Chronic Chagas disease results in significant disability with great social and economic impact, including unemployment and decreased earning ability. Since its discovery by Carlos Chagas in 1909, Chagas disease, which is caused by the flagellated protozoan Trypanosoma cruzi and transmitted by hematophagous insect or triatomines, has been a public health problem in rural and urban areas. In Brazil, vector transmission occurs in all states of the northeast region and primarily depends on the presence of vectors in households. The northeastern region of Brazil is considered endemic for Chagas disease and is second among the top regions infested by triatomines.
Global View
Approximately 8 million cases;
14,000 deaths per year;
430,000 disability adjusted life years (DALYs) are lost per year.
Chagas disease is the leading cause of infectious cardiomyopathy worldwide.
Geography
Endemic in 21 Latin American countries;
7.6 million people are infected, 2 million living in Brazil, and 108 million are at risk of the disease;
More than 14,000 deaths are estimated to occur annually from CD worldwide, with around 5,000 deaths in Brazil.
Furthermore, CD causes the highest disease burden of any parasitic disease in the Western Hemisphere, with an infection rate estimated at 1.4% in endemic areas, and with a geographic variation from 0.1% to 45.2%. Migration from Latin America to the United States, Canada, Europe, Japan and Australia has resulted in the global spread of patient populations.
Disease burden
Vector control programs were launched and did contribute to a decrease in the incidence of CD. However, these programs did not benefit the millions of infected people and patients already suffering from Chagas-associated heart and gastrointestinal diseases. As a result of the intense transmission until the middle of 20th century, it is estimated that between 1.2 million and 4.6 million people in Brazil have the chronic form of CD, with about six thousand deaths per year, mainly due to heart failure, which affects about 30% of people who are infected, according to the WHO. (FAPESP, 2019).
The impact on worker productivity, premature disability, and death from CD remains high (430,000 DALYs), and these losses will continue until new effective treatments for CD, with fewer side effects, are developed. According to the Brazilian Society of Tropical Diseases, in the Second Consensus of Chagas Disease in the State of São Paulo from 1985 to 2006, there were 40,002 Chagas-disease-related deaths. Chagas disease was an underlying cause in 34,917 (87.3%) and an associated cause in 5,085 (12.7%). The mortality rate, according to the underlying cause, declined by 56.1%, but remained stable in terms of associated cause of death.
Current treatments
To date, the only two existing drugs, benznidazole and nifurtimox, were developed decades ago, and are known to cause serious toxicity with unsatisfactory cure rates, especially when used in adult chronic CD patients.
These drugs require long administration times and are poorly tolerated, limiting patients’ adherence to treatment as well as their broader use in adult patients with chronic CD. Therefore, there is a consensus among physicians and researchers throughout the world that new treatment alternatives are clearly needed.
The development of new safe, effective and affordable treatments for the millions of individuals suffering from T. cruzi infections, to prevent the complications arising from the chronic stage of the disease, is recognized as a key disease control priority.
Patient treatment needs
A new oral drug, for the treatment of both the acute and chronic stages of the disease, which is safe, efficacious and adapted to the field, according to the disease TPP. In addition, the treatment period should not require more than 30 days of oral drug administration for all age groups.
Literature
- WHO Department of Control of Neglected Tropical Diseases, Sustaining the drive to overcome the global impact of neglected tropical diseases – Second WHO report on neglected tropical diseases; 2013.
- Jackson, Y.; Myers, C.; Diana, A.; Marti, H. P.; Wolff, H.; Chappuis, F.; Loutan, L.; Gervaix, A., Congenital Transmission of Chagas Disease in Latin American Immigrants in Switzerland. Emerging Infectious Diseases 2009, 15 (4), 601-603.
- DNDi, Chagas Disease – Current Treatments. http://www.dndi.org/diseasesprojects/diseases/chagas/current-treatment.html (accessed Marth 7th 2015).
- Diniz, L. D.; Urbina, J. A.; de Andrade, I. M.; Mazzeti, A. L.; Martins, T. A. F.; Caldas, I. S.; Talvani, A.; Ribeiro, I.; Bahia, M. T., Benznidazole and Posaconazole in Experimental Chagas Disease: Positive Interaction in Concomitant and Sequential Treatments. Plos Neglected Tropical Diseases 2013, 7 (8), e2367.
- FIDALGO, Arduina Sofia Ortet de Barros Vasconcelos et al . Insect vectors of Chagas disease (Trypanosoma cruzi) in Northeastern Brazil. Rev. Soc. Bras. Med. Trop., Uberaba , v. 51, n. 2, p. 174-182, Apr. 2018. Access on 22 July 2020. https://doi.org/10.1590/0037-8682-0408-2017.
Leishmaniases are diseases with significant clinical and epidemiological diversity, which involves many different species of Leishmania parasites, phlebotomine sandfly vectors, and reservoir hosts in both zoonotic and anthroponotic cycles of transmission. The disease is related to poverty and affects the poorest of the poor. There is a remarkable increase in risk factors for leishmaniases worldwide and the disease burden is increasing. Visceral leishmaniasis (VL) is the most devastating form of leishmaniases because it is usually fatal if untreated.
Global view
The morbidity and mortality caused by leishmaniasis, among all parasitic diseases, is largely invisible. However, its impact is only surpassed by malaria and lymphatic filariases. Currently, approximately 50,000 – 90,000 new cases of VL are reported each year, with an estimated 350 million people at risk of the disease, most of them children. Visceral leishmaniasis (VL) causes 30,000 deaths annually and 1,974,000 DALYs globally.
Geography
Leishmaniasis is endemic to 90 countries on five continents. In fact, only seven countries, including Brazil, represent 90% of all new VL cases. In Latin America, and particularly in Brazil, the disease has spread from rural areas throughout the national territory over the past 30 years, causing large epidemics of zoonotic visceral leishmaniasis in the fast-growing peripheries of many large and medium-sized cities.
Disease burden
According to PAHO´s last epidemiological report on leishmaniasis in the Americas, 38,808 cases of VL were recorded in more than ten countries during the period 2001 to 2011, with 96.6% of the cases reported in Brazil alone. In Brazil, 3,894 new VL cases, with a mortality rate of 6.7%, were reported in 2011.
Current treatments
Current treatments are predominantly from the development of new drugs, including paromomycin, miltefosine and lipid formulations of amphotericin B (pentamidine, ketoconazole, and AmBisome). Antimonial drugs, including sodium stibogluconate and meglumine antimoniate, require up to 28 days of parenteral administration, have variable efficacy, and treatment failure has been demonstrated. Amphotericin B is effective against antimonial-resistant VL; however, slow parenteral infusion (4 h) is required due to toxicity. While its efficacious lipid formulations have reduced toxicity and increased plasma half-life, they remain prohibitively expensive. Currently, miltefosine is the only oral treatment for leishmaniasis; however, its use is limited by its gastrointestinal side effects, teratogenicity and cost.
Patient treatment needs
The available treatments have serious drawbacks in terms of toxicity, potential of resistance development, stability and cost. Current treatments are difficult to administer, require long treatment durations, and have low tolerability. New oral treatments with fewer side effects and greater efficacy against all geographical variations and local realities are essential. The ideal treatment for VL, as defined by its TPP, would be safe, efficacious against all species of parasite in all regions, and administered orally, and would have a short course of treatment (10 days maximum) and be also efficacious against PKDL (a disseminated skin infection that is a common sequel of VL).
Literature
- WHO Department of Control of Neglected Tropical Diseases, Sustaining the drive to overcome the global impact of neglected tropical diseases - Second WHO report on neglected tropical diseases; 2013.
- Monge-Maillo, B.; Lopez-Velez, R., Therapeutic Options for Visceral Leishmaniasis. Drugs 2013, 73 (17), 1863-1888.
- DNDi, New VL treatments - Latin America http://www.dndi.org/diseases-projects/portfolio/new-vltreatments-latin-america.html (accessed March 7th, 2014).
- Dorlo, T. P. C.; Balasegaram, M.; Beijnen, J. H.; de Vries, P. J., Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. Journal of Antimicrobial Chemotherapy 2012, 67 (11), 2576-2597.
- DANTAS-TORRES, Filipe; BRANDAO-FILHO, Sinval Pinto. Visceral leishmaniasis in Brazil: revisiting paradigms of epidemiology and control. Rev. Inst. Med. trop. S. Paulo, São Paulo , v. 48, n. 3, p. 151-156, June 2006 . Access on 22 July 2020. https://doi.org/10.1590/S0036-46652006000300007.
Malaria is caused by Plasmodium parasites. The parasites are spread to people through the bites of infected female Anopheles mosquitoes, called "malaria vectors." There are 5 parasite species that cause malaria in humans, and 2 of these species – P. falciparum and P. vivax – pose the greatest threat.
Global view
Globally, 53% of the P. vivax burden is in the WHO South-East Asia Region, with the majority being in India (47%). P. vivax is the predominant parasite in the WHO Region of the Americas, representing 75% of malaria cases. In 2018, there were an estimated 405,000 deaths from malaria globally, compared with 416,000 estimated deaths in 2017 and 585,000 in 2010. Overall, about 24 million children were estimated to be infected with P. falciparum in 2018 in sub-Saharan Africa, and an estimated 1.8 million of them were likely to have severe anaemia.
Geography
An estimated 228 million cases of malaria occurred worldwide in 2018 (95% confidence interval [CI]: 206–258 million) compared with 251 million cases in 2010 (95% CI: 231–278 million) and 231 million cases in 2017 (95% CI: 211–259 million). P. vivax is the predominant parasite in the WHO Region of the Americas (75%) and is responsible for 50% of cases in the WHO South-East Asia Region and 29% in the WHO Eastern Mediterranean Region.
Disease burden
There were about 155 million malaria cases in the 11 high burden to high impact (HBHI) countries in 2018, compared with 177 million in 2010. The Democratic Republic of the Congo and Nigeria accounted for 84 million (54%) of total cases. Of the ten highest burden countries in Africa, Ghana and Nigeria reported the highest absolute increases in cases of malaria in 2018 compared with 2017. The burden in 2018 was similar to that of 2017 in all other countries, apart from in Uganda and India, where there were reported decreases of 1.5 and 2.6 million malaria cases, respectively, in 2018 compared with 2017.
Current treatments
The control and eradication of malaria demands a multifaceted approach. At present we have a range of good tools, including insecticide spraying and long-lasting, insecticide-treated bed nets help to prevent the transmission of the infection via the mosquito vector. But no preventative strategy is 100% effective – there will always be cases that slip through the net. The current WHO-recommended first-line treatment for the majority of malaria cases is artemisinin-based combination therapy (ACT). These medicines, in addition to diagnostics, are available to treat and in some cases prevent malaria. Treatment of malaria depends on the malaria species, as well as on the severity of the disease. The World Health Organization's guidelines for the treatment of malaria provides recommendations on topics such as:
- Treatment of uncomplicated p. falciparum malaria
- Treatment of uncomplicated malaria caused by p. vivax
- Treatment of severe malaria
- Mass drug administration
- .... and more
Patient treatment needs
MMV’s portfolio focuses on delivering efficacious medicines that are affordable, accessible and appropriate for use in malaria-endemic areas. Specifically, the goal is to develop products that will provide: efficacy against drug-resistant strains of Plasmodium falciparum, potential for intermittent treatments (infants and pregnancy), safety in small children (less than 6 months old), safety in pregnancy, efficacy against Plasmodium vivax (including radical cure), efficacy against severe malaria and transmission-blocking treatment.
Literature
- WHO Malaria https://www.who.int/malaria/en/ (accessed June 15, 2020)
- WHO World Malaria Report 2019 https://www.who.int/publications/i/item/world-malaria-report-2019 (accessed June 15, 2020)
- MMV, Developing effective antimalarials to save lives, https://www.mmv.org/malaria-medicines/malaria-treatment (accessed June, 2020)
