Activity of Nitazoxanide Against Viral Gastroenteritis: A Systematic Review

Document Type : Systematic Review

Authors

1 Division of Infectious Diseases, Mayo Clinic, Rochester, USA

2 Nebraska Medical Center, Omaha, USA

3 Hematology and Oncology, Mayo Clinic, Rochester, USA

Abstract

Introduction: Nitazoxanide is an oral anti-parasitic agent that has been found to have broad antiviral activity. Its role in the treatment of viral gastroenteritis is not well-studied. Given the worldwide prevalence of viral gastroenteritis, particularly in developing nations, a systematic review of this topic would be valuable.
Methods: A formal literature search with the assistance of a reference librarian included randomized controlled trials, cohort studies, case-control studies, and case reports. Studies were included if they pertained to nitazoxanide use for viral gastroenteritis and excluded if nitazoxanide was used for parasitic or other viral illnesses.
Results: Based on inclusion and exclusion criteria, 5 randomized controlled trials (2 in Egypt and 1 each in Peru, India, and Bolivia) were included in the systematic review. Four of the studies enrolled children only; one study included adults. All studies noted a statistically significant reduction in time from the first dose of nitazoxanide to resolution of illness (approximately one to 2 days) in patients compared to the receiving placebos (approximately 3 days). There were 9 case series or reports on nitazoxanide use for viral gastroenteritis in immunocompromised hosts; of these, only one case reported a noticeable effect of nitazoxanide in reducing symptom duration and severity.
Conclusion: Despite the limited number of studies and the potential risk of bias introduced by the funding source, a benefit of nitazoxanide in reducing duration of illness from viral gastroenteritis was demonstrated for immunocompetent children. Randomized controlled trials are needed to elucidate the role of nitazoxanide for treating viral gastroenteritis in immunocompromised hosts.

Keywords

References

Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014;110:94-103. doi:10.1016/j.antiviral.2014.07.014.
Fox LM, Saravolatz LD. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis 2005;40:1173-1180. doi: 10.1086/428839.
La Frazia S, Ciucci A, Arnoldi F, et al. Thiazolides, a new class of antiviral agents effective against rotavirus infection, target viral morphogenesis, inhibiting viroplasm formation. J Virol 2013;87(20):11096-11106. doi: 10.1128/JVI.01213-13.
Rossignol JF. Thiazolides: a new class of antiviral drugs. Expert Opin Drug Metab Toxicol. 2009;5:667-674. doi: 10.1517/17425250902988487.
Fletcher SM, McLaws ML, Ellis JT. Prevalence of gastrointestinal pathogens in developed and developing countries: systematic review and meta-analysis. J Public Health Res 2013;2(1):42-53. doi: 10.4081/jphr.2013.e9.
Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis. 2003;9(5):565-572. doi:10.3201/eid0905.020562.
Lopman B. Global Burden of Norovirus and Prospects for Vacine Development. CDC; 2015.
van Beek J, van der Eijk AA, Fraaij PL, et al. Chronic norovirus infection among solid organ recipients in a tertiary care hospital, the Netherlands, 2006-2014. Clin Microbiol Infect. 2017;23(4):265. e9-265.e13. doi: 10.1016/j.cmi.2016.12.010.
Bok K, Green KY. Norovirus gastroenteritis in immunocompromised patients. N Engl J Med. 2012;367:2126-2132. doi:10.1056/NEJMra1207742.
Rossignol JF, Abu-Zekry M, Hussein A, Santoro MG. Effect of nitazoxanide for treatment of severe rotavirus diarrhoea: randomised double-blind placebo-controlled trial. Lancet. 2006;368(9530):124-129. doi: 10.1016/S0140-6736(06)68852-1.
Rossignol JF, El-Gohary YM. Nitazoxanide in the treatment of viral gastroenteritis: a randomized double-blind placebo-controlled clinical trial. Aliment Pharm Therap. 2006;24:1423-1430. doi: 10.1111/j.1365-2036.2006.03128.x.
Teran CG, Teran-Escalera CN, Villarroel P. Nitazoxanide vs. probiotics for the treatment of acute rotavirus diarrhea in children: a randomized, single-blind, controlled trial in Bolivian children. Int J Infect Dis. 2009;13(4):518-523. doi: 10.1016/j.ijid.2008.09.014.
Rossignol JF, Lopez-Chegne N, Julcamoro LM, Carrion ME, Bardin MC. Nitazoxanide for the empiric treatment of pediatric infectious diarrhea. Trans R Soc Trop Med Hyg. 2012;106(3):167-173. doi: 10.1016/j.trstmh.2011.11.007.
Mahapatro S, Mahilary N, Satapathy AK, Das RR. Nitazoxanide in acute rotavirus diarrhea: a randomized control trial from a developing country. J Trop Med. 2017;2017:7942515. doi: 10.1155/2017/7942515.
Avery RK, Lonze BE, Kraus ES, Marr KA, Montgomery RA. Severe chronic norovirus diarrheal disease in transplant recipients: Clinical features of an under-recognized syndrome. Transpl Infect Dis 2017;19(2):e12674. doi: 10.1111/tid.12674.
Morris J, Morris C. Nitazoxanide is effective therapy for norovirus gastroenteritis after chemotherapy and hematopoietic stem cell transplantation (HSCT). Blood 2013;122:4581.
Patte M, Canioni D, Frange P, Rabant M, Talbotec C, Lacaille F. Severity of diarrhoea due to norovirus in children after intestinal transplantation. Pediatr Transplant. 2017 May 16. doi:10.1111/petr.12930.
Jurgens PT, Allen LA, Ambardekar AV, McIlvennan CK. Chronic norovirus infections in cardiac transplant patients: considerations for evaluation and management. Prog Transplant. 2017;27(1):69- 72. doi: 10.1177/1526924816679843.
Capizzi T, Makari-Judson G, Steingart R, Mertens WC. Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases. BMC Infect Dis. 2011;11:131. doi: 10.1186/1471-2334-11-131.
Crawford C. Immunocompromised transplant patient shows promising findings to serum-derived bovine immunoglobulin/ protein isolate (SBI). Am J Gastroenterol. 2014;109:S444.
Echenique IA, Stosor V, Gallon L, Kaufman D, Qi C, Zembower TR. Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus. Transplant Infectious Disease 2016;18(1):98-104. doi: 10.1111/tid.12472.
Kempf B, Edgar JD, Mc Caughey C, Devlin LA. Nitazoxanide is an ineffective treatment of chronic norovirus in patients with x-linked agammaglobulinemia and may yield false-negative polymerase chain reaction findings in stool specimens. J Infect Dis. 2017;215(3):486-487. doi: 10.1093/infdis/jiw497.
Siddiq DM, Koo HL, Adachi JA, Viola GM. Norovirus gastroenteritis successfully treated with nitazoxanide. J Infect. 2011;63:394-397. doi: 10.1016/j.jinf.2011.08.002.
Keeffe EB, Rossignol JF. Treatment of chronic viral hepatitis with nitazoxanide and second generation thiazolides. World J Gastroenterol. 2009;15(15):1805-1808. doi:10.3748/wjg.15.1805.
Arun Babu T, Venkatesh C. Nitazoxanide use in rota viral diarrhea. Cure or controversy? Indian J Pediatr 2010;77(12):1450. doi: 10.1007/s12098-010-0268-x.
Ramani S, Kang G. Viruses causing childhood diarrhoea in the developing world. Curr Opin Infect Dis. 2009;22(5):477-482. doi: 10.1097/QCO.0b013e328330662f.
Rodriguez L, Cervantes E, Ortiz R. Malnutrition and gastrointestinal and respiratory infections in children: a public health problem. Int J Environ Res Public Health. 2011;8(4):1174-1205. doi:10.3390/ijerph8041174.
Woodward J, Gkrania-Klotsas E, Kumararatne D. Chronic norovirus infection and common variable immunodeficiency. Clin Exp Immunol. 2017;188(3):363-370. doi: 10.1111/cei.12884.
Thorne L, Arias A, Goodfellow I. Advances toward a norovirus antiviral: from classical inhibitors to lethal mutagenesis. J Infect Dis 2016;213 Suppl 1:S27-S31. doi: 10.1093/infdis/jiv280.
Echenique IA, Stosor V, Gallon L, Kaufman D, Qi C, Zembower TR. Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus. Transpl Infect Dis 2016;18(1):98-104. doi: 10.1111/tid.12472.
Siddiq DM, Koo HL, Adachi JA, Viola GM. Norovirus gastroenteritis successfully treated with nitazoxanide. J Infect. 2011;63(5):394- 397. doi: 10.1016/j.jinf.2011.08.002.
International Journal of Travel Medicine and Global Health
Volume 5, Issue 4
Autumn 2017
Pages 107-112

Files

History

  • Receive Date: 24 February 2017
  • Revise Date: 24 May 2017
  • Accept Date: 28 May 2017

Share

How to cite

Statistics