A F Francisco1; S Jayawardhana1; M C Taylor1; M Lewis1; J M Kelly1;
1 Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT., UK
DiscussionThe insect-transmitted protozoan parasite Trypanosoma
cruzi is the
causative agent of Chagas disease (CD), and infects 5-8 million people in Latin
America. CD is characterised by an acute phase, which is partially resolved by
the immune system, but then develops as a chronic infection. Approximately 30%
of those infected with T. cruzi develop
chronic stage pathology, but this can take decades to become symptomatic.
Because of this, and with difficulties in demonstrating parasitological cure,
it has been difficult to assess the extent to which anti-parasitic therapy can
prevent the development of pathology. We sought to address this question using highly
sensitive bioluminescent imaging methodology and murine models BALB/c and
C3H/HeN infected with CL Brener and JR strain, respectively. We monitored heart
inflammation and fibrosis, two widely markers of cardiac pathology. This in vivo imaging procedure has a limit of
detection of 100-1000 parasites, and facilitates the real-time tracking of
parasite burden in individual mice during chronic infections. These experiments
demonstrated that curative benznidazole treatment early in murine T. cruzi infections prevents the
development of cardiac fibrosis. Treatment during the chronic stage can also
block pathology, but the effectiveness of this varies between infection models.
If these findings are extendable to humans, it will imply that widespread
chemotherapeutic intervention targeted at early stage infections could play a
crucial role in reducing CD morbidity at a population level.