¹Department of Infectious Diseases, Infection Control and Employee Health, MD Anderson Cancer Center, Houston, TX, USA

Correspondence: A Safdar, E-mail: asafdar@mdanderson.org

Most hematopoietic SCT recipients with human metapneumovirus (hMPV) infection are symptomless,¹ and even prolonged (3 months) nasopharyngeal viral shedding is not associated with respiratory dysfunction.² The occasional hMPV upper respiratory tract infection often resolves spontaneously and the usual brief illness seldom progresses to the lower respiratory tract.³ However, in severely immunosuppressed transplant recipients, hMPV may rarely cause life-threatening pulmonary^{4, 5} and brain infection.⁶

Ribavirin disrupts viral purine metabolism and inhibits viral RNA polymerase. It shows good in vivo activity against experimental hMPV infection.⁷ Ribavirin through upregulation of CD4 and CD8 T-lymphocyte-derived IL-2, tumor necrosis factor-, interferon- and downregulation of T-helper 2 cytokines such as IL-10 enhances containment of viral infection.⁸ This drug-induced restoration of T-cell hyporesponsiveness that follows prolonged viral replication is critical in resolution of infection.⁹ It is intriguing to realize that ribavirin may improve outcomes in transplant recipients with serious hMPV infection by direct antiviral effect and restoration of host's cellular immune response.^{10, 11} Increases in proinflammatory cytokines, however, may potentially worsen and precipitate respiratory failure. Systemic corticosteroids are therefore used to abrogate unwarranted exacerbation of pulmonary inflammation in patients with viral hMPV pneumonitis while receiving ribavirin therapy.^{7, 11}

In immunosuppressed transplant recipients, hMPV can lead to systemic, disseminated disease and aerosolized ribavirin therapy will have limited systemic antiviral and immune restoration activity. Intravenous ribavirin is not currently approved in the United States but may be obtained in the selected cases after regulatory approval. The author suggests that i.v. therapy should be entertained early in the course of unresponsive pulmonary or disseminated hMPV infection. Treatment with i.v. ribavirin needs close monitoring as patients who develop drug-induced intravascular hemolysis require prompt discontinuation of the drug and if further antiviral treatment is needed, ribavirin can be given by aerosolized route.¹¹

The diagnosis of hMPV requires a high level of clinical suspicion and confirmation by reverse transcriptase PCR.¹¹ Routine use of this highly sensitive diagnostic PCR assay, however, should be approached with caution as in most patients following SCT, the presence of hMPV RNA in nasopharyngeal samples may not represent active viral disease or serve as an indication for antiviral therapy.^{1, 2, 3}

hMPV can lead to serious disease in SCT recipients, and intravenous ribavirin appears to be promising therapy that requires further investigation.