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Trypanosoma brucei,
the microorganism, that causes African sleeping sickness, was named after Sir David
Bruce, who discovered these parasites in cattle in 1895. The human blood form
of the pathogen was  first identified by
Forde and Dutton (Steverding 2008).
The T. brucei  subspecies; comprising of T. brucei gambiense; T. brucei rhodesiense are
responsible for human African trypanosomiasis(HAT) and animal trypanosomiasis(found
in domesticated animals in Africa). 
Animal trypanosomiasis is commonly known as nagana. T. brucei gambiense and T. brucei rhodesiense are mainly associated with the human form
of the disease, whereas T. brucei brucei
non pathogenic to humans, but is known to cause the animal form of the
disease or nagana. Nagana is of profound agricultural and economic importance
in the affected regions of Africa and is capable of hindering agricultural
development(Wilkinson and Kelly 2009).
 Infected cattle are unable produce milk
or meat and suffer from repeated prostration
and intercurrent infections which are fatal.  Trypanosomatids are members to protozoan
order known as Kinteplastida. Kinetoplastids
are flagellated protozoans that are charcterized by the possession of a mitochondrial
DNA-containing region, called “kinetoplast,” (Stuart, Brun et
al. 2008).


These parasites are vector borne
and have their lifecycle bet­­­ween the insect vector, glossina spp (Tsetse
fly) and their human hosts. Once infected, the disease manifests itself in two stages
in 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 lymphatic
systems. Symptoms are non specific and range from intermittent fevers, headaches,
joint pains and may develop into other complications such as inflamed lymph
glands and spleen, local oedema and cardiac abnormalities. The cerebral phase
begins when parasites cross the blood–brain barrier. Disease manifestations at
this stage include neurologically related symptoms such as severe headaches, changes
in the affected individual’s sleeping pattern, personality change, mental
impairment and weight loss. If left untreated at this stage, patients get into
a comatose stage and in due course may lose their lives(Wilkinson and Kelly 2009)  Add more references.

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 Trypanosoma gambiense and rhodesiense cause
geographically distinct diseases. They are responsible for the West African and
East African sleeping sickness respectively(Barrett, Burchmore et al. 2003).
The two forms of the disease are distinguished by duration of advancement from
the haemolyphatic stage to the cerebral stage. 
The West African trypanosomiasis, takes months to progress from the blood/lymphatic
stage to the cerebral stage, hence the infection is termed chronic. On the contrary,
the East African trypanosomiasis is more acute and disease progression is more
rapid. It takes between 1–3 weeks to move from the early haemolymphatic stage
to the late cerebral stage.  Both forms
of trypanosomiasis are zoonotic, although humans are the main reservoir of
T. b. Gambiense. In contrast, the major reservoirs with T. b. Rhodesiense are wild and domestic
animals, 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 gambiense
are morphologically alike with their non-human pathogen relative Trypanosoma brucei brucei  but can be
differentiated from latter by the
genes encoding serum resistance-associated (SRA) protein and T.b.
gambiense–specific glycoprotein, which are found only in the genomes
of T.b. rhodesiense and T.b. gambiense,
respectively;  but not in T.b. brucei  (Radwanska,
Chamekh et al. 2002).


accurs when the Tsetse fly feeds on the mammalian host and inserts the
metacyclic trypomastigotes into the skin tissue where it then moves onto the
lymphatic system and passed onto the bloodstream where they multiply and become
blood stream trypomastigotes. The parasite is then transported to different
parts of the body, as the blood circulates. They remain extracellular and
continue to divide by binary fission. The parasite can occasionally escape the blood
brain barrier and infect the cerebral cortex leading the 2nd stage
of the disease associated neuropathological symptoms such as sleeping
disorder  which gives it the name sleeping
sickness. The next stage of the parasitic life begins when the tsetsefly bites
the infected mammalian host and gets infected with the blood stream
trypanomastigote which migrate to the fly’s midgut and transform into procyclic
trypomastigote, multiplies by binary fission and migrate from the gut to become
epimastigote, which also undergo further cell division by binary fission to
become metacyclic trypomastigotes in the fly’s salivary glands. This form of
the parasite is readily transmitted to the next host (CDC).



Over the past decades, concerted
effort in surveillance, insect vector control and better housing (Stuart, Brun et al. 2008, Hall, Meredith et al. 2012)and
treatment programmes in the affected regions have resulted in significant
decline in the prevalence and mortality due of HAT, leading to a mortality rate
of less than 100 000 annually(Barrett 2006).
However, in war thorn and unstable regions such Angola, the Democratic Republic
of Congo and southern Sudan, the mortality rate exceeds that of malaria and
HIV/AIDS (human immunodeficiency virus and acquired immune deficiency syndrome
in 20…  Despite the reduction in cases
in endemic regions, tourism and migration, blood transfusion, organ donation
and illegal drug use have led to the emergence of trypanosomiasis in places of
non 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 a
surface coat made of a single antigen, known as the variant surface
glycoprotein (VSG). The parasite evades the mammalian immune system by a
process of antigenic variation.  It periodically
changes its VSG expression to one of its more than 2000 antigenically distinct
surface glycoproteins encoded by the large repertoire of VSG genes. As a result
of this constant antigenic variation of the VSG, vaccine development against
this T.brucei is not thought to be a feasible
option for now. Chemotherapy is therefore the only
viable option to fight this disease. However, current drugs are either toxic or
prohibitively expensive; require medical supervision to administer them; have
adverse 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 to
treat of HAT.  Additional
problems associated with HAT therapy is that chemotherapy is further
complicated by the fact that the effectiveness of some drugs is subspecies
dependant 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 treatment
of early stage T. b gambiense and T. b. Rhodesiense  HAT respectively.  These drugs
have been in use for decades. For example, suramin was developed in 1916 and
pentamidine in 1937(Steverding 2008). Until recently,  eflornithine had been the only monotherapy for
stage two T. b. gambiense HAT.  A
combination therapy comprising of Nofurtimox and eflornithine(NECT) has also been
introduced against cerebral stage T. b. gambiense HAT
HAT(Wilkinson and Kelly 2009).  NECT has equivalent
therapeutic efficacy to eflornithine monotherapy, but has the added advantage
of 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 forms
of HAT during stage two disease, though its use can cauce devastating reactive
encephalitis in 5–10% of cases, believed to be caused by the massive release of
parasite 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 late
stage HAT. The intoduction of NECT as an alternative therapy resulted to a decrease
in melarsoprol use   To
address all these issues, it is therefore urgent to replace or complement these
treatments with new (Hall,
Meredith et al. 2012) and better tailored chemotherapies. New
drugs that are on clinical trials may be available in the near future include; fexnidazole, an orally active
nitroimidazole, and the benzoxaborole, SCYX-7158, respectively(Jacobs, Nare et al. 2011, Barrett and Croft 2012,
Alsford, Kelly et al. 2013). 

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