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Climatic change, deforestation, globalization, trade agreements, close association and genetic selection in links with environmental, vector, reservoir and potential susceptible hosts' parameters have led to emergence of atypical human trypanosomosis (a\u2010HT). Poor recording of such neglected tropical disease, low awareness in health professions and farming community has approached a serious intimidation for mankind. Reports of animal <jats:italic>Trypanosoma<\/jats:italic> species are now gradually increasing in humans, and lack of any compiled literature has diluted the issue. In the present review, global reports of livestock and rodent trypanosomes reported from human beings are assembled and discrepancies with the available literature are discussed along with morphological features of <jats:italic>Trypanosoma<\/jats:italic> species. We have described 21 human cases from the published information. Majority of cases 10 (47%) are due to <jats:italic>T.\u00a0lewisi<\/jats:italic>, followed by 5 (24%) cases of <jats:italic>T.\u00a0evansi<\/jats:italic>, 4 (19%) cases of <jats:italic>T.\u00a0brucei<\/jats:italic> and 1 (5%) case each of <jats:italic>T.\u00a0vivax<\/jats:italic> and <jats:italic>T.\u00a0congolense<\/jats:italic>. Indian subcontinent witnessed 13 cases of a\u2010HT, of which 9 cases are reported from India, which includes 7 cases of <jats:italic>T.\u00a0lewisi<\/jats:italic> and 2 cases of <jats:italic>T.\u00a0evansi<\/jats:italic>. Apart from, a\u2010HT case reports, epidemiological investigation and treatment aspects are also discussed. An attempt has been made to provide an overview of the current situation of atypical human trypanosomosis caused by salivarian animal <jats:italic>Trypanosoma<\/jats:italic> globally. The probable role of <jats:italic>Trypanosoma<\/jats:italic> lytic factors (TLF) present in normal human serum (NHS) in providing innate immunity against salivarian animal <jats:italic>Trypanosoma<\/jats:italic> species and the existing paradox in medical science after the finding on intact functional apolipoprotein L1 (ApoL1) in Vietnam <jats:italic>T.\u00a0evansi<\/jats:italic> Type A case is also discussed to provide an update on all aspects of a\u2010HT. Insufficient data and poor reporting in Asian and African countries are the major hurdle resulting in under\u2010reporting of a\u2010HT, which is a potential emerging threat. Therefore, concerted efforts must be directed to address attentiveness, preparedness and regular surveillance in suspected areas with training of field technicians, medical health professionals and veterinarians. Enhancing a one health approach is specifically important in case of trypanosomosis.<\/jats:p>","DOI":"10.1111\/zph.12945","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T04:25:28Z","timestamp":1648700728000},"page":"259-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Atypical human trypanosomosis: Potentially emerging disease with lack of understanding"],"prefix":"10.1111","volume":"69","author":[{"given":"Rajender","family":"Kumar","sequence":"first","affiliation":[{"name":"Parasitology Lab ICAR\u2010National Research Centre on Equines  Hisar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehil","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Veterinary Parasitology Lala Lajpat Rai University of Veterinary and Animal Sciences  Hisar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangchuk Dorjee","family":"Bhutia","sequence":"additional","affiliation":[{"name":"Parasitology Lab ICAR\u2010National Research Centre on Equines  Hisar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh Kumar","family":"Vaid","sequence":"additional","affiliation":[{"name":"NCVTC ICAR\u2010National Research Centre on Equines  Hisar India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Parasitology Lab ICAR\u2010National Research Centre on Equines  Hisar India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"issue":"2","key":"e_1_2_16_2_1","first-page":"185","article-title":"Further studies on the Trypanosoma brucei group trypanosome, isolated from a patient infected in Anger\u2010Didessa Valley, West Ethiopia, using the blood incubation infectivity test (BIIT)","volume":"45","author":"Abebe M.","year":"1988","journal-title":"Acta Tropica"},{"issue":"2","key":"e_1_2_16_3_1","first-page":"230","article-title":"Epidemiology of blood parasitic infections in the urban rat population in peninsular Malaysia","volume":"31","author":"Alias S. 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