Chagas Disease (NTD)

Health Burden

Chagas disease is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi, and was discovered in 1909.

Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). It is found mainly in Latin America, where it is mostly transmitted to humans by the faeces of triatomine bugs, also known as ‘kissing bugs’. An estimated 10 million people are infected worldwide, mostly in Latin America where Chagas disease is endemic. More than 25 million people are at risk of the disease. It is estimated that in 2008, Chagas disease killed more than 10 000 people worldwide (Rassi, Jr. et al., 2010;WHO, 2012). Also in Europe and USA the numbers of infected people are growing due to migration.

Endemic Chagas disease in Latin America began as a neglected disease of poor, rural and forgotten human populations, but the wild triatomines progressively adapted to the domestic environment and millions of people have been infected, developed the disease and even died without the possibility of even getting a diagnosis, let alone medical assistance. Nowadays, significant foci of domestic infestation are found especially in areas of Bolivia, which has the highest prevalence rate of human infection, and in 17 other Latin American countries that have not controlled vector transmission. Progressive urbanization of the rural population in Latin America, mainly since the 1940s, has made Chagas disease an important urban medical and social problem. This has introduced new risks, such as the possibility of T. cruzi transmission through blood transfusion (Coura and Vinas, 2010).

Non-endemic countries having significant population exchange with Latin America, mainly in the form of migration, have seen a rise in the number of Chagas cases in recent years. In fact, the T. cruzi parasite is travelling with population movements from endemic to non-endemic countries such as North America (United States and Canada), the western Pacific region (particularly Japan and Australia) and, more recently in Europe (mainly Belgium, Spain, France, Italy, the United Kingdom and Switzerland). It has been estimated that there are now >300,000 individuals infected with T. cruzi in the United States, >5,500 in Canada, >80,000 in Europe and in the western Pacific region, >3,000 in Japan and >1,500 in Australia.

The extent of the health problems posed by Chagas in Latin America and the US has been emphasized by a recent editorial, in which the current outbreak of Chagas disease was compared to the early years of the HIV/AIDS pandemic.

Disease

Chagas disease presents itself in two phases. The initial acute phase lasts for about two months after the initial infection of the host. During this acute phase, a high number of parasites circulate in the blood. However in most cases, symptoms are mild and can include fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling and abdominal or chest pain. In less than 50% of people bitten by a triatomine bug, characteristic first visible signs can be a skin lesion or a purplish swelling of the lids of one eye.

Following the end of the acute phase and during the chronic phase of the infection, the parasites hide mainly in the heart and digestive muscle of the host. Over time, about 30% of patients gradually start suffering from cardiac disorders and up to 10% will suffer from digestive (typically enlargement of the oesophagus or colon), neurological or mixed alterations. Later in life, up to 20 years following the initial infection, the presence of the parasites can lead to sudden death or heart failure caused by progressive destruction of the heart muscle.

Treatment

There are currently only two drugs of proven efficacy against Chagas disease. Both drugs can be taken orally. There exists a strong resistance against these current treatments and strong adverse affects are observed. Treatment efficacy in longer term chronic infections and in recurrent infections is highly controversial. This leads many doctors to view the risk-benefit ratio of such treatments as unfavorable. Despite important advances in preclinical studies, no new drugs against Chagas disease have entered clinical trials in more than a decade.

D121

Oleylphosphocholine belongs to the chemical family of alkylphosphocholines, which represent a class of biologically active compounds originally derived from alkyl-glycerophosphocholines and analogues (alkyllysolecithins). Oleylphosphocholine has a broad therapeutic window, which would allow short and effective dosing regimens associated with low side effects, hereby meeting existing medical needs for Chagas disease. Oleylphosphocholine has excellent in vitro activity against Trypanosoma cruzi. In vivo studies with oleylphosphocholine in a mouse model of Chagas disease are underway.