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Parasitology Aug 2020Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense and caused devastating epidemics during the 20th... (Review)
Review
Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense and caused devastating epidemics during the 20th century. Due to effective control programs implemented in the last two decades, the number of reported cases has fallen to a historically low level. Although fewer than 977 cases were reported in 2018 in endemic countries, HAT is still a public health problem in endemic regions until it is completely eliminated. In addition, almost 150 confirmed HAT cases were reported in non-endemic countries in the last three decades. The majority of non-endemic HAT cases were reported in Europe, USA and South Africa, due to historical alliances, economic links or geographic proximity to disease-endemic countries. Furthermore, with the implementation of the 'Belt and Road' project, sporadic imported HAT cases have been reported in China as a warning sign of tropical diseases prevention. In this paper, we explore and interpret the data on HAT incidence and find no positive correlation between the number of HAT cases from endemic and non-endemic countries. This data will provide useful information for better understanding the imported cases of HAT globally in the post-elimination phase.
Topics: Communicable Diseases, Imported; Endemic Diseases; Humans; Incidence; Trypanosomiasis, African
PubMed: 32338232
DOI: 10.1017/S0031182020000645 -
Journal of Medical Entomology Mar 2022Human African trypanosomiasis (HAT), despite considerable progress in the control, is still occurring in many countries in both west and central African regions. The HAT... (Review)
Review
Human African trypanosomiasis (HAT), despite considerable progress in the control, is still occurring in many countries in both west and central African regions. The HAT situation in the Republic of Congo has always been overshadowed by its neighbor the Democratic Republic of Congo where over 60% of all HAT cases occur. In the Republic of Congo, HAT cases have been significantly reduced to about 20 reported cases yearly and the disease is still prevalent in few foci across the country. Although continuous assessment of HAT situation in Congo is been led by the National Control Program for HAT, research on the vector, parasite, and vector control has received little attention. Because there have not been enough reviews summarizing key findings from studies conducted so far, there is still a poor understanding of the global situation of HAT in Congo. In order to achieve sustainable elimination of HAT in Congo a deep appraisal of HAT situation is required. The present study provides a review of studies conducted on HAT in the republic of Congo since the 1950s to date in order to identify gaps in knowledge and help consolidate the gains and progress towards the elimination of sleeping sickness.
Topics: Animals; Democratic Republic of the Congo; Humans; Trypanosomiasis, African
PubMed: 35137146
DOI: 10.1093/jme/tjab225 -
Infectious Diseases of Poverty Jan 2022In recent years, a programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections led to a rapid decline in cases in...
BACKGROUND
In recent years, a programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections led to a rapid decline in cases in the Mandoul focus of Chad. To represent the biology of transmission between humans and tsetse, we previously developed a mechanistic transmission model, fitted to data between 2000 and 2013 which suggested that transmission was interrupted by 2015. The present study outlines refinements to the model to: (1) Assess whether elimination of transmission has already been achieved despite low-level case reporting; (2) quantify the role of intensified interventions in transmission reduction; and (3) predict the trajectory of gHAT in Mandoul for the next decade under different strategies.
METHOD
Our previous gHAT transmission model for Mandoul was updated using human case data (2000-2019) and a series of model refinements. These include how diagnostic specificity is incorporated into the model and improvements to the fitting method (increased variance in observed case reporting and how underreporting and improvements to passive screening are captured). A side-by-side comparison of fitting to case data was performed between the models.
RESULTS
We estimated that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (95% credible interval (CI) 99.9-100%, Specificity = 99.9%), the high screening and low infection levels mean that some recently reported cases with no parasitological confirmation might be false positives. We also find that the focus-wide tsetse reduction estimated through model fitting (95% CI 96.1-99.6%, Reduction = 99.1%) is comparable to the reduction previously measured by the decline in tsetse catches from monitoring traps. In line with previous results, the model suggests that transmission was interrupted in 2015 due to intensified interventions.
CONCLUSIONS
We recommend that additional confirmatory testing is performed in Mandoul to ensure the endgame can be carefully monitored. More specific measurement of cases, would better inform when it is safe to stop active screening and vector control, provided there is a strong passive surveillance system in place.
Topics: Animals; Chad; Humans; Mass Screening; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 35074016
DOI: 10.1186/s40249-022-00934-8 -
Chemical Derivatization and Characterization of Novel Antitrypanosomals for African Trypanosomiasis.Molecules (Basel, Switzerland) Jul 2021The search for novel antitrypanosomals and the investigation into their mode of action remain crucial due to the toxicity and resistance of commercially available...
The search for novel antitrypanosomals and the investigation into their mode of action remain crucial due to the toxicity and resistance of commercially available antitrypanosomal drugs. In this study, two novel antitrypanosomals, tortodofuordioxamide (compound ) and tortodofuorpyramide (compound ), were chemically derived from the natural N-alkylamide tortozanthoxylamide (compound ) through structural modification. The chemical structures of these compounds were confirmed through spectrometric and spectroscopic analysis, and their in vitro efficacy and possible mechanisms of action were, subsequently, investigated in () one of the causative species of African trypanosomiasis (AT). The novel compounds and displayed significant antitrypanosomal potencies in terms of half-maximal effective concentrations (EC) and selectivity indices (SI) (compound , EC = 7.3 μM, SI = 29.5; compound , EC = 3.2 μM, SI = 91.3; compound , EC = 4.5 μM, SI = 69.9). Microscopic analysis indicated that at the EC values, the compounds resulted in the coiling and clumping of parasite subpopulations without significantly affecting the normal ratio of nuclei to kinetoplasts. In contrast to the animal antitrypanosomal drug diminazene, compounds , and exhibited antioxidant absorbance properties comparable to the standard antioxidant Trolox (Trolox, 0.11 A; diminazene, 0.50 A; compound , 0.10 A; compound , 0.09 A; compound , 0.11 A). The analysis of growth kinetics suggested that the compounds exhibited a relatively gradual but consistent growth inhibition of at different concentrations. The results suggest that further pharmacological optimization of compounds and may facilitate their development into novel AT chemotherapy.
Topics: Animals; Mice; RAW 264.7 Cells; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosomiasis, African
PubMed: 34361641
DOI: 10.3390/molecules26154488 -
BMC Public Health Dec 2022Human African trypanosomiasis (HAT) is one of the world's classical neglected tropical diseases representing a major public health threat in sub-Saharan Africa. Although...
BACKGROUND
Human African trypanosomiasis (HAT) is one of the world's classical neglected tropical diseases representing a major public health threat in sub-Saharan Africa. Although the parasitic disease is in decline in the Republic of Congo, the better understanding of the epidemiological situation of active foci is required to reduce the risk of disease resurgence which could impede progress registered so far. The aim of this study was to determine the prevalence of HAT and the associated risk factors in individuals living in remote areas of the Republic of Congo.
METHODS
A cross-sectional survey was carried out in volunteers living in rural settings from June 2020 to January 2021. Socio-demographic and Clinical parameters of the participants were recorded. The presence of HAT-specific antibodies was assessed in whole blood, and then confirmed in serial diluted plasma samples using Card-Agglutination Trypanosomiasis Test (CATT)/T.b. gambiense CATT. The Capillary Tube Centrifugation (CTC) and Lymph nodes (LN) examination were done for detecting trypanosome parasites in CATT-serum positive cases. The staging of positive participants was determined by cerebrospinal fluid (CSF) examination.
RESULTS
Out of 8556 enrolled participants, 48.5% were more than 15 years old, 57.7% were unschooled and 67.2% practiced peasant activities. The prevalence of HAT infection was 0.3% with the predominance of patients at stage 1 of the disease (84.0%). The districts of Mindouli (OR: 25.9 (5.2-468); p = 0.0016) and Mpouya (OR: 13.3 (2.5-246); p = 0.0140) was revealed as the foci of high risk of HAT infection. Several factors were associated with an increased risk of HAT infection mainly including the non-schooling (OR: 5.1 (1.2-21.9); p = 0.0268), the life in couple or married (OR: 3.3 (1.0-11.3); p = 0.0545) and the practice of peasant activities (OR: 6.9 (2.4-29.3); p = 0.0017).
CONCLUSION
This study highlights the need of revising and strengthening the strategies of HAT control in Republic of Congo, using an approach which will take into account the education level, the marital status and the occupation of the population at risk.
Topics: Animals; Humans; Adolescent; Trypanosomiasis, African; Trypanosoma brucei gambiense; Cross-Sectional Studies; Agglutination Tests; Risk Factors
PubMed: 36510162
DOI: 10.1186/s12889-022-14577-9 -
Veterinary Parasitology Jul 2016African Animal Trypanosomiasis (AAT) is endemic in at least 37 of the 54 countries in Africa. It is estimated to cause direct and indirect losses to the livestock... (Review)
Review
African Animal Trypanosomiasis (AAT) is endemic in at least 37 of the 54 countries in Africa. It is estimated to cause direct and indirect losses to the livestock production industry in excess of US$ 4.5 billion per annum. A century of intervention has yielded limited success, owing largely to the extraordinary complexity of the host-parasite interaction. Trypanotolerance, which refers to the inherent ability of some African livestock breeds, notably Djallonke sheep, N'Dama cattle and West African Dwarf goats, to withstand a trypanosomiasis challenge and still remain productive without any form of therapy, is an economically sustainable option for combatting this disease. Yet trypanotolerance has not been adequately exploited in the fight against AAT. In this review, we describe new insights into the genetic basis of trypanotolerance and discuss the potential of exploring this phenomenon as an integral part of the solution for AAT, particularly, in the context of African animal production systems.
Topics: Africa; Animal Husbandry; Animals; Breeding; Disease Resistance; Livestock; Trypanosomiasis, African
PubMed: 27369574
DOI: 10.1016/j.vetpar.2016.05.003 -
Parasite Immunology 2004Human African trypanosomiasis or sleeping sickness is caused by infection with two subspecies of the tsetse-fly-vectored haemoflagellate parasite Trypanosoma brucei.... (Review)
Review
Human African trypanosomiasis or sleeping sickness is caused by infection with two subspecies of the tsetse-fly-vectored haemoflagellate parasite Trypanosoma brucei. Historically, epidemic sleeping sickness has caused massive loss of life, and related animal diseases have had a crucial impact on development in sub-Saharan Africa. After a period of moderately successful control during the mid-part of the 20th century, sleeping sickness incidence is currently rising, and control is hampered by a combination of factors, including civil unrest and the possible development of drug resistance by the parasites. The prevailing view is that the disease is invariably fatal without anti-trypanosomal drug treatment. However, there have also been intriguing reports of wide variations in disease severity as well as evidence of asymptomatic carriers of trypanosomes. These differences in the presentation of the disease will be discussed in the context of our knowledge of the immunology of trypanosomiasis. The impact of dysregulated inflammatory responses in both systemic and CNS pathology will be examined and the potential for host genotype variation in disease severity and control will be discussed.
Topics: Animals; Humans; Severity of Illness Index; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis, African; Tsetse Flies
PubMed: 15771682
DOI: 10.1111/j.0141-9838.2004.00731.x -
Parasitology Dec 2016Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic... (Review)
Review
Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.
Topics: Africa; Animals; Asia; Cattle; Drug Resistance; Insect Vectors; South America; Trypanocidal Agents; Trypanosoma; Trypanosomiasis; Trypanosomiasis, African; Trypanosomiasis, Bovine; Tsetse Flies
PubMed: 27719692
DOI: 10.1017/S0031182016001268 -
Clinical Infectious Diseases : An... Jul 2021The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection of living trypanosome... (Observational Study)
Observational Study
BACKGROUND
The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection of living trypanosome parasites in the blood or lymph node aspirate. Live parasites can, however, remain undetected in some seropositive individuals, who, we hypothesize, are infected with Trypanosoma brucei gambiense parasites in their extravascular dermis.
METHODS
To test this hypothesis, we conducted a prospective observational cohort study in the gHAT focus of Forecariah, Republic of Guinea. Of the 5417 subjects serologically screened for gHAT, 66 were enrolled into our study and underwent a dermatological examination. At enrollment, 11 seronegative, 8 unconfirmed seropositive, and 18 confirmed seropositive individuals had blood samples and skin biopsies taken and examined for trypanosomes by molecular and immunohistological methods.
RESULTS
In seropositive individuals, dermatological symptoms were significantly more frequent, relative to seronegative controls. T.b. gambiense parasites were present in the blood of all confirmed cases (n = 18) but not in unconfirmed seropositive individuals (n = 8). However, T. brucei parasites were detected in the extravascular dermis of all unconfirmed seropositive individuals and all confirmed cases. Skin biopsies of all treated cases and most seropositive untreated individuals progressively became negative for trypanosomes 6 and 20 months later.
CONCLUSIONS
Our results highlight the skin as a potential reservoir for African trypanosomes, with implications for our understanding of this disease's epidemiology in the context of its planned elimination and underlining the skin as a novel target for gHAT diagnostics.
Topics: Animals; Guinea; Humans; Prospective Studies; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 32638003
DOI: 10.1093/cid/ciaa897 -
Expert Review of Anti-infective Therapy Nov 2014Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of... (Review)
Review
Treatment of second-stage gambiense human African trypanosomiasis relied on toxic arsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine, initially in monotherapy and more recently in combination with nifurtimox (NECT), has drastically improved the prognosis of treated patients. However, NECT logistic and nursing requirements remain obstacles to its deployment and use in peripheral health structures in rural sub-Saharan Africa. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development. The main scope of this article is to discuss the potential impact of new oral therapies to improve diagnosis-treatment algorithms and patients' access to treatment, and to contribute to reach the objectives of the recently launched gambiense human African trypanosomiasis elimination program.
Topics: Animals; Disease Progression; Drug Therapy, Combination; Humans; Trypanocidal Agents; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 25204360
DOI: 10.1586/14787210.2014.959496