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Safety and effectiveness of triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole in reducing lymphatic filariasis prevalence and clearing circulating filarial antigens in Mombasa, Kenya.
IF 8.1 1区 医学 Pub Date : 2025-02-24 DOI: 10.1186/s40249-025-01282-z
Christabel Khaemba, Sammy M Njenga, Wyckliff P Omondi, Elvis Kirui, Margaret Oluka, Anastacia Guantai, Eleni Aklillu

Background: In 2018, Kenya introduced triple-drug therapy with ivermectin, diethylcarbamazine, albendazole (IDA) through mass drug administration (MDA) to accelerate the elimination of lymphatic filariasis (LF). This community-based surveillance study assessed the safety and effectiveness of IDA-MDA in reducing LF-antigenemia prevalence and circulating filarial antigens (CFA) clearance among LF infected individuals.

Methods: A total of 8928 residents in Mombasa, Kenya, were screened for CFA using the Filarial Test Strip: 3464 were screened in 2018 and 5464 in 2021 after two annual IDA-MDA rounds. CFA-positive individuals in 2021 were re-tested at two and four months of post-MDA for CFA-clearance rates. Adverse events (AEs) associated with IDA-MDA were monitored via door-to-door visits on days 1, 2, and 7 post-MDA to document the incidence, type and risk factors. Efficacy outcomes included post-MDA LF-antigenemia prevalence reduction after two rounds of annual MDA and CFA clearance rate. Chi-square test compared proportions, and logistic regression analysis identified AE predictors.

Results: LF antigenemia prevalence significantly decreased from 1.39% (n = 48) in 2018 to 0.66% (n = 36) in 2021 [P < 0.001; 95% confidence interval (CI) for difference in proportions: 0.003-0.012]. CFA clearance rates were 63.2% (12/19, 95% CI: 41.0-80.1%) at 2 months and 68.4% (13/19, 95% CI: 46.0-86.6%) at 4 months post-MDA. Among 53 CFA-positive individuals monitored, the cumulative 7-day AE incidence was 37.7% (95% CI: 25.6-51.7), higher than the general population's 27.3% (95% CI: 26.4-28.2). Common AEs included nausea (11.3%), diarrhea (11.3%), abdominal pain (7.6%), and headache (5.7%). Risk factors for AEs included age, overweight status, concomitant medication use, chronic illness, and fasting before MDA.

Conclusions: Triple therapy with IDA is safe and well-tolerated, with some mild-to-moderate and transient adverse events among LF-infected individuals. The high incidence of AEs highlights the need for safety monitoring during MDA. The significant reductions in LF antigenemia prevalence and high CFA clearance rates underscore IDA's effectiveness in reducing LF transmission, positioning it as a key strategy for eliminating LF as a public health problem by 2030.

{"title":"Safety and effectiveness of triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole in reducing lymphatic filariasis prevalence and clearing circulating filarial antigens in Mombasa, Kenya.","authors":"Christabel Khaemba, Sammy M Njenga, Wyckliff P Omondi, Elvis Kirui, Margaret Oluka, Anastacia Guantai, Eleni Aklillu","doi":"10.1186/s40249-025-01282-z","DOIUrl":"10.1186/s40249-025-01282-z","url":null,"abstract":"<p><strong>Background: </strong>In 2018, Kenya introduced triple-drug therapy with ivermectin, diethylcarbamazine, albendazole (IDA) through mass drug administration (MDA) to accelerate the elimination of lymphatic filariasis (LF). This community-based surveillance study assessed the safety and effectiveness of IDA-MDA in reducing LF-antigenemia prevalence and circulating filarial antigens (CFA) clearance among LF infected individuals.</p><p><strong>Methods: </strong>A total of 8928 residents in Mombasa, Kenya, were screened for CFA using the Filarial Test Strip: 3464 were screened in 2018 and 5464 in 2021 after two annual IDA-MDA rounds. CFA-positive individuals in 2021 were re-tested at two and four months of post-MDA for CFA-clearance rates. Adverse events (AEs) associated with IDA-MDA were monitored via door-to-door visits on days 1, 2, and 7 post-MDA to document the incidence, type and risk factors. Efficacy outcomes included post-MDA LF-antigenemia prevalence reduction after two rounds of annual MDA and CFA clearance rate. Chi-square test compared proportions, and logistic regression analysis identified AE predictors.</p><p><strong>Results: </strong>LF antigenemia prevalence significantly decreased from 1.39% (n = 48) in 2018 to 0.66% (n = 36) in 2021 [P < 0.001; 95% confidence interval (CI) for difference in proportions: 0.003-0.012]. CFA clearance rates were 63.2% (12/19, 95% CI: 41.0-80.1%) at 2 months and 68.4% (13/19, 95% CI: 46.0-86.6%) at 4 months post-MDA. Among 53 CFA-positive individuals monitored, the cumulative 7-day AE incidence was 37.7% (95% CI: 25.6-51.7), higher than the general population's 27.3% (95% CI: 26.4-28.2). Common AEs included nausea (11.3%), diarrhea (11.3%), abdominal pain (7.6%), and headache (5.7%). Risk factors for AEs included age, overweight status, concomitant medication use, chronic illness, and fasting before MDA.</p><p><strong>Conclusions: </strong>Triple therapy with IDA is safe and well-tolerated, with some mild-to-moderate and transient adverse events among LF-infected individuals. The high incidence of AEs highlights the need for safety monitoring during MDA. The significant reductions in LF antigenemia prevalence and high CFA clearance rates underscore IDA's effectiveness in reducing LF transmission, positioning it as a key strategy for eliminating LF as a public health problem by 2030.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"11"},"PeriodicalIF":8.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Snail control as a crucial approach to schistosomiasis elimination: evidence from the People's Republic of China.
IF 8.1 1区 医学 Pub Date : 2025-02-21 DOI: 10.1186/s40249-025-01281-0
Shan Lv, Jing Xu, Yin-Long Li, Zi-Ping Bao, Li-Juan Zhang, Kun Yang, Dan-Dan Lin, Jian-Bing Liu, Tian-Ping Wang, Guang-Hui Ren, Bo Zhong, Yi Dong, Li Cai, Li-Yong Wen, Zhi-Hua Jiang, Zhuo-Hui Deng, Han-Guo Xie, Shi-Zhu Li, Robert Bergquist, Jürg Utzinger, Xiao-Nong Zhou

Background: Asian schistosomiasis is projected to be eliminated by 2030 according to World Health Organization road map for neglected tropical diseases 2021-2030. Snail control is an important measure but has not yet been systematically evaluated at a country scale. Here, we report the findings from a nationwide survey to demonstrate the dynamics of Oncomelania and its potential role in transmission interruption of schistisomiasis in the People's Republic of China (P.R. China).

Methods: Between March 2016 and December 2017, we conducted a nationwide census on Oncomelania snail habitats in P.R. China. All historically recorded snail habitats were identified and reviewed. Information on habitat attributes, including the infestation of snails, was collected. The shape of habitats was determined using global positioning system and geographical information system technologies. The relationship between snail control and schistosomiasis elimination was established in 378 endemic counties. The comparison of accumulated snail-infested range (ASR) and the median ratio of eliminated ASR between the transmission-interrupted and endemic counties was tested by a non-parametric test (Mann-Whitney) with a significance level of 0.05.

Results: Overall, 15,377.7 million m2 of potential snail habitats with a total of 356,550 snail habitats were identified in P.R. China. The ASR amounted to 86.0% of the total area. Most of the ASR (94.9%) and habitats (68.5%) were distributed in the middle and lower reaches of the Yangtze River. Snail habitats were found up to an altitude of 2859 m above the mean sea level. By 2017, 85.1% of habitats (73.0% of the ASR) had been eliminated with almost half of them eliminated between 1965 and 1982. The elimination of snail habitats promoted transmission interruption of schistosomiasis, but showed variable patterns in different landscapes. The ratio of eliminated ASR was 99.6 and 91.4% in water network and hilly areas, respectively, while it was only 64.8% in marshland areas, particularly in Hunan and Jiangxi where the two largest freshwater lakes of P.R. China are located. Marshland habitats were seen as the most difficult for transmission interruption, which calls for additional control measures in these settings.

Conclusions: Our results support recent recommendations by the World Health Organization to implement snail control and demonstrate that schistosomiasis elimination can be achieved. The nationwide, high-resolution map of Oncomelania snail habitats in P.R. China will support further efforts to eliminate schistosomiasis.

{"title":"Snail control as a crucial approach to schistosomiasis elimination: evidence from the People's Republic of China.","authors":"Shan Lv, Jing Xu, Yin-Long Li, Zi-Ping Bao, Li-Juan Zhang, Kun Yang, Dan-Dan Lin, Jian-Bing Liu, Tian-Ping Wang, Guang-Hui Ren, Bo Zhong, Yi Dong, Li Cai, Li-Yong Wen, Zhi-Hua Jiang, Zhuo-Hui Deng, Han-Guo Xie, Shi-Zhu Li, Robert Bergquist, Jürg Utzinger, Xiao-Nong Zhou","doi":"10.1186/s40249-025-01281-0","DOIUrl":"10.1186/s40249-025-01281-0","url":null,"abstract":"<p><strong>Background: </strong>Asian schistosomiasis is projected to be eliminated by 2030 according to World Health Organization road map for neglected tropical diseases 2021-2030. Snail control is an important measure but has not yet been systematically evaluated at a country scale. Here, we report the findings from a nationwide survey to demonstrate the dynamics of Oncomelania and its potential role in transmission interruption of schistisomiasis in the People's Republic of China (P.R. China).</p><p><strong>Methods: </strong>Between March 2016 and December 2017, we conducted a nationwide census on Oncomelania snail habitats in P.R. China. All historically recorded snail habitats were identified and reviewed. Information on habitat attributes, including the infestation of snails, was collected. The shape of habitats was determined using global positioning system and geographical information system technologies. The relationship between snail control and schistosomiasis elimination was established in 378 endemic counties. The comparison of accumulated snail-infested range (ASR) and the median ratio of eliminated ASR between the transmission-interrupted and endemic counties was tested by a non-parametric test (Mann-Whitney) with a significance level of 0.05.</p><p><strong>Results: </strong>Overall, 15,377.7 million m<sup>2</sup> of potential snail habitats with a total of 356,550 snail habitats were identified in P.R. China. The ASR amounted to 86.0% of the total area. Most of the ASR (94.9%) and habitats (68.5%) were distributed in the middle and lower reaches of the Yangtze River. Snail habitats were found up to an altitude of 2859 m above the mean sea level. By 2017, 85.1% of habitats (73.0% of the ASR) had been eliminated with almost half of them eliminated between 1965 and 1982. The elimination of snail habitats promoted transmission interruption of schistosomiasis, but showed variable patterns in different landscapes. The ratio of eliminated ASR was 99.6 and 91.4% in water network and hilly areas, respectively, while it was only 64.8% in marshland areas, particularly in Hunan and Jiangxi where the two largest freshwater lakes of P.R. China are located. Marshland habitats were seen as the most difficult for transmission interruption, which calls for additional control measures in these settings.</p><p><strong>Conclusions: </strong>Our results support recent recommendations by the World Health Organization to implement snail control and demonstrate that schistosomiasis elimination can be achieved. The nationwide, high-resolution map of Oncomelania snail habitats in P.R. China will support further efforts to eliminate schistosomiasis.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"10"},"PeriodicalIF":8.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between Loa loa microfilaremia and anatomical hyposplenia in a rural area of the Republic of Congo: a population-based cross-sectional study.
IF 8.1 1区 医学 Pub Date : 2025-02-08 DOI: 10.1186/s40249-025-01277-w
Charlotte Boullé, Elodie Lebredonchel, Jérémy T Campillo, Valentin Dupasquier, Marlhand C Hemilembolo, Sébastien D S Pion, Jean Claude Djontu, Ludovic Rancé, Philippe Souteyrand, François Missamou, Michel Boussinesq, Francine Ntoumi, Cédric B Chesnais

Background: Data suggest excess mortality is associated with loiasis, which is endemic to Central Africa, although the underlying mechanisms remain unknown. We hypothesized that there could be an association between Loa loa microfilarial densities (MFD) and lower spleen volume (SV) due to micro-obstruction linked to circulating microfilariae (mf). This could result in functional hyposplenia and a higher burden of infections. Our objective was to investigate the impact of L. loa MFD and malaria on spleen's bi-dimensional dimensions, volume, and parenchymal lesions.

Methods: We included 981 participants aged 18-88 years in a cross-sectional study conducted in May-June 2022 in the Republic of the Congo. Centralized ultrasonographic examination was performed. The primary outcomes included SV, splenomegaly (cranio-caudal-distance ≥ 13 cm), and anatomical hyposplenia (AH) (SV ≤ 80, ≤ 110 or ≤ 150 cm3). Blood samples were analyzed for L. loa MFD, Plasmodium-PCR, Anti-Plasmodium falciparum-IgG, total IgM, sickle-cell disease status, and hematological abnormalities. Linear and logistic regressions were used to assess these associations.

Results: Among 981 participants, 139 (14.1%) had splenomegaly, and 26 (2.7%) and 175 (17.8%) had SV ≤ 80 and ≤ 150 cm3, respectively. L. loa microfilariae were detected in 353 (35.6%) participants. A gradient effect was observed in each model, with the highest MFD (> 30,000 mf/ml) having the highest adjusted odds ratio of 17.94 (95% CI: 2.91-110.76, P = 0.002), 5.94 (95% CI: 1.40-25.17, P = 0.016), and 5.77 (95% CI: 1.95-17.12, P = 0.002) for SV ≤ 80, 110, and 150 cm3, respectively. Anti-P. falciparum-IgG levels were gradually associated with splenomegaly. Fourteen participants met the criterion for hyper-reactive malarial splenomegaly (HMS). Conversely, higher L. loa MFD was correlated with AH, with an attributable fraction of 25%, and the presence of splenic parenchymal lesions.

Conclusions: This study provides a detailed description of spleen morphology and the factors influencing its size in a rural central African population. It demonstrates a strong association between L. loa MFD and reduced SV, suggesting that loiasis may lead to AH, and potentially to functional hyposplenia, with consequences such as increased susceptibility to bacterial infections. Malaria was associated with splenomegaly, with a figure of HMS consistent with estimates from other African countries.

{"title":"Association between Loa loa microfilaremia and anatomical hyposplenia in a rural area of the Republic of Congo: a population-based cross-sectional study.","authors":"Charlotte Boullé, Elodie Lebredonchel, Jérémy T Campillo, Valentin Dupasquier, Marlhand C Hemilembolo, Sébastien D S Pion, Jean Claude Djontu, Ludovic Rancé, Philippe Souteyrand, François Missamou, Michel Boussinesq, Francine Ntoumi, Cédric B Chesnais","doi":"10.1186/s40249-025-01277-w","DOIUrl":"10.1186/s40249-025-01277-w","url":null,"abstract":"<p><strong>Background: </strong>Data suggest excess mortality is associated with loiasis, which is endemic to Central Africa, although the underlying mechanisms remain unknown. We hypothesized that there could be an association between Loa loa microfilarial densities (MFD) and lower spleen volume (SV) due to micro-obstruction linked to circulating microfilariae (mf). This could result in functional hyposplenia and a higher burden of infections. Our objective was to investigate the impact of L. loa MFD and malaria on spleen's bi-dimensional dimensions, volume, and parenchymal lesions.</p><p><strong>Methods: </strong>We included 981 participants aged 18-88 years in a cross-sectional study conducted in May-June 2022 in the Republic of the Congo. Centralized ultrasonographic examination was performed. The primary outcomes included SV, splenomegaly (cranio-caudal-distance ≥ 13 cm), and anatomical hyposplenia (AH) (SV ≤ 80, ≤ 110 or ≤ 150 cm<sup>3</sup>). Blood samples were analyzed for L. loa MFD, Plasmodium-PCR, Anti-Plasmodium falciparum-IgG, total IgM, sickle-cell disease status, and hematological abnormalities. Linear and logistic regressions were used to assess these associations.</p><p><strong>Results: </strong>Among 981 participants, 139 (14.1%) had splenomegaly, and 26 (2.7%) and 175 (17.8%) had SV ≤ 80 and ≤ 150 cm<sup>3</sup>, respectively. L. loa microfilariae were detected in 353 (35.6%) participants. A gradient effect was observed in each model, with the highest MFD (> 30,000 mf/ml) having the highest adjusted odds ratio of 17.94 (95% CI: 2.91-110.76, P = 0.002), 5.94 (95% CI: 1.40-25.17, P = 0.016), and 5.77 (95% CI: 1.95-17.12, P = 0.002) for SV ≤ 80, 110, and 150 cm<sup>3</sup>, respectively. Anti-P. falciparum-IgG levels were gradually associated with splenomegaly. Fourteen participants met the criterion for hyper-reactive malarial splenomegaly (HMS). Conversely, higher L. loa MFD was correlated with AH, with an attributable fraction of 25%, and the presence of splenic parenchymal lesions.</p><p><strong>Conclusions: </strong>This study provides a detailed description of spleen morphology and the factors influencing its size in a rural central African population. It demonstrates a strong association between L. loa MFD and reduced SV, suggesting that loiasis may lead to AH, and potentially to functional hyposplenia, with consequences such as increased susceptibility to bacterial infections. Malaria was associated with splenomegaly, with a figure of HMS consistent with estimates from other African countries.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"8"},"PeriodicalIF":8.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Global progress, challenges and strategies in eliminating public threat of viral hepatitis.
IF 8.1 1区 医学 Pub Date : 2025-02-08 DOI: 10.1186/s40249-025-01275-y
Sihui Zhang, Fuqiang Cui

Background: The problem caused by viral hepatitis is a major public health challenge faced in the past decade, and the global goal of eliminating viral hepatitis by 2030 is still far away. With the use of hepatitis B vaccine and the launch of new drugs, there are more means to control viral hepatitis and more technologies to prevent, diagnose and treat it. While improving the coverage of vaccine use, drugs for treating hepatitis B are not only becoming more effective, but also decreasing in price. The objective of this article was to explore the urgent issues that need to be addressed in global viral hepatitis with the increasing availability of vaccines and antiviral drugs.

Main text: The updated World Health Organization guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection (2024 edition) and Chinese guidelines for the prevention and treatment of chronic hepatitis B (version 2022) simplify clinical algorithms for the diagnosis, treatment, and monitoring of hepatitis B, expand treatment eligibility criteria, and provide alternative treatment options, which will cover a higher proportion of all hepatitis B surface antigen positive populations. These actions promote the global goal of eliminating the public health hazards of viral hepatitis by 2030. Among the countries that have made remarkable progress in eliminating viral hepatitis policies, the key strategy is to simplify the diagnosis and treatment plan. Furthermore, the World Health Organization has identified 38 priority countries for viral hepatitis. Expand access to viral hepatitis services in these countries.

Conclusions: Regions and countries with the high burden of viral hepatitis still need to take urgent action regarding the new measures proposed by the WHO to achieve the 2030 targets. First, countries must establish a complete public health system aligned with the World Health Organization's strategy. Second, provide effective, people-oriented services and public prevention strategies. Third, prioritize the implementation of health strategies in the 38 identified priority countries. Finally, use complete and measurable data to monitor progress.

{"title":"Global progress, challenges and strategies in eliminating public threat of viral hepatitis.","authors":"Sihui Zhang, Fuqiang Cui","doi":"10.1186/s40249-025-01275-y","DOIUrl":"10.1186/s40249-025-01275-y","url":null,"abstract":"<p><strong>Background: </strong>The problem caused by viral hepatitis is a major public health challenge faced in the past decade, and the global goal of eliminating viral hepatitis by 2030 is still far away. With the use of hepatitis B vaccine and the launch of new drugs, there are more means to control viral hepatitis and more technologies to prevent, diagnose and treat it. While improving the coverage of vaccine use, drugs for treating hepatitis B are not only becoming more effective, but also decreasing in price. The objective of this article was to explore the urgent issues that need to be addressed in global viral hepatitis with the increasing availability of vaccines and antiviral drugs.</p><p><strong>Main text: </strong>The updated World Health Organization guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection (2024 edition) and Chinese guidelines for the prevention and treatment of chronic hepatitis B (version 2022) simplify clinical algorithms for the diagnosis, treatment, and monitoring of hepatitis B, expand treatment eligibility criteria, and provide alternative treatment options, which will cover a higher proportion of all hepatitis B surface antigen positive populations. These actions promote the global goal of eliminating the public health hazards of viral hepatitis by 2030. Among the countries that have made remarkable progress in eliminating viral hepatitis policies, the key strategy is to simplify the diagnosis and treatment plan. Furthermore, the World Health Organization has identified 38 priority countries for viral hepatitis. Expand access to viral hepatitis services in these countries.</p><p><strong>Conclusions: </strong>Regions and countries with the high burden of viral hepatitis still need to take urgent action regarding the new measures proposed by the WHO to achieve the 2030 targets. First, countries must establish a complete public health system aligned with the World Health Organization's strategy. Second, provide effective, people-oriented services and public prevention strategies. Third, prioritize the implementation of health strategies in the 38 identified priority countries. Finally, use complete and measurable data to monitor progress.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"9"},"PeriodicalIF":8.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Environmental, socioeconomic, and sociocultural drivers of monkeypox transmission in the Democratic Republic of the Congo: a One Health perspective.
IF 8.1 1区 医学 Pub Date : 2025-02-07 DOI: 10.1186/s40249-025-01278-9
Guangyu Lu, Zeyin Chong, Enyu Xu, Ce Na, Kaixuan Liu, Liying Chai, Pengpeng Xia, Kai Yang, Guoqiang Zhu, Jinkou Zhao, Olaf Müller

Background: Monkeypox (mpox) is an emerging zoonotic disease that has persistently impacted public health in endemic regions of West and Central Africa for over half a century. The Democratic Republic of the Congo (DRC) remains one of the countries most affected. Understanding the risk factors for disease transmission from a One Health perspective is of great importance in the risk assessment, prevention, and control of zoonotic diseases. Therefore, this study aimed to investigate the risk factors for human mpox transmission at the human-animal-environment interface in the DRC.

Methods: Epidemiological, environmental, socioeconomic, and sociocultural data from the DRC from 2000 to 2015 were obtained from publicly available dataset. Using these data, we applied negative binomial regression model, least absolute shrinkage and selection operator regression model, and principal component analysis (PCA) to identify key environmental, socioeconomic, and sociocultural factors contributing to mpox transmission. Moreover, a grey prediction model GM (1, n) was constructed to predict the epidemic trend of mpox post-2015 and validated using suspected mpox case data in the DRC from 2016 to 2021, sourced from the United States Centers for Disease Control and Prevention.

Results: Between 2000 and 2021, a total of 43,628 suspected mpox cases were reported in the DRC, with a peak of 6216 cases in 2020. From 2016 to 2021, suspected cases accounted for over half (24,379/43,628, 55.9%) of the total reported during the 2000-2021 period. The proportion of primary forest [incidence rate ratio (IRR): 1.023, 95% confidence interval (CI): 1.018-1.027], index of economic well-being (IRR: 1.046, 95% CI: 1.039-1.052), and mean annual precipitation (IRR 1.040, 95% CI: 1.031-1.049) were positively associated with mpox incidence. PCA identified five principal components, explaining 69% of the variance in the environmental, socioeconomic, and sociocultural variables. The first component was characterized by socioeconomic factors. The GM (1, n) model, based on the proportion of primary forest, index of economic well-being, and mean annual precipitation, predicted the epidemic trend (revealed relative error: 2.69).

Conclusions: Both socioeconomic and environmental factors play important roles in mpox transmission. Our study further highlighted the importance of considering the interconnectedness among humans, animals, and the environment, and treating these factors as a whole to explain the transmission and emergence of mpox outbreaks in the DRC according to the One Health concept.

{"title":"Environmental, socioeconomic, and sociocultural drivers of monkeypox transmission in the Democratic Republic of the Congo: a One Health perspective.","authors":"Guangyu Lu, Zeyin Chong, Enyu Xu, Ce Na, Kaixuan Liu, Liying Chai, Pengpeng Xia, Kai Yang, Guoqiang Zhu, Jinkou Zhao, Olaf Müller","doi":"10.1186/s40249-025-01278-9","DOIUrl":"10.1186/s40249-025-01278-9","url":null,"abstract":"<p><strong>Background: </strong>Monkeypox (mpox) is an emerging zoonotic disease that has persistently impacted public health in endemic regions of West and Central Africa for over half a century. The Democratic Republic of the Congo (DRC) remains one of the countries most affected. Understanding the risk factors for disease transmission from a One Health perspective is of great importance in the risk assessment, prevention, and control of zoonotic diseases. Therefore, this study aimed to investigate the risk factors for human mpox transmission at the human-animal-environment interface in the DRC.</p><p><strong>Methods: </strong>Epidemiological, environmental, socioeconomic, and sociocultural data from the DRC from 2000 to 2015 were obtained from publicly available dataset. Using these data, we applied negative binomial regression model, least absolute shrinkage and selection operator regression model, and principal component analysis (PCA) to identify key environmental, socioeconomic, and sociocultural factors contributing to mpox transmission. Moreover, a grey prediction model GM (1, n) was constructed to predict the epidemic trend of mpox post-2015 and validated using suspected mpox case data in the DRC from 2016 to 2021, sourced from the United States Centers for Disease Control and Prevention.</p><p><strong>Results: </strong>Between 2000 and 2021, a total of 43,628 suspected mpox cases were reported in the DRC, with a peak of 6216 cases in 2020. From 2016 to 2021, suspected cases accounted for over half (24,379/43,628, 55.9%) of the total reported during the 2000-2021 period. The proportion of primary forest [incidence rate ratio (IRR): 1.023, 95% confidence interval (CI): 1.018-1.027], index of economic well-being (IRR: 1.046, 95% CI: 1.039-1.052), and mean annual precipitation (IRR 1.040, 95% CI: 1.031-1.049) were positively associated with mpox incidence. PCA identified five principal components, explaining 69% of the variance in the environmental, socioeconomic, and sociocultural variables. The first component was characterized by socioeconomic factors. The GM (1, n) model, based on the proportion of primary forest, index of economic well-being, and mean annual precipitation, predicted the epidemic trend (revealed relative error: 2.69).</p><p><strong>Conclusions: </strong>Both socioeconomic and environmental factors play important roles in mpox transmission. Our study further highlighted the importance of considering the interconnectedness among humans, animals, and the environment, and treating these factors as a whole to explain the transmission and emergence of mpox outbreaks in the DRC according to the One Health concept.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"7"},"PeriodicalIF":8.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine learning for predicting severe dengue in Puerto Rico.
IF 8.1 1区 医学 Pub Date : 2025-02-04 DOI: 10.1186/s40249-025-01273-0
Zachary J Madewell, Dania M Rodriguez, Maile B Thayer, Vanessa Rivera-Amill, Gabriela Paz-Bailey, Laura E Adams, Joshua M Wong

Background: Distinguishing between non-severe and severe dengue is crucial for timely intervention and reducing morbidity and mortality. World Health Organization (WHO)-recommended warning signs offer a practical approach for clinicians but have limited sensitivity and specificity. This study aims to evaluate machine learning (ML) model performance compared to WHO-recommended warning signs in predicting severe dengue among laboratory-confirmed cases in Puerto Rico.

Methods: We analyzed data from Puerto Rico's Sentinel Enhanced Dengue Surveillance System (May 2012-August 2024), using 40 clinical, demographic, and laboratory variables. Nine ML models, including Decision Trees, K-Nearest Neighbors, Naïve Bayes, Support Vector Machines, Artificial Neural Networks, AdaBoost, CatBoost, LightGBM, and XGBoost, were trained using fivefold cross-validation and evaluated with area under the receiver operating characteristic curve (AUC-ROC), sensitivity, and specificity. A subanalysis excluded hemoconcentration and leukopenia to assess performance in resource-limited settings. An AUC-ROC value of 0.5 indicates no discriminative power, while values closer to 1.0 reflect better performance.

Results: Among the 1708 laboratory-confirmed dengue cases, 24.3% were classified as severe. Gradient boosting algorithms achieved the highest predictive performance, with an AUC-ROC of 97.1% (95% CI: 96.0-98.3%) for CatBoost using the full 40-variable feature set. Feature importance analysis identified hemoconcentration (≥ 20% increase during illness or ≥ 20% above baseline for age and sex), leukopenia (white blood cell count < 4000/mm3), and timing of presentation at 4-6 days post-symptom onset as key predictors. When excluding hemoconcentration and leukopenia, the CatBoost AUC-ROC was 96.7% (95% CI: 95.5-98.0%), demonstrating minimal reduction in performance. Individual warning signs like abdominal pain and restlessness had sensitivities of 79.0% and 64.6%, but lower specificities of 48.4% and 59.1%, respectively. Combining ≥ 3 warning signs improved specificity (80.9%) while maintaining moderate sensitivity (78.6%), resulting in an AUC-ROC of 74.0%.

Conclusions: ML models, especially gradient boosting algorithms, outperformed traditional warning signs in predicting severe dengue. Integrating these models into clinical decision-support tools could help clinicians better identify high-risk patients, guiding timely interventions like hospitalization, closer monitoring, or the administration of intravenous fluids. The subanalysis excluding hemoconcentration confirmed the models' applicability in resource-limited settings, where access to laboratory data may be limited.

{"title":"Machine learning for predicting severe dengue in Puerto Rico.","authors":"Zachary J Madewell, Dania M Rodriguez, Maile B Thayer, Vanessa Rivera-Amill, Gabriela Paz-Bailey, Laura E Adams, Joshua M Wong","doi":"10.1186/s40249-025-01273-0","DOIUrl":"10.1186/s40249-025-01273-0","url":null,"abstract":"<p><strong>Background: </strong>Distinguishing between non-severe and severe dengue is crucial for timely intervention and reducing morbidity and mortality. World Health Organization (WHO)-recommended warning signs offer a practical approach for clinicians but have limited sensitivity and specificity. This study aims to evaluate machine learning (ML) model performance compared to WHO-recommended warning signs in predicting severe dengue among laboratory-confirmed cases in Puerto Rico.</p><p><strong>Methods: </strong>We analyzed data from Puerto Rico's Sentinel Enhanced Dengue Surveillance System (May 2012-August 2024), using 40 clinical, demographic, and laboratory variables. Nine ML models, including Decision Trees, K-Nearest Neighbors, Naïve Bayes, Support Vector Machines, Artificial Neural Networks, AdaBoost, CatBoost, LightGBM, and XGBoost, were trained using fivefold cross-validation and evaluated with area under the receiver operating characteristic curve (AUC-ROC), sensitivity, and specificity. A subanalysis excluded hemoconcentration and leukopenia to assess performance in resource-limited settings. An AUC-ROC value of 0.5 indicates no discriminative power, while values closer to 1.0 reflect better performance.</p><p><strong>Results: </strong>Among the 1708 laboratory-confirmed dengue cases, 24.3% were classified as severe. Gradient boosting algorithms achieved the highest predictive performance, with an AUC-ROC of 97.1% (95% CI: 96.0-98.3%) for CatBoost using the full 40-variable feature set. Feature importance analysis identified hemoconcentration (≥ 20% increase during illness or ≥ 20% above baseline for age and sex), leukopenia (white blood cell count < 4000/mm<sup>3</sup>), and timing of presentation at 4-6 days post-symptom onset as key predictors. When excluding hemoconcentration and leukopenia, the CatBoost AUC-ROC was 96.7% (95% CI: 95.5-98.0%), demonstrating minimal reduction in performance. Individual warning signs like abdominal pain and restlessness had sensitivities of 79.0% and 64.6%, but lower specificities of 48.4% and 59.1%, respectively. Combining ≥ 3 warning signs improved specificity (80.9%) while maintaining moderate sensitivity (78.6%), resulting in an AUC-ROC of 74.0%.</p><p><strong>Conclusions: </strong>ML models, especially gradient boosting algorithms, outperformed traditional warning signs in predicting severe dengue. Integrating these models into clinical decision-support tools could help clinicians better identify high-risk patients, guiding timely interventions like hospitalization, closer monitoring, or the administration of intravenous fluids. The subanalysis excluding hemoconcentration confirmed the models' applicability in resource-limited settings, where access to laboratory data may be limited.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"5"},"PeriodicalIF":8.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11796212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Post-COVID-19 resurgence of scabies' cases in the Lazio Region, Italy: a new emerging public health threat?
IF 8.1 1区 医学 Pub Date : 2025-02-04 DOI: 10.1186/s40249-025-01279-8
Martina Spaziante, Alessandro Agresta, Maurizio D'Amato, Gabriella De Carli, Gilda Tonziello, Valentina Vantaggio, Giorgio Nicolò Malatesta, Enrico Girardi, Alessandra Barca, Paola Scognamiglio, Francesco Vairo

Scabies represents a global health issue and in 2017 was added to the World Health Organization's list of neglected tropical diseases. In European and Middle Eastern countries, cases are sporadic while recent surveillance data have pointed out an increasing incidence among vulnerable populations. Regional cases for Lazio, Italy, reported from 2017 to 2023 to the national infectious disease surveillance system were analyzed. In Lazio, just after the coronavirus disease 2019 (COVID-19) pandemic onset, a significant and immediate reduction in the incidence of scabies was recorded (- 79.6%) followed by a progressive and relevant increase (143.4% from 2020 to 2021, 142.3% from 2021 to 2022 and 170.3% from 2022 to 2023). Consistently, the number of scabies outbreaks, after a decrease following the first COVID-19 wave, has progressively increased over time, mainly due to the occurrence of outbreaks in long term facilities (750% from 2020 to 2023). The increased incidence may also be driven by the "pseudo-resistance" phenomenon (under dosed/early-discontinued treatment, suboptimal adherence, reduced drug bioavailability), but also by reduced in-vitro susceptibility to the mainly used scabicides. The rapidly evolving epidemiology of scabies in our country, as documented also in other regions, calls for a comprehensive approach to effectively address the problem.

疥疮是一个全球性的健康问题,2017 年被世界卫生组织列入被忽视的热带疾病名单。在欧洲和中东国家,疥疮病例时有发生,而最近的监测数据表明,易感人群的发病率在不断上升。我们对意大利拉齐奥地区从 2017 年至 2023 年向国家传染病监测系统报告的病例进行了分析。在拉齐奥,2019 年冠状病毒病(COVID-19)大流行刚刚爆发,疥疮发病率就立即大幅下降(-79.6%),随后出现了相关的逐步上升(2020 年至 2021 年为 143.4%,2021 年至 2022 年为 142.3%,2022 年至 2023 年为 170.3%)。疥疮暴发的数量在 COVID-19 第一波后有所减少,但随着时间的推移又逐渐增加,这主要是由于在长期护理设施中暴发(2020 年至 2023 年增加了 750%)。发病率上升的原因可能还包括 "假抗药性 "现象(用药不足/过早停药、依从性不佳、药物生物利用度降低),以及对主要使用的杀疥剂的体外敏感性降低。疥疮流行病学在我国迅速发展,这在其他地区也有记载,因此需要采取综合方法来有效解决这一问题。
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引用次数: 0
An updated systematic review with meta-analysis and meta-regression of the factors associated with human visceral leishmaniasis in the Americas.
IF 8.1 1区 医学 Pub Date : 2025-01-30 DOI: 10.1186/s40249-025-01274-z
Anna Gabryela Sousa Duarte, Guilherme Loureiro Werneck, Sarah de Farias Lelis, Thays Santos Mendonça, Daniela Dias Vasconcelos, Tiago Silveira Gontijo, Álisson Oliveira Dos Santos, Lucas Edel Donato, Vinícius Silva Belo

Background: Human visceral leishmaniasis (VL) is a systemic disease with high case-fatality rates and a widespread distribution. Continuous evaluation of the risk factors for VL is essential to ensure the effective implementation of prevention and control measures. The present study reviews the factors associated with VL in the Americas.

Methods: This systematic review updates a previous 2013 report by including cross-sectional, cohort and case-control studies published between July 2011 and April 2024. Associations between VL and risk factors were analyzed using random-effects meta-analysis, subgroup analysis, and meta-regression models. Studies were classified according to level of evidence using the GRADE approach and the evolution in the quality of investigations was assessed.

Results: Forty-six studies were included in the review and 21 variables were evaluated in the meta-analyses. Combination of all study types revealed that men had greater chances of VL than women, but the association was strong and significant only in case-control studies. Although higher chances of VL in children and in households with dogs or chickens/other fowl were identified in case-control studies, an inverse association was observed in cross-sectional and cohort studies. Higher chances of VL were associated with poor economic/living conditions, individuals living in domiciles with backyards or with seropositive dogs, and individuals with prior contact with infected household members/relatives/neighbors. The level of evidence for associations of VL with sex and age was classified as moderate whilst that for all other associations was either low or very low. The methodological quality of recent studies showed a positive progression but shortcomings were still evident regarding selection criteria and methods of data analysis.

Conclusion: While there is a higher incidence of symptomatic VL among men and children, the likelihood of infection is similar between the groups. There is insufficient evidence to support the claim that the presence of dogs or fowl at the domicile increases the chances of VL. However, socioeconomic and living conditions, as well as previous occurrence of human and canine VL, are influential factors. Future research should be conducted with greater statistical power and using molecular diagnostic techniques, preferably involving cohort studies in diverse Latin American countries.

{"title":"An updated systematic review with meta-analysis and meta-regression of the factors associated with human visceral leishmaniasis in the Americas.","authors":"Anna Gabryela Sousa Duarte, Guilherme Loureiro Werneck, Sarah de Farias Lelis, Thays Santos Mendonça, Daniela Dias Vasconcelos, Tiago Silveira Gontijo, Álisson Oliveira Dos Santos, Lucas Edel Donato, Vinícius Silva Belo","doi":"10.1186/s40249-025-01274-z","DOIUrl":"10.1186/s40249-025-01274-z","url":null,"abstract":"<p><strong>Background: </strong>Human visceral leishmaniasis (VL) is a systemic disease with high case-fatality rates and a widespread distribution. Continuous evaluation of the risk factors for VL is essential to ensure the effective implementation of prevention and control measures. The present study reviews the factors associated with VL in the Americas.</p><p><strong>Methods: </strong>This systematic review updates a previous 2013 report by including cross-sectional, cohort and case-control studies published between July 2011 and April 2024. Associations between VL and risk factors were analyzed using random-effects meta-analysis, subgroup analysis, and meta-regression models. Studies were classified according to level of evidence using the GRADE approach and the evolution in the quality of investigations was assessed.</p><p><strong>Results: </strong>Forty-six studies were included in the review and 21 variables were evaluated in the meta-analyses. Combination of all study types revealed that men had greater chances of VL than women, but the association was strong and significant only in case-control studies. Although higher chances of VL in children and in households with dogs or chickens/other fowl were identified in case-control studies, an inverse association was observed in cross-sectional and cohort studies. Higher chances of VL were associated with poor economic/living conditions, individuals living in domiciles with backyards or with seropositive dogs, and individuals with prior contact with infected household members/relatives/neighbors. The level of evidence for associations of VL with sex and age was classified as moderate whilst that for all other associations was either low or very low. The methodological quality of recent studies showed a positive progression but shortcomings were still evident regarding selection criteria and methods of data analysis.</p><p><strong>Conclusion: </strong>While there is a higher incidence of symptomatic VL among men and children, the likelihood of infection is similar between the groups. There is insufficient evidence to support the claim that the presence of dogs or fowl at the domicile increases the chances of VL. However, socioeconomic and living conditions, as well as previous occurrence of human and canine VL, are influential factors. Future research should be conducted with greater statistical power and using molecular diagnostic techniques, preferably involving cohort studies in diverse Latin American countries.</p>","PeriodicalId":48820,"journal":{"name":"Infectious Diseases of Poverty","volume":"14 1","pages":"4"},"PeriodicalIF":8.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of hemorrhagic fever with renal syndrome associated with meteorological factors in diverse epidemic regions: a nationwide longitudinal study in China. 不同流行地区肾综合征出血热风险与气象因素的相关性:一项中国全国纵向研究
IF 8.1 1区 医学 Pub Date : 2025-01-16 DOI: 10.1186/s40249-024-01272-7
Nan Chang, Wenzhong Huang, Yanlin Niu, Zhihu Xu, Yuan Gao, Tingting Ye, Zihao Wang, Xiaohui Wei, Yuming Guo, Qiyong Liu

Background: Hemorrhagic fever with renal syndrome (HFRS) is a climate-sensitive zoonotic disease that poses a significant public health burden worldwide. While previous studies have established associations between meteorological factors and HFRS incidence, there remains a critical knowledge gap regarding the heterogeneity of these effects across diverse epidemic regions. Addressing this gap is essential for developing region-specific prevention and control strategies. This study conducted a national investigation to examine the associations between meteorological factors and HFRS in three distinct epidemic regions.

Methods: We collected daily meteorological data (temperature and relative humidity) and HFRS incidence cases of 285 cities in China from the Resource and Environment Science and Data Center and the Chinese National Notifiable Infectious Disease Reporting Information System from 2005-2022. Study locations were stratified into three distinct epidemic categories (Rattus-dominant, Apodemus-dominant, and mixed) based on the seasonality of peak incidence. The associations between meteorological variables and HFRS incidence were investigated using a time-stratified case-crossover design combined with distributed lag nonlinear modeling for each epidemic category.

Results: The exposure-response relationships between meteorological factors and HFRS incidence revealed significant heterogeneity across epidemic regions, as evidenced by Cochran's Q test for temperature (Q = 324.40, P < 0.01) and relative humidity (Q = 30.57, P < 0.01). The optimal daily average temperature for HFRS transmission in Rattus-dominant epidemic regions (- 6.6 °C), characterized by spring epidemics, was lower than that observed in Apodemus-dominant epidemic regions (13.7 °C), where primary cases occurred during autumn and winter months. Furthermore, the association between relative humidity and HFRS incidence exhibited as a monotonic negative correlation in Rattus-dominant regions, while Apodemus-dominant regions showed a nonlinear, inverted U-shaped association.

Conclusions: This study highlights the heterogeneous effects of meteorological factors on HFRS incidence across different epidemic regions. Targeted preventive measures should be taken during cold and dry spring days in Rattus-dominant regions, and during warm and moderately humid winter days in Apodemus-dominant regions. In mixed epidemic regions, both scenarios require attention. These findings provide novel scientific evidence for the formulation and implementation of region-specific HFRS prevention policies.

背景:肾综合征出血热(HFRS)是一种气候敏感的人畜共患疾病,在世界范围内造成了重大的公共卫生负担。虽然以前的研究已经确定了气象因素与HFRS发病率之间的关联,但对于这些影响在不同流行地区的异质性,仍然存在重大的知识差距。解决这一差距对于制定针对特定区域的预防和控制战略至关重要。本研究在三个不同的流行地区开展了一项全国调查,以检查气象因素与HFRS之间的关系。方法:收集2005-2022年中国285个城市资源环境科学与数据中心和中国国家法定传染病报告信息系统的每日气象资料(温度、相对湿度)和HFRS发病病例。根据发病率高峰的季节性,将研究地点分为三种不同的流行类别(以家鼠为主、以姬鼠为主和混合)。采用时间分层病例交叉设计,结合每种流行类别的分布滞后非线性建模,研究气象变量与HFRS发病率之间的关系。结果:气象因素与HFRS发病的暴露-反应关系在不同疫区之间存在显著的异质性,温度的Cochran’s Q检验(Q = 324.40, P)证明了这一点。结论:本研究突出了气象因素对不同疫区HFRS发病的异质性影响。在家鼠占优势的地区,应在春季寒冷干燥的季节,在姬鼠占优势的地区,应在冬季温暖湿润的季节,采取针对性的预防措施。在混合流行地区,这两种情况都需要引起注意。这些发现为制定和实施具有区域特异性的HFRS预防政策提供了新的科学依据。
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引用次数: 0
Overexpression of multiple cytochrome P450 genes with and without knockdown resistance mutations confers high resistance to deltamethrin in Culex quinquefasciatus. 致倦库蚊对溴氰菊酯具有高抗性,其细胞色素P450基因的高表达具有或不具有低敲抗性突变。
IF 8.1 1区 医学 Pub Date : 2025-01-13 DOI: 10.1186/s40249-024-01269-2
Saowanee Chamnanya, Benyapa Kiddela, Jassada Saingamsook, Woottichai Nachaiwieng, Nongkran Lumjuan, Pradya Somboon, Jintana Yanola

Background: The cytochrome P450s-mediated metabolic resistance and the target site insensitivity caused by the knockdown resistance (kdr) mutation in the voltage-gated sodium channel (vgsc) gene were the main mechanisms conferring resistance to deltamethrin in Culex quinquefasciatus from Thailand. This study aimed to investigate the expression levels of cytochrome P450 genes and detect mutations of the vgsc gene in deltamethrin-resistant Cx. quinquefasciatus populations in Thailand.

Methods: Two field-collected strains of Cx. quinquefasciatus, Cq_SP and Cq_NiH, were selected with deltamethrin to generate the resistant strains Cq_SP-R and Cq_NiH-R, respectively. Bioassays were tested on larvae and adults of each strain according to WHO methods. Eight cytochrome P450 genes were analyzed for the expression level using quantitative real time-PCR. The cDNA of mosquitoes was amplified and sequenced for four fragments of vgsc gene. The kdr L1014F mutation and the haplotype of the CYP9M10 gene were detected in survivor and dead mosquitoes after exposure to the deltamethrin WHO test paper. Statistical analyses were performed using Fisher's exaction test.

Results: Bioassay tests revealed a significantly higher resistance level in Cq_SP-R than in Cq_NiH-R strains in both larvae and adults. All eight cytochrome P450 genes were significantly overexpressed in larvae of Cq_NiH-R strain compared to the parent and susceptible Cq_Sus strains. The CYP6AA7 and CYP9J34 genes had the highest expression ratios, exceeding 24-fold in Cq_NiH-R larvae. In Cq_SP-R strain, the CYP4H34 and CYP9J34 genes were overexpressed in both stages. The kdr L1014F mutation was found in Cq_SP-R and its parent Cq_SP strains with a significantly higher mutant allele frequency in the survivor mosquitoes than in dead mosquitoes (P < 0.0001). The V240M and novel L925F mutations were found only in Cq_SP-R strain. Heterozygous genotype for the D-Cu( +)/Cu(-) of CYP9M10 gene was detected in Cq_NiH and Cq_NiH-R strains but other strains were mostly homozygous for the Cu(-)/Cu(-).

Conclusions: Overexpression of multiple cytochrome P450 genes alone has a relatively minor impact on resistance. The combined mechanisms of cytochrome P450- and kdr-mediated resistance result in significantly higher resistance to deltamethrin in Cx. quinquefasciatus. This study supports sustainable public health initiatives in Thailand to address the evolving challenges of insecticide resistance.

背景:泰国致倦库蚊对溴氰菊酯产生抗性的主要机制是细胞色素p450s介导的代谢抗性和电压门控钠通道(vgsc)基因敲低抗性(kdr)突变引起的靶位不敏感。本研究旨在研究抗溴氰菊酯Cx细胞色素P450基因的表达水平,并检测vgsc基因的突变。泰国致倦库蚊种群。方法:野外采集的2株Cx菌。用溴氰菊酯对致倦库蚊Cq_SP和Cq_NiH进行筛选,得到Cq_SP- r和Cq_NiH- r抗性菌株。按照世卫组织的方法对每个菌株的幼虫和成虫进行了生物测定。采用实时荧光定量pcr分析8个细胞色素P450基因的表达水平。扩增蚊虫vgsc基因cDNA,并对其进行测序。在接触溴氰菊酯WHO试纸后的存活和死亡蚊子中检测到kdr L1014F突变和CYP9M10基因单倍型。采用Fisher严格检验进行统计分析。结果:Cq_SP-R在幼虫和成虫体内的抗性水平均明显高于Cq_NiH-R。与亲本和敏感菌株Cq_Sus相比,Cq_NiH-R菌株的8个细胞色素P450基因均显著过表达。CYP6AA7和CYP9J34基因在Cq_NiH-R幼虫中表达率最高,超过24倍。在Cq_SP-R菌株中,CYP4H34和CYP9J34基因在两个阶段均过表达。在Cq_SP- r及其亲本Cq_SP株中发现kdr L1014F突变,且存活蚊的突变频率明显高于死亡蚊(P)。结论:单独过表达多个细胞色素P450基因对抗性的影响相对较小。细胞色素P450-和kdr介导的联合抗性机制导致Cx对溴氰菊酯的抗性显著提高。quinquefasciatus。这项研究支持泰国的可持续公共卫生举措,以应对不断演变的杀虫剂耐药性挑战。
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Infectious Diseases of Poverty
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