scholarly journals Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

PLoS Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. e3000796
Author(s):  
Marcos Sterkel ◽  
Lee R. Haines ◽  
Aitor Casas-Sánchez ◽  
Vincent Owino Adung’a ◽  
Raquel J. Vionette-Amaral ◽  
...  
Keyword(s):  
Degradation Pathway ◽  
Tyrosine Aminotransferase ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Environment Friendly ◽  
Insect Pollinator ◽  
Pollinator Species ◽  
Tyrosine Metabolism ◽  
Neurotoxic Insecticides ◽  
Sub Saharan

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.

scholarly journals Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

2020 ◽  
Author(s):  
Marcos Sterkel ◽  
Lee R. Haines ◽  
Aitor Casas-Sánchez ◽  
Vincent Owino Adung’a ◽  
Raquel J. Vionette-Amaral ◽  
...  
Keyword(s):  
Degradation Pathway ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Environment Friendly ◽  
Rnai Silencing ◽  
Insect Pollinator ◽  
Pollinator Species ◽  
Tyrosine Metabolism ◽  
Neurotoxic Insecticides ◽  
Sub Saharan

AbstractTsetse 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 insect pollinator species. Here we present a promising, environment-friendly alternative that targets insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded. RNAi silencing of either the first two enzymes in the tyrosine degradation pathway (TAT and 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, it did not affect bumblebee survival. A mathematical model shows that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current elimination programmes.

scholarly journals Chemotherapy of Human African Trypanosomiasis

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Cyrus J. Bacchi
Keyword(s):  
Combination Chemotherapy ◽  
Human African Trypanosomiasis ◽  
Economic Loss ◽  
Chemotherapeutic Agents ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Physical Suffering ◽  
Rural Clinics ◽  
Sub Saharan

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.

Optimizing stabilization of laterite as walling unit

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Sarfo Mensah ◽  
Collins Ameyaw ◽  
Blondel Akun Abaitey ◽  
Hayford Obeng Yeboah
Keyword(s):  
Compressive Strength ◽  
Building Material ◽  
Sub Saharan Africa ◽  
Target Strength ◽  
Environment Friendly ◽  
Suitable Alternative ◽  
Content Type ◽  
Sea Sand ◽  
Cement Stabilization ◽  
Sub Saharan

Purpose Over dependence on river/sea sand as building material has impacted the environment negatively. However, laterite, which is an environment-friendly indigenous building material in sub-Saharan Africa, has been less exploited as a suitable alternative. This paper aims to ascertain the optimum cement–laterite mix proportion at which laterite can be stabilized for production of walling units. Design/methodology/approach Using an experimental method, laterite was collected from three borrow pit sites. Sieve analysis was performed to determine the particle size distribution. Also, the degree of workability of the cement–laterite mix was ascertained using slump test. Compressive strengths were determined at cement stabilization percentages of 3%, 7% and 10% on 12 cubes of100 mm cast and cured for 14 and 28 days, respectively. Findings The results showed that the lateritic soil investigated, achieves its optimum strength in 28 days of curing, at a stabilization level of 10%. An average compressive strength of 2.41 N/mm2, which is 20.5% greater than the target strength, was achieved. Practical implications To meet the desired compressive strength of alternative walling units while achieving environmental sustainability and efficiency in production, cement stabilization of lateritic soils should become a recommended practice by built environment professionals in sub-Saharan Africa. Originality/value This paper is one of the first research works that attempts to determine the optimum level at which the abundant sub-Saharan laterite can be chemically stabilized for the production of non-load bearing walling units. This research promotes an environment-friendly alternative building material to sea sand, river sand and off-shore sand.

scholarly journals Assessment of animal African trypanosomiasis (AAT) vulnerability in cattle-owning communities of sub-Saharan Africa

2016 ◽  
Vol 9 (1) ◽  
Author(s):  
H. R. Holt ◽  
R. Selby ◽  
C. Mumba ◽  
G. B. Napier ◽  
J. Guitian
Keyword(s):  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Animal African Trypanosomiasis ◽  
Sub Saharan

scholarly journals Generation of neuroinflammation in human African trypanosomiasis

2019 ◽  
Vol 6 (6) ◽  
pp. e610 ◽  
Author(s):  
Jean Rodgers ◽  
Israel Steiner ◽  
Peter G. E Kennedy
Keyword(s):  
Human African Trypanosomiasis ◽  
Clinical Symptoms ◽  
Parasite Burden ◽  
Brain Inflammation ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Peripheral Tissues ◽  
Neuroinflammatory Response ◽  
Proinflammatory Mediators ◽  
Sub Saharan

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.

scholarly journals Slippery customers: How African trypanosomes evade mammalian defences

2009 ◽  
Vol 31 (4) ◽  
pp. 8-11
Author(s):  
Mark Carrington
Keyword(s):  
Cell Biology ◽  
Sub Saharan Africa ◽  
Mammalian Host ◽  
Tsetse Flies ◽  
Insect Vector ◽  
African Trypanosomiasis ◽  
Long Distance ◽  
African Trypanosomes ◽  
Endemic Areas ◽  
Sub Saharan

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.

scholarly journals New Insights in Staging and Chemotherapy of African Trypanosomiasis and Possible Contribution of Medicinal Plants

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Paul F. Seke Etet ◽  
M. Fawzi Mahomoodally
Keyword(s):  
Medicinal Plants ◽  
Life Quality ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Neuroinflammatory Disease ◽  
Disease Staging ◽  
Alternative Drug ◽  
Sub Saharan ◽  
Trypanocidal Drugs ◽  
Made In

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.

scholarly journals N-(Isobutyl)-3,4-methylenedioxy Cinnamoyl Amide

Molbank ◽  
10.3390/m1070 ◽  
2019 ◽  
Vol 2019 (3) ◽  
pp. M1070 ◽  
Author(s):  
Dofuor ◽  
Kwain ◽  
Osei ◽  
Tetevi ◽  
Okine ◽  
...  
Keyword(s):  
2D Nmr ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Diminazene Aceturate ◽  
Medicinal Species ◽  
Animal African Trypanosomiasis ◽  
Full Structure ◽  
Liquid Chromatography Tandem Mass ◽  
Sub Saharan ◽  
Potent Drug

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.

scholarly journals Towards Point-of-Care Diagnostic and Staging Tools for Human African Trypanosomiaisis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Enock Matovu ◽  
Anne Juliet Kazibwe ◽  
Claire Mack Mugasa ◽  
Joseph Mathu Ndungu ◽  
Zablon Kithingi Njiru
Keyword(s):  
Diagnostic Tests ◽  
Human African Trypanosomiasis ◽  
Point Of Care ◽  
Body Fluids ◽  
Accurate Diagnosis ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
Recent Advances ◽  
Sub Saharan ◽  
Unacceptable Toxicity

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.

scholarly journals Human African Trypanosomiasis: Ethnomedical and Biomedical Relationships

2000 ◽  
Vol 14 (1) ◽  
Author(s):  
Justin Brown
Keyword(s):  
Human African Trypanosomiasis ◽  
Explanatory Models ◽  
Sub Saharan Africa ◽  
World Health ◽  
African Trypanosomiasis ◽  
Sub Saharan ◽  
Biomedical Practitioners ◽  
Models Of Disease ◽  
Health Organization ◽  
The Relationship

Human African Trypanosomiasis (HAT) threatens more than 55 million people in sub-Saharan Africa. The focus of this paper is the relationship that exists between ethnomedical and biomedical practitioners regarding treatment of HAT. The relationship has been one of conflict. Biomedical practitioners have attempted to remove ethnomedicine from African society. This practice has been unsuccessful, especially in rural regions. Ethnomedical practitioners have adopted some aspects of biomedicine, but inadequate application and resources limit their efficacy. The biomedical community, including the World Health Organization, has not recognized the resource potential within ethnomedicine. An examination of the areas of conflict reveals differences in the explanatory models of disease causation and treatment methods. There has been some progress toward a cooperative model of healthcare, but most biomedical practitioners disregard ethnomedical techniques as primitive and ineffective. The conclusion of this paper presents a bleak future for the prevention and treatment of HAT in Africa. This future may be avoided with an increased level of cooperation and understanding between the two systems.

Sign in / Sign up

Export Citation Format

Share Document