Pub Date : 2024-01-29DOI: 10.3389/fitd.2024.1287025
Leon E. Hugo, Karla van Huyssteen, Olamide K. Oloniniyi, Laura Donnelly, Anna Conn, Katharine A. Collins, H. Mitchell, James S. McCarthy, Joanne Macdonald
Vector surveillance of Plasmodium falciparum is critical for monitoring and reducing one of the most severe forms of malaria, which causes high morbidity and mortality in children under five and pregnant women. Here we developed a rapid and highly sensitive test for the detection of P. falciparum (Pf)-infected mosquitoes (Rapid Pf test), with high suitability for low-resource vector surveillance implementation. The Rapid Pf test had similar analytical sensitivity to laboratory-based tests, detecting down to 4 copies/μL of a 18S rRNA DNA standard. In addition, the Rapid Pf test could be completed in less than 30 minutes, and only required a liquid sample preparation reagent, pestle, tube, and 39°C heating block for operation, indicating amenability for low-resource implementation. Diagnostic testing was performed using Anopheles stephensi mosquitoes, either uninfected, or fed with P. falciparum gametocyte cultures. These P. falciparum fed mosquitoes were determined to have 79% infection prevalence based on parallel microscopy and qPCR testing on a subset of 19 mosquitoes. However, our Rapid Pf test determined a 90% positive test rate when testing individual infected mosquitoes (n=30), and did not detect 40 uninfected mosquitoes regardless of blood-fed status (n=40), suggesting the true prevalence of infection in the mosquitoes may have been higher than calculated by qPCR and microscopy. The Rapid Pf test was demonstrated to detect infection in individual mosquitoes (both fresh and frozen/thawed), as well as pools of 1 infected mosquito mixed with 19 known uninfected mosquitoes, and individual mosquitoes left in traps for up to 8 days. After testing on infected and uninfected mosquitoes (n=148) the Rapid Pf test was conservatively estimated to achieve 100% diagnostic sensitivity (95% confidence interval, CI: 91%-100%) and 97% diagnostic specificity (CI: 92%-99%) compared to the estimated prevalence from combined microscopy and qPCR results. These results indicate the Rapid Pf test could provide a highly effective tool for weekly surveillance of infected mosquitoes, to assist with P. falciparum monitoring and intervention studies.
{"title":"Rapid low-resource detection of Plasmodium falciparum in infected Anopheles mosquitoes","authors":"Leon E. Hugo, Karla van Huyssteen, Olamide K. Oloniniyi, Laura Donnelly, Anna Conn, Katharine A. Collins, H. Mitchell, James S. McCarthy, Joanne Macdonald","doi":"10.3389/fitd.2024.1287025","DOIUrl":"https://doi.org/10.3389/fitd.2024.1287025","url":null,"abstract":"Vector surveillance of Plasmodium falciparum is critical for monitoring and reducing one of the most severe forms of malaria, which causes high morbidity and mortality in children under five and pregnant women. Here we developed a rapid and highly sensitive test for the detection of P. falciparum (Pf)-infected mosquitoes (Rapid Pf test), with high suitability for low-resource vector surveillance implementation. The Rapid Pf test had similar analytical sensitivity to laboratory-based tests, detecting down to 4 copies/μL of a 18S rRNA DNA standard. In addition, the Rapid Pf test could be completed in less than 30 minutes, and only required a liquid sample preparation reagent, pestle, tube, and 39°C heating block for operation, indicating amenability for low-resource implementation. Diagnostic testing was performed using Anopheles stephensi mosquitoes, either uninfected, or fed with P. falciparum gametocyte cultures. These P. falciparum fed mosquitoes were determined to have 79% infection prevalence based on parallel microscopy and qPCR testing on a subset of 19 mosquitoes. However, our Rapid Pf test determined a 90% positive test rate when testing individual infected mosquitoes (n=30), and did not detect 40 uninfected mosquitoes regardless of blood-fed status (n=40), suggesting the true prevalence of infection in the mosquitoes may have been higher than calculated by qPCR and microscopy. The Rapid Pf test was demonstrated to detect infection in individual mosquitoes (both fresh and frozen/thawed), as well as pools of 1 infected mosquito mixed with 19 known uninfected mosquitoes, and individual mosquitoes left in traps for up to 8 days. After testing on infected and uninfected mosquitoes (n=148) the Rapid Pf test was conservatively estimated to achieve 100% diagnostic sensitivity (95% confidence interval, CI: 91%-100%) and 97% diagnostic specificity (CI: 92%-99%) compared to the estimated prevalence from combined microscopy and qPCR results. These results indicate the Rapid Pf test could provide a highly effective tool for weekly surveillance of infected mosquitoes, to assist with P. falciparum monitoring and intervention studies.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"227 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140489900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-18DOI: 10.3389/fitd.2023.1297896
S. C. Ogunleye, M. Olorunshola, Kolapo A. Fasina, A. Aborode, O. C. Akinsulie, Abimbola Amoo, Boluwatife J. Olatoye, Akeem B. Bakare, Mariam A. Lawal, Oluwabori Adekanye, Ezemba C. Chinyere
The (re)emergence of several infectious zoonoses underlines the need for the re-evaluation of the transmission patterns and key players responsible for effective inter-species transfer of diseases. Anthrax is caused by Bacillus anthracis, a zoonotic rod-shaped, Gram-positive, spore-forming bacterium that is highly fatal to both human and animal populations. B. anthracis is widespread across several regions of the world, including Africa, Asia, southern Europe, North and South America, and Australia, and it has a remarkably high attendant impact on the sustainability and profitability of livestock. The current trend in the global distribution of anthrax necessitates an urgent contextual understanding of the key drivers of the spread of B. anthracis in different parts of the world toward the end goal of an anthrax-free world. The understanding of the drivers is integral for the development of control and preventive measures, and also the development of agents such as therapeutics and vaccines against B. anthracis. This review presents a holistic description of the transmission pattern and epidemiology of B. anthracis, and updates on the diagnostic techniques and approaches available for the detection of B. anthracis. In addition, this review highlights plausible prevention and control strategies for the bacterium. This review further underscores the need for participatory epidemiology, hygiene, and safety protocols, the establishment of comprehensive surveillance systems, and global collaborative efforts toward vaccine development as critical steps in controlling anthrax.
{"title":"Anthrax outbreak: exploring its biological agents and public health implications","authors":"S. C. Ogunleye, M. Olorunshola, Kolapo A. Fasina, A. Aborode, O. C. Akinsulie, Abimbola Amoo, Boluwatife J. Olatoye, Akeem B. Bakare, Mariam A. Lawal, Oluwabori Adekanye, Ezemba C. Chinyere","doi":"10.3389/fitd.2023.1297896","DOIUrl":"https://doi.org/10.3389/fitd.2023.1297896","url":null,"abstract":"The (re)emergence of several infectious zoonoses underlines the need for the re-evaluation of the transmission patterns and key players responsible for effective inter-species transfer of diseases. Anthrax is caused by Bacillus anthracis, a zoonotic rod-shaped, Gram-positive, spore-forming bacterium that is highly fatal to both human and animal populations. B. anthracis is widespread across several regions of the world, including Africa, Asia, southern Europe, North and South America, and Australia, and it has a remarkably high attendant impact on the sustainability and profitability of livestock. The current trend in the global distribution of anthrax necessitates an urgent contextual understanding of the key drivers of the spread of B. anthracis in different parts of the world toward the end goal of an anthrax-free world. The understanding of the drivers is integral for the development of control and preventive measures, and also the development of agents such as therapeutics and vaccines against B. anthracis. This review presents a holistic description of the transmission pattern and epidemiology of B. anthracis, and updates on the diagnostic techniques and approaches available for the detection of B. anthracis. In addition, this review highlights plausible prevention and control strategies for the bacterium. This review further underscores the need for participatory epidemiology, hygiene, and safety protocols, the establishment of comprehensive surveillance systems, and global collaborative efforts toward vaccine development as critical steps in controlling anthrax.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"108 42","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139614442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-17DOI: 10.3389/fitd.2023.1303873
Teniel Ramkhelawan, Pragalathan Naidoo, Z. Mkhize-Kwitshana
The most common soil-transmitted helminthic infection is caused by Ascaris lumbricoides (A. lumbricoides). Approximately 4 billion people are at risk of infection globally. The World Health Organisation recommends the administration of benzimidazole- containing deworming drugs (Albendazole and Mebendazole) to all susceptible populations. Due to this high drug pressure, these parasites may develop resistance to current benzimidazole drugs. The β-tubulin gene family is the target gene for benzimidazole deworming drugs. This systematic review aimed to highlight work that explored the genetic mutations in the β-tubulin gene family of A. lumbricoides that are associated with potential benzimidazole resistance.An electronic search of several online databases was used to extract eligible articles using specific keywords related to the topic of interest.The majority of ascariasis infections occur in the subtropical and tropical regions of sub-Saharan Africa, the Americas and East Asia, although not enough studies were done to extensively cover this geographical range. In the β-tubulin gene family of A. lumbricoides the mutations at codons F200Y (TTC/Phenylalanine to TAC/Tyrosine), E198A (GAG, GAA/Glutamic acid to GCG, GCA/Alanine) and F167Y (TTC, TTT/Phenylalanine to TAC, TAT/Tyrosine) were associated with potential benzimidazole resistance.Resistant mutations were found in A. lumbricoides samples at codon F167Y from Haiti, Kenya and Panama. The first evidence of the mutation at codon F200Y was observed in Brazil. The codon E198A mutation was the least prevalent and most undetected.There is a serious shortage of studies investigating the prevalence of β-tubulin gene family mutations in A. lumbricoides populations from endemic areas; this is a serious concern as resistance will negatively impact current mass drug administration programmes.
{"title":"Single nucleotide polymorphisms in the β-tubulin gene family of Ascaris lumbricoides and their potential role in benzimidazole resistance: a systematic review","authors":"Teniel Ramkhelawan, Pragalathan Naidoo, Z. Mkhize-Kwitshana","doi":"10.3389/fitd.2023.1303873","DOIUrl":"https://doi.org/10.3389/fitd.2023.1303873","url":null,"abstract":"The most common soil-transmitted helminthic infection is caused by Ascaris lumbricoides (A. lumbricoides). Approximately 4 billion people are at risk of infection globally. The World Health Organisation recommends the administration of benzimidazole- containing deworming drugs (Albendazole and Mebendazole) to all susceptible populations. Due to this high drug pressure, these parasites may develop resistance to current benzimidazole drugs. The β-tubulin gene family is the target gene for benzimidazole deworming drugs. This systematic review aimed to highlight work that explored the genetic mutations in the β-tubulin gene family of A. lumbricoides that are associated with potential benzimidazole resistance.An electronic search of several online databases was used to extract eligible articles using specific keywords related to the topic of interest.The majority of ascariasis infections occur in the subtropical and tropical regions of sub-Saharan Africa, the Americas and East Asia, although not enough studies were done to extensively cover this geographical range. In the β-tubulin gene family of A. lumbricoides the mutations at codons F200Y (TTC/Phenylalanine to TAC/Tyrosine), E198A (GAG, GAA/Glutamic acid to GCG, GCA/Alanine) and F167Y (TTC, TTT/Phenylalanine to TAC, TAT/Tyrosine) were associated with potential benzimidazole resistance.Resistant mutations were found in A. lumbricoides samples at codon F167Y from Haiti, Kenya and Panama. The first evidence of the mutation at codon F200Y was observed in Brazil. The codon E198A mutation was the least prevalent and most undetected.There is a serious shortage of studies investigating the prevalence of β-tubulin gene family mutations in A. lumbricoides populations from endemic areas; this is a serious concern as resistance will negatively impact current mass drug administration programmes.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":" 751","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139617433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-11DOI: 10.3389/fitd.2023.1297109
S. Agnandji, M. Loembe, Armel V. Mbouna, Fallowne Mbadinga, P. Essone, G. Mombo-Ngoma, Rose Leke, Yvonne K. Mburu, J. Muyembe‐Tamfum, J. Okwo-Bele, Samba Sow, Charles S Wiysonge, Alimuddin Zumla, A. A. Adegnika, Michael Ramharter, Peter G. Kremsner, P. Matsiegui, Y. Boum, Francine Ntoumi
{"title":"Making clinical trials a public norm for health decisions in sub-Saharan Africa","authors":"S. Agnandji, M. Loembe, Armel V. Mbouna, Fallowne Mbadinga, P. Essone, G. Mombo-Ngoma, Rose Leke, Yvonne K. Mburu, J. Muyembe‐Tamfum, J. Okwo-Bele, Samba Sow, Charles S Wiysonge, Alimuddin Zumla, A. A. Adegnika, Michael Ramharter, Peter G. Kremsner, P. Matsiegui, Y. Boum, Francine Ntoumi","doi":"10.3389/fitd.2023.1297109","DOIUrl":"https://doi.org/10.3389/fitd.2023.1297109","url":null,"abstract":"","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"8 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.3389/fitd.2023.1327349
D. Tchouassi, Juliah W. Jacob, X. Cheseto, Lydia S. Chepkemoi, I. B. Hassaballa, B. Torto
Phlebotomine sand flies are medically important as vectors of the protozoan parasites that cause leishmaniasis and other bacterial and viral pathogens. Previous work demonstrated that both sexes of certain species of sandflies are attracted to 1-octen-3-ol (octenol). Since 1-octen-3-ol exists as two enantiomeric isomers ─ ((R)-(-)- (R-form) and (S)-(+)- (S-form), we tested the hypothesis that the two enantiomeric forms and racemic mixture (R/S) attracted different sand fly species. We carried out field trials in a leishmaniasis endemic foci in Baringo County, Kenya. In a randomized design, trap captures of sandflies in CDC light traps baited with the R-, S- and racemic (R/S) forms of 1-octen-3-ol in hexane varied with the form and dose of the compound. Interestingly, of the captured species, only Phlebotomus martini, the vector of the parasite causing visceral leishmaniasis, exhibited a dose-dependent response to octenol; captures of both sexes of the species being generally 1.7-fold higher with the R- than S-form. There was no significant effect of treatment on captures of Sergentomyia species (S. schwetzi, S. antennata, S, clydei). Our findings have implications for surveillance of sandfly populations as part of leishmaniasis epidemiologic investigation.
{"title":"Enzyme-catalyzed kinetic resolution of racemic 1-octen-3-ol and field evaluation of its enantiomeric isomers as attractants of sandflies","authors":"D. Tchouassi, Juliah W. Jacob, X. Cheseto, Lydia S. Chepkemoi, I. B. Hassaballa, B. Torto","doi":"10.3389/fitd.2023.1327349","DOIUrl":"https://doi.org/10.3389/fitd.2023.1327349","url":null,"abstract":"Phlebotomine sand flies are medically important as vectors of the protozoan parasites that cause leishmaniasis and other bacterial and viral pathogens. Previous work demonstrated that both sexes of certain species of sandflies are attracted to 1-octen-3-ol (octenol). Since 1-octen-3-ol exists as two enantiomeric isomers ─ ((R)-(-)- (R-form) and (S)-(+)- (S-form), we tested the hypothesis that the two enantiomeric forms and racemic mixture (R/S) attracted different sand fly species. We carried out field trials in a leishmaniasis endemic foci in Baringo County, Kenya. In a randomized design, trap captures of sandflies in CDC light traps baited with the R-, S- and racemic (R/S) forms of 1-octen-3-ol in hexane varied with the form and dose of the compound. Interestingly, of the captured species, only Phlebotomus martini, the vector of the parasite causing visceral leishmaniasis, exhibited a dose-dependent response to octenol; captures of both sexes of the species being generally 1.7-fold higher with the R- than S-form. There was no significant effect of treatment on captures of Sergentomyia species (S. schwetzi, S. antennata, S, clydei). Our findings have implications for surveillance of sandfly populations as part of leishmaniasis epidemiologic investigation.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"15 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139382778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.3389/fitd.2023.1317092
Tereza Magalhaes, Ana Barreto, Jamerson Mesquita-Silva, Kamile M. L. Serravalle, Marcela Valente de Andrade, Rita C. L. Gomes, Romero J. Nazaré, Rosa M. G. A. Calado, Guilherme S. Ribeiro, Uriel D Kitron
We present a study of the tailoring of a One Health (OH) course for its integration into an established non-OH graduate program at a large public university in Brazil. The graduate program focuses on topics such as environmental resource management, impacts on ecosystems, precariousness of the work environment and relationships, workers’ health, social determinants of health, and public policies. Tailoring the OH syllabus involved addressing broader OH concepts, condensing or adapting aspects of infectious diseases, covering non-infectious disease OH topics, and linking OH aspects to ongoing projects in the program. Despite the small class size, students brought diverse backgrounds, significantly enriching discussions. The course was offered in a longer (51 contact hours) and a shorter format (34 contact hours), both of which worked well within a lecture- and discussion-based structure. The extended format allowed more time for student activities and in-depth discussions. The multisectoral and transdisciplinary nature of lectures played a critical role in the course’s success. This information may prove valuable for those designing OH courses for implementation in diverse settings, with the ultimate goal of disseminating OH concepts, fostering discussions, and facilitating the development and implementation of OH approaches in groups not typically exposed to this concept.
{"title":"Tailoring a One Health course for an established non-One Health graduate program in Brazil","authors":"Tereza Magalhaes, Ana Barreto, Jamerson Mesquita-Silva, Kamile M. L. Serravalle, Marcela Valente de Andrade, Rita C. L. Gomes, Romero J. Nazaré, Rosa M. G. A. Calado, Guilherme S. Ribeiro, Uriel D Kitron","doi":"10.3389/fitd.2023.1317092","DOIUrl":"https://doi.org/10.3389/fitd.2023.1317092","url":null,"abstract":"We present a study of the tailoring of a One Health (OH) course for its integration into an established non-OH graduate program at a large public university in Brazil. The graduate program focuses on topics such as environmental resource management, impacts on ecosystems, precariousness of the work environment and relationships, workers’ health, social determinants of health, and public policies. Tailoring the OH syllabus involved addressing broader OH concepts, condensing or adapting aspects of infectious diseases, covering non-infectious disease OH topics, and linking OH aspects to ongoing projects in the program. Despite the small class size, students brought diverse backgrounds, significantly enriching discussions. The course was offered in a longer (51 contact hours) and a shorter format (34 contact hours), both of which worked well within a lecture- and discussion-based structure. The extended format allowed more time for student activities and in-depth discussions. The multisectoral and transdisciplinary nature of lectures played a critical role in the course’s success. This information may prove valuable for those designing OH courses for implementation in diverse settings, with the ultimate goal of disseminating OH concepts, fostering discussions, and facilitating the development and implementation of OH approaches in groups not typically exposed to this concept.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"11 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139381023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-03DOI: 10.3389/fitd.2023.1337327
Emanuele Nicastri, Edwin Michael, Alfonso J. Rodriguez-Morales
{"title":"Editorial: The intersection of COVID-19 and tropical diseases","authors":"Emanuele Nicastri, Edwin Michael, Alfonso J. Rodriguez-Morales","doi":"10.3389/fitd.2023.1337327","DOIUrl":"https://doi.org/10.3389/fitd.2023.1337327","url":null,"abstract":"","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"12 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139451616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-07-29DOI: 10.3389/fitd.2024.1404943
Jiho Kim, Jenn Davis, Jinhee Lee, Sang-Nae Cho, Kiyoung Yang, Jaekyoon Yang, Sungmin Bae, Joohee Son, Boyoung Kim, Dale Whittington, Afzal A Siddiqui, Darrick Carter, Sean A Gray
Introduction: Schistosomiasis is a neglected tropical disease that puts over 200 million people at risk, and prevention options are sparse with no approved vaccine. Our vaccine candidate, SchistoShield®, is based on an approximately 87 kDa large subunit of calcium activated neutral protease - termed Sm-p80 - combined with a potent TLR4 agonist-based adjuvant. SchistoShield® has been shown to prevent disease throughout the parasitic life cycle - including egg, juvenile, and adult worm stages - in numerous animal models up to and including baboons. SchistoShield® has been shown safe in both preclinical toxicology studies in rabbits and in a Phase 1 clinical trial in the USA. A Phase 1b trial was initiated in 2023 in endemic regions of Africa, and to date no serious safety signals have been reported.
Methods: In preparation for large-scale Phase 2 clinical trials and eventual vaccine deployment, the Sm-p80 antigen production process has been transferred to a manufacturing organization, Quratis Corporation in South Korea, which specializes in preparation of vaccines for large-scale European and African trials. The process of scaling from our current production level of ~2000 vaccine doses, to a process that will generate more than 100 million doses has required multiple improvement steps in the process including fermentation, downstream purification of the protein antigen, lyophilization, and fill and finish.
Results: In this study, we detail the large-scale production process of the SchistoShield® protein product by Quratis. In addition, an effort was made to analyze and compare the Quratis-made lot of Sm-p80, referred to as QTP-105, to the cGMP lot of Sm-p80 which is in use in human trials in the USA and Africa, referred to as Sm-p80 DP (made in USA). We show that QTP-105 demonstrates excellent potency, purity, identity, and endotoxin levels compared to our Phase 1 Sm-p80 DP and is suitable for use in Phase 2 studies and beyond.
{"title":"An assessment of a GMP schistosomiasis vaccine (SchistoShield<sup>®</sup>).","authors":"Jiho Kim, Jenn Davis, Jinhee Lee, Sang-Nae Cho, Kiyoung Yang, Jaekyoon Yang, Sungmin Bae, Joohee Son, Boyoung Kim, Dale Whittington, Afzal A Siddiqui, Darrick Carter, Sean A Gray","doi":"10.3389/fitd.2024.1404943","DOIUrl":"10.3389/fitd.2024.1404943","url":null,"abstract":"<p><strong>Introduction: </strong>Schistosomiasis is a neglected tropical disease that puts over 200 million people at risk, and prevention options are sparse with no approved vaccine. Our vaccine candidate, SchistoShield<sup>®</sup>, is based on an approximately 87 kDa large subunit of calcium activated neutral protease - termed Sm-p80 - combined with a potent TLR4 agonist-based adjuvant. SchistoShield<sup>®</sup> has been shown to prevent disease throughout the parasitic life cycle - including egg, juvenile, and adult worm stages - in numerous animal models up to and including baboons. SchistoShield<sup>®</sup> has been shown safe in both preclinical toxicology studies in rabbits and in a Phase 1 clinical trial in the USA. A Phase 1b trial was initiated in 2023 in endemic regions of Africa, and to date no serious safety signals have been reported.</p><p><strong>Methods: </strong>In preparation for large-scale Phase 2 clinical trials and eventual vaccine deployment, the Sm-p80 antigen production process has been transferred to a manufacturing organization, Quratis Corporation in South Korea, which specializes in preparation of vaccines for large-scale European and African trials. The process of scaling from our current production level of ~2000 vaccine doses, to a process that will generate more than 100 million doses has required multiple improvement steps in the process including fermentation, downstream purification of the protein antigen, lyophilization, and fill and finish.</p><p><strong>Results: </strong>In this study, we detail the large-scale production process of the SchistoShield<sup>®</sup> protein product by Quratis. In addition, an effort was made to analyze and compare the Quratis-made lot of Sm-p80, referred to as QTP-105, to the cGMP lot of Sm-p80 which is in use in human trials in the USA and Africa, referred to as Sm-p80 DP (made in USA). We show that QTP-105 demonstrates excellent potency, purity, identity, and endotoxin levels compared to our Phase 1 Sm-p80 DP and is suitable for use in Phase 2 studies and beyond.</p>","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-22DOI: 10.3389/fitd.2023.1308660
Ashley Preston, Carlos Torres Vitolas, Alain Claver Kouamin, Johara Nadri, Suzanne Lobohon Lavry, Neerav Dhanani, Norbert Dje, Alain Toh, Fiona M. Fleming, A. Méité
Female genital schistosomiasis (FGS) is a neglected gynecological condition, putting women at-risk of poor sexual and reproductive health (SRH), including pregnancy complications or infertility. Early treatment of schistosomiasis with praziquantel is important to avoid disease progression to FGS as it is not always possible to reverse these symptoms. However, prevention programs with praziquantel have historically focused on school-aged children. Therefore, there is a gap to provide prevention services for young women in endemic areas, including Côte d’Ivoire.We piloted integration of FGS prevention services into routine SRH care in seven health centers (Soubré district, Côte d’Ivoire, November 2020 to April 2021) and enrolled 56 health workers. We used mixed methods including key informant interviews, focus group discussions, and questionnaires to determine effectiveness, feasibility and acceptability of integration across health system decision makers, health workers and female patients (15 to 29 years old). For qualitative data, we used an inductive coding process to analyze themes. We used descriptive statistics to analyze quantitative data.Interviewed health workers perceived that the integrated services increased access and improved health outcomes for women (15 to 29 years old) due to the more comprehensive approach, although barriers to access included lack of transportation. Female patients surveyed at baseline (n=448) indicated there were no routine FGS prevention services. During the pilot, FGS prevention services were provided to >8500 women at-risk. Health workers interviewed at the end of the pilot indicated they could feasibly provide FGS prevention services as part of routine patient consultations, and they maintained knowledge from training on the key FGS health education points and the consultation processes to follow. The greatest challenge expressed by health workers was the high workload.Provision of integrated healthcare in the health center setting is an effective and acceptable way to increase access to prevention services and provide holistic care for women (15 to 29 years old) in this setting in Côte d’Ivoire. Future scale-up will require further streamlining of the strategy, building on existing platforms, whilst ensuring reduced impact on workload and consideration of how to overcome barriers to accessing health centers.
{"title":"Improved prevention of female genital schistosomiasis: piloting integration of services into the national health system in Côte d’Ivoire","authors":"Ashley Preston, Carlos Torres Vitolas, Alain Claver Kouamin, Johara Nadri, Suzanne Lobohon Lavry, Neerav Dhanani, Norbert Dje, Alain Toh, Fiona M. Fleming, A. Méité","doi":"10.3389/fitd.2023.1308660","DOIUrl":"https://doi.org/10.3389/fitd.2023.1308660","url":null,"abstract":"Female genital schistosomiasis (FGS) is a neglected gynecological condition, putting women at-risk of poor sexual and reproductive health (SRH), including pregnancy complications or infertility. Early treatment of schistosomiasis with praziquantel is important to avoid disease progression to FGS as it is not always possible to reverse these symptoms. However, prevention programs with praziquantel have historically focused on school-aged children. Therefore, there is a gap to provide prevention services for young women in endemic areas, including Côte d’Ivoire.We piloted integration of FGS prevention services into routine SRH care in seven health centers (Soubré district, Côte d’Ivoire, November 2020 to April 2021) and enrolled 56 health workers. We used mixed methods including key informant interviews, focus group discussions, and questionnaires to determine effectiveness, feasibility and acceptability of integration across health system decision makers, health workers and female patients (15 to 29 years old). For qualitative data, we used an inductive coding process to analyze themes. We used descriptive statistics to analyze quantitative data.Interviewed health workers perceived that the integrated services increased access and improved health outcomes for women (15 to 29 years old) due to the more comprehensive approach, although barriers to access included lack of transportation. Female patients surveyed at baseline (n=448) indicated there were no routine FGS prevention services. During the pilot, FGS prevention services were provided to >8500 women at-risk. Health workers interviewed at the end of the pilot indicated they could feasibly provide FGS prevention services as part of routine patient consultations, and they maintained knowledge from training on the key FGS health education points and the consultation processes to follow. The greatest challenge expressed by health workers was the high workload.Provision of integrated healthcare in the health center setting is an effective and acceptable way to increase access to prevention services and provide holistic care for women (15 to 29 years old) in this setting in Côte d’Ivoire. Future scale-up will require further streamlining of the strategy, building on existing platforms, whilst ensuring reduced impact on workload and consideration of how to overcome barriers to accessing health centers.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"89 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138945384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-19DOI: 10.3389/fitd.2023.1080218
Cindy Alves Dias, Túllio Romão Ribeiro da Silva, Marcelo Gordo, D. F. Conga, Natália Aparecida de Souza Lima, A. V. S. D. Medeiros, Edson Rodrigues Costa, Sérgio Luiz Bessa Luz, Carlos Henrique Aguiar Costa, Ana Carolina Paulo Vicente, Thaís Pinto Nascimento, Francisca Helena Aguiar-Silva, Viviane Costa da Silva, Diogo César Lagroteria, Laerzio Chiesorin Neto, Alessandra Ferreira Dales Nava
The pied tamarin, or Saguinus bicolor, is a callitrichid that inhabits Amazon Forest fragments encased within the municipalities of Manaus, Rio Preto da Eva, and Itacoatiara and their outskirts. Therefore, this primate lives in great proximity to humans, and is in critical danger of extinction, resulting from ongoing anthropogenic pressures, with habitat fragmentation being the most prominent threat. Greater conservation efforts and more studies concerning public health need to be carried out in this situation, such as the study of infectious diseases that can affect this primate, including those involving helminths. In this study, we combined necropsy, microscopy with blood smears and quick Panoptic stains, and molecular methods like nested polymerase chain reaction (PCR) targeting the internal transcribed spacer-1 (ITS-1) region, Sanger sequencing and shotgun sequencing to detect and identify filarial parasites in 71 S. bicolor samples. We detected 24 adult filarial worms in 6.45% of the thoracic cavities, microfilaria in 6.38% from blood smears, and filarial DNA in 28.57% positive blood samples via PCR. We identified eight of the adult worms as being from the Onchocercidae family using Sanger sequencing and one specifically as Dipetalonema gracile, using shotgun sequencing. For the positive blood samples, 70.58% of them were for Mansonella sp., 17.64% for Dipetalonema sp., and 11.76% could only be identified as belonging to the Onchocercidae family. There was an event of coinfection that involved Dipetalonema sp. adult worm and Mansonella sp. microfilaria. This is the first report of the detection of Dipetalonema gracile and the genus Mansonella in S. bicolor, as well as an event of coinfection, pointing out this primate as a new host. It is also another step to understand the situation of filarial infections occurring in Amazonian Regions and its municipalities.
{"title":"First report of Mansonella sp. and Dipetalonema gracile in the Amazonian city-dwelling threatened primate, Saguinus bicolor","authors":"Cindy Alves Dias, Túllio Romão Ribeiro da Silva, Marcelo Gordo, D. F. Conga, Natália Aparecida de Souza Lima, A. V. S. D. Medeiros, Edson Rodrigues Costa, Sérgio Luiz Bessa Luz, Carlos Henrique Aguiar Costa, Ana Carolina Paulo Vicente, Thaís Pinto Nascimento, Francisca Helena Aguiar-Silva, Viviane Costa da Silva, Diogo César Lagroteria, Laerzio Chiesorin Neto, Alessandra Ferreira Dales Nava","doi":"10.3389/fitd.2023.1080218","DOIUrl":"https://doi.org/10.3389/fitd.2023.1080218","url":null,"abstract":"The pied tamarin, or Saguinus bicolor, is a callitrichid that inhabits Amazon Forest fragments encased within the municipalities of Manaus, Rio Preto da Eva, and Itacoatiara and their outskirts. Therefore, this primate lives in great proximity to humans, and is in critical danger of extinction, resulting from ongoing anthropogenic pressures, with habitat fragmentation being the most prominent threat. Greater conservation efforts and more studies concerning public health need to be carried out in this situation, such as the study of infectious diseases that can affect this primate, including those involving helminths. In this study, we combined necropsy, microscopy with blood smears and quick Panoptic stains, and molecular methods like nested polymerase chain reaction (PCR) targeting the internal transcribed spacer-1 (ITS-1) region, Sanger sequencing and shotgun sequencing to detect and identify filarial parasites in 71 S. bicolor samples. We detected 24 adult filarial worms in 6.45% of the thoracic cavities, microfilaria in 6.38% from blood smears, and filarial DNA in 28.57% positive blood samples via PCR. We identified eight of the adult worms as being from the Onchocercidae family using Sanger sequencing and one specifically as Dipetalonema gracile, using shotgun sequencing. For the positive blood samples, 70.58% of them were for Mansonella sp., 17.64% for Dipetalonema sp., and 11.76% could only be identified as belonging to the Onchocercidae family. There was an event of coinfection that involved Dipetalonema sp. adult worm and Mansonella sp. microfilaria. This is the first report of the detection of Dipetalonema gracile and the genus Mansonella in S. bicolor, as well as an event of coinfection, pointing out this primate as a new host. It is also another step to understand the situation of filarial infections occurring in Amazonian Regions and its municipalities.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":" 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138960660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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