Trypanosomiasis

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Trypanosomiasis
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Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus Trypanosoma . In humans this includes African trypanosomiasis and Chagas disease. A number of other diseases occur in other animals.

Contents

African trypanosomiasis, which is caused by either Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense, threatens some 65 million people in sub-Saharan Africa, especially in rural areas and populations disrupted by war or poverty. The number of cases has been going down due to systematic eradication efforts: in 1998 almost 40,000 cases were reported but almost 300,000 cases were suspected to have occurred; in 2009, the number dropped below 10,000; and in 2018 it dropped below 1000. [1] Chagas disease causes 21,000 deaths per year mainly in Latin America. [2]

Signs and symptoms

The tsetse fly bite erupts into a red chancre sore and within a few weeks, the person can experience fever, swollen lymph glands, blood in urine, aching muscles and joints, headaches and irritability. In the first phase, the patient has only intermittent bouts of fever with lymphadenopathy together with other non-specific signs and symptoms. The second stage of the disease is marked by involvement of the central nervous system with extensive neurological effects like changes in personality, alteration of the biological clock (the circadian rhythm), confusion, slurred speech, seizures and difficulty in walking and talking. These problems can develop over many years and if not treated, the person dies. It is common in Subsaharan Africa.

Diagnosis

Cattle may show enlarged lymph nodes and internal organs. Haemolytic anaemia is a characteristic sign. Systemic disease and reproductive wastage are common, and cattle appear to waste away.

Horses with dourine show signs of ventral and genital edema and urticaria.

Infected dogs and cats may show severe systemic signs.

Diagnosis relies on recognition of the flagellate on a blood smear. Motile organisms may be visible in the buffy coat when a blood sample is spun down. Serological testing is also common.

One common way in which trypanosomiasis can be diagnosed in humans is through the detection of antibodies against trypanosomes made by host organisms. [3] One commonly used antibody test which operated based on this principle is the card agglutination test, C.A.T.T. for T. gambiense. [3] [4] In this test, reagent is mixed with blood and shaken. Within a matter of minutes, a researcher or public health professional can determine whether someone has made these antibodies and therefore is infected with trypanosomes. [5] Regarding the accuracy of this test, it is reported to have an 87 to 98 percent sensitivity rating. [3]

Another way to diagnose trypanosomiasis in humans is to detect the trypanosome protozoans themselves. [3] One way to do this would be to use lymph node aspirate. In this test, which has a sensitivity of between 40 and 80 percent, a healthcare worker will first find a cervical lymph node which is enlarged. [3] [6] Once the healthcare worker has punctured that lymph node, its aspirate is examined under a microscope for trypanosomes to confirm diagnosis. [3]

Prevention

The use of trypanotolerant breeds for livestock farming should be considered if the disease is widespread. Fly control is another option but is difficult to implement. The main approaches to controlling African trypanosomiasis are to reduce the reservoirs of infection and the presence of the tsetse fly. Screening of people at risk helps identify patients at an early stage. Diagnosis should be made as early as possible and before the advanced stage to avoid complicated, difficult and risky treatment procedures.[ citation needed ]

Treatment

Stage I of the condition is usually treated with pentamidine or suramin through intramuscular injection or intravenous infusion if sufficient observation is possible. Stage II of the disease is typically treated with melarsoprol or eflornithine preferably introduced to the body intravenously. Both pentamidine and suramin have limited side effects. Melarsoprol is extremely effective but has many serious side effects which can cause neurological damage to a patient, however, the drug is often a patient's last hope in many late stage cases. Eflornithine is extremely expensive but has side effects that may be treated with ease. [7] In regions of the world where the disease is common eflornithine is provided for free by the World Health Organization.[ citation needed ]

Epidemiology

Trypanosomes and trypanosomiasis disease is transmitted through the tsetse fly. As many as 90 percent of sleeping sickness cases are caused by the Glossina fuscipes subspecies of the fly. [8] The palpalis subspecies contributes the majority of the rest of the cases. The different subspecies of fly dominate different habitats. For instance, the Glossina Morsitans subspecies inhabits savannahs while the Glossina Palpalis subspecies prefers woody riverine habitats. [9] However, all flies are susceptible to extremes in temperature (outside of the 16-40 degree Celsius range). Furthermore, trypanosomes are only able to reproduce in tsetse flies between the 25 to 30 Celsius range. These factors mean that only a minority of tsetse flies, around 20 percent, are estimated to carry trypanosomes. [9] These flies can also adapt to human activity, thus causing changes in disease patterns. For example, when brush is cleared for agriculture, the flies can retreat into the savannah and conversely when humans move into brush, the flies will reproduce and feed more frequently. [10] As a result, large increases of population associated with expansion into woody habitats often coincides with trypanosomiasis epidemics. [10]

Humans, their livestock, or wild animals can all act as reservoirs of trypanosomiasis disease. [10] However, the reservoirs used differ based on subspecies of trypanosoma protozoans and thus the variants of trypanosomiasis disease. There are two main variants of trypanosomoiasis which are in turn transmitted by different subspecies of the trypanosome protozoans. [11] Trypanosoma brucei rhodiense tends to result in more acute forms of disease and is mainly transmitted form one human to another. Most patients with this variant of disease will die within six months of infection. [12] Cattle can also act as a reservoir in areas where disease incidence is lower. [10] Trypanosoma brucei gambiense is the second type of protozoan which usually results in more chronic disease patterns. [11] Its main reservoir is the cattle populations. Although it is also fatal, death can take months or years to occur. [13] Geographical separation of these two variants of trypanosomes occurs along the Rift Valley. Trypanosoma brucei rhodiense is usually found on the eastern side of the valley while the gambiense variant resides on the western side. [8] The ranges of the two disease variants could overlap in Uganda, Tanzania, and Congo in the future. [14]  

Trypanosomiasis case numbers reported to the WHO from 2000-2013. Data used came from Franco, J. R., Simarro, P. P., Diarra, A., & Jannin, J. G. (2014). Epidemiology of human African trypanosomiasis. Clinical epidemiology, 257-275. TrypanosomiasisCaseNumbers2000-2013.png
Trypanosomiasis case numbers reported to the WHO from 2000-2013. Data used came from Franco, J. R., Simarro, P. P., Diarra, A., & Jannin, J. G. (2014). Epidemiology of human African trypanosomiasis. Clinical epidemiology, 257-275.

Research

Trypanosomiasis could, in future be prevented by genetically altering the tsetse fly. As the tsetse fly is the main vector of transmission, making the fly immune to the disease by altering its genome could be the main component in an effort to eradicate the disease. New technologies such as CRISPR allowing cheaper and easier genetic engineering could allow for such measures.[ citation needed ] A pilot program in Senegal, funded by the International Atomic Energy Agency, has considerably reduced the tsetse fly population by introducing male flies which have been sterilized by exposure to gamma rays. [15] This has allowed a change of cattle breeds from lower producing trypanotolerant breeds to higher-producing foreign breeds, and was selected as one of the Best Sustainable Development Practices on Food Security by EXPO Milan 2015. [16]

Other animals

Chagas endemic zones (in red) Carte maladie Chagas.png
Chagas endemic zones (in red)

Some species of cattle such as the African buffalo, N'dama, and Keteku appear trypanotolerant and do not develop symptoms. Calves are more resistant than adults.[ citation needed ]

Tsetse-borne species of trypanosomes have entered zoos outside the traditional tsetse zone in infected animals imported for the zoo. [17] [18]

Related Research Articles

<span class="mw-page-title-main">African trypanosomiasis</span> Parasitic disease also known as sleeping sickness

African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species Trypanosoma brucei. Humans are infected by two types, Trypanosoma brucei gambiense (TbG) and Trypanosoma brucei rhodesiense (TbR). TbG causes over 92% of reported cases. Both are usually transmitted by the bite of an infected tsetse fly and are most common in rural areas.

<span class="mw-page-title-main">Tsetse fly</span> Genus of disease-spreading insects

Tsetse are large, biting flies that inhabit much of tropical Africa. Tsetse flies include all the species in the genus Glossina, which are placed in their own family, Glossinidae. The tsetse is an obligate parasite, which lives by feeding on the blood of vertebrate animals. Tsetse has been extensively studied because of their role in transmitting disease. They have a pronounced economic impact in sub-Saharan Africa as the biological vectors of trypanosomes, causing human and animal trypanosomiasis.

<i>Trypanosoma</i> Genus of parasitic flagellate protist in the Kinetoplastea class

Trypanosoma is a genus of kinetoplastids, a monophyletic group of unicellular parasitic flagellate protozoa. Trypanosoma is part of the phylum Sarcomastigophora. The name is derived from the Greek trypano- (borer) and soma (body) because of their corkscrew-like motion. Most trypanosomes are heteroxenous and most are transmitted via a vector. The majority of species are transmitted by blood-feeding invertebrates, but there are different mechanisms among the varying species. Some, such as Trypanosoma equiperdum, are spread by direct contact. In an invertebrate host they are generally found in the intestine, but normally occupy the bloodstream or an intracellular environment in the vertebrate host.

<span class="mw-page-title-main">Melarsoprol</span> Medication used to treat sleeping sickness

Melarsoprol is an arsenic-containing medication used for the treatment of sleeping sickness. It is specifically used for second-stage disease caused by Trypanosoma brucei rhodesiense when the central nervous system is involved. For Trypanosoma brucei gambiense, eflornithine or fexinidazole is usually preferred. It is effective in about 95% of people. It is given by injection into a vein.

<span class="mw-page-title-main">Eflornithine</span>

Eflornithine, sold under the brand name Vaniqa among others, is a medication used to treat African trypanosomiasis and excessive hair growth on the face in women. Specifically it is used for the 2nd stage of sleeping sickness caused by T. b. gambiense and may be used with nifurtimox. It is taken intravenously or topically. It has also been given orally on at least some rare occasions for the treatment of African trypanosomiasis.

<i>Trypanosoma brucei</i> Species of protozoan parasite

Trypanosoma brucei is a species of parasitic kinetoplastid belonging to the genus Trypanosoma that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclusively extracellular and inhabits the blood plasma and body fluids. It causes deadly vector-borne diseases: African trypanosomiasis or sleeping sickness in humans, and animal trypanosomiasis or nagana in cattle and horses. It is a species complex grouped into three subspecies: T. b. brucei, T. b. gambiense and T. b. rhodesiense. The first is a parasite of non-human mammals and causes nagana, while the latter two are zoonotic infecting both humans and animals and cause African trypanosomiasis.

<span class="mw-page-title-main">David Bruce (microbiologist)</span> Scottish pathologist (1855–1931)

Major-General Sir David Bruce was a Scottish pathologist and microbiologist who made some of the key contributions in tropical medicine. In 1887, he discovered a bacterium, now called Brucella, that caused what was known as Malta fever. In 1894, he discovered a protozoan parasite, named Trypanosoma brucei, as the causative pathogen of nagana.

Trypanosoma suis is a species of excavate trypanosome in the genus Trypanosoma that causes one form of the surra disease in animals. It infects pigs. It does not infect humans.

<span class="mw-page-title-main">Animal trypanosomiasis</span> Parasitic disease of vertebrates

Animal trypanosomiasis, also known as nagana and nagana pest, or sleeping sickness, is a disease of vertebrates. The disease is caused by trypanosomes of several species in the genus Trypanosoma such as T. brucei. T. vivax causes nagana mainly in West Africa, although it has spread to South America. The trypanosomes infect the blood of the vertebrate host, causing fever, weakness, and lethargy, which lead to weight loss and anemia; in some animals the disease is fatal unless treated. The trypanosomes are transmitted by tsetse flies.

<span class="mw-page-title-main">Nifurtimox</span> Anti-parasitic medical drug

Nifurtimox, sold under the brand name Lampit, is a medication used to treat Chagas disease and sleeping sickness. For sleeping sickness it is used together with eflornithine in nifurtimox-eflornithine combination treatment. In Chagas disease it is a second-line option to benznidazole. It is given by mouth.

<i>Trypanosoma congolense</i> Protozoan parasite, cause of nagana

Trypanosoma congolense is a species of trypanosomes and is the major pathogen responsible for the disease nagana in cattle and other animals including sheep, pigs, goats, horses and camels, dogs, as well as laboratory mice. It is the most common cause of nagana in east Africa, but is also a major cause of nagana in west Africa. This parasite is spread by tsetse flies. In its mammalian host, Trypanosoma congolense only lives in blood vessels, and causes in particular anaemia.

Wendy Gibson is Professor of Protozoology at University of Bristol, specialising in trypanosomes and molecular parasitology.

Fexinidazole is a medication used to treat African trypanosomiasis caused by Trypanosoma brucei gambiense. It is effective against both first and second stage disease. Also a potential new treatment for Chagas disease, a neglected tropical disease that affects millions of people worldwide. It is taken by mouth.

<span class="mw-page-title-main">Acoziborole</span> Antiprotozoal drug to treat sleeping sickness

Acoziborole (SCYX-7158) is an antiprotozoal drug invented by Anacor Pharmaceuticals in 2009, and now under development by the Drugs for Neglected Diseases Initiative for the treatment of African trypanosomiasis.

Nifurtimox/eflornithine is a combination of two antiparasitic drugs, nifurtimox and eflornithine, used in the treatment of African trypanosomiasis. It is included in the World Health Organization's Model List of Essential Medicines.

Glossina fuscipes is a riverine fly species in the genus Glossina, which are commonly known as tsetse flies. Typically found in sub-Saharan Africa but with a small Arabian range, G. fuscipes is a regional vector of African trypanosomiasis, commonly known as sleeping sickness, that causes significant rates of morbidity and mortality among humans and livestock. Consequently, the species is among several being targeted by researchers for population control as a method for controlling the disease.

A trypanotolerant organism is one which is relatively less affected by trypanosome infestation.

The Sleeping Sickness Commission was a medical project established by the British Royal Society to investigate the outbreak of African sleeping sickness or African trypanosomiasis in Africa at the turn of the 20th century. The outbreak of the disease started in 1900 in Uganda, which was at the time a protectorate of the British Empire. The initial team in 1902 consisted of Aldo Castellani and George Carmichael Low, both from the London School of Hygiene and Tropical Medicine, and Cuthbert Christy, a medical officer on duty in Bombay, India. From 1903, David Bruce of the Royal Army Medical Corps and David Nunes Nabarro of the University College Hospital took over the leadership. The commission established that species of blood protozoan called Trypanosoma brucei, named after Bruce, was the causative parasite of sleeping sickness.

Keith Roland Matthews,, , is a British cell biologist and parasitologist, currently Professor of Parasite Biology in the School of Biological Sciences at the University of Edinburgh. His research focuses on African trypanosomes, which cause human sleeping sickness and the equivalent cattle disease nagana.

References

  1. ↑ WHO. "Trypanosomiasis, Human African (sleeping sickness)". Fact sheet N°259. World Health Organization. Retrieved 25 February 2014.
  2. ↑ Maya JD, Cassels BK, Iturriaga-Vásquez P, et al. (2007). "Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host". Comp. Biochem. Physiol. A. 146 (4): 601–20. doi:10.1016/j.cbpa.2006.03.004. PMID   16626984.
  3. 1 2 3 4 5 6 Chappuis, François; Loutan, Louis; Simarro, Pere; Lejon, Veerle; Büscher, Philippe (January 2005). "Options for Field Diagnosis of Human African Trypanosomiasis". Clinical Microbiology Reviews. 18 (1): 133–146. doi:10.1128/CMR.18.1.133-146.2005. ISSN   0893-8512. PMC   544181 . PMID   15653823.
  4. ↑ Mitashi, Patrick; Hasker, Epco; Lejon, Veerle; Kande, Victor; Muyembe, Jean-Jacques; Lutumba, Pascal; Boelaert, Marleen (2012-11-29). "Human African Trypanosomiasis Diagnosis in First-Line Health Services of Endemic Countries, a Systematic Review". PLOS Neglected Tropical Diseases. 6 (11): e1919. doi: 10.1371/journal.pntd.0001919 . ISSN   1935-2735. PMC   3510092 . PMID   23209860.
  5. ↑ Bonnet, Julien; Boudot, Clotilde; Courtioux, Bertrand (2015-10-04). "Overview of the Diagnostic Methods Used in the Field for Human African Trypanosomiasis: What Could Change in the Next Years?". BioMed Research International. 2015: e583262. doi: 10.1155/2015/583262 . ISSN   2314-6133. PMC   4609347 . PMID   26504815.
  6. ↑ Vanhecke, C; Guevart, E; Ezzedine, K; Receveur, M-C; Jamonneau, V; Bucheton, B; Camara, M; Vincendeau, P; Malvy, D (2010-02-01). "[Human African trypanosomiasis in mangrove epidemiologic area. Presentation, diagnosis and treatment in Guinea, 2005-2007]". Pathologie-biologie. 58 (1): 110–116. doi:10.1016/j.patbio.2009.07.033. ISSN   1768-3114. PMID   19854583.
  7. ↑ Oxford Textbook of Medicine (Forth ed.). New York: Oxford University Press. 2003. pp. 770, 771.
  8. 1 2 Kargbo, Alpha; Kuye, Rex A. (2020-06-19). "Epidemiology of tsetse flies in the transmission of trypanosomiasis: technical review of The Gambia experience". International Journal of Biological and Chemical Sciences. 14 (3): 1093–1102. doi: 10.4314/ijbcs.v14i3.35 . ISSN   1997-342X.
  9. 1 2 Jordan, A M (December 1979). "Trypanosomiasis control and land use in Africa". Outlook on Agriculture. 10 (3): 123–129. doi:10.1177/003072707901000304. ISSN   0030-7270. S2CID   155470767.
  10. 1 2 3 4 Arden., Hoppe, Kirk (2003). Lords of the fly : sleeping sickness control in British East Africa, 1900-1960. Praeger. ISBN   0-325-07123-3. OCLC   51216398.{{cite book}}: CS1 maint: multiple names: authors list (link)
  11. 1 2 "CDC - African Trypanosomiasis - Biology". www.cdc.gov. 2020-03-09. Retrieved 2023-02-28.
  12. ↑ Odiit, M.; Kansiime, F.; Enyaru, J. C. (December 1997). "Duration of symptoms and case fatality of sleeping sickness caused by Trypanosoma brucei rhodesiense in Tororo, Uganda". East African Medical Journal. 74 (12): 792–795. ISSN   0012-835X. PMID   9557424.
  13. ↑ Pépin, J.; Méda, H. A. (2001). "The epidemiology and control of human African trypanosomiasis". Advances in Parasitology. 49: 71–132. doi:10.1016/s0065-308x(01)49038-5. ISBN   978-0-12-031749-3. ISSN   0065-308X. PMID   11461032.
  14. 1 2 Franco, Jose R.; Simarro, Pere P.; Diarra, Abdoulaye; Jannin, Jean G. (2014). "Epidemiology of human African trypanosomiasis". Clinical Epidemiology. 6: 257–275. doi: 10.2147/CLEP.S39728 . ISSN   1179-1349. PMC   4130665 . PMID   25125985.
  15. ↑ Paquette, Danielle (2019-05-31). "A U.S.-funded nuclear project to zap a killer fly into extinction is saving West Africa's cows". The Washington Post . Retrieved 2019-06-01.
  16. ↑ "The Tsetse Fly Eradication Project in Senegal Wins Award for Best Sustainable Development Practices". IAEA . 23 July 2015. Retrieved 2021-11-16.
  17. ↑ Mbaya, A. W.; Aliyu, M. M.; Ibrahim, U. I. (2009-04-02). "The clinico-pathology and mechanisms of trypanosomosis in captive and free-living wild animals: A review". Veterinary Research Communications . Springer. 33 (7): 793–809. doi: 10.1007/s11259-009-9214-7 . ISSN   0165-7380. PMID   19340600.
  18. ↑ Adler, Peter H.; Tuten, Holly C.; Nelder, Mark P. (2011-01-07). "Arthropods of Medicoveterinary Importance in Zoos". Annual Review of Entomology . Annual Reviews. 56 (1): 123–142. doi:10.1146/annurev-ento-120709-144741. ISSN   0066-4170. PMID   20731604.

Bibliography

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