Neglected tropical disease research and development

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Neglected tropical diseases (NTDs) are a set of infectious diseases affecting an estimated 1.4 billion people worldwide. The classification of this group of neglected diseases is linked to their frequent neglect in public and private sector expenditure and attention at local, national, and international levels, and their concentration among the poor. Research and development yielding safe, effective drugs and vaccines for their treatment and prevention has been recognized as a global health priority.

Overview[edit]

The structure of ivermectin, an important drug in the control of Onchocerciasis.

Neglected tropical diseases are a set of infectious communicable diseases arising from a diverse group of parasitic worms, bacteria, and vector-borne protozoa.[1] The NTDs result in an estimated 534,000 deaths annually[2] and 57 million disability-adjusted life years (DALYs) lost.[3] The social, economic, and health burden of these diseases falls primarily on low and middle income countries where the diseases are most prevalent.[4] The NTDs represent the sixth greatest global health burden in terms of DALYs, equal to or potentially surpassing global malaria burden.[3][5]

NTD interventions include both programs to address environmental and social determinants of health (e.g., vector control, water quality, sanitation), and programs offering mass drug administration for disease prevention and treatment. Drug treatments exist[6] to confront many of the NTDs and represent some of the world's essential medicines.[7][8] Despite significant health and economic improvements using available medicines,[4][9][10][11] the low number of new compounds being researched and developed for NTDs is an ongoing and significant challenge.[7][12][13] The dearth of candidates in pharmaceutical company drug pipelines is primarily attributed to the high costs of drug development and the fact that NTDs are concentrated among the worlds' poor.[12][14] Other disincentives to investment include weak existing infrastructure for distribution and sales, and concerns regarding intellectual property protection.[11] However, the major stakeholders in NTD drug development—governments, foundations, pharmaceutical companies, academia, and NGOs—are involved in activities to help address the research and development shortfall and meet the many challenges presented by neglected tropical diseases.[15] Initiatives include public private partnerships, global R&D capacity building, priority vouchers to speed drug approval processes, open source scientific collaborations, and harmonization of global governance structures concerning NTDs.

NTD list[edit]

The diseases considered neglected tropical diseases vary. Malaria, HIV, and tuberculosis have received an amount of public attention and increased funding to no longer be considered neglected by some researchers. Outside "The Big Three", the seven most prevalent neglected tropical diseases in order of their global prevalence are ascariasis, trichuriasis, hookworm infection, schistosomiasis, lymphatic filariasis, and trachoma.[3] These seven are among a larger list of thirteen major NTDs: onchocerciasis, leishmaniasis, Chagas' disease, leprosy, Human African trypanosomiasis (sleeping sickness), Dracunculiasis, and Buruli ulcer.[3]

The World Health Organization's 2010 report dedicated to neglected tropical diseases offers an expanded list including dengue, rabies, yaws, cysticercosis, echinococcosis, and foodborne trematode infections.[16]

Neglected Tropical Diseases Worldwide Burden
Disease DALYs (million) Deaths/Yr Global Prevalence (million) Population at Risk (million)
Schistosomiasis 4.5 280,000 207 780
Hookworm 22.1 65,000 576 3200
Ascariasis 10.5 60,000 807 4200
Leishmaniasis 2.1 51,000 12 350
Trypanosomiasis 1.5 48,000 0.3 60
Chagas disease 0.7 14,000 8 25
Trichuriasis 6.4 10,000 604 3200
Leprosy 0.2 6,000 0.4 ND
Lymphatic filariasis 5.8 0 120 1300
Trachoma 2.3 0 84 590
Onchocerciasis 0.5 0 37 90
Cryptococcosis 12 400,000 1 8

ND=Not Determined[2][3]

Deficient market[edit]

In their 2002 review of the U.S. Food and Drug Administration (FDA) databases and the European Agency for the Evaluation of Medicinal Products, Troullier et al found that 16 out of 1393 new chemical entities were approved for NTDs between 1975 and 1999 (~1%).[7] Cohen et al revisited the data and using the same methodology found 32 new chemical entities during the time period.[8] In a second analysis using an expanded list of NTDs based on the G-FINDER survey,[17] the number was slightly higher, with 46 new drugs and vaccines approved (~3% of the total including HIV drugs).[8] Between 2000 and 2009, there has been some increase with an additional 26 newly approved drugs and vaccines for NTDs.[8]

A number of factors are recognized as contributing to the low number. The barrier most reported is the high cost of drug development. Estimates are that pharmaceutical companies' development costs to approval fall between $500 million and $2 billion.[18] DiMasi, Hansen, and Grabowski calculated an average of $802 million in year 2000 dollars.[19] Furthermore, the time that drugs are approved for use averages seven years out of the twenty years on-patent, meaning a tendency for the market to focus on diseases of developed nations where high prices can be used to recoup research and development costs, and subsidize failed R&D efforts. In short, NTD research and development is considered a high investment risk given that NTDs predominantly affect the poor in low and middle income countries.[12][14] Additional barriers include drug safety regulatory requirements, intellectual property protection problems, and poor infrastructure for distribution and sales.[11][12]

Although drug companies have not invested heavily in the NTDs, in several cases, rather than focus on profits, some have decided to donate key drugs to address NTDs. For example, Merk has had a program since the mid-1980s to donate ivermectin (Mectizan) indefinitely to support the global fight of onchoceriasis. GlaxoSmithKline and several other large pharmaceutical companies have donation programs as well. Drug donation however, does not ameliorate the deficiency of new chemical entities being researched and developed. This is especially of concern with reports of emerging resistance among existing drugs.[20][21]

Policy initiatives[edit]

Public private partnerships[edit]

Melinda and Bill Gates speak during press conference at the World Economic Forum in Davos, Switzerland, January 30, 2009.

Governments, foundations, the non-profit sector, and private sector have found new connections to help address market deficiencies by providing funding support and spreading both the costs and risks of NTD research and development. The proliferation of public private partnerships (PPPs) has been recognized as a key innovation in the past decade, helping to unlock existing and new resources.

Major PPPs for NTDs include: the Sabin Vaccine Institute, Norvartis Vaccines Institute for Global Health, MSD Wellcome Trust Hilleman Laboratories, Infectious Diseases Research Institute, Institut Pasteur and INSERM, and the International Vaccine Institute.[14] Likewise, a number of new academic drug development centers have been created in recent years drawing in industry partners. Support for these centers is frequently traced to the Bill and Melinda Gates Foundation, the Sandler Foundation, and the Wellcome Trust.[22]

R&D capacity building in middle income countries[edit]

Growing NTD research and development capacity in middle income countries is an area of policy interest. A 2009 study of biotechnology companies in India, China, Brazil, and South Africa revealed sixty-two NTD products in development and on the market out of approximately five hundred products offered (~14%). When products to fight HIV, malaria, and TB were included in the analysis, the number increased to one hundred twenty-three products, approximately 25% of the total products offered.

Researchers have argued that unlike most multinationals, small and mid-sized "Global South" companies see significant business opportunities in the development of NTD-related diagnostics, biologics, pharmaceuticals, and services.[23] Potential actions to improve and expand this R&D capacity have been recommended including expansion of human capital, increased private investment, knowledge and patent sharing, infrastructure building for business incubation and innovation support.

Innovation prizes and grants[edit]

Competitive innovation prizes have been used to spur development in a range of fields such as aerospace engineering, clean technology, and genomics. The X-Prize Foundation is launching a competition for high speed, point-of-care diagnostics for tuberculosis.[citation needed] A more widely defined annual "Global Health EnterPrize" for neglected tropical diseases has been proposed to reward health innovators, particularly those based in countries where NTDs represent a serious health burden.[citation needed]

The Bill & Melinda Gates Foundation offers the Grand Challenges Explorations Opportunities on a rolling basis. This grant program allows individuals from any organization or background to apply to address priority global health issues. Each project award is $100,000 dollars and is drawn from a Foundation funding pool of $100 million. Awardees have tended to offer research projects on topics that are highly speculative but offer potentially game-changing breakthroughs in global health.

FDA priority review vouchers (PRV)[edit]

In 2006, Ridley et al recommended the development of a priority review voucher (PRV) in the journal Health Affairs. It gained interest by Senator Sam Brownback of Kansas who championed its introduction in the FDA Amendments Act of 2007. Under the enacted law, FDA approval of a non-NTD drug can be accelerated through the drug review process if paired to a drug that addresses a NTD. The potential economic benefit to a pharmaceutical company is estimated to be potentially as high as $300 million per drug. One drug has come to market so far using this mechanism, Novartis' Coartem, an anti-malarial medication.

The PRV isn't limited to the pairing of drugs within a single company, rather can be transferred between companies. Companies with NTD drug candidates in their pipelines but without a blockbuster drug, are able to sell their voucher producing financial returns. In the EU, similar priority review incentives are now under consideration to increase the speed of regulatory pricing and reimbursement decisions.

However, PRVs have been criticized as being open to manipulation and possibly encouraging errors through too rapid regulatory decision-making.[24]

Open source collaboration initiatives[edit]

The Drugs for Neglected Diseases Initiative, a web focused not-for-profit drug R&D organization dedicated to creating new NTD treatments.

Several companies and scientific organizations are participating in open source initiatives to share drug data and patent information over the web, and facilitate virtual collaboration on NTD research.

One rich area to explore is in the wealth of genomic data resulting from the sequencing of parasite genomes. These data offer opportunities for the exploration of new therapeutic products using computational, and open source collaboration methods for drug discovery.[25][26] The Tropical Disease Initiative, for example, has used large amounts of computing power to generate the protein structures for ten parasite genomes. An open source drug bank was matched algorithmically to determine compounds with protein interaction activity, and two candidates were identified. In general, such methods may hold important opportunities for off-label use of existing approved drugs.

References[edit]

  1. ^ Feasey N, Wansbrough-Jones M, Mabey DC, Solomon AW. Neglected tropical diseases. Br Med Bull. 2010;93:179-200. Epub 2009 Dec 10. Review.
  2. ^ a b Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med 2006 Jan;3(5):e102.
  3. ^ a b c d e Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, et al. Control of neglected tropical diseases. N Engl J Med 2007 Sep 6;357(10):1018-1027.
  4. ^ a b Conteh L, Engels T, Molyneux DH. Socioeconomic aspects of neglected tropical diseases. Lancet 2010 Jan 16;375(9710):239-247.
  5. ^ Hotez P, Ottesen E, Fenwick A, Molyneux D. The neglected tropical diseases: the ancient afflictions of stigma and poverty and the prospects for their control and elimination. Adv Exp Med Biol 2006;582:23-33.
  6. ^ Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, Rochon PA. Oral drug therapy for multiple neglected tropical diseases: a systematic review. JAMA 2007 Oct 24;298(16):1911-1924.
  7. ^ a b c Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet 2002 Jun 22;359(9324):2188-2194.
  8. ^ a b c d Cohen J, Dibner MS, Wilson A. Development of and access to products for neglected diseases. PLoS One 2010 May 12;5(5):e10610.
  9. ^ Chu BK, Hooper PJ, Bradley MH, McFarland DA, Ottesen EA. The economic benefits resulting from the first 8 years of the Global Programme to Eliminate Lymphatic Filariasis (2000-2007). PLoS Negl Trop Dis. 2010 Jun 1;4(6):e708.
  10. ^ Merck Mectizan Drug Donation Program http://www.mectizan.org/
  11. ^ a b c Villa S, Compagni A, Reich MR. Orphan drug legislation: lessons for neglected tropical diseases. Int J Health Plann Manage 2009 Jan-Mar;24(1):27-42.
  12. ^ a b c d Trouiller P, Torreele E, Olliaro P, White N, Foster S, Wirth D, et al. Drugs for neglected diseases: a failure of the market and a public health failure? Trop Med Int Health 2001 Nov;6(11):945-951.
  13. ^ Chirac P, Torreele E. Global framework on essential health R&D. Lancet. 2006 May 13;367(9522):1560-1.
  14. ^ a b c Bethony JM, Cole RN, Guo X, Kamhawi S, Lightowlers MW, Loukas A, et al. Vaccines to combat the neglected tropical diseases. Immunol Rev 2011 Jan;239(1):237-270.
  15. ^ Liese B, Rosenberg M, Schratz A. Programmes, partnerships, and governance for elimination and control of neglected tropical diseases. Lancet 2010 Jan 2;375(9708):67-76.
  16. ^ World Health Organization. Working to overcome the global impact of neglected tropical diseases: first WHO report on neglected tropical diseases. 2010.
  17. ^ G-FINDER Database http://www.georgeinstitute.org/about-us/media-centre/g-finder-database-open-public
  18. ^ Adams CP, Brantner VV. Estimating the cost of new drug development: is it really 802 million dollars? Health Aff (Millwood). 2006 Mar-Apr;25(2):420-8.
  19. ^ DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Econ. 2003 Mar;22(2):151-85.
  20. ^ Tchuem Tchuente LA. Control of soil-transmitted helminths in sub-Saharan Africa: Diagnosis, drug efficacy concerns and challenges. Acta Trop 2010 Jul 21.
  21. ^ Smits HL. Prospects for the control of neglected tropical diseases by mass drug administration. Expert Rev Anti Infect Ther 2009 Feb;7(1):37-56.
  22. ^ Renslo AR, McKerrow JH. Drug discovery and development for neglected parasitic diseases. Nat Chem Biol 2006 Dec;2(12):701-710.
  23. ^ Frew SE, Liu VY, Singer PA. A business plan to help the 'global South' in its fight against neglected diseases. Health Aff (Millwood) 2009 Nov-Dec;28(6):1760-1773.
  24. ^ Kesselheim AS. Drug development for neglected diseases - the trouble with FDA review vouchers. N Engl J Med 2008 Nov 6;359(19):1981-1983.
  25. ^ Kar S. Opinion: Open innovation: an answer for neglected diseases. Future Med Chem 2010 Sep;2(9):1411-5.
  26. ^ Ortí L, Carbajo RJ, Pieper U, Eswar N, Maurer SM, Rai AK, Taylor G, Todd MH, Pineda-Lucena A, Sali A, Marti-Renom MA. A kernel for open source drug discovery in tropical diseases. PLoS Negl Trop Dis 2009;3(4):e418.

Further reading[edit]

Progress and challenges in neglected tropical diseases. Lancet 2010 Oct 23;376(9750):1363.

Remembering the neglected tropical diseases. Lancet 2007 Dec 8;370(9603):1880.

WHO and Sanofi-Aventis expand programme to fight neglected tropical diseases. Indian J Med Sci 2006 Nov;60(11):487.

Research versus treatment for neglected diseases. Lancet 2006 Feb 11;367(9509):448.

Aksoy S. Solutions to neglected tropical diseases require vibrant local scientific communities. PLoS Negl Trop Dis 2010 Mar 30;4(3):e662.

Allotey P, Reidpath DD, Pokhrel S. Social sciences research in neglected tropical diseases: the ongoing neglect in the neglected tropical diseases. Health Res Policy Syst 2010 Oct 21;8:32.

Alvar J, Yactayo S, Bern C. Leishmaniasis and poverty. Trends Parasitol 2006 Dec;22(12):552-557.

Ameen M. Cutaneous leishmaniasis: therapeutic strategies and future directions. Expert Opin Pharmacother 2007 Nov;8(16):2689-2699.

Ault SK. Intersectoral approaches to neglected diseases. Ann N Y Acad Sci 2008;1136:64-69.

Ault SK, Nicholls RS. Integrated approach to neglected tropical diseases in Latin America and the Caribbean: an ethical imperative to reach justice and social equity. Biomedica 2010 Jun;30(2):159-163.

Baker MC, Mathieu E, Fleming FM, Deming M, King JD, Garba A, et al. Mapping, monitoring, and surveillance of neglected tropical diseases: towards a policy framework. Lancet 2010 Jan 16;375(9710):231-238.

Bethony JM, Diemert DJ, Oliveira SC, Loukas A. Can schistosomiasis really be consigned to history without a vaccine? Vaccine 2008 Jun 25;26(27-28):3373-3376.

Bitran R, Martorell B, Escobar L, Munoz R, Glassman A. Controlling and eliminating neglected diseases in Latin America and the Caribbean. Health Aff (Millwood) 2009 Nov-Dec;28(6):1707-1719.

Bockarie MJ, Deb RM. Elimination of lymphatic filariasis: do we have the drugs to complete the job? Curr Opin Infect Dis 2010 Dec;23(6):617-620.

Bockarie MJ, Pedersen EM, White GB, Michael E. Role of vector control in the global program to eliminate lymphatic filariasis. Annu Rev Entomol 2009;54:469-487.

Boelaert M, Meheus F, Robays J, Lutumba P. Socio-economic aspects of neglected diseases: sleeping sickness and visceral leishmaniasis. Ann Trop Med Parasitol 2010 Oct;104(7):535-542.

Bottazzi ME, Brown AS. Model for product development of vaccines against neglected tropical diseases: a vaccine against human hookworm. Expert Rev Vaccines 2008 Dec;7(10):1481-1492.

Bottazzi ME, Miles AP, Diemert D, Hotez PJ. An ounce of prevention on a budget: a nonprofit approach to developing vaccines against neglected diseases. Expert Rev Vaccines 2006 Apr;5(2):189-198.

Brady MA, Hooper PJ, Ottesen EA. Projected benefits from integrating NTD programs in sub-Saharan Africa. Trends Parasitol 2006 Jul;22(7):285-291.

Brownback S. Eliminating neglected diseases: impact of published paper. Health Aff (Millwood) 2007 Sep-Oct;26(5):1509.

Butler D. Neglected disease boost. Nature 2009 Feb 12;457(7231):772-773.

Canning D. Priority setting and the 'neglected' tropical diseases. Trans R Soc Trop Med Hyg 2006 Jun;100(6):499-504.

Cavalli A, Bamba SI, Traore MN, Boelaert M, Coulibaly Y, Polman K, et al. Interactions between Global Health Initiatives and country health systems: the case of a neglected tropical diseases control program in Mali. PLoS Negl Trop Dis 2010 Aug 17;4(8):e798.

Chaves LF, Pascual M. Comparing models for early warning systems of neglected tropical diseases. PLoS Negl Trop Dis 2007 Oct 22;1(1):e33.

Croft SL. Public-private partnership: from there to here. Trans R Soc Trop Med Hyg 2005 Oct;99 Suppl 1:S9-14.

Crowther GJ, Shanmugam D, Carmona SJ, Doyle MA, Hertz-Fowler C, Berriman M, et al. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach. PLoS Negl Trop Dis 2010 Aug 24;4(8):e804.

Dantas-Torres F, Marcondes CB. Fighting neglected tropical diseases in the postgenomic era. Trends Parasitol 2008 Apr;24(4):156-7; author reply 157-8.

Denery JR, Nunes AA, Hixon MS, Dickerson TJ, Janda KD. Metabolomics-based discovery of diagnostic biomarkers for onchocerciasis. PLoS Negl Trop Dis 2010 Oct 5;4(10):e834.

Dybul M. Neglected tropical diseases and HIV/AIDS. Lancet 2006 Nov 25;368(9550):1865.

Ebrahim GJ. Neglected tropical diseases. J Trop Pediatr 2009 Jun;55(3):141-144.

Engels D, Savioli L. Reconsidering the underestimated burden caused by neglected tropical diseases. Trends Parasitol 2006 Aug;22(8):363-366.

Fenwick A, Webster JP, Bosque-Oliva E, Blair L, Fleming FM, Zhang Y, et al. The Schistosomiasis Control Initiative (SCI): rationale, development and implementation from 2002-2008. Parasitology 2009 Nov;136(13):1719-1730.

Frearson J, Wyatt P. Drug Discovery in Academia- the third way? Expert Opin Drug Discov 2010 Oct 1;5(10):909-919.

Frezard F, Demicheli C. New delivery strategies for the old pentavalent antimonial drugs. Expert Opin Drug Deliv 2010 Dec;7(12):1343-1358.

Germani Y, Sansonetti P. "Neglected diseases": it is better to respond to future challenges—the model of a pilot North-South program on enteric infections integrating many research components. C R Biol 2008 Dec;331(12):973-981.

Gloeckner C, Garner AL, Mersha F, Oksov Y, Tricoche N, Eubanks LM, et al. Repositioning of an existing drug for the neglected tropical disease Onchocerciasis. Proc Natl Acad Sci USA 2010 Feb 23;107(8):3424-3429.

Gray DJ, Forsyth SJ, Li RS, McManus DP, Li Y, Chen H, et al. An innovative database for epidemiological field studies of neglected tropical diseases. PLoS Negl Trop Dis 2009 May 26;3(5):e413.

Gray DJ, McManus DP, Li Y, Williams GM, Bergquist R, Ross AG. Schistosomiasis elimination: lessons from the past guide the future. Lancet Infect Dis 2010 Oct;10(10):733-736.

Grepin KA, Reich MR. Conceptualizing integration: a framework for analysis applied to neglected tropical disease control partnerships. PLoS Negl Trop Dis 2008 Apr 30;2(4):e174.

Gustavsen K, Hanson C. Progress in public-private partnerships to fight neglected diseases. Health Aff (Millwood) 2009 Nov-Dec;28(6):1745-1749.

Gyapong JO, Gyapong M, Yellu N, Anakwah K, Amofah G, Bockarie M, et al. Integration of control of neglected tropical diseases into health-care systems: challenges and opportunities. Lancet 2010 Jan 9;375(9709):160-165.

Hanvoravongchai P, Warakamin B, Coker R. Critical interactions between Global Fund-supported programmes and health systems: a case study in Thailand. Health Policy Plan 2010 Nov;25 Suppl 1:i53-57.

Hopkins AD. Challenges for the integration of mass drug administrations against multiple 'neglected tropical diseases'. Ann Trop Med Parasitol 2009 Oct;103 Suppl 1:S23-31.

Hotez P. A national school of tropical medicine and neglected infections of poverty for North America. PLoS Negl Trop Dis 2010 Jun 29;4(6):e735.

Hotez P. Neglected diseases amid wealth in the United States and Europe. Health Aff (Millwood) 2009 Nov-Dec;28(6):1720-1725.

Hotez P, Raff S, Fenwick A, Richards F,Jr, Molyneux DH. Recent progress in integrated neglected tropical disease control. Trends Parasitol 2007 Nov;23(11):511-514.

Hotez PJ. Neglected tropical disease control in the "post-American world". PLoS Negl Trop Dis 2010 Aug 31;4(8):e812.

Hotez PJ. A plan to defeat neglected tropical diseases. Sci Am 2010 Jan;302(1):90-4, 96.

Hotez PJ. One world health: neglected tropical diseases in a flat world. PLoS Negl Trop Dis 2009;3(4):e405.

Hotez PJ. Mass drug administration and integrated control for the world's high-prevalence neglected tropical diseases. Clin Pharmacol Ther 2009 Jun;85(6):659-664.

Hotez PJ. Neglected infections of poverty in the United States of America. PLoS Negl Trop Dis 2008 Jun 25;2(6):e256.

Hotez PJ. The giant anteater in the room: Brazil's neglected tropical diseases problem. PLoS Negl Trop Dis 2008 Jan 30;2(1):e177.

Hotez PJ. Reinventing Guantanamo: from detainee facility to Center for Research on Neglected Diseases of Poverty in the Americas. PLoS Negl Trop Dis 2008 Feb 27;2(2):e201.

Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Diemert D, Loukas A. New technologies for the control of human hookworm infection. Trends Parasitol 2006 Jul;22(7):327-331.

Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J. Helminth infections: the great neglected tropical diseases. J Clin Invest 2008 Apr;118(4):1311-1321.

Hotez PJ, Brown AS. Neglected tropical disease vaccines. Biologicals 2009 Jun;37(3):160-164.

Hotez PJ, Ehrenberg JP. Escalating the global fight against neglected tropical diseases through interventions in the Asia Pacific region. Adv Parasitol 2010;72:31-53.

Hotez PJ, Fenwick A, Savioli L, Molyneux DH. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 2009 May 2;373(9674):1570-1575.

Hotez PJ, Ferris MT. The antipoverty vaccines. Vaccine 2006 Jul 26;24(31-32):5787-5799.

Hotez PJ, Molyneux DH, Fenwick A, Savioli L, Takeuchi T. A Global Fund to Fight Neglected Tropical Diseases: is the G8 Hokkaido Toyako 2008 Summit ready? PLoS Negl Trop Dis 2008 Mar 26;2(3):e220.

Hotez PJ, Molyneux DH, Stillwaggon E, Bentwich Z, Kumaresan J. Neglected tropical diseases and HIV/AIDS. Lancet 2006 Nov 25;368(9550):1865-1866.

Hotez PJ, Pecoul B. "Manifesto" for advancing the control and elimination of neglected tropical diseases. PLoS Negl Trop Dis 2010 May 25;4(5):e718.

Hotez PJ, Thompson TG. Waging peace through neglected tropical disease control: a US foreign policy for the bottom billion. PLoS Negl Trop Dis 2009;3(1):e346.

Hunter PR. Bibliometrics, research quality, and neglected tropical diseases. Lancet 2009 Feb 21;373(9664):630-631.

Huppatz C, Durrheim DN. Control of neglected tropical diseases. N Engl J Med 2007 Dec 6;357(23):2407; author reply 2407-8.

John JE, Pharma Research for Tropical Diseases, Current Science, vol 91(9), page 1127, 10th November 2006, Bangalore (Indian Academy of Sciences), India.

John JE, Anti-Infective Agents: Spectrum and Selectivity, Current Science, vol 92(2), page 159, 25th Jan 2007, Bangalore (Indian Academy of Sciences), India.

John JE, Tropical diseases research and anti-fungal research linked with cancer research, Current Science, 2009, 25th Dec, 97(12), 1704.

John JE, Medicines for tropical diseases; support through tax-incentives, Drug Discovery Today, 2011, volume 16 (3/4), 91–92.

Kabatereine N. The unsung hero of neglected tropical diseases: interview with Narcis Kabatereine by Gavin Yamey. PLoS Negl Trop Dis 2009 Dec 22;3(12):e546.

Kabatereine NB, Malecela M, Lado M, Zaramba S, Amiel O, Kolaczinski JH. How to (or not to) integrate vertical programmes for the control of major neglected tropical diseases in sub-Saharan Africa. PLoS Negl Trop Dis 2010 Jun 29;4(6):e755.

Kettler HE, Modi R. Building local research and development capacity for the prevention and cure of neglected diseases: the case of India. Bull World Health Organ 2001;79(8):742-747.

King CH, Bertino AM. Asymmetries of poverty: why global burden of disease valuations underestimate the burden of neglected tropical diseases. PLoS Negl Trop Dis 2008 Mar 26;2(3):e209.

Kuepfer I, Burri C. Reflections on clinical research in sub-Saharan Africa. Int J Parasitol 2009 Jul 15;39(9):947-954.

Kuhn I, Kellenberger E, Said-Hassane F, Villa P, Rognan D, Lobstein A, et al. Identification by high-throughput screening of inhibitors of Schistosomamansoni NAD(+) catabolizing enzyme. Bioorg Med Chem 2010 Nov 15;18(22):7900-7910.

Mahmoud A, Zerhouni E. Neglected tropical diseases: moving beyond mass drug treatment to understanding the science. Health Aff (Millwood) 2009 Nov-Dec;28(6):1726-1733.

Maltezou HC. Drug resistance in visceral leishmaniasis. J Biomed Biotechnol 2010;2010:617521.

Mathers CD, Ezzati M, Lopez AD. Measuring the burden of neglected tropical diseases: the global burden of disease framework. PLoS Negl Trop Dis 2007 Nov 7;1(2):e114.

Matter A, Keller TH. Impact of non-profit organizations on drug discovery: opportunities, gaps, solutions. Drug Discov Today 2008 Apr;13(7-8):347-352.

May RM. Parasites, people and policy: infectious diseases and the Millennium Development Goals. Trends Ecol Evol 2007 Oct;22(10):497-503.

Millet P. Status of research and development for control of tropical diseases: hypocrisy, indifference or lack of coordination. Med Trop (Mars) 2006 Dec;66(6):542-548.

Molyneux DH. Neglected tropical diseases—beyond the tipping point? Lancet 2010 Jan 2;375(9708):3-4.

Molyneux DH. "Neglected" diseases but unrecognised successes—challenges and opportunities for infectious disease control. Lancet 2004 Jul 24-30;364(9431):380-383.

Molyneux DH, Hotez PJ, Fenwick A. "Rapid-impact interventions": how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor. PLoS Med 2005 Nov;2(11):e336.

Molyneux DH, Hotez PJ, Fenwick A, Newman RD, Greenwood B, Sachs J. Neglected tropical diseases and the Global Fund. Lancet 2009 Jan 24;373(9660):296-297.

Morel CM. Neglected diseases: under-funded research and inadequate health interventions. Can we change this reality? EMBO Rep 2003 Jun;4 Spec No:S35-8.

Morel CM, Serruya SJ, Penna GO, Guimaraes R. Co-authorship network analysis: a powerful tool for strategic planning of research, development and capacity building programs on neglected diseases. PLoS Negl Trop Dis 2009 Aug 18;3(8):e501.

Morris K. Time to overcome the neglect of neglected tropical diseases. Lancet Infect Dis 2010 Dec;10(12):820-821.

Muela Ribera J, Peeters Grietens K, Toomer E, Hausmann-Muela S. A word of caution against the stigma trend in neglected tropical disease research and control. PLoS Negl Trop Dis 2009 Oct 27;3(10):e445.

Musgrove P, Hotez PJ. Turning neglected tropical diseases into forgotten maladies. Health Aff (Millwood) 2009 Nov-Dec;28(6):1691-1706.

Narain JP, Dash AP, Parnell B, Bhattacharya SK, Barua S, Bhatia R, et al. Elimination of neglected tropical diseases in the South-East Asia Region of the World Health Organization. Bull World Health Organ 2010 Mar;88(3):206-210.

Nelson K. Stimulating research in the most neglected diseases. Lancet 2002 Mar 23;359(9311):1042.

Nickerson EK, West TE, Day NP, Peacock SJ. Staphylococcus aureus disease and drug resistance in resource-limited countries in south and east Asia. Lancet Infect Dis 2009 Feb;9(2):130-135.

Nkengasong JN, Nsubuga P, Nwanyanwu O, Gershy-Damet GM, Roscigno G, Bulterys M, et al. Laboratory systems and services are critical in global health: time to end the neglect? Am J Clin Pathol 2010 Sep;134(3):368-373.

Norman FF, Perez de Ayala A, Perez-Molina JA, Monge-Maillo B, Zamarron P, Lopez-Velez R. Neglected tropical diseases outside the tropics. PLoS Negl Trop Dis 2010 Jul 27;4(7):e762.

Normile D. Singapore. Novartis kicks off institute for neglected diseases. Science 2003 Feb 7;299(5608):811.

Nwaka S, Ramirez B, Brun R, Maes L, Douglas F, Ridley R. Advancing drug innovation for neglected diseases-criteria for lead progression. PLoS Negl Trop Dis 2009 Aug 25;3(8):e440.

Olveda R, Leonardo L, Zheng F, Sripa B, Bergquist R, Zhou XN. Coordinating research on neglected parasitic diseases in Southeast Asia through networking. Adv Parasitol 2010;72:55-77.

Pang T. Vaccines for the prevention of neglected diseases—dengue fever. Curr Opin Biotechnol 2003 Jun;14(3):332-336.

Parker M, Allen T. Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda. Health Res Policy Syst 2011 Jan 6;9:3.

Parker M, Allen T, Hastings J. Resisting control of neglected tropical diseases: dilemmas in the mass treatment of schistosomiasis and soil-transmitted helminths in north-west Uganda. J Biosoc Sci 2008 Mar;40(2):161-181.

Payne L, Fitchett JR. Bringing neglected tropical diseases into the spotlight. Trends Parasitol 2010 Sep;26(9):421-423.

Pecoul B. New drugs for neglected diseases: from pipeline to patients. PLoS Med 2004 Oct;1(1):e6.

Pokhrel S, Reidpath D, Allotey P. Social sciences research in neglected tropical diseases: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation. Health Res Policy Syst 2011 Jan 6;9(1):2.

Remme JH, Blas E, Chitsulo L, Desjeux PM, Engers HD, Kanyok TP, et al. Strategic emphases for tropical diseases research: a TDR perspective. Trends Microbiol 2002 Oct;10(10):435-440.

Ridley RG, Fletcher ER. Making a difference: 30 years of TDR. Nat Rev Microbiol 2008 May;6(5):401-407.

Sachs JD. The neglected tropical diseases. Sci Am 2007 Jan;296(1):33A.

Sakisaka K, Nakamura J. Donors' commitments to neglected tropical diseases: not all bad. Lancet 2010 Mar 13;375(9718):892-893.

Shotton D, Portwin K, Klyne G, Miles A. Adventures in semantic publishing: exemplar semantic enhancements of a research article. PLoS Comput Biol 2009 Apr;5(4):e1000361.

Singer BH, Ryff CD. Neglected tropical diseases, neglected data sources, and neglected issues. PLoS Negl Trop Dis 2007 Nov 7;1(2):e104.

Siqueira-Neto JL, Song OR, Oh H, Sohn JH, Yang G, Nam J, et al. Antileishmanial high-throughput drug screening reveals drug candidates with new scaffolds. PLoS Negl Trop Dis 2010 May 4;4(5):e675.

Solomon AW, Nayagam S, Pasvol G. Recent advances in tropical medicine. Trans R Soc Trop Med Hyg 2009 Jul;103(7):647-652.

Sommerfeld J, Oduola AM. Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development. Afr J Med Med Sci 2007;36 Suppl:1-5.

Stich A, Barrett MP, Krishna S. Waking up to sleeping sickness. Trends Parasitol 2003 May;19(5):195-197.

Stoever K, Kim A. Global health as a factor in economic and social stability. Health Prog 2007 May-Jun;88(3):57-59.

Stothard JR, Chitsulo L, Kristensen TK, Utzinger J. Control of schistosomiasis in sub-Saharan Africa: progress made, new opportunities and remaining challenges. Parasitology 2009 Nov;136(13):1665-1675.

Tanne JH. Collaborations aim to develop new drugs for neglected tropical diseases. BMJ 2009 Jun 29;338:b2638.

Thylefors B, Alleman MM, Twum-Danso NA. Operational lessons from 20 years of the Mectizan Donation Program for the control of onchocerciasis. Trop Med Int Health 2008 May;13(5):689-696.

Traynor K. FDA program could boost treatments for neglected diseases. Am J Health Syst Pharm 2008 Sep 1;65(17):1595-1596.

Tuon FF, Amato VS. Neglected tropical diseases: beyond the wars. Rev Inst Med Trop Sao Paulo 2008 Sep-Oct;50(5):313-314.

Utzinger J, de Savigny D. Control of neglected tropical diseases: integrated chemotherapy and beyond. PLoS Med 2006 Jan;3(5):e112.

Utzinger J, N'goran EK, Caffrey CR, Keiser J. From innovation to application: Social-ecological context, diagnostics, drugs and integrated control of schistosomiasis. Acta Trop 2010 Sep 8.

Vanderelst D, Speybroeck N. Quantifying the lack of scientific interest in neglected tropical diseases. PLoS Negl Trop Dis 2010 Jan 26;4(1):e576.

Vellay SG, Latimer NE, Paillard G. Interactive text mining with Pipeline Pilot: a bibliographic web-based tool for PubMed. Infect Disord Drug Targets 2009 Jun;9(3):366-374.

Villafuerte-Galvez J, Curioso WH, Miranda JJ. The role of medical students in the fight to control neglected tropical diseases: a view from Peru. PLoS Negl Trop Dis 2008 Sep 24;2(9):e292.

Voelker R. Attention sought for neglected diseases. JAMA 2009 May 6;301(17):1755-1756.

Vogel G. Infectious diseases. Tackling neglected diseases could offer more bang for the buck. Science 2006 Feb 3;311(5761):592-593.

Walgate R. New non-profit organization will support research to combat neglected diseases. Bull World Health Organ 2002;80(10):842-843.

Walker D, Fox-Rushby JA. Economic evaluation of communicable disease interventions in developing countries: a critical review of the published literature. Health Econ 2000 Dec;9(8):681-698.

Waltz E. FDA launches priority vouchers for neglected-disease drugs. Nat Biotechnol 2008 Dec;26(12):1315-1316.

Weiss MG. Stigma and the social burden of neglected tropical diseases. PLoS Negl Trop Dis 2008 May 14;2(5):e237.

Witty A. Eliminating neglected diseases in poor countries: a conversation with Andrew Witty. Interview by Susan Dentzer. Health Aff (Millwood) 2009 May-Jun;28(3):w411-6.

Yamey G, Hotez P. Neglected tropical diseases. BMJ 2007 Aug 11;335(7614):269-270.

Zarocostas J. Gates foundation pledges new funds to fight neglected diseases. BMJ 2009 Feb 3;338:b454.

Zhang Y, MacArthur C, Mubila L, Baker S. Control of neglected tropical diseases needs a long-term commitment. BMC Med 2010 Oct 29;8:67.

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