Difference between revisions of "Team:Oxford/Chagas Disease"

Introduction

Chagas disease is a neglected tropical disease named after a 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, 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 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 form of the transmission among the human population, with prevalence in some rural areas of Bolivia being as high as 70.5%.

Parasitology

T.cruzi follows the life-cycle shown in the diagram above:

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 2.

Figure 2. Scheme of evolution of T.cruzi trypomastigotes in the blood of a human host

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 current cost-effective diagnostic 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.

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, prolong onset of the chronic phase leads to 30% of patients develop cardiac disorders and up to 10% develop digestive, neurological or mixed alterations that cause 1200 deaths per year. The main diagnostic methods currently used to diagnose Chagas are summarised in the table below: