key: cord-0729617-ccmaa3dn authors: Perez-Garcia, Luis A.; Mejias-Carpio, Isis E.; Delgado-Noguera, Lourdes A.; Manzanarez-Motezuma, Jean P.; Escalona-Rodriguez, Maria A.; Sordillo, Emilia M.; Mogollon-Rodriguez, Euler A.; Hernandez-Pereira, Carlos E.; Marquez-Colmenarez, Marilianna C.; Paniz-Mondolfi, Alberto E. title: Ivermectin: repurposing a multipurpose drug for Venezuela's humanitarian crisis date: 2020-05-29 journal: Int J Antimicrob Agents DOI: 10.1016/j.ijantimicag.2020.106037 sha: e53fb2ca00de29a43fa47604c03eb4338f7f8a0d doc_id: 729617 cord_uid: ccmaa3dn Abstract For decades, Ivermectin (IVM) has been recognized as a robust antiparasitic drug with excellent tolerance and safety profiles. Historically it has been used as the drug of choice for onchocerciasis and lymphatic filariasis global elimination programs. IVM is also a standard treatment against intestinal helminths and ectoparasites given its action as an oral insecticide. The current humanitarian crisis in Venezuela is a regional public health threat that requires immediate action. Venezuela's public health system has now crumbled due to a 70% shortage of medicines in public hospitals, low vaccination campaigns, and the massive exodus of medical personnel. Herein we discuss the repurposing of IVM to attenuate the burden imposed by the most prevalent neglected tropical diseases (NTDs) in Venezuela including soil-transmitted helminths, ectoparasites and, possibly, vector-borne diseases such as malaria. Additionally, novel experimental evidence has shown that IVM is active and efficacious against Chagas disease, Leishmaniases, arboviruses, and SARS-CoV-2 in vitro. In crisis-hit Venezuela, all of the aforementioned infectious diseases are public health emergencies that have been long ignored and that also require immediate attention. IVM's versatile nature could serve as a powerful tool to tackle the multiple overlapping endemic and emergent diseases that affect Venezuela today. The repurposing of this multipurpose drug would be without a doubt a timely therapeutical approach to help mitigate the tremendous burden of NTDs nationwide. For decades, Ivermectin (IVM) has been recognized as a robust antiparasitic drug with excellent 32 tolerance and safety profiles. Historically it has been used as the drug of choice for 33 onchocerciasis and lymphatic filariasis global elimination programs. IVM is also a standard 34 treatment against intestinal helminths and ectoparasites given its action as an oral insecticide. 35 The current humanitarian crisis in Venezuela is a regional public health threat that requires 36 immediate action. Venezuela"s public health system has now crumbled due to a 70% shortage of 37 medicines in public hospitals, low vaccination campaigns, and the massive exodus of medical 38 personnel. Herein we discuss the repurposing of IVM to attenuate the burden imposed by the 39 most prevalent neglected tropical diseases (NTDs) in Venezuela including soil-transmitted 40 helminths, ectoparasites and, possibly, vector-borne diseases such as malaria. Additionally, novel 41 experimental evidence has shown that IVM is active and efficacious against Chagas disease, 42 Leishmaniases, arboviruses, and SARS-CoV-2 in vitro. In crisis-hit Venezuela, all of the 43 aforementioned infectious diseases are public health emergencies that have been long ignored 44 and that also require immediate attention. IVM"s versatile nature could serve as a powerful tool 45 to tackle the multiple overlapping endemic and emergent diseases that affect Venezuela today. The repurposing of this multipurpose drug would be without a doubt a timely therapeutical 47 approach to help mitigate the tremendous burden of NTDs nationwide. infections such as the Leishmaniases, American trypanosomiasis (Chagas disease) and malaria. In addition, tropical areas are fertile ground for a plethora of endemic viral (mostly arboviral) 65 infections such as Dengue, Zika, Yellow fever, and Chikungunya [2] . The history of IVM as a deworming drug is well documented. IVM was derived from the 67 avermectins produced by Streptomyces avermitilis, an actinobacterium isolated by Satoshi Although IVM is currently regarded as a robust antiparasitic drug, its myriad alternative uses 79 continue to be underestimated. And, despite its excellent tolerance and safety profile that made it Hereby we propose a call for action to use IVM as a strategy to combat the most preponderant 84 NTDs and other emergent diseases in crisis-hit Venezuela. Venezuela: a desperate call for action 86 The current humanitarian crisis in Venezuela is a regional public health threat and requires 87 immediate action. Venezuela"s public health system has now crumbled due to the 70% deficit in resources, and has led to a spillover to neighboring countries [2] . but it can also inhibit parasite replication inside the vector [10,11]. Therefore, it can rapidly 137 reduce the mean incidence of malaria infections [1, 9] . For these reasons, repurposing orally-138 administered IVM could be a sensible complement to the long-established vector control 139 protocols [1, 9] . This is particularly appropriate for Venezuela, where national malaria incidence 140 increased 10-fold over a decade, and where persistent hot-spots make diseases control 141 particularly difficult [2] . Venezuela [2] . Although no effective all-stage antitrypanosomal drug has been described to date, 166 IVM has been reported to increase triatomine mortality [1] . Thus, IVM is emerging as a potential where these diseases overlap in distribution [20] . Venezuela is in urgent need of humanitarian assistance. Despite recognition of the severity of the 215 crisis by international organizations, efforts thus far have been unable to mitigate the crisis. 216 Moreover, Venezuela's refugee crisis, the largest ever reported in the Western hemisphere is Ivermectin : enigmatic multifaceted " wonder " drug continues to surprise and 242 exceed expectations Venezuela"s humanitarian crisis, resurgence of vector-borne 245 diseases, and implications for spillover in the region Mass treatment with ivermectin: An underutilized public health 248 strategy Resurgence of Vaccine-Preventable Diseases in Venezuela as a 251 Regional Public Health Threat in the Americas Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian 255 focus Diagnosis of 260 intestinal parasites in a rural community of Venezuela: Advantages and disadvantages of 261 using microscopy or RT-PCR World health organization model list of essential medicines. Ment Holist 264 Heal Some Int Perspect Advancing the repurposing of ivermectin for malaria Ivermectin inhibits the sporogony of 268 Plasmodium falciparum in Anopheles gambiae Promising approach to reducing Malaria transmission by ivermectin: Sporontocidal effect 271 against Plasmodium vivax in the South American vectors Anopheles aquasalis and 272 Ivermectin-derived leishmanicidal compounds Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity : new prospects for an old drug The FDA-approved Drug 281 Ivermectin inhibits the replication of SARS-CoV-2 in vitro The 284 role of water, sanitation and hygiene interventions in reducing soil-transmitted helminths: 285 Interpreting the evidence and identifying next steps A framework for 288 targeting water, sanitation and hygiene interventions in pastoralist populations in the Afar 289 region of Ethiopia Efficacy of recommended drugs against soil transmitted 292 helminths: systematic review and network meta-analysis The impact of a school-295 based hygiene, water quality and sanitation intervention on soil-transmitted helminth 296 reinfection: a cluster-randomized trial Efficacy 299 and safety of co-administered ivermectin plus albendazole for treating soil-transmitted 300 helminths: A systematic review, meta-analysis and individual patient data analysis Rationale for the coadministration of albendazole and ivermectin to humans for malaria 304 parasite transmission control Workshop on integrating deworming 307 intervention into preschool child packages in the