Trypanosoma brucei,the microorganism, that causes African sleeping sickness, was named after Sir DavidBruce, who discovered these parasites in cattle in 1895. The human blood formof the pathogen was first identified byForde and Dutton (Steverding 2008).The T.
brucei subspecies; comprising of T. brucei gambiense; T. brucei rhodesiense areresponsible for human African trypanosomiasis(HAT) and animal trypanosomiasis(foundin domesticated animals in Africa). Animal trypanosomiasis is commonly known as nagana. T. brucei gambiense and T. brucei rhodesiense are mainly associated with the human formof the disease, whereas T. brucei bruceinon pathogenic to humans, but is known to cause the animal form of thedisease or nagana.
Nagana is of profound agricultural and economic importancein the affected regions of Africa and is capable of hindering agriculturaldevelopment(Wilkinson and Kelly 2009). Infected cattle are unable produce milkor meat and suffer from repeated prostrationand intercurrent infections which are fatal. Trypanosomatids are members to protozoanorder known as Kinteplastida. Kinetoplastidsare flagellated protozoans that are charcterized by the possession of a mitochondrialDNA-containing region, called “kinetoplast,” (Stuart, Brun etal. 2008).
These parasites are vector borneand have their lifecycle between the insect vector, glossina spp (Tsetsefly) and their human hosts. Once infected, the disease manifests itself in two stagesin humans: the early (haemolymphatic) stage and the late (encephalitic) phase (Barrett, Burchmore et al. 2003, Stuart, Brun et al. 2008).
In initial phase, parasites are seen in both the blood and the lymphaticsystems. Symptoms are non specific and range from intermittent fevers, headaches,joint pains and may develop into other complications such as inflamed lymphglands and spleen, local oedema and cardiac abnormalities. The cerebral phasebegins when parasites cross the blood–brain barrier. Disease manifestations atthis stage include neurologically related symptoms such as severe headaches, changesin the affected individual’s sleeping pattern, personality change, mentalimpairment and weight loss.
If left untreated at this stage, patients get intoa comatose stage and in due course may lose their lives(Wilkinson and Kelly 2009) Add more references. Trypanosoma gambiense and rhodesiense causegeographically distinct diseases. They are responsible for the West African andEast African sleeping sickness respectively(Barrett, Burchmore et al. 2003).The two forms of the disease are distinguished by duration of advancement fromthe haemolyphatic stage to the cerebral stage. The West African trypanosomiasis, takes months to progress from the blood/lymphaticstage to the cerebral stage, hence the infection is termed chronic.
On the contrary,the East African trypanosomiasis is more acute and disease progression is morerapid. It takes between 1–3 weeks to move from the early haemolymphatic stageto the late cerebral stage. Both formsof trypanosomiasis are zoonotic, although humans are the main reservoir ofT.
b. Gambiense. In contrast, the major reservoirs with T. b. Rhodesiense are wild and domesticanimals, especially cattle (Wilkinson and Kelly 2009).
More than 90% of HAT cases are due to T. b. Rhodensiense(Alsford, Kelly et al. 2013). Trypanosoma brucei rhodensiense and gambienseare morphologically alike with their non-human pathogen relative Trypanosoma brucei brucei but can bedifferentiated from latter by thegenes encoding serum resistance-associated (SRA) protein and T.b.gambiense–specific glycoprotein, which are found only in the genomesof T.
b. rhodesiense and T.b. gambiense,respectively; but not in T.b. brucei (Radwanska,Chamekh et al.
2002). Transmissionaccurs when the Tsetse fly feeds on the mammalian host and inserts themetacyclic trypomastigotes into the skin tissue where it then moves onto thelymphatic system and passed onto the bloodstream where they multiply and becomeblood stream trypomastigotes. The parasite is then transported to differentparts of the body, as the blood circulates. They remain extracellular andcontinue to divide by binary fission. The parasite can occasionally escape the bloodbrain barrier and infect the cerebral cortex leading the 2nd stageof the disease associated neuropathological symptoms such as sleepingdisorder which gives it the name sleepingsickness. The next stage of the parasitic life begins when the tsetsefly bitesthe infected mammalian host and gets infected with the blood streamtrypanomastigote which migrate to the fly’s midgut and transform into procyclictrypomastigote, multiplies by binary fission and migrate from the gut to becomeepimastigote, which also undergo further cell division by binary fission tobecome metacyclic trypomastigotes in the fly’s salivary glands. This form ofthe parasite is readily transmitted to the next host (CDC).
Over the past decades, concertedeffort in surveillance, insect vector control and better housing (Stuart, Brun et al. 2008, Hall, Meredith et al. 2012)andtreatment programmes in the affected regions have resulted in significantdecline in the prevalence and mortality due of HAT, leading to a mortality rateof less than 100 000 annually(Barrett 2006).
However, in war thorn and unstable regions such Angola, the Democratic Republicof Congo and southern Sudan, the mortality rate exceeds that of malaria andHIV/AIDS (human immunodeficiency virus and acquired immune deficiency syndromein 20… Despite the reduction in casesin endemic regions, tourism and migration, blood transfusion, organ donationand illegal drug use have led to the emergence of trypanosomiasis in places ofnon endemicity such as Europe and the United States of America,(Urech, Neumayr et al. 2011)(Gautret, Clerinx et al. 2009)which is a cause for concern. T.
brucei is an extracellular pathogen, with asurface coat made of a single antigen, known as the variant surfaceglycoprotein (VSG). The parasite evades the mammalian immune system by aprocess of antigenic variation. It periodicallychanges its VSG expression to one of its more than 2000 antigenically distinctsurface glycoproteins encoded by the large repertoire of VSG genes. As a resultof this constant antigenic variation of the VSG, vaccine development againstthis T.
brucei is not thought to be a feasibleoption for now. Chemotherapy is therefore the onlyviable option to fight this disease. However, current drugs are either toxic orprohibitively expensive; require medical supervision to administer them; haveadverse effects on patients and there is equally an emerging trend of resistance(Wilkinson and Kelly 2009),(Alsford, Kelly et al. 2013). Furthermore, only few drugs are licensed totreat of HAT. Additionalproblems associated with HAT therapy is that chemotherapy is furthercomplicated by the fact that the effectiveness of some drugs is subspeciesdependant and the disease stage at which the patient presents. The Licensed drugs for treatment of HAT are namely;Suramin, pentamidine, mlarsoprol, and eflornithine. Pentamidine or suramin are used for treatmentof early stage T.
b gambiense and T. b. Rhodesiense HAT respectively. These drugshave been in use for decades. For example, suramin was developed in 1916 andpentamidine in 1937(Steverding 2008). Until recently, eflornithine had been the only monotherapy forstage two T.
b. gambiense HAT. Acombination therapy comprising of Nofurtimox and eflornithine(NECT) has also beenintroduced against cerebral stage T. b. gambiense HATHAT(Wilkinson and Kelly 2009). NECT has equivalenttherapeutic efficacy to eflornithine monotherapy, but has the added advantageof reduced dosing resulting in greater patient acceptance (Priotto et al.
2009). Melarsoprol,which has been in use since 1949, is the only drug effective against both formsof HAT during stage two disease, though its use can cauce devastating reactiveencephalitis in 5–10% of cases, believed to be caused by the massive release ofparasite antigens and a subsequent autoimmune reaction (Pepin and Milord,1994). Until the introduction of eflornithine and NECT for the treatment of T.b. gambiense HAT, melarsoprol was the only drug effective against either latestage HAT. The intoduction of NECT as an alternative therapy resulted to a decreasein melarsoprol use Toaddress all these issues, it is therefore urgent to replace or complement thesetreatments with new (Hall,Meredith et al. 2012) and better tailored chemotherapies.
Newdrugs that are on clinical trials may be available in the near future include; fexnidazole, an orally activenitroimidazole, and the benzoxaborole, SCYX-7158, respectively(Jacobs, Nare et al. 2011, Barrett and Croft 2012,Alsford, Kelly et al. 2013).