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1

VICKERMAN, KEITH. "The Trypanosomiases (ed. Maudlin, I., Holmes, P. H. & Miles, M. A.), pp. 624. International CABI Publishing, UK, 2004. ISBN 0 85199 475 X. £99.50 (US$185.00)." Parasitology 131, no. 3 (August 16, 2005): 436–37. http://dx.doi.org/10.1017/s0031182005238581.

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Back in the early 1960s, when the curtain was falling on British colonial administration in Africa, the newly-created Ministry of Overseas Development decided to gather together for posterity the expertise and experience of authorities on tsetse and trypanosomiasis control. Weighing in at three and a half pounds, the resulting publication, ‘The African Trypanosomiases’ edited by Colonel Hugh Mulligan and published in 1969, has since been a baseline not only for investigators in the field but also for pure scientists working on related problems at the laboratory bench. The editors of the present volume were inspired by the enormous progress made in trypanosomiasis research over the last thirty years to produce ‘an update of Mulligan’ – so, how do the two books compare? Well, amazingly, their weights are exactly the same – but content and coverage are, as might be expected, very different.
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2

Parwan, Deepika, Ranjan Kumar, and Sumit Aggrawal. "African Trypanosomiasis in Young Female in North India - A Rare Case Report." Annals of Pathology and Laboratory Medicine 8, no. 4 (May 10, 2021): C71–73. http://dx.doi.org/10.21276/apalm.2997.

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Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. It is caused by infection with protozoan parasites belonging to the genus Trypanosoma. They are transmitted to humans by tsetse fly (Glossina genus) bites which have acquired their infection from human beings or from animals harboring human pathogenic parasites. Tsetse flies are found just in sub-Saharan Africa though only certain species transmit the disease. We report a case of human African trypanosomiasis in a 28-year-old Indian female who had a travel history to sub–Saharan Africa, Uganda and she presented with a history of fever, body ache, headache, decreased oral intake, pain lower abdomen, swelling and discharge from forearm chancre since last 4-5 days. Peripheral smear showed heavy parasitemia by flagellated forms of Trypanosoma and the diagnosis of Trypanosoma brucei was given on Peripheral smear report. Serological testing was also done and a diagnosis of West-African trypanosomiasis was confirmed. The patient was successfully treated and made a good recovery. So West-African trypanosomiasis should be considered in the differential diagnosis with presentation of fever with chancre in every person with recent history of travel to African countries as it is universally fatal without treatment.
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3

Mulenga, Gloria M., Lars Henning, Kalinga Chilongo, Chrisborn Mubamba, Boniface Namangala, and Bruce Gummow. "Insights into the Control and Management of Human and Bovine African Trypanosomiasis in Zambia between 2009 and 2019—A Review." Tropical Medicine and Infectious Disease 5, no. 3 (July 11, 2020): 115. http://dx.doi.org/10.3390/tropicalmed5030115.

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Tsetse transmitted trypanosomiasis is a fatal disease commonly known as Nagana in cattle and sleeping sickness in humans. The disease threatens food security and has severe economic impact in Africa including most parts of Zambia. The level of effectiveness of commonly used African trypanosomiasis control methods has been reported in several studies. However, there have been no review studies on African trypanosomiasis control and management conducted in the context of One Health. This paper therefore seeks to fill this knowledge gap. A review of studies that have been conducted on African trypanosomiasis in Zambia between 2009 and 2019, with a focus on the control and management of trypanosomiasis was conducted. A total of 2238 articles were screened, with application of the search engines PubMed, PubMed Central and One Search. Out of these articles, 18 matched the required criteria and constituted the basis for the paper. An in-depth analysis of the 18 articles was conducted to identify knowledge gaps and evidence for best practices. Findings from this review provide stakeholders and health workers with a basis for prioritisation of African trypanosomiasis as an important neglected disease in Zambia and for formulation of One Health strategies for better control and/or management of the disease.
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4

Simarro, Pere P., Giuliano Cecchi, José R. Franco, Massimo Paone, Eric M. Fèvre, Abdoulaye Diarra, José Antonio Ruiz Postigo, Raffaele C. Mattioli, and Jean G. Jannin. "Risk for Human African Trypanosomiasis, Central Africa, 2000–2009." Emerging Infectious Diseases 17, no. 12 (December 2011): 2322–24. http://dx.doi.org/10.3201/eid1712.110921.

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5

Torr, S. J., G. A. Vale, and J. F. Morton. "Less is more: restricted application of pyrethroids for controlling tsetse." Proceedings of the British Society of Animal Science 2005 (2005): 31. http://dx.doi.org/10.1017/s175275620000942x.

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In Africa, the animal trypanosomiases kill about 3 million cattle each year with related annual losses in animal productivity of ∼£3 billion. 32 of the 36 affected countries have per capita incomes of less than US$1 per day. The most effective method of combating the trypanosomiases is to eradicate their vectors, the tsetse. Up to the early 1980s, responsibility for vector control in Africa was largely taken by government agencies, using techniques such as large-scale aerial and ground spraying. Following economic crises, structural adjustment and decline or privatisation of veterinary services, much of the onus for controlling tsetse has fallen on livestock keepers themselves (Eisler et al. 2003), but partly as a consequence of trypanosomiasis, many are too poor to afford the cost. Treating cattle with synthetic pyrethroids may provide a way of breaking this cycle of poverty and disease.
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6

Bacchi, Cyrus J. "Chemotherapy of Human African Trypanosomiasis." Interdisciplinary Perspectives on Infectious Diseases 2009 (2009): 1–5. http://dx.doi.org/10.1155/2009/195040.

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Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.
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7

Katabazi, Aziz, Adamu Almustapha Aliero, Sarah Gift Witto, Martin Odoki, and Simon Peter Musinguzi. "Prevalence of Trypanosoma congolense and Trypanosoma vivax in Lira District, Uganda." BioMed Research International 2021 (June 14, 2021): 1–7. http://dx.doi.org/10.1155/2021/7284042.

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Trypanosomes are the causative agents of animal African trypanosomiasis (AAT) and human African trypanosomiasis (HAT), the former affecting domestic animals prevalent in Sub-Saharan Africa. The main species causing AAT in cattle are T. congolense, T. vivax, and T. b. brucei. Northern Uganda has been politically unstable with no form of vector control in place. The return of displaced inhabitants led to the restocking of cattle from AAT endemic areas. It was thus important to estimate the burden of trypanosomiasis in the region. This study was designed to compare the prevalence of animal African trypanosomes in cattle in Lira District using microscopy and polymerase chain reaction amplification (PCR) methods. In this cross-sectional study, a total of 254 cattle from the three villages of Acanakwo A, Barropok, and Acungkena in Lira District, Uganda, were selected by simple random sampling technique and screened for trypanosomiasis using microscopy and PCR methods. The prevalence of trypanosomiasis according to microscopic results was 5/254 (2.0%) as compared to 11/254 (4.3%) trypanosomiasis prevalence according to PCR analysis. The prevalence of trypanosomiasis infection in the animal studied is 11/254 (4.3%). Trypanosoma congolense was the most dominant trypanosome species with a proportion of 9/11 (81.8%), followed by T. vivax 1/11 (9.1%) and mixed infection of T. congolense/T. vivax1/11 (9.1%). Barropok village had the highest prevalence of trypanosomiasis with 6/11 (54.5%). There is a statistically significant relationship ( OR = 6.041 ; 95% CI: 1.634-22.331; p < 0.05 ) between abnormal PCV and trypanosome infection. Polymerase reaction amplification was the most reliable diagnostic method due to its high sensitivity and specificity as compared to the conventional microscopic method. Polymerase reaction amplification appears to have adequate accuracy to substitute the use of a microscope where facilities allow. This study, therefore, underscores the urgent need for local surveillance schemes more especially at the grassroots in Uganda to provide data for reference guideline development needed for the control of trypanosomiasis in Uganda.
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8

Rogers, D. J. "Satellite imagery, tsetse and trypanosomiasis in Africa." Preventive Veterinary Medicine 11, no. 3-4 (December 1991): 201–20. http://dx.doi.org/10.1016/s0167-5877(05)80005-4.

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9

Kubata, Bruno Kilunga, Michael Duszenko, Zakayi Kabututu, Marc Rawer, Alexander Szallies, Ko Fujimori, Takashi Inui, et al. "Identification of a Novel Prostaglandin F2α Synthase in Trypanosoma brucei." Journal of Experimental Medicine 192, no. 9 (November 6, 2000): 1327–38. http://dx.doi.org/10.1084/jem.192.9.1327.

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Members of the genus Trypanosoma cause African trypanosomiasis in humans and animals in Africa. Infection of mammals by African trypanosomes is characterized by an upregulation of prostaglandin (PG) production in the plasma and cerebrospinal fluid. These metabolites of arachidonic acid (AA) may, in part, be responsible for symptoms such as fever, headache, immunosuppression, deep muscle hyperaesthesia, miscarriage, ovarian dysfunction, sleepiness, and other symptoms observed in patients with chronic African trypanosomiasis. Here, we show that the protozoan parasite T. brucei is involved in PG production and that it produces PGs enzymatically from AA and its metabolite, PGH2. Among all PGs synthesized, PGF2α was the major prostanoid produced by trypanosome lysates. We have purified a novel T. brucei PGF2α synthase (TbPGFS) and cloned its cDNA. Phylogenetic analysis and molecular properties revealed that TbPGFS is completely distinct from mammalian PGF synthases. We also found that TbPGFS mRNA expression and TbPGFS activity were high in the early logarithmic growth phase and low during the stationary phase. The characterization of TbPGFS and its gene in T. brucei provides a basis for the molecular analysis of the role of parasite-derived PGF2α in the physiology of the parasite and the pathogenesis of African trypanosomiasis.
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10

Frean, John, Willi Sieling, Hussein Pahad, Evan Shoul, and Lucille Blumberg. "Clinical management of East African trypanosomiasis in South Africa: Lessons learned." International Journal of Infectious Diseases 75 (October 2018): 101–8. http://dx.doi.org/10.1016/j.ijid.2018.08.012.

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11

Magez, Stefan, Joar Esteban Pinto Torres, Seoyeon Oh, and Magdalena Radwanska. "Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms That Ensure Survival in Plain Sight of the Adaptive Immune System." Pathogens 10, no. 6 (May 31, 2021): 679. http://dx.doi.org/10.3390/pathogens10060679.

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Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing human African trypanosomiasis (HAT—sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal trypanosomiasis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Saharan Africa. Through mechanical transmission, T. vivax has also been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical human trypanosomiasis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasites, but the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies that allow trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well as the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.
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12

Allsopp, R. "Options for vector control against trypanosomiasis in Africa." Parasitology Today 17, no. 1 (January 1, 2001): 15–19. http://dx.doi.org/10.1016/s0169-4758(00)01828-7.

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13

Allsopp, Reg. "Options for vector control against trypanosomiasis in Africa." Trends in Parasitology 17, no. 1 (January 2001): 15–19. http://dx.doi.org/10.1016/s1471-4922(00)01828-6.

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14

Schofield, Chris J., and John P. Kabayo. "Trypanosomiasis vector control in Africa and Latin America." Parasites & Vectors 1, no. 1 (2008): 24. http://dx.doi.org/10.1186/1756-3305-1-24.

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15

Croft, S. L., L. Vivas, and S. Brooker. "Recent advances in research and control of malaria, leishmaniasis, trypanosomiasis and schistosomiasis." Eastern Mediterranean Health Journal 9, no. 4 (September 21, 2003): 518–33. http://dx.doi.org/10.26719/2003.9.4.518.

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In the Eastern Mediterranean Region of the World Health Organization [WHO], malaria, schistosomiasis, leishmaniasis and trypanosomiasis are the parasitic diseases of major importance. Our review focuses on recent advances in the control and treatment of these diseases with particular reference to diagnosis, chemotherapy, vaccines, vector and environmental control. The Roll Back Malaria Programme, for example, emphasizes the use of insecticide treated bednets in Africa and targets a 30-fold increase in treated bednet use by 2007. Increasing risk factors for leishmaniasis include urbanization, extended agricultural projects and civil unrest and the increase in patients with Leishmania infantum and HIV co-infection in the Region may signal a new threat. In the past 20 years, human African trypanosomiasis has resurged in sub-Saharan Africa; within the Region it has become more common in the southern Sudan where anthroponotic and zoonotic sub-species infections overlap. Schistosomiasis in the Region is caused by either Schistosoma haematobium or S. mansoni and large-scale control efforts include providing regular treatment to at-risk groups and supporting drug delivery through schools.
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16

Carrington, Mark. "Slippery customers: How African trypanosomes evade mammalian defences." Biochemist 31, no. 4 (August 1, 2009): 8–11. http://dx.doi.org/10.1042/bio03104008.

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African trypanosomes are excellent parasites and can maintain an infection of a large mammalian host for months or years. In endemic areas, Human African Trypanosomiasis, also called sleeping sickness, has been largely unaffected by the advent of modern medicine, and trypanosomiasis of domestic livestock is a major restraint on productivity in endemic areas and is arguably the major contributor to the institutionalized poverty in much of rural sub-Saharan Africa1,2. A simple way of visualizing the effect of the livestock disease is to compare maps showing the distribution of livestock (www.ilri.org/InfoServ/Webpub/Fulldocs/Mappoverty/index.htm) and tsetse flies, the insect vector (www.fao.org/ag/AGAinfo/programmes/en/paat/maps.html): the lack of overlap is remarkable. Tsetse flies are only present in sub-Saharan Africa, and this probably restricted the spread of African trypanosomiasis until historical times. Livestock infections are now present in much of South Asia and South America, a product of long distance trade and adaptation of the trypanosomes to mechanical transmission3. The majority of research is on Trypanosoma brucei as this includes the human infective subspecies. This article provides a description of progress in the understanding the molecular details of how the trypanosome interacts with the mammalian immune system and how these studies have extended beyond this to fundamental aspects of eukaryotic cell biology.
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17

Dofuor, Kwain, Osei, Tetevi, Okine, Ohashi, Gwira, and Kyeremeh. "N-(Isobutyl)-3,4-methylenedioxy Cinnamoyl Amide." Molbank 2019, no. 3 (July 5, 2019): M1070. http://dx.doi.org/10.3390/m1070.

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The plant Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler is one of the most important medicinal species of the genus Zanthoxylum on the African continent. It is used in the treatment and management of parasitic diseases in sub-Saharan Africa. These properties have inspired scientists to investigate species within the genus for bioactive compounds. However, a study, which details a spectroscopic, spectrometric and bioactivity guided extraction and isolation of antiparasitic compounds from the genus Zanthoxylum is currently non-existent. Tortozanthoxylamide (1), which is a derivative of the known compound armatamide was isolated from Z. zanthoxyloides and the full structure determined using UV, IR, 1D/2D-NMR and high-resolution liquid chromatography tandem mass spectrometry (HRESI-LC-MS) data. When tested against Trypanosoma brucei subsp. brucei, the parasite responsible for animal African trypanosomiasis in sub-Saharan Africa, 1 (IC50 7.78 µM) was just four times less active than the commercially available drug diminazene aceturate (IC50 1.88 µM). Diminazene aceturate is a potent drug for the treatment of animal African trypanosomiasis. Tortozanthoxylamide (1) exhibits a significant antitrypanosomal activity through remarkable alteration of the cell cycle in T. brucei subsp. brucei, but it is selectively non-toxic to mouse macrophages RAW 264.7 cell lines. This suggests that 1 may be considered as a scaffold for the further development of natural antitrypanosomal compounds.
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18

Nesbitt, S. Tarimo, B. C. Njau, and L. H. Otieno. "Epizootiology of trypanosomiasis in Lambwe Valley, Kenya, East Africa." International Journal of Tropical Insect Science 12, no. 04 (August 1991): 379–84. http://dx.doi.org/10.1017/s1742758400011243.

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19

Dräger, N. "Tsetse fly control and Trypanosomiasis in Africa, quo vadis?" Bulletin de la Société de pathologie exotique 104, no. 1 (November 19, 2010): 90–92. http://dx.doi.org/10.1007/s13149-010-0087-3.

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20

HOLMES, P. H., E. KATUNGUKA-RWAKISHAYA, J. J. BENNISON, G. J. WASSINK, and J. J. PARKINS. "Impact of nutrition on the pathophysiology of bovine trypanosomiasis." Parasitology 120, no. 7 (May 2000): 73–85. http://dx.doi.org/10.1017/s0031182099005806.

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Trypanosomiasis is a major veterinary problem over much of sub-Saharan Africa and is frequently associated with undernutrition. There is growing evidence that nutrition can have a profound effect on the pathophysiological features of animal trypanosomiasis. These features include anaemia, pyrexia, body weight changes, reduced feed intake and diminished productivity including reduced draught work output, milk yield and reproductive capacity. Anaemia is a principal characteristic of trypanosomiasis and the rate at which it develops is influenced by both protein and energy intakes. Pyrexia is associated with increased energy demands for maintenance which is ultimately manifested by reductions in voluntary activity levels and productivity. Weight changes in trypanosomiasis are markedly influenced by the levels of protein intake. High intakes allow infected animals to grow at the same rate as uninfected controls providing energy intake is adequate whilst low energy levels can exacerbate the adverse effects of trypanosomiasis on body weight. Reductions in feed intake are less apparent in animals which are provided with high protein diets and where intake is limited by the disease animals will often exhibit preferential selection of higher quality browse. Further studies are required to evaluate the minimum levels of protein and energy supplementation required to ameliorate the adverse effect of trypanosomiasis, the nature and quality of protein supplement to achieve these benefits and the influence these have on digestive physiology.
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21

Sterkel, Marcos, Lee R. Haines, Aitor Casas-Sánchez, Vincent Owino Adung’a, Raquel J. Vionette-Amaral, Shannon Quek, Clair Rose, et al. "Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis." PLOS Biology 19, no. 1 (January 26, 2021): e3000796. http://dx.doi.org/10.1371/journal.pbio.3000796.

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Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.
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Keck, Devin, Callie Stuart, Josie Duncan, Emily Gullette, and Rodrigo Martinez-Duarte. "Highly Localized Enrichment of Trypanosoma brucei Parasites Using Dielectrophoresis." Micromachines 11, no. 6 (June 26, 2020): 625. http://dx.doi.org/10.3390/mi11060625.

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Human African trypanosomiasis (HAT), also known as sleeping sickness, is a vector-borne neglected tropical disease endemic to rural sub-Saharan Africa. Current methods of early detection in the affected rural communities generally begin with general screening using the card agglutination test for trypanosomiasis (CATT), a serological test. However, the gold standard for confirmation of trypanosomiasis remains the direct observation of the causative parasite, Trypanosoma brucei. Here, we present the use of dielectrophoresis (DEP) to enrich T. brucei parasites in specific locations to facilitate their identification in a future diagnostic assay. DEP refers to physical movement that can be selectively induced on the parasites when exposing them to electric field gradients of specific magnitude, phase and frequency. The long-term goal of our work is to use DEP to selectively trap and enrich T. brucei in specific locations while eluting all other cells in a sample. This would allow for a diagnostic test that enables the user to characterize the presence of parasites in specific locations determined a priori instead of relying on scanning a sample. In the work presented here, we report the characterization of the conditions that lead to high enrichment, 780% in 50 s, of the parasite in specific locations using an array of titanium microelectrodes.
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Abro, Zewdu, Menale Kassie, Beatrice Muriithi, Michael Okal, Daniel Masiga, Gift Wanda, Ouedraogo Gisèle, et al. "The potential economic benefits of controlling trypanosomiasis using waterbuck repellent blend in sub-Saharan Africa." PLOS ONE 16, no. 7 (July 20, 2021): e0254558. http://dx.doi.org/10.1371/journal.pone.0254558.

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Trypanosomiasis is a significant productivity-limiting livestock disease in sub-Saharan Africa, contributing to poverty and food insecurity. In this paper, we estimate the potential economic gains from adopting Waterbuck Repellent Blend (WRB). The WRB is a new technology that pushes trypanosomiasis-transmitting tsetse fly away from animals, improving animals’ health and increasing meat and milk productivity. We estimate the benefits of WRB on the production of meat and milk using the economic surplus approach. We obtained data from an expert elicitation survey, secondary and experimental sources. Our findings show that the adoption of WRB in 5 to 50% of the animal population would generate an economic surplus of US$ 78–869 million per annum for African 18 countries. The estimated benefit-cost ratio (9:1) further justifies an investment in WRB. The technology’s potential benefits are likely to be underestimated since our estimates did not include the indirect benefits of the technology adoption, such as the increase in the quantity and quality of animals’ draught power services and human and environmental health effects. These benefits suggest that investing in WRB can contribute to nutrition security and sustainable development goals.
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Chappuis, François, Louis Loutan, Pere Simarro, Veerle Lejon, and Philippe Büscher. "Options for Field Diagnosis of Human African Trypanosomiasis." Clinical Microbiology Reviews 18, no. 1 (January 2005): 133–46. http://dx.doi.org/10.1128/cmr.18.1.133-146.2005.

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SUMMARY Human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense or T. b. rhodesiense remains highly prevalent in several rural areas of sub-Saharan Africa and is lethal if left untreated. Therefore, accurate tools are absolutely required for field diagnosis. For T. b. gambiense HAT, highly sensitive tests are available for serological screening but the sensitivity of parasitological confirmatory tests remains insufficient and needs to be improved. Screening for T. b. rhodesiense infection still relies on clinical features in the absence of serological tests available for field use. Ongoing research is opening perspectives for a new generation of field diagnostics. Also essential for both forms of HAT is accurate determination of the disease stage because of the high toxicity of melarsoprol, the drug most widely used during the neurological stage of the illness. Recent studies have confirmed the high accuracy of raised immunoglobulin M levels in the cerebrospinal fluid for the staging of T. b. gambiense HAT, and a promising simple assay (LATEX/IgM) is being tested in the field. Apart from the urgent need for better tools for the field diagnosis of this neglected disease, improved access to diagnosis and treatment for the population at risk remains the greatest challenge for the coming years.
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Rodgers, Jean, Israel Steiner, and Peter G. E. Kennedy. "Generation of neuroinflammation in human African trypanosomiasis." Neurology - Neuroimmunology Neuroinflammation 6, no. 6 (August 29, 2019): e610. http://dx.doi.org/10.1212/nxi.0000000000000610.

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Human African trypanosomiasis (HAT) is caused by infection due to protozoan parasites of the Trypanosoma genus and is a major fatal disease throughout sub-Saharan Africa. After an early hemolymphatic stage in which the peripheral tissues are infected, the parasites enter the CNS causing a constellation of neurologic features. Although the CNS stage of HAT has been recognized for over a century, the mechanisms generating the neuroinflammatory response are complex and not well understood. Therefore a better understanding of the mechanisms utilized by the parasites to gain access to the CNS compartment is critical to explaining the generation of neuroinflammation. Contrast-enhanced MRI in a murine model of HAT has shown an early and progressive deterioration of blood-CNS barrier function after trypanosome infection that can be reversed following curative treatment. However, further studies are required to clarify the molecules involved in this process. Another important determinant of brain inflammation is the delicate balance of proinflammatory and counterinflammatory mediators. In mouse models of HAT, proinflammatory mediators such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and CXCL10 have been shown to be crucial to parasite CNS invasion while administration of interleukin (IL)-10, a counter inflammatory molecule, reduces the CNS parasite burden as well as the severity of the neuroinflammatory response and the clinical symptoms associated with the infection. This review focuses on information, gained from both infected human samples and animal models of HAT, with an emphasis on parasite CNS invasion and the development of neuroinflammation.
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Holmes, P. H., and S. J. Torr. "The Control of Animal Trypanosomiasis in Africa: Current Methods and Future Trends." Outlook on Agriculture 17, no. 2 (June 1988): 54–60. http://dx.doi.org/10.1177/003072708801700203.

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Current methods of trypanosomiasis control in Africa largely depend on eradication of the insect vector and the use of trypanocidal drugs. Both methods can be highly successful but suffer from various constraints. Recent studies have demonstrated how both methods may gain wider and more effective usage in the future.
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Gervas, Hamenyimana Emanuel, Nicholas Kwasi-Do Ohene Opoku, and Shamsuddeen Ibrahim. "Mathematical Modelling of Human African Trypanosomiasis Using Control Measures." Computational and Mathematical Methods in Medicine 2018 (November 22, 2018): 1–13. http://dx.doi.org/10.1155/2018/5293568.

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Human African trypanosomiasis (HAT), commonly known as sleeping sickness, is a neglected tropical vector-borne disease caused by trypanosome protozoa. It is transmitted by bites of infected tsetse fly. In this paper, we first present the vector-host model which describes the general transmission dynamics of HAT. In the tsetse fly population, the HAT is modelled by three compartments, while in the human population, the HAT is modelled by four compartments. The next-generation matrix approach is used to derive the basic reproduction number, R0, and it is also proved that if R0≤1, the disease-free equilibrium is globally asymptotically stable, which means the disease dies out. The disease persists in the population if the value of R0>1. Furthermore, the optimal control model is determined by using the Pontryagin’s maximum principle, with control measures such as education, treatment, and insecticides used to optimize the objective function. The model simulations confirm that the use of the three control measures is very efficient and effective to eliminate HAT in Africa.
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Matovu, Enock, Anne Juliet Kazibwe, Claire Mack Mugasa, Joseph Mathu Ndungu, and Zablon Kithingi Njiru. "Towards Point-of-Care Diagnostic and Staging Tools for Human African Trypanosomiaisis." Journal of Tropical Medicine 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/340538.

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Human African trypanosomiasis is a debilitating disease prevalent in rural sub-Saharan Africa. Control of this disease almost exclusively relies on chemotherapy that should be driven by accurate diagnosis, given the unacceptable toxicity of the few available drugs. Unfortunately, the available diagnostics are characterised by low sensitivities due to the inherent low parasitaemia in natural infections. Demonstration of the trypanosomes in body fluids, which is a prerequisite before treatment, often follows complex algorithms. In this paper, we review the available diagnostics and explore recent advances towards development of novel point-of-care diagnostic tests.
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Rajavel, Abirami, Felix Heinrich, Armin Otto Schmitt, and Mehmet Gültas. "Identifying Cattle Breed-Specific Partner Choice of Transcription Factors during the African Trypanosomiasis Disease Progression Using Bioinformatics Analysis." Vaccines 8, no. 2 (May 23, 2020): 246. http://dx.doi.org/10.3390/vaccines8020246.

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African Animal Trypanosomiasis (AAT) is a disease caused by pathogenic trypanosomes which affects millions of livestock every year causing huge economic losses in agricultural production especially in sub-Saharan Africa. The disease is spread by the tsetse fly which carries the parasite in its saliva. During the disease progression, the cattle are prominently subjected to anaemia, weight loss, intermittent fever, chills, neuronal degeneration, congestive heart failure, and finally death. According to their different genetic programs governing the level of tolerance to AAT, cattle breeds are classified as either resistant or susceptible. In this study, we focus on the cattle breeds N’Dama and Boran which are known to be resistant and susceptible to trypanosomiasis, respectively. Despite the rich literature on both breeds, the gene regulatory mechanisms of the underlying biological processes for their resistance and susceptibility have not been extensively studied. To address the limited knowledge about the tissue-specific transcription factor (TF) cooperations associated with trypanosomiasis, we investigated gene expression data from these cattle breeds computationally. Consequently, we identified significant cooperative TF pairs (especially D B P − P P A R A and D B P − T H A P 1 in N’Dama and D B P − P A X 8 in Boran liver tissue) which could help understand the underlying AAT tolerance/susceptibility mechanism in both cattle breeds.
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Mulenga, Gloria M., Boniface Namangala, Kalinga Chilongo, Chrisborn Mubamba, Kyoko Hayashida, Lars Henning, and Bruce Gummow. "Challenges in the Diagnostic Performance of Parasitological and Molecular Tests in the Surveillance of African Trypanosomiasis in Eastern Zambia." Tropical Medicine and Infectious Disease 6, no. 2 (April 30, 2021): 68. http://dx.doi.org/10.3390/tropicalmed6020068.

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African animal trypanosomiasis (AAT) control programs rely on active case detection through the screening of animals reared in disease endemic areas. This study compared the application of the polymerase chain reaction (PCR) and microscopy in the detection of trypanosomes in cattle blood in Mambwe, a rural district in eastern Zambia. Blood samples were collected from 227 cattle and tested for infection with trypanosomes using microscopy and Ribosomal RNA Internal Transcribed Spacers (ITS)-PCR. Microscopy on the buffy coat detected 17 cases, whilst thin and thick smears detected 26 cases and 28 cases, respectively. In total, microscopy detected 40 cases. ITS-PCR-filter paper (FP) on blood spots stored on FP detected 47 cases, and ITS-PCR-FTA on blood spots stored on Whatman FTA Classic cards detected 83 cases. Using microscopy as the gold standard, ITS-PCR-FTA had a better specificity (SP) and sensitivity (SE) (SP = 72.2%; SE = 77.5%; kappa = 0.35) than ITS-PCR-FP (SP = 88%; SE = 60%; kappa = 0.45). The prevalence of Trypanosoma brucei s.l. was higher on ITS-PCR-FTA (19/227) than on ITS-PCR-FP (0/227). Our results illustrate the complexities around trypanosomiasis surveillance in rural Africa and provide evidence of the impact that field conditions and staff training can have on diagnostic results, which in turn impact the success of tsetse and trypanosomiasis control programs in the region.
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31

Dickie, Emily A., Federica Giordani, Matthew K. Gould, Pascal Mäser, Christian Burri, Jeremy C. Mottram, Srinivasa P. S. Rao, and Michael P. Barrett. "New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story." Tropical Medicine and Infectious Disease 5, no. 1 (February 19, 2020): 29. http://dx.doi.org/10.3390/tropicalmed5010029.

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The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associated with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa. The Drugs for Neglected Disease initiative (DNDi), founded in 2003, has developed the first all oral therapy for both stage 1 and stage 2 HAT in fexinidazole. DNDi has also brought forward another oral therapy, acoziborole, potentially capable of curing both stage 1 and stage 2 disease in a single dosing. In this review article, we describe the remarkable successes in combating HAT through the twenty first century, bringing the prospect of the elimination of this disease into sight.
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Michel-Todó, Lucas, Pascal Bigey, Pedro A. Reche, María-Jesus Pinazo, Joaquim Gascón, and Julio Alonso-Padilla. "Design of an Epitope-Based Vaccine Ensemble for Animal Trypanosomiasis by Computational Methods." Vaccines 8, no. 1 (March 16, 2020): 130. http://dx.doi.org/10.3390/vaccines8010130.

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African animal trypanosomiasis is caused by vector-transmitted parasites of the genus Trypanosoma. T. congolense and T. brucei brucei are predominant in Africa; T. evansi and T. vivax in America and Asia. They have in common an extracellular lifestyle and livestock tropism, which provokes huge economic losses in regions where vectors are endemic. There are licensed drugs to treat the infections, but adherence to treatment is poor and appearance of resistances common. Therefore, the availability of a prophylactic vaccine would represent a major breakthrough towards the management and control of the disease. Selection of the most appropriate antigens for its development is a bottleneck step, especially considering the limited resources allocated. Herein we propose a vaccine strategy based on multiple epitopes from multiple antigens to counteract the parasites´ biological complexity. Epitopes were identified by computer-assisted genome-wide screenings, considering sequence conservation criteria, antigens annotation and sub-cellular localization, high binding affinity to antigen presenting molecules, and lack of cross-reactivity to proteins in cattle and other breeding species. We ultimately provide 31 B-cell, 8 CD4 T-cell, and 15 CD8 T-cell epitope sequences from 30 distinct antigens for the prospective design of a genetic ensemble vaccine against the four trypanosome species responsible for African animal trypanosomiasis.
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33

Rogers, D. J., and B. G. Williams. "Monitoring trypanosomiasis in space and time." Parasitology 106, S1 (January 1993): S77—S92. http://dx.doi.org/10.1017/s0031182000086133.

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SUMMARYThe paper examines the possible contributions to be made by Geographic Information Systems (GIS) to studies on human and animal trypanosomiasis in Africa. The epidemiological characteristics of trypanosomiasis are reviewed in the light of the formula for the basic reproductive rate or number of vector-borne diseases. The paper then describes how important biological characteristics of the vectors of trypanosomiasis in West Africa may be monitored using data from the NOAA series of meteorological satellites. This will lead to an understanding of the spatial distribution of both vectors and disease. An alternative, statistical approach to understanding the spatial distribution of tsetse, based on linear discriminant analysis, is illustrated with the example of Glossina morsitans in Zimbabwe, Kenya and Tanzania. In the case of Zimbabwe, a single climatic variable, the maximum of the mean monthly temperature, correctly predicts the pre-rinderpest distribution of tsetse over 82% of the country; additional climatic and vegetation variables do not improve considerably on this figure. In the cases of Kenya and Tanzania, however, another variable, the maximum of the mean monthly Normalized Difference Vegetation Index, is the single most important variable, giving correct predictions over 69 % of the area; the other climatic and vegetation variables improve this to 82 % overall. Such statistical analyses can guide field work towards the correct biological interpretation of the distributional limits of vectors and may also be used to make predictions about the impact of global change on vector ranges. Examples are given of the areas of Zimbabwe which would become climatically suitable for tsetse given mean temperature increases of 1, 2 and 3 °Centigrade. Five possible causes for sleeping sickness outbreaks are given, illustrated by the analysis of field data or from the output of mathematical models. One cause is abiotic (variation in rainfall), three are biotic (variation in vectorial potential, host immunity, or parasite virulence) and one is historical (the impact of explorers, colonizers and dictators). The implications for disease monitoring, in order to anticipate sleeping sickness outbreaks, are briefly discussed. It is concluded that present data are inadequate to distinguish between these hypotheses. The idea that sleeping sickness outbreaks are periodic (i.e. cyclical) is only barely supported by hard data. Hence it is even difficult to conclude whether the major cause of sleeping sickness outbreaks is biotic (which, in model situations, tends to produce cyclical epidemics) or abiotic. The conclusions emphasize that until we understand more about the variation in space and time of tsetse and trypanosomiasis distribution and abundance we shall not be in a position to benefit from the advances made by GIS. The potential is there, however, to re-introduce the spatial and temporal elements into epidemiological studies that are currently often neglected.
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MacLean, Lorna, John E. Chisi, Martin Odiit, Wendy C. Gibson, Vanessa Ferris, Kim Picozzi, and Jeremy M. Sternberg. "Severity of Human African Trypanosomiasis in East Africa Is Associated with Geographic Location, Parasite Genotype, and Host Inflammatory Cytokine Response Profile." Infection and Immunity 72, no. 12 (December 2004): 7040–44. http://dx.doi.org/10.1128/iai.72.12.7040-7044.2004.

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ABSTRACT The mechanisms underlying virulence in human African trypanosomiasis are poorly understood, although studies with experimental mice suggest that unregulated host inflammatory responses are associated with disease severity. We identified two trypanosomiasis foci with dramatically different disease virulence profiles. In Uganda, infections followed an acute profile with rapid progression to the late stage (meningoencephalitic infection) in the majority of patients (86.8%). In contrast, infections in Malawi were of a chronic nature, in which few patients progressed to the late stage (7.1%), despite infections of several months' duration. All infections were confirmed to be Trypanosoma brucei rhodesiense by testing for the presence of the serum resistance-associated (SRA) gene, but trypanosomes isolated from patients in Uganda or Malawi were distinguished by an SRA gene polymorphism. The two disease profiles were associated with markedly different levels of tumor necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β) in plasma. In Uganda but not Malawi early-stage TNF-α was elevated, while in Malawi but not Uganda early-stage TGF-β was elevated. Thus, rapid disease progression in Uganda is associated with TNF-α-mediated inflammatory pathology, whereas in the milder disease observed in Malawi this may be ameliorated by counterinflammatory cytokines. These differing host responses may result either from differing virulence phenotypes of northern and southern trypanosomes or from immune response polymorphisms in the different host populations.
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35

Mose, Jared Isaboke. "Gender and Transaction Costs in Crush-Pen Spraying for Trypanosomiasis Control in Kenya." Journal of Agricultural Science 9, no. 11 (October 16, 2017): 144. http://dx.doi.org/10.5539/jas.v9n11p144.

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Trypanosomiasis a widespread constraint in livestock production, mixed farming and human health in Africa has necessitated development of several technologies to ameliorate the effects of the disease. However delivery of these technologies to farmers has been undertaken on trial and error basis without a proper strategy leading to more failure than success and wastage of scarce resources. The purpose of this paper was to carry out an analysis of transaction costs associated with the use of communal crushpen in tsetse fly and trypanosomiasis control among smallholder cattle farms in Busia County, Kenya. The study utilized cross-sectional survey design and was guided by the New Institutional Economics approach. Stratified and simple random sampling technique was adopted to get 211 respondents. Data was collected by use of structured questionnaires and analyzed using descriptive and inferential statistics. Conjoint results showed that price was the most important factor influencing the farmers’ decision for crushpen use, accounting for 55.58%; distance accounted for 20.7% while trust accounted for 14.6% and group affiliation 8.7%. It is recommended that crush pens should be close to farms, managed by trustworthy people preferably belonging to farmers’ groups and charges levied for spraying the cows should be within the reach of farmers. The necessity of developing affordable Tsetse fly and Trypanosomiasis control methods in the war against Tsetse and Trypanosomiasis is supported by this study.
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36

Pereira, Claudio A., León A. Bouvier, María de los Milagros Cámara, and Mariana R. Miranda. "Singular Features of Trypanosomatids' Phosphotransferases Involved in Cell Energy Management." Enzyme Research 2011 (April 4, 2011): 1–12. http://dx.doi.org/10.4061/2011/576483.

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Trypanosomatids are responsible for economically important veterinary affections and severe human diseases. In Africa, Trypanosoma brucei causes sleeping sickness or African trypanosomiasis, while in America, Trypanosoma cruzi is the etiological agent of Chagas disease. These parasites have complex life cycles which involve a wide variety of environments with very different compositions, physicochemical properties, and availability of metabolites. As the environment changes there is a need to maintain the nucleoside homeostasis, requiring a quick and regulated response. Most of the enzymes required for energy management are phosphotransferases. These enzymes present a nitrogenous group or a phosphate as acceptors, and the most clear examples are arginine kinase, nucleoside diphosphate kinase, and adenylate kinase. Trypanosoma and Leishmania have the largest number of phosphotransferase isoforms ever found in a single cell; some of them are absent in mammals, suggesting that these enzymes are required in many cellular compartments associated to different biological processes. The presence of such number of phosphotransferases support the hypothesis of the existence of an intracellular enzymatic phosphotransfer network that communicates the spatially separated intracellular ATP consumption and production processes. All these unique features make phosphotransferases a promising start point for rational drug design for the treatment of human trypanosomiasis.
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37

Madeja, Ulrich-Dietmar, and Ulrike Schroeder. "From Colonial Research Spirit to Global Commitment: Bayer and African Sleeping Sickness in the Mirror of History." Tropical Medicine and Infectious Disease 5, no. 1 (March 10, 2020): 42. http://dx.doi.org/10.3390/tropicalmed5010042.

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In the early 20th century, a series of epidemics across equatorial Africa brought African sleeping sickness (human African trypanosomiasis, HAT) to the attention of the European colonial administrations. This disease presented an exciting challenge for microbiologists across Europe to study the disease, discover the pathogen and search for an effective treatment. In 1923, the first “remedy for tropical diseases”—Suramin—manufactured by Bayer AG came onto the market under the brand name “Germanin.” The development and life cycle of this product—which today is still the medicine of choice for Trypanosoma brucei (T.b), hodesiense infections—reflect medical progress as well as the successes and failures in fighting the disease in the context of historic political changes over the last 100 years.
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38

Nayupe, Symon F. "The use of molecular technology to investigate trypanosome infections in tsetse flies at Liwonde Wild Life Reserve." Malawi Medical Journal 31, no. 4 (December 31, 2020): 233–37. http://dx.doi.org/10.4314/mmj.v31i4.3.

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BackgroundTrypanosomes are protozoan flagellates that cause human African trypanosomiasis (HAT) and African animal trypanosomiasis (AAT). HAT is caused by Trypanosoma brucei rhodesiense in East and Central Africa and T.b. gambiense in West Africa, whereas AAT is caused by a number of trypanosome species, including T. brucei brucei, T. evansi, T. vivax, T. congolense, T. godfreyi and T. simiae. The aim of this study was to establish if tsetse flies at Liwonde Wild Life Reserve (LWLR) are infected with these trypanosomes and thus pose a risk to both humans and animals within and surrounding the LWLR. MethodsA total of 150 tsetse flies were caught. Of these, 82 remained alive after capture and were dissected such that the mid-gut could be examined microscopically for trypanosomes. DNA extractions were performed from both mid-guts and the 68 dead flies using a Qiagen Kit. Amplification techniques involved the Internal Transcriber Spacer 1 (ITS 1) conventional polymerase chain reaction (PCR) with primers designed to identify trypanosome species, and Repetitive Insertion Mobile Element – Loop Mediated Isothermal Amplification (RIME LAMP), a sequence specific to T. brucei.ResultsAnalysis showed that 79/82 (96.3%) of the mid-guts examined microscopically were positive for trypanosomes and that 75/150 (50%) of the DNA extracts (from the mid-gut, and tsetse fly carcasses) were positive for T. brucei, as determined by the RIME LAMP method. ITS1 PCR further showed that 87/150 (58.0%) flies were positive for trypanosomes, of which 56/87 (64.4%) were T. brucei, 9/87 (10.3%) were T. vivax; 7/87 (8.1%) were T. simiae; 6/87 (6.9%) were T. congolense, and 6/87 (6.9%) were T. godfreyi. Ten samples had a mixture of infections. ConclusionOur analysis demonstrated a mixture of infections from trypanosome species in tsetse flies at LWLR, and that T. brucei, the species that causes HAT, was the most common. Our study successfully used molecular techniques to demonstrate the presence of T. b. rhodesiense at LWLR, a species that causes HAT in both East and Central Africa.
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39

Mckendrick, Iain J., George Gettinby, Yiqun Gu, Andrew Peregrine, and Crawford Revie. "Hybrid Information Systems for Agriculture: The Case of Cattle Trypanosomiasis in Africa." Outlook on Agriculture 23, no. 4 (December 1994): 261–67. http://dx.doi.org/10.1177/003072709402300405.

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Large scale population growth in sub-Saharan Africa makes it imperative to achieve an equivalent increase in food production in this area. It is also important that any increase be sustainable in the long-term, not causing lasting damage to local ecosystems. Recent advances in information technology make the successful diffusion of relevant expertise to farmers a more practical option than ever before. How this might be achieved is described in this paper, which considers the transfer of expertise in the diagnosis, treatment and management of trypanosomiasis in cattle. Using current technology, the combination of different software systems in one integrated hybrid system could allow the delivery of high quality, well focused information to the potential user.
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40

Krafsur, E. S., J. G. Marquez, and J. O. Ouma. "Phylogeography and genealogy of the tsetse fly Glossina pallidipes (Diptera: Glossinidae)." International Journal of Tropical Insect Science 36, no. 01 (February 3, 2016): 32–47. http://dx.doi.org/10.1017/s1742758415000223.

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Glossina pallidipes, a widely but discontinuously distributed African savanna species, is one of the economically important tsetse flies because it is a vector of trypanosomiasis, a lethal disease of cattle and other domestic animals. DNA sequences of ribosomal (r16S2, 249 bp) and cytochrome oxidase I (COI, 421 bp) concatenated mitochondrial genes were analysed in 23 geographically diverse samples ofG. pallidipesfrom Ethiopia, Kenya, Tanzania, Zambia and Zimbabwe. Among 873 flies, we detected 181 composite haplotypes and found that their spatial diversities and frequency distributions were heterogeneous. Haplotype and nucleotide diversities were greatest in Ethiopia and least in southern Africa. We observed little haplotype and nucleotide diversity among regions, and detected severely limited maternal gene flow among the sampled populations (ΦST= 0.42). Tests for demographic stability and analysis of mismatch distributions revealed regionally contrasting demographic histories. The Ethiopian populations were phylogenetically the oldest and genetically the most diverse, and exhibited successive waves of contraction and expansion. The southern African populations were phylogenetically the youngest and genetically the least diverse, and showed only a single, recent expansion. Likely ecological correlates of historical tsetse fly demography include population suppression trials in East Africa and recurring rinderpest epizootics in southern Africa, beginning in the late nineteenth century that reduced host mammalian populations.
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41

Munang'andu, Hetron Mweemba, Victor Siamudaala, Musso Munyeme, and King Shimumbo Nalubamba. "A Review of Ecological Factors Associated with the Epidemiology of Wildlife Trypanosomiasis in the Luangwa and Zambezi Valley Ecosystems of Zambia." Interdisciplinary Perspectives on Infectious Diseases 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/372523.

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Trypanosomiasis has been endemic in wildlife in Zambia for more than a century. The disease has been associated with neurological disorders in humans. Current conservation strategies by the Zambian government of turning all game reserves into state-protected National Parks (NPs) and game management areas (GMAs) have led to the expansion of the wildlife and tsetse population in the Luangwa and Zambezi valley ecosystem. This ecological niche lies in the common tsetse fly belt that harbors the highest tsetse population density in Southern Africa. Ecological factors such as climate, vegetation and rainfall found in this niche allow for a favorable interplay between wild reservoir hosts and vector tsetse flies. These ecological factors that influence the survival of a wide range of wildlife species provide adequate habitat for tsetse flies thereby supporting the coexistence of disease reservoir hosts and vector tsetse flies leading to prolonged persistence of trypanosomiasis in the area. On the other hand, increase in anthropogenic activities poses a significant threat of reducing the tsetse and wildlife habitat in the area. Herein, we demonstrate that while conservation of wildlife and biodiversity is an important preservation strategy of natural resources, it could serve as a long-term reservoir of wildlife trypanosomiasis.
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42

Kwedi Nolna, Sylvie, Rodrigue Ntonè, Nicole Fouda Mbarga, Severin Mbainda, Willy Mutangala, Bernard Boua, Miriam Niba, and Aline Okoko. "Integration of Traditional Healers in Human African Trypanosomiasis Case Finding in Central Africa: A Quasi-Experimental Study." Tropical Medicine and Infectious Disease 5, no. 4 (November 17, 2020): 172. http://dx.doi.org/10.3390/tropicalmed5040172.

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Background: Based on the premise that Africans in rural areas seek health care from traditional healers, this study investigated a collaborative model between traditional healers and the national Human African Trypanosomiasis (HAT) programs across seven endemic foci in seven central African countries by measuring the model’s contribution to HAT case finding. Method: Traditional healers were recruited and trained by health professionals to identify HAT suspects based on its basics signs and symptoms and to refer them to the National Sleeping Sickness Control Program (NSSCP) for testing and confirmatory diagnosis. Results: 35 traditional healers were recruited and trained, 28 finally participated in this study (80%) and referred 278 HAT suspects, of which 20 (7.19%) were CATT positive for the disease. Most cases originated from Bandundu (45%) in the Democratic Republic of Congo and from Ngabe (35%) in Congo. Twelve (4.32%) patients had confirmatory diagnosis. Although a statistically significant difference was not shown in terms of case finding (p = 0.56), traditional healers were able to refer confirmed HAT cases that were ultimately cared for by NCSSPs. Conclusion: Integrating traditional healers in the control program of HAT will likely enhance the detection of cases, thereby, eventually contributing to the elimination of HAT in the most affected communities.
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43

Kwofie, Kofi D., Nguyen Huu Tung, Mitsuko Suzuki-Ohashi, Michael Amoa-Bosompem, Richard Adegle, Maxwell M. Sakyiamah, Frederick Ayertey, et al. "Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth." Antimicrobial Agents and Chemotherapy 60, no. 6 (March 7, 2016): 3283–90. http://dx.doi.org/10.1128/aac.01916-15.

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Trypanosoma bruceiparasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide.Morinda lucidaBenth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl3fraction ofM. lucidaleaves, which possess activity against the GUTat 3.1 strain ofT. brucei brucei. The 50% inhibitory concentrations (IC50) of molucidin, ML-2-3, and ML-F52 were 1.27 μM, 3.75 μM, and 0.43 μM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form ofTrypanosomaparasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.
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44

ADAMS, E. R., P. B. HAMILTON, A. C. RODRIGUES, I. I. MALELE, V. DELESPAUX, M. M. G. TEIXEIRA, and W. GIBSON. "NewTrypanosoma (Duttonella) vivaxgenotypes from tsetse flies in East Africa." Parasitology 137, no. 4 (December 7, 2009): 641–50. http://dx.doi.org/10.1017/s0031182009991508.

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SUMMARYSalivarian trypanosomes pose a substantial threat to livestock, but their full diversity is not known. To survey trypanosomes carried by tsetse in Tanzania, DNA samples from infected proboscides ofGlossina pallidipesandG. swynnertoniwere identified using fluorescent fragment length barcoding (FFLB), which discriminates species by size polymorphisms in multiple regions of the ribosomal RNA locus. FFLB identified the trypanosomes in 65 of 105 (61·9%) infected proboscides, revealing 9 mixed infections. Of 7 different FFLB profiles, 2 were similar but not identical to reference West AfricanTrypanosoma vivax; 5 other profiles belonged to known species also identified in fly midguts. Phylogenetic analysis of the glycosomal glyceraldehyde phosphate dehydrogenase gene revealed that the TanzanianT. vivaxsamples fell into 2 distinct groups, both outside the main clade of African and South AmericanT. vivax. These newT. vivaxgenotypes were common and widespread in tsetse in Tanzania. TheT. brucei-like trypanosome previously described from tsetse midguts was also found in 2 proboscides, demonstrating a salivarian transmission route. Investigation of mammalian host range and pathogenicity will reveal the importance of these new trypanosomes for the epidemiology and control of animal trypanosomiasis in East Africa.
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MacLeod, Michael, Vera Eory, William Wint, Alexandra Shaw, Pierre Gerber, Giuliano Cecchi, Raffaele Mattioli, Alasdair Sykes, and Timothy Robinson. "Assessing the Greenhouse Gas Mitigation Effect of Removing Bovine Trypanosomiasis in Eastern Africa." Sustainability 10, no. 5 (May 18, 2018): 1633. http://dx.doi.org/10.3390/su10051633.

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Trail, J. C. M., M. Murray, K. Sones, J. M. C. Jibbo, J. Durkin, and D. Light. "Boran cattle maintained by chemoprophylaxis under trypanosomiasis risk." Journal of Agricultural Science 105, no. 1 (August 1985): 147–66. http://dx.doi.org/10.1017/s0021859600055829.

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SUMMARYReproductive performance, mortality, growth, and culling and replacement rates based on 20000 calving records were evaluated for grade Boran beef cattle maintained with trypanocidal drugs in an area of high trypanosomiasis risk in Tanzania. Under ranching conditions, over a 10-year period in this area of high Glossina morsitans morsitans, G. pallidipes and G. brevipalpis challenge, a calving interval of 15·9 months, pre-weaning mortality of 8%, annual cow mortality of 5·8% and 8-month weaning weight of 133·5 kg resulted in a herd productivity of 96 kg of weaner calf per cow per year. The proportion of heifers required as replacements (45%) and the generation interval (6·9 years) indicated scope for implementation of selection programmes on growth traits. The level of productivity achieved compared favourably with major data sets recently analysed from pure Boran cattle under trypanosomiasis-free ranching conditions in Kenya, and from trypanotolerant N'Dama cattle in West Africa. These results indicate the possibility of improving livestock production in tsetse-infested areas by the rational use of chemoprophylaxis as an integral part of management.Year, season, cow age, calf sex and location on ranch had significant effects on practically all the traits of calving interval, pre-weaning mortality and growth, and cow productivity. Superior performance where bush clearance and tsetse fly control had taken place suggests that economic evaluation of these interventions should be attempted. The season of calving had a major effect on productivity. Cows of 5–8 years of age were the most productive, as were animals producing male calves, features well recognized in beef cattle production.An average of 4·4 treatments with Samorin, a prophylactic, and 0·6 treatments with Berenil, a therapeutic, were required per year. The number of treatments varied from year to year and by area, being greater in the south of the ranch where the tsetse challenge was considered higher. However, the age and season of calving had little effect on the number of treatments required. Despite such extensive use of trypanocidal drugs, there was no indication that drug resistance had developed or evidence that repeated inoculation of Samorin had affected productivity.Grading-up of small East African Zebu cattle to Boran over an 8-year period allowed annual comparison of birth weights, pre-weaning growth and weaning weights of two groups of calves, one having a higher level of Boran genes (varying from 12 to 6% higher annually) than the other. Those with the higher level of Boran genes performed better by 3·3% for all attributes studied, but as the percentage difference in Boran genes decreased, so did this difference. In an environment improved through bush clearance and tsetse fly control, the calves with higher levels of Boran genes were superior, but this superiority was not expressed in the unimproved environment.
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47

Seke Etet, Paul F., and M. Fawzi Mahomoodally. "New Insights in Staging and Chemotherapy of African Trypanosomiasis and Possible Contribution of Medicinal Plants." Scientific World Journal 2012 (2012): 1–16. http://dx.doi.org/10.1100/2012/343652.

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Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the speciesTrypanosoma brucei(T.b.). The increasing trend of HAT cases has been reversed, but according to WHO experts, new epidemics of this disease could appear. In addition, HAT is still a considerable burden for life quality and economy in 36 sub-Saharan Africa countries with 15–20 million persons at risk. Following joined initiatives of WHO and private partners, the fight against HAT was re-engaged, resulting in considerable breakthrough. We present here what is known at this day about HAT etiology and pathogenesis and the new insights in the development of accurate tools and tests for disease staging and severity monitoring in the field. Also, we elaborate herein the promising progresses made in the development of less toxic and more efficient trypanocidal drugs including the potential of medicinal plants and related alternative drug therapies.
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48

Ngay, Lukusa, Veerle Lejon, and Mumba Ngoyi. "PO 8421 LITERATURE REVIEW OF BIOMARKERS FOR HUMAN AFRICAN TRYPANOSOMIASIS POST-TREATMENT FOLLOW-UP." BMJ Global Health 4, Suppl 3 (April 2019): A35.3—A36. http://dx.doi.org/10.1136/bmjgh-2019-edc.92.

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IntroductionHuman African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and rhodesiense and is transmitted to humans by tsetse flies in sub-Saharan Africa. To detect cure or treatment failure, patients are followed up after treatment integrating the use of biomarkers in blood or cerebrospinal fluid (CSF).MethodsA systematic review of the literature according to the PRISMA Statement for Reporting Systematic Reviews was done, focusing on biological markers for HAT post-treatment follow-up. Articles were retrieved from PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) by using keywords: Human African Trypanosomiasis, Biomarkers, Follow up, Post treatment.ResultsA panel of biomarkers is used to detect relapses or to confirm recovery. For post-treatment follow-up, an examination of the CSF is performed. White blood cell counts in CSF with a defined cut-off value have been proven to be the most accurate to assess the treatment outcome. The intrathecal immunoglobulin M synthesis is a specific and sensitive parameter for the detection of CNS involvement in cases of HAT caused by T. brucei gambiense. The decrease of trypanosome-specific antibodies concentrations in CSF could be a good parameter for definite cure. High CSF IL-10 levels during treatment follow-up indicate recurring CNS inflammation and treatment failure. An increase of Neopterin in CSF and the presence of trypanosome spliced leader RNA in the blood have a high potential as predictors for treatment failure but need further validation.ConclusionNew biomarkers for post-treatment follow-up in HAT should 1) have high diagnostic specificity and sensitivity; 2) be applicable in field conditions; 3) preferentially be performed on blood and thus avoid the painful lumbar puncture during post-treatment control visits; and 4) shorten the follow-up period.
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Chritz, Kendra L., Fiona B. Marshall, M. Esperanza Zagal, Francis Kirera, and Thure E. Cerling. "Environments and trypanosomiasis risks for early herders in the later Holocene of the Lake Victoria basin, Kenya." Proceedings of the National Academy of Sciences 112, no. 12 (March 9, 2015): 3674–79. http://dx.doi.org/10.1073/pnas.1423953112.

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Specialized pastoralism developed ∼3 kya among Pastoral Neolithic Elmenteitan herders in eastern Africa. During this time, a mosaic of hunters and herders using diverse economic strategies flourished in southern Kenya. It has been argued that the risk for trypanosomiasis (sleeping sickness), carried by tsetse flies in bushy environments, had a significant influence on pastoral diversification and migration out of eastern Africa toward southern Africa ∼2 kya. Elmenteitan levels at Gogo Falls (ca. 1.9–1.6 kya) preserve a unique faunal record, including wild mammalian herbivores, domestic cattle and caprines, fish, and birds. It has been suggested that a bushy/woodland habitat that harbored tsetse fly constrained production of domestic herds and resulted in subsistence diversification. Stable isotope analysis of herbivore tooth enamel (n = 86) from this site reveals, instead, extensive C4 grazing by both domesticates and the majority of wild herbivores. Integrated with other ecological proxies (pollen and leaf wax biomarkers), these data imply an abundance of C4 grasses in the Lake Victoria basin at this time, and thus little risk for tsetse-related barriers to specialized pastoralism. These data provide empirical evidence for the existence of a grassy corridor through which small groups of herders could have passed to reach southern Africa.
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Shibata, Sayaka, J. Robert Gillespie, Angela M. Kelley, Alberto J. Napuli, Zhongsheng Zhang, Kuzma V. Kovzun, Ranae M. Pefley, et al. "Selective Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Trypanosoma brucei Infection in Mice." Antimicrobial Agents and Chemotherapy 55, no. 5 (January 31, 2011): 1982–89. http://dx.doi.org/10.1128/aac.01796-10.

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ABSTRACTHuman African trypanosomiasis continues to be an important public health threat in extensive regions of sub-Saharan Africa. Treatment options for infected patients are unsatisfactory due to toxicity, difficult administration regimes, and poor efficacy of available drugs. The aminoacyl-tRNA synthetases were selected as attractive drug targets due to their essential roles in protein synthesis and cell survival. Comparative sequence analysis disclosed differences between the trypanosome and mammalian methionyl-tRNA synthetases (MetRSs) that suggested opportunities for selective inhibition using drug-like molecules. Experiments using RNA interference on the single MetRS ofTrypanosoma bruceidemonstrated that this gene product was essential for normal cell growth. Small molecules (diaryl diamines) similar to those shown to have potent activity on prokaryotic MetRS enzymes were synthesized and observed to have inhibitory activity on theT. bruceiMetRS (50% inhibitory concentration, <50 nM) and on bloodstream forms ofT. bruceicultures (50% effective concentration, as low as 4 nM). Twenty-one compounds had a close correlation between enzyme binding/inhibition andT. bruceigrowth inhibition, indicating that they were likely to be acting on the intended target. The compounds had minimal effects on mammalian cell growth at 20 μM, demonstrating a wide therapeutic index. The most potent compound was tested in the murine model of trypanosomiasis and demonstrated profound parasite suppression and delayed mortality. A homology model of theT. bruceiMetRS based on other MetRS structures was used to model binding of the lead diaryl diamine compounds. Future studies will focus on improving the pharmacological properties of the MetRS inhibitors.
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