Nitazoxanide Is Effective Therapy for Norovirus Gastroenteritis after Chemotherapy and Hematopoietic Stem Cell Transplantation (HSCT)

   Norovirus is a major cause of nonbacterial gastroenteritis and is a self-limited in immunocompetent patients.   However, in immune compromised pts it causes prolonged infection, GVHD  and sepsis due to mucosal breakdown.  Supportive care is the current therapy as attempts to treat with ribavirin or oral immunoglobulin have failed.  We report our experience treating norovirus gastroenteritis occurring in 14 patients (pts) after (11) and prior (3) to HSCT with Nitazoxanide.  

     From Nov 2012 to Dec 2013, 14 pts (2 receiving chemotherapy, 2 auto HSCT and 10 allo HSCT) developed norovirus gastroenteritis.  Ages ranged from 1 to 21 years (median 10) diagnoses included ALL/AML (6), aplastic anemia (2),  Wiskott Aldrich (2), neuroblastoma (2) and 1  osteopetrosis  and  1 medulloblastoma. Norovirus was detected by RNA RT-PCR test of stool performed by Focus Diagnostics, Cypress, Ca.  The dose of Nitazoxanide was 100 mg po BID for ages 1 to 4 years, 200 mg po BID for age 4 to 11 years, and 500 mg po BID for greater than 11 years.

     1 pt, 33 months post allo HSCT with normal immune studies was not treated as symptoms resolved prior to test result.  All other pts clinically responded with improvements in diarrhea, nausea, and abdominal pain in 2-4 days (median 2 days).  3 pts were pre-HSCT on chemo/immunotherapy and 11 were 17 days to 34 months after HSCT.  All the treated pts were on immune suppression or chemotherapy. 9 allo HSCT pts were on immunosuppression and 5 of these had GVHD at onset of symptoms.  Immune suppression included tacrolimus/solumedrol (3), cellcept/solumedrol (2) plus infliximab (1), tacrolimus (1), cyclosporine (1), tacrolimus/cellcept (1).  3 pts were receiving immunotherapy (1), or chemotherapy for solid tumors (2) prior to planned HSCT. 1 pt was 10 months post auto HSCT. Clearance of stool virus was variable.  2/ 3 pts treated prior to HSCT  became negative on stool study within 5-14 days of treatment (1 unknown duration).  Among  pts treated after HSCT 4/ 9 had persistent viral shedding, 2 received drug until death (1 adenovirus, 1 CHF) both were treated greater than 2 months, 3 with GVHD still shed virus after 6 months of treatment, and 4 are off therapy and remain negative for norovirus RNA.  1 auto HSCT pt stopped viral shedding 2 months post starting Nitazoxanide. 2 HSCT pts with clinical resolution but persistent viral shedding stopped treatment and had clinical symptoms return.  These pts responded to restarting therapy within 2 days but continue to shed virus.  UGI endoscopy/ colonoscopy were performed in 5 pts at the time of infection, all showed inflammation/edema but no GVHD was seen on histology.  Peripheral blood CD4 counts among those with persistent viral shedding ranged from <50-445/ul and for those that cleared virus 143-1222/ul.

     Nitazoxanide is effective therapy for norovirus gastroenteritis in immune compromised patients.  Therapy needs to be continued until stool RNA studies become negative.