Immunity And The Antiviral Approach Against The Monkeypox Virus

Year 2022, , 94 - 100, 30.08.2022

Ferhan Kerget , Emine Parlak

https://doi.org/10.34084/bshr.1163122

Abstract

Human monkeypox is a zoonotic infection caused by the monkeypox virus (MPV), a member of the Orthopox genus in the family Poxviridae among the double-stranded DNA (dsDNA) viruses. It was first described in a nine-month-old baby in the Democratic Republic of the Congo in 1970. Since that time, Poxviridae have resulted in five epidemics in Central and West Africa, and sometimes in Europe and North America. Human infections in endemic regions have been described in association with close contact through hunting and skinning infected animals and or rodent infestations in the home. Human-to-human transmission has also been described in home contacts of index cases, particularly among those not vaccinated against smallpox. Transmission occurs through saliva, respiratory secretions, cutaneous lesions, bodily fluids, or contaminated objects. An increase in hosts susceptible to monkeypox has been observed following the eradication of smallpox and after routine smallpox vaccination. The smallpox vaccine is estimated to provide 85% protection against monkeypox disease.

MPV disease resolves with medical treatment in the majority of cases. Clinical care and support therapy must be provided in order to ameliorate symptoms and reduce complications. Patients with gastrointestinal symptoms involving fluid loss, such as vomiting and diarrhea, require oral or intravenous fluid therapy. Appropriate agent-specific antibiotic therapy must be given in case of secondary bacterial infection. Treatment can also be considered for monkeypox infection in atypical regions (such as the mouth, eyes, and genital region).

Various medications have been investigated, but their effectiveness remains uncertain. Antivirals thought to be potentially efficacious include tecovirimat (TCV), brincidofovir (BCV), and cidofovir (CDV). Although some experts may recommend dual TCV and CDV therapy in patients with severe disease, TCV is currently the preferred treatment.

There are currently two vaccines capable of reducing the risk of MPV disease. Vaccination within 14 days of contact is recommended for individuals with high-risk exposure. Post-expose vaccination is not indicated for individuals with low-risk exposure.

Keywords

monkeypox, treatment, immunization

Maymun Çiçeği Virüsüne Karşı Antiviral Yaklaşım ve Bağışıklık

Abstract

İnsan maymun çiçeği, çift sarmallı DNA (dsDNA) virüslerinin Poxviridae ailesindeki Orthopoxvirus cinsinin bir üyesi olan maymun çiçeği virüsünün neden olduğu zoonotik bir enfeksiyondur. İlk olarak 1970 yılında Demokratik Kongo Cumhuriyeti'nde dokuz aylık bir bebekte tanımlandı. O zamandan beri, Orta ve Batı Afrika'da ve bazen Avrupa ve Kuzey Amerika'da beş salgınla sonuçlandı. Endemik bölgelerdeki insan enfeksiyonları, enfekte hayvanlarla avlanma ve deri yüzme yoluyla yakın temas veya evde kemirgen istilası ile ilişkili olarak tanımlanmıştır. İnsandan insana bulaşma, özellikle çiçek hastalığına karşı aşılanmamış olanlar arasında, indeks vakaların ev temaslılarında da tanımlanmıştır. Bulaşma yolları, tükürük, solunum salgıları, cilt lezyonları, vücut sıvıları veya kontamine cisimlerle temasdır. Çiçek hastalığının eradikasyonundan ve rutin çiçek aşısından sonra Maymun çiçeği hastalığına karşı duyarlı konaklarda artış izlenmiştir. Çiçek aşısının maymun hastalığına karşı %85 koruma sağladığı tahmin edilmektedir.
Maymun çiçeği virüsü hastalığı (MÇVH) hastaların çoğunda medikal tedavi ile birlikte iyileşmektedir. Semptomları hafifletmek, komplikasyonları azaltmak için klinik bakım ve destekleyici tedavi verilmelidir. Kusma, ishal gibi sıvı kayıplarının olduğu gastrointestinal semptomları olan hastalara oral ya da intravenöz sıvı tedavisi gerekmektedir. Sekonder bakteriyel enfeksiyon izlendiği durumlarda etkene özgü ve uygun antibiyotik tedavisi verilmelidir. Atipik bölgelerdeki (örneğin ağız, gözler, genital bölge) maymun çiçeği enfeksiyonu için tedavi de düşünülebilir.
Bir takım ilaçlar denenmiştir ama etkinliği net değildir. Etkinliği olabileceği düşünülen antiviraller; Tecovirimat (TCV), brincidofovir (BCV) ve cidofovir (CDV)’ dir. Bazı uzmanlar şiddetli hastalığı olan hastalarda TCV ve CDV ile ikili tedavi önerebilse de, şu anda TCV tercih edilen tedavidir.
MÇVH riskini azaltabilecek iki mevcut aşı vardır. Yüksek risk maruziyeti olan bireylere temas sonrası 14 gün içinde aşılama önerilir. Maruziyet sonrası aşılama, düşük risk maruziyeti olanlar için endike değildir.

Keywords

maymun çiçeği, tedavi, bağışıklama

References

• Kaye D. FDA Approves the First Drug with an Indication for Treatment of Smallpox. OXFORD UNIV PRESS INC JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA; 2018.
• Grosenbach DW, Honeychurch K, Rose EA, et al. Oral tecovirimat for the treatment of smallpox. New England Journal of Medicine. 2018;379(1):44-53.
• Yang G, Pevear DC, Davies MH, et al. An orally bioavailable antipoxvirus compound (ST-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus challenge. Journal of virology. 2005;79(20):13139-13149.
• Duraffour S, Snoeck R, De Vos R, et al. Activity of the anti-orthopoxvirus compound ST-246 against vaccinia, cowpox and camelpox viruses in cell monolayers and organotypic raft cultures. Antiviral therapy. 2007;12(8):1205-1216.
• Huggins J, Goff A, Hensley L, et al. Nonhuman primates are protected from smallpox virus or monkeypox virus challenges by the antiviral drug ST-246. Antimicrobial agents and chemotherapy. 2009;53(6):2620-2625.
• Quenelle DC, Prichard MN, Keith KA, et al. Synergistic efficacy of the combination of ST-246 with CMX001 against orthopoxviruses. Antimicrobial agents and chemotherapy. 2007;51(11):4118-4124.
• Zaitseva M, Shotwell E, Scott J, et al. Effects of postchallenge administration of ST-246 on dissemination of IHD-J-Luc vaccinia virus in normal mice and in immune-deficient mice reconstituted with T cells. Journal of Virology. 2013;87(10):5564-5576.
• Siegrist EA, Sassine J. Antivirals with Activity Against Monkeypox: A Clinically Oriented Review. Clinical Infectious Diseases. 2022.
• Kern ER, Hartline C, Harden E, et al. Enhanced inhibition of orthopoxvirus replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir. Antimicrobial Agents and Chemotherapy. 2002;46(4):991-995.
• Ciesla SL, Trahan J, Wan WB, et al. Esterification of cidofovir with alkoxyalkanols increases oral bioavailability and diminishes drug accumulation in kidney. Antiviral research. 2003;59(3):163-171.
• Tippin TK, Morrison ME, Brundage TM, Momméja-Marin H. Brincidofovir is not a substrate for the human organic anion transporter 1: a mechanistic explanation for the lack of nephrotoxicity observed in clinical studies. Therapeutic Drug Monitoring. 2016;38(6):777.
• Hutson CL, Kondas AV, Mauldin MR, et al. Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model. MSphere. 2021;6(1):e00927-20.
• Chittick G, Morrison M, Brundage T, Nichols WG. Short-term clinical safety profile of brincidofovir: A favorable benefit–risk proposition in the treatment of smallpox. Antiviral research. 2017;143:269-277.
• De Clercq E. Cidofovir in the treatment of poxvirus infections. Antiviral research. 2002;55(1):1-13.
• Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369:1227-1236.
• Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and treatment of monkeypox. Drugs. 2022:1-7.
• Magee WC, Hostetler KY, Evans DH. Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrobial agents and chemotherapy. 2005;49(8):3153-3162.
• Hostetler KY. Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art. Antiviral research. 2009;82(2):A84-A98.
• Quenelle DC, Collins DJ, Kern ER. Efficacy of multiple-or single-dose cidofovir against vaccinia and cowpox virus infections in mice. Antimicrobial agents and chemotherapy. 2003;47(10):3275-3280.
• Simpson LA, Macdonald KE, Searle EF, et al. Rapid Response for Notification of Monkeypox Exposure, Exposure Risk Assessment and Stratification, and Symptom Monitoring. medRxiv. 2022.
• Organization WH. Surveillance, case investigation and contact tracing for monkeypox: interim guidance, 22 May 2022.
• Organization WH. Vaccines and immunization for monkeypox: interim guidance, 14 June 2022. 2022.