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.

OBJECTIVE: To investigate the prognosis of two rare imported patients with human African trypanosomias (HAT) after treatment in a follow-up study, and to evaluate the therapeutic efficacy, so as to provide insights into the treatment of imported HAT patients.
METHODS: The white blood cells in cerebrospinal fluid samples and the trypomastigotes in cerebrospinal fluid and blood samples were monitored in an imported case with Trypanosoma brucei rhodesiense infection 1, 3, 11 and 25 months post-treatment and in an imported case with T. brucei gambiense infection 1, 3, 8 and 12 months post-treatment to evaluate the therapeutic efficacy and prognosis.
RESULTS: There were 1, 1, 4 and 2 white blood cells in per μL of cerebrospinal fluid in the case with T. brucei rhodesiense infection 1, 3, 11 and 25 months post-treatment, and there were 3, 6, 4 and 3 white blood cells in per μL of cerebrospinal fluid in the case with T. brucei gambiense infection 1, 3, 8 and 12 months post-treatment. In addition, no trypomastigotes were identified in the cerebrospinal fluid or blood samples of either case with T. brucei rhodesiense or T. brucei gambiense infection.
CONCLUSIONS: Following standardized treatment, two imported cases with human African trypanosomiasis cases recover satisfactorily, without any signs of relapse.
［摘要］ 目的 对2例罕见的输入性非洲锥虫病 (human african trypanosomiasis, HAT) 病例治疗后进行随访研究, 评判治 疗效果, 从而为输入性锥虫病临床治疗提供参考依据。方法 1例输入性罗德西锥虫病病例在治疗完成后第1、3、11、25 个月以及1例输入性冈比亚锥虫病病例在治疗完成后第1、3、8、12个月, 分别检测患者脑脊液中白细胞计数及脑脊液和 血液中锥鞭毛体, 比较治疗时、治疗后生理生化指标变化, 根据其检测结果进行治疗效果和预后评判。结果 罗德西亚 锥虫病病例在治疗后第1、3、11、25个月, 脑脊液中白细胞计数分别为1、1、4、2个/μL; 冈比亚锥虫病病例在治疗后第1、 3、8、12个月, 脑脊液中白细胞计数分别为3、6、4、3个/μL。2例病例在随访中均未在脑脊液和血液中查见锥鞭毛体。结论 经过规范治疗, 2例输入性锥虫病病例恢复良好, 没有复发迹象。.

While both human and animal trypanosomiasis continue to present as major human and animal public health constraints globally, detailed analyses of trypanosome wildlife reservoir hosts remain sparse. African animal trypanosomiasis (AAT) affects both livestock and wildlife carrying a significant risk of spillover and cross-transmission of species and strains between populations. Increased human activity together with pressure on land resources is increasing wildlife-livestock-human infections. Increasing proximity between human settlements and grazing lands to wildlife reserves and game parks only serves to exacerbate zoonotic risk. Communities living and maintaining livestock on the fringes of wildlife-rich ecosystems require to have in place methods of vector control for prevention of AAT transmission and for the treatment of their livestock. Major Trypanosoma spp. include Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma cruzi, pathogenic for humans, and Trypanosoma vivax, Trypanosoma congolense, Trypanosoma evansi, Trypanosoma brucei brucei, Trypanosoma dionisii, Trypanosoma thomasbancrofti, Trypanosma elephantis, Trypanosoma vegrandis, Trypanosoma copemani, Trypanosoma irwini, Trypanosoma copemani, Trypanosoma gilletti, Trypanosoma theileri, Trypanosoma godfreyi, Trypansoma simiae, and Trypanosoma (Megatrypanum) pestanai. Wildlife hosts for the trypansomatidae include subfamilies of Bovinae, Suidae, Pantherinae, Equidae, Alcephinae, Cercopithecinae, Crocodilinae, Pteropodidae, Peramelidae, Sigmodontidae, and Meliphagidae. Wildlife species are generally considered tolerant to trypanosome infection following centuries of coexistence of vectors and wildlife hosts. Tolerance is influenced by age, sex, species, and physiological condition and parasite challenge. Cyclic transmission through Glossina species occurs for T. congolense, T. simiae, T. vivax, T. brucei, and T. b. rhodesiense, T. b. gambiense, and within Reduviid bugs for T. cruzi. T. evansi is mechanically transmitted, and T. vixax is also commonly transmitted by biting flies including tsetse. Wildlife animal species serve as long-term reservoirs of infection, but the delicate acquired balance between trypanotolerance and trypanosome challenge can be disrupted by an increase in challenge and/or the introduction of new more virulent species into the ecosystem. There is a need to protect wildlife, animal, and human populations from the infectious consequences of encroachment to preserve and protect these populations. In this review, we explore the ecology and epidemiology of Trypanosoma spp. in wildlife.

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.

We report the first imported case in China of human African trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense, in a sailor returning from Gabon in 2014. The diagnosis was delayed and relapse led to death, despite treatment with eflornithine, as recommended by the World Health Organization for late-stage HAT. This case shows that early diagnosis of HAT and close follow-up with proper retreatment are critical.

Bovine trypanosomosis is a problem in the livestock industry in Nigeria. A longitudinal survey of cattle sampled during the wet and dry seasons was conducted from April 2016 to March 2017. Blood samples were collected by random sampling from 745 cattle in southwest Nigeria and screened for trypanosomes by internal transcribed spacer-polymerase chain reaction (ITS-PCR). Cattle positive for Trypanozoon DNA were further screened with the Rode Trypanozoon antigen type (RoTat) 1.2 PCR and Trypanosoma brucei gambiense glycoprotein (TgsGP) genes for T. evansi and T. b. gambiense respectively. Trypanosome DNA was amplified in 23.8% (95%CI: 20.8-26.9) of cattle with significantly higher prevalence in wet season (95%CI: 22.9-30.8) when compared to the dry season (95%CI: 14.3-23.6). A high prevalence was observed in Fulani cattle farms 54.1% (95%CI: 42.78-64.93%) while the prevalence was lower in institutional farms 14.7% (95%CI: 10.10-20.97%). Trypanosoma vivax was the most prevalent trypanosome observed (11.54% (95%CI: 9.44-14.04%)), followed by T. congolense 8.5% (95%CI: 6.67-10.67%) T. b. brucei 4.8% (95%CI: 3.51-6.62%) and T. evansi 1.74% (95%CI: 1.02-2.96%). Mixed infections were observed in 2.8% (95%CI: 1.85-4.27%) of cattle. Seasonal variation revealed a predominance of T. congolense and T. vivax in wet and dry season, respectively. The high prevalence of Trypanosoma species in cattle indicates a need for expanded surveillance for AAT in southwest Nigeria. Migration, settlement patterns, increased marketing and management types were some of the risk factors identified for AAT.

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It is textbook knowledge that human infective forms of Trypanosoma brucei, the causative agent of sleeping sickness, enter the brain across the blood-brain barrier after an initial phase of weeks (rhodesiense) or months (gambiense) in blood. Based on our results using an animal model, both statements seem questionable. As we and others have shown, the first infection relevant crossing of the blood brain border occurs via the choroid plexus, i.e. via the blood-CSF barrier. In addition, counting trypanosomes in blood-free CSF obtained by an atlanto-occipital access revealed a cyclical infection in CSF that was directly correlated to the trypanosome density in blood infection. We also obtained conclusive evidence of organ infiltration, since parasites were detected in tissues outside the blood vessels in heart, spleen, liver, eye, testis, epididymis, and especially between the cell layers of the pia mater including the Virchow-Robin space. Interestingly, in all organs except pia mater, heart and testis, trypanosomes showed either a more or less degraded appearance of cell integrity by loss of the surface coat (VSG), loss of the microtubular cytoskeleton and loss of the intracellular content, or where taken up by phagocytes and degraded intracellularly within lysosomes. This is also true for trypanosomes placed intrathecally into the brain parenchyma using a stereotactic device. We propose a different model of brain infection that is in accordance with our observations and with well-established facts about the development of sleeping sickness.