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Neglected Tropical Diseases: Control & Research P.Olliaro, WHO/TDR NTDs in poor populations Previously neglected diseases TB Neglected tropical diseases HIV/AIDS Malaria Anthrax Soil transmitted helminthiasis Schistosomiasis Bovine tuberculosis Lymphatic filariasis Cysticercosis Onchocerciasis Brucellosis Leprosy Trachoma Echinococcosis Leishmaniasis Zoonotic trypanosomiasis Buruli ulcer Chagas disease Rabies HAT Dengue Neglected zoonoses … Global distribution of NTDs . ~ 1 billion people have >1 NTDs Burden of disease (DALYs) for infectious & parasitic diseases others infectious diseases, 87.2, 24% helminth infections, 49.9, 14% "others" = 29.6 % neglected tropical diseases, 56.6, 16% HIV/AIDS, 84.5, 23% malaria, 46.5, 13% tuberculosis, 34.7, 10% "big three" = 46.1% Countries affected by NTDs by income group High-income group, 10% Upper middleincome group, 17% Lower middleincome group, 32% Low-income group, 41% More than 70% of countries and territories affected by neglected tropical diseases are low-income and low middle-income countries 100% of low-income countries are affected by at least 5 neglected tropical diseases Health and poverty Ill health is both a cause and a consequence of poverty: sick people are more likely to become poor and the poor are more vulnerable to disease and disability Good health is central to creating and sustaining the capabilities that poor people need to escape from poverty Good health is not just an outcome of development: it is a way of achieving development Large scale interventions Lymphatic filariasis Leprosy Onchocerciasis Schistosomiasis Helminthiasis Trachoma Yaws Case management and development of new tools Human African trypanosomiasis Chagas diseases Buruli ulcer Leishmaniasis Dengue Rapid Impact Interventions Improving access Focused interventions Improving innovation Dengue Dengue is the most common mosquito-borne viral disease of humans that in recent years has become a major international public health concern. Globally, 2.5 billion people live in areas where dengue viruses can be transmitted. The geographical spread of both the mosquito vectors and the viruses has led to the global resurgence of epidemic dengue fever and emergence of dengue hemorrhagic fever (dengue/DHF) in the past 25 years with the development of hyperendemicity in many urban centers of the tropics. Human African trypanosomiasis Spread by the bite of the tsetse fly, the disease flourishes in impoverished rural parts of Africa. Untreated, the disease is invariably fatal. Death follows prolonged agony. In 2006 some 70 000 people are estimated to be infected. Leishmaniasis 12 millions are currently infected and 350 million people are at risk of infection. Around 1.5 million to 2 million new infections occur each year. Buruli ulcer BU has been reported from 30 countries, left untreated, the disease progresses to massive destruction of the skin and, in some cases, of bone, eyes, and other tissues. Limb amputations may be needed to save a patient's life. Trachoma Blinding trachoma affects more than 80 million people around the world. Children are mainly concerned by the infection, and every 4 people blind from trachoma 3 are women. Africa is the continent with the greatest number of endemic countries, but America, Middle-East and Asia are also endemic. SAFE strategy (Surgery, Antibiotics, Facial cleanliness, Environmental improvement) has proven its effectiveness in eliminating this scourge from humanity. Leprosy Leprosy is considered shameful and people hid their symptoms for fear of ostracism despite free and effective multidrug therapy. Today, the diagnosis and treatment of leprosy is easy. MDT treatment has been made available by WHO free of charge to all patients worldwide since 1995, and provides a simple yet highly effective cure for all types of leprosy. Lymphatic filariasis (LF) Over 120 million people are currently infected and around 1.3 billion people in more than 80 countries are at risk of infection. Drugs used against lymphatic filariasis are either donated – albendazole and ivermectin, or very inexpensive DEC. Albendazole and Ivermectin are donated by GlaxoSmithKline and Merck & C for mass administration to at-risk populations. Schistosomiasis Schistosoma haematobium is endemic in 53 countries in the Middle East and most of the African continent including the islands of Madagascar and Mauritius. In sub-Saharan Africa alone there are reckoned to be 112 million infections with S. haematobium. Praziquantel at the single dose of 40 mg/Kg body weight is a very safe and effective treatment against S. haematobium and the cost of treatment is less than 0.15 Euro. Hookworms Hookworms infect one billion people. It is calculated that 500 million women are infected by hookworms and at globally least 44 million are pregnant and infected at any time. Safe single dose treatment costs < 0.02 Euro a dose. Free and timely access to high-quality medicines Medicine Donator Conditions Albendazole GlaxoSmithKline Unlimited quantity for lymphatic filariasis only (not for soil-transmitted helminthiasis) Eflornithine sanofi-aventis Unlimited quantity by 2012 for human African trypanosomiasis Melarsoprol sanofi-aventis Unlimited quantity by 2012 for human African trypanosomiasis Extract from the opening speech by DG Nifurtimox Bayer Pentamidine sanofi-aventis Unlimited quantity by 2012 for human African trypanosomiasis Praziquantel Merck KGaA 200 million tablets 2008-2017 for Schistosomiasis Suramine Bayer Unlimited quantity by 2012 for human African trypanosomiasis Triclabendazole Novartis 600 000 tablets 2007-2009 for fascioliasis "Industry is&present. YourDirectly donations oflymphatic drugs andandother Merck Co Inc. to countries for filariasis onchocerciasis Ivermectin * support opened an opportunity which public health has MDT and Clofazimine Novartis Unlimited quantity for Leprosy and its complications seized. Your engagement has given us the tools to take 50 million tablets in 2007 for Soil-transmitted helminths control programmes Johnson & Johnson Mebendazole * for children action on an unprecedented scale." * Donation made not directly to WHO 500 000 tablets (120 mg) permeeting year byon 2012 for19-20 treatment Chagas disease at the first WHO global partners' NTD, Aprilof2007 RESEARCH: Develop new tools Pharmaceutical gap Existing tools: Optimise Improve use/access Operational gap FINANCING RESEARCH PARTNERING TO CONDUCT RESEARCH Ascariasis Trichuriasis Hookworm disease Modified from Ridley D. et al Health Affairs 2006 Drug R&D investments, pipeline & burden log DALY (millions) 100 Tuberculosis , 7 Intestinal nematodes 10 M alaria , 15 Lymphatic filariasis Schistosomiasis Trachoma Onchocerciasis 1 Leishmaniasis African Trypanosomiasis Vs. R&D costs ? Chagas disease 0 0 50 100 150 Drug R&D investments (million $) 200 250 Research needs Innovation/ pharmaceutical Gap Basic science Product discovery "Operational" Research Health Systems Product Development (R&D) Product use Schools, Communities "Tool deficient" "Tool ready" Human African trypanosomiasis, Chagas dis. Lymphatic filariasis, Leprosy, Onchocerciasis, Buruli ulcer, Leishmaniasis, Dengue Schistosomiasis, Helminthiasis, Trachoma, Yaws (VL in Indian subcontinent) "Vulnerable diseases" Lymphatic filariasis, Onchocerciasis, Schistosomiasis, (Helminthiases) Current global R&D portfolio disease Onchocerciasis potential candidates emodepside lymphatic filariasis Schistosomiasis L-praziquantel Soil-transmitted Helminths Human African Trypanosomiasis product from animal health? DB backups fexinidazole backups Chagas disease DEVELOPMENT moxidectin (Ph3) [WHO/TDR + Wyeth] OPTIMIZATION albendazole/Loaloa praziquantel dosing praziquantel combos? fexinidazole (Ph1) [DNDi + sanofi-aventis] Nifurtimox+eflornithine (approved EML) pentamidine shortened Rx pediatric benznidazole Leishmaniasis buparvaquone oral AmphoB Dengue options considered combinations: AmBisome+Miltefosine AmBisome+Paromomycin Miltefosine+Paromomycin