Human African trypanosomiasis, sleeping sickness, or Congo trypanosomiasis, the disease is endemic in some regions of Sub-Saharan Africa, covering about 36 countries and 60 million people. It is estimated that 50,000 to 70,000 people are currently infected, the number having declined somewhat in recent years. Three major epidemics have occurred in recent history, one lasting from 1896–1906 and the other two in 1920 and 1970. In 2008 there was an epidemic in Uganda.
African Trypanosomiasis Epidemiology
The disease is found in two forms, depending on the parasite, either ''Trypanosoma brucei gambiense'' or ''Trypanosoma brucei rhodesiense''. ''T. b. gambiense'' is found in central and western Africa; it causes a chronic condition that can extend in a passive phase for months or years before symptoms emerge. ''T. b. rhodesiense'', is the acute form of the disease but has a much more limited range. It is found in southern and eastern Africa; its infection emerges in a few weeks and is more virulent and faster developing.
According to recent estimates, the disability adjusted life years (9 to 10 years) (DALYs) lost due to sleeping sickness are 2.0 million.
Recent estimates indicate that over 60 million people living in some 250 locations are at risk of contracting the disease, and there are about 300,000 new cases each year.
The disease has been recorded as occurring in 36 countries, all in sub-Saharan Africa. It is endemic in southeast Uganda and western Kenya and kills more than 40,000 Africans a year.
African Trypanosomiasis Life Cycle
The tsetse fly is large, brown and stealthy. While taking blood from a 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
- are carried to other sites throughout the body, reach other blood fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission
- 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
- In the fly's midgut, the parasites transform into procyclic trypomastigotes,
- multiply by binary fission,
- leave the midgut, and
- transform into epimastigotes
- The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission.
The cycle in the fly takes approximately 3 weeks to progress.
African Trypanosomiasis Laboratory Diagnosis
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.
Three similar serological tests are available for detection of the parasite; the micro-CATT, wb-CATT, and wb-LATEX. The first uses dried blood while the other two use whole blood samples. A 2002 study found the wb-CATT to be the most efficient for diagnosis, while the wb-LATEX is a better exam for situations where greater sensitivity is required.
African Trypanosomiasis Treatment
First line, first stage
The current standard treatment for first stage disease is:
- Intravenous or intramuscular pentamidine (for ''T.b. gambiense''); or
- Intravenous suramin (for ''T.b. rhodesiense'')
The drug Eflornithine — previously used only as an alternative treatment for sleeping sickness due to its labour-intensive administration — was found to be safe and effective as a first-line treatment for the disease in 2008, according to the Science and Development Network's Sub-Saharan Africa news updates. Researchers tracked over 1,000 adults and children at a centre in Ibba, Southern Sudan—the first use of eflornithine on a large scale— and it was highly effective in treating the issue.
According to a treatment study of Trypanosoma gambiense caused human African trypanosomiasis, use of eflornithine (DMFO) resulted in fewer adverse events than treatment with melarsoprol.
All patients should be followed up for two years with lumbar punctures every six months to look for relapse.
First line, second stage
The current standard treatment for second stage (later stage) disease is:
- Intravenous melarsoprol 2.2 mg/kg daily for 10 consecutive days.
Alternative first line therapies include:
- Intravenous melarsoprol 0.6 mg/kg on day 1, 1.2 mg/kg IV melarsoprol on day 2, and 1.2 mg/kg/day IV melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3 to 10; or
- Intravenous eflornithine 50 mg/kg every six hours for 14 days.
Combination therapy with eflornithine and nifurtimox is safer and easier than treatment with eflornithine alone, and appears to be equally or more effective. It has been recommended as first-line treatment for second stage ''T. b. gambiensis'' disease.
In areas with melarsoprol resistance or in patients who have relapsed after melarsoprol monotherapy, the treatment should be:
- melarsoprol and nifurtimox, or
The following traditional regimens should no longer be used:
- (old "standard" 26-day melarsoprol therapy) Intravenous melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously for 3 days, with 7-day breaks between the series) (this regimen is less convenient and patients are less likely to complete therapy);
- (incremental melarsoprol therapy) 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3–10) (previously thought to reduce the risk of treatment-induced encephalopathy, but now known to be associated with an increased risk of relapse and a higher incidence of encephalopathy)
Trypanosomiasis vaccines are undergoing research.
African Trypanosomiasis Drug Targets and Drug Discovery
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 why 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.
Recent findings indicate that the parasite is unable to survive in the bloodstream without its flagellum. This insight gives researchers a new angle with which to attack the parasite.
A new treatment based on a truncated version of the apolipoprotein L-1 of high density lipoprotein and a nanobody has recently been found to work in mice, but has not been tested in humans.
The cover story of the August 25, 2006 issue of Cell journal describes an advance; Dr. Lee Soo Hee and colleagues, working at Johns Hopkins, have investigated the pathway by which the organism makes myristate, a 14-carbon length fatty acid. Myristate is a component of the variant surface glycoprotein (VSG), the molecule that makes up the trypanosome's outer layer. This outer surface coat of VSG is vital to the trypanosome's avoidance of immunological capture. Dr. Lee and colleagues discovered trypanosomes use a novel fatty acid synthesis pathway involving fatty acid elongases to make myristate and other fatty acids.
African Trypanosomiasis Prevention and Control
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. Instances of sleeping sickness are being reduced by the use of the sterile insect technique.
Regular active surveillance, involving case detection and treatment, in addition to tsetse fly control, is the backbone of the strategy for control of sleeping sickness. Systematic screening of communities in identified foci is the best approach as case-by-case screening is not practically possible in highly endemic regions. Systematic screening may be in the form of mobile clinics or fixed screening centres where teams travel daily to the foci. The nature of gambiense disease is such that patients do not seek treatment early enough because the symptoms at that stage are not evident or serious enough to warrant seeking medical attention, considering the remoteness of some affected areas. Also, diagnosis of the disease is difficult and most health workers may not be able to detect it. Systematic screening allows early-stage disease to be detected and treated before the disease progresses, and removes the potential human reservoir. There is a single case report of sexual transmission of West African sleeping sickness, but this is not believed to be an important route of transmission.
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