Chagas disease is a neglected tropical disease named after the Brazilian scientist, Carlos Chagas, who first described the life cycle of the parasite – Trypanosoma cruzi (T. cruzi) that causes the disease. Chagas is primarily transmitted via the faeces of triatomine bugs (also known as 'kissing bugs') when they take a blood meal. Other forms of transmission include: blood transfusions, orally via ingestion of contaminated fluids, vertical transmission. Chagas is endemic to Latin America but increased migration of infected people has led to it spreading to non-endemic countries, consequently increasing the number of people susceptible to the disease and causing it to be a growing global concern.
Since the 1990s, strategies to reduce the impact of Chagas in endemic countries have largely focused on preventing transmission through vector control programmes and screening blood banks. Although these achievements have significantly reduced its incidence, they are not sufficient to combat the spread of the disease vertically from a mother to her child. Therefore, congenital Chagas disease is growing in epidemiological importance, as it is now one of the most persistent forms of the transmission among the human population, with prevalence in some rural areas of Bolivia being as high as 70.5%.
All life stages of T.cruzi secrete a specific protease, known as cruzipain, which allow the presence of the trypomastigotes to be detected by our biosensor. However, the levels of trypomastigotes in the human blood falls with time after infection, as shown in Figure 1.
Figure 1: Lifecycle of T. cruzi
Acute and chronic phases
Within 4-8 weeks of being bitten, adults move from the acute phase of Chagas disease to the chronic phase if untreated.
During the chronic phase, cruzipain levels are very low in the blood and cost effective diagnosis of adults focuses on detecting antibodies specific to T. cruzi. However, antibody based diagnosis is unsuitable for newborns who lack a fully developed immune system. Newborns infected with congenital Chagas disease remain in the acute phase for up to 9 months, during which period there is no cost-effective diagnostic currently available. We hope to fill this gap in the ability to diagnose congenital Chagas disease in newborns, using synthetic biology to create a specific protease detection system.
Figure 2: Scheme of evolution of T. cruzi trypomastigotes in the blood of a human host
Symptoms and current diagnosis
Diagnosis of Chagas disease is difficult, as the disease is mostly asymptomatic in the acute phase and for the majority of the chronic phase. However, prolonged onset of the chronic phase leads to 30% of patients developing cardiac disorders and up to 10% developing digestive, neurological or mixed alterations that cause 12,000 deaths per year. The main diagnostic methods currently used to diagnose Chagas are summarised in the table below:
Table 1: Main diagnostic methods currently used to diagnose Chagas disease
|Test||How it works||Benefits||Limitations||Suitable for newborns|
|Whole parasite microscopy||
|Polymerase Chain Reaction (PCR)||
The table highlights the lack of a rapid and feasible diagnostic for congenital Chagas disease. Moreover, in June 2016 the WHO and experts on Chagas disease based in Latin America regarded a point-of-care diagnostic for congenital Chagas as their top priority in terms of the diagnostic needs for Chagas disease. The diagnostic needs were ranked following considerations of existing diagnostic tools and the expected clinical and epidemiological scenario of Chagas disease in the next five years. Strategies to tackle Chagas disease in an optimal fashion using our diagnostic device in the current Latin American society in Bolivia is outlined in our public policy proposal that can be found below:
An 8 week course of benznidazole or nifurtimox can be used to kill the parasite and treat Chagas disease. The younger the patient and the closer to acquisition of the infection, the higher the probability of parasitologic cure. Therefore, newborns with congenital Chagas disease have the greatest chance for cure, with data from Argentina indicating that the cure rate is higher than 90% if treatment is given within the first year of life. In most cases the potential benefits of medication in curing, preventing or delaying Chagas is balanced against the possible adverse reactions that occur in up to 40% of treated patients. However, newborns are least affected by side effects of benznidazole or nifurtimox, due to the lower weight-accounted dosage, making treatment a very viable option. If the chronic phase is left untreated, additional specific treatment for cardiac or digestive manifestations may be required.
Ana María Cevallos and Roberto Hernández, 2014. “Chagas’ Disease: Pregnancy and
Congenital Transmission,” BioMed Research International, vol. 2014, Article ID 401864, 10
Marin-Neto, J. A., Cunha-Neto, E., Maciel, B. C., & Simões, M. V. 2007 Pathogenesis of
chronic Chagas heart disease. Circulation, 115(9), 1109-1123.