Pub Date : 2024-11-15DOI: 10.1016/j.actatropica.2024.107472
Mackenzie L Kwak, Shintaro Nakagawa, So Shinya, Paula Andrea Jiménez, Greg Markowsky, Daniel McInnes, Yurie Taya, Shouta M M Nakayama, Mayumi Ishizuka, Nariaki Nonaka, Ryo Nakao
Subtropical Asia has a rich diversity of reptiles and ticks, though the role of reptiles in the sylvatic cycles of medically important ticks in the region is poorly known. Habu vipers (Protobothrops flavoviridis) are widespread and common in the Japanese subtropics but their role as hosts for ticks has not been carefully explored. For 15 months in 2023/24, habu vipers were screened for ticks and were found to be important hosts for immature stages of the tick Amblyomma testudinarium, with a 22% infestation rate. Amblyomma testudinarium was found to have weak attachment site preferences on P. flavoviridis and host body length was found to have no relationship with either the risk of infestation or the tick load in infested snakes. The phenological profile of A. testudinarium was mapped for the first time in the subtropics based on mean tick loads on P. flavoviridis and historical flagging data. March-April were identified as the period of highest activity, May to July was a period of declining activity, August-September was a period of almost complete inactivity, and October to February was a periods of increasing activity. The role of habu vipers in the sylvatic cycle of A. testudinarium in subtropical Asia is discussion. Additionally, the potential of habu vipers to serve as reservoirs of pathogens or as dilution hosts is also explored.
{"title":"Habu vipers (Protobothrops flavoviridis) are an overlooked but important reservoir of the zoonotic tick Amblyomma testudinarium (Acari: Ixodidae) in subtropical Asia.","authors":"Mackenzie L Kwak, Shintaro Nakagawa, So Shinya, Paula Andrea Jiménez, Greg Markowsky, Daniel McInnes, Yurie Taya, Shouta M M Nakayama, Mayumi Ishizuka, Nariaki Nonaka, Ryo Nakao","doi":"10.1016/j.actatropica.2024.107472","DOIUrl":"https://doi.org/10.1016/j.actatropica.2024.107472","url":null,"abstract":"<p><p>Subtropical Asia has a rich diversity of reptiles and ticks, though the role of reptiles in the sylvatic cycles of medically important ticks in the region is poorly known. Habu vipers (Protobothrops flavoviridis) are widespread and common in the Japanese subtropics but their role as hosts for ticks has not been carefully explored. For 15 months in 2023/24, habu vipers were screened for ticks and were found to be important hosts for immature stages of the tick Amblyomma testudinarium, with a 22% infestation rate. Amblyomma testudinarium was found to have weak attachment site preferences on P. flavoviridis and host body length was found to have no relationship with either the risk of infestation or the tick load in infested snakes. The phenological profile of A. testudinarium was mapped for the first time in the subtropics based on mean tick loads on P. flavoviridis and historical flagging data. March-April were identified as the period of highest activity, May to July was a period of declining activity, August-September was a period of almost complete inactivity, and October to February was a periods of increasing activity. The role of habu vipers in the sylvatic cycle of A. testudinarium in subtropical Asia is discussion. Additionally, the potential of habu vipers to serve as reservoirs of pathogens or as dilution hosts is also explored.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107472"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leishmaniasis is a neglected tropical disease and is one of the major causes of mortality in poverty-stricken areas. A limited chemotherapeutics arsenal is available to tackle this deadly infection. Thus, identifying novel potent scaffolds using innovative strategies is the need of the hour. High-throughput screening (HTS) is a critical technique that can accelerate the process of drug discovery by evaluating millions of drug-like molecules using various automation tools and biological assays. In the present study, we have employed the HTS strategy to identify potent hits against Leishmania donovani sterol C-24 methyltransferase (LdSMT) from the in-house ChemBridge library. Firstly, a robust dataset was prepared with previously reported sterol C-24 methyltransferase inhibitors, belonging to diverse structural classes. Then, ligand-based virtual screening using similarity search was performed to screen the ChemBridge library having ∼20,000 molecules. This computational approach yielded 81 candidate compounds, which were selected for further molecular docking and biological evaluation. Anti-leishmanial assays revealed that out of 81 molecules, seven showed potential parasitic killing. Three molecules namely IIIM-CB-14, IIIM-CB-29, and IIIM-CB-45 were the most potent ones with 50% inhibitory concentration (IC50) of 5.76, 8.08, and 10.64 µg/mL, respectively. SEM analyses suggest that these potent hits cause considerable morphological alterations. ADME studies of the potent hit molecules indicate that all the hits have considerable drug-likeness properties. Further, molecular dynamics studies were also performed to check the stable confirmation of LdSMT protein with the top two hits (IIIM-CB-14 and IIIM-CB-45). Thus, the present study harnesses computational and experimental approaches to unravel potent anti-leishmanial scaffolds.
{"title":"Harnessing computational and experimental approaches to identify potent hits against Leishmania donovani sterol C-24 methyltransferase from ChemBridge library.","authors":"Diksha Kumari, Tashi Palmo, Somdutt Mujwar, Kuljit Singh","doi":"10.1016/j.actatropica.2024.107473","DOIUrl":"https://doi.org/10.1016/j.actatropica.2024.107473","url":null,"abstract":"<p><p>Leishmaniasis is a neglected tropical disease and is one of the major causes of mortality in poverty-stricken areas. A limited chemotherapeutics arsenal is available to tackle this deadly infection. Thus, identifying novel potent scaffolds using innovative strategies is the need of the hour. High-throughput screening (HTS) is a critical technique that can accelerate the process of drug discovery by evaluating millions of drug-like molecules using various automation tools and biological assays. In the present study, we have employed the HTS strategy to identify potent hits against Leishmania donovani sterol C-24 methyltransferase (LdSMT) from the in-house ChemBridge library. Firstly, a robust dataset was prepared with previously reported sterol C-24 methyltransferase inhibitors, belonging to diverse structural classes. Then, ligand-based virtual screening using similarity search was performed to screen the ChemBridge library having ∼20,000 molecules. This computational approach yielded 81 candidate compounds, which were selected for further molecular docking and biological evaluation. Anti-leishmanial assays revealed that out of 81 molecules, seven showed potential parasitic killing. Three molecules namely IIIM-CB-14, IIIM-CB-29, and IIIM-CB-45 were the most potent ones with 50% inhibitory concentration (IC<sub>50</sub>) of 5.76, 8.08, and 10.64 µg/mL, respectively. SEM analyses suggest that these potent hits cause considerable morphological alterations. ADME studies of the potent hit molecules indicate that all the hits have considerable drug-likeness properties. Further, molecular dynamics studies were also performed to check the stable confirmation of LdSMT protein with the top two hits (IIIM-CB-14 and IIIM-CB-45). Thus, the present study harnesses computational and experimental approaches to unravel potent anti-leishmanial scaffolds.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107473"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.actatropica.2024.107474
Julieta A Achaga, Darío Vezzani
Estimating the abundance of immature mosquitoes in discarded water-filled tyres is a laborious task due to their shape and size. Our objective was to develop a procedure that allows, by counting individuals in a water sample, to estimate their total abundance. Polynomial functions linking water column height and water volume were fitted for five tyre categories (from cars to tractors) and horizontal/vertical storage positions. A total of 358 discarded water-filled tyres were then surveyed using this method in 16 piles of tyres in temperate Argentina. Tyre capacity was greater in vertical than horizontal position, reaching a maximum of 95.6 L in tractor tyres. In contrast, the volume of water retained under field conditions showed the opposite pattern, being greater in horizontal tyres. Water volume increased significantly across tyre categories in both horizontal (J-T=7306, p<0.001) and vertical (J-T=10792, p<0.001) positions. Most infested tyres (n=150) showed low abundances and a few extremely high values, both for all mosquito species grouped and for Culex pipiens and Aedes aegypti separately. The median abundance of mosquitoes per infested tyre was 35, decreasing to 30 for Cx. pipiens and 17 for Ae. aegypti. These values increased significantly across tyre categories for mosquitoes (J-T=5525, p<0.001) and Cx. pipiens (J-T=2275, p<0.05), but not for Ae. aegypti (J-T=1526, p=0.472). The comparison between vertical and horizontal positions was not significant for both vector species. Our methodological approach could be particularly useful in research addressing the assessment of disease risk associated with mosquito productivity.
{"title":"A methodological proposal to estimate the total abundance of immature mosquitoes in discarded tyres: Aedes aegypti and Culex pipiens as study cases.","authors":"Julieta A Achaga, Darío Vezzani","doi":"10.1016/j.actatropica.2024.107474","DOIUrl":"https://doi.org/10.1016/j.actatropica.2024.107474","url":null,"abstract":"<p><p>Estimating the abundance of immature mosquitoes in discarded water-filled tyres is a laborious task due to their shape and size. Our objective was to develop a procedure that allows, by counting individuals in a water sample, to estimate their total abundance. Polynomial functions linking water column height and water volume were fitted for five tyre categories (from cars to tractors) and horizontal/vertical storage positions. A total of 358 discarded water-filled tyres were then surveyed using this method in 16 piles of tyres in temperate Argentina. Tyre capacity was greater in vertical than horizontal position, reaching a maximum of 95.6 L in tractor tyres. In contrast, the volume of water retained under field conditions showed the opposite pattern, being greater in horizontal tyres. Water volume increased significantly across tyre categories in both horizontal (J-T=7306, p<0.001) and vertical (J-T=10792, p<0.001) positions. Most infested tyres (n=150) showed low abundances and a few extremely high values, both for all mosquito species grouped and for Culex pipiens and Aedes aegypti separately. The median abundance of mosquitoes per infested tyre was 35, decreasing to 30 for Cx. pipiens and 17 for Ae. aegypti. These values increased significantly across tyre categories for mosquitoes (J-T=5525, p<0.001) and Cx. pipiens (J-T=2275, p<0.05), but not for Ae. aegypti (J-T=1526, p=0.472). The comparison between vertical and horizontal positions was not significant for both vector species. Our methodological approach could be particularly useful in research addressing the assessment of disease risk associated with mosquito productivity.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107474"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-14DOI: 10.1016/j.actatropica.2024.107469
Juan C Hernandez-Valencia, Paola Muñoz-Laiton, Giovan F Gómez, Margarita M Correa
The characterization of non-retroviral integrated RNA virus sequences (NIRVS) in mosquitoes has emerged as a significant area of research that could yield insight into virus-host interactions. This study aimed to characterize NIRVS in the Anopheles darlingi reference genome and identify putative transcribed NIRVS in field-collected mosquitoes from Colombia. The An. darlingi reference genome was analyzed to identify and characterize NIRVS by conducting a BLAST query with all the virus sequences previously identified in arthropods available in the NCBI-virus repository. In addition, An. darlingi field-collected mosquitoes were examined for NIRVS using a metatranscriptomic approach. As a result, 44 NIRVS were identified in the An. darlingi genome, constituting integrations of negative single-stranded RNA viruses (ssRNA-) from the families Rhabdoviridae, Chuviridae and Phasmaviridae, and integrations of double-stranded RNA viruses (dsRNA) from the families Partitiviridae and Sedoreoviridae. These NIRVS were not randomly distributed but clustered in specific regions of the genome enriched with BEL/Pao and Ty3/Gypsy long terminal repeat elements. Furthermore, putative NIRVS-like sequences were present in the transcriptomic data from all the Colombian An. darlingi natural populations. This study is significant as it represents the first identification of NIRVS in the most important malaria vector of the Neotropics. The findings help in understanding the intricate relationship between the mosquito and its virome, and the regulation of viruses' mechanisms in the Anopheles genus.
{"title":"Evidence of endogenous Non-retroviral RNA Virus Sequences into the genome and transcriptome of the malaria vector Anopheles darlingi.","authors":"Juan C Hernandez-Valencia, Paola Muñoz-Laiton, Giovan F Gómez, Margarita M Correa","doi":"10.1016/j.actatropica.2024.107469","DOIUrl":"https://doi.org/10.1016/j.actatropica.2024.107469","url":null,"abstract":"<p><p>The characterization of non-retroviral integrated RNA virus sequences (NIRVS) in mosquitoes has emerged as a significant area of research that could yield insight into virus-host interactions. This study aimed to characterize NIRVS in the Anopheles darlingi reference genome and identify putative transcribed NIRVS in field-collected mosquitoes from Colombia. The An. darlingi reference genome was analyzed to identify and characterize NIRVS by conducting a BLAST query with all the virus sequences previously identified in arthropods available in the NCBI-virus repository. In addition, An. darlingi field-collected mosquitoes were examined for NIRVS using a metatranscriptomic approach. As a result, 44 NIRVS were identified in the An. darlingi genome, constituting integrations of negative single-stranded RNA viruses (ssRNA-) from the families Rhabdoviridae, Chuviridae and Phasmaviridae, and integrations of double-stranded RNA viruses (dsRNA) from the families Partitiviridae and Sedoreoviridae. These NIRVS were not randomly distributed but clustered in specific regions of the genome enriched with BEL/Pao and Ty3/Gypsy long terminal repeat elements. Furthermore, putative NIRVS-like sequences were present in the transcriptomic data from all the Colombian An. darlingi natural populations. This study is significant as it represents the first identification of NIRVS in the most important malaria vector of the Neotropics. The findings help in understanding the intricate relationship between the mosquito and its virome, and the regulation of viruses' mechanisms in the Anopheles genus.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107469"},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.actatropica.2024.107467
Chinazom Enukoha , Asghar Talbalaghi , Sahar Hassandoust , Fabio Fossati , Marco Bazzoni , Simone Parisato , David Puccioni , Laura Erbetta , Peyman Ghaffari
The effect of unprecedented climate change conditions on the environment has attracted the attention of experts from various disciplines who wish to predict its evolution. This is due to its interaction with population health and people's quality of life. The emergence of vector-borne diseases (VBD) in Europe, particularly caused by invasive mosquitoes, has resulted in autochthonous transmission of Dengue and Chikungunya virus cases. In this contribution, we delve into the significant decline in the population of tiger mosquitoes and the noticeable reduction in their size, related to the changes that occur often in years with low rainfall and high temperatures during the summer months. This change can be traced to the morphology of the species, which has been analysed in this work and related to the possible enhanced transmission efficiency and susceptibility of vectors to VBD dissemination. Due to the greater susceptibility to pathogen replication and subsequent transmission of the pathogens to a host during blood feeding, these morphologically distinct species relatively seem to be an efficient vector. The relationship between the sizes of studied mosquitoes and rainfall levels requires more research by mathematical epidemiologists.
{"title":"Interplay of climate change with physiological changes in adult Aedes albopictus","authors":"Chinazom Enukoha , Asghar Talbalaghi , Sahar Hassandoust , Fabio Fossati , Marco Bazzoni , Simone Parisato , David Puccioni , Laura Erbetta , Peyman Ghaffari","doi":"10.1016/j.actatropica.2024.107467","DOIUrl":"10.1016/j.actatropica.2024.107467","url":null,"abstract":"<div><div>The effect of unprecedented climate change conditions on the environment has attracted the attention of experts from various disciplines who wish to predict its evolution. This is due to its interaction with population health and people's quality of life. The emergence of vector-borne diseases (VBD) in Europe, particularly caused by invasive mosquitoes, has resulted in autochthonous transmission of Dengue and Chikungunya virus cases. In this contribution, we delve into the significant decline in the population of tiger mosquitoes and the noticeable reduction in their size, related to the changes that occur often in years with low rainfall and high temperatures during the summer months. This change can be traced to the morphology of the species, which has been analysed in this work and related to the possible enhanced transmission efficiency and susceptibility of vectors to VBD dissemination. Due to the greater susceptibility to pathogen replication and subsequent transmission of the pathogens to a host during blood feeding, these morphologically distinct species relatively seem to be an efficient vector. The relationship between the sizes of studied mosquitoes and rainfall levels requires more research by mathematical epidemiologists.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"260 ","pages":"Article 107467"},"PeriodicalIF":2.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.actatropica.2024.107468
Nouman Javed, Adam J López-Denman, Prasad N Paradkar, Asim Bhatti
Accurate counting of mosquito larval populations is essential for maintaining optimal conditions and population control within rearing facilities, assessing disease transmission risks, and implementing effective vector control measures. While existing methods for counting mosquito larvae have faced challenges such as the impact on larval mortality rate, multiple parameters adjustment and limitations in availability and affordability, recent advancements in artificial intelligence, particularly in AI-driven visual analysis, hold promise for addressing these issues. Here, we introduce LarvaeCountAI, an open-source convolutional neural network (CNN)-based tool designed to automatically count Culex annulirostris mosquito larvae from videos captured in laboratory environments. LarvaeCountAI does not require videos to be recorded using an advanced setup; it can count larvae with high accuracy from videos captured using a simple setup mainly consisting of a camera and commonly used plastic trays. Using the videos enables LarvaeCountAI to capitalise on the continuous movement of larvae, enhancing the likelihood of accurately counting a greater number of larvae. LarvaeCountAI adopts a non-invasive approach, where larvae are simply placed in trays and imaged, minimising any potential impact on larval mortality. This approach addresses the limitations associated with previous methods involving mechanical machines, which often increase the risk of larval mortality as larvae pass through multiple sections for counting purposes. The performance of LarvaeCountAI was tested using 10 video samples. Validation results demonstrated the excellent performance of LarvaeCountAI, with an accuracy ranging from 96.25 % to 99.13 % across 10 test videos and an average accuracy of 97.88 %. LarvaeCountAI represents a remarkable advancement in mosquito surveillance technology, offering a robust and efficient solution for monitoring larval populations. LarvaeCountAI can contribute to developing effective strategies for reducing disease transmission and safeguarding public health by providing timely and accurate data on mosquito larvae abundance.
{"title":"LarvaeCountAI: a robust convolutional neural network-based tool for accurately counting the larvae of Culex annulirostris mosquitoes.","authors":"Nouman Javed, Adam J López-Denman, Prasad N Paradkar, Asim Bhatti","doi":"10.1016/j.actatropica.2024.107468","DOIUrl":"10.1016/j.actatropica.2024.107468","url":null,"abstract":"<p><p>Accurate counting of mosquito larval populations is essential for maintaining optimal conditions and population control within rearing facilities, assessing disease transmission risks, and implementing effective vector control measures. While existing methods for counting mosquito larvae have faced challenges such as the impact on larval mortality rate, multiple parameters adjustment and limitations in availability and affordability, recent advancements in artificial intelligence, particularly in AI-driven visual analysis, hold promise for addressing these issues. Here, we introduce LarvaeCountAI, an open-source convolutional neural network (CNN)-based tool designed to automatically count Culex annulirostris mosquito larvae from videos captured in laboratory environments. LarvaeCountAI does not require videos to be recorded using an advanced setup; it can count larvae with high accuracy from videos captured using a simple setup mainly consisting of a camera and commonly used plastic trays. Using the videos enables LarvaeCountAI to capitalise on the continuous movement of larvae, enhancing the likelihood of accurately counting a greater number of larvae. LarvaeCountAI adopts a non-invasive approach, where larvae are simply placed in trays and imaged, minimising any potential impact on larval mortality. This approach addresses the limitations associated with previous methods involving mechanical machines, which often increase the risk of larval mortality as larvae pass through multiple sections for counting purposes. The performance of LarvaeCountAI was tested using 10 video samples. Validation results demonstrated the excellent performance of LarvaeCountAI, with an accuracy ranging from 96.25 % to 99.13 % across 10 test videos and an average accuracy of 97.88 %. LarvaeCountAI represents a remarkable advancement in mosquito surveillance technology, offering a robust and efficient solution for monitoring larval populations. LarvaeCountAI can contribute to developing effective strategies for reducing disease transmission and safeguarding public health by providing timely and accurate data on mosquito larvae abundance.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107468"},"PeriodicalIF":2.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.actatropica.2024.107465
Iva Benvin , Daniel Fitz , Vesna Mojčec Perko , Maja Maurić Maljković , Vlasta Đurić , Josipa Habuš , Zrinka Štritof , Matko Perharić , Suzana Hađina , Iva Zečević , Nenad Turk
Leptospirosis, a globally re-emerging zoonosis caused by pathogenic Leptospira spp., poses a significant threat to public health. Leptospirosis in cats is often neglected due to its high underdiagnosis. Therefore, the role of cats in disease transmission and bacterial maintenance in the environment remains unclear. For this study, 54 serum samples, 54 urine samples and 27 EDTA-anticoagulated blood samples from pet cats presenting to the Veterinary Teaching Hospital due to health problems were used. The serum samples were tested for antibodies against 12 pathogenic serovars of Leptospira spp. using the microscopic agglutination test (MAT). EDTA-anticoagulated blood and urine samples were tested for the lipL32 gene of pathogenic Leptospira spp. by conventional (PCR) and real-time (qPCR) polymerase chain reaction. Agglutinating antibodies were detected in 18.52% (10/54) of the sera with a titre range of 1:50 to 1:12800. The most common serogroup was Pomona, followed by Sejroe, Icterohaemorrhagiae, Australis and Javanica. Leptospira spp. DNA was found in 1.85% (1/54) of the urine samples, while all EDTA-anticoagulated blood samples were negative. A statistically significant difference in seropositivity regarding lifestyle was found between outdoor/indoor and indoor-only cats, while the presence of another cat in the household significantly increased the likelihood of seropositivity. Cats with immunocompromising conditions showed a significantly increased risk of seropositivity, especially those undergoing immunosuppressive treatment. In addition, respiratory signs and changes in lung structure associated with the presence of leptospiral antibodies, and these cats were more likely to be infected with the Pomona serogroup. Moreover, cats with anaemia, leucocytosis, and thrombocytopenia were significantly more likely to have antibodies against Leptospira spp., while seropositive cats had significantly lower urine-specific gravity compared to seronegative cats. The results underline the importance of raising awareness of feline leptospirosis in veterinary care and recognising pet cats as potential carriers of leptospires. Further research is needed to clarify the specific role of the Pomona serogroup as a potentially highly evolutionary drifting serogroup in terms of pathogenicity and to clarify the zoonotic potential of infected cats, which is crucial for the implementation of effective public health measures and veterinary interventions.
{"title":"Insights into Leptospira spp. infection in pet cats in Croatia: Clinical, serological and molecular findings with emphasis on the potential important role of serogroup Pomona","authors":"Iva Benvin , Daniel Fitz , Vesna Mojčec Perko , Maja Maurić Maljković , Vlasta Đurić , Josipa Habuš , Zrinka Štritof , Matko Perharić , Suzana Hađina , Iva Zečević , Nenad Turk","doi":"10.1016/j.actatropica.2024.107465","DOIUrl":"10.1016/j.actatropica.2024.107465","url":null,"abstract":"<div><div>Leptospirosis, a globally re-emerging zoonosis caused by pathogenic <em>Leptospira</em> spp., poses a significant threat to public health. Leptospirosis in cats is often neglected due to its high underdiagnosis. Therefore, the role of cats in disease transmission and bacterial maintenance in the environment remains unclear. For this study, 54 serum samples, 54 urine samples and 27 EDTA-anticoagulated blood samples from pet cats presenting to the Veterinary Teaching Hospital due to health problems were used. The serum samples were tested for antibodies against 12 pathogenic serovars of <em>Leptospira</em> spp. using the microscopic agglutination test (MAT). EDTA-anticoagulated blood and urine samples were tested for the <em>lipL32</em> gene of pathogenic <em>Leptospira</em> spp. by conventional (PCR) and real-time (qPCR) polymerase chain reaction. Agglutinating antibodies were detected in 18.52% (10/54) of the sera with a titre range of 1:50 to 1:12800. The most common serogroup was Pomona, followed by Sejroe, Icterohaemorrhagiae, Australis and Javanica. <em>Leptospira</em> spp. DNA was found in 1.85% (1/54) of the urine samples, while all EDTA-anticoagulated blood samples were negative. A statistically significant difference in seropositivity regarding lifestyle was found between outdoor/indoor and indoor-only cats, while the presence of another cat in the household significantly increased the likelihood of seropositivity. Cats with immunocompromising conditions showed a significantly increased risk of seropositivity, especially those undergoing immunosuppressive treatment. In addition, respiratory signs and changes in lung structure associated with the presence of leptospiral antibodies, and these cats were more likely to be infected with the Pomona serogroup. Moreover, cats with anaemia, leucocytosis, and thrombocytopenia were significantly more likely to have antibodies against <em>Leptospira</em> spp., while seropositive cats had significantly lower urine-specific gravity compared to seronegative cats. The results underline the importance of raising awareness of feline leptospirosis in veterinary care and recognising pet cats as potential carriers of leptospires. Further research is needed to clarify the specific role of the Pomona serogroup as a potentially highly evolutionary drifting serogroup in terms of pathogenicity and to clarify the zoonotic potential of infected cats, which is crucial for the implementation of effective public health measures and veterinary interventions.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"260 ","pages":"Article 107465"},"PeriodicalIF":2.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.actatropica.2024.107461
Xiaoyuan Wei , Pallavi Malla , Zenglei Wang , Zhaoqing Yang , Yaming Cao , Chengqi Wang , Liwang Cui
This study aimed to assess the baseline genetic diversity of the Plasmodium vivax population in an endemic area of northeast Myanmar at the onset of the malaria elimination campaign in the Greater Mekong Subregion. We genotyped 125 P vivax clinical samples at two merozoite surface protein loci, PvMSP1 and PvMSP3α, by amplicon deep sequencing. Our study revealed that the parasite population in this region was highly diverse, identifying 60 PvMSP1 and 98 PvMSP3α haplotypes, with haplotype diversity of 0.929 and 0.944, respectively. Remarkably, 97.6 % (122/125) of the patients harbored multiclonal infections with a mean multiplicity of infection of 4.18, indicating a relatively high transmission intensity. Neutrality tests and network analysis suggested a recent parasite population expansion, consistent with the concurrent malaria outbreak in the region. These findings underscore the existence of a highly diverse P. vivax population at the China-Myanmar border, highlighting the need for effective malaria control strategies to achieve the goal of regional malaria elimination.
{"title":"Genetic diversity of Plasmodium vivax population in northeast Myanmar assessed by amplicon sequencing of PvMSP1 and PvMSP3α","authors":"Xiaoyuan Wei , Pallavi Malla , Zenglei Wang , Zhaoqing Yang , Yaming Cao , Chengqi Wang , Liwang Cui","doi":"10.1016/j.actatropica.2024.107461","DOIUrl":"10.1016/j.actatropica.2024.107461","url":null,"abstract":"<div><div>This study aimed to assess the baseline genetic diversity of the <em>Plasmodium vivax</em> population in an endemic area of northeast Myanmar at the onset of the malaria elimination campaign in the Greater Mekong Subregion. We genotyped 125 <em>P vivax</em> clinical samples at two merozoite surface protein loci, <em>PvMSP1</em> and <em>PvMSP3α</em>, by amplicon deep sequencing. Our study revealed that the parasite population in this region was highly diverse, identifying 60 <em>PvMSP1</em> and 98 <em>PvMSP3α</em> haplotypes, with haplotype diversity of 0.929 and 0.944, respectively. Remarkably, 97.6 % (122/125) of the patients harbored multiclonal infections with a mean multiplicity of infection of 4.18, indicating a relatively high transmission intensity. Neutrality tests and network analysis suggested a recent parasite population expansion, consistent with the concurrent malaria outbreak in the region. These findings underscore the existence of a highly diverse <em>P. vivax</em> population at the China-Myanmar border, highlighting the need for effective malaria control strategies to achieve the goal of regional malaria elimination.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"260 ","pages":"Article 107461"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.actatropica.2024.107464
Chunhui Hu , Xueping Zhong , Chaoqun Li , Haiying Yan
Based on the supersaturation theory, this study devised two albendazole (ABZ) salt-polymer complexes that enhance the oral bioavailability and efficacy of secondary hepatic alveolar echinococcosis (HAE) in rats. Solid characteristics, microstructure, and stability of ABZ benzenesulfonate (ABZ-BSA) and ABZ methanesulfonate (ABZ-MSA) were evaluated. The equilibrium solubility and intrinsic dissolution rate of salt were measured across different pH environments to determine its potential for generating supersaturation. Polymer crystallization inhibitors were subsequently introduced to assess their impact on sustaining supersaturation. The pharmacokinetics and anti-echinococcosis effects of ABZ were evaluated in healthy SD and HAE rats. The characteristic peaks corresponding to amino acid esters and benzimidazole in the ABZ salt structure either shifted or disappeared, corroborated by PXRD, signifying successful ABZ salt preparation. Furthermore, reductions in the melting point and enthalpy of the salts were observed, along with discernible differences in microstructure compared to ABZ. The drug salts exhibited a significant increase in apparent solubility and intrinsic dissolution rate of ABZ, thus laying the groundwork for supersaturation. Stability assessments indicated that salts were susceptible to moisture absorption, necessitating stringent humidity control measures. Notably, HPMC-AS demonstrated promising capabilities in sustaining supersaturation. Finally, pharmacokinetic analyses revealed a substantial increase in the AUC of ABZ-BSA-H and ABZ-MSA-H by 7.6 and 20.3 times, respectively, compared to ABZ in vivo. After a 30-day once-daily oral administration of the Salts and ABZ to SD rats with hepatic alveolar echinococcosis, the ABZ-BSA-H and ABZ-MSA-H formulation demonstrated a cysts inhibition effect 9.2-fold and 15.3-fold greater than that of ABZ. The salt-HPMC-AS complex could potentially be developed into an improved anti-AE drug therapy. Therefore, the salt-HPMC-AS complex could be developed into an enhanced anti-AE drug therapy.
{"title":"Supersaturated drug delivery system of albendazole salt-polymer complex for improving oral bioavailability and efficacy anti-secondary E. multilocularis","authors":"Chunhui Hu , Xueping Zhong , Chaoqun Li , Haiying Yan","doi":"10.1016/j.actatropica.2024.107464","DOIUrl":"10.1016/j.actatropica.2024.107464","url":null,"abstract":"<div><div>Based on the supersaturation theory, this study devised two albendazole (ABZ) salt-polymer complexes that enhance the oral bioavailability and efficacy of secondary hepatic alveolar echinococcosis (HAE) in rats. Solid characteristics, microstructure, and stability of ABZ benzenesulfonate (ABZ-BSA) and ABZ methanesulfonate (ABZ-MSA) were evaluated. The equilibrium solubility and intrinsic dissolution rate of salt were measured across different pH environments to determine its potential for generating supersaturation. Polymer crystallization inhibitors were subsequently introduced to assess their impact on sustaining supersaturation. The pharmacokinetics and anti-echinococcosis effects of ABZ were evaluated in healthy SD and HAE rats. The characteristic peaks corresponding to amino acid esters and benzimidazole in the ABZ salt structure either shifted or disappeared, corroborated by PXRD, signifying successful ABZ salt preparation. Furthermore, reductions in the melting point and enthalpy of the salts were observed, along with discernible differences in microstructure compared to ABZ. The drug salts exhibited a significant increase in apparent solubility and intrinsic dissolution rate of ABZ, thus laying the groundwork for supersaturation. Stability assessments indicated that salts were susceptible to moisture absorption, necessitating stringent humidity control measures. Notably, HPMC-AS demonstrated promising capabilities in sustaining supersaturation. Finally, pharmacokinetic analyses revealed a substantial increase in the AUC of ABZ-BSA-H and ABZ-MSA-H by 7.6 and 20.3 times, respectively, compared to ABZ <em>in vivo</em>. After a 30-day once-daily oral administration of the Salts and ABZ to SD rats with hepatic alveolar echinococcosis, the ABZ-BSA-H and ABZ-MSA-H formulation demonstrated a cysts inhibition effect 9.2-fold and 15.3-fold greater than that of ABZ. The salt-HPMC-AS complex could potentially be developed into an improved anti-AE drug therapy. Therefore, the salt-HPMC-AS complex could be developed into an enhanced anti-AE drug therapy.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"260 ","pages":"Article 107464"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.actatropica.2024.107471
Fadwa M Arafa, Nehal Nassef Hezema, Ateyatallah Aljuhani, Mohamed R Aouad, Mohamed Hagar, Ahmed Zakaria, Nadjet Rezki, Marwa M Shaaban, Sara Ahmed Abdel Salam
Toxoplasmosis remains a challenge for both public health and animal husbandry which created a constant demand to develop novel compounds using innovative methods. To join this relentless quest for an ideal chemotherapeutic agent, herein, we developed newly synthesized isatin-1,2,3-triazole derivatives. Three compounds (5a, 5b and 5c) were synthesized, characterized, and loaded on chitosan nanoparticles (CNPs) and then evaluated accordingly. Initially, a molecular docking study was carried out which revealed the effective interaction with the target enzymes; purine nucleoside phosphorylase (PNPase) and T. gondii calcium-dependent protein kinase-1 (TgCDPK1). This was further substantiated by in vivo evaluation of the three compounds (5a-c) and their nanoformulae (5a-CNPs, 5b-CNPs, and 5c-CNPs) against acute Toxoplasma gondii infection in murine model. It is worthy of note that all tested compounds and their nanoformulae produced a significant reduction of parasite burden in both peritoneal fluid and liver impression smear and profound ultrastructural alterations, detected by scanning electron microscopy, compared to the infected non-treated control. The nanoformula 5c-CNPs yielded the most outstanding results with the highest tachyzoite reduction percentage in both peritoneal fluid (98.1%) and liver impression smear (95.3%). Furthermore, the serum levels of liver enzymes (aspartate transaminase (AST) and alanine transaminase (ALT), and renal function tests (urea and creatinine) in mice were within normal limits which makes them more appealing candidates with proven safety. To the best of our knowledge, the present work is the first in silico and in vivo study proving the anti-Toxoplasma effect of isatin-1,2,3- triazoles which paves the way for further development of isatin and triazole-based leads for the treatment of toxoplasmosis.
{"title":"Isatin-1,2,3-triazole derivatives: synthesis, molecular docking and evaluation against acute experimental toxoplasmosis.","authors":"Fadwa M Arafa, Nehal Nassef Hezema, Ateyatallah Aljuhani, Mohamed R Aouad, Mohamed Hagar, Ahmed Zakaria, Nadjet Rezki, Marwa M Shaaban, Sara Ahmed Abdel Salam","doi":"10.1016/j.actatropica.2024.107471","DOIUrl":"https://doi.org/10.1016/j.actatropica.2024.107471","url":null,"abstract":"<p><p>Toxoplasmosis remains a challenge for both public health and animal husbandry which created a constant demand to develop novel compounds using innovative methods. To join this relentless quest for an ideal chemotherapeutic agent, herein, we developed newly synthesized isatin-1,2,3-triazole derivatives. Three compounds (5a, 5b and 5c) were synthesized, characterized, and loaded on chitosan nanoparticles (CNPs) and then evaluated accordingly. Initially, a molecular docking study was carried out which revealed the effective interaction with the target enzymes; purine nucleoside phosphorylase (PNPase) and T. gondii calcium-dependent protein kinase-1 (TgCDPK1). This was further substantiated by in vivo evaluation of the three compounds (5a-c) and their nanoformulae (5a-CNPs, 5b-CNPs, and 5c-CNPs) against acute Toxoplasma gondii infection in murine model. It is worthy of note that all tested compounds and their nanoformulae produced a significant reduction of parasite burden in both peritoneal fluid and liver impression smear and profound ultrastructural alterations, detected by scanning electron microscopy, compared to the infected non-treated control. The nanoformula 5c-CNPs yielded the most outstanding results with the highest tachyzoite reduction percentage in both peritoneal fluid (98.1%) and liver impression smear (95.3%). Furthermore, the serum levels of liver enzymes (aspartate transaminase (AST) and alanine transaminase (ALT), and renal function tests (urea and creatinine) in mice were within normal limits which makes them more appealing candidates with proven safety. To the best of our knowledge, the present work is the first in silico and in vivo study proving the anti-Toxoplasma effect of isatin-1,2,3- triazoles which paves the way for further development of isatin and triazole-based leads for the treatment of toxoplasmosis.</p>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":" ","pages":"107471"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}