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PLoS Neglected Tropical Diseases Dec 2016Control operations targeting Animal African Trypanosomiasis and its primary vector, the tsetse, were covering approximately 128,000 km2 of Africa in 2001, which is a... (Review)
Review
BACKGROUND
Control operations targeting Animal African Trypanosomiasis and its primary vector, the tsetse, were covering approximately 128,000 km2 of Africa in 2001, which is a mere 1.3% of the tsetse infested area. Although extensive trypanosomiasis and tsetse (T&T) control operations have been running since the beginning of the 20th century, Animal African Trypanosomiasis is still a major constraint of livestock production in sub-Saharan Africa.
METHODOLOGY/PRINCIPAL FINDINGS
We performed a systematic review of the existing literature describing T&T control programmes conducted in a selection of five African countries, namely Burkina Faso, Cameroon, Ethiopia, Uganda and Zambia, between 1980 and 2015. Sixty-eight documents were eventually selected from those identified by the database search. This was supplemented with information gathered through semi-structured interviews conducted with twelve key informants recruited in the study countries and selected based on their experience and knowledge of T&T control. The combined information from these two sources was used to describe the inputs, processes and outcomes from 23 major T&T control programmes implemented in the study countries. Although there were some data gaps, involvement of the target communities and sustainability of the control activities were identified as the two main issues faced by these programmes. Further, there was a lack of evaluation of these control programmes, as well as a lack of a standardised methodology to conduct such evaluations.
CONCLUSIONS/SIGNIFICANCE
Past experiences demonstrated that coordinated and sustained control activities require careful planning, and evidence of successes, failures and setbacks from past control programmes represent a mine of information. As there is a lack of evaluation of these programmes, these data have not been fully exploited for the design, analyses and justification of future control programmes.
Topics: Animals; Burkina Faso; Cameroon; Ethiopia; Insect Control; Trypanosomiasis, African; Tsetse Flies; Uganda; Zambia
PubMed: 28027299
DOI: 10.1371/journal.pntd.0005247 -
Pathogens (Basel, Switzerland) Sep 2022Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of... (Review)
Review
Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0−91.6); I2 = 96.99% (95% CI: 94.6−98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94−59.09) and 6.56% (3.06−11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr.
PubMed: 36297157
DOI: 10.3390/pathogens11101100 -
Tropical Medicine and Infectious Disease Aug 2022African trypanocide resistance is an emerging public health emergency whose control requires a revisit on farmer's knowledge, attitudes, and practices in developing... (Review)
Review
BACKGROUND
African trypanocide resistance is an emerging public health emergency whose control requires a revisit on farmer's knowledge, attitudes, and practices in developing countries. African animal trypanocide resistance (AATr) is rife in an environment where drug use and policy decisions are disjointed. The objective of the study was to identify community factors responsible for the development of AATr. This was important since diminazene aceturate (DA), isometamidium chloride (ISM), and homidium bromide (HB) have existed for over 30 years and no new drugs have been provided to farmers.
METHODS
An electronic keyword search across 12 databases was conducted using a search criterion from 1806 to June 2022. This generated a total of 24 publications, but after removing duplicates, review articles, and nonrelated articles, a total of eight papers were included in the analysis by following the PRISMA checklist. A meta-analysis was conducted on the data extracted and the risk ratio and inverse variance at 95% confidence interval were calculated using RevMan.
RESULTS
All the eight articles in the study showed that DA was the most preferred trypanocide in both West and Eastern Africa. Poor farmer knowledge of AATr and limited drug options were major drivers for trypanocide resistance. In addition, farmer treatments, use of untrained personnel, poor administration, poor dosing, and preparation of trypanocides were major drivers for the development of AATr and similarities were identified in DA and ISM practices (P = 0.13).
CONCLUSIONS
AATr is spread in developing countries due to a lack of community knowledge, attitudes, and drug-use practices. This situation could be reversed through interdisciplinary collaborations in endemic communities by promoting effective treatments and responsible drug handling.
PubMed: 36136616
DOI: 10.3390/tropicalmed7090205 -
Cureus Aug 2021Human African trypanosomiasis (HAT), or sleeping sickness disease, is an infection caused mainly by human African trypanosomiasis (g-HAT) and is transmitted by tsetse... (Review)
Review
Human African trypanosomiasis (HAT), or sleeping sickness disease, is an infection caused mainly by human African trypanosomiasis (g-HAT) and is transmitted by tsetse flies. The disease goes through two stages: hemolymphatic and meningo-encephalic phases. The treatment for the second stage has changed from melarsoprol or eflornithine to nifurtimox-eflornithine combination therapy (NECT) and fexinidazole. We aimed to systematically review the literature on the efficacy and toxicity of fexinidazole and NECT. We used PubMed advanced strategy and Google Scholar databases, including clinical trials and observational studies on humans in the last 20 years in the English literature. Applying the inclusion/exclusion criteria, we reviewed eight studies. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol. For assessing bias, we used the Cochrane Collaboration's tool for risk assessment of the clinical trials and the Robins-I tool for the observational studies. Overall, the clinical trials showed that NECT was non-inferior to eflornithine. The proportion of patients discharged alive is higher in patients treated with NECT vs. patients treated with eflornithine. Gastrointestinal complaints are a common side effect of NECT therapy, while fearful but relatively rare convulsions can also occur. The main limitation among the studies of NECT was the lack of blinding because most of them were open-label. Fexinidazole, the new oral medication showed is effective and safe for the treatment of g-HAT infection. Because of their convenience, fexinidazole is preferred over NECT therapy, oral vs. IV infusion in the first and second stages of the disease. Compared to older therapies, fexinidazole and NECT are more effective and safer than eflornithine and melarsoprol monotherapy.
PubMed: 34513456
DOI: 10.7759/cureus.16881 -
Frontiers in Veterinary Science 2022African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The...
BACKGROUND
African animal trypanocide resistance (AATr) continues to undermine global efforts to eliminate the transmission of African trypanosomiasis in endemic communities. The continued lack of new trypanocides has precipitated drug misuse and overuse, thus contributing to the development of the AATr phenotype. In this study, we investigated the threat associated with AATr by using the major globally available chemotherapeutical agents.
METHODS
A total of seven electronic databases were screened for an article on trypanocide resistance in AATr by using keywords on preclinical and clinical trials with the number of animals with treatment relapse, days taken to relapse, and resistant gene markers using the PRISMA checklist. Data were cleaned using the SR deduplicator and covidence and analyzed using Cochrane RevMan®. Dichotomous outputs were presented using risk ratio (RR), while continuous data were presented using the standardized mean difference (SMD) at a 95% confidence interval.
RESULTS
A total of eight publications in which diminazene aceturate (DA), isometamidium chloride (ISM), and homidium chloride/bromide (HB) were identified as the major trypanocides were used. In all preclinical studies, the development of resistance was in the order of HB > ISM > DA. DA vs. ISM (SMD = 0.15, 95% CI: -0.54, 0.83; = 46%, = 0.05), DA vs. HB (SMD = 0.96, 95% CI: 0.47, 1.45; = 0%, = 0.86), and HB vs. ISM (SMD = -0.41, 95% CI: -0.96, 0.14; = 5%, = 0.38) showed multiple cross-resistance. Clinical studies also showed evidence of multi-drug resistance on DA and ISM (RR = 1.01, 95% CI: 0.71-1.43; = 46%, = 0.16). To address resistance, most preclinical studies increased the dosage and the treatment time, and this failed to improve the patient's prognosis. Major markers of resistance explored include AT1, P1/P2 transporters, folate transporters, such as F-I, F-II, F-III, and polyamine biosynthesis inhibitors. In addition, immunosuppressed hosts favor the development of AATr.
CONCLUSION
AATr is a threat that requires a shift in the current disease control strategies in most developing nations due to inter-species transmission. Multi-drug cross-resistance against the only accessible trypanocides is a major public health risk, justifying the need to revise the policy in developing countries to promote control of African trypanosomiasis.
PubMed: 36686196
DOI: 10.3389/fvets.2022.950248 -
Scientific Reports Nov 2023African animal trypanosomiasis (AAT) is one of the major constraints to animal health and production in sub-Saharan Africa. To inform AAT control in Uganda and help...
African animal trypanosomiasis (AAT) is one of the major constraints to animal health and production in sub-Saharan Africa. To inform AAT control in Uganda and help advance along the progressive control pathway (PCP), we characterized AAT prevalence among eight host species in Uganda and explored factors that influence the prevalence variation between studies. We retrieved AAT prevalence publications (n = 2232) for Uganda (1980-2022) from five life sciences databases, focusing on studies specifying AAT detection methods, sample size, and the number of trypanosome-positive animals. Following PRISMA guidelines, we included 56 publications, and evaluated publication bias by the Luis Furuya-Kanamori (LFK) index. National AAT prevalence under DNA diagnostic methods for cattle, sheep and goats was 22.15%, 8.51% and 13.88%, respectively. Under DNA diagnostic methods, T. vivax was the most common Trypanosoma sp. in cattle (6.15%, 95% CI: 2.91-10.45) while T. brucei was most common among small ruminants (goats: 8.78%, 95% CI: 1.90-19.88, and sheep: 8.23%, 95% CI: 4.74-12.50, respectively). Northern and Eastern regions accounted for the highest AAT prevalence. Despite the limitations of this study (i.e., quality of reviewed studies, underrepresentation of districts/regions), we provide insights that could be used for better control of AAT in Uganda and identify knowledge gaps that need to be addressed to support the progressive control of AAT at country level and other regional endemic countries with similar AAT eco-epidemiology.
Topics: Animals; Cattle; Sheep; Animals, Domestic; Livestock; Prevalence; Uganda; Trypanosomiasis, African; Trypanosoma; Ruminants; Goats; DNA; Tsetse Flies
PubMed: 37990067
DOI: 10.1038/s41598-023-47141-5 -
Scientific Reports Dec 2021Human African trypanosomiasis (HAT) is endemic in Africa; hence, the possibility of co-infection with malaria among patients with HAT exists. The present study... (Meta-Analysis)
Meta-Analysis
Human African trypanosomiasis (HAT) is endemic in Africa; hence, the possibility of co-infection with malaria among patients with HAT exists. The present study investigated co-infection with malaria among patients with HAT to provide current evidence and characteristics to support further studies. Potentially relevant studies that reported Plasmodium spp. infection in patients with HAT was searched in PubMed, Web of Science, and Scopus. The risk of bias among the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. The pooled prevalence of Plasmodium spp. infection in patients with HAT was quantitatively synthesized using a random-effects model. Subgroup analyses of study sites and stages of HAT were performed to identify heterogeneity regarding prevalence among the included studies. The heterogeneity of the outcome among the included studies was assessed using Cochran's Q and I statistics for consistency. Publication bias was assessed if the number of included studies was 10 or more. For qualitative synthesis, a narrative synthesis of the impact of Plasmodium spp. infection on the clinical and outcome characteristics of HAT was performed when the included studies provided qualitative data. Among 327 studies identified from three databases, nine studies were included in the systematic review and meta-analysis. The prevalence of Plasmodium spp. co-infection (692 cases) among patients with HAT (1523 cases) was 50% (95% confidence interval [CI] = 28-72%, I = 98.1%, seven studies). Subgroup analysis by type of HAT (gambiense or rhodesiense HAT) revealed that among patients with gambiense HAT, the pooled prevalence of Plasmodium spp. infection was 46% (95% CI = 14-78%, I = 96.62%, four studies), whereas that among patients with rhodesiense HAT was 44% (95% CI = 40-49%, I = 98.3%, three studies). Qualitative syntheses demonstrated that Plasmodium spp. infection in individuals with HAT might influence the risk of encephalopathy syndrome, drug toxicity, and significantly longer corrected QT time. Moreover, longer hospital stays and higher treatment costs were recorded among co-infected individuals. Because of the high prevalence of malaria among patients with HAT, some patients were positive for malaria parasites despite being asymptomatic. Therefore, it is suggested to test every patient with HAT for malaria before HAT treatment. If malaria is present, then antimalarial treatment is recommended before HAT treatment. Antimalarial treatment in patients with HAT might decrease the probability of poor clinical outcomes and case fatality in HAT.
Topics: Africa; Coinfection; Geography, Medical; Humans; Malaria; Patient Outcome Assessment; Prevalence; Public Health Surveillance; Publication Bias; Registries; Trypanosomiasis, African
PubMed: 34893680
DOI: 10.1038/s41598-021-03295-8 -
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 -
The Cochrane Database of Systematic... Jun 2013Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment. Few drugs are currently available for second-stage sleeping sickness, with considerable adverse events and variable efficacy.
OBJECTIVES
To evaluate the effectiveness and safety of drugs for treating second-stage human African trypanosomiasis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register (January 2013), CENTRAL (The Cochrane Library Issue 12 2012) , MEDLINE (1966 to January 2013), EMBASE (1974 to January 2013), LILACS (1982 to January 2013 ), BIOSIS (1926-January 2013), mRCT (January 2013) and reference lists. We contacted researchers working in the field and organizations.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials including adults and children with second-stage HAT, treated with anti-trypanosomal drugs.
DATA COLLECTION AND ANALYSIS
Two authors (VL and AK) extracted data and assessed methodological quality; a third author (JS) acted as an arbitrator. Included trials only reported dichotomous outcomes, and we present these as risk ratio (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Nine trials with 2577 participants, all with Trypansoma brucei gambiense HAT, were included. Seven trials tested currently available drugs: melarsoprol, eflornithine, nifurtimox, alone or in combination; one trial tested pentamidine, and one trial assessed the addition of prednisolone to melarsoprol. The frequency of death and number of adverse events were similar between patients treated with fixed 10-day regimens of melarsoprol or 26-days regimens. Melarsoprol monotherapy gave fewer relapses than pentamidine or nifurtimox, but resulted in more adverse events.Later trials evaluate nifurtimox combined with eflornithine (NECT), showing this gives few relapses and is well tolerated. It also has practical advantages in reducing the frequency and number of eflornithine slow infusions to twice a day, thus easing the burden on health personnel and patients.
AUTHORS' CONCLUSIONS
Choice of therapy for second stage Gambiense HAT will continue to be determined by what is locally available, but eflornithine and NECT are likely to replace melarsoprol, with careful parasite resistance monitoring. We need research on reducing adverse effects of currently used drugs, testing different regimens, and experimental and clinical studies of new compounds, effective for both stages of the disease.
Topics: Animals; Antiprotozoal Agents; Drug Therapy, Combination; Eflornithine; Humans; Melarsoprol; Nifurtimox; Pentamidine; Prednisolone; Randomized Controlled Trials as Topic; Recurrence; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 23807762
DOI: 10.1002/14651858.CD006201.pub3 -
PLoS Neglected Tropical Diseases Jan 2012A range of molecular amplification techniques have been developed for the diagnosis of Human African Trypanosomiasis (HAT); however, careful evaluation of these tests... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A range of molecular amplification techniques have been developed for the diagnosis of Human African Trypanosomiasis (HAT); however, careful evaluation of these tests must precede implementation to ensure their high clinical accuracy. Here, we investigated the diagnostic accuracy of molecular amplification tests for HAT, the quality of articles and reasons for variation in accuracy.
METHODOLOGY
Data from studies assessing diagnostic molecular amplification tests were extracted and pooled to calculate accuracy. Articles were included if they reported sensitivity and specificity or data whereby values could be calculated. Study quality was assessed using QUADAS and selected studies were analysed using the bivariate random effects model.
RESULTS
16 articles evaluating molecular amplification tests fulfilled the inclusion criteria: PCR (n = 12), NASBA (n = 2), LAMP (n = 1) and a study comparing PCR and NASBA (n = 1). Fourteen articles, including 19 different studies were included in the meta-analysis. Summary sensitivity for PCR on blood was 99.0% (95% CI 92.8 to 99.9) and the specificity was 97.7% (95% CI 93.0 to 99.3). Differences in study design and readout method did not significantly change estimates although use of satellite DNA as a target significantly lowers specificity. Sensitivity and specificity of PCR on CSF for staging varied from 87.6% to 100%, and 55.6% to 82.9% respectively.
CONCLUSION
Here, PCR seems to have sufficient accuracy to replace microscopy where facilities allow, although this conclusion is based on multiple reference standards and a patient population that was not always representative. Future studies should, therefore, include patients for which PCR may become the test of choice and consider well designed diagnostic accuracy studies to provide extra evidence on the value of PCR in practice. Another use of PCR for control of disease could be to screen samples collected from rural areas and test in reference laboratories, to spot epidemics quickly and direct resources appropriately.
Topics: Humans; Molecular Diagnostic Techniques; Parasitology; Sensitivity and Specificity; Trypanosomiasis, African
PubMed: 22253934
DOI: 10.1371/journal.pntd.0001438