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Microbiology: African Sleeping Sickness

Sleeping sickness aka African trypanosomiasis
--parasitic disease in people and animals
--caused by protozoa of genus Trypanosoma
--transmitted by the tsetse fly
--endemic in certain regions of Sub-Saharan Africa (36 countries and 60 million people)
--estimated 50,000 to 70,000 current infx
--3 major epidemics: 1896–1906, 1920 and 1970.
--tse tse flies mainly found by rivers and lakes, in gallery-forests and in wooded savannah
--Sleeping sickness occurs only in sub-Saharan Africa in regions where there are tsetse flies that can transmit the disease.
--For reasons that are so far unexplained, there are many regions where tsetse flies are found, but sleeping sickness is not.
--Worldwide, 25,000 new cases of both East and West African trypanosomiasis are reported each year
--World Health Organization says it is vastly underreported.
--Human African trypanosomiasis (HAT)
--caused by flagellate protozoan, Trypanosoma brucei, which exists in 2 morphologically identical subspecies: Trypanosoma brucei rhodesiense (East African or Rhodesian African trypanosomiasis) and Trypanosoma brucei gambiense (West African or Gambian African trypanosomiasis)
--Both parasites transmitted to human hosts by bites of infected tsetse flies (Glossina species)
--tse tse flies are found only in Africa

--reservoirs of infection for these vectors are exclusively human in West African trypanosomiasis
--West African trypanosomiasis causes a chronic infection lasting years (Trypanosoma brucei gambiense)

--East African trypanosomiasis is a zoonotic infection with animal vectors. African trypanosomiasis is distinct from American trypanosomiasis, which is caused by Trypanosoma cruzi and has different vectors, clinical manifestations, and therapies. (emedicine)
--East African trypanosomiasis causes acute illness lasting several weeks (Trypanosoma brucei rhodesiense)

--red-painful swelling at bite site
--fever, headaches, and joint pains
--lymph nodes often swell up to tremendous sizes
--Winterbottom's sign: telltale swollen lymph glands along the back of the neck
--later: fear, mood swings, personality change, etc.

--slowly overcomes the defenses of the infected person-->anemia, endocrine, cardiac, kidney probs
--later-->passes BBB enters neurological phase, symptoms give the disease its name
--confusion and reduced coordination
--disturbed sleep cycle
--bouts of fatigue punctuated with manic periods progressing to daytime slumber and nighttime insomnia
--Without treatment, coma and death
--damage from neurological phase can be irreversible

--tsetse fly
--Mother to child infection: the trypanosome can cross the placenta-->perinatal death
--accidental lab infx from handling blood
--Blood transfusion
--Sexual contact (n=1)
--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.
--Horse-flies (Tabanidae) and Stomoxydinae possibly COULD play a role by mechanical transmission (in special situations) not only of Nagana (the animal form of sleeping sickness) but also of the human disease form.
--a single case report of sexual transmission of West African sleeping sickness, featured on House
--rural populations living in regions where transmission occurs and which depend on agriculture, fishing, animal husbandry or hunting are the most exposed to the bite of the tsetse fly and therefore to the disease.
--occurs & spreads in remote rural areas where health systems are weak or non-existent. The disease spreads in poor settings, displaced populations, people stressed by war
--Trypanosoma brucei gambiense (T.b.g.) is found in west and central Africa. This form represents more than 90% of reported cases of sleeping sickness and causes a chronic infection. A person can be infected for months or even years without major signs or symptoms of the disease. When symptoms do emerge, the patient is often already in an advanced disease stage when the central nervous system is affected.
--Trypanosoma brucei rhodesiense (T.b.r.) is found in eastern and southern Africa. This form represents less than 10% of reported cases and causes an acute infection. First signs and symptoms are observed after a few months or weeks. The disease develops rapidly and invades the central nervous system.
--Another form of trypanosomiasis occurs in 15 Central and South American countries. It is known as American Trypanosomiasis or Chagas disease. The causal organism is a different species from those causing the African form of the disease.
--other parasite species and sub-species of the Trypanosoma Genus are pathogenic to animals and cause animal Trypanosomiasis in many wild and domestic animal species (in cattle the disease is called Nagana, a Zulu word meaning “to be depressed”). Animals can host the human pathogen parasites, especially T.b. rhodesiense; thus domestic and wild animals are an important parasite reservoir. Animals can also be infected with T.b. gambiense, however the precise epidemiological role of this reservoir is not yet well known. This disease kills animals.
--The disease in domestic animals and particularly cattle is a major obstacle to the economic development of the rural areas affected.

--present in Africa since at least the 14th century, and probably before
--causative agent and vector were not identified until 1902–1903 by Sir David Bruce
--differentiation between protozoa was not made until 1910
--first effective treatment, Atoxyl, an arsenic based drug developed by Paul Ehrlich and Kiyoshi Shiga was introduced in 1910 but blindness was a serious side effect
--epidemics: 1896-1906 in Uganda and Congo Basin, 1920, 1970 epidemic still inj progress.
--it practically disappeared between 1960 and 1965, screening and effective surveillance were relaxed and the disease has reappeared in endemic form in several foci over the last thirty years.

--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
--about 300,000 new cases each year.[4] The disease has been recorded as occurring in 36 countries, all in sub-Saharan Africa.
--2005 saw major outbreaks in: Angola, the Democratic Republic of Congo and Sudan
--also still present in Central African Republic, Chad, Congo, Côte d’Ivoire, Guinea, Malawi, Uganda and United Republic of Tanzania
--low incidence in: Burkina Faso, Cameroon, Equatorial Guinea, Gabon, Kenya, Mozambique, Nigeria, Rwanda, Zambia and Zimbabwe (fewer than 50 new cases per year)
--very low incidence in: Benin, Botswana, Burundi, Ethiopia, Gambia, Ghana, Guinea Bissau, Liberia, Mali, Namibia, Niger, Senegal, Sierra Leone Swaziland and Togo (transmission seems to have stopped)

--demonstrate trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, or, in the late stages of infection, cerebrospinal fluid
--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 (centrifugation)
--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
--Three similar serological tests are available for detection of the parasite

--iv drugs, lots of options and history here
--lots of research ongoing
--type of treatment depends on the stage of the disease
--drugs for first stage are less toxic, easier to administer and more effective
--early ID increases odds of cure
--first stage tx options: Pentamidine, Suramin
--second stage needs drug that can cross BBB, toxic and difficult to administer
--Four drugs are registered for the treatment of sleeping sickness and provided free of charge to endemic countries through a WHO private partnership with sanofi-aventis (pentamidine, melarsoprol-contains arsenic and eflornithine) and Bayer AG (suramin)



( 5 comments — Leave a comment )
Mar. 13th, 2008 12:34 am (UTC)
You are awesome!

A la Wayne and Garth, "I am not worthy! I am not worthy!"
Mar. 13th, 2008 12:57 am (UTC)
=D Thanks.
Mar. 13th, 2008 11:45 am (UTC)
Thanks Teresa!
Mar. 13th, 2008 02:23 pm (UTC)
You betcha.
Mar. 15th, 2008 01:56 pm (UTC)
microbiol... I forgot the other part of the word...
Good Lord!! You're amazing! Thanks for delving into the depths of the unknown.

( 5 comments — Leave a comment )



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