Response from Dr Hohenthal

This response to the letter by Miall et al (Bone Marrow Transplantation 2002; 29:6 541–542) was inadvertently omitted from the last issue of Bone Marrow Transplantation.

The report by Miall et al describes an interesting case of human parainfluenza type 4 virus (hPIV4) infection provoking many questions regarding the role of this virus as the causative agent of respiratory tract infections in the post-transplant setting. These issues involve the frequency and clinical severity of the hPIV4 disease as well as the need for rapid virological diagnostics in patients undergoing BMT.

The authors refer to our paper¹ on a cluster of nine patients with hPIV3 infection in a hematology unit during a 2-month period. This and additional recent reports^2,3 on outbreaks in BMT units demonstrate the clinical importance of hPIV3 as a nosocomial pathogen. In contrast, as pointed out by these authors, there are few documented cases of hPIV4 infection in immunocompromised patients. This may indicate that the virus is, indeed, uncommon or merely that it is seldom detected using the presently available diagnostic methods.

The clinical presentation of the patient described by Miall et al was severe with pleural and pericardial effusions, pneumonia and respiratory failure requiring continuous positive airway pressure support. It seems reasonable to assume that this patient might have benefitted from ribavirin therapy, if hPIV4 as the causative agent of infection had been identified early on. During the outbreak in our unit, ribavirin was administered in all four hPIV3-positive patients who had infiltrates on chest radiograph; all survived.¹ This is of note considering the high mortality rate of up to 50% previously reported in BMT recipients with lower respiratory tract infection caused by hPIV3.^4,5,6 Our experience supports the concept that it may be possible to avoid mortality from hPIV lower respiratory tract infection in BMT recipients and other hematological patients, provided that efforts are made to obtain a rapid etiological diagnosis. The clinical features do not reliably distinguish this syndrome from that caused by other respiratory pathogens.

The case described above does not include any data on or suspicion of potential transmission of hPIV4 from this patient to other patients in that unit. Neither are we aware of other reports on nosocomial transmission of hPIV4 among immunocompromised patients. Nevertheless, whenever hPIV is introduced into hospital, there is a danger of nosocomial viral transmission. hPIV3 is characterized by prolonged shedding: in BMT recipients, the shedding may continue for many months, even despite ribavirin treatment.² Some of our patients continued to shed the virus for several weeks.¹ We believe that the imminent outbreak in our unit was contained by nasopharyngeal sampling of patients and by prompt implementation of strict hygienic measures when a patient was shown to be positive for hPIV3 on antigen detection.

The main issue of Miall et al is to remind us that hPIV4 is not detected when currently available commercial immunofluorescent reagents are used for rapid diagnostics. On the other hand, an hPIV4 immunofluorescent reagent in monoclonal antibody form is not widely used. Moreover, there are data showing that hPIV4 is the most difficult hPIV to grow in cell culture, being rarely isolated despite relatively common serological evidence of infection.⁷ These data clearly indicate that there is a need to develop and adopt new diagnostic methods for detection of hPIV4 in a clinical setting. Aguilar et al⁷ have published an interesting paper showing that a multiplex reverse transcription-PCR (m-RT-PCR) assay was able to detect and differentiate all known hPIVs. This m-RT-PCR assay was more sensitive than either cell culture isolation or indirect immunofluorescence with monoclonal antibodies for the detection of hPIV infections. Among 64 hPIVs detected by this assay in 201 nasopharyngeal samples from pediatric patients hospitalized for lower respiratory tract infection, hPIV1 and hPIV3 were the most prevalent hPIVs, but hPIV4 was more frequent than hPIV2 (10 vs 7 isolates). Based on this and a few other studies⁸ in which the presence of hPIV4 was confirmed by viral culture, it has been hypothesized that this infection may be more common than previously believed.

We totally agree with Miall et al in their conclusion that rapid methods used in virological diagnostics should also detect hPIV4. In addition to ensuring early commencement of specific antiviral therapy for severe lower respiratory tract infections caused by hPIV4, accurate diagnostics renders possible prompt implementation of hygiene measures to prevent nosocomial viral spread. Due to the potentially serious nature of hPIV infection in immunocompromised patients, this is especially important in BMT units.