Human African trypanosomiasis, is commonly referred to as sleeping sickness. It is a parasitic vector-borne disease. The infection is caused by a protozoan parasite of the Trypanosoma genus. Bite from infected tsetse fly (Glossinagenus) transmits the infection to human; the infected tsetse fly may either acquire the infection from man or animal who are carriers of the pathogenic parasites. Human African trypanosomiasis is found in remote sub-Saharan areas where health systems are often weak. The disease is usually fatal, without prompt diagnosis and treatment the parasites multiply in the body, cross the blood–brain barrier and invade the central nervous system.

BRIEF HISTORY OF THE DISEASE

The slave trade is closely linked to the history of the human African trypanosomiasis. Ship medical officers and doctors who worked for the slave trade companies were the first to report sleeping sickness. The infection was weird. The increasing losses caused by the infection to the ship-owners and slave traders propelled them to request for an investigation of the infection by their ship medical officer. The first precise medical report on African sleeping sickness was published in 1734 by John Aktins; an English naval surgeon. Aktins described the neurological symptoms of the late phase of sleeping sickness.

In 1803, swollen lymph glands along the back region of the neck was published by Thomas Winter bottom as an early phase sign of the disease. He acknowledged that the symptom had been discovered long ago by the Arabian slave-traders in that, they majorly refrained from buying slaves who possess such sign. In the 19th century, as the sickness report increases the disease became notable throughout the century.

MODE OF TRANSMISSION OF THE AFRICAN HUMAN TRYPANOSOMIASIS.

The infected tsetse fly bite transmits the infection. The insect bite is more like a hot needle being stuck into ones’ skin. The parasite is being injected into the skin tissue by the infected insect (tsetse fly) during a blood suck on the new host. The parasites enter the lymphatic system and gets into the bloodstream. The parasite undergoes transformation in the blood stream of the host and are transported to other parts of the body. It reaches other body fluids as well (e.g., the spinal fluid,lymph) and by binary fission they replicate progressively. A tsetse fly becomes infected when taking a blood suck on an infected host and the cycle of infection continues.

Though the disease is majorly transmitted through the bite of an infected tsetse fly, the disease is also contractible through:

Mother-child infection: This occurs when the trypanosome crosses the placenta to infect the fetus. It can result in perinatal death.

Laboratories: Although infection through this means is less common. The infection through this route is majorly as a result of laboratory accident, for example, through improper handling of infected person’s blood or transplantation of organs.

Transmission of the parasite through sexual contact has also been documented.

SIGNS AND SYMPTOMS

The human African trypanosomiasis has two stages.

In the first stage, the trypanosomes multiply in the subcutaneous tissues, blood and lymph. This is known as haemo-lymphatic stage, which results in bouts of fever, headaches, joint pains and itching.

In the second stage the parasites cross the blood-brain barrier to affect the central nervous system. This is referred to as the neurological or meningo-encephalic stage.The appearance of clear signs and symptoms occurs at this stage, such as; behavioural changes, improper coordination, sensory disturbance and confusion. The notable sleep cycle disturbance feature of the disease gave rise to its name (sleeping sickness).

The disease progression rate and clinical features of African trypanosomiasis depends largely on the subspecies and the form of parasite (T. b. rhodesiense or T. b. gambiense) causing the infection.However, infection with either form has the tendency to lead to coma and death if not treated.

FORMS OF HUMAN AFRICAN TRYPANOSOMIASIS

Human African trypanosomiasis takes 2 forms, depending on the parasite involved:

Trypanosoma brucei gambiense is found in west and central Africa. It accounts for 98% of reported cases of sleeping sickness. It progresses more slowly and causes a chronic infection. An infected person may show no major sign or symptom of the disease for months or years. The persons may present with: headaches, intermittent fevers, malaise,joint and muscle aches. The person can also experience weight loss, swollen lymph nodes and itching skin. Evident symptoms such as hormonal imbalances or where the central nervous system (CNS) is affected causing partial paralysis or problems with balance or walking are signs of the advanced stage of the disease.

Trypanosoma brucei rhodesiense: This form is majorly found in southern and eastern Africa. It accounts for less than 2% of reported cases and causes an acute infection. The first observable signs and symptoms can be seen few weeks or months after the infection. This form rapidly progresses and invades the central nervous system. Although in separate zones, only Uganda has been found to present with both forms of the disease.

DISEASE MANAGEMENT: DIAGNOSIS

Disease management is made in 3 steps:

Screening for infection.This can be done through serological tests and checking for clinical signs – usually swollen cervical lymph nodes.The test is only available for T.b.gambiense.

Establish the presence of the parasite in body fluids by diagnosing whether the parasite is present in body fluids.

Determine the disease progression state by staging. This requires a clinical examination and in some situations the cerebro-spinal fluid analysis.

Early diagnosis must be made to interrupt the disease progression into the neurological stage and to avoid risky treatment procedures and future complications.

Active at risk population screening is recommended because of the sleeping sickness first stage (T. b. gambiense) relatively long asymptomatic so as to identify patients early and also reduce the transmission rate by status reservoir removal. Effective screening requires a major resources investment (man, money, materials). Resources are often scarce in Africa particularly in add to reach areas where the disease are mostly common and this may result in the death of some infected individuals before they can ever be diagnosed and treated.

TREATMENT OF THE AFRICAN HUMAN TRYPANOSOMIASIS

There are different drugs for the treatment of the disease depending on the stage of the disease. Compare to the drugs used for the second stage treatment, the first stage treatments are safe and simple to administer. Also, the earlier the disease diagnosis the more the chances of survival or cure. The second stage treatment success hinges on using medications that can reach the parasite by crossing the blood-brain barrier. Most of such drugs are toxic and difficult to administer.

The first stage treatment drugs are:

Pentamidine: It is generally well tolerated by patients. It has non-negligible undesirable effects

Suramin: It provokes certain undesirable effects, including urinary tract and allergic reactions.

Drugs used in second stage treatment:

Melarsoprol:This drug is used to treat infections from both gambiense and rhodesiense. It has fatal and undesirable side effects e.g.encephalopathic syndrome (reactive encephalopathy). Drug resistant has been observed in several regions, especially in Central Africa. The drug is the current recommended first line treatment for the rhodesiense form and a second alternative for the gambiense form.

Eflornithine:This drug is less toxic compared to melarsoprol. The regimen is complex and difficult to apply. The drug is only active against T.b. gambiense.

Nifurtimox: In 2009, the combination of nifurtimox and eflornithinewas introduced.  Nifurtimox is registered for the treating American trypanosomiasis and not for human African trypanosomiasis. The efficacy and safety of the drug was ascertained by a clinical trial. Hence, its present use in combination with eflornithine and inclusion in the “WHO List of Essential Medicines“. it is a first-line treatment for the gambiense form of infection.

Fexinidazole: It is an oral treatment for gambience form of human African trypanosomiasis. This molecule is indicated for first stage and non-severe second stage and it can simplify and facilitate case management of gambiense human African trypanosomiasis.

PREVENTION AND CONTROL

There is no vaccine or drug for prophylaxis against African trypanosomiasis. There are two control strategies for the African trypanosomiasis:

Reduction of the disease reservoir: T. b. gambiensemajor disease reservoir are humans therefore case finding through active population screening and provision of treatment to identified infected persons is a control strategy geared towards the reduction of the disease reservoir for this sub species. Due to the variety of T. b. rhodesiense animal hosts;reducing the disease reservoir is more difficult.

Vector (tsetse fly) control: The fundamental strategy in use is vector control.Tsetse fly traps are at some time or the other used in addition to other strategy.This is usually done with traps or screens, in combination with insecticides and odours that attract the flies.

The Preventive measure focuses on minimizing contact with tsetse flies. Some of the helpful preventive measures include:

Wearing long-sleeved shirts and pants of medium-weight material with neutral colours that blend with the environment background. The vector (Tsetse fly) is attracted to bright or dark colour and they can bite through clothing that has light weight.

Inspect vehicles before entering. Motion and dust from moving vehicles attract the fly.

Avoid bushes.  The flies are less lively or energetic during the hottest part of the day but may bite if disturbed.

Use insect repellent. Wear a cloth impregnated with permethrin. The effectiveness of insect repellent against tsetse fly has not been proven, but they will protect against other insect bites that can cause illness.

THE DISEASE BURDEN FOR AFRICAN HUMAN TRYPANOSOMIASIS

Tsetse flies, the vector for trypanosomiasis disease transmission are found in sub-Saharan Africa but only specific species has been found to transmit the disease. But for yet unexplained reasons, in many other regions where tsetse flies are found, sleeping sickness is not. Rural populations living in regions where transmission occurs are at a higher risk as a result of their exposure to the vector (tsetse fly). Agriculture,animal husbandry,fishing or hunting are the main means of livelihood for most of the people in those rural area.  The disease spread ranges from a single village to an entire region. Within an infected area, the magnitude of the disease can vary across villages.

In 36 countries in sub-Saharan Africa sleeping sickness threatens millions of people. Dwellers in rural areas, with inadequate health services are the most affected population. The limited access to health service results in; surveillance, diagnosis and treatment complications. Rural-urban migration, displacement of populations (by war etc.) and poverty are important factors that aid transmission.

About 40 000 cases were reported in 1998, but estimates were that 300 000 cases were undiagnosed and therefore untreated. During epidemic the prevalence reached 50% in several villages in Angola, the Democratic Republic of the Congo, and South Sudan. Sleeping sickness, ahead of HIV/AIDS was positioned among the greatest cause of mortality in those communities.

TRENDS OF IMPROVEMENT IN THE PREVENTION, CONTROL AND TREATMENT OF THE DISEASE.

After continued control interventions in 2009, the number of reported cases declined to about 10 000 (9878) for the first time in 50 years.

Since the commencement of the global systematic data collection (80 years ago) the lowest level of decline in the number of cases was recorded in 2018 (997 new case) and has continued ever since. 65 million people are estimated to be at risk of the disease.

Transmission of the disease seems to have stopped in some countries but there are still some areas where it is difficult to assess the exact situation because of unstable social circumstances which possess difficulty to accessibility thereby hindering surveillance and diagnostic activities. The disease incidence differs from one country to another as well as in different parts of a single country.

In the last 10 years, over 70% of reported cases occurred in the Democratic Republic of the Congo.

Angola, Central African Republic, Chad, Congo, Gabon, Guinea, Malawi and South Sudan declared between 10 and 100 new cases in 2018.

Countries such as Burkina Faso, Cameroon, Côte d’Ivoire, Equatorial Guinea, Ghana, Nigeria, Uganda, United Republic of Tanzania, Zambia and Zimbabwe are reporting in the previous years’ sporadic cases fewer than 10 new cases per year.

Over a decade no new case has been recorded in countries like Botswana, Benin, Burundi, Ethiopia, Guinea Bissau, Gambia, Kenya, Liberia, Mozambique, Mali, Namibia, Niger, Rwanda, Sierra Leone, Senegal, Swaziland and Togo.

CHALLENGES

The regimen for the treatment is complex and difficult to apply. Some has undesirable effects.

Weak health system: Human African trypanosomiasis is found in remote sub-Saharan areas where health systems are often weak.

Poor economic status: Poverty and low socio-economic status are common in low and middle income countries and the regions with high incidence falls in these countries. Effective screening requires a major resources investment (man, money, materials). In Africa most of the disease cases are found in remote areas where resources are often scarce and this may result in the death of some infected individuals before they can ever be diagnosed and treated.

Corruption and poor attitude/ concern for citizen’s well-being: Poor governance and corruption are constantly reported issues in most sub-Saharan Africa. Improved quality of life and access to adequate health care by the masses are of less concern to most of the ruling government in most low and middle income countries therefore resources meant to be channel into the improvement of the health system are being diverted.

Poor health seeking/ health promoting behaviour: The attention given to personal hygiene and environmental sanitation in most low and middle income countries is low. Poverty among other factors has restricted most infected individual from seeking health care intervention when they are sick.

SUGGESTED WAY FORWARD

Public private partnership should be encouraged to strengthen the weak health system so as to be able to tackle trypanosomiasis and other neglected tropical diseases.

Health care facilities should be that which is accessible, affordable and acceptable by the intended users

Resources should be mobilized to regions where high incidence are still recorded. Countries should share strategies on how they have been able to tackle the disease in their different regions and such interventional strategies should be modified to suit the country adopting it.

Research should be more funded to develop vaccines and drug which has less undesirable effects. The regimen should not be complex and difficult to apply and should be generally well tolerated by patients.

Reviewed on 16/04/2020

REFERENCES
Bray PG, Barrett MP, Ward SA, de Koning HP: Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends Parasitol. 2003, 19: 232-239. 10.1016/S1471-4922(03)00069-2.

Castellani A: On the discovery of a species of Trypanosoma in the cerebro-spinal fluid of cases of sleeping sickness. Proc R Soc Lond. 1903, 71: 501-508.

Cox FEG: History of sleeping sickness (African trypanosomiasis). Infect Dis Clin N Am. 2004, 18: 231-245. 10.1016/j.idc.2004.01.004.

de Raadt P: The history of sleeping sickness. 2005, World Health Org, [​http://www.who.int/trypanosomiasis_african/country/history/en/print.html​]

Haag J, O’hUigin C, Overath P: The molecular phylogeny of trypanosomes: evidence for an early divergence of the Salivaria. Mol Biochem Parasitol. 1998, 91: 37-49. 10.1016/S0166-6851(97)00185-0.

Hide G: History of sleeping sickness in East Africa. Clin Microbiol Rev. 1999, 12: 112-125.

Kabayo JP: Aiming to eliminate tsetse from Africa. Trends Parasitol. 2002, 18: 473-475. 10.1016/S1471-4922(02)02371-1.

Molyneux DH, Pentreath V, Doua F: African trypanosomiasis in man. Manson’s Tropical Diseases. Edited by: Cook GC. 1996, London: W.B. Saunders Company Ltd, 1171-1196. 20

Priotto G, Fogg C, Balasegaram M, Erphas O, Louga A, Checchi F, Ghabri S, Piola P: Three drug combinations for late-stage Trypanosoma brucei gambiensesleeping sickness: a randomized clinical trial in Uganda. PLoS Clin Trials. 2006, 1: e39-10.1371/journal.pctr.0010039.

Stephens JWW, Fantham HB: On the peculiar morphology of a trypanosome from a case of sleeping sickness and the possibility of its being a new species (T. rhodesiense). Proc R Soc Lond B. 1910, 83: 28-33. 10.1098/rspb.1910.0064.

Steverding D: A new initiative for the development of new diagnostic tests for human African trypanosomiasis. Kinetoplastid Biol Dis. 2006, 5: 1-10.1186/1475-9292-5-1.

WHO: Human African trypanosomiasis (sleeping sickness): epidemiological update. Weekly Epidemiol Rec. 2006, 81 (8): 71-80.

Williams BI: African trypanosomiasis. The Wellcome Trust Illustrated History of Tropical Diseases. Edited by: Cox FEG. 1996, London: The Wellcome Trust, 178-191.

Winkle S: Geißeln der Menschheit. Kulturgeschichte der Seuchen. 2005, Düsseldorf: Artemis & Winkler

World Health Organization: African trypanosomiasis (sleeping sickness). 2006, World Health Organ Fact Sheet, [​http://www.who.int/mediacentre/factsheets/fs259/en/​].