Variant Surface Glycoproteins (VSGs) of Trypanosomes

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Trypanosomes

Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.

By Kelly Wahl


Trypranasomes are single celled flagellated eukaryotic parasites that infect humans and livestock causing trypanosomiasis, more commonly as sleeping sickness in Africa and Chagas disease in the Americas. These parasites are usually introduced into the body via an arthropod vector. The tsetse fly (subgenus Glossina morsitans), transmits the strains Trypanosoma brucei gambiense (95% of reported cases and found exclusively in West Africa) and Trypanosoma brucei rhodesiense (5% of reported cases, only seen in East Africa) responsible for sleeping sickness through its bite. Oddly the geographic range of these two strains do not overlap. The kissing bug (subfamily : Triatominae) spreads Trypanosoma cruzi when its feces enter the body through the mucosal membranes, or broken skin (bite marks or scratches). Besides T. brucei, and T. cruzi, there are many other strains of trypanosomes that affect mainly domesticated animals like; cows, camels, deer, horses, antelope, and donkey.

These parasites fall under the order Kinetoplastidia and are related to another pathogenic parasite, Leishmania. Kinetoplasts are called such because of the kinetoplast at the base of their flagellum. A kinetoplast is a mitochondrion with coiled mitochondrial DNA and 10% of the total genomic DNA of the parasite. The kinetoplast changes size and shape throughout the parasites life cycle and is the target site of some anti-parasitic drugs (like?). Kinetoplasts broke off from the common ancestor fairly early on and consequently transcription of their genome is unlike most other organism and is under intensive study as a potential vaccine or drug target. (Epigenetics and…)(kinetoplast wiki)(that cool site)

Trypanosome Infection; Sleeping Sickness, and Chagas Disease

Sleeping Sickness

Stage one of T. brucei infection is the haemolymphatic stage. Parasites circulate and multiply by binary fission in the blood and lymph systems. infection with T. b. rhodesiense often begins as a sore called a chancre and is followed a week or two of headaches, fevers, and muscle and joint pain. Enlarged lymph nodes are common and some patients also present with a rash. Large inflamed lymph nodes is a characteristic sign of infection called Winterbottom’s sign. T. b. gambiense infection shows the same symptoms but they are not as severe and last for a longer period of time.

The second stage of infection is neurological. The parasites have crossed the blood-brain barrier and are now multiplying in the central nervous system. classic symptoms include rapid weight loss, impaired motor skills, seizures, confusion, and changes in personality. A disrupted circadian rhythm where a patient lies awake at night but sleeps during the day is where this disease gets its namesake. Without treatment T. b. rhodesiense infection progress to coma and death within a few months. Often times T. b. rhodesiense infection moves so quickly that malnutrition, heart failure, and pneumonia cause death before the neurological problems ever manifest themselves. The progression of T. b. gambiense infection takes much longer and a person can take years to show neurological symptoms. The different clinical manifestations of the two strains stems from differences in the two strains stimulation of the immune system. T. b. gambiense infection stimulates a huge response from the immune system that results in death of host cells and observed anemia, weakness, pain, and inflammation.

Chagas Disease

Chagas disease is similar to sleeping sickness in many ways. There is an acute stage when the parasite is circulating in the bloodstream and the initial site of infection swells and a patient may present with a fever or show no signs of infection. One of the classic signs of acute Chagas infection is Romana’s sign, the swelling of the area around the eye where the conjunctiva (mucosal tissue around the eye) or a site near the eye was point of infection. Serious symptoms are rare in this stage of infection but are possible. They include heart failure, chest pain, seizures, or paralysis.

Unlike sleeping sickness, Chagas disease only progresses to the chronic form of the disease in 20 to 30% or people infected. The remaining 70 to 80% of people infected remain asymptomatic for life and may never know they are infected. As the parasite replicates in the target tissues; cardiac muscle and digestive smooth muscle those infected show a variety of cardiac problems such as irregular heartbeat, blood flow disorders, issues with heart muscle function, and blood clots. As well as problems with the digestive tracts such as ulcers.

Treatment

Symptomatic trypanasome infection is usually fatal if left untreated. While there is no vaccine or prophylactic drugs to prevent T. brucei infection there are drugs available for treatment a recent infection as well as cases that have already become symptomatic. The earlier the diagnosis is made the easier it is to manage symptoms with less toxic drugs that target the parasite outside of the central nervous system. once the infection has become symptomatic strong drugs with much higher toxicity must be used to cross the blood-brain barrier and attack the parasite in the CNS. If the infection has progressed to this point it is likely that a lengthy hospital stay is required to clear up infection. There is a need for new drugs to combat this disease because the toxicity associated with some of the drugs used to treat the infection are almost as bad as the infection itself.

Why Are Trypanosomes of Public health and Economic Interest?

African trypanosomiasis is of public health and economic importance for a number of reasons. Besides affecting humans, trypanosomes also infect domesticated cattle making cattle sick with disease called Nagana and hindering economic development in affected areas. The inability to raise cattle in sub-Saharan African further contributes to malnutrition in the area. Animals also serve as reservoirs to the parasites, most importantly the T. b. rhodesiense strain making it difficult to eradicate the parasite in a given area. These parasites are only found within the tsetse flys’ geographic range, sub-Saharan Africa and have devastating economic effects on the people infected because of the length of infection and the nature of those infected. Those who rely on farming, fishing, and hunting are most at risk to be bitten by an infected tsetse fly and are also commonly the breadwinners in poor, rural populations. While the WHO only reports about 10,000 new cases a year this number is most likely a gross underestimate of the true number of cases and other estimates put the number around 100,000 although others still caution that these numbers are underestimated when close to 50,000,000 are at risk.

Both African trypanosomiasis and Chagas disease considered neglected tropical diseases under which a projected 534,000 deaths a year and account for millions of year of functional life lost due to disability or years of life lost due to ill health. Those affected are primarily low and middle income countries in areas where the disease is most prevalent. Under international public health trypanosome diseases are important for the lives lost and emerging rural economies stunted by this disease. Domestically, Chagas presents a threat to blood and organ transplant recipients. It is estimated that there are more than 300,000 people living with T. cruzi infections in the U.S.. Although natural transmission through triatomines found in North America is possible it is very rare and iatrogenic (through transplants) exposure represents the greatest risk of route of domestic exposure. In this increasingly globalized world diseases that once hid in the jungles of South America and the plains of sub-Saharan Africa have ended up on the doorstep of industrialized nations. Although trypanosomiasis is still considered a third-world disease infections are continually diagnosed in the first world and represent a real risk to anyone that can get on a plane and travel to an affected area.

Transmission and Life Cycle

Transmission

Although the most common route of infection is for T. brucei, and T. cruzi are run-ins with the arthropods Glossina morsitans and : Triatominae these parasites can be passed from mother to child during pregnancy. Blood transfusion and sex can also spread these parasites but this is very rare.

Life cycle