Table 2 Overview of small-molecule anti-infective drugs evaluated alone or in combination in the past 10 years for NTDs for which they are not registered or included in current WHO NTD strategies

WHO objective

NTD [Drugs included in WHO strategies] [1, 2]

Gaps in/actions required for anti-infective drugs as per 2030 roadmap [1, 2]

1.In at least Phase 2 development for regulatory approval or recently approved [2]

2.Evaluated in the past 10 years for off-label use as per ICTRP records

Eradication

 Yaws [azithromycin, benzathine benzylpenicillin]

–

1.None

2.None

 Guinea worm

[–]

Drugs for case management

1.None

2.None

Elimination of transmission

 Leprosy [rifampicin, dapsone, clofazimine, clarithromycin, minocycline or a quinolone (ofloxacin, levofloxacin or moxifloxacin)

New drugs or combinations

1.Bedaquiline

2.Sparfloxacin, acedapsone [21]

 Human African trypanosomiasis (gambiense) [fexinidazole, eflornithine-nifurtimox, pentamidine]

Safe and efficient single oral dose for both stages to help integration of treatment into primary health system

Oral formulation for children < 6 years

1.Acoziborole

2.None

 Onchocerciasis [ivermectin]

Macrofilaricide

Efficacy and safety of moxidectin in children and community settings

Safe drugs safe in Loa loa co-endemic areas

1.Moxidectin, emodepside, flubentylosin (TylAMac, ABBV-4083), oxantel pamoate, Oxfendazole

2.Albendazole in combination with ivermectin, albendazole and diethylcarbamazine in combination with ivermectin,

antibiotics (rifampicin, rifapentin, moxifloxacin); Loiasis focussed: imatinib (discontinued), levamisole

Elimination as a public health problem

 Rabies [none]

Monoclonal antibodies

Anti-virals and agents promoting entry of drugs, antibodies and immune effectors cells across the blood-brain barrier

1.None

2.None

 Trachoma [azithromycin, tetracycline]

–

1.None

2.None

 Chagas disease [benznidazole, nifurtimox]

Dosage and duration of benznidazole and nifurtimox treatment

Combination treatment, new drugs

1.Fexinidazole,

fosravuconazole (discontinued)

2.Azoles (itraconazole, fluconazole, ketoconazole, posaconazole and ravuconazole)

disulfiram

 Human African Trypanosomiasis (rhodesiense) [suramin, melarsoprol]

Safe, efficient treatments to replace toxic arsenic-based melarsoprol

1.Fexinidazole

2.None

 Visceral leishmaniasis [pentavalent antimonials, liposomal amphotericin B, paromomycin, miltefosine]

New, safe, cheap oral drugs not requiring cold chain

Shorter first line regimens in East Africa

More treatment options including combination treatments to mitigate risk of resistance

1.LXE408

2.None

 Lymphatic filariasis [albendazole, ivermectin, diethylcarbamazine]

Macrofilaricide, drug safe in Loa loa-infected individuals

1.Moxidectin

2.Antibiotics: doxycycline [22], rifampicin

 Schistosomiasis [praziquantel]

Improved praziquantel and pediatric formulation

New drugs to complement praziquantel in case of resistance

1.None

2.Antimalarial drugs (arterolane, piperaquine, artesunate, artemether, lumefantrine, mefloquine)

 Soil transmitted helminths including strongyloidiasis [albendazole, mebendazole]

More effective medicines and drug combinations against T. trichiura and hookworm infections

Drugs and drug combinations to be used in case of emergence of drug resistance

1.Moxidectin, emodepside, oxantel pamoate, oxfendazole

2.Ivermectin, ivermectin-albendazole combination, tribendimidine, pyrantel pamoate (montherapy or in combination with albendazole, mebendazole, oxantel), nitazoxanide

Control

 Dengue and chikungunya [none]

Anti-viral drugs

1.JNJ‑64281802

2.Chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B [23], ivermectin, doxycycline

 Buruli ulcer [rifampicin, clarithromycin, moxifloxacin]

New treatment options with reduced treatment duration and lower toxicity, especially for children

1.None

2.Streptomycin, amoxicillin/ clavulanate

 Mycetoma [antibiotics for actinomycetoma, antifungals for eumycetoma]

Better treatment regimens (shorter duration, higher efficacy)

1.Fosravuconazole

2.None

 Chromoblastomycosis and other deep mycoses [itraconazole, amphotericin B]

Prospectively obtained effectiveness of itraconazole and other antifungals;

Improved treatment regimens (shorter duration and increased efficacy)

1.None

2.Fluconazole, isavuconazonium

 Cutaneous leishmaniasis [pentavalent antimoniate (with or without allopurinol), liposomal amphotericin B, amphotericin B deoxycholate, paromomycin, miltefosine, pentamidine, fluconazole, ketoconazole]

Oral/topical treatment suitable for health center and community level use

1.Potentially LX408

2.Clarithromycin, dapsone (for others see [24,25,26,27])

 Echinococcosis [albendazole, mebendazole]

Identification of optimal albendazole treatment courses (indicates that drugs with improved efficacy would add value)

1.Oxfendazole, oxantel pamoate

2.None

 Foodborne trematodiasis [praziquantel, triclabendazole]

–

1. Oxantel pamoate

2.Tribendimidine, albendazole, mebendazole [28], nitazoxanide

 Taeniasis and cysticercosis [albendazole, praziquantel, niclosamide]

Efficacy of current treatment strategies

1.Oxfendazole

2.None

 Scabies [ivermectin, topical: permethrin, benzyl benzoate, malathion, sulphur]

Determine efficacy of single dose IVM for programmatic use and safe dose in children < 15 kg, < 90 cm or < 5 years

Identify alternative strategies for ivermectin MDA including for loiasis co-endemic areas

Evaluate moxidectin

1.Moxidectin

2.None