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 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.

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.

scholarly journals APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Anneli Cooper ◽  
Hamidou Ilboudo ◽  
V Pius Alibu ◽  
Sophie Ravel ◽  
John Enyaru ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Human African Trypanosomiasis ◽  
Disease Risk ◽  
African Ancestry ◽  
Sub Saharan Africa ◽  
African Trypanosomiasis ◽  
African Trypanosomes ◽  
Risk Variants ◽  
Deleterious Alleles ◽  
Sub Saharan

Reduced susceptibility to infectious disease can increase the frequency of otherwise deleterious alleles. In populations of African ancestry, two apolipoprotein-L1 (APOL1) variants with a recessive kidney disease risk, named G1 and G2, occur at high frequency. APOL1 is a trypanolytic protein that confers innate resistance to most African trypanosomes, but not Trypanosoma brucei rhodesiense or T.b. gambiense, which cause human African trypanosomiasis. In this case-control study, we test the prevailing hypothesis that these APOL1 variants reduce trypanosomiasis susceptibility, resulting in their positive selection in sub-Saharan Africa. We demonstrate a five-fold dominant protective association for G2 against T.b. rhodesiense infection. Furthermore, we report unpredicted strong opposing associations with T.b. gambiense disease outcome. G2 associates with faster progression of T.b. gambiense trypanosomiasis, while G1 associates with asymptomatic carriage and undetectable parasitemia. These results implicate both forms of human African trypanosomiasis in the selection and persistence of otherwise detrimental APOL1 kidney disease variants.

scholarly journals α-d-Glucopyranosyl-(1→2)-[6-O-(l-tryptophanyl)-β-d-fructofuranoside]

Molbank ◽  
10.3390/m1066 ◽  
2019 ◽  
Vol 2019 (2) ◽  
pp. M1066
Author(s):  
Kwaku Kyeremeh ◽  
Samuel Kwain ◽  
Gilbert Mawuli Tetevi ◽  
Anil Sazak Camas ◽  
Mustafa Camas ◽  
...  
Keyword(s):  
Human African Trypanosomiasis ◽  
2D Nmr ◽  
Sub Saharan Africa ◽  
Western Region ◽  
Mangrove Plant ◽  
Chemical Profiling ◽  
Coptis Japonica ◽  
Full Structure ◽  
Sub Saharan ◽  
Uptake And Metabolism

The Mycobacterium sp. BRS2A-AR2 is an endophyte of the mangrove plant Rhizophora racemosa G. Mey., which grows along the banks of the River Butre, in the Western Region of Ghana. Chemical profiling using 1H-NMR and HRESI-LC-MS of fermentation extracts produced by the strain led to the isolation of the new compound, α-d-Glucopyranosyl-(1→2)-[6-O-(l-tryptophanyl)-β-d–fructofuranoside] or simply tortomycoglycoside (1). Compound 1 is an aminoglycoside consisting of a tryptophan moiety esterified to a disaccharide made up of β-d-fructofuranose and α-d-glucopyranose sugars. The full structure of 1 was determined using UV, IR, 1D, 2D-NMR and HRESI-LC-MS data. When tested against Trypanosoma brucei subsp. brucei, the parasite responsible for Human African Trypanosomiasis in sub-Saharan Africa, 1 (IC50 11.25 µM) was just as effective as Coptis japonica (Thunb.) Makino. (IC50 8.20 µM). The extract of Coptis japonica (Thunb.) Makino. is routinely used as laboratory standard due to its powerful antitrypanosomal activity. It is possible that, compound 1 interferes with the normal uptake and metabolism of tryptophan in the T. brucei subsp. brucei parasite.

scholarly journals Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gregory C. Davenport ◽  
James B. Hittner ◽  
Vincent Otieno ◽  
Zachary Karim ◽  
Harshini Mukundan ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Parasite Burden ◽  
Sub Saharan Africa ◽  
Mediation Model ◽  
Multiple Mediation ◽  
Mediators Of Inflammation ◽  
Threatening Condition ◽  
Life Threatening ◽  
Sub Saharan

Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[−]) enteric Bacilli andPlasmodium falciparum(Pf[+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/μL), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children (n=206, aged <3 yrs): healthy;Pf[+] alone; G[−] coinfected; and G[+] coinfected.Staphylococcus aureusand non-TyphiSalmonellawere the most frequently isolated G[+] and G[−] organisms, respectively. Coinfected children, particularly those with G[−] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN-γ, and IFN-αand decreased TNF-αrelative to malaria alone. Children with G[−] coinfection had higher IL-1βand IL-1Ra and lower IL-10 than thePf[+] group and higher IFN-γthan the G[+] group. To determine how the immune response to malaria regulates parasitemia, cytokine production was investigated with a multiple mediation model. Cytokines with the greatest mediational impact on parasitemia were IL-4, IL-10, IL-12, and IFN-γ. Results here suggest that enhanced immune activation, especially in G[−] coinfected children, acts to reduce malaria parasite burden.

scholarly journals PO 8421 LITERATURE REVIEW OF BIOMARKERS FOR HUMAN AFRICAN TRYPANOSOMIASIS POST-TREATMENT FOLLOW-UP

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A35.3-A36
Author(s):  
Lukusa Ngay ◽  
Veerle Lejon ◽  
Mumba Ngoyi
Keyword(s):  
Treatment Failure ◽  
Human African Trypanosomiasis ◽  
Post Treatment ◽  
Immunoglobulin M ◽  
Sub Saharan Africa ◽  
Tsetse Flies ◽  
African Trypanosomiasis ◽  
Cell Counts ◽  
Specificity And Sensitivity

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.

scholarly journals Innovative Partnerships for the Elimination of Human African Trypanosomiasis and the Development of Fexinidazole

2020 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
Philippe Neau ◽  
Heinz Hänel ◽  
Valérie Lameyre ◽  
Nathalie Strub-Wourgaft ◽  
Luc Kuykens
Keyword(s):  
Human African Trypanosomiasis ◽  
Oral Treatment ◽  
Treatment Options ◽  
European Medicines Agency ◽  
Neglected Diseases ◽  
African Trypanosomiasis ◽  
African Countries ◽  
Scientific Opinion ◽  
Sub Saharan ◽  
New Treatments

Human African Trypanosomiasis (HAT or sleeping sickness) is a life-threatening neglected tropical disease that is endemic in 36 sub-Saharan African countries. Until recently, treatment options were limited and hampered by unsatisfactory efficacy, toxicity, and long and cumbersome administration regimens, compounded by infrastructure inadequacies in the remote rural regions worst affected by the disease. Increased funding and awareness of HAT over the past two decades has led to a steady decline in reported cases (<1000 in 2018). Recent drug development strategies have resulted in development of the first all-oral treatment for HAT, fexinidazole. Fexinidazole received European Medicines Agency positive scientific opinion in 2018 and is now incorporated into the WHO interim guidelines as one of the first-line treatments for HAT, allowing lumbar puncture to become non-systematic. Here, we highlight the role of global collaborations in the effort to control HAT and develop new treatments. The long-standing collaboration between the WHO, Sanofi and the Drugs for Neglected Diseases initiative (Geneva, Switzerland) was instrumental for achieving the control and treatment development goals in HAT, whilst at the same time ensuring that efforts were led by national authorities and control programs to leave a legacy of highly trained healthcare workers and improved research and health infrastructure.

scholarly journals LINKING SATELLITE REMOTE SENSING BASED ENVIRONMENTAL PREDICTORS TO DISEASE: AN APPLICATION TO THE SPATIOTEMPORAL MODELLING OF SCHISTOSOMIASIS IN GHANA

2016 ◽  
Vol XLI-B8 ◽  
pp. 215-221
Author(s):  
M. Wrable ◽  
A. Liss ◽  
A. Kulinkina ◽  
M. Koch ◽  
N. K. Biritwum ◽  
...  
Keyword(s):  
Remote Sensing ◽  
Disease Transmission ◽  
Land Surface ◽  
Health Surveys ◽  
Risk Model ◽  
Clinical Symptoms ◽  
Sub Saharan Africa ◽  
Small Scale ◽  
Environmental Predictors ◽  
Sub Saharan

90% of the worldwide schistosomiasis burden falls on sub-Saharan Africa. Control efforts are often based on infrequent, small-scale health surveys, which are expensive and logistically difficult to conduct. Use of satellite imagery to predictively model infectious disease transmission has great potential for public health applications. Transmission of schistosomiasis requires specific environmental conditions to sustain freshwater snails, however has unknown seasonality, and is difficult to study due to a long lag between infection and clinical symptoms. To overcome this, we employed a comprehensive 8-year time-series built from remote sensing feeds. The purely environmental predictor variables: accumulated precipitation, land surface temperature, vegetative growth indices, and climate zones created from a novel climate regionalization technique, were regressed against 8 years of national surveillance data in Ghana. All data were aggregated temporally into monthly observations, and spatially at the level of administrative districts. The result of an initial mixed effects model had 41% explained variance overall. Stratification by climate zone brought the R<sup>2</sup> as high as 50% for major zones and as high as 59% for minor zones. This can lead to a predictive risk model used to develop a decision support framework to design treatment schemes and direct scarce resources to areas with the highest risk of infection. This framework can be applied to diseases sensitive to climate or to locations where remote sensing would be better suited than health surveys.

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.

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