Neglected Tropical Diseases
Neglected Tropical Diseases (NTDs), caused by infections by parasites (protists and worms), bacteria and viruses form still, in 2013, a tremendous health problem in most tropical and subtropical areas of the world, affecting, according to most recent estimates by WHO, approximately 2.7 billion people and killing over 500,000 humans worldwide each year. For many of these diseases no adequate treatment is available, while resistance is in several cases eroding the usefulness the few good therapeutics available. New efficacious, affordable drugs are badly needed, but efforts by the pharmaceutical industry have been limited because the low prospects for financial returns for its investments, explaining why these diseases are ‘neglected’.
Malaria
Malaria is spread over 90 countries worldwide and is responsible for approximately 300 million acute cases each year, with 1.5 to 2.0 million fatalities. Nearly 90% of the deaths occur in sub-Saharan African regions. The protozoan Plasmodium falciparum is the etiological agent of the most severe and life-threatening form of disease.
The emergence of resistance to the current most affordable drugs, such as chloroquine, mefloquine and sulfadoxine-pyrimethamine, represents a major problem for malaria control. Accordingly, many countries must consider alternative approaches to slow the development of resistance, for instance, artemisinins analogues or drug combinations (e.g., atovaquone-proguanil, amodiaquine-artesunate).
Chagas disease
Chagas disease, or American trypanosomiasis, is a major cause of morbidity and death throughout 21 countries in Latin America. The Trypanosoma cruzi, the causative agent of Chagas disease, is the largest parasitic killer in the Americas where there are, approximately, 8 million cases, with 14,000 deaths each year. In addition, nearly, 30% of the infected people develop serious cardiovascular, gastrointestinal, or neurological disease. In the absence of diagnosis or treatment in the early stage of the disease, one out of four patients develops the fatal symptoms.
Although more than 100 years had passed since the discovery and description of the disease, currently, there are only two drugs available to treat Chagas disease, benznidazole and nifurtimox. Both compounds were developed over 35 years ago in campaigns that were not aimed at discovering new drugs for the disease. Furthermore, the drugs exhibit poor efficacy and severe side-effects. Therefore, new efficacious and affordable drugs are urgently needed to treat this illness.
Schistosomiasis
Schistosomiasis, a major cause of illness, long-term disability and death, is caused by several species of trematode parasite of the genus Schistosoma. The disease is endemic in tropical regions, affecting more than 200 million people spread over about 80 developing countries. Approximately 20 million infected people exhibit severe disease manifestations, including chronic hepatic, intestinal fibrosis and calcification of the urinary tract.
Praziquantel is the only effective drug available for the treatment of schistosomiasis. Although the treatment is considerably affordable, less than 20% of those in need currently receive the drug. Additionally, praziquantel has been in use for more than 20 years and significant resistance to the chemotherapy has emerged. Therefore, this scenario highlights the urgent need for the development of new drugs for the chemotherapy of schistosomiasis.
Tuberculosis
Tuberculosis (TB) is an important disease due to infection by Mycobacterium tuberculosis (Mtb) which primarily affects the respiratory tract. According to the World Health Organization (WHO), there are nearly ten million new cases of TB and 1.8 million deaths each year. The situation is further worsened by the co–infection with HIV, due to the devastating effects of Mtb on the the vulnerable immune system of the patients.
Despite of the BCG vaccine (Bacillus Calmette-Guerin) and the combined chemotherapy with antibiotics (isoniazid, ethambutol, rifampicin, pyrazinamide), Mtb is the agent which causes more deaths from infection in the world. The chemotherapy involves the use of these four antibiotics for 6 to 9 months, resulting in significant lack of patient adherence to long term therapy . The global emergence of multidrug-resistant (MDR) strains of Mtb is also a serious health problem.2 For these reasons, there is an urgent need for new safe and effective anti-TB drugs.
