Conducting active screening for human African trypanosomiasis with rapid diagnostic tests: The Guinean experience (2016 –2021)
by Oumou Camara, Justin Windingoudi Kabor é, Aïssata Soumah, Mamadou Leno, Mohamed Sam Bangoura, Dominique N’Diaye, Adrien Marie Gaston Belem, Sylvain Biéler, Mamadou Camara, Jean-Mathieu Bart, Brice Rotureau, Bruno Bucheton Strategies to detect Human African Trypanosomiasis (HAT) cases rely on serological screening of populations exposed to trypanosomes. In Guinea, mass medical screening surveys performed with the Card Agglutination Test for Trypanosomiasis have been progressively replaced by door-to-door approaches using Rapid Diagnostic Tests (RDTs) since 2016. However, RDTs availability represents a major concern...
Source: PLoS Neglected Tropical Diseases - February 20, 2024 Category: Tropical Medicine Authors: Oumou Camara Source Type: research

Tractable Quinolone Hydrazides Exhibiting Sub-Micromolar and Broad Spectrum Antitrypanosomal Activities
ChemMedChem. 2024 Feb 7:e202300667. doi: 10.1002/cmdc.202300667. Online ahead of print.ABSTRACTNagana and Human African Trypanosomiasis (HAT), caused by (sub)species of Trypanosoma, are diseases that impede human and animal health, and economic growth in Africa. The few drugs available have drawbacks including suboptimal efficacy, adverse effects, drug resistance, and difficult routes of administration. New drugs are needed. A series of 20 novel quinolone compounds with affordable synthetic routes was made and evaluated in vitro against Trypanosoma brucei and HEK293 cells. Of the 20 compounds, 12 had sub-micromolar potenci...
Source: ChemMedChem - February 7, 2024 Category: Chemistry Authors: Kgothatso A Chirwa Karol R Francisco Phelelisiwe S Dube Hayoung Park Lesetja J Legoabe Thaiz Rodrigues Teixeira Conor R Caffrey Richard Beteck Source Type: research

Exploring the latest breakthroughs in rhodesain inhibitors for African trypanosomiasis
AbstractHuman African Trypanosomiasis is a serious public health concern, and new chemical therapeutic agents need to be developed to combat this disease. Rhodesain (RhD) inhibitors have shown promising results in medicinal chemistry, specifically againstTrypanosoma brucei. These inhibitors target the cysteine protease RhD, which is essential for the survival ofT. brucei. However, as the pharmaceutical industry lacks interest in these inhibitors, the development of drugs based on them is challenging. In this review, we showed the impact of RhD inhibitors on medicinal chemistry in the past 10 years (2013 –2022), particula...
Source: Medicinal Chemistry Research - February 2, 2024 Category: Chemistry Source Type: research

Design, Synthesis, and Evaluation of An Anti-trypanosomal [1,2,4]Triazolo[1,5-a]pyrimidine Probe for Photoaffinity Labeling Studies
ChemMedChem. 2024 Jan 26:e202300656. doi: 10.1002/cmdc.202300656. Online ahead of print.ABSTRACTStudies have shown that depending on the substitution pattern, microtubule (MT)-targeting 1,2,4-triazolo[1,5-a]pyrimidines (TPDs) can produce different cellular responses in mammalian cells that may be due to these compounds interacting with distinct binding sites within the MT structure. Selected TPDs are also potently bioactive against the causative agent of human African trypanosomiasis, Trypanosoma brucei, both in vitro and in vivo. So far, however, there has been no direct evidence of tubulin engagement by these TPDs in T. ...
Source: ChemMedChem - January 26, 2024 Category: Chemistry Authors: Bobby Lucero Karol R Francisco Carmine Varricchio Lawrence J Liu Yuemang Yao Andrea Brancale Kurt R Brunden Conor R Caffrey Carlo Ballatore Source Type: research

The current status of neglected tropical diseases in Japan: A scoping review
by Yuriko Harada, Hanako Iwashita, Taeko Moriyasu, Sachiyo Nagi, Nobuo Saito, Mariko Sugawara-Mikami, Kota Yoshioka, Rie Yotsu, on behalf of Japan NTD Study Group Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of ...
Source: PLoS Neglected Tropical Diseases - January 2, 2024 Category: Tropical Medicine Authors: Yuriko Harada Source Type: research

Exploring microalgal and cyanobacterial metabolites with antiprotozoal activity against Leishmania and Trypanosoma parasites
Acta Trop. 2023 Dec 28:107116. doi: 10.1016/j.actatropica.2023.107116. Online ahead of print.ABSTRACTNeglected tropical diseases (NTD) like Leishmaniasis and trypanosomiasis affect millions of people annually, while currently used antiprotozoal drugs have serious side effects. Drug research based on natural products has shown that microalgae and cyanobacteria are a promising platform of biochemically active compounds with antiprotozoal activity. These unicellular photosynthetic organisms are rich in polyunsaturated fatty acids, pigments including phycocyanin, chlorophylls and carotenoids, polyphenols, bioactive peptides, t...
Source: Acta Tropica - December 30, 2023 Category: Infectious Diseases Authors: Ângelo Paggi Matos Fl ávia Marisa Prado Saldanha-Corrêa Roberto da Silva Gomes Gabriela Ramos Hurtado Source Type: research

Spatial confinement of < i > Trypanosoma brucei < /i > in microfluidic traps provides a new tool to study free swimming parasites
by Mariana De Niz, Emmanuel Frachon, Samy Gobaa, Philippe BastinTrypanosoma brucei is the causative agent of African trypanosomiasis and is transmitted by the tsetse fly (Glossina spp.). All stages of this extracellular parasite possess a single flagellum that is attached to the cell body and confers a high degree of motility. While several stages are amenable to culturein vitro, longitudinal high-resolution imaging of free-swimming parasites has been challenging, mostly due to the rapid flagellar beating that constantly twists the cell body. Here, using microfabrication, we generated various microfluidic devices with trap...
Source: PLoS One - December 22, 2023 Category: Biomedical Science Authors: Mariana De Niz Source Type: research

Trypanocide usage in the cattle belt of southwestern Uganda
ConclusionThis study highlights the complexity of issues involved in the fight against AAT using drug treatment. A multistakeholder campaign to increase awareness among farmers, drug shop attendants, and extension workers of the importance of adherence to recommended drug dosing, using the sanative pair and following recommended drug withdrawal guidance would promote best practice, reduce the risk of emergence of resistant strains of trypanosomes, and support enhanced food safety. (Source: Frontiers in Microbiology)
Source: Frontiers in Microbiology - December 13, 2023 Category: Microbiology Source Type: research

Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis
Antimicrob Agents Chemother. 2023 Dec 8:e0073123. doi: 10.1128/aac.00731-23. Online ahead of print.ABSTRACTThe intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and an...
Source: Antimicrobial Agents and Chemotherapy - December 8, 2023 Category: Microbiology Authors: Jose Ignacio Escrig Yukiko Miyamoto Alejandro Delgado Aznar Lars Eckmann Anjan Debnath Source Type: research

In vitro trypanocidal potency and in vivo treatment efficacy of oligomeric ethylene glycol-tethered nitrofurantoin derivatives
Eur J Pharm Sci. 2023 Dec 7;192:106668. doi: 10.1016/j.ejps.2023.106668. Online ahead of print.ABSTRACTAfrican trypanosomiasis is a significant vector-borne disease of humans and animals in the tsetse fly belt of Africa, particularly affecting production animals such as cattle, and thus, hindering food security. Trypanosoma congolense (T. congolense), the causative agent of nagana, is livestock's most virulent trypanosome species. There is currently no vaccine against trypanosomiasis; its treatment relies solely on chemotherapy. However, pathogenic resistance has been established against trypanocidal agents in clinical use...
Source: European Journal of Pharmaceutical Sciences - December 8, 2023 Category: Drugs & Pharmacology Authors: Helena D Janse van Rensburg David D N'Da Keisuke Suganuma Source Type: research

Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis
Antimicrob Agents Chemother. 2023 Dec 8:e0073123. doi: 10.1128/aac.00731-23. Online ahead of print.ABSTRACTThe intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and an...
Source: Antimicrobial Agents and Chemotherapy - December 8, 2023 Category: Microbiology Authors: Jose Ignacio Escrig Yukiko Miyamoto Alejandro Delgado Aznar Lars Eckmann Anjan Debnath Source Type: research

Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis
Antimicrob Agents Chemother. 2023 Dec 8:e0073123. doi: 10.1128/aac.00731-23. Online ahead of print.ABSTRACTThe intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and an...
Source: Antimicrobial Agents and Chemotherapy - December 8, 2023 Category: Microbiology Authors: Jose Ignacio Escrig Yukiko Miyamoto Alejandro Delgado Aznar Lars Eckmann Anjan Debnath Source Type: research

Differences in gene expression profiles in early and late stage rhodesiense HAT individuals in Malawi
by Peter Nambala, Julius Mulindwa, Harry Noyes, Vincent Pius Alibu, Barbara Nerima, Joyce Namulondo, Oscar Nyangiri, Enock Matovu, Annette MacLeod, Janelisa Musaya, on behalf of the TrypanoGEN+ Research Group as Members of the H3Africa ConsortiumT.b.rhodesiense is the causative agent of Rhodesian human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood...
Source: PLoS Neglected Tropical Diseases - December 6, 2023 Category: Tropical Medicine Authors: Peter Nambala Source Type: research

Impact of a small-scale tsetse fly control operation with deltamethrin impregnated “Tiny Targets” on tsetse density and trypanosomes’ circulation in the Campo sleeping sickness focus of South Cameroon
by Tito Tresor Melachio Tanekou, Calmes Ursain Bouaka Tsakeng, Inaki Tirados, Alphonse Acho, Jude Bigoga, Charles Sinclair Wondji, Flobert Njiokou BackgroundSignificant progress has been made towards African sleeping sickness elimination in the last decade. Indeed, the World Health Organization (WHO) global goal of eliminating the chronic form of the disease as a public health problem was achieved in 2020 (i.e., (Source: PLoS Neglected Tropical Diseases)
Source: PLoS Neglected Tropical Diseases - November 27, 2023 Category: Tropical Medicine Authors: Tito Tresor Melachio Tanekou Source Type: research

Discovery of an orally active nitrothiophene-based antitrypanosomal agent
Eur J Med Chem. 2023 Nov 15;263:115954. doi: 10.1016/j.ejmech.2023.115954. Online ahead of print.ABSTRACTHuman African Trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense and rhodesiense, is a parasitic disease endemic to sub-Saharan Africa. Untreated cases of HAT can be severely debilitating and fatal. Although the number of reported cases has decreased progressively over the last decade, the number of effective and easily administered medications is very limited. In this work, we report the antitrypanosomal activity of a series of potent compounds. A subset of molecules in the series are highly selective for tr...
Source: European Journal of Medicinal Chemistry - November 20, 2023 Category: Chemistry Authors: Oluwatomi Ajayi Damilohun S Metibemu Olamide Crown Olawale S Adeyinka Marcel Kaiser Nathalie Shoji Mariana Silva Ana Rodriguez Ifedayo Victor Ogungbe Source Type: research