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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 -
Parasites & Vectors May 2018African animal trypanosomiasis is an economically significant disease that affects the livestock industry in Nigeria. It is caused by several parasites of the genus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
African animal trypanosomiasis is an economically significant disease that affects the livestock industry in Nigeria. It is caused by several parasites of the genus Trypanosoma. National estimates of the disease prevalence in livestock and tsetse flies are lacking, therefore a systematic review and meta-analysis were performed to understand the trend of the disease prevalence over the years.
METHODS
Publications were screened in Web of Science, Ovid MEDLINE, Global Health, EMBASE and PubMed databases. Using four-stage (identification, screening, eligibility and inclusion) process in the PRIMSA checklist, only studies that met the inclusion criteria for AAT and tsetse infections were analysed. Point estimates prevalence and subgroup analyses based on diagnostic techniques in livestock were evaluated at 95% confidence interval (CI).
RESULTS
A total of 74 eligible studies published between 1960 and 2017 were selected for meta-analysis. This covers the six geopolitical zones, involving a total of 53,924 animals. The overall prevalence of AAT was 16.1% (95% CI: 12.3-20.3%). Based on diagnostic techniques, the prevalence of AAT in cattle was highest in PCR followed by serology and microscopy while the highest prevalence in pigs was observed with serology. Out of 12,552 tsetse flies examined from 14 eligible studies, an overall prevalence of 17.3% (95% CI: 4.5-36.0%) and subgroup prevalence of 49.7% (95% CI: 30.7-68.8%), 11.5% (95% CI: 6.1-18.5) and 4.5% (95% CI: 1.8-8.8%) in G. morsitans, G. tachinoides and G. palpalis, respectively, were observed using the random effects-model.
CONCLUSIONS
The prevalence of trypanosomes in both vectors and animal hosts was high in Nigeria. Therefore, further research on risk factors, seasonal and transhumance effects, vectoral capacity and competence are warranted for an effective control of AAT in Nigeria.
Topics: Animals; Cattle; Insect Vectors; Livestock; Nigeria; Polymerase Chain Reaction; Prevalence; Risk Factors; Swine; Swine Diseases; Trypanosoma; Trypanosomiasis, African; Trypanosomiasis, Bovine; Tsetse Flies
PubMed: 29720251
DOI: 10.1186/s13071-018-2801-0 -
International Journal of Health... Nov 2023African trypanosomiasis is a tsetse-borne parasitic infection that affects humans, wildlife, and domesticated animals. Tsetse flies are endemic to much of Sub-Saharan...
BACKGROUND
African trypanosomiasis is a tsetse-borne parasitic infection that affects humans, wildlife, and domesticated animals. Tsetse flies are endemic to much of Sub-Saharan Africa and a spatial and temporal understanding of tsetse habitat can aid surveillance and support disease risk management. Problematically, current fine spatial resolution remote sensing data are delivered with a temporal lag and are relatively coarse temporal resolution (e.g., 16 days), which results in disease control models often targeting incorrect places. The goal of this study was to devise a heuristic for identifying tsetse habitat (at a fine spatial resolution) into the future and in the temporal gaps where remote sensing and proximal data fail to supply information.
METHODS
This paper introduces a generalizable and scalable open-access version of the tsetse ecological distribution (TED) model used to predict tsetse distributions across space and time, and contributes a geospatial Bayesian Maximum Entropy (BME) prediction model trained by TED output data to forecast where, herein the Morsitans group of tsetse, persist in Kenya, a method that mitigates the temporal lag problem. This model facilitates identification of tsetse habitat and provides critical information to control tsetse, mitigate the impact of trypanosomiasis on vulnerable human and animal populations, and guide disease minimization in places with ephemeral tsetse. Moreover, this BME analysis is one of the first to utilize cluster and parallel computing along with a Monte Carlo analysis to optimize BME computations. This allows for the analysis of an exceptionally large dataset (over 2 billion data points) at a finer resolution and larger spatiotemporal scale than what had previously been possible.
RESULTS
Under the most conservative assessment for Kenya, the BME kriging analysis showed an overall prediction accuracy of 74.8% (limited to the maximum suitability extent). In predicting tsetse distribution outcomes for the entire country the BME kriging analysis was 97% accurate in its forecasts.
CONCLUSIONS
This work offers a solution to the persistent temporal data gap in accurate and spatially precise rainfall predictions and the delayed processing of remotely sensed data collectively in the - 45 days past to + 180 days future temporal window. As is shown here, the BME model is a reliable alternative for forecasting future tsetse distributions to allow preplanning for tsetse control. Furthermore, this model provides guidance on disease control that would otherwise not be available. These 'big data' BME methods are particularly useful for large domain studies. Considering that past BME studies required reduction of the spatiotemporal grid to facilitate analysis. Both the GEE-TED and the BME libraries have been made open source to enable reproducibility and offer continual updates into the future as new remotely sensed data become available.
Topics: Animals; Humans; Bayes Theorem; Entropy; Reproducibility of Results; Trypanosomiasis, African; Tsetse Flies
PubMed: 37974150
DOI: 10.1186/s12942-023-00349-0 -
Acta Tropica Jan 2023African Trypanosomiasis is a debilitating disease in both humans and animals that occurs in sub-Saharan Africa and has a severe negative impact on the livelihood of...
African Trypanosomiasis is a debilitating disease in both humans and animals that occurs in sub-Saharan Africa and has a severe negative impact on the livelihood of people in the affected areas. The disease is caused by protozoan parasites of the genus Trypanosoma, which is often described simply as blood-borne; however, a number of studies have shown the parasite inhabits many different environments within the host. Control of the disease involves measures that include the use of trypanocidal drugs to which there are growing number of reported cases of resistance. Here, the patterns of trypanosome DNA presence during a diminazene aceturate treatment round on a cohort of cattle in Adidome, Ghana were assessed. A group of 24 cows were selected irrespective of age and sex and the infecting trypanosome species followed for 18 days before and after treatment with diminazene aceturate in the blood and skin of the animals using a diagnostic nested PCR that targeted the alpha-beta tubulin gene array. Persistence of trypanosome DNA was observed over the period and parasite DNA was readily detected in both the skin and blood, with parasite DNA disappearing and reappearing in both across the study. Moreover, there was limited correlation between the parasite DNA detected in the skin and blood. Overall, the data show the patterns of a natural trypanosome infection during drug treatment. In addition, the diagnostic potential of sampling the skin for African trypanosomiasis is highlighted.
Topics: Humans; Female; Cattle; Animals; Trypanosomiasis, African; Farms; Ghana; Trypanosoma; Diminazene; Trypanocidal Agents; Drug Resistance
PubMed: 36257455
DOI: 10.1016/j.actatropica.2022.106721 -
PLoS Neglected Tropical Diseases May 2020In 2012 human African trypanosomiasis (HAT), also known as sleeping sickness, was targeted for elimination as a public health problem, set to be achieved by 2020. The...
BACKGROUND
In 2012 human African trypanosomiasis (HAT), also known as sleeping sickness, was targeted for elimination as a public health problem, set to be achieved by 2020. The World Health Organization (WHO) provides here the 2018 update on the progress made toward that objective. Global indicators are reviewed, in particular the number of reported cases and the areas at risk. Recently developed indicators for the validation of HAT elimination at the national level are also presented.
METHODOLOGY/PRINCIPAL FINDINGS
With 977 cases reported in 2018, down from 2,164 in 2016, the main global indicator of elimination is already well within the 2020 target (i.e. 2,000 cases). Areas at moderate or higher risk (i.e. ≥ 1 case/10,000 people/year) are also steadily shrinking (less than 200,000 km2 in the period 2014-2018), thus nearing the 2020 target [i.e. 90% reduction (638,000 km2) from the 2000-2004 baseline (709,000 km2)]. Health facilities providing diagnosis and treatment of gambiense HAT continued to increase (+7% since the previous survey), with a better coverage of at-risk populations. By contrast, rhodesiense HAT health facilities decreased in number (-10.5%) and coverage. At the national level, eight countries meet the requirements to request validation of gambiense HAT elimination as a public health problem (i.e. Benin, Burkina Faso, Cameroon, Côte d'Ivoire, Ghana, Mali, Rwanda, and Togo), while for other endemic countries more efforts are needed in surveillance, control, or both.
CONCLUSIONS/SIGNIFICANCE
The 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status. Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal), by preparing for both the expected challenges (e.g. funding, coordination, integration of HAT control into regular health systems, development of more adapted tools, cryptic trypanosome reservoirs, etc.) and the unexpected ones.
Topics: Disease Eradication; Disease Transmission, Infectious; Global Health; Humans; Incidence; Trypanosomiasis, African; World Health Organization
PubMed: 32437391
DOI: 10.1371/journal.pntd.0008261 -
PLoS Neglected Tropical Diseases Mar 2019Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to Trypanosoma brucei subspecies. In addition to the well-established...
BACKGROUND
Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to Trypanosoma brucei subspecies. In addition to the well-established environmental and behavioural risks of becoming infected, there is evidence for a genetic component to the response to trypanosome infection. We undertook a candidate gene case-control study to investigate genetic associations further.
METHODOLOGY
We genotyped one polymorphism in each of seven genes (IL1A, IL1RN, IL4RN, IL6, HP, HPR, and HLA-G) in 73 cases and 250 controls collected from 19 ethno-linguistic subgroups stratified into three major ethno-linguistic groups, 2 pooled ethno-linguistic groups and 11 ethno-linguistic subgroups from three Cameroonian HAT foci. The seven polymorphic loci tested consisted of three SNPs, three variable numbers of tandem repeat (VNTR) and one INDEL.
RESULTS
We found that the genotype (TT) and minor allele (T) of IL1A gene as well as the genotype 1A3A of IL1RN were associated with an increased risk of getting Trypanosoma brucei gambiense and develop HAT when all data were analysed together and also when stratified by the three major ethno-linguistic groups, 2 pooled ethno-linguistic subgroups and 11 ethno-linguistic subgroups.
CONCLUSION
This study revealed that one SNP rs1800794 of IL1A and one VNTR rs2234663 of IL1RN were associated with the increased risk to be infected by Trypanosoma brucei gambiense and develop sleeping sickness in southern Cameroon. The minor allele T and the genotype TT of SNP rs1800794 in IL1A as well as the genotype 1A3A of IL1RN rs2234663 VNTR seem to increase the risk of getting Trypanosoma brucei gambiense infections and develop sleeping sickness in southern Cameroon.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Cameroon; Case-Control Studies; Child; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Neglected Diseases; Polymorphism, Single Nucleotide; Risk; Trypanosoma brucei gambiense; Trypanosomiasis, African; Young Adult
PubMed: 30908482
DOI: 10.1371/journal.pntd.0007283 -
PloS One 2017The incidence of gambiense human African trypanosomiasis (gHAT) in Uganda has been declining, from 198 cases in 2008, to only 20 in 2012. Interruption of transmission of...
INTRODUCTION
The incidence of gambiense human African trypanosomiasis (gHAT) in Uganda has been declining, from 198 cases in 2008, to only 20 in 2012. Interruption of transmission of the disease by early diagnosis and treatment is core to the control and eventual elimination of gHAT. Until recently, the format of available screening tests had restricted screening and diagnosis to central health facilities (passive screening). We describe a novel strategy that is contributing to elimination of gHAT in Uganda through expansion of passive screening to the entire population at risk.
METHODOLOGY / PRINCIPAL FINDINGS
In this strategy, patients who are clinically suspected of having gHAT at primary health facilities are screened using a rapid diagnostic test (RDT), followed by parasitological confirmation at strategically located microscopy centres. For patients who are positive with the RDT and negative by microscopy, blood samples undergo further testing using loop-mediated isothermal amplification (LAMP), a molecular test that detects parasite DNA. LAMP positive patients are considered strong suspects, and are re-evaluated by microscopy. Location and upgrading of facilities to perform microscopy and LAMP was informed by results of georeferencing and characterization of all public healthcare facilities in the 7 gHAT endemic districts in Uganda. Three facilities were upgraded to perform RDTs, microscopy and LAMP, 9 to perform RDTs and microscopy, and 200 to screen patients with RDTs. This reduced the distance that a sick person must travel to be screened for gHAT to a median distance of 2.5km compared to 23km previously. In this strategy, 9 gHAT cases were diagnosed in 2014, and 4 in 2015.
CONCLUSIONS
This enhanced passive screening strategy for gHAT has enabled full coverage of the population at risk, and is being replicated in other gHAT endemic countries. The improvement in case detection is making elimination of the disease in Uganda an imminent possibility.
Topics: Blood Buffy Coat; DNA, Protozoan; Health Facilities; Humans; Incidence; Microscopy; Nucleic Acid Amplification Techniques; Trypanosoma brucei gambiense; Trypanosomiasis, African; Uganda
PubMed: 29023573
DOI: 10.1371/journal.pone.0186429 -
Cell Host & Microbe Jul 2010Pathogens interact with their hosts at different spatial and temporal scales. Studying these interactions therefore requires a wide range of imaging tools and approaches... (Review)
Review
Pathogens interact with their hosts at different spatial and temporal scales. Studying these interactions therefore requires a wide range of imaging tools and approaches that bridge physics and biology, as shown by this Minireview focusing on recent studies of the causative agents of malaria, toxoplasmosis, and sleeping sickness.
Topics: Animals; Diagnostic Imaging; Host-Parasite Interactions; Malaria; Parasites; Trypanosomiasis, African
PubMed: 20638638
DOI: 10.1016/j.chom.2010.06.013 -
PLoS Neglected Tropical Diseases Sep 2021Spliced Leader (SL) trypanosome RNA is detectable only in the presence of live trypanosomes, is abundant and the Trypanozoon subgenus has a unique sequence. As...
BACKGROUND
Spliced Leader (SL) trypanosome RNA is detectable only in the presence of live trypanosomes, is abundant and the Trypanozoon subgenus has a unique sequence. As previously shown in blood from Guinean human African trypanosomiasis (HAT) patients, SL-RNA is an accurate target for diagnosis. Detection of SL-RNA in the cerebrospinal fluid (CSF) has never been attempted. In a large group of Congolese gambiense HAT patients, the present study aims i) to confirm the sensitivity of SL-RNA detection in the blood and; ii) to assess the diagnostic performance of SL-RNA compared to trypanosome detection in CSF.
METHODOLOGY/PRINCIPAL FINDINGS
Blood and CSF from 97 confirmed gambiense HAT patients from the Democratic Republic of Congo were collected using PAXgene blood RNA Tubes. Before RNA extraction, specimens were supplemented with internal extraction control RNA to monitor the extraction, which was performed with a PAXgene Blood RNA Kit. SL-RNA qPCR was carried out with and without reverse transcriptase to monitor DNA contamination. In blood, 92/97 (94.8%) HAT patients tested SL-RNA positive, which was significantly more than combined trypanosome detection in lymph and blood (78/97 positive, 80.4%, p = 0.001). Of 96 CSF RNA specimens, 65 (67.7%) were SL-RNA positive, but there was no significant difference between sensitivity of SL-RNA and trypanosome detection in CSF. The contribution of DNA to the Cq values was negligible. In CSF with normal cell counts, a fraction of SL-RNA might have been lost during extraction as indicated by higher internal extraction control Cq values.
CONCLUSIONS/SIGNIFICANCE
Detection of SL-RNA in blood and CSF allows sensitive demonstration of active gambiense HAT infection, even if trypanosomes remain undetectable in blood or lymph. As this condition often occurs in treatment failures, SL-RNA detection in blood and CSF for early detection of relapses after treatment deserves further investigation.
TRIAL REGISTRATION
This study was an integral part of the diagnostic trial "New Diagnostic Tools for Elimination of Sleeping Sickness and Clinical Trials: Early tests of Cure" (DiTECT-HAT-WP4, ClinicalTrials.gov Identifier: NCT03112655).
Topics: Democratic Republic of the Congo; Humans; RNA, Protozoan; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 34534223
DOI: 10.1371/journal.pntd.0009739 -
Journal of the Royal Society, Interface May 2012Climate warming over the next century is expected to have a large impact on the interactions between pathogens and their animal and human hosts. Vector-borne diseases...
Climate warming over the next century is expected to have a large impact on the interactions between pathogens and their animal and human hosts. Vector-borne diseases are particularly sensitive to warming because temperature changes can alter vector development rates, shift their geographical distribution and alter transmission dynamics. For this reason, African trypanosomiasis (sleeping sickness), a vector-borne disease of humans and animals, was recently identified as one of the 12 infectious diseases likely to spread owing to climate change. We combine a variety of direct effects of temperature on vector ecology, vector biology and vector-parasite interactions via a disease transmission model and extrapolate the potential compounding effects of projected warming on the epidemiology of African trypanosomiasis. The model predicts that epidemics can occur when mean temperatures are between 20.7°C and 26.1°C. Our model does not predict a large-range expansion, but rather a large shift of up to 60 per cent in the geographical extent of the range. The model also predicts that 46-77 million additional people may be at risk of exposure by 2090. Future research could expand our analysis to include other environmental factors that influence tsetse populations and disease transmission such as humidity, as well as changes to human, livestock and wildlife distributions. The modelling approach presented here provides a framework for using the climate-sensitive aspects of vector and pathogen biology to predict changes in disease prevalence and risk owing to climate change.
Topics: Africa; Animals; Climate Change; Feeding Behavior; Female; Humans; Insect Bites and Stings; Insect Vectors; Male; Models, Biological; Temperature; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 22072451
DOI: 10.1098/rsif.2011.0654