chapter 1 - Bentham Science

176 Chemoinformatics: Directions Toward Combating Neglected Diseases Taft et al.
1.10. Giardiasis
Giardiasis infects over 2.5 million people annually. In humans, it is caused by the infection of the small
intestine by a single-celled organism and occurs worldwide with a prevalence of 20-30% in developing
countries. It has a wide range of human and other mammalian hosts making it very difficult to eliminate [46].
1.11. Amebiasis
Amebiasis is an intestinal illness that is typically transmitted when someone eats or drinks something
contaminated with a microscopic parasite. In many cases, the parasite lives in a person's large intestine
without causing any symptoms. But sometimes, it invades the lining of the large intestine, causing bloody
diarrhea, stomachaches, cramping, nausea, loss of appetite, or fever. In rare cases, it can spread into other
organs such as the liver, lungs, and brain [47].
2. CAUSATIVE AGENTS
2.1. Trypanosoma cruzi
The hemoflagellate protozoan T. cruzi is the causative agent of the Chagas`s disease, which is transmitted
to humans either by blood-sucking reduviid bugs or directly by the transfusion of infected blood. After 10-
20 years, a chronic form of the disease often develops causing irreversible damage to colon, heart and
esophagus, which can lead to death. In rural areas, the disease is transmitted by bugs such as Rhodnius
prolixus and Triatoma infestans.
T. cruzi multiplies within the insect gut as an epimastigote form and is spread as a non-dividing metacycle
trypomastigote from the insect excrements by contamination of intact mucosa or wounds produced by the
blood-sucking activity of the vector. In the mammalian host, it proliferates intracellularly in the amastigote
form and releases into the blood stream as a non-dividing infective trypomastigote [11, 47].
2.2. Trypanosoma brucei
These parasites are the cause of human African trypanosomiasis, i.e., sleeping sickness, which is fatal if
untreated. The causative agents are phenotypically and morphologically similar. T. brucei is characterized
by the presence of a DNA-containing organelle in the mitochondrion. It also contains a cell membrane
(complex grid of microfilaments and microtubules). The outer surface is covered with a single
glycoprotein. The parasite has the capability to synthesize aminoacids, and polyamines, compounds
essential for proliferation and differentiation of the bloodstream stages. The main thiol is trypanothione,
whose metabolism plays an important role in trypanosomal survival.
T. brucei is transmitted by species of tsetse flies. The insect vector takes a blood meal from mammals
injecting metacyclic trypomastigotes, which transform into bloodstream trypomastigotes, transported to
other sites and profilerating by binary fission to different body fluids such as blood, lymph and spinal fluid.
The procyclic cell acts as a prototype for the basic architecture of T. brucei. Regulatory pathways
controlling the eukaryotic cell cycle involve regulatory proteins such as cyclin dependent kinases and
inhibitors possessing distinct roles in the different life cycle stages [4, 11, 47].
2.3. Protozoan leishmania
Leishmaniasis is caused by 20 species of Leishmania (order of Kinetoplastida, family Trypanosomatidae)
and transmitted by 30 species of sand fly. Leishmania species are divided into species by geographic
location of endemic species. The parasite is carried by the female phlebotamine sandfly of the genus
phlebotamus or Lutzomyia. Only two Leishmania species can maintain anthroponotic human-human cycle,
i.e., L. donovani, and L. tropica.
In the mammalian host, the parasite proliferates as amastigotes intracelluarly within a phagolysosome
compartment of macrophages. The extracellular flagellated promastigotes proliferates in the gut of their
sand fly vectors, where they multiply and differentiate before emerging as an infectious species. The