04720nas a2200829   4500000000100000008004100001260001200042653001500054653001600069653001600085653001500101653001700116653001500133653001500148653001700163653001100180653001600191653001200207653001500219653001600234653001900250653001600269653001200285653002300297653001500320653001600335653002100351653002100372653001600393653001300409653002000422653001700442653001500459653001700474653001500491653001700506653001600523653001500539653001500554653001700569653003100586653001700617653001800634653001600652653001200668653001600680653001700696653001700713653002100730653001700751653001400768653001500782653001600797653001700813653001700830653001900847653001000866100001200876700001200888700001600900700001600916700001500932700001400947700001200961700001300973245015700986856009301143300000901236490000701245520262401252022001403876       2023                            d  c10/202310aAcedapsone10aAlbendazole10aAmoxicillin10aArtemether10aArtemisinins10aArterolane10aArtesunate10aAzithromycin10aAzoles10aBalapiravir10aCURE ID10aCelgosivir10aChloroquine10aClarithromycin10aClavulanate10aDapsone10aDiethylcarbamazine10aDisulfiram10aDoxycycline10aDrug reprofiling10aDrug repurposing10aFluconazole10aImatinib10aIsavuconazonium10aItraconazole10aIvermectin10aKetoconazole10aLevamisole10aLumefantrine10aMebendazole10aMefloquine10aMoxidectin10aMoxifloxacin10aneglected topical diseases10aNitazoxanide10aOff-Label Use10aOxamniquine10aOxantel10aPiperaquine10aPosaconazole10aPraziquantel10aPyrantel pamoate10aRavuconazole10aRibavirin10aRifampicin10aRifapentine10aSparfloxacin10aStreptomycin10aTribendimidine10aUV-4B1 aPfarr K1 aKrome A1 aAl-Obaidi I1 aBatchelor H1 aVaillant M1 aHoerauf A1 aOpoku N1 aKuesel A00aThe pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use.  uhttps://parasitesandvectors.biomedcentral.com/counter/pdf/10.1186/s13071-023-05909-8.pdf  a1-220 v163 a<p>In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for 'off-label' use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with 'off-label' treatment of diseases with insufficient treatment options as pursued by the 'CURE ID' initiative.</p>
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