Communicable diseases
Liam J. Donaldson, Paul D. Rutter in Donaldsons' Essential Public Health, 2017
Chagas disease is caused by a protozoan parasite, Trypanosoma cruzi. It largely occurs in Latin America, where around 7 million people are affected. It is starting to appear in some other countries. Its main route of infection is via the faeces of triatomine bugs, but it can result from blood transfusion or transplantation of organs. In the early stages of infection, symptoms are mild and nonspecific, although in a proportion of people there is a characteristic unilateral purple swelling of the eyelid. If the infection is not treated, it progresses so that parasites enter the heart, bowel or nervous system. It can then become life threatening. In the early stage of infection, antimicrobial drugs are highly effective but therapeutic benefit wanes the longer the person has the disease. Insecticide spraying in and around homes (the vector bug lives in the cracks and crevices within houses) can be very effective in destroying this vector.
Chemical Hybridization Approaches Applied to Natural and Synthetic Compounds for the Discovery of Drugs Active Against Neglected Tropical Diseases
Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay in Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Chagas disease is a zoonotic disease caused by the protozoan parasite Trypanosoma cruzi that can be transmitted to humans by blood-sucking triatomine bugs (also known as the “kissing” bug) belonging to the genera Triatoma, Rhodnius, and Panstrongylus (Centers for Disease Control and Prevention 2018a). The parasite life cycle is divided in human (host) stages and triatomine bug stages. Chagas disease is currently treated with nifurtimox 1 and benznidazole 2 (Figure 1). Structure of active ingredients (nifurtimox and benznidazole) of drugs for Chagas disease.
Evidence for a Role of Infections in the Activation of Autoreactive T Cells and the Pathogenesis of Autoimmunity
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
The A/J strain of mouse is susceptible to T. cruzi infection-induced myocarditis, and interestingly to both the CVB3 and MCMV-induced models of myocarditis. In addition, the C57B1/6 strain is resistant to all three pathogen-induced heart diseases. This suggests a common mechanism may be involved in all three models. Two main hypotheses have been used to explain the pathology observed in Chagas disease. The parasite persistence model suggests that disease severity, progression and perpetuation directly correlates to the presence of parasite DNA in muscle tissue.109 The immunosuppression of mice infected with T. cruzi leads to exacerbation of disease severity and infection,110,111 whereas alternatively, enhancing the anti-parasite response leads to a decreased severity of disease.112 This evidence supports the parasite presence hypothesis.
Promiscuity in drug discovery on the verge of the structural revolution: recent advances and future chances
Published in Expert Opinion on Drug Discovery, 2023
Sarah Naomi Bolz, Michael Schroeder
Chagas disease is a potentially life-threatening infection caused by the protozoan parasite Trypanosoma cruzi that affects about 6–7 million people globally. It is recognized as a neglected tropical disease that primarily affects poor and marginalized populations in Latin America, leading to serious health consequences and socioeconomic burdens [96,97]. There are currently limited treatment options for Chagas disease, which have severe side effects and are only partially effective [98]. To identify novel medications, Adasme et al. performed a structure-based drug repositioning screening using interaction fingerprints [99]. They extracted the non-covalent protein–ligand interaction patterns from the available complex structures of 16 Chagas targets and screened the PDB to identify complexes with a similar binding mode. The screening yielded 38 top-hit compounds that showed high chemical diversity. Three of these repositioning candidates – ciprofloxacin, naproxen, and folic acid – displayed activity against the parasite when tested in vivo [99].
The senseless orphanage of Chagas disease
Published in Expert Opinion on Orphan Drugs, 2019
Cristina Alonso-Vega, Irene Losada-Galván, María-Jesus Pinazo, Javier Sancho Mas, Joaquim Gascón Brustenga, Julio Alonso-Padilla
Chagas disease or American trypanosomiasis is a systemic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi). The infection is transmitted in the feces of infected hematophagous vectors such as Triatoma infestans, that, upon a bloodmeal, defecate near the bite site or near mucosal tissue [1]. Parasites in the feces will then gain access to the bloodstream through micro-injuries caused by scratching the bite site or through the mucosa [2]. Oral transmission due to the ingestion of parasite-contaminated food or drink has been documented as well [3,4]. Vector-independent transmission routes such as blood transfusion, organ transplant, and congenital have been described too [1]. Another possible route of infection can occur in case of a biohazard incident in the laboratory upon manipulating parasite containing samples [5].
Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections
Published in Expert Opinion on Therapeutic Targets, 2022
Christopher Schwake, Michael Hyon, Athar H. Chishti
Trypanosoma cruzi is the etiologic agent of Chagas’ disease and Trypanosoma brucei rhodesiense and gambiense are the etiologic agents of African sleeping sickness (Human African Trypanosomiasis, HAT). Both diseases present high mortality throughout their geographic regions. Chagas’ disease is transmitted by a triatomine vector, known by those in endemic regions as the kissing bug. Worldwide, Chagas’ affects 6 million people mainly in Latin-American countries as well as 300,000 people living in the US [44]. Triatomine bugs have established populations in the Southern United States, some of which are infected with T. cruzi [45]. The extent to which endemic transmission occurs in the US is unknown due to the low incidence of testing and diagnostic assays, but there has been reports of locally acquired Chagas’ disease in the past [46,47]. Disease can progress to a chronic infection resulting in serious heart inflammation and intestinal problems in those afflicted [48]. Chagas’ disease has very few treatment options with only two currently available drugs, benznidazole and nifurtimox. However, both compounds exhibit low efficacy toward the chronic form of the disease and deleterious side effects over a long treatment period can lead to noncompliance [48].
Related Knowledge Centers
- Lymph Node
- Megaesophagus
- Parasitic Disease
- Trypanosoma Cruzi
- Cardiovascular Disease
- Tropical Disease
- Triatominae
- Arthropod Bites & Stings
- Chronic Condition
- Heart Failure