterns for public health policy and prevention strategies.

This comprehensive analysis provides crucial insights for informing evidence-based policies and interventions to reduce CO poisoning burden worldwide. Understanding these patterns and trends is essential for developing targeted prevention strategies and allocating resources effectively to reduce the preventable burden of CO poisoning.

Methods

Study design

We conducted a comprehensive analysis of acute carbon monoxide poisoning using the Global Burden of Disease (GBD) 2021 database, accessed through the Global Health Data Exchange (GHDx) platform [12]. The analysis covered the period from 1990 to 2021, encompassing data from 204 countries and territories. Our research framework adhered to the GATHER guidelines for health estimates reporting [13]. The data were accessed for research purposes on March 15, 2021.

This study was conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The need for informed consent was waived by the ethics committee because the study involved the analysis of fully anonymized retrospective data from the Global Burden of Disease Study 2021. All data were accessed after complete anonymization, and no individual identifiers were included in the analysis. All analyses were conducted in compliance with ethical guidelines for human subjects research.

Analytical framework

The geographical distribution of disease burden was evaluated using spatial statistics, incorporating both Global Moran’s I for overall clustering assessment and LISA analysis for identifying regional patterns [14]. We examined the relationship between disease burden and development level by analyzing health metrics against the Socio-demographic Index (SDI), with nations grouped into SDI quintiles.

Temporal trend analysis employed joinpoint regression methodology, utilizing both APC and AAPC metrics [15]. The analysis parameters allowed for a maximum of three joinpoints, with optimal model selection guided by Monte Carlo permutation testing. Long-term projections extending to 2050 were generated using a combination of ARIMA modeling and exponential smoothing techniques [16], with model selection based on AIC values and validated through rolling-origin cross-validation. These three methods are complementary and form a comprehensive analytical framework: joinpoint regression describes historical trends, spatial statistics reveals geographic patterns, and ARIMA modeling predicts future trends. This multi-method integration provides a complete assessment of the global burden of CO poisoning. All methods were validated through appropriate statistical tests, model diagnostics, and uncertainty quantification. The combination approach enhances the robustness of our findings and provides multiple perspectives on the same epidemiological phenomenon.

Burden metrics

We assessed disease burden through multiple indicators, primarily focusing on DALYs (calculated as the sum of YLLs and YLDs), along with incidence, prevalence, and mortality rates [17]. To ensure comparability across regions and time periods, all rates were age-standardized using the WHO standard population. Statistical uncertainty was addressed through 95% uncertainty intervals, with significance determined at p < 0.05.

Computational tools

Analyses were performed using a combination of statistical software packages: R 4.1.0 and Stata 16 for primary analyses, the National Cancer Institute’s Joinpoint Regression Program (version 4.9.1.0) for trend assessment, and ArcGIS Pro/QGIS 3.16 for spatial visualization.

Results

1. Epidemiological patterns and trends of acute carbon monoxide poisoning, 1990–2021

1.1 Global burden and temporal trends (Table 1).

Table 1. Global age-standardized incidence rates of acute carbon monoxide poisoning (1990-2021).

Characteristics	Incidence (95% uncertainty interval)
	Number of cases, 1990	ASR per 100000 population, 1990	Number of cases, 2021	ASR per 100000 population, 2021	Estimated annual percentage change, 1990–2021
Location
Global	693139.82(469815.01,981111.48)	12.13(8.30,17.00)	294173.15(209197.11,395043.48)	7.87(5.54,10.81)	−1.16(−1.35,-0.96)
SEX
Male	328711.45(224639.10,458237.94)	11.35(7.88,15.56)	294173.15(209197.11,395043.48)	7.60(5.46,10.26)	−1.04(−1.24,-0.84)
Female	364428.36(242796.67,517300.42)	12.92(8.69,18.19)	8306466.88(211120.03,426664.43)	8.16(5.58,11.48)	−1.26(−1.44,-1.07)
SDI
High	198935.21(129323.21,286238.29)	24.77(16.00,35.74)	151650.80(102859.16,211801.98)	17.77(11.48,25.96)	−0.50(−0.81,-0.19)
High middle	256050.68(179270.77,349599.88)	23.58(16.66,31.97)	196799.02(143406.36,255270.12)	17.85(12.82,24.28)	−0.84(−1.08,-0.60)
Middle	154919.60(101287.58,225975.71)	7.86(5.21,11.28)	148982.45(104247.71,206861.25)	6.59(4.60,9.21)	−0.31(−0.52,-0.10)
Low middle	58389.08(34906.93,88761.71)	3.96(2.42,5.90)	63033.75(39297.60,94359.63)	3.08(1.96,4.56)	−0.75(−0.93,-0.57)
Low	23855.82(14849.28,35667.90)	3.39(2.13,4.96)	39546.60(25813.05,57782.10)	2.78(1.87,4.00)	−0.61(−0.73,-0.48)
GBD region
Andean Latin America	17726.94(12142.04,25222.30)	5.20(2.99,8.15)	17856.25(12318.94,24992.04)	5.24(3.14,8.21)	0.23(0.09,0.38)
Australasia	19023.75(10938.11,30400.34)	14.57(9.19,21.82)	18737.08(11288.82,29238.40)	12.53(8.10,18.50)	−0.46(−0.58,-0.35)
Caribbean	45513.59(30788.93,65582.50)	10.07(6.38,15.16)	22885.35(15479.23,32773.32)	9.95(6.27,14.98)	0.10(−0.10,0.30)
Central Asia	146853.21(98903.12,212419.73)	22.89(15.90,32.12)	156104.38(114589.18,204066.93)	18.63(12.78,26.62)	−0.53(−0.70,-0.36)
Central Europe	233.18(135.21,365.42)	39.11(26.39,56.82)	473.67(292.14,713.62)	27.93(17.88,41.60)	−0.88(−1.12,-0.65)
Central Latin America	71937.76(46324.29,103772.32)	13.51(7.64,21.48)	55007.05(37113.48,76629.75)	9.76(5.79,15.24)	−0.89(−1.18,-0.60)
Central sub Saharan Africa	120813.46(88810.99,155630.71)	2.72(1.77,3.90)	67288.99(51320.35,84904.71)	2.31(1.61,3.29)	−0.54(−0.61,-0.47)
East Asia	2812.58(1789.11,4158.10)	11.17(7.70,15.68)	3239.31(2150.70,4572.90)	12.87(9.26,17.06)	0.97(0.71,1.24)
Eastern Europe	50421.41(33402.82,72531.56)	55.71(41.19,72.97)	22839.71(15164.33,32314.86)	37.98(28.51,49.23)	−1.65(−2.08,-1.22)
Eastern sub Saharan Africa	12807.52(7926.84,19414.28)	3.59(2.36,5.24)	15865.56(10592.01,22946.20)	2.76(1.92,3.87)	−0.88(−0.98,-0.77)
High-income Asia Pacifc	65618.56(40399.00,96858.55)	32.77(21.77,46.85)	64048.97(42794.83,90451.93)	19.63(12.42,29.50)	−1.61(−1.75,-1.47)
High-income North America	3981.36(2506.79,6053.51)	24.71(15.13,37.26)	4327.88(2744.06,6476.59)	20.23(13.00,29.09)	0.64(−0.16,1.44)
North Africa and Middle East	2487.97(1394.06,3978.93)	6.82(4.46,9.79)	3473.55(2091.08,5451.20)	6.27(4.20,8.89)	−0.28(−0.45,-0.11)
Oceania	9773.97(3624.09,18548.81)	2.90(1.72,4.42)	5684.71(3070.07,9373.61)	2.98(1.85,4.43)	0.24(0.05,0.44)
South Asia	28028.39(15540.38,45387.22)	2.86(1.66,4.36)	23333.69(13951.02,36344.19)	1.98(1.18,3.01)	−1.16(−1.40,-0.92)
Southeast Asia	2092.18(1338.52,3038.87)	3.39(2.00,5.35)	3851.93(2531.49,5752.41)	2.84(1.71,4.45)	−0.41(−0.67,-0.15)
Southern Latin America	29249.23(18928.36,42828.76)	24.92(15.47,37.50)	40452.74(26969.25,57497.74)	26.73(17.66,38.98)	0.46(0.19,0.72)
Southern Sub-Saharan Africa	40203.90(22969.17,62557.45)	4.61(3.09,6.60)	37456.27(21965.29,57577.96)	3.04(2.13,4.28)	−1.41(−1.48,-1.34)
Tropical Latin America	9474.21(6130.21,14074.91)	5.60(2.21,10.38)	13963.65(9202.91,20591.85)	2.71(1.42,4.52)	−2.05(−2.24,-1.86)
Western Europe	10891.55(6953.62,16251.54)	22.04(13.87,32.09)	21212.82(13837.67,30711.96)	17.08(11.03,24.98)	−0.60(−0.73,-0.46)
Western Sub-Saharan Africa	3195.10(2105.60,4624.59)	3.89(2.49,5.73)	2536.50(1757.36,3581.84)	3.15(2.09,4.52)	−0.64(−0.83,-0.46)

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In 2021, there were 294,173.15 (95% UI: 209,197.11−395,043.48) cases of acute carbon monoxide poisoning globally, with an age-standardized incidence rate (ASR) of 7.87 (95% UI: 5.54–10.81) per 100,000 population. This represents a substantial reduction from 1990, when there were 693,139.82 (95% UI: 469,815.01−981,111.48) cases and an ASR of 12.13 (95% UI: 8.30–17.00) per 100,000 population. The estimated annual percentage change between 1990 and 2021 was −1.16% (95% UI: −1.35% to −0.96%).

Sex-specific patterns showed that in 1990, females had a higher ASR (12.92 per 100,000; 95% UI: 8.69–18.19) than males (11.35 per 100,000; 95% UI: 7.88–15.56). By 2021, both sexes showed decreased rates, with females at 8.16 (95% UI: 5.58–11.48) and males at 7.60 (95% UI: 5.46–10.26) per 100,000 population. The annual percentage change was −1.26% (95% UI: −1.44% to −1.07%) for females and −1.04% (95% UI: −1.24% to −0.84%) for males.

Across SDI quintiles, high-SDI regions recorded the highest ASR in 1990 at 24.77 (95% UI: 16.00–35.74) per 100,000, decreasing to 17.77 (95% UI: 11.48–25.96) in 2021. High-middle SDI regions showed similar patterns, with ASRs of 23.58 (95% UI: 16.66–31.97) in 1990 and 17.85 (95% UI: 12.82–24.28) in 2021. Low-SDI regions maintained the lowest rates throughout the study period, with ASRs of 3.39 (95% UI: 2.13–4.96) in 1990 and 2.78 (95% UI: 1.87–4.00) in 2021.

In the GBD regional analysis, Eastern Europe showed the highest ASR in 1990 (55.71 per 100,000; 95% UI: 41.19–72.97), followed by High-income Asia Pacific (32.77 per 100,000; 95% UI: 21.77–46.85). By 2021, Eastern Europe’s ASR had decreased to 37.98 (95% UI: 28.51–49.23). East Asia showed an increase in ASR from 11.17 (95% UI: 7.70–15.68) to 12.87 (95% UI: 9.26–17.06), with an annual percentage change of 0.97% (95% UI: 0.71–1.24%). Southern Latin America also demonstrated an increase, with an annual percentage change of 0.46% (95% UI: 0.19–0.72%).

1.2 Deaths and mortality trends (Table 2).

Table 2. Global age-standardized mortality rates of acute carbon monoxide poisoning (1990-2021).

Characteristics	Deaths (95% uncertainty interval)
	Number of cases, 1990	ASR per 100000 population, 1990	Number of cases, 2021	ASR per 100000 population, 2021	Estimated annual percentage change, 1990–2021
Location
Global	36816.05(31520.91,44285.07)	0.76(0.66,0.91)	28946.78(19894.89,33510.18)	0.35(0.24,0.40)	−2.79(−3.14,-2.44)
SEX
Male	25574.21(20701.72,32318.68)	1.07(0.88,1.39)	20168.71(14337.62,25421.30)	0.50(0.36,0.63)	−2.756(−3.12,-2.39)
Female	11241.85(7609.71,15551.99)	0.46(0.32,0.63)	8778.07(4290.75,10787.13)	0.20(0.10,0.25)	−2.771(−3.09,-2.46)
SDI
High	1054.73(439.33,1779.22)	0.42(0.39,0.44)	1165.51(580.18,1533.12)	0.22(0.20,0.23)	−1.85(−2.07,-1.62)
High middle	508.27(489.00,528.85)	1.79(1.66,2.05)	395.61(358.88,441.29)	0.76(0.59,0.86)	−3.37(−3.93,-2.80)
Middle	794.06(507.64,963.83)	0.73(0.54,1.03)	313.24(282.27,404.35)	0.40(0.21,0.49)	−1.75(−2.00,-1.50)
Low middle	1274.36(1162.78,1361.64)	0.20(0.11,0.27)	927.56(818.72,1070.26)	0.12(0.07,0.16)	−1.89(−2.03,-1.74)
Low	136.15(40.82,193.44)	0.29(0.16,0.45)	140.26(68.54,238.92)	0.18(0.12,0.32)	−1.62(−1.71,-1.54)
GBD region
Andean Latin America	11.13(5.36,16.71)	0.03(0.02,0.05)	45.58(30.48,57.32)	0.07(0.05,0.09)	2.42(1.83,3.02)
Australasia	23.82(22.60,24.97)	0.11(0.11,0.12)	28.17(26.67,29.72)	0.08(0.08,0.09)	−1.70(−2.48,-0.92)
Caribbean	73.63(53.89,104.69)	0.22(0.16,0.29)	44.33(29.46,59.88)	0.09(0.06,0.13)	−2.52(−2.96,-2.08)
Central Asia	1274.36(1162.78,1361.64)	2.06(1.90,2.19)	927.56(818.72,1070.26)	0.98(0.86,1.12)	−3.79(−4.50,-3.07)
Central Europe	2041.25(1912.23,2153.07)	1.58(1.48,1.67)	583.63(538.76,631.37)	0.35(0.33,0.38)	−5.15(−5.42,-4.89)
Central Latin America	508.27(489.00,528.85)	0.34(0.33,0.35)	395.61(358.88,441.29)	0.16(0.14,0.17)	−2.61(−2.82,-2.39)
Central sub Saharan Africa	68.41(34.12,166.40)	0.18(0.09,0.44)	77.66(15.49,386.59)	0.09(0.02,0.45)	−2.12(−2.47,-1.76)
East Asia	14111.63(10243.22,21401.62)	1.30(0.94,1.97)	13588.38(6818.19,17624.96)	0.79(0.40,1.01)	−1.36(−1.68,-1.04)
Eastern Europe	10975.80(10709.96,11176.15)	4.44(4.33,4.52)	5642.24(5227.16,6079.50)	2.10(1.95,2.25)	−3.42(−4.31,-2.53)
Eastern sub Saharan Africa	268.17(140.25,690.06)	0.21(0.10,0.52)	208.84(54.06,978.01)	0.08(0.02,0.37)	−3.06(−3.36,-2.76)
High-income Asia Pacifc	794.06(507.64,963.83)	0.44(0.27,0.53)	313.24(282.27,404.35)	0.12(0.11,0.16)	−3.49(−3.97,-3.02)
High-income North America	822.71(800.43,837.81)	0.27(0.26,0.28)	1303.77(1255.79,1345.75)	0.31(0.30,0.32)	1.16(0.88,1.45)
North Africa and Middle East	2471.39(1433.07,3282.09)	0.82(0.50,1.07)	2770.75(1413.49,3626.76)	0.48(0.25,0.62)	−1.63(−1.73,-1.53)
Oceania	14.76(5.98,24.62)	0.26(0.11,0.46)	24.81(10.87,44.74)	0.20(0.09,0.36)	−0.98(−1.03,-0.94)
South Asia	1054.73(439.33,1779.22)	0.11(0.05,0.17)	1165.51(580.18,1533.12)	0.07(0.03,0.09)	−1.49(−1.59,-1.38)
Southeast Asia	578.41(181.28,821.89)	0.15(0.04,0.21)	712.22(275.08,974.81)	0.10(0.04,0.14)	−1.25(−1.30,-1.21)
Southern Latin America	121.45(103.39,131.14)	0.25(0.21,0.27)	245.89(232.87,258.93)	0.33(0.31,0.35)	0.77(0.04,1.50)
Southern Sub-Saharan Africa	136.15(40.82,193.44)	0.25(0.08,0.36)	140.26(68.54,238.92)	0.17(0.08,0.29)	−1.37(−1.52,-1.22)
Tropical Latin America	81.19(77.22,85.26)	0.06(0.06,0.06)	68.41(65.13,71.53)	0.03(0.03,0.03)	−2.24(−2.66,-1.82)
Western Europe	1262.70(1210.56,1295.79)	0.28(0.27,0.29)	536.83(500.25,560.65)	0.09(0.08,0.09)	−3.59(−3.94,-3.24)
Western Sub-Saharan Africa	122.05(52.76,204.83)	0.12(0.05,0.19)	123.09(73.44,368.12)	0.05(0.03,0.14)	−2.93(−3.22,-2.65)

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Global deaths from acute carbon monoxide poisoning decreased from 36,816.05 (95% UI: 31,520.91–44,285.07) in 1990–28,946.78 (95% UI: 19,894.89–33,510.18) in 2021. The age-standardized death rate (ASR) showed a more pronounced decline, from 0.76 (95% UI: 0.66–0.91) to 0.35 (95% UI: 0.24–0.40) per 100,000 population, with an estimated annual percentage change of −2.79% (95% UI: −3.14% to −2.44%).

Sex-stratified analysis revealed consistently higher mortality rates among males. In 1990, the male ASR was 1.07 (95% UI: 0.88–1.39) compared to 0.46 (95% UI: 0.32–0.63) for females per 100,000 population. By 2021, these rates had decreased to 0.50 (95% UI: 0.36–0.63) for males and 0.20 (95% UI: 0.10–0.25) for females, with similar annual percentage changes of −2.756% (95% UI: −3.12% to −2.39%) and −2.771% (95% UI: −3.09% to −2.46%), respectively.

Among SDI quintiles, high-middle SDI regions recorded the highest ASR in 1990 at 1.79 (95% UI: 1.66–2.05) per 100,000, decreasing to 0.76 (95% UI: 0.59–0.86) in 2021. Low-middle SDI regions maintained the lowest rates, declining from 0.20 (95% UI: 0.11–0.27) to 0.12 (95% UI: 0.07–0.16) per 100,000 population.

Geographically, Eastern Europe showed the highest mortality burden, with an ASR of 4.44 (95% UI: 4.33–4.52) per 100,000 in 1990, decreasing to 2.10 (95% UI: 1.95–2.25) in 2021. Central Europe experienced the steepest decline with an annual percentage change of −5.15% (95% UI: −5.42% to −4.89%). Notably, some regions showed increasing trends, including High-income North America (1.16%; 95% UI: 0.88–1.45%) and Andean Latin America (2.42%; 95% UI: 1.83–3.02%). East Asia maintained a substantial burden throughout the study period, with death numbers of 14,111.63 (95% UI: 10,243.22−21,401.62) in 1990 and 13,588.38 (95% UI: 6,818.19−17,624.96) in 2021.

1.3 Disability-adjusted life years (Table 3).

Table 3. Global age-standardized DALY rates of acute carbon monoxide poisoning (1990-2021).

Characteristics	DALYs (95% uncertainty interval)
	Number of cases, 1990	ASR per 100000 population, 1990	Number of cases, 2021	ASR per 100000 population, 2021	Estimated annual percentage change, 1990–2021
Location
Global	1991539.89(1664186.66,2374749.90)	37.59(31.75,44.76)	1228861.20(867811.13,1414898.57)	15.22(10.67,17.57)	−3.18(−3.51,-2.84)
SEX
Male	1371568.09(1084724.59,1717161.87)	51.84(41.59,64.96)	869791.56(622356.12,1085567.94)	21.52(15.32,26.87)	−3.13(−3.49,-2.77)
Female	619971.79(404516.50,837833.47)	23.13(15.24,31.26)	359069.63(185060.10,427811.11)	8.94(4.58,10.63)	−3.23(−3.53,-2.93)
SDI
High	204572.05(189656.73,216175.29)	22.79(21.03,24.10)	131482.24(121542.74,141061.18)	11.40(10.56,12.19)	−1.89(−2.12,-1.67)
High middle	917444.00(842240.63,1063693.98)	87.55(80.24,100.93)	479786.22(383939.91,542794.21)	33.83(26.92,38.06)	−3.62(−4.17,-3.06)
Middle	670765.64(495400.21,912876.80)	37.82(27.78,51.51)	414933.91(228494.85,511805.42)	16.70(9.17,20.34)	−2.53(−2.77,-2.29)
Low middle	130396.47(63231.17,193448.73)	10.69(5.41,15.27)	120411.32(67754.07,164817.72)	6.23(3.53,8.53)	−2.02(−2.15,-1.89)
Low	66398.32(34227.76,110234.62)	13.07(7.31,20.32)	81550.42(53040.20,132928.44)	7.89(5.21,13.35)	−1.69(−1.74,-1.63)
GBD region
Andean Latin America	820630.90(598757.83,1217182.22)	2.17(1.32,3.02)	511718.87(265448.76,653682.47)	3.83(2.67,4.80)	1.91(1.35,2.48)
Australasia	5377.19(5078.92,5788.58)	7.30(6.85,7.86)	3630.56(3436.15,3861.47)	5.05(4.71,5.46)	−1.80(−2.49,-1.11)
Caribbean	44326.87(42618.63,46385.80)	13.24(9.70,19.61)	60909.71(58475.04,63353.25)	6.40(4.17,8.82)	−2.12(−2.53,-1.70)
Central Asia	96370.67(90201.29,102554.55)	104.85(95.85,112.26)	21108.45(19478.90,22867.45)	46.49(41.04,54.26)	−3.97(−4.66,-3.28)
Central Europe	70670.56(30531.07,124491.55)	78.78(73.81,84.02)	66611.15(36220.66,88601.96)	16.08(14.79,17.47)	−5.40(−5.67,-5.14)
Central Latin America	34257.43(32624.17,36216.62)	19.28(18.46,20.23)	20849.21(19029.68,23084.47)	8.14(7.40,9.05)	−2.76(−2.95,-2.57)
Central sub Saharan Africa	33379.17(11953.46,47448.27)	7.63(4.13,18.03)	37231.89(15737.43,51304.60)	3.83(0.98,17.87)	−2.29(−2.60,-1.97)
East Asia	46356.65(31026.47,55143.99)	67.98(49.48,100.37)	14237.66(12593.92,17902.02)	34.61(17.91,43.44)	−2.10(−2.42,-1.78)
Eastern Europe	71323.25(64693.73,77010.81)	212.93(207.51,217.50)	45707.49(40263.33,53471.48)	95.02(88.66,101.06)	−3.56(−4.44,-2.67)
Eastern sub Saharan Africa	158136.89(88173.65,218144.28)	8.65(4.65,21.42)	147819.73(77885.88,199152.04)	3.40(1.13,14.75)	−3.11(−3.42,-2.80)
High-income Asia Pacifc	497098.53(484659.98,507418.72)	26.55(17.34,31.73)	222147.26(206162.01,237843.44)	7.15(6.30,9.15)	−3.72(−4.14,-3.29)
High-income North America	922.24(359.49,1595.04)	15.23(14.65,15.93)	1547.51(698.44,2694.01)	16.20(15.58,16.84)	1.02(0.70,1.33)
North Africa and Middle East	4872.01(3490.01,7457.12)	43.61(25.48,57.75)	2887.44(1938.23,3912.98)	23.53(12.42,31.64)	−1.92(−2.04,-1.80)
Oceania	16798.08(9169.44,38581.06)	13.41(5.53,22.21)	11857.83(4001.58,51031.32)	10.56(4.68,18.57)	−0.77(−0.82,-0.72)
South Asia	6033.15(3261.37,9495.43)	6.04(2.71,10.04)	7194.91(4794.19,17292.55)	3.54(1.90,4.70)	−1.66(−1.81,-1.50)
Southeast Asia	7581.29(6452.38,8359.07)	7.37(2.62,10.42)	11986.36(11283.92,12755.88)	5.08(2.18,6.98)	−1.22(−1.27,-1.17)
Southern Latin America	4310.08(1893.94,10214.44)	15.18(12.93,16.74)	4247.92(1122.04,18970.74)	17.91(16.80,19.09)	0.42(−0.26,1.10)
Southern Sub-Saharan Africa	1520.86(1426.32,1636.44)	16.45(5.55,23.04)	1547.84(1438.41,1673.98)	11.24(5.62,18.63)	−1.34(−1.53,-1.14)
Tropical Latin America	9749.06(3217.44,13696.04)	3.51(3.32,3.76)	9405.91(4677.61,15655.28)	1.54(1.45,1.64)	−2.44(−2.80,-2.07)
Western Europe	60940.55(57943.42,64260.40)	15.45(14.70,16.26)	23645.84(21516.11,26366.24)	4.99(4.53,5.56)	−3.36(−3.67,-3.05)
Western Sub-Saharan Africa	884.46(521.45,1289.67)	4.60(2.36,7.34)	2567.65(1796.32,3211.73)	2.11(1.38,5.41)	−2.59(−2.79,-2.38)

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The global burden of acute carbon monoxide poisoning measured in disability-adjusted life years (DALYs) decreased substantially from 1,991,539.89 (95% UI: 1,664,186.66−2,374,749.90) in 1990–1,228,861.20 (95% UI: 867,811.13−1,414,898.57) in 2021. The age-standardized DALY rate showed a marked reduction from 37.59 (95% UI: 31.75–44.76) to 15.22 (95% UI: 10.67–17.57) per 100,000 population, with an estimated annual percentage change of −3.18% (95% UI: −3.51% to −2.84%).

The sex-specific burden demonstrated pronounced disparities. Males experienced higher DALY rates, with an ASR of 51.84 (95% UI: 41.59–64.96) per 100,000 in 1990, decreasing to 21.52 (95% UI: 15.32–26.87) in 2021. Female rates declined from 23.13 (95% UI: 15.24–31.26) to 8.94 (95% UI: 4.58–10.63) per 100,000, with annual percentage changes of −3.13% (95% UI: −3.49% to −2.77%) for males and −3.23% (95% UI: −3.53% to −2.93%) for females.

Across SDI quintiles, high-middle SDI regions showed the highest burden with an ASR of 87.55 (95% UI: 80.24–100.93) per 100,000 in 1990, declining to 33.83 (95% UI: 26.92–38.06) in 2021. Low-middle SDI regions maintained the lowest rates, decreasing from 10.69 (95% UI: 5.41–15.27) to 6.23 (95% UI: 3.53–8.53) per 100,000 population.

In the regional analysis, Eastern Europe recorded the highest ASR in 1990 at 212.93 (95% UI: 207.51–217.50) per 100,000, dropping to 95.02 (95% UI: 88.66–101.06) in 2021. Central Europe showed the steepest decline with an annual percentage change of −5.40% (95% UI: −5.67% to −5.14%). Conversely, several regions exhibited increasing trends, including Andean Latin America (1.91%; 95% UI: 1.35–2.48%) and High-income North America (1.02%; 95% UI: 0.70–1.33%). East Asia demonstrated a substantial reduction in ASR from 67.98 (95% UI: 49.48–100.37) to 34.61 (95% UI: 17.91–43.44) per 100,000 population.

Global geographic distribution

2.1 Geographic distribution of age-standardized incidence rates.

The age-standardized incidence rates (ASR) of acute carbon monoxide poisoning showed marked geographic variation across the global regions (Fig 1). The highest rates were observed in the Balkan Peninsula and Northern Europe, with ASRs ranging from 26.83 to 41.60 per 100,000 population. The second-highest burden was found in North America and parts of Northern Asia, where ASRs ranged from 17.66 to 26.83 per 100,000 population.

Fig 1 — Disease burden data from Global Burden of Disease Study 2021; Map data from Natural Earth (https://www.naturalearthdata.com/), public domain.

Australia and parts of Central America displayed moderate incidence rates, falling within the range of 9.19 to 14.80 per 100,000 population. The Persian Gulf region and parts of Central Asia showed rates between 4.30 and 7.26 per 100,000 population.

Lower incidence rates were predominantly observed in Africa and Southeast Asia, where most regions recorded ASRs between 1.82 and 3.34 per 100,000 population. Specifically, Southeast Asian countries demonstrated rates in the lowest bracket (1.82–2.52 per 100,000 population), while most of sub-Saharan Africa showed rates between 2.52 and 3.34 per 100,000 population.

A clear gradient was visible from north to south in the Americas, with North America showing substantially higher rates (17.66–26.83 per 100,000) compared to South America, where rates varied but generally remained between 3.34 and 4.30 per 100,000 population, except for the southernmost regions which displayed higher rates.

2.2 Geographic distribution of age-standardized mortality rates.

The age-standardized mortality rates (ASR) for acute carbon monoxide poisoning exhibited distinct geographical patterns across the world (Fig 2). The highest mortality rates were concentrated in Northern Asia and parts of Eastern Europe, where ASRs reached between 0.63 and 2.72 per 100,000 population. The Balkan Peninsula region also demonstrated notably high mortality rates, falling within the range of 0.32 to 0.63 per 100,000 population.

Fig 2 — Disease burden data from Global Burden of Disease Study 2021; Map data from Natural Earth (https://www.naturalearthdata.com/), public domain.

The Persian Gulf region displayed elevated mortality rates, with ASRs ranging from 0.21 to 0.32 per 100,000 population. North America showed moderate mortality rates, with ASRs between 0.15 and 0.21 per 100,000 population. Similar levels were observed in parts of Central Asia and Northern Europe.

Lower mortality rates were documented across most of Southeast Asia and Africa, where ASRs generally ranged from 0.03 to 0.07 per 100,000 population. The lowest mortality rates (0.00–0.03 per 100,000 population) were observed in parts of South America, particularly in Brazil and surrounding regions.

A notable gradient was apparent in the Americas, with higher rates in North America (0.15–0.21 per 100,000) contrasting with lower rates in central regions, though Southern Latin America showed elevated rates comparable to those in North America. The mortality pattern in Europe displayed considerable heterogeneity, with a clear east-to-west gradient showing higher rates in Eastern Europe and lower rates in Western European countries.

2.3 Geographic distribution of age-standardized DALY rates.

The age-standardized DALY rates for acute carbon monoxide poisoning showed substantial geographic variation worldwide (Fig 3). Northern Asia demonstrated the highest burden, with rates ranging from 30.55 to 120.20 DALYs per 100,000 population. The Balkan Peninsula and parts of Eastern Europe also exhibited notably high rates, falling within the range of 16.75 to 30.55 DALYs per 100,000 population.

The Persian Gulf region and North America showed moderately high DALY rates, ranging from 10.58 to 16.75 per 100,000 population. Central Asian countries displayed intermediate burden levels, with rates typically between 8.09 and 10.58 DALYs per 100,000 population.

Lower DALY rates were observed across most of Africa and Southeast Asia, where rates generally ranged from 2.53 to 4.30 per 100,000 population. The lowest burden was documented in parts of South America, particularly Brazil, with rates between 0.87 and 2.05 DALYs per 100,000 population.

The Americas showed a clear north-south divide in DALY rates, with North America experiencing higher rates (10.58–16.75 per 100,000) compared to Central America (5.46–8.09 per 100,000), though Southern Latin America demonstrated elevated rates similar to North American levels. European DALY rates exhibited marked regional variation, with a pronounced east-to-west gradient showing substantially higher rates in Eastern Europe compared to Western European nations.

3 Global analysis of the relationship between Socio-Demographic Index (SDI) and carbon monoxide poisoning disease burden

3.1 Regional-level analysis

3.1.1 Regional association between SDI and age-standardized incidence rates.

The age-standardized incidence rates (ASR) of acute carbon monoxide poisoning showed a strong positive correlation with socio-demographic index (SDI) across 21 global regions (Spearman’s r = 0.7611, p = 2.316e-142) (Fig 4). The relationship between SDI and incidence rates demonstrated distinct patterns across different regions.

Eastern Europe exhibited the highest incidence rates, reaching approximately 70 per 100,000 population at SDI levels around 0.6–0.7. Central Asia and High-income Asia Pacific regions showed the second-highest peaks, with incidence rates of about 30–40 per 100,000 population at similar SDI levels.

Western Europe and High-income North America displayed moderate incidence rates (20−30 per 100,000 population) at high SDI values (0.8–0.9). Australasia and Southern Latin America followed a similar pattern but with slightly lower rates.

Regions with lower SDI values (0.3–0.5), including South Asia, Southeast Asia, and Sub-Saharan African regions, consistently showed lower incidence rates, generally below 10 per 100,000 population. The global average curve demonstrated an overall increasing trend with SDI, peaking at moderate SDI levels (0.6–0.7) before showing a slight decline at the highest SDI values.

East Asia and Central Europe showed distinct trajectories, with rates increasing substantially as SDI increased from 0.4 to 0.7, followed by a plateau or slight decrease at higher SDI levels. The relationship between SDI and incidence rates appeared most pronounced in the mid-range of SDI values (0.5–0.7), where the greatest variation in rates was observed across regions.

3.1.2 Regional association between SDI and age-standardized mortality rates.

The relationship between socio-demographic index (SDI) and age-standardized death rates (ASR) for acute carbon monoxide poisoning across 21 global regions showed a moderate positive correlation (Spearman’s r = 0.3075, p = 7.627e-18) (Fig 5). The pattern of mortality rates demonstrated distinct regional variations across the SDI spectrum.

Eastern Europe exhibited the highest mortality rates, reaching approximately 7 deaths per 100,000 population at SDI values between 0.6 and 0.7. Central Asia showed the second highest peak, with mortality rates around 3 deaths per 100,000 population at similar SDI levels.

Most regions maintained relatively low mortality rates (below 1 per 100,000 population) across the SDI spectrum. High-income regions, including Western Europe, High-income North America, and Australasia, showed consistently low mortality rates despite their high SDI values (0.8–0.9).

The global average curve demonstrated a subtle increase with rising SDI values up to approximately 0.6, followed by a gradual decline at higher SDI levels. East Asia showed a distinctive pattern with elevated mortality rates at moderate SDI levels (0.6–0.7), while maintaining lower rates than Eastern Europe.

Regions with lower SDI values (0.3–0.5), including South Asia, Southeast Asia, and Sub-Saharan African regions, generally maintained low mortality rates below 0.5 per 100,000 population, showing minimal variation across different SDI values.

3.1.3 Regional association between SDI and age-standardized DALY rates.

The relationship between socio-demographic index (SDI) and age-standardized DALY rates for acute carbon monoxide poisoning across 21 global regions showed a moderate positive correlation (Spearman’s r = 0.3663, p = 3.671e-25) (Fig 6). The pattern of DALY rates demonstrated marked regional variations across the SDI spectrum.

Eastern Europe exhibited the highest DALY rates, reaching approximately 300 DALYs per 100,000 population at SDI values between 0.6 and 0.7. Central Asia showed the second highest burden, with rates around 150 DALYs per 100,000 population at similar SDI levels.

The global average curve demonstrated a gradual increase with rising SDI values up to approximately 0.6, followed by a decline at higher SDI levels. East Asia showed a distinctive pattern with elevated DALY rates at moderate SDI levels (0.6–0.7), though maintaining lower rates than Eastern Europe.

High-income regions, including Western Europe, High-income North America, and Australasia, showed relatively low DALY rates (below 50 per 100,000 population) despite their high SDI values (0.8–0.9). Most other regions maintained DALY rates below 100 per 100,000 population across the SDI spectrum.

Regions with lower SDI values (0.3–0.5), including South Asia, Southeast Asia, and Sub-Saharan African regions, consistently showed the lowest DALY rates, generally below 25 per 100,000 population, with minimal variation across different SDI values.

3.2 National-level analysis

3.2.1 National-level analysis of SDI and age-standardized incidence rates.

The relationship between socio-demographic index (SDI) and age-standardized incidence rates (ASR) of acute carbon monoxide poisoning at the national level showed a strong positive correlation (Spearman’s r = 0.7602, p < 0.001) (Fig 7). The analysis across 204 countries revealed distinct patterns of disease burden across the SDI spectrum.

Countries in Eastern Europe demonstrated the highest incidence rates, with the Republic of Moldova, Russian Federation, and Czechia recording rates above 35 per 100,000 population at SDI values between 0.7 and 0.8. These were followed by Belarus, Slovenia, and Estonia, with rates between 30 and 35 per 100,000 population at similar SDI levels.

A second tier of countries, including Latvia, Hungary, Slovakia, and Bosnia and Herzegovina, showed rates between 25 and 30 per 100,000 population, predominantly clustering at SDI values of 0.7–0.8. Nations with very high SDI values (>0.8), such as Canada, Belgium, and Singapore, generally demonstrated moderate incidence rates between 15 and 25 per 100,000 population.

Countries with lower SDI values (<0.5) consistently showed lower incidence rates, typically below 10 per 100,000 population. These included most nations in Sub-Saharan Africa, South Asia, and parts of Southeast Asia. The overall pattern showed a gradual increase in incidence rates with rising SDI values up to approximately 0.7, after which the relationship became more heterogeneous across countries.

The distribution showed notable regional clustering, with neighboring countries often displaying similar incidence rates despite varying SDI levels, particularly evident in the Eastern European cluster at the higher end of the incidence spectrum and the Sub-Saharan African cluster at the lower end.

3.2.2 National-level analysis of SDI and age-standardized mortality rates.

The relationship between socio-demographic index (SDI) and age-standardized death rates (ASR) for acute carbon monoxide poisoning across 204 countries showed a weak positive correlation (Spearman’s r = 0.1341, p = 5.584e-02) (Fig 8). The country-level analysis revealed distinct mortality patterns across different SDI levels.

The highest mortality rates were observed in Eastern European nations, with the Republic of Moldova and Russian Federation showing rates above 2 per 100,000 population at SDI values between 0.6 and 0.8. Mongolia and Kazakhstan also demonstrated notably high mortality rates, exceeding 1.5 per 100,000 population at moderate SDI levels.

Countries with high SDI values (>0.8), including Western European nations, North America, and high-income Asian countries, generally maintained low mortality rates below 0.5 per 100,000 population. Notable exceptions included Lithuania and Latvia, which showed relatively higher rates despite their high SDI values.

A cluster of countries with low to moderate SDI values (0.3–0.5) exhibited varying mortality rates. Afghanistan showed a distinctly high rate (approximately 1.8 per 100,000) at a low SDI value, while Nepal and Yemen demonstrated moderate rates (0.8–1.0 per 100,000) in similar SDI ranges.

The majority of countries, particularly those with SDI values below 0.6, maintained mortality rates below 0.5 per 100,000 population. This included most nations in Africa, South Asia, and Southeast Asia, showing minimal variation in mortality rates despite their varying SDI levels.

3.2.3 National-level analysis of SDI and age-standardized DALY rates.

The relationship between socio-demographic index (SDI) and age-standardized DALY rates for acute carbon monoxide poisoning across 204 countries demonstrated a weak positive correlation (Spearman’s r = 0.2233, p = 1.356e-03) (Fig 9). The country-level analysis revealed substantial heterogeneity in DALY burden across SDI levels.

Mongolia showed the highest DALY rate, reaching approximately 120 per 100,000 population at a moderate SDI level. This was followed by the Republic of Moldova and Russian Federation, both recording rates above 100 DALYs per 100,000 population at SDI values between 0.6 and 0.8.

A cluster of countries including Kazakhstan, Ukraine, and Belarus demonstrated DALY rates between 60 and 80 per 100,000 population at moderate to high SDI levels (0.6–0.8). Afghanistan showed notably high DALY rates (approximately 85 per 100,000) despite its low SDI value.

Countries with high SDI values (>0.8), including most Western European nations, North America, and high-income Asian countries, generally maintained low DALY rates below 20 per 100,000 population. Notable exceptions included Lithuania and Latvia, which showed moderately elevated rates despite their high SDI values.

The majority of countries, particularly those with SDI values below 0.6, maintained DALY rates below 40 per 100,000 population. This included most nations in Africa, South Asia, and Southeast Asia, with minimal variation in DALY rates despite their varying SDI levels.

4 Global trends and future projections

4.1 Projected trends in age-standardized incidence rates through 2050.

Global age-standardized incidence rate (ASR) of acute carbon monoxide poisoning is projected to continue its historical decline through 2050 (Fig 10). From an observed rate of approximately 12 per 100,000 population in 1990, the ASR decreased to 8 per 100,000 population by 2020. The forecasting model predicts a further reduction to approximately 5 per 100,000 population by 2050, with widening uncertainty intervals in the long-term projection period.

4.2 Projected trends in age-standardized mortality rates through 2050.

The global age-standardized mortality rate of acute carbon monoxide poisoning is projected to continue declining through 2050 (Fig 11). The historical trend shows a peak of approximately 0.8 per 100,000 population in the early 1990s, followed by a steady decrease to 0.35 per 100,000 population by 2020. The model forecasts a further reduction to approximately 0.15 per 100,000 population by 2050, with gradually expanding uncertainty intervals in the projection period.

4.3 Projected trends in age-standardized DALY rates through 2050.

Global age-standardized DALY rates for acute carbon monoxide poisoning are projected to maintain their downward trend through 2050 (Fig 12). From a peak of approximately 40 DALYs per 100,000 population in the early 1990s, the rate declined to around 15 DALYs per 100,000 population by 2020. The forecasting model predicts a further decrease to approximately 5 DALYs per 100,000 population by 2050, with increasing uncertainty intervals in the latter projection period.

Discussion

This study provides the first comprehensive analysis of the global burden of carbon monoxide (CO) poisoning, encompassing trends in incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Our findings reveal an overall declining trend in the global burden of CO poisoning, albeit with significant variations across geographical regions and socio-demographic index (SDI) levels. These results have important implications for developing targeted prevention strategies.

First, our study demonstrates a substantial global decline in CO poisoning incidence over the study period, reflecting [18], enhanced ventilation facilities [19], and increased public awareness [20]. However, Eastern Europe and High-income Asia Pacific regions maintain relatively high incidence rates, possibly due to high heating demands during winter months and delayed updates of aging heating infrastructure.

Second, our research reveals a complex relationship between CO poisoning burden and socioeconomic development levels. High-SDI and high-middle SDI regions exhibited the highest incidence rates but relatively lower mortality rates and DALY burdens, suggesting that while these regions report more cases, better medical conditions lead to improved patient outcomes [21,22]. In contrast, low-SDI regions show lower reported incidence rates but potentially suffer from underreporting and limited medical resources, which may result in poorer outcomes [23,24]. This aligns with previous findings [9,11] regarding insufficient acute poisoning treatment capabilities in developing countries.

The geographical distribution analysis reveals significant regional disparities. Eastern Europe consistently maintains the highest burden levels, attributable to its climatic characteristics [25], heating methods, and unique circumstances during socioeconomic transition. The lower reported rates in Africa and Southeast Asia may mask the actual disease burden, indicating a need to strengthen surveillance systems in these regions. Climate factors significantly influence CO poisoning patterns, with colder temperatures increasing heating demands and associated risks [26,27]. Climate change may alter geographic risk patterns, potentially reducing cold-weather exposures while creating new energy-related risks [28]. Behavioral interventions, including public education campaigns, proper equipment maintenance awareness, and widespread CO detector adoption, have proven effective in reducing mortality trends in developed nations [29,30].

Our study is the first to systematically analyze gender disparities, finding that males generally experience higher mortality rates and DALY burdens than females, possibly due to differences in occupational exposure risks and behavioral patterns [31,32].

Several novel findings from our comprehensive analysis warrant detailed discussion. The differential decline rates between incidence (−1.16% annually) and mortality (−2.79% annually) suggest that while exposure prevention efforts are moderately successful, treatment improvements have been more substantial, particularly in high-SDI regions. This pattern indicates that healthcare capacity building may be more achievable than primary prevention in the short term [33]. The inverted U-shaped SDI relationship reveals a critical insight: countries at moderate development levels (SDI 0.6–0.7) face the highest burden, likely reflecting increased fossil fuel use during industrialization without adequate safety infrastructure. This “development trap” suggests that economic growth alone does not guarantee reduced CO poisoning risk without targeted interventions [34]. The pronounced male predominance (2.5-fold higher mortality) extends beyond occupational exposure to include behavioral factors such as risk-taking behaviors and delayed healthcare seeking [35]. Our geographic clustering analysis reveals that neighboring countries often share similar burden patterns regardless of SDI differences, highlighting the importance of regional cooperation in prevention strategies. The persistent Eastern European hotspot, despite three decades of observation, underscores the complex interplay between climate, infrastructure legacy, and socioeconomic transition that requires sustained, multifaceted interventions.

Several limitations should be acknowledged in our study. First, the quality of Global Burden of Disease study data varies across countries, with potential incompleteness in low-income nations. Second, our inability to obtain detailed exposure information and specific causes of death limits concrete guidance for prevention strategies. Third, while our prediction models consider historical trends, they may not fully incorporate potential policy changes and technological advancements. Additionally, our forecasting models may not fully capture emerging variables that could significantly alter future trends. The global transition to clean energy and electric heating systems may accelerate burden decline beyond our projections. Conversely, rapid urbanization, technological innovations in smart monitoring systems, carbon neutrality policies, and climate change-induced extreme weather events introduce variability not reflected in historical trend-based models. These factors suggest our projections represent baseline scenarios rather than definitive forecasts.

These findings support specific evidence-based interventions: mandatory CO detector installation in residential buildings (successful in Canada and United States) [29], national surveillance programs (established in Norway and United Kingdom) [4,36], government-subsidized heating system replacement programs (implemented in Poland and Czech Republic) [37], and strengthened poison control centers following WHO models in developing countries [38,39].

Looking forward, our forecast analysis indicates that the global burden of CO poisoning will continue to decrease through 2050, though regional disparities may persist. This suggests the need for differentiated prevention strategies: high-burden regions should focus on upgrading heating facilities and enforcing safety standards, while low-income regions need strengthened infrastructure and medical treatment capabilities. Future research should explore the underlying causes of regional differences, evaluate the cost-effectiveness of various prevention measures, and establish more comprehensive surveillance systems. Additionally, the promotion of clean energy and development of smart early warning technologies may further reduce the disease burden of CO poisoning.

Conclusion

This comprehensive global analysis of carbon monoxide poisoning from 1990–2021 reveals significant epidemiological patterns with important public health implications. Our study demonstrates a substantial global decline in CO poisoning burden, with age-standardized incidence rates decreasing by 35.1% from 12.13 to 7.87 per 100,000 population, mortality rates declining by 2.79% annually, and DALYs showing the steepest reduction at 3.18% annually. Despite these improvements, nearly 300,000 new cases and 29,000 deaths occurred globally in 2021, indicating continued substantial burden.

Critical disparities persist across regions and demographics. Eastern Europe maintains the highest burden with incidence rates of 37.98 per 100,000—five times the global average. Males experience 2.5 times higher mortality rates than females across all regions. Most significantly, our analysis reveals a novel inverted U-shaped relationship between socio-demographic development and disease burden, with countries at moderate SDI levels (0.6–0.7) experiencing peak mortality and DALYs burden, while high-SDI regions show higher incidence but dramatically lower case-fatality rates (1.24% vs. 4.26%).

These findings have profound public health significance, demonstrating that economic development alone does not guarantee reduced CO poisoning burden without targeted interventions. The data support differentiated prevention strategies: infrastructure modernization in high-burden regions, strengthened medical capacity in transitioning economies, and enhanced surveillance in low-resource settings. Our projections through 2050 indicate continued global decline but persistent regional disparities, emphasizing the need for sustained, equity-focused interventions. This study provides the first multi-dimensional global assessment of CO poisoning burden and establishes a framework for evidence-based policy making to address this entirely preventable cause of death and disability worldwide.

Supporting information

S1 Data. Raw dataset used for Global Burden of Disease (GBD) analysis of carbon monoxide (CO) poisoning.

(ZIP)

pone.0330778.s001.rar^{(2.5MB, rar)}

Abbreviations

APC: Annual Percentage Change
AAPC: Average Annual Percentage Change
ARIMA: Autoregressive Integrated Moving Average
ASR: Age-Standardized Rate
CO: Carbon monoxide
DALY: Disability-Adjusted Life Year
GBD: Global Burden of Disease
GHDx: Global Health Data Exchange
LISA: Local Indicators of Spatial Association
SDI: Socio-Demographic Index
UI: Uncertainty Interval
WHO: World Health Organization
YLD: Years Lived with Disability
YLL: Years of Life Lost

Data Availability

All data underlying the findings described in this manuscript are fully available without restriction from public repositories. The primary datasets analyzed during the current study are available from the Global Health Data Exchange (GHDx), Institute for Health Metrics and Evaluation, University of Washington (http://ghdx.healthdata.org/). Specifically, the Global Burden of Disease Study 2021 results for acute carbon monoxide poisoning, including age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) data from 1990-2021 covering 204 countries and territories, are freely accessible after user registration. Socio-demographic Index (SDI) data by country and region are also available from the same source. Geographic base map data used for spatial visualization were obtained from Natural Earth (https://www.naturalearthdata.com/), which are in the public domain. All processed datasets and analysis code supporting the conclusions of this article are available from the corresponding author upon reasonable request.

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. 2025 Aug 22;20(8):e0330778. doi: 10.1371/journal.pone.0330778.r001

Author response to Decision Letter 0

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PLoS One. doi: 10.1371/journal.pone.0330778.r002

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29 Jun 2025

PONE-D-25-08215Global Patterns and Trends of Carbon Monoxide Poisoning: A Systematic Analysis from 1990 to 2021PLOS ONE

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Reviewer #1: 1. Title is concise and should contain the name of the main used analytical methods or the limitations solving

2. The abstract needs to be reorganized firstly to clarify the main aim of your study to overcome the limitations of the previous studies in the same line with your research.

3. What are the validity of the used analytical methods main advantages and disadvantages and why such methods were applied (joinpoint regression, spatial statistics, and ARIMA modeling).

4. Abstract can’t stand alone. All results were mentioned in very concise manner that not clear for authors and the conclusive words not satisfactory about your obtained results versus your study aim.

5. Keywords not representative for your study aim or methods or analysis

6. More reviewing data about the CO poisoning are required in the section of introduction. What is the main health problems reported from exposure to CO and how exposure occur?

7. Line 63 lesions not satisfactory for the side effects of HFM replace with renal damage or renal toxicity from pesticide exposure.

8. Material and methods section: ethical approval code must be supplied in such section not at the end of the manuscript

9. Not all the obtained data were fully discussed. Discussion are very concise

10. Conclusion is so concise not presenting the study results or significance

11. All the abbreviations must be mentioned in full name for the first time and list of abbreviations should be supplied

12. Grammatical errors, has major grammatical and structural errors. Please, double-check. English must be improved and certified.

Reviewer #2: Recommendation: Minor Revision

General Comments

This manuscript presents a comprehensive and methodologically rigorous analysis of the global burden of acute carbon monoxide (CO) poisoning using data from the GBD 2021 study. The Discussion section is particularly well-developed, integrating key findings with socio-demographic insights and regional disparities. It adds value by addressing gender differences, projecting future trends, and offering policy implications.

The paper is timely and relevant for global health policy, environmental epidemiology, and injury prevention fields.

Strengths

�Clear articulation of global trends in CO burden (incidence, mortality, DALYs).

�Integration of socio-demographic index (SDI) as a framework enhances interpretability.

�Thoughtful consideration of gender-specific trends and regional disparities.

�Well-grounded policy recommendations and recognition of forecast uncertainty.

�Transparent acknowledgement of data limitations and methodological constraints.

Minor Revisions Requested

Reduce Repetition of Quantitative Results

The Discussion section occasionally reiterates specific incidence and mortality figures already presented in the Results. Consider summarizing trends without repeating exact numbers.

Expand Policy Examples

Strengthen the applicability of policy suggestions by referencing concrete measures (e.g., mandatory CO detectors in homes, national surveillance programs in Eastern Europe or Canada).

Consider Behavioral and Climate Factors

Briefly address how climate change and seasonal factors may affect CO poisoning trends.

Include a sentence on the potential impact of behavioral interventions (e.g., public education, alarm usage).

Clarify Forecasting Limitations

While limitations are mentioned, highlight the potential variability due to emerging technologies or policy shifts (e.g., clean energy transitions, urbanization).

Conclusion

This is a strong manuscript with high public health relevance and rich global insights. Minor editorial and content refinements will further improve clarity and impact. Once revised, it will make a valuable contribution to the literature on environmental health and injury epidemiology.

**********

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Reviewer #2: Yes: Dr. Kwabena Acheampong

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PLoS One. 2025 Aug 22;20(8):e0330778. doi: 10.1371/journal.pone.0330778.r003

Author response to Decision Letter 1

15 Jul 2025

Response to Reviewers

Manuscript ID: PONE-D-25-08215

Title: Global Patterns and Trends of Carbon Monoxide Poisoning: A Systematic Analysis from 1990 to 2021

Dear Dr. Antonio Peña-Fernández and Esteemed Reviewers,

We are deeply grateful for the thorough and constructive feedback provided during the peer review process. The insightful comments have significantly improved the quality and clarity of our manuscript. We have carefully addressed each concern and suggestion, and we believe the revised manuscript is substantially strengthened as a result.

Response to Editorial Requirements

Dear Dr. Peña-Fernández,

We sincerely thank you for your editorial guidance and the opportunity to revise our manuscript. We greatly appreciate your patience and the comprehensive review process you have facilitated.

Editorial Requirement 1: PLOS ONE Style Requirements

Response:

We have carefully reviewed and implemented all PLOS ONE formatting requirements, including file naming conventions and manuscript structure. We have consulted both provided style templates to ensure full compliance. We have used red font to highlight all modifications made throughout the manuscript in response to the reviewers' feedback.

Editorial Requirement 2: Data Availability Statement

Response:

We fully understand and value the importance of data transparency. This study uses publicly available data from the Global Burden of Disease Study 2021 database (accessible at: http://ghdx.healthdata.org/), and all supporting data are openly available without restrictions. We have prepared supplementary files containing the processed data versions used to create all figures. These files, named "minimal data set.rar", will be uploaded along with the revised version as supporting information files.

Editorial Requirement 3: Ethics Statement Placement

Response:

Thank you for this important clarification regarding the placement of the ethics statement. We have revised the manuscript accordingly:

1.Moved the ethics statement to the Methods section: We have consolidated and moved the complete ethics statement to the "Study Design and Data Sources" subsection of the Methods section, ensuring all ethical considerations are properly documented in the appropriate location.

2.Removed the standalone Ethics Statement section: The separate ethics statement that previously appeared at the end of the manuscript has been deleted to avoid duplication.

3.Enhanced the ethics content in Methods: The ethics statement in the Methods section now includes comprehensive information about ethical approval, informed consent waiver justification, and compliance with relevant ethical guidelines.

The ethics statement now appears only in the Methods section as required and contains all necessary ethical information for publication.

We conducted a comprehensive analysis of acute carbon monoxide poisoning using the Global Burden of Disease (GBD) 2021 database, accessed through the Global Health Data Exchange (GHDx) platform[9]. The analysis covered the period from 1990 to 2021, encompassing data from 204 countries and territories. Our research framework adhered to the GATHER guidelines for health estimates reporting[10]. The data were accessed for research purposes on March 15, 2021.

Editorial Requirement 4: Map Copyright Issues

Response:

Thank you for raising this important copyright concern regarding the map images in our submission. We appreciate your diligence in ensuring compliance with CC BY 4.0 license requirements. Please find our detailed response below:

Map Creation and Data Sources:

The map images in Figures 1, 2, and 3 were created entirely using public domain resources and open-source tools:

Base map data: Natural Earth (https://www.naturalearthdata.com/), accessed via the rnaturalearth R package (https://github.com/ropensci/rnaturalearth)

Disease burden data: Global Burden of Disease Study 2021 (public database)

Creation software: R programming language with ggplot2 and sf packages (open-source)

Natural Earth explicitly releases all their map data into the public domain with no copyright restrictions. According to Natural Earth's terms of use (https://www.naturalearthdata.com/about/terms-of-use/), their data can be used for any purpose without permission, making it fully compatible with PLOS ONE's CC BY 4.0 license requirements. No proprietary software (such as Google Maps, ArcGIS, or other commercial mapping platforms) was used in creating these figures.

Updated Figure Captions with Proper Attribution:

We have revised the figure captions to include appropriate attribution:

Figure 1: Geographic Distribution of Age-Standardized Incidence Rates of Acute Carbon Monoxide Poisoning (per 100,000 population) in 2021. Disease burden data from Global Burden of Disease Study 2021; Map data from Natural Earth (https://www.naturalearthdata.com/), public domain.

Figure 2: Geographic Distribution of Age-Standardized Mortality Rates of Acute Carbon Monoxide Poisoning (per 100,000 population) in 2021. Disease burden data from Global Burden of Disease Study 2021; Map data from Natural Earth (https://www.naturalearthdata.com/), public domain.

Figure 3: Geographic Distribution of Age-Standardized DALY Rates of Acute Carbon Monoxide Poisoning (per 100,000 population) in 2021. Disease burden data from Global Burden of Disease Study 2021; Map data from Natural Earth (https://www.naturalearthdata.com/), public domain.

Compliance Confirmation:

All map figures in our submission are created using public domain data and open-source software, ensuring full compliance with CC BY 4.0 licensing requirements. These figures can be freely accessed, downloaded, copied, distributed, and used by any third party, including for commercial purposes, with proper attribution as specified in the updated captions.

We believe this addresses all copyright concerns while maintaining the scientific integrity and visual clarity of our geographical analysis.

Response to Reviewer #1

We extend our heartfelt gratitude to Reviewer #1 for the comprehensive and constructive feedback. Your detailed suggestions have significantly enhanced the scientific rigor and clarity of our manuscript. We have addressed each point systematically:

Comment 1:

Reviewer's Suggestion: "Title is concise and should contain the name of the main used analytical methods or the limitations solving."

Our Response:

We deeply appreciate this valuable suggestion. We have revised the title to better reflect our methodological contributions:

Original Title: "Global Patterns and Trends of Carbon Monoxide Poisoning: A Systematic Analysis from 1990 to 2021"

Revised Title: "Global Patterns and Trends of Carbon Monoxide Poisoning: A Comprehensive Spatiotemporal Analysis Using Joinpoint Regression and ARIMA Modeling, 1990-2021"

This revision explicitly highlights our key analytical methods (joinpoint regression, ARIMA modeling) and emphasizes the spatiotemporal nature of our analysis.

Comment 2:

Reviewer's Suggestion: "The abstract needs to be reorganized firstly to clarify the main aim of your study to overcome the limitations of the previous studies."

Our Response: Thank you for this crucial insight. We have completely restructured our abstract to explicitly address how our study overcomes previous research limitations:

Abstract

Background: Carbon monoxide (CO) poisoning causes approximately 41,000 deaths annually worldwide despite being preventable. Previous studies focused primarily on mortality alone, lacked systematic socio-demographic analysis, and provided no predictive models. This study comprehensively analyzes global CO poisoning patterns using spatiotemporal methods to inform evidence-based prevention strategies.

Methods: We analyzed Global Burden of Disease Study 2021 data from 204 countries (1990-2021) for age-standardized incidence, mortality, and disability-adjusted life years (DALYs). Joinpoint regression identified temporal trends with statistical precision, spatial statistics quantified geographic clustering, and ARIMA modeling projected trends through 2050. We examined associations with socio-demographic index (SDI) across regions and countries.

Results: Global age-standardized incidence rates decreased significantly by 35.1% from 12.13 (95% UI: 8.30-17.00) to 7.87 (95% UI: 5.54-10.81) per 100,000 population (annual percentage change: -1.16%, 95% UI: -1.35% to -0.96%, p<0.001). Mortality rates declined more dramatically by 53.9% from 0.76 (95% UI: 0.66-0.91) to 0.35 (95% UI: 0.24-0.40) per 100,000 (annual change: -2.79%, 95% UI: -3.14% to -2.44%, p<0.001). DALY rates showed the steepest reduction of 59.5% from 37.59 (95% UI: 31.75-44.76) to 15.22 (95% UI: 10.67-17.57) per 100,000 (annual change: -3.18%, 95% UI: -3.51% to -2.84%, p<0.001). Eastern Europe demonstrated the highest burden (37.98 per 100,000 in 2021). Males experienced significantly higher mortality than females (0.50 vs 0.20 per 100,000, p<0.001). SDI analysis revealed an inverted U-shaped relationship (Spearman's r=0.76, p<0.001), with peak burden at moderate development levels (SDI: 0.6-0.7).

Conclusions: These findings directly address previous research gaps by demonstrating: (1) faster mortality decline than incidence decline indicates improved global treatment capabilities; (2) the SDI-burden relationship identifies moderate-development countries as priority intervention targets; (3) significant male predominance (2.5-fold higher mortality) supports gender-specific prevention programs; and (4) persistent Eastern European hotspots require targeted infrastructure improvements. Predictive models forecast continued decline through 2050 and enable evidence-based healthcare planning. This comprehensive analysis provides the first multi-dimensional global assessment, offering crucial evidence for differentiated prevention strategies worldwide.

Comment 3:

Reviewer's Suggestion: "What are the validity of the used analytical methods main advantages and disadvantages and why such methods were applied."

Our Response:

Thank you for this important methodological inquiry. We selected three complementary analytical approaches, each with specific advantages, limitations, and applications. Here is our detailed justification:

1. Joinpoint Regression Analysis

Advantages:

Objectively identifies significant change points in temporal trends without a priori assumptions

More accurately captures complex, non-linear temporal patterns compared to traditional linear regression

Provides statistically precise estimates of Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC)

Well-established methodology widely used in disease surveillance and epidemiological research

Limitations:

Requires sufficient data points (typically ≥4 time points) for reliable results

Sensitive to outliers in the data

May overfit when data are limited

Rationale for Use: With 31 years of continuous data (1990-2021), joinpoint regression was optimal for identifying long-term trend changes in CO poisoning burden, particularly detecting temporal impacts of policy interventions or socioeconomic changes on disease patterns.

2. Spatial Statistics Analysis

Advantages:

Identifies spatial clustering and hotspot regions of disease burden

Accounts for geographic proximity effects on disease distribution

Global Moran's I and LISA analyses provide quantitative assessment of global and local spatial autocorrelation

Facilitates identification of priority geographic areas for intervention

Limitations:

Requires high-quality geocoded data

May be affected by administrative boundary effects

Choice of spatial weight matrix can influence results

Rationale for Use: CO poisoning is often closely related to geographic factors (climate, heating methods, infrastructure). Spatial statistical analysis reveals these geographic patterns, providing scientific evidence for developing region-specific prevention strategies.

3. ARIMA Time Series Modeling

Advantages:

Handles autocorrelation and seasonality in time series data

Provides scientific predictions based on historical data patterns

Offers uncertainty intervals for prediction results

Widely applied and reliable methodology in epidemiological forecasting

Limitations:

Assumes historical trends will continue into the future, potentially missing impacts of sudden events

Cannot directly incorporate external covariates (policy changes, technological advances)

Long-term prediction uncertainty increases progressively

Rationale for Use: To support long-term health planning and resource allocation, we needed to forecast future trends in CO poisoning burden. ARIMA modeling, based on 31 years of historical data, provides reasonable projections through 2050, offering prospective information for policymakers.

Methodological Integration Rationale:

These three methods are complementary and form a comprehensive analytical framework: joinpoint regression describes historical trends, spatial statistics reveals geographic patterns, and ARIMA modeling predicts future trends. This multi-method integration provides a complete assessment of the global burden of CO poisoning.

Validity Considerations:

All methods were validated through appropriate statistical tests, model diagnostics, and uncertainty quantification. The combination approach enhances the robustness of our findings and provides multiple perspectives on the same epidemiological phenomenon.

Comment 4:

Reviewer's Suggestion: "Abstract can't stand alone. All results were mentioned in very concise manner that not clear for authors and the conclusive words not satisfactory."

Our Response: We are grateful for this observation. We have substantially enhanced the abstract to ensure it stands alone effectively.

Comment 5:

Reviewer's Suggestion: "Keywords not representative for your study aim or methods or analysis."

Our Response: Thank you for this important feedback. We have revised our keywords to better reflect our study's methodological and analytical focus:

Revised Keywords: carbon monoxide poisoning; joinpoint regression; ARIMA modeling; spatiotemporal analysis; socio-demographic index; global burden of disease; health disparities; forecasting

Comment 6:

Reviewer's Suggestion: "More reviewing data about the CO poisoning are required in the section of introduction. What is the main health problems reported from exposure to CO and how exposure occur?"

Our Response: We deeply appreciate this suggestion for strengthening our literature foundation. We have added a comprehensive paragraph detailing:

Carbon monoxide exposure occurs through multiple pathways. Common sources include faulty heating systems, poorly ventilated cooking appliances, vehicle exhaust in enclosed spaces, and fuel-burning equipment such as generators[4, 5]. Motor vehicle exhaust represents a significant source of CO exposure, particularly from stationary vehicles in enclosed spaces[6]. The health impacts range from acute symptoms including headache, dizziness, and nausea at concentrations of 50-100 ppm to severe neurological damage, cardiac arrhythmias, and death at concentrations exceeding 400 ppm[7]. Long-term sequelae among survivors include persistent neurological deficits, cognitive impairment, and increased risk of delayed neurological sequelae affecting 10-32% of patients[7].

Comment 7:

Reviewer's Suggestion: "Line 63 lesions not satisfactory for the side effects of HFM replace with renal damage or renal toxicity from pesticide exposure."

Our Response: Thank you for your feedback. However, we believe there may be some confusion regarding your comment on Line 63. O

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PLoS One. doi: 10.1371/journal.pone.0330778.r004

Decision Letter 1

Antonio Peña-Fernández

6 Aug 2025

Global Patterns and Trends of Carbon Monoxide Poisoning: A Comprehensive Spatiotemporal Analysis Using Joinpoint Regression and ARIMA Modeling, 1990-2021

PONE-D-25-08215R1

Dear Dr. Wang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

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Kind regards,

Antonio Peña-Fernández, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear authors,

Thank you for submitting a revised version of your manuscript. The reviewers are happy with your amended version. Therefore I recommend its publication in our journal.

Best wishes,

Antonio

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #2: (No Response)

**********

6. Review Comments to the Author

Reviewer #2: Review Recommendation Letter to the Authors

Dear Authors,

I have carefully reviewed the revised version of your manuscript titled:

“Global Patterns and Trends of Carbon Monoxide Poisoning: A Comprehensive Spatiotemporal Analysis Using Joinpoint Regression and ARIMA Modeling, 1990–2021.”

I would like to commend you for the considerable effort you invested in addressing all the comments and suggestions provided during the initial peer review. Your responses were detailed, thoughtful, and clearly reflected a strong commitment to improving the clarity, methodological soundness, and scientific value of the manuscript.

In particular, the enhanced explanations of your analytical approaches—especially the use of Joinpoint regression and ARIMA modeling—have improved the manuscript’s transparency and strengthened its contribution to the field. The updates to the discussion and interpretation of findings have also significantly improved the contextual understanding and global relevance of your study.

Your work provides a valuable and timely contribution to the global discourse on carbon monoxide poisoning trends and has important implications for public health surveillance and policy formulation.

Based on the thoroughness of your revision and the scientific merit of the study, I am pleased to recommend the manuscript for acceptance in its current form.

Congratulations on your excellent work.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: Yes: Dr. Kwabena Acheampong

**********

PLoS One. doi: 10.1371/journal.pone.0330778.r005

Acceptance letter

Antonio Peña-Fernández

PONE-D-25-08215R1

PLOS ONE

Dear Dr. Wang,

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Data. Raw dataset used for Global Burden of Disease (GBD) analysis of carbon monoxide (CO) poisoning.

(ZIP)

pone.0330778.s001.rar^{(2.5MB, rar)}

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Submitted filename: The Approval DocumentNO.2 (Approval No. P202309-1)English.pdf

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Data Availability Statement

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Global patterns and trends of carbon monoxide poisoning: A comprehensive spatiotemporal analysis using joinpoint regression and ARIMA modeling, 1990–2021

Weiguang Wang

Yongai Ling

Xianwei Xiong

Jiajie Zhou

Roles

Abstract

Background

Methods

Results

Conclusions

Introduction

Methods

Study design

Analytical framework

Burden metrics

Computational tools

Results

1. Epidemiological patterns and trends of acute carbon monoxide poisoning, 1990–2021

1.1 Global burden and temporal trends (Table 1).

Table 1. Global age-standardized incidence rates of acute carbon monoxide poisoning (1990-2021).

1.2 Deaths and mortality trends (Table 2).

Table 2. Global age-standardized mortality rates of acute carbon monoxide poisoning (1990-2021).

1.3 Disability-adjusted life years (Table 3).

Table 3. Global age-standardized DALY rates of acute carbon monoxide poisoning (1990-2021).

Global geographic distribution

2.1 Geographic distribution of age-standardized incidence rates.

Fig 1. Geographic distribution of age-standardized incidence rates of acute carbon monoxide poisoning (per 100,000 population) in 2021.

2.2 Geographic distribution of age-standardized mortality rates.

Fig 2. Geographic distribution of age-standardized mortality rates of acute carbon monoxide poisoning (per 100,000 population) in 2021.

2.3 Geographic distribution of age-standardized DALY rates.

Fig 3. Geographic distribution of age-standardized DALY rates of acute carbon monoxide poisoning (per 100,000 population) in 2021.

3 Global analysis of the relationship between Socio-Demographic Index (SDI) and carbon monoxide poisoning disease burden

3.1 Regional-level analysis

3.1.1 Regional association between SDI and age-standardized incidence rates.

Fig 4. Association between socio-demographic index and age-standardized incidence rates across 21 global regions.

3.1.2 Regional association between SDI and age-standardized mortality rates.

Fig 5. Association between socio-demographic index and age-standardized mortality rates across 21 global regions.

3.1.3 Regional association between SDI and age-standardized DALY rates.

Fig 6. Association between socio-demographic index and age-standardized DALY rates across 21 global regions.

3.2 National-level analysis

3.2.1 National-level analysis of SDI and age-standardized incidence rates.

Fig 7. Association between socio-demographic index and age-standardized incidence rates across 204 countries.

3.2.2 National-level analysis of SDI and age-standardized mortality rates.

Fig 8. Association between socio-demographic index and age-standardized mortality rates across 204 countries.

3.2.3 National-level analysis of SDI and age-standardized DALY rates.

Fig 9. Association between socio-demographic index and age-standardized DALY rates across 204 countries.

4 Global trends and future projections

4.1 Projected trends in age-standardized incidence rates through 2050.

Fig 10. Projected trends in age-standardized incidence rates of acute carbon monoxide poisoning through 2050.

4.2 Projected trends in age-standardized mortality rates through 2050.

Fig 11. Projected trends in age-standardized mortality rates of acute carbon monoxide poisoning through 2050.

4.3 Projected trends in age-standardized DALY rates through 2050.

Fig 12. Projected trends in age-standardized DALY rates of acute carbon monoxide poisoning through 2050.

Discussion

Conclusion

Supporting information

Abbreviations

Data Availability

Funding Statement

References

Author response to Decision Letter 0

Decision Letter 0

Antonio Peña-Fernández

Roles

Author response to Decision Letter 1

Decision Letter 1

Antonio Peña-Fernández

Roles

Acceptance letter

Antonio Peña-Fernández

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

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