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BioMed Research International 2021Trypanosomes are the causative agents of animal African trypanosomiasis (AAT) and human African trypanosomiasis (HAT), the former affecting domestic animals prevalent in...
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 , , and . 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%). was the most dominant trypanosome species with a proportion of 9/11 (81.8%), followed by 1/11 (9.1%) and mixed infection of /1/11 (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; < 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.
Topics: Animals; Cattle; Communicable Disease Control; Cross-Sectional Studies; Geography; Humans; Polymerase Chain Reaction; Prevalence; Public Health; Reproducibility of Results; Trypanosoma congolense; Trypanosoma vivax; Trypanosomiasis, African; Uganda
PubMed: 34222483
DOI: 10.1155/2021/7284042 -
Metabolomics : Official Journal of the... Mar 2022Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (also known as sleeping sickness), a disease causing serious neurological disorders and fatal... (Review)
Review
BACKGROUND
Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (also known as sleeping sickness), a disease causing serious neurological disorders and fatal if left untreated. Due to its lethal pathogenicity, a variety of treatments have been developed over the years, but which have some important limitations such as acute toxicity and parasite resistance. Metabolomics is an innovative tool used to better understand the parasite's cellular metabolism, and identify new potential targets, modes of action and resistance mechanisms. The metabolomic approach is mainly associated with robust analytical techniques, such as NMR and Mass Spectrometry. Applying these tools to the trypanosome parasite is, thus, useful for providing new insights into the sleeping sickness pathology and guidance towards innovative treatments.
AIM OF REVIEW
The present review aims to comprehensively describe the T. brucei biology and identify targets for new or commercialized antitrypanosomal drugs. Recent metabolomic applications to provide a deeper knowledge about the mechanisms of action of drugs or potential drugs against T. brucei are highlighted. Additionally, the advantages of metabolomics, alone or combined with other methods, are discussed.
KEY SCIENTIFIC CONCEPTS OF REVIEW
Compared to other parasites, only few studies employing metabolomics have to date been reported on Trypanosoma brucei. Published metabolic studies, treatments and modes of action are discussed. The main interest is to evaluate the metabolomics contribution to the understanding of T. brucei's metabolism.
Topics: Animals; Drug Discovery; Humans; Metabolomics; Trypanosoma brucei brucei; Trypanosomiasis, African
PubMed: 35305174
DOI: 10.1007/s11306-022-01880-0 -
The American Journal of Tropical... Dec 2020Human African trypanosomiasis (HAT) remains a serious public health problem with diagnostic and treatment challenges in many African countries. The absence of a...
Human African trypanosomiasis (HAT) remains a serious public health problem with diagnostic and treatment challenges in many African countries. The absence of a gold-standard biomarker has been a major difficulty for accurate disease staging and treatment follow-up. We therefore attempted to develop a simple, affordable, and noninvasive biomarker for HAT diagnosis and staging. Simultaneous actigraphy and polysomnography as well as cerebrospinal fluid (CSF) white blood cell (WBC) count, trypanosome presence, and C-X-C motif ligand (CXCL)-10 cytokine levels were performed in 20 HAT patients and nine healthy individuals (controls) using standard procedures. The International HIV Dementia Scale (IHDS) was scored in some patients as a surrogate for clinical assessment. From actigraphic parameters, we developed a novel sleep score and used it to determine correlations with other HAT markers, and compared their performance in differentiating between patients and controls and between HAT stages. The novel actigraphy sleep score (ASS) had the following ranges: 0-25 (healthy controls), 67-103 (HAT stage I), 111-126 (HAT intermediate), and 133-250 (HAT stage II). Compared with controls, stage I patients displayed a 7-fold increase in the ASS ( < 0.01), intermediate stage patients a 10-fold increase ( < 0.001), and HAT stage II patients an almost 20-fold increase ( < 0.001). CXCL-10 showed high interindividual differences. White blood cell counts were only marked in HAT stage II patients with a high interindividual variability. The International HIV Dementia Scale score negatively correlated with the ASS. We report the development and better performance of a new biomarker, ASS, for HAT diagnosis, disease staging, and monitoring that needs to be confirmed in large cohort studies.
Topics: Actigraphy; Adolescent; Adult; Biomarkers; Child; Child, Preschool; Female; Humans; Leukocyte Count; Male; Middle Aged; Sleep; Trypanosoma brucei gambiense; Trypanosomiasis, African; Young Adult
PubMed: 33078699
DOI: 10.4269/ajtmh.20-0340 -
Revue Scientifique Et Technique... Jun 1990Tsetse-transmitted trypanosomiasis is one of the major constraints on the expansion of the livestock and agricultural industries in Africa. The disease affects animals... (Review)
Review
Tsetse-transmitted trypanosomiasis is one of the major constraints on the expansion of the livestock and agricultural industries in Africa. The disease affects animals and man, with direct and indirect losses estimated in billions of dollars annually. Because of the phenomenon of antigenic variation, no vaccine is available. Current prophylactic efforts must rely on tsetse control by the use of insecticides and on trypanocidal drugs. However, recent advances in our knowledge of tsetse and trypanosome biology are offering hope for alternative methods of trapping tsetse, new drugs and even vaccination. Possibly of even greater significance is the increasing sense that Africa herself might be able to contribute to the resolution of this problem. Over a period of several thousand years, she has generated cattle, such as the taurine N'Dama and West African Shorthorn breeds of West and Central Africa, that are now known to possess a significant degree of innate resistance to trypanosomiasis and several other important infectious diseases. These cattle are extremely well adapted to the environment and are now recognised as having considerable production potential. The ability to resist the development of anaemia in the face of infection, as assessed by packed red cell volume percent (PCV), has been shown to be correlated with the capacity to be productive, thereby identifying regulation of PCV as a key trait of trypanotolerance. Thus, an estimate of the ability of an infected animal to maintain PCV, following either experimental or field infection, could be used as a method for identifying trypanotolerant individuals. This could provide a means of estimating trypanotolerance heritability, thereby permitting rational breeding programmes to be instituted. Africa may thus provide the answer.
Topics: Animals; Breeding; Cattle; Immunity, Innate; Insect Control; Insect Vectors; Trypanosomiasis, African; Trypanosomiasis, Bovine; Tsetse Flies; Vaccination
PubMed: 2132686
DOI: 10.20506/rst.9.2.506 -
PLoS Neglected Tropical Diseases Oct 2020The Democratic Republic of the Congo (DRC) accounts for the majority of the reported gambiense human African trypanosomiasis (HAT) cases. Kongo Central province in the...
BACKGROUND
The Democratic Republic of the Congo (DRC) accounts for the majority of the reported gambiense human African trypanosomiasis (HAT) cases. Kongo Central province in the DRC reports a relatively low, yet steady number of cases, and forms a transboundary focus with Angola and the Republic of Congo. This paper describes an intervention aimed at reducing the case burden in Kongo Central by improving passive case detection, complemented with reactive screening.
METHODOLOGY/PRINCIPAL FINDINGS
At the initiation of this programme in August 2015, 620 health facilities were identified and equipped with Rapid Diagnostic Tests (RDTs) for HAT screening. Of these, 603 (97%) reported use of RDTs, and 584 (94%) that continued to use RDTs to the last quarter of 2016 were used in the analysis going forward. Among all health facilities involved, 23 were equipped to confirm HAT by microscopy, and 4 of the latter were equipped to perform molecular testing with loop-mediated isothermal amplification (LAMP). Patients clinically suspected of HAT were tested with an RDT and those with a positive RDT result were referred to the nearest microscopy facility for confirmatory testing. If RDT positive patients were negative by microscopy, they were tested by LAMP, either on fresh blood or blood that was dried on filter paper and transported to a facility performing LAMP. This network of diagnostic facilities reduced the median distance for a patient to travel to a screening facility from 13.7km when the classical card agglutination test for trypanosomiasis (CATT) was used as a screening test in the past, to 3.4km. As a consequence, passive case detection was improved by between 30% and 130% compared to the period before. Furthermore, the proportion of HAT cases detected in early stage disease by passive screening increased from 27% to 64%. Reactive screening took place in 20 villages where cases were reported by passive screening, and in 45 villages in the neighbourhood of these villages. Reactive screening was responsible for detection of 40% of cases, of which, 90% were in first stage of the disease.
CONCLUSIONS
This programme has demonstrated that it is possible to deploy passive screening for HAT at sub-country or country levels in the DRC, and this is made more effective when supplemented with reactive screening. Results and achievements showed an increase in the number of HAT cases detected, the majority of them in early disease, demonstrating that this strategy enables better population coverage and early detection of cases, which is critical in removing the HAT reservoir and interrupting transmission, and could contribute to HAT elimination in regions where it is implemented.
Topics: Animals; Democratic Republic of the Congo; Diagnostic Tests, Routine; Humans; Mass Screening; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 33057341
DOI: 10.1371/journal.pntd.0008779 -
Trends in Parasitology Sep 2008African trypanosomiasis is the collective name for a wide variety of trypanosome infections that affect humans and livestock. In recent years, experimental mice... (Review)
Review
African trypanosomiasis is the collective name for a wide variety of trypanosome infections that affect humans and livestock. In recent years, experimental mice infection models have provided new insights into both human and animal trypanosomiasis. Mouse models seem to be a valuable and versatile tool in trypanosomiasis-associated pathology and immunology research and highlight the variety shown by African trypanosomiases. Indeed, inbred mouse strains have enabled the study of genetic determinants of susceptibility and of the roles of anti-parasite antibodies, inflammatory mediators and anti-inflammatory mediators for each trypanosome species. Remarkable advances relating to the encephalitic stage of sleeping sickness have also been achieved thanks to murine models. The different contributions of murine models to the African trypanosomiases knowledge are presented here. Future search directions are finally proposed, with respect to mouse model opportunities and limitations.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Protozoan; Disease Models, Animal; Female; Interferon-gamma; Interleukin-10; Male; Mice; Mice, Inbred Strains; Mice, Knockout; Nitric Oxide; Nucleic Acid Hybridization; Trypanosomiasis, African; Tumor Necrosis Factor-alpha
PubMed: 18684669
DOI: 10.1016/j.pt.2008.05.010 -
PLoS Neglected Tropical Diseases Jul 2022Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly...
Gambiense human African trypanosomiasis (gHAT) has been targeted for elimination of transmission (EoT) to humans by 2030. Whilst this ambitious goal is rapidly approaching, there remain fundamental questions about the presence of non-human animal transmission cycles and their potential role in slowing progress towards, or even preventing, EoT. In this study we focus on the country with the most gHAT disease burden, the Democratic Republic of Congo (DRC), and use mathematical modelling to assess whether animals may contribute to transmission in specific regions, and if so, how their presence could impact the likelihood and timing of EoT. By fitting two model variants-one with, and one without animal transmission-to the human case data from 2000-2016 we estimate model parameters for 158 endemic health zones of the DRC. We evaluate the statistical support for each model variant in each health zone and infer the contribution of animals to overall transmission and how this could impact predicted time to EoT. We conclude that there are 24/158 health zones where there is substantial to decisive statistical support for some animal transmission. However-even in these regions-we estimate that animals would be extremely unlikely to maintain transmission on their own. Animal transmission could hamper progress towards EoT in some settings, with projections under continuing interventions indicating that the number of health zones expected to achieve EoT by 2030 reduces from 68/158 to 61/158 if animal transmission is included in the model. With supplementary vector control (at a modest 60% tsetse reduction) added to medical screening and treatment interventions, the predicted number of health zones meeting the goal increases to 147/158 for the model including animal transmission. This is due to the impact of vector reduction on transmission to and from all hosts.
Topics: Animals; Democratic Republic of the Congo; Forecasting; Humans; Models, Theoretical; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 35816487
DOI: 10.1371/journal.pntd.0010599 -
Pathogens and Global Health Jul 2013Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task.... (Review)
Review
Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol's toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox-eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT.
Topics: Africa; Antiprotozoal Agents; Drug Resistance; Drug Therapy; Drug Therapy, Combination; Humans; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 23916333
DOI: 10.1179/2047773213Y.0000000105 -
PLoS Neglected Tropical Diseases 2008Gambiense human African trypanosomiasis (HAT, sleeping sickness) is widely assumed to be 100% pathogenic and fatal. However, reports to the contrary exist, and human... (Review)
Review
Gambiense human African trypanosomiasis (HAT, sleeping sickness) is widely assumed to be 100% pathogenic and fatal. However, reports to the contrary exist, and human trypano-tolerance has been postulated. Furthermore, there is uncertainty about the actual duration of both stage 1 and stage 2 infection, particularly with respect to how long a patient remains infectious. Understanding such basic parameters of HAT infection is essential for optimising control strategies based on case detection. We considered the potential existence and relevance of human trypano-tolerance, and explored the duration of infectiousness, through a review of published evidence on the natural progression of gambiense HAT in the absence of treatment, and biological considerations. Published reports indicate that most gambiense HAT cases are fatal if untreated. Self-resolving and asymptomatic chronic infections probably constitute a minority if they do indeed exist. Chronic carriage, however, deserves further study, as it could seed renewed epidemics after control programmes cease.
Topics: Animals; Cameroon; Cote d'Ivoire; Disease Progression; Disease Reservoirs; Humans; Prevalence; Remission, Spontaneous; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 19104656
DOI: 10.1371/journal.pntd.0000303 -
PLoS Neglected Tropical Diseases 2012While the incidence of Human African Trypanosomiasis (HAT) is decreasing, the control approach is shifting from active population screening by mobile teams to passive... (Review)
Review
While the incidence of Human African Trypanosomiasis (HAT) is decreasing, the control approach is shifting from active population screening by mobile teams to passive case detection in primary care centers. We conducted a systematic review of the literature between 1970 and 2011 to assess which diagnostic tools are most suitable for use in first-line health facilities in endemic countries. Our search retrieved 16 different screening and confirmation tests for HAT. The thermostable format of the Card Agglutination Test for Trypanosomiasis (CATT test) was the most appropriate screening test. Lateral flow antibody detection tests could become alternative screening tests in the near future. Confirmation of HAT diagnosis still depends on visualizing the parasite in direct microscopy. All other currently available confirmation tests are either technically too demanding and/or lack sensitivity and thus rather inappropriate for use at health center level. Novel applications of molecular tests may have potential for use at district hospital level.
Topics: Diagnostic Tests, Routine; Endemic Diseases; Humans; Parasitology; Trypanosomiasis, African
PubMed: 23209860
DOI: 10.1371/journal.pntd.0001919