Communicable diseases
Liam J. Donaldson, Paul D. Rutter in Donaldsons' Essential Public Health, 2017
African trypanosomiasis (sleeping sickness) is caused by a parasite (Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense) spread by the bite of infected tsetse flies. The parasite invades the central nervous system, causing a range of unusual and debilitating symptoms, including alteration of the biological clock (hence the term sleeping sickness). These symptoms develop over a period of months to years. Trypanosomiasis is fatal if untreated. The gambiense form accounts for 98% of cases, and affects 24 countries in western and central Africa. The rhodesiene form is more rapidly progressive and affects 13 countries, in eastern and southern Africa. Oral antiparasitic drugs are effective treatment. The mainstays of control are prompt diagnosis and treatment of cases, and measures to reduce the presence of the tsetse fly.
Engineering control of insect-borne diseases
Sandy Cairncross, Richard Feachem in Environmental Health Engineering in the Tropics, 2018
There are two forms of sleeping sickness, both transmitted by tsetse flies (Glossina spp.; Figure 15.7c), which affect between them a huge area of tropical Africa. The first, caused by Trypanosoma gambiense, is transmitted in West and Central Africa by the G. palpalis and G. fusca riverine and forest-dwelling species groups. The riverine tsetse species can be considered a water-related vector (Category 4, Table 1.2), as it breeds and lives around trees and bushes along the banks of streams and around water holes, and bites people visiting the stream to water cattle or collect water for their families. Several bites by infected flies are usually required to cause sleeping sickness, and transmission is often concentrated near to tsetse breeding sites. The disease is thus potentially controlled if the need to visit breeding sites is reduced by providing adequate water supplies in the village. Tsetse control has also been achieved in parts of West Africa by clearing vegetation from the banks of streams and lakes to remove suitable breeding sites.
Whose Knowledge Matters?
Kevin Bardosh in One Health, 2016
Despite the donors pulling out, there have been a few other funding options that have emerged recently, such as the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) established in 2000. African heads of state agreed to a continent-wide campaign coordinated by the African Union, funded within Africa, and mobilized with local resources. This follows the ‘Zambian narrative’ as the plan was renegotiated with regional governments to eliminate the vector from the southern tsetse belt: ‘Botswana has provided staff, expertise … Namibia has used [a] specialist airfield for aerial spraying, Zambia and Angola have [given] … US$8.5 million of funding’ (Senior, 2009). Aerial spraying and localized use of insecticides has eradicated the tsetse fly that carries Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense from 36,000 km2 across Botswana, Namibia, Angola and Zambia. However, there seems to be latent politics at play within PATTEC itself. One interviewee attended a PATTEC meeting, which he described as being ‘all over the place’ regarding control measures. In Zambia and Zimbabwe, PATTEC seems to be concentrating on the use of what is often considered a controversial control modality: the Sterile Insect Technique (SIT) (see Scoones, this book). But Zambia is struggling to fund this – several interviewees commented that there are lots of ideas without any funds attached.
Metabolomic profile, anti-trypanosomal potential and molecular docking studies of Thunbergia grandifolia
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Heba A. S. El-Nashar, Ahmed M. Sayed, Hany A. M. El-Sherief, Mostafa E. Rateb, Lina Akil, Ibrahim Khadra, Taghreed A. Majrashi, Sara T. Al-Rashood, Faizah A. Binjubair, Mahmoud A. El Hassab, Wagdy M. Eldehna, Usama Ramadan Abdelmohsen, Nada M. Mostafa
Trypanosomiasis or sleeping sickness is a protozoan disease that infects animals and humans transmitted by the bite of Glossina (tsetse) fly carrying Trypanosoma brucei1. Currently, trypanosomiasis affects more than 50 million cattle and 70 million people in sub-Saharan Africa2. The available current medicines record lack of efficiency, resistance, and toxicity, so there is an urgent need for the development of novel, safe, efficacious, cost-effective drugs with new mechanism of action3,4. In African countries where trypanosomiasis is prevalent, natural products (herbal extracts) have traditionally been utilised for centuries and are still extensively used to cure infections and other parasitic diseases5,6. Interestingly, about 30% of the world population has confidence in traditional therapies due to their wide availability and affordability7. Moreover, various drugs like quinine and artemisinin were established as plant-derived potential antiprotozoal agents8.
Benzoxaborole compounds for therapeutic uses: a patent review (2010- 2018)
Published in Expert Opinion on Therapeutic Patents, 2018
Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Human African trypanosomiasis (HAT), also known as African sleeping sickness, is commonly caused by protozoan parasites Trypanosoma brucei, which are transmitted through the tsetse fly of the genus Glossina [69]. The huge need for new, orally active drugs to safely treat HAT, and which are effective against all known strains of the parasite, led to wide screenings onto the library of benzoxaboroles (Figure 11), which resulted into the identification of 5 (SCYX-7158-AN5568, Figure 2) and 13 (Figure 13) as promising agents for HAT treatment [70]. SCYX-7158 entered phase I clinical trials in March 2012 [71]. It has been shown that the presence of the heterocyclic boron atom is essential for the antiparasitic activity, with the corresponding carbon analogs and acyclic boronic acids being inactive against T. brucei [70]. Chalcone–benzoxaborole hybrids (14, Figure 12) were designed to link two antitrypanosomal structures (benzoxaborole and chalcone) together to achieve greater efficacy [72].
Immunotoxins and nanobody-based immunotoxins: review and update
Published in Journal of Drug Targeting, 2021
Mohammad Reza Khirehgesh, Jafar Sharifi, Fatemeh Safari, Bahman Akbari
African protozoan parasite Trypanosoma brucei causes African trypanosomiasis or sleeping sickness. Apolipoprotein L-I (apoL-I) lysis the African trypanosomes except for resistant forms such as Trypanosoma brucei rhodesiense because of expression of a protein known as apoL-I neutralising serum resistance-associated (SRA). Tr-apoL-I, a modified format of apoL-I without the SRA-interacting domain, can overcome this resistance. The cell surface of Trypanosoma brucei rhodesiense is covered by a variant surface glycoprotein (VSG). As a result, many anti-VSG nanobodies are developed. For example, NbAn33, a non-trypanolytic Nb, can access the preserved cryptic epitopes of the VSG. Conjugation of NbAn33 to the Tr-apoL-I led to the generation of recombinant IT (NbAn33–Tr-apoL-I). The IT recognised and lysed the resistant Trypanosoma strains in the in vitro study in a dose-dependent manner. Also, in vivo studies in mouse models showed that the IT leads to complete parasite clearance and did not show any adverse symptoms [155].
Related Knowledge Centers
- African Trypanosomiasis
- Antigenic Variation
- Kinetoplast
- Trypanosoma
- Tsetse Fly
- Animal Trypanosomiasis
- Species Complex
- Disease Vector
- Variant Surface Glycoprotein
- Blood–Brain Barrier