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Bridging the Innovation Gap for Neglected Tropical Diseases in Mexico

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Bridging the Innovation Gap for Neglected Tropical Diseases in Mexico Bol Med Hosp Infant Mex 2011;68(2):138-146 article Bridging the innovation gap for neglected tropical diseases in Mexico: capacity building for the development of a new generation of antipoverty vaccines Maria Elena Bottazzi,1 Eric Dumonteil,2 Jesus G. Valenzuela,3 Miguel Betancourt-Cravioto,4 Roberto Tapia-Conyer,5 and Peter J. Hotez1,6 ABSTRACT The neglected tropical diseases (NTDs) represent a group of chronic parasitic and related infections that promote poverty because of their impact on child development, pregnancy, and worker productivity. The estimated 20 million Mexicans who live below the poverty line suf- fer disproportionately from a high prevalence of neglected tropical diseases such as amebiasis, Chagas disease, dengue, leishmaniasis, soil-transmitted helminth infections, trachoma, and vivax malaria. However, because the NTDs occur predominantly among the poor, new industrial and financial models are required to establish innovative technologies to address these conditions in Mexico and elsewhere in Latin America. In response, the Slim Initiative for Antipoverty Vaccine Development was established to foster a public/private partnership between key academic, government, and industrial institutions in the U.S. and Mexico. Initial emphasis will be placed on developing new vaccines for Chagas disease and leishmaniasis, two of the highest burden NTDs in Mexico and Mesoamerica. Key words: public/private partnerships, vaccines, product development, technology transfer, vaccine manufacture. InTRODuCTIOn infectious diseases that promote poverty because of their impact on child growth and development, pregnancy, and Today in the Latin American and Caribbean region an es- worker productivity.2 Some estimate that in Latin America timated 40% of the population lives in poverty with more the burden of disease resulting from the NTDs may exceed than 100 million people living on less than US$2 per day.1 that of HIV/AIDS.1 Simultaneously, the NTDs represent Generally speaking, Latin America’s “bottom one hundred important, yet often unrecognized, reasons why the poorest million” live as subsistence farmers in rural areas and ur- people in the Americas cannot escape poverty. ban slums. Almost all of this region’s most impoverished people suffer from one or more neglected tropical diseases Mexico and the nTDs (NTDs), generally defined as chronic parasitic or related The estimated 112 million people living in Mexico also suffer from their share of poverty and NTDs. The na- tion is ranked 56 in terms of its human development index (HDI), an HDI that is roughly equivalent to that of 1 Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, D.C., USA Panama, Malaysia, Trinidad, and Tobago.3 However, this 2 Laboratorio de Parasitology C.I.R., Universidad Autónoma de level of development is highly maldistributed, with 47% Yucatán, Mérida, Yucatán, México 3 Vector Molecular Biology Section, Laboratory of Malaria and of Mexico’s population living below the poverty line as Vector Research, NIAID, NIH, Rockville, Maryland, USA of 20044 and 3.3% (approximately 3.7 million Mexicans) 4 Director de Soluciones Globales, Instituto Carlos Slim de la 5 Salud, México, D.F., México living on wages lower than US$2 per day. This bottom 3.7 5 Facultad de Medicina, Universidad Nacional Autónoma de million people also disproportionately suffer from NTDs, México, Dirección General, Instituto Carlos Slim de la Salud, México D.F., México especially in the southern most impoverished Mexican 6 Sabin Vaccine Institute, Washington, D.C., USA states. In Table 1 we show the total cumulative number of cases of the major infectious diseases identified in the Received for publication: 1-24-11 Accepted for publication: 1-27-11 past 10 years (2000-2010) as reported by the Ministry 138 Bol Med Hosp Infant Mex Bridging the innovation gap for neglected tropical diseases in Mexico: capacity building for the development of a new generation of antipoverty vaccines Table 1. Reported cases for major infectious diseases in Mexico Table 2. High-prevalence neglected tropical disease burden in (2000-2010) Mexico Disease Total cases Disease Estimated number of cases Reference (cumulative) Trichuriasis 18 million 7 Amebiasis 8,831,400 Ascariasis 9 million 7 Ascariasis 2,001,925 Amoebiasis >8 million 49 Giardia 425,234 Chagas disease 1-2 million (based on 2% 10 Dengue 332,117 seroprevalence); 68,000 new Tuberculosis 156,267 cases annually Malaria (P. vivax) 37,735 Malaria (P. vivax) 1.2 million 9 AIDS 36,897 Hookworm 1 million 7 Brucellosis 24,655 Dengue 27.2 cases/100,000 11 Leishmaniasis 9,038 Leishmaniasis ND – SARS 5,656 ND = not determined. Cysticercosis 4,328 Chagas disease 3,551 ditions,12 a risk factor common to both dengue and Chagas Leprosy 2,862 disease. In addition, leishmaniasis remains endemic in Leptospira 1,119 Rabies 21 Mexico, particularly in the south-southeast areas of the country and is unfortunately underreported. Other NTDs Data obtained from CENAVECE, Secretaría de Salud. Informes de Morbilidad 2010 and include up to epidemiologic week 22 for 2010.49 such as trachoma, cysticercosis, and onchocerciasis are also concentrated in areas near the states of Chiapas and Oaxaca.1 of Health in Mexico. However, with few exceptions, the The Mexican population who live below the poverty actual number of persons infected with an NTD is greatly line4,5 have a fundamental right to access not only essen- underestimated. Universally, NTDs are considered forgot- tial medicines but innovation as well. However, because ten diseases among forgotten people.6 there is inadequate financial remuneration for new drugs, Alternative estimates for the prevalence of several diagnostics, and vaccines for NTDs, most multinational NTDs in Mexico (Table 2) indicate that almost 20 mil- companies have shied away from investing in research lion people are infected with one or more soil-transmitted and development for these products.13 Nonetheless, new helminth infections, i.e., trichuriasis (Trichuris trichiura vaccines for the high prevalence NTDs, including hook- whipworm infection), ascariasis (Ascaris lumbricoides worm infection, dengue, vivax malaria, Chagas disease, roundworm infection), or hookworm infection caused pre- and leishmaniasis, could become new and important life- dominantly by Necator americanus,1,7 an important figure saving technologies. Because of the propensity of NTDs given that some studies have shown that chronic hook- to promote poverty, vaccines to combat such NTDs also worm infection in childhood reduces future wage-earning represent important economic development interventions by 40% or more.2,8 In addition, 1.2 million Mexicans are and are even sometimes referred to as “antipoverty vac- infected with Plasmodium vivax malaria9 and, based on cines.”14 However, in the absence of obvious financial 2% seroprevalence estimates among prospective blood incentives, almost all of the antipoverty vaccines are being donors, at least two million suffer from Chagas disease, developed either in academic laboratories or through new a disease that can cause serious and debilitating heart non-profit product development partnerships.13,15 Here we disease. However, some estimates suggest that as many outline steps for the development of antipoverty vaccines as 6 million or more persons may be infected nationwide, for Mexico’s leading NTDs, with initial emphasis on whereas in some southern Mexican states more than 10% Chagas disease and leishmaniasis. of the population may be infected.10 In addition, dengue fever and its dreaded complication, dengue hemorrhagic Chagas Disease and Leishmaniasis fever, are emerging in Mexico11 especially among people Chagas disease is a parasitic infection caused by the pro- who live in poor-quality dwellings with poor sanitary con- tozoa Trypanosoma cruzi, which is transmitted to humans Vol. 68, March-April 2011 139 Maria Elena Bottazzi, Eric Dumonteil, Jesus G. Valenzuela, Miguel Betancourt-Cravioto, Roberto Tapia-Conyer, and Peter J. Hotez by infected triatomine kissing bugs. In the acute stages, Burden and Distribution of Leishmaniasis and Chagas symptoms include fever, swollen glands, liver and spleen Disease in Mexico and, in acute cases, meningitis and heart enlargement, Leishmaniasis and Chagas disease are two of the most which can lead to death. Between 30 and 40 percent frequently neglected diseases of poverty (Table 1). In of cases develop into a chronic stage of the disease, the case of Chagas disease, the first cases were identified which leads to cardiac complications and dilation of the in Mexico in the 1930s19 but, since then, information on esophagus and the intestine.16 Cardiac manifestations Chagas disease burden has been scarce and the importance from chronic chagasic cardiomyopathy are especially of the disease has been largely ignored. Very few cases debilitating and can lead to sudden death. Chagas disease have been reported to the Ministry of Health of Mexico is one of the most common parasitic diseases in Latin during the past 15 years, although there has been a large America occurring in poor rural areas and, increasingly, increase of cases reported in recent years (Figure 1A). in many new urban and peri-urban areas especially where This is mostly due to improvements in epidemiological the quality of dwellings is poor and kissing bugs may surveillance and the decentralization of diagnostic ac- flourish. There are approximately eight to nine million tivities to regional laboratories.
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