or '''African trypanosomiasis''' is a
Parasitic Disease in people and in animals. Caused by
Protozoa of genus ''
Trypanosoma '' and transmitted by the '''
Tsetse Fly ''', the disease is endemic in certain regions of
Sub-Saharan Africa , covering about 36 countries and 60 million people. It is estimated that 300,000 - 500,000 people are infected, and about 40,000 die every year. Three major
Epidemic s have occurred in the past hundred years, in 1896 - 1906, 1920, and 1970.
The condition has been present in Africa from at least the 14th century. The causative agent and the vector were not identified until 1902 - 1903 by
Sir David Bruce , and the differentiation between protozoa was not made until 1910. The first effective treatment,
Atoxyl , an
Arsenic based drug developed by
Paul Ehrlich and
Kiyoshi Shiga was introduced in 1906(?), but blindness was a serious side effect. Numerous drugs have been introduced since then - see the treatment section for details.
There have been three severe epidemics in Africa over the last century: one between 1896 and 1906, mostly in Uganda and the Congo Basin, one in 1920 in several African countries, and one that began in 1970 and is still in progress. The 1920 epidemic was arrested due to mobile teams systematically screening millions of people at risk. The disease had practically disappeared between 1960 and 1965. After that success, screening and effective surveillance were relaxed, and the disease has reappeared in endemic form in several foci over the last thirty years.
The British statesman Lord
Alfred Milner died of sleeping sickness in 1923, shortly after returning from a visit to
South Africa .
The disease has been recorded as occurring in 36 countries, all in sub-Saharan Africa.
Humans are the main reservoir for ''Trypanosoma brucei gambiense'', but this species can also be found in pigs and other animals. Wild game animals and cattle are the main reservoir of ''T. b. rhodesiense''.
During a blood meal on the mammalian host, an infected tsetse fly (genus ''Glossina'') injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream . Inside the host, they transform into bloodstream trypomastigotes '''(2)''', are carried to other sites throughout the body, reach other blood fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission '''(3)'''. The entire life cycle of African Trypanosomes is represented by extracellular stages. A tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host '''(4,5)'''. In the fly's midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission '''(6)''', leave the midgut, and transform into epimastigotes '''(7)'''. The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission '''(8)'''. The cycle in the fly takes approximately 3 weeks to digest.
Symptoms begin with fever, headaches, and joint pains. If untreated, the disease slowly overcomes the defenses of the infected person, and symptoms spread to and reduced coordination, the
Sleep Cycle is disturbed with bouts of
Fatigue punctuated with manic periods progressing to daytime
Slumber and nighttime
Insomnia . Without treatment, the disease is fatal, with progressive mental deterioration leading to coma and death. Damage caused in the neurological phase can be irreversible.
In addition to the bite of the tsetse fly, the disease is contractable in the following ways:
- Mother to child infection: the trypanosome can cross the placenta and infect the fetus, causing abortion and perinatal death.
- Laboratories: accidental infections, for example, through the handling of blood of an infected person, although this is uncommon.
The diagnosis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, or, in the late stages of infection, cerebrospinal fluid. A wet preparation should be examined for the motile trypanosomes, and in addition a smear should be fixed, stained with Giemsa (or Field), and examined. Concentration techniques can be used prior to microscopic examination. For blood samples, these include centrifugation followed by examination of the
Buffy Coat ; mini anion-exchange/centrifugation; and the Quantitative Buffy Coat (QBC) technique. For other samples such as spinal fluid, concentration techniques include centrifugation followed by examination of the sediment. Isolation of the parasite by inoculation of rats or mice is a sensitive method, but its use is limited to ''T. b. rhodesiense''. Antibody detection has sensitivity and specificity that are too variable for clinical decisions. In addition, in infections with ''T. b. rhodesiense'', seroconversion occurs after the onset of clinical symptoms and thus is of limited use.
Suramin was introduced in 1920 to treat the first stage of the disease. Later, it was generally combined with tryparsamide in the treatment of the second stage. In 1922 Tryparsamide, another pentavalent organo-arsenic drug entered the market. It is effective in the second stage of the disease of the gambiense form. It was used during the grand epidemic in West and Central Africa in millions of people and was the mainstay of therapy until 1969.
Pentamidine , a highly effective drug for the first stage of the disease, has been used since 1939. During the fifties, it was widely used as a
Prophylactic agent in Western Africa, leading to a sharp decline in infection rates. At the time, it was thought that eradication of the disease was at hand.
The organo-arsenical
Melarsoprol (Arsobal) was developed in the 1940s, and is effective for patients with second stage sleeping sickness. However, 3 - 10% of those injected have reactive
Encephalopathy (convulsions, progressive coma, or psychotic reactions), and 10 - 70% die; it can cause
Brain Damage in those that survive the encephalopathy. However, due to its effectiveness,
Melarsoprol is still used today.
Eflornithine (difluoromethylornithine or DFMO), the most modern treatment, was developed in the 1970s by
Albert Sjoerdsmanot and underwent clinical trials in the 1980s. The drug was approved by the United States
Food And Drug Administration in 1990, but
Aventis , the company responsible for its manufacture, halted production in 1999. In
2001 , however, Aventis, in association with
Médecins Sans Frontières and the
World Health Organization , signed a long-term agreement to manufacture and donate the drug.
The genome of the parasite has been decoded and several proteins have been identified as potential targets for drug treatment. The decoded DNA also revealed the reason that generating a vaccine for this disease has been so difficult. ''T. brucei'' has over 800 genes that manufacture proteins that the disease mixes and matches to evade immune system detection. (Berriman, ''et al.'', 2005)
The primary condition is typically treated with either
Suramin (''T. b. rhodesiense/gambiense'') or
Pentamidine (''T. b. gambiense''). Advanced cases can be treated with
Melarsoprol or
Eflornithine . All these drugs, especially melarsoprol, have many undesirable
Side-effect s, and the treatment regimen is often difficult to enforce.
An international research team working in the
Democratic Republic Of The Congo ,
New Sudan and
Angola involving
Immtech International and
University Of North Carolina At Chapel Hill have completed a
Phase IIb clinical trial and commenced a
Phase III trial in 2005 testing the efficacy of the first oral treatment for Sleeping Sickness, known at this point as "DB289".
Recent findings indicate that the parasite is unable to survive in the bloodstream without its "tail" (called a
Flagellum ). This insight gives researchers a new angle with which to attack the parasite.
7
Prevention and control focus on, where it is possible, the eradication of the parasitic host, the tsetse fly. Two alternative strategies have been used in the attempts to reduce the African trypanosomiases. One tactic is primarily medical or veterinary and targets the disease directly using monitoring, prophylaxis, treatment, and surveillance to reduce the number of organisms which carry the disease. The second strategy is generally entomological and intends to disrupt the cycle of transmission by reducing the number of flies. ''For in depth information on prevention of the disease via tse tse fly control see
Tsetse Fly Control ''
Instances of sleeping sickness are being reduced by the use of the
Sterile Atomic Fly .
There is a single case report of sexual transmission of West African sleeping sickness.
