Pub Date : 2024-01-31DOI: 10.3389/fitd.2023.1334705
Margaret M Harnett, James Doonan, Anuradha Tarafdar, Miguel A Pineda, Josephine Duncombe-Moore, Geraldine Buitrago, Piaopiao Pan, Paul A Hoskisson, Colin Selman, William Harnett
The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62's prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220+ and CD3+ cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62's ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62's targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62's actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice.
寄生蠕虫衍生的免疫调节剂 ES-62 能挽救产生 IL-10 的调节性 B 细胞（Bregs）的缺陷水平，并抑制 Th1/Th17 驱动的慢性炎症，从而保护类风湿性关节炎的小鼠胶原诱导关节炎（CIA）模型免受关节破坏。这种自身免疫性关节炎还与肠道微生物群失调和肠道屏障完整性破坏有关。我们最近进一步利用 CIA 模型表明，ES-62 预防关节破坏与保护肠道屏障完整性和肠道微生物群正常化有关，从而抑制了 CIA 小鼠自身免疫和关节损伤发生前的肠道病变。由于肠道微生物群的状态会影响造血功能，从而影响免疫反应，因此我们研究了 ES-62 是否能利用调节肠道-骨髓（BM）轴的平衡机制来解决促进 CIA 自身免疫和关节破坏的慢性炎症。研究发现，ES-62 能够抵消骨髓中与慢性炎症和感染相关的骨髓/淋巴细胞偏向。这主要是通过 ES-62 的作用来实现的，ES-62 能够维持在健康小鼠中观察到的淋巴细胞系（B220+ 和 CD3+ 细胞）的水平，但这些淋巴细胞系在 CIA 小鼠的 BM 中却消失了。此外，研究还发现 ES-62 预防破坏骨的破骨细胞生成的能力与其抑制 CIA 诱导的破骨细胞祖细胞（OCPs）在 BM 中的上调有关。重要的是，ES-62以肠道-BM轴为靶点，这种炎症性造血的重构在微生物群被破坏的小鼠中消失了，这也支持了ES-62的靶向作用。ES-62在恢复稳态造血方面的作用强调了其重要性，研究表明，B淋巴细胞和T淋巴细胞的生化水平与CIA小鼠关节损伤的严重程度成反比，而OCPs的水平则成正比。
{"title":"The parasitic worm product ES-62 protects against collagen-induced arthritis by resetting the gut-bone marrow axis in a microbiome-dependent manner.","authors":"Margaret M Harnett, James Doonan, Anuradha Tarafdar, Miguel A Pineda, Josephine Duncombe-Moore, Geraldine Buitrago, Piaopiao Pan, Paul A Hoskisson, Colin Selman, William Harnett","doi":"10.3389/fitd.2023.1334705","DOIUrl":"10.3389/fitd.2023.1334705","url":null,"abstract":"<p><p>The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62's prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220<sup>+</sup> and CD3<sup>+</sup> cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62's ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62's targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62's actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice.</p>","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159705","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 : 2024-01-29DOI: 10.3389/fitd.2024.1329639
Md. Ilias Kamal Risat, Gail Davey, Peter Mugume, Shahaduz Zaman
Globally, a total of almost 4 million people live with podoconiosis in 32 potentially endemic countries including Rwanda. Podoconiosis is a non-infectious geochemical disease that causes massive swelling of the lower leg and is caused by long-term exposure to red clay soil found in tropical highland areas. The disease is a disabling neglected tropical disease (NTD) and is associated with profound stigma, discrimination and comorbid mental health conditions. Treatment interventions are commonly known as morbidity management and disability prevention. Both biomedical and traditional treatments are used by affected people. However, understandings informed by the social sciences of care in the context of NTDs are largely unexplored. This study explored the perspectives and experiences of care among care receivers (podoconiosis patients) and caregivers (family members, traditional healers) in the district of Huye, Rwanda.The study used qualitative methods including seventeen InDepth Interviews (eleven patients, two traditional healers, two care professionals, and two family members) and participant observation in a health centre and patients’ houses.A caring network was found amongst the podoconiosis patients, their family members, care professionals and traditional healers. Caring network is not only about the medical treatments, but also about the caring relationship amongst them.Using notions of ‘Network’ and ‘Collectives’, from the care ethics literature the study shows that in addition to care work requiring professional know-how, it is also about the relationships between patients, their families, traditional healers, and biomedical care professionals.
{"title":"Understanding the caring network of podoconiosis patients in Rwanda: a qualitative study","authors":"Md. Ilias Kamal Risat, Gail Davey, Peter Mugume, Shahaduz Zaman","doi":"10.3389/fitd.2024.1329639","DOIUrl":"https://doi.org/10.3389/fitd.2024.1329639","url":null,"abstract":"Globally, a total of almost 4 million people live with podoconiosis in 32 potentially endemic countries including Rwanda. Podoconiosis is a non-infectious geochemical disease that causes massive swelling of the lower leg and is caused by long-term exposure to red clay soil found in tropical highland areas. The disease is a disabling neglected tropical disease (NTD) and is associated with profound stigma, discrimination and comorbid mental health conditions. Treatment interventions are commonly known as morbidity management and disability prevention. Both biomedical and traditional treatments are used by affected people. However, understandings informed by the social sciences of care in the context of NTDs are largely unexplored. This study explored the perspectives and experiences of care among care receivers (podoconiosis patients) and caregivers (family members, traditional healers) in the district of Huye, Rwanda.The study used qualitative methods including seventeen InDepth Interviews (eleven patients, two traditional healers, two care professionals, and two family members) and participant observation in a health centre and patients’ houses.A caring network was found amongst the podoconiosis patients, their family members, care professionals and traditional healers. Caring network is not only about the medical treatments, but also about the caring relationship amongst them.Using notions of ‘Network’ and ‘Collectives’, from the care ethics literature the study shows that in addition to care work requiring professional know-how, it is also about the relationships between patients, their families, traditional healers, and biomedical care professionals.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"44 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140489062","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 : 2024-01-29DOI: 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}
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