Increased use of ivermectin in Brazil and the risk of scabies outbreaks
Keywords:
Ivermectin; Scabies; Drug resistance.Abstract
Following the onset of the pandemic caused by SARS-CoV-2, ivermectin was identified as a drug with antiviral potential for treating patients - initially hospitalized and then outpatients - with COVID-19. However, ivermectin may be related to resistance development mechanisms of parasites such as Sarcoptes scabiei. Although the consumption of this antiparasitic has increased nearly 10 times in Brazil, the contamination and death curves related to COVID-19 did not change. Judgments from the Brazilian Ministry of Health and the pharmaceutical industry, added to scientific evidence unfavorable to the outpatient use of ivermectin, were not able to prevent prescription and self-medication based on this drug. Furthermore, factors such as evidence of resistance of Sarcoptes scabiei to ivermectin and intensification of factors related to the incidence of scabies such as poverty, low education, family confinement and increased sharing of household objects can lead to the outbreak of scabies waves. This increase can be especially harmful to low-income pediatric patients, as well to health risks for the general population. The risk of increased resistance to ivermectin adds to the scenario presented here, being an alert for measures to control its use and monitoring of this drug to be discussed and implemented.
References
Ashour D. S. (2019). Ivermectin: From theory to clinical application. International journal of antimicrobial agents, 54(2), 134–142. https://doi.org/10.1016/j.ijantimicag.2019.05.003
Bhat, S., Mounsey, K., Liu, X., & Walton, S. (2017). Host immune responses to the itch mite, Sarcoptes scabiei, in humans. Parasites & Vectors, 10(1). 10.1186/s13071-017-2320-4
Caly, L., Druce, J., Catton, M., Jans, D., & Wagstaff, K. (2020). The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research, 178, 104787. 10.1016/j.antiviral.2020.104787
CDC - Scabies - Resources for Health Professionals - Medications. (2021). https://www.cdc.gov/parasites/scabies/health_professionals/meds.html
Cestari, T., & Martignago, B. (2005). Scabies, pediculosis, bedbugs, and stinkbugs: uncommon presentations. Clinics In Dermatology, 23(6), 545-554. 10.1016/j.clindermatol.2005.01.013
Chowdhury, A. (2021). A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients. Eurasian Journal Of Medicine And Oncology. 10.14744/ejmo.2021.16263
Currie, B., Connors, C., & Krause, V. (1994). Scabies programs in Aboriginal communities. Medical Journal Of Australia, 161(10), 636-637. 10.5694/j.1326-5377.1994.tb127655.x
Currie, B., Harumal, P., McKinnon, M., & Walton, S. (2004). First Documentation of In Vivo and In Vitro Ivermectin Resistance in Sarcoptes scabiei. Clinical Infectious Diseases, 39(1), e8-e12. 10.1086/421776
Elgazzar, A., Hany, B., Youssef, S., Hafez, M., Moussa, H., & Eltaweel, A. (2020). Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic. https://doi.org/10.21203/rs.3.rs-100956/v2
Engelman, D., & Steer, A. (2018). Control Strategies for Scabies. Tropical Medicine And Infectious Disease, 3(3), 98. 10.3390/tropicalmed3030098
Garegnani, L., Madrid, E., & Meza, N. (2021). Misleading clinical evidence and systematic reviews on ivermectin for COVID-19. BMJ Evidence-Based Medicine, bmjebm-2021-111678. 10.1136/bmjebm-2021-111678
Gheibi, N., Shakhsi Niaee, M., Namdar, P., Allami, A., Zolghadr, L., & Javadi, A. et al. (2021). Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial. Asian Pacific Journal Of Tropical Medicine, 14(6), 266. 10.4103/1995-7645.318304
Gonzalez, J., González Gámez, M., Enciso, E., Maldonado, R., Hernández Palacios, D., & Dueñas Campos, S. et al. (2021). Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial. 10.1101/2021.02.18.21252037
Guzzo, C., Furtek, C., Porras, A., Chen, C., Tipping, R., & Clineschmidt, C. et al. (2013). Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects. Journal Of Clinical Pharmacology, 42(10), 1122-1133. 10.1177/009127002401382731
Hariyanto, T., Halim, D., Rosalind, J., Gunawan, C., & Kurniawan, A. (2021). Ivermectin and outcomes from Covid‐19 pneumonia: A systematic review and meta‐analysis of randomized clinical trial studies. Reviews In Medical Virology. 10.1002/rmv.2265
Hashim, H., Maulood, M., Rasheed, A., Fatak, D., Kabah, K., & Abdulamir, A. (2020). Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq. 10.1101/2020.10.26.20219345
Heidary, F., & Gharebaghi, R. (2020). Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. The Journal Of Antibiotics, 73(9), 593-602. 10.1038/s41429-020-0336-z
Hicks, M., & Elston, D. (2009). Scabies. Dermatologic Therapy, 22(4), 279-292. 10.1111/j.1529-8019.2009.01243.x
Huffam, S., & Currie, B. (1998). Ivermectin for Sarcoptes scabiei hyperinfestation. International Journal Of Infectious Diseases, 2(3), 152-154. 10.1016/s1201-9712(98)90118-7
Kishoria, N., Mathur, S., Parmar, V., Kaur, R., Agarwal, H., Parihar, B., & Verma, S. (2020). Ivermectin As Adjuvant To Hydroxycholoroquine In Patients Resistant To Standard Treatment For Sars-Cov-2: Results Of An Open-Label Randomized Clinical Study. Paripex Indian Journal Of Research, 1-4. 10.36106/paripex/4801859
Leung, A., Lam, J., & Leong, K. (2020). Scabies: A Neglected Global Disease. Current Pediatric Reviews, 16(1), 33-42. 10.2174/1573396315666190717114131.
Lopes, J. G. de A., Santos, D. F., Cabral, H. R., Silva Júnior, P. R., Silva, A. A., Moura, Y. da S., Silva, C. E. N. D., & Leal, A. A. de F. (2020). Ivermectin as a possible ally in the treatment of COVID-19: perspectives on its antiviral action. Research, Society and Development, 9(8), e892986234. https://doi.org/10.33448/rsd-v9i8.6234
López-Medina, E., López, P., Hurtado, I., Dávalos, D., Ramirez, O., & Martínez, E. et al. (2021). Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19. JAMA, 325(14), 1426. 10.1001/jama.2021.3071
Mahmud, R., Rahman, M., Alam, I., et al. (2020). Clinical trial of ivermectin plus doxycycline for the treatment of confirmed covid‐19 infection. ClinicalTrials.gov: NCT04523831.
Mega, E. (2020). Latin America’s embrace of an unproven COVID treatment is hindering drug trials. Nature, 586(7830), 481-482. 10.1038/d41586-020-02958-2
Mohan, A., Tiwari, P., Suri, T, et al. Ivermectin in mild and moderate COVID‐19 (RIVETCOV): a randomized, placebo‐controlled trial. Research Square. 2021. https://doi.org/10.21203/rs.3.rs‐191648/v1
Molento, M. (2009). Parasite control in the age of drug resistance and changing agricultural practices. Veterinary Parasitology, 163(3), 229-234. 10.1016/j.vetpar.2009.06.007
Molento, M. (2021). Ivermectin against COVID-19: The unprecedented consequences in Latin America. One Health, 13, 100250. 10.1016/j.onehlt.2021.100250
Momekov, G., & Momekova, D. (2020). Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens. Biotechnology & Biotechnological Equipment, 34(1), 469-474. 10.1080/13102818.2020.1775118
Mounsey, K., Holt, D., McCarthy, J., Currie, B., & Walton, S. (2009). Longitudinal Evidence of Increasing In Vitro Tolerance of Scabies Mites to Ivermectin in Scabies-Endemic Communities. Archives Of Dermatology, 145(7). 10.1001/archdermatol.2009.125
Mounsey, K., Holt, D., McCarthy, J., Currie, B., & Walton, S. (2008). Scabies: molecular perspectives and therapeutic implications in the face of emerging drug resistance. Future Microbiology, 3(1), 57-66. 10.2217/17460913.3.1.57.
Mounsey, K. E., & McCarthy, J. S. (2013). Treatment and control of scabies. Current opinion in infectious diseases, 26(2), 133–139. https://doi.org/10.1097/QCO.0b013e32835e1d57.
Okumus, N., Demirtürk, N., Çetinkaya, R., Güner, R., Avcı, İ., & Orhan, S. et al. (2021). Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients. BMC Infectious Diseases, 21(1). 10.1186/s12879-021-06104-9
Pasternak J (2008). Perspectives and therapeutic implications in treatment of scabies. Einstein 6(3):380-381.
Peña‐Silva, R., Duffull, S., Steer, A., Jaramillo‐Rincon, S., Gwee, A., & Zhu, X. (2020). Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID‐19. British Journal Of Clinical Pharmacology, 87(3), 1589-1590. 10.1111/bcp.14476
Podder, C., Chowdhury, N., Sina, M., & Haque, W. (2021). Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study. IMC Journal Of Medical Science, 14(2), 11-18. 10.3329/imcjms.v14i2.52826
Pott-Junior, H., Paoliello, M., Miguel, A., da Cunha, A., de Melo Freire, C., & Neves, F. et al. (2021). Use of ivermectin in the treatment of Covid-19: A pilot trial. Toxicology Reports, 8, 505-510. 10.1016/j.toxrep.2021.03.003
Ravikirti, Roy, R., Pattadar, C., Raj, R., Agarwal, N., & Biswas, B. et al. (2021). Ivermectin as a potential treatment for mild to moderate COVID-19 – A double blind randomized placebo-controlled trial. 10.1101/2021.01.05.21249310
Pfarma. (2021). https://pfarma.com.br/coronavirus/6213-merck-msd-ivermectina-covid19.html
Romani, L., Steer, A., Whitfeld, M., & Kaldor, J. (2015). Prevalence of scabies and impetigo worldwide: a systematic review. The Lancet Infectious Diseases, 15(8), 960-967. 10.1016/s1473-3099(15)00132-2
Rosumeck, S., Nast, A., & Dressler, C. (2018). Ivermectin and permethrin for treating scabies. Cochrane Database Of Systematic Reviews. 10.1002/14651858.cd012994
Sanei-Dehkordi, A., Soleimani-Ahmadi, M., Zare, M., & Jaberhashemi, S. (2021). Risk factors associated with scabies infestation among primary schoolchildren in a low socio-economic area in southeast of Iran. BMC Pediatrics, 21(1). 10.1186/s12887-021-02721-0
Scaramuzzo, M. (2021). Venda de remédios do ‘kit covid’ movimenta R$ 500 mi em 2020. https://valor.globo.com/empresas/noticia/2021/02/05/venda-de-remedios-do-kit-covid-movimenta-r-500-mi-em-2020.ghtml
Secretaria Municipal de Saúde. (2020). Protocolo de tratamento precoce e profilaxia da infecção por covid-19. Campo Grande- MS.
Secretaria Municipal de Saúde. (2020). Protocolo para a abordagem inicial e seguimento clínico ambulatorial dos pacientes acometidos pelo SARS-CoV-2, no âmbito da Atenção Básica (AB). Boa Vista.
Shah Bukhari, K., Asghar, A., Perveen, N., Hayat, A., Mangat, S., & Butt, K. et al. (2021). Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease. 10.1101/2021.02.02.21250840
Shouman W, Nafae RM, Ragab M, et al. Use of Ivermectin as a prophylactic option in asymptomatic family close contacts for patients with COVID‐19. ClinicalTrials.gov. 2020. NCT04422561.
Sohrabi, C., Alsafi, Z., O'Neill, N., Khan, M., Kerwan, A., & Al-Jabir, A. et al. (2020). World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). International Journal Of Surgery, 76, 71-76. 10.1016/j.ijsu.2020.02.034
Solomons, S. (2021). Do Not Use Ivermectin for Animals as Treatment for COVID-19 in Humans. https://www.fda.gov/animal-veterinary/product-safety-information/fda-letter-stakeholders-do-not-use-ivermectin-intended-animals-treatment-covid-19-humans.
Sousa, F. das C. A., Santos, I. S. dos, Barbosa, S. M., Mesquita, A. K. de F., Silva, W. C., Silva, F. L., Reis, L. C. de M., Sousa, M. A. A. de, Medeiros, J. da S., & Figueredo, E. G. (2021). Analysis of drug consumption that suffered changes in its health regulation during the COVID-19 pandemic. Research, Society and Development, 10(7), e42710716758. https://doi.org/10.33448/rsd-v10i7.16758.
Thompson, R., Westbury, S., & Slape, D. (2021). Paediatrics: how to manage scabies. Drugs In Context, 10, 1-13. 10.7573/dic.2020-12-3
Turkmen, D., Altunisik, N., Mantar, I., Durmaz, I., Sener, S., & Colak, C. (2020). Comparison of patients’ diagnoses in a dermatology outpatient clinic during the COVID‐19 pandemic period and pre‐pandemic period. International Journal Of Clinical Practice, 75(4). 10.1111/ijcp.13948.
van den Hoek, J. A., van de Weerd, J. A., Baayen, T. D., Molenaar, P. M., Sonder, G. J., van Ouwerkerk, I. M., & de Vries, H. J. (2008). A persistent problem with scabies in and outside a nursing home in Amsterdam: indications for resistance to lindane and ivermectin. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 13(48), 19052.
Yeoh, D., Bowen, A., & Carapetis, J. (2016). Impetigo and scabies – Disease burden and modern treatment strategies. Journal Of Infection, 72, S61-S67. 10.1016/j.jinf.2016.04.024
Zaheer, T., Pal, K., Abbas, R., & Torres, M. (2021). COVID-19 and Ivermectin: Potential threats associated with human use. Journal Of Molecular Structure, 1243, 130808. 10.1016/j.molstruc.2021.130808
Zeeshan Khan Chachar, A., Ahmad Khan, K., Asif, M., Tanveer, K., Khaqan, A., & Basri, R. (2020). Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients. International Journal Of Sciences, 9(09), 31-35. 10.18483/ijsci.2378
Zein, A., Sulistiyana, C., Raffaelo, W., & Pranata, R. (2021). Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15(4), 102186. 10.1016/j.dsx.2021.102186
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Copyright (c) 2021 Alfredo Dias de Oliveira-Filho; Lucas Tenorio Carmo do Nascimento Bezerra; Natalia da Silva Alves; Sabrina Joany Felizardo Neves
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