Related Research Articles
Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by Trypanosoma cruzi. It is spread mostly by insects in the subfamily Triatominae, known as "kissing bugs". The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or swelling at the site of the bite. After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms. Up to 45% of people with chronic infections develop heart disease 10–30 years after the initial illness, which can lead to heart failure. Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.
African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species Trypanosoma brucei. Humans are infected by two types, Trypanosoma brucei gambiense (TbG) and Trypanosoma brucei rhodesiense (TbR). TbG causes over 92% of reported cases. Both are usually transmitted by the bite of an infected tsetse fly and are most common in rural areas.
Trypanosomatida is a group of kinetoplastid unicellular organisms distinguished by having only a single flagellum. The name is derived from the Greek trypano (borer) and soma (body) because of the corkscrew-like motion of some trypanosomatid species. All members are exclusively parasitic, found primarily in insects. A few genera have life-cycles involving a secondary host, which may be a vertebrate, invertebrate or plant. These include several species that cause major diseases in humans. Some trypanosomatida are intracellular parasites, with the important exception of Trypanosoma brucei.
Immunoglobulin A is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other types of antibody combined. In absolute terms, between three and five grams are secreted into the intestinal lumen each day. This represents up to 15% of total immunoglobulins produced throughout the body.
In biology and biochemistry, protease inhibitors, or antiproteases, are molecules that inhibit the function of proteases. Many naturally occurring protease inhibitors are proteins.
Trypanosoma is a genus of kinetoplastids, a monophyletic group of unicellular parasitic flagellate protozoa. Trypanosoma is part of the phylum Sarcomastigophora. The name is derived from the Greek trypano- (borer) and soma (body) because of their corkscrew-like motion. Most trypanosomes are heteroxenous and most are transmitted via a vector. The majority of species are transmitted by blood-feeding invertebrates, but there are different mechanisms among the varying species. Trypanosoma equiperdum is spread between horses and other equine species by sexual contact. They are generally found in the intestine of their invertebrate host, but normally occupy the bloodstream or an intracellular environment in the vertebrate host.
Carlos Justiniano Ribeiro Chagas, or Carlos Chagas, was a Brazilian sanitary physician, scientist, and microbiologist who worked as a clinician and researcher. Most well known for the discovery of an eponymous protozoal infection called Chagas disease, also called American trypanosomiasis, he also discovered the causative fungi of the pneumocystis pneumonia. He described the two pathogens in 1909, while he was working at the Oswaldo Cruz Institute in Rio de Janeiro, and named the former Trypanosoma cruzi to honour his friend Oswaldo Cruz.
Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya. It is the namesake member of the papain-like protease family.
Cathepsins are proteases found in all animals as well as other organisms. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption. Cathepsins have a vital role in mammalian cellular turnover.
Trypanosoma brucei is a species of parasitic kinetoplastid belonging to the genus Trypanosoma that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclusively extracellular and inhabits the blood plasma and body fluids. It causes deadly vector-borne diseases: African trypanosomiasis or sleeping sickness in humans, and animal trypanosomiasis or nagana in cattle and horses. It is a species complex grouped into three subspecies: T. b. brucei, T. b. gambiense and T. b. rhodesiense. The first is a parasite of non-human mammals and causes nagana, while the latter two are zoonotic infecting both humans and animals and cause African trypanosomiasis.
Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad.
Trypanosoma cruzi is a species of parasitic euglenoids. Among the protozoa, the trypanosomes characteristically bore tissue in another organism and feed on blood (primarily) and also lymph. This behaviour causes disease or the likelihood of disease that varies with the organism: Chagas disease in humans, dourine and surra in horses, and a brucellosis-like disease in cattle. Parasites need a host body and the haematophagous insect triatomine is the major vector in accord with a mechanism of infection. The triatomine likes the nests of vertebrate animals for shelter, where it bites and sucks blood for food. Individual triatomines infected with protozoa from other contact with animals transmit trypanosomes when the triatomine deposits its faeces on the host's skin surface and then bites. Penetration of the infected faeces is further facilitated by the scratching of the bite area by the human or animal host.
Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease, the effectiveness decreases in those who have long-term infection. It is the first-line treatment given its moderate side effects compared to nifurtimox. It is taken by mouth.
Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are now classified in the supergroups Excavata, Amoebozoa, SAR, and Archaeplastida.
Trypanosoma rangeli is a species of hemoflagellate excavate parasites of the genus Trypanosoma. Although infecting a variety of mammalian species in a wide geographical area in Central and South America, this parasite is considered non-pathogenic to these hosts. T. rangeli is transmitted by bite of infected triatomine bugs of the Reduviidae family, commonly known as barbeiro, winchuka(vinchuca), chinche, pito ou chupão.
A Trypanosomiasis vaccine is a vaccine against trypanosomiasis. No effective vaccine currently exists, but development of a vaccine is the subject of current research.
Hookworm vaccine is a vaccine against hookworm. No effective vaccine for the disease in humans has yet been developed. Hookworms, parasitic nematodes transmitted in soil, infect approximately 700 million humans, particularly in tropical regions of the world where endemic hookworms include Ancylostoma duodenale and Necator americanus. Hookworms feed on blood and those infected with hookworms may develop chronic anaemia and malnutrition. Helminth infection can be effectively treated with benzimidazole drugs, and efforts led by the World Health Organization have focused on one to three yearly de-worming doses in schools because hookworm infections with the heaviest intensities are most common in school-age children. However, these drugs only eliminate existing adult parasites and re-infection can occur soon after treatment. School-based de-worming efforts do not treat adults or pre-school children and concerns exist about drug resistance developing in hookworms against the commonly used treatments, thus a vaccine against hookworm disease is sought to provide more permanent resistance to infection.
VNI is an experimental drug for treating Chagas disease currently being studied at Vanderbilt University. The molecule acts by inhibiting Trypanosoma cruzi sterol 14α-desmethylase activity in vitro. It exhibits no toxicity in mouse cells and unlike the related compounds posaconazole and fluconazole, increasing the dose is not required to maintain anti-parasitic activity.
Papain-like proteases are a large protein family of cysteine protease enzymes that share structural and enzymatic properties with the group's namesake member, papain. They are found in all domains of life. In animals, the group is often known as cysteine cathepsins or, in older literature, lysosomal peptidases. In the MEROPS protease enzyme classification system, papain-like proteases form Clan CA. Papain-like proteases share a common catalytic dyad active site featuring a cysteine amino acid residue that acts as a nucleophile.
Gallinamide A is potent and selective inhibitor of the human cysteine protease cathepsin L that was first used as a moderate antimalarial agent. Gallinamide A is produced by marine cyanobacteria from Schizothrix species and Symploca sp. which have also shown to have possible anticancer agent, infectious diseases like leishmaniasis, trypanosomiasis and possible uses in Alzheimer's disease, among others.
References
- ↑ Lalmanach G, Boulangé A, Serveau C, Lecaille F, Scharfstein J, Gauthier F, Authié E (May 2002). "Congopain from Trypanosoma congolense: drug target and vaccine candidate" (PDF). Biological Chemistry. 383 (5): 739–49. doi:10.1515/BC.2002.077. PMID 12108538. S2CID 22315392.
- 1 2 Cerny, Natacha; Bivona, Augusto Ernesto; Sanchez Alberti, Andrés; Trinitario, Sebastián Nicolás; Morales, Celina; Cardoso Landaburu, Alejandro; Cazorla, Silvia Inés; Malchiodi, Emilio Luis (2020). "Cruzipain and Its Physiological Inhibitor, Chagasin, as a DNA-Based Therapeutic Vaccine Against Trypanosoma cruzi". Frontiers in Immunology. 11: 565142. doi: 10.3389/fimmu.2020.565142 . ISSN 1664-3224. PMC 7583359 . PMID 33162979.
- ↑ Juan San Francisco, Iván Barría, Bessy Gutiérreza, Iván Neira, Christian Muñoza, Hernán Sagua, Jorge E. Araya, Juan Carlos Andradea, Anibal Zailberger, Alejandro Catalána, Francisco Remonsellez, José Luis Vega, Jorge González (January 2017). "Decreased cruzipain and gp85/trans-sialidase family protein expression contributes to loss of Trypanosoma cruzi trypomastigote virulence". Microbes and Infection. 19 (1): 55–61. doi:10.1016/j.micinf.2016.08.003. PMID 27553285.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ↑ Reyes-Espinosa, Francisco, Juárez-Saldivar, Alfredo, Rivera, Gildardo, Herrera-Mayorga, Verónica, Palos, Isidro, García-Pérez, Carlos (Mar 2019). "In Silico Analysis of Homologous Heterodimers of Cruzipain-Chagasin from Structural Models Built by Homology". International Journal of Molecular Sciences. 20 (6): 1320. doi: 10.3390/ijms20061320 . PMC 6470822 . PMID 30875920.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ↑ Duschak VG, Couto AS (2009). "Cruzipain, the major cysteine protease of Trypanosoma cruzi: a sulfated glycoprotein antigen as relevant candidate for vaccine development and drug target. A review". Current Medicinal Chemistry. 16 (24): 3174–202. doi:10.2174/092986709788802971. PMID 19689291.
- 1 2 3 Uehara LA, Moreira OC, Oliveira AC, Azambuja P, Lima AP, Britto C, et al. (December 2012). "Cruzipain promotes Trypanosoma cruzi adhesion to Rhodnius prolixus midgut". PLOS Neglected Tropical Diseases. 6 (12): e1958. doi: 10.1371/journal.pntd.0001958 . PMC 3521651 . PMID 23272264.
- ↑ Vidarsson G, Dekkers G, Rispens T (2014-10-20). "IgG subclasses and allotypes: from structure to effector functions". Frontiers in Immunology. 5: 520. doi: 10.3389/fimmu.2014.00520 . PMC 4202688 . PMID 25368619.
- ↑ Larrieu E, Mujica G, Gauci CG, Vizcaychipi K, Seleiman M, Herrero E, et al. (2017-06-01). "Pilot Field Trial of the EG95 Vaccine Against Ovine Cystic Echinococcosis in Rio Negro, Argentina: Second Study of Impact". PLOS Neglected Tropical Diseases. 9 (10): e0004134. doi: 10.1371/journal.pntd.0004134 . PMC 4627725 . PMID 26517877.
- ↑ María L. Sbaraglini, Carolina L. Bellera, Laura Fraccaroli, Luciana Larocca, Carolina Carrillo, Alan Talevi, Catalina D. Alba Soto (July 2016). "Novel cruzipain inhibitors for the chemotherapy of chronic Chagas disease". International Journal of Antimicrobial Agents. 48 (1): 91–95. doi:10.1016/j.ijantimicag.2016.02.018. PMID 27216381.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
