***** This information provided is researched by students if at any time you
come in contact with a person infected with this virus or think you have any of
the symptoms listed contact a doctor immediately. We are not in any way medical
proffesionals this information provided is for a reseach project only.
Trypanosoma brucei belongs to the large group of protozoa known as
flagellates. Its cell structure is fairly typical of eukaryotes and it contains
all major organelles. It also features a
unique and notable variable surface glycoprotein (VSG) coat in order to avoid
the host's immune system. Another unusual
feature of this microorganism is the single large mitochondria with the
mitochondrial DNA structure known as the kinetoplast and its association with
the basal body of the flagellum. The
cytoskeleton is made up primarily of microtubules. The cell surface of the
bloodstream form features a dense coat of variable surface glycoproteins (VSGs)
which is replaced by an equally dense coat of procyclins when the parasite
differentiates into the procylic in the tsetse fly midgut. T. brucei
undergoes complex changes during its life cycle to facilitate its survival
in the insect gut and the mammalian bloodstream. T. brucei is found as a
trypomastigote in the slender, stumpy, procyclic and metacyclic forms. The
procylic form differentiates to the proliferitive epimastigote form in the
salivary glands of the insect. Unlike some other trypanosomatids, the
promastigote and amastigote form do not form part of the T.brucei life cycle. These microorganisms have complex life cycles
that require differential protein expression. Protein coding mRNAs are
synthesized, processed, translated and recycled in stage-specific ways in order
to allow parasite to thrive in diverse environments. Another unique characteristic of all
trypanosome mRNAs is a 5’ end leader sequence called the spliced leader. This
spliced leader provides a hypermethylated cap to mRNAs which enables long
polycistronic pre-mRNAs to be resolved into functional mRNAs.
There are 2 hosts of the sleeping sickness:
· Insect Vector - This fly is only found in Africa. Its survival is in the insect gut of the tsetse fly- parasite. It lives in the midgut and migrates to the salivary glands for injection to mammalian host on biting
· Mammalian Host- bloodstream parasite lives in the bloodstream where it can reinfect the fly vector after biting
T. brucei can be transmitted human to human via bodily fluid exchange but is primarily transferred via blood transfer
The most recent estimates 50,000-70,000 human cases currently exists currently about 17,000 new cases each year are reported to the World Health Organization (2006)
This illness can be fatal if left untreated. All patients diagnosed with African Trypanosomiasis must have their cerebrospinal fluid examined to determine whether there is involvement with the central nervous system. The WOC criteria for central nervous system involvement include a white blood cell count more than 5 and increased protein in cerebrospinal fluid. The purpose of this test is because the treatment drugs depend on the disease stage. Trypanosomes can frequently be observed in the cerebrospinal fluid in those with 2nd stage infection.
The people who are mostly exposed to the tsetse fly reside in rural populations that are dependent on agriculture, fishing, animal husbandry, or hunting.
Alternate Forms:
Animal Trypanosomiasis-
In cattle, this disease is called Nagana. This is a Zulu word that means "to be depressed." Animals can also be infected with T. brucei gambiense and act as a reservoir. This is a major obstacle to the economic development of affected rural areas.
Trypanosoma brucei rhodesiense-
This form is found in Eastern and Southern Africa and currently represents under 5% of reported cases. It causes acute infection and the initial signs and symptoms are observed a few months or weeks after infection. This disease rapidly develops and invades the central nervous system.
Stages of Infection:
During the initial stage trypanosomes multiply in subcutaneous tissues, blood, and lymph known as "haemolymphatic phase." Symptoms include headache, weakness, fever, joint pains, and itching.
During 2nd stage, the parasites cross the blood-brain barrier to infect the central nervous system. Symptoms appear as changes of behavior, confusion, sensory disturbances, poor coordination, anemia, cardiovascular problems, and kidney disorders. Important symptoms that occur during the 2nd stage which gave the disease its name include extreme exhaustion, fatigue during the day hours, although insomnia at night time, coma and ultimately death.
Diagnosis - 3 steps
1. Screening for potential infection involves using serological test and checking for clinical signs such as swollen cervical glands
2. Diagnosing whether parasite is present
3. Staging to determine state of disease progression which entails examining cerebrospinal fluid that is obtained by lumbar puncture and is used to determine the course of treatment
This disease is most commonly transmitted by a bite of tsetse fly, but there are other methods of transmission such as
* Mother to child infection: the trypanosome can cross the placenta and infect the fetus
* Mechanical transmission through other blood sucking insects is a possibility
* Accidental infections have occurred in laboratories due to pricks from contaminated needles
Treatment:
First stage of treatment medicine:
Drugs Administered -
· Pentamidine- This drug was discovered in 1941 and is used in the 1st stage of T.brucei gambiense
· Sumarin- This drug was discovered in 1921 and is used for the 1st stage of T. brucei rhodesiense. It provokes certain undesirable effects in the urinary tract and causes allergic reactions.
Second stage treatment medicine:
· Melarsoprol- discovered in 1949 used in both forms of infection derived from arsenic
· Eflornithine- registered in 1990 only effective against T.b.gambiense this regimen is strict and difficult to apply
· Combination treatment of nifurtimox and eflornithine recently introduced in 2009 not effective for T.b.rhodesiense
· Nifurtimox is registered for treatment of American Trypanosomiasis
Pentamidine
Common Side Effects:
- Bad taste in mouth, cough, decreased appetite, diarrhea, headache, nausea, night sweats, and sinus inflammation
Severe Side Effects:
- Severe allergic reactions(rash hives, difficulty breathing, tightness in chest, swelling of the mouth, face, lips, or tongue), blurred vision, chest pain, dark urine, fast or irregular heartbeat, fevers, chills, or sore throat, herpes infection(e.g. shingles) increased or decreased urination; increased thirst, mental or mood changes, one-sided weakness, red, swollen, blistered, or peeling skin; seizures, severe or persistent dizziness, slurred speech, unusual bruising or bleeding, wheezing, white patches in throat or mouth, and yellowing of the skin or eyes
Sumarin
- Metal taste in mouth, abdomen pain, fever, and discomforting feeling
Common Side Effects:
- Cloudy urine, vomiting, crawling sensation on skin, fatigue, diarrhea, tenderness in palm and feet, fainting, skin swelling, headaches, stinging skin, discoloration, rash, irritability, numbness in hands, feet, and legs, joint pains, decreased appetite, and nausea.
Severe Side Effects:
- Yellowing of skin, changes of vision or vision loss, extreme sensitivity to light in the eyes, abnormal fatigue and weakness, pain in the glands, abnormal bleeding, pains in the groin, swollen glands, pain in the armpits or neck, swelling in the abdomen, hypo tension or low blood pressure, fever, chills, sore throat, paleness of skin, abnormal bruising, reddening of skin, scales or thickening, and rapid heart.
Melarsoprol
- Highly dangerous treatment - only administered by injection under the supervision of a physician, as it can produce similar effects as arsenic poisoning.
- Known to cause a range of side effects including convulsions, fever, loss of consciousness, rashes, bloody stools, nausea, and vomiting. It is fatal in and of itself in around 8% of cases.
Eflornithine
- Effective only for West African sleeping sickness (caused by Trypanosoma brucei gambiense); it has no effect on East African sleeping sickness (caused by Trypanosoma brucei rhodesiense).
- Topical Use – most frequently reported side effect is acne (7-14%). Other side effects commonly (> 1%) reported are skin problems, such as skin reactions from in-growing hair, hair loss, burning, stinging or tingling sensations, dry skin, itching, redness or rash.
- Side effects related to systemic use of Ornidyl through injection – Usually reversible by discontinuing the drug or decreasing the dose. Hematologic abnormalities occur frequently, ranging from 10–55%. Seizures in approximately 8% of patients (may be related to the disease state rather than the drug). Reversible hearing loss has occurred in 30–70% of patients receiving long-term therapy
Nifurtimox
Side effects:
Combo of Nifurtimox and Eflornithine
- Relatively new treatment approach so side effects are not clearly known