35 No. 3
Neglected tropical diseases (NTD) affect millions of people, especially in Latin America, but the efforts of researchers around the world to find good, effective treatments have proved insufficient. The IUPAC project “A Survey of Research into New Drugs for Neglected Tropical Diseases in Latin America” (project 2009-033-1-700) aims to coordinate the efforts and interests of researchers in the Latin American region, and to connect them with research groups throughout the world, in an attempt to form a critical mass for finding new treatments for NTD.
Among the United Nation’s Millennium Goals, proposed by consensus in 2000 with the goal of completion by 2015,1 is “eradicating or reducing malaria and other endemic diseases such as Chagas, tuberculosis, …” However, research efforts so far have been inadequate for a variety of reasons, including low interest in developed countries, since the NTD don’t affect their populations, and a lack of funding from companies because of the difficulty in recovering investments from new drug discovery.2
In response to these challenges, a number of different initiatives are underway3 and the number of researchers throughout the world dedicated to studying these diseases has increased in recent years. This is evident in the growing number of papers on NTDs that appear in scientific journals.
NTDs are not just limited to isolated areas as they were in the past. Population movements in the last century have resulted in the introduction of tropical diseases into more populated areas. It is now not unusual to find malaria, for example, in countries where it had never appeared before.
The search for drugs for the treatment of NTD is special because it is developed countries that have the technology and yet it is the less developed countries where the diseases are found. This means that the pre-clinical aspect of research and development for new drugs can be carried out in any country, while the clinical part can only take place in the countries suffering these diseases. Simple consideration of this reality implies the need for collaboration in order to be effective.
The terms “developed” and “developing” are misleading because they only consider mean numbers in the classification of countries. Yet, in many of these countries one can find citizens with great purchasing power. A major characteristic of the developed countries, however, is the presence of a well-developed middle class, which is something that does not occur in the developing countries. It is in this context that we can place the search for new drugs for the treatment of NTD in Latin America.
Latin America has approximately 561 million inhabitants.4 The projected population for this area in the year 2050 is over 800 million.5 Comprising the Southern and Central American continent, the region possesses important, traditional knowledge about the use of natural products from terrestrial plants for the treatment of various diseases. Yet, there has been little development of compounds of synthetic origin based on natural products from Latin America.
Much has been written about NTDs and a great deal of research is being carried out in this area. It is important to note that when viewed from a distance, one only gets a partial view of the problem.
With generosity, and a certain degree of frequency, the advanced industrialized nations do try to help resolve the problems of less-developed countries. This is good, and the greater the aid, the better. However, a more valid approach for the 21st century is for countries that have these problems to also participate in their solution.
These less-developed countries are destined to always be dependent on others if they are not involved in the research and innovation. It should not be a matter of providing people with fish, but rather teaching them how to fish. There is an important critical mass of well-trained scientists in many universities and centers in Latin America. However, they are sometimes unable to develop their ideas because they lack equipment and funds.
|Participating groups in the R&D network of novel drugs for Neglected Tropical Diseases (IUPAC: 2011–2012).
View full table of participating groups.
From the point of view of northern countries, these issues of the developing countries are often related to poverty. But this is only partly true. Poverty should not be viewed simply in terms of Gross National Product or economics. When considering NTDs, sociopolitical aspects are equally important. Other factors are more subtle, but just as decisive, such as race, gender, and children.
Race is important. Latin America is a melting pot of societies descended from ancient, indigenous civilizations, Europeans, and Africans, with each group of people having its own sociological and cultural behaviors, all of which should be taken into consideration.
Another important question is the role of the women and children in Latin American society, especially in rural areas. In these areas, farming and cattle raising are largely carried out by women and children, in an intense relationship with the environment. In this context, for example, Chagas disease is most important because it leads to labor absenteeism and lower productivity. A clear example of a relationship between disease and poverty.
In 2002, Novartis established a National Institute for Tropical Diseases in Singapore to search for new compounds for the treatment of tuberculosis, dengue, and malaria. When Dr. P. Herrling was asked why, he said “… if you want to make medicines for patients, you need to know their environment.”6 Astra Zeneca offers a similar rationale for its research site in Bangalore, India, that focuses on tuberculosis: “We’ve got about a quarter of the world’s population of TB patients in India …”. In addition, the company stated that “the universities are globally competitive, the cost of research is cheaper and, perhaps most importantly, there is access to clinical material. But it is not just because it is cheaper; building a culture of drug-discovery takes time.”
The same type of research arrangement that these companies have in India, could also be applied to Latin America. The region has a valid infrastructure for carrying out fundamental research, which is what ultimately leads to the discovery of new effective drugs and their potential introduction into the pharmaceutical market.
Another very important aspect is the region’s extensive knowledge of therapeutic properties of natural products obtained from regional plants. Latin America has some of the greatest biodiversity of anywhere in the world. The discovery of new drugs, based on traditional knowledge of plants in Latin America, raises issues of property rights that need to be resolved for the benefit of all parties involved, but especially to help these less-developed societies.
Using indices such as publications and patents, it is clear that countries in Latin America are not as advanced as countries of the North, but nevertheless, they do have much scientific activity and considerable research potential.
In the present context, the term collaboration between societies is something in which each party can contribute work of great interest in searching for new drugs. This involves forming networks in which each country contributes that which it is able to give, with the total sum benefiting everyone.
|Rhodnius prolixus is the principal vector for Chagas disease in Colombia, Venezuela, Guatemala, Honduras, and some parts of Nicaragua and El Salvador.
This issue has been perfectly understood by society, and a good part of the funds made available for this matter has a social origin. There are examples of purely philanthropic organizations such as the Bill & Melinda Gates Foundation7 or Wellcome Trust8 or other organizations of interest, either private or public, such as the Drugs for Neglected Diseases Initiative9 or Medicines for Malaria Venture,10 and even international organizations, such as UNESCO.11 Pharmaceutical companies, including Novartis, GlaxoSmithKline, Astra-Zeneca, and Merck, among others, are also collaborating in the study of NTDs.
What piece is missing from the puzzle? Naturally, increased social involvement and more participation on the part of companies and businesses would be good as there can never be enough. In addition, increased participation from supranational governments would also be most welcomed. But a new and determined participant needs to appear on the scene, namely the governments of the countries that are most directly suffering from these diseases. Financial aid for treating Chagas cannot be demanded by the countries suffering this disease if these same countries do not invest their own money, to the degree to which they are able, to solve their own problems.
Sometimes, it appears that these governments are content to rely on someone else to solve the problems at hand. When studying the funds allotted for R&D of these diseases in the countries that suffer from them, the impression one gets is not always favorable. In the hope of developing internationalized solutions, the involvement of the Latin American governments is an original approach that we propose in this study.
In this work, we are referring to diseases which, according to The World Health Organization, affect one-sixth of the world’s population, approximately 1 billion people, and to which worldwide dedicated efforts are less than they should be. According to the 2009 World Health Organization publication Neglected Tropical Diseases: Hidden Successes, Emerging Opportunities:
“NTD tend to be hidden below the radar screens of health services and politicians because they afflict populations that are marginalized, with little political voice. Although frequently causing severe pain and life-long disabilities, these diseases are generally not major killers. Under resource-limited conditions, high mortality diseases such as HIV/AIDS or tuberculosis are prioritized to the detriment of neglected tropical diseases. Less than 1 percent of the 1393 new drugs registered during 1975–1999 were for tropical diseases. Less than 0.001 percent of the USD 60–70 billion spent on new drugs went towards developing new and urgently needed treatments for tropical diseases.”
There are 149 countries and territories affected by at least one NTD. More than 70 percent of them are affected by two or more diseases; 28 countries are afflicted by more than six. Most of them are low-income economies experiencing humanitarian emergencies. NTDs thrive under conditions of poverty, poor sanitation, unsafe water, and malnutrition. However, a growing body of evidence clearly demonstrates that, even under these conditions, significant and sustainable gains can be made against NTDs in immediate and visible ways. The control of these diseases brings a number of collateral benefits in terms of improved health status of populations, increased worker productivity, and long-term increases in the domestic pool of resources, thus contributing to educational improvement and economic growth.”
Among the NTDs, the 13 most-widespread diseases are ascariasis, ankylostomiasis and trichuriasis, caused by helminths from the ground, lymphatic filariasis, onchocerciasis, dracunculosis, schistosomiasis, Chagas, human African trypanosomiasis, leishmaniasis, Buruli ulcer, lepra, and trachoma. This initial list can be expanded to include dengue, dengue hemorrhagic fever, trepanomatosis, leptospirosis, strongyloidiasis, neurocysticercosis, scabies, and trematodes transmitted by food.
One aim of the project is to find research groups in Latin America that are interested in the discovery of new products for the treatment of NTDs. It is our hope to form a group with enough critical mass to do an effective job discovering new drugs.
In addition, we propose to make the philanthropic societies, pharmaceutical companies, and governments aware of these scientific groups to facilitate ties and establish relationships that could result in improved efficacy. One incentive behind this proposal is that the papers of Latin American research groups are not always published in higher-profile journals. Although their work is of high quality and based on good projects, they lack sufficient means for carrying out state-of-the art research. Yet, in many other cases, Latin American research centers are just as advanced as in any other country.
One advantage for Latin American researchers is that they have these diseases within their borders and therefore know them first hand, especially with regard to the clinical setting. In addition, they have knowledge of their local factors such as climate and race. It is equally important that these countries keep in close contact with the technological developments, considered to be vital for this topic.
So far, approximately 30 universities and research centers from 10 Latin American countries have signed onto this project (see map below and table at www.iupac.org/publications/ci/2013/3503/1_table.html). The diseases represented by the different participating groups include Chagas, leishmaniasis, malaria, sickle cell disease, dengue, junin virus, plasmodium, trichomonas, amoebiasis, giardiasis, Acinetobacter baumannii, giardiasis, cysticercosis, African trypanosomiasis, and paracoccidiodomicosis.
Of the large variety of diseases represented in this project, there are research groups that concentrate on just a limited number of them. Joining this program is voluntary and does not imply that there are not other groups also working on NTDs.
The collection of data for this project was carried out based on documents developed by the Ciencia y Tecnología para el Desarrollo/Ibero-American Program of Science and Technology for Development, which was initially promoted by the Spanish government and in which all of the Latin American countries participate. Inevitably, there are gaps that can be covered in future successive approaches of this IUPAC study.
It is important that IUPAC initiate the diffusion of this project, which we anticipate will grow with new participants in successive reviews.
- Mary Moran et al.; “Neglected Diseases Research and Development: How Much are We Really Spending.” PLoS Medicine. www.plosmedicine.org. February 2009, vol. 6 (2), 1–10. http://dx.doi.org/10.1371/journal.pmed.1000030
- “Innovative Lead Discovery Strategies for Tropical Diseases.” J. Nwaka and A. Hudson. Nature Reviews/Drug Discovery, vol. 5, 941–955 (2006)
- Sarah Houlton; "Drugs for a Developing World." Chemistry World; September 2009. 48.51
- www.who.int/iris/handle/10665/44214 WHO Library Cataloguing-in-Publication Data. Neglected Tropical Diseases, Hidden Successes, Emerging Opportunities. WHO/HTM/NTD/2009.2
- A.B.Llanes; "Las Enfermedades Olvidadas en la Lucha contra la Pobreza." Eidon; 34 (Oct 2010), 46–52
last modified 13 May 2013.
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