Archives of Virology

, Volume 161, Issue 11, pp 3073–3080 | Cite as

Efficacy and safety of interferon-α2b spray in the treatment of hand, foot, and mouth disease: a multicenter, randomized, double-blind trial

  • Hailong Lin
  • Leting Huang
  • Jian Zhou
  • Kaichun Lin
  • Hongjiao Wang
  • Xia Xue
  • Chan Xia
Original Article


Hand, foot, and mouth disease (HFMD) is a common infectious enterovirus disease, occurring mostly in infants and children younger than 7 years with potentially fatal complications. Therefore, we evaluated the clinical efficacy and safety of recombinant human interferon (IFN)-α2b spray for treating mild HFMD in 400 patients in a randomized, open, controlled clinical trial. The patients were randomized to the IFN-α2b spray and placebo groups, and their temperature, skin rash, oral lesions, and appetite were monitored, while pathogen levels and safety were evaluated with a 7-day follow-up. The mean age of the patients was 20.1 ± 10.2 months. The median duration of fever, oral ulcers or vesicles (or both), and skin rash in addition to median time to regain appetite in the IFN-α2b spray group were shorter than they were in the placebo group. The number of virus-positive cases differed statistically between the two groups for the three follow-up detections. Additionally, the incidences of adverse events (AEs) and severe AEs (SAEs) were not significantly different between the two groups, and the SAEs were evidently unrelated to the IFN-α2b spray or placebo. Therefore, the IFN-α2b spray is suitable for topical treatment of HFMD, and it rapidly relieved fever, promoted oral lesions and subsidence of rash, enhanced appetite, promoted disease recovery, and was safe for application.


Oral Lesion Oral Ulcer Mouth Disease Andrographolide Viral Infectious Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Medical Science and Technology Project of Zhejiang Province, China (No. 2013RCB011) and Hualida Pharmaceutical Co., Ltd., People’s Republic of China.

Compliance with ethical standards

Conflict of interest

We declare there is no financial and personal conflict of interest with other people or any organizations.


  1. 1.
    Wong SS, Yip CC, Lau SK, Yuen KY (2010) Human enterovirus 71 and hand, foot and mouth disease. Epidemiol Infect 138:1071–1089CrossRefPubMedGoogle Scholar
  2. 2.
    Sarma N (2013) Hand, foot, and mouth disease: current scenario and Indian perspective. Indian J Dermatol Venereol Leprol 79:165–175CrossRefPubMedGoogle Scholar
  3. 3.
    Rosencrantz R, Schilsky M (2011) Wilson disease: pathogenesis and clinical considerations in diagnosis and treatment. Semin Liver Dis J 31:245–259CrossRefGoogle Scholar
  4. 4.
    AbuBakar S, Chee HY, Al-Kobaisi MF, Xiaoshan J, Chua KB, Lam SK (1999) Identification of enterovirus 71 isolates from an outbreak of hand, foot and mouth disease (HFMD) with fatal cases of encephalomyelitis in Malaysia. Virus Res 61:1–9CrossRefPubMedGoogle Scholar
  5. 5.
    Centers for Disease Control and Prevention (CDC) (1998) Deaths among children during an outbreak of hand, foot, and mouth disease–Taiwan, Republic of China, April-July 1998. MMWR Morb Mortal Wkly Rep 47:629–632Google Scholar
  6. 6.
    Ding NZ, Wang XM, Sun SW, Song Q, Li SN, He CQ (2009) Appearance of mosaic enterovirus 71 in the 2008 outbreak of China. Virus Res 145:157–161CrossRefPubMedGoogle Scholar
  7. 7.
    Wu Y, Yeo A, Phoon MC, Tan EL, Poh CL, Quak SH, Chow VT (2010) The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains. Int J Infect Dis 14:e1076–e1081CrossRefPubMedGoogle Scholar
  8. 8.
    Zhuang ZC, Kou ZQ, Bai YJ, Cong X, Wang LH, Li C, Zhao L, Yu XJ, Wang ZY, Wen HL (2015) Epidemiological Research on Hand, Foot, and Mouth Disease in Mainland China. Viruses 7:6400–6411CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bian L, Wang Y, Yao X, Mao Q, Xu M, Liang Z (2015) Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks world wide. Expert Rev Anti Infect Ther. 13:1061–1071CrossRefPubMedGoogle Scholar
  10. 10.
    Mao QY, Wang Y, Bian L, Xu M, Liang Z (2016) EV71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (HFMD). Expert Rev Vaccines. 14:1–8Google Scholar
  11. 11.
    Caine EA, Fuchs J, Das SC, Partidos CD, Osorio JE (2015) Efficacy of a trivalent hand, foot, and mouth disease vaccine against enterovirus 71 and coxsackieviruses A16 and A6 in mice. Viruses 7:5919–5932CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ershov FI, Narovlyansky AN (2015) Usage of interferon inducers during viral infections. Vopr Virusol 60:5–10PubMedGoogle Scholar
  13. 13.
    Shul’diakov AA, Barkhatova TS, Satarova SA, Perminova TA (2012) Herpetic infection in patients with psoriasis: the improvement of therapy. Klin Med (Mosk) 90:61–63Google Scholar
  14. 14.
    Tan CW, Lai JK, Sam IC, Chan YF (2014) Recent developments in antiviral agents against enterovirus 71 infection. J Biomed Sci 21:14CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhang D, Lu J, Lu J (2010) Enterovirus 71 vaccine: close but still far. Int J Infect Dis 14:e739–e743CrossRefPubMedGoogle Scholar
  16. 16.
    Larke RP (1966) Interferon: a changing picture. Can Med Assoc J. 94:23–31PubMedPubMedCentralGoogle Scholar
  17. 17.
    Stetson DB, Medzhitov R (2006) Type I interferons in host defense. Immunity. 25:373–381CrossRefPubMedGoogle Scholar
  18. 18.
    Gonzalez-Navajas JM, Lee J, David M, Raz E (2012) Immunomodulatory functions of type I interferons. Nat Rev Immunol 12:125–135PubMedPubMedCentralGoogle Scholar
  19. 19.
    Aghemo A, Rumi MG, Colombo M (2010) Pegylated interferons alpha2a and alpha2b in the treatment of chronic hepatitis C. Nature reviews Gastroenterology & hepatology. 7:485–494CrossRefGoogle Scholar
  20. 20.
    Lavanchy D (2014) Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral hepatit 11:97–107CrossRefGoogle Scholar
  21. 21.
    Boasso A, Type I (2013) Interferon at the interface of antiviral immunity and immune regulation: the curious case of HIV-1. Scientifica 2013:580968CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhao HL, Yao XQ, Xue C, Wang Y, Xiong XH, Liu ZM (2008) Increasing the homogeneity, stability and activity of human serum albumin and interferon-alpha2b fusion protein by linker engineering. Protein Express Purific 61:73–77CrossRefGoogle Scholar
  23. 23.
    Russell CD, Schwarze J (2014) The role of pro-resolution lipid mediators in infectious disease. Immunology 141:166–173CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Khademian M, Farhangpajouh N, Shahsanaee A, Bahreynian M, Mirshamsi M, Kelishadi R (2014) Effects of zinc supplementation on subscales of anorexia in children: a randomized controlled trial. Pak J Med Sci 30:1213–1217PubMedPubMedCentralGoogle Scholar
  25. 25.
    Zhuang ZC, Kou ZQ, Bai YJ, Cong X, Wang LH, Li C, Zhao L, Yu XJ, Wang ZY, Wen HL (2015) Epidemiological research on hand, foot, and mouth disease in Mainland China. Viruses 7:6400–6411CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Gantt S, Yao L, Kollmann TR, Casper C, Zhang J, Self SG (2013) Implications of Age-Dependent Immune Responses to Enterovirus 71 Infection for Disease Pathogenesis and Vaccine Design. J Pediatric Infect Dis Soc 2:162–170CrossRefPubMedGoogle Scholar
  27. 27.
    Tian H, Yang QZ, Liang J, Dong SY, Liu ZJ, Wang LX (2012) Clinical features and management outcomes of severe hand, foot and mouth disease. Med Princ Pract 21:355–359CrossRefPubMedGoogle Scholar
  28. 28.
    Zhu Q, Hao Y, Ma J, Yu S, Wang Y (2011) Surveillance of hand, foot, and mouth disease in mainland China (2008–2009). Biomed Environ Sci 24:349–356PubMedGoogle Scholar
  29. 29.
    Fang Y, Wang S, Zhang L, Guo Z, Huang Z, Tu C, Zhu BP (2014) Risk factors of severe hand, foot and mouth disease: a meta-analysis. Scand J Infect Dis 46:515–522CrossRefPubMedGoogle Scholar
  30. 30.
    Zeng H, Wen F, Gan Y, Huang W (2012) MRI and associated clinical characteristics of EV71-induced brainstem encephalitis in children with hand-foot-mouth disease. J Neuroradiol 54:623–630CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Department of Pediatric InfectionThe Second Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
  2. 2.Department of PediatricsThe first people’s Hospital of YongkangJinhuaChina
  3. 3.Department of PediatricsThe Affiliated Children’s Hospital of Zhejiang University Medical CollegeHangzhouChina

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