HUMAN PARAINFLUENZA 2 RELATED ILLNESS AND A DEATH IN A GROUP OF CAPTIVE WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA).

An onset of respiratory disease in a captive bachelor group (n = 3) of western lowland gorillas (Gorilla gorilla gorilla) was concomitant with peak attendance of visitors at the institution and with unwanted occurrences of food items being thrown in the gorillas' enclosure. While the condition of two individuals improved with supportive therapy and antibiotics, the third gorilla died three days following initiation of treatment. A fatal bacterial pneumonia, secondary to an infection by a human parainfluenza virus 2 (HIPV-2), was considered to be the cause of death based on histopathology, lung cultures, and reverse transcription PCR. HPIV-2 activity in the human population of the province was detected for that period, including the same viral strain. This report confirms a HPIV-2 respiratory illness and associated death in a gorilla. Clinical presentation and context suggest conspecifics were also affected and that contaminated food thrown by visitors may have been the source of infection.

Verification of genetic loci responsible for the resistance/susceptibility to the Sendai virus infection using congenic mice.

Sendai virus (SeV) is one of the most important pathogens in the specific-pathogen free rodents. It is known that there are some inbred mouse strains susceptible or resistant to SeV infection. The C57BL/6 (B6) and DBA/2 (D2) mice are representative of the resistant and susceptible strains, respectively. Previous study with the quantitative trait locus (QTL) analysis identified three QTLs responsible for resistance or susceptibility to SeV infection on different chromosomes and indicated that resistance or susceptibility to SeV infection was almost predicted by genotypes of these three QTLs. In this paper, to verify the above hypothesis, congenic lines were generated as follows; B6-congenic lines carrying one of the D2 alleles of three QTLs and combination of these three QTLs, and D2-congenic lines carrying single or combination of B6 alleles of three QTLs. All these congenic lines were then challenged with SeV infection. D2 congenic lines introgressed single or combination of B6 alleles of QTLs changed to resistance to SeV infection. Especially, a D2 triple-congenic line became resistant as similar level to B6-parental strain. However, B6-congenic lines introgressed single or combination of D2 alleles of QTLs all remained to be resistant to SeV infection. Both IL-6 and TNF-α in broncho-alveolar lavage fluid of D2 triple-congenic line were decreased to the similar level of B6 mice, suggesting that this is a part of factors that D2 triple-congenic line became resistant to the similar level of B6 mice. Data obtained from these congenic mice verified that three QTLs identified previously were indeed responsible for the resistance/susceptibility to SeV infection in B6 and D2 mice.

Lower Respiratory Tract Diseases Caused by Common Respiratory Viruses among Stem Cell Transplantation Recipients: A Single Center Experience in Korea.

PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea. RESULTS: Seventy-one CRV-LRDs were identified in 67 (6.5%) patients. The human parainfluenza virus (HPIV) was the most common causative pathogen of CRV-LRDs at 100 days [cumulative incidence estimate, 23.5%; 95% confidence interval (CI), 3.3-43.7] and 1 year (cumulative incidence estimate, 69.2%; 95% CI, 45.9-92.5) following SCT. The 30-day overall mortality rates due to influenza-LRDs, respiratory syncytial virus-LRDs, HPIV-LRDs, and human rhinovirus-LRDs were 35.7, 25.8, 31.6, and 42.8%, respectively. Co-pathogens in respiratory specimens were detected in 23 (33.8%) patients. The overall mortality at day 30 after CRV-LRD diagnosis was 32.8% (22/67). High-dose steroid usage (p=0.025), a severe state of immunodeficiency (p=0.033), and lymphopenia (p=0.006) were significantly associated with death within 30 days following CRV-LRD diagnosis in a univariate analysis. Multivariate logistic regression analysis revealed that high-dose steroid usage [odds ratio (OR), 4.05; 95% CI, 1.12-14.61; p=0.033] and lymphopenia (OR, 6.57; 95% CI, 1.80-24.03; p=0.004) were independent risk factors for mortality within 30 days of CRV-LRDs. CONCLUSION: CRV-LRDs among SCT recipients showed substantially high morbidity and mortality rates. Therefore, the implement of an active diagnostic approaches for CRV infections is required for SCT recipients with respiratory symptoms, especially those receiving high-dose steroids or with lymphopenia.

A parainfluenza-3 outbreak in a SCT unit: sepsis with multi-organ failure and multiple co-pathogens are associated with increased mortality.

The estimated frequency of parainfluenza virus 3 (PIV-3) infections following haematopoietic SCT (HSCT) is 2-7%, whereas reported mortality ranges from 18 to 33%. We report a retrospective outcome analysis following an outbreak of PIV-3 infection in our transplant unit. A total of 16 HSCT patients developed PIV-3 infection. All patients had upper respiratory tract infection, whereas lower respiratory tract infection occurred in 8 patients. Overall, 13 patients were treated with aerosolised Ribavirin (2 g t.d.s. for 5 days) and i.v. Ig (0.5 g/kg) as per standard protocol. One patient refused treatment, whereas two patients with full immune reconstitution were not treated. Overall mortality was 62.5%. Sepsis with multi-organ failure and the presence of pulmonary co-pathogens were both significantly associated with PIV-3-related mortality. Our series confirms that high mortality is associated with PIV-3 infection in HSCT recipients. In patients who develop PIV-3 infection, despite strict enforcement of infection control policies, the best strategy might be careful risk assessment, with effective broad-spectrum anti-microbials in those who are at risk of secondary infection.

Residues in the heptad repeat a region of the fusion protein modulate the virulence of Sendai virus in mice.

While the molecular basis of fusion (F) protein refolding during membrane fusion has been studied extensively in vitro, little is known about the biological significance of membrane fusion activity in parainfluenza virus replication and pathogenesis in vivo. Two recombinant Sendai viruses, F-L179V and F-K180Q, were generated that contain F protein mutations in the heptad repeat A region of the ectodomain, a region of the protein known to regulate F protein activation. In vitro, the F-L179V virus caused increased syncytium formation (cell-cell membrane fusion) yet had a rate of replication and levels of F protein expression and cleavage similar to wild-type virus. The F-K180Q virus had a reduced replication rate along with reduced levels of F protein expression, cleavage, and fusogenicity. In DBA/2 mice, the hyperfusogenic F-L179V virus induced greater morbidity and mortality than wild-type virus, while the attenuated F-K180Q virus was much less pathogenic. During the first week of infection, virus replication and inflammation in the lungs were similar for wild-type and F-L179V viruses. After approximately 1 week of infection, the clearance of F-L179V virus was delayed, and more extensive interstitial inflammation and necrosis were observed in the lungs, affecting entire lobes of the lungs and having significantly greater numbers of syncytial cell masses in alveolar spaces on day 10. On the other hand, the slower-growing F-K180Q virus caused much less extensive inflammation than wild-type virus, presumably due to its reduced replication rate, and did not cause observable syncytium formation in the lungs. Overall, the results show that residues in the heptad repeat A region of the F protein modulate the virulence of Sendai virus in mice by influencing both the spread and clearance of the virus and the extent and severity of inflammation. An understanding of how the F protein contributes to infection and inflammation in vivo may assist in the development of antiviral therapies against respiratory paramyxoviruses.

Airway epithelial versus immune cell Stat1 function for innate defense against respiratory viral infection.

The epithelial surface is often proposed to actively participate in host defense, but evidence that this is the case remains circumstantial. Similarly, respiratory paramyxoviral infections are a leading cause of serious respiratory disease, but the basis for host defense against severe illness is uncertain. Here we use a common mouse paramyxovirus (Sendai virus) to show that a prominent early event in respiratory paramyxoviral infection is activation of the IFN-signaling protein Stat1 in airway epithelial cells. Furthermore, Stat1-/- mice developed illness that resembled severe paramyxoviral respiratory infection in humans and was characterized by increased viral replication and neutrophilic inflammation in concert with overproduction of TNF-alpha and neutrophil chemokine CXCL2. Poor control of viral replication as well as TNF-alpha and CXCL2 overproduction were both mimicked by infection of Stat1-/- airway epithelial cells in culture. TNF-alpha drives the CXCL2 response, because it can be reversed by TNF-alpha blockade in vitro and in vivo. These findings pointed to an epithelial defect in Stat1-/- mice. Indeed, we next demonstrated that Stat1-/- mice that were reconstituted with wild-type bone marrow were still susceptible to infection with Sendai virus, whereas wild-type mice that received Stat1-/- bone marrow retained resistance to infection. The susceptible epithelial Stat1-/- chimeric mice also exhibited increased viral replication as well as excessive neutrophils, CXCL2, and TNF-alpha in the airspace. These findings provide some of the most definitive evidence to date for the critical role of barrier epithelial cells in innate immunity to common pathogens, particularly in controlling viral replication.

Molecular investigations of an outbreak of parainfluenza virus type 3 and respiratory syncytial virus infections in a hematology unit.

A large simultaneous outbreak of respiratory syncytial virus (RSV) and parainfluenza type 3 (PIV-3) infections occurred on an adult hematology unit. Implementation of enhanced infection control was complicated by cocirculation of the two different viruses, with prolonged viral shedding from infected patients, and placed great pressure on health care staff; of 27 infected hematopoietic stem cell transplant patients, 9 died, and the unit was closed for 2 months. Retrospective molecular investigation of the virus strains involved in the outbreak was performed by analyzing part of the fusion gene of PIV-3 and part of the glycoprotein gene of RSV. Reverse transcription-PCR on nasopharyngeal aspirates from patients infected before and during the simultaneous outbreak generated amplicons for sequence analysis. A single strain of RSV and a single strain of PIV-3 had spread from person to person within the unit; 7 patients were infected with RSV, 22 were infected with PIV-3, and 4 were infected with both viruses. The PIV-3 outbreak had started at the beginning of August 3 months before the RSV outbreak; it had arisen when PIV-3 was introduced from the community by a patient and passed to another patient, who became chronically infected with the identical strain and, in spite of being nursed in isolation, was most likely the source from which widespread infection occurred in November. Had these early cases been linked to a common PIV-3 strain at the time of diagnosis, enhanced infection control precautions might have prevented the eventual extensive spread of PIV-3, making it much easier to deal with the later RSV outbreak.

Parainfluenza type 3 infection post stem cell transplant: high prevalence but low mortality.

Parainfluenza type 3 (PIV 3) is a well-recognized cause of respiratory illness after stem cell transplantation (SCT), with an estimated incidence of 2-7% and a high mortality rate associated with lower respiratory tract infection (LRTI). A 12-month retrospective study was undertaken in which 23 positive cases of PIV 3 occurred in SCT recipients. The frequency of infection was 36.1% in matched unrelated donor SCT recipients, 23.8% in sibling allogeneic SCT recipients and 2.3% in autologous transplant recipients. Seventeen cases were outpatient or community acquired despite standard infection control measures. Eleven patients only developed upper respiratory tract symptoms. LRTI symptoms developed in 12 patients, of whom eight had a new infiltrate on chest X-ray. Overall mortality at 30 days from PIV 3 diagnosis was 4% (one patient). Four patients died within 100 days of PIV 3 diagnosis, but PIV 3 was not believed to be the primary cause of death in any of these patients. Early ribavirin was used in eight patients and only one patient who received ribavirin died. These results suggest a higher prevalence of PIV 3 but a lower mortality than documented previously, particularly in allogeneic transplant recipients. The authors propose that the high prevalence reflects the unit's policy of active surveillance for respiratory viruses and the difficulty in preventing transmission of PIV 3, especially in the outpatient setting during an outbreak period. Ribavirin treatment may improve outcome in patients with LRTI but is not required in all patients with PIV 3.

Contamination of a specific-pathogen-free rat breeding colony with Human parainfluenzavirus type 3.

Routine antibody surveillance for Sendai virus in a breeding colony suggested viral invasion into laboratory rats. A more specific haemagglutination-inhibition test implied that the agent was related closely to Human parainfluenza virus type 3 (hPIV3), rather than Sendai virus. To isolate this virus, Vero cells were inoculated with lung homogenates of 30 young animals from the colony. One of the cultures became positive at the second passage by RT-PCR directed to the hPIV3 NP and L genes. Cytopathic effect with cell fusion was observed at the third passage. The HN gene of this virus (KK24) had >93 % similarity to those of other hPIV3 isolates, suggesting a human origin of KK24. Experimental intranasal inoculation of KK24 into SD rats showed virus replication in the lungs at 3-5 days post-infection (p.i.). Pathological examination of the lungs at day 5 p.i. indicated a moderate detachment, degradation and apoptosis of bronchial epitheliocytes with peribronchial mononuclear infiltrations. At day 7 p.i., these changes became less prominent, and no lesions were apparent at day 10 p.i. or later. The infected rats seroconverted at day 7 p.i. On the contrary, none of the 30 experimentally infected ICR mice showed any pathological lesions in their lungs, despite seroconversion at 7 days p.i. These results suggest that hPIV3 can invade rat colonies and has a moderate and transient pathogenicity in rats. This is the first report of non-experimental hPIV3 infection in laboratory rats, unexpectedly detected by antibody screening for Sendai virus.

The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae.

An association exists between respiratory viruses and bacterial infections. Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality. The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to prevent the synergism between a paramyxovirus and Streptococcus pneumoniae was examined in this study. A model of secondary bacterial pneumonia after infection with a recombinant Sendai virus whose hemagglutinin-neuraminidase gene was replaced with that of human parainfluenza virus type 1 [rSV(hHN)] was established in mice. Challenge of mice with a sublethal dose of S. pneumoniae 7 days after a sublethal infection with rSV(hHN) (synergistic group) caused 100% mortality. Bacterial infection preceding viral infection had no effect on survival. The mean bacterial titers in the synergistic group were significantly higher than in mice infected with bacteria only. The virus titers were similar in mice infected with rSV(hHN) alone and in dually infected mice. Intranasal administration of BCX 2798 at 10 mg/kg per day to the synergistic group of mice starting 4 h before virus infection protected 80% of animals from death. This effect was accompanied by a significant reduction in lung viral and bacterial titers. Treatment of mice 24 h after the rSV(hHN) infection showed no protection against synergistic lethality. Together, our results indicate that parainfluenza viruses can prime for secondary bacterial infections. Prophylaxis of parainfluenza virus infections with antivirals might be an effective strategy for prevention of secondary bacterial complications in humans.

Low mortality rates related to respiratory virus infections after bone marrow transplantation.

Respiratory viruses (RVs) frequently cause severe respiratory disease in bone marrrow transplant (BMT) recipients. To evaluate the frequency of RV, nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection (URI). Direct immunofluorescence assay was performed for respiratory syncytial virus (RSV), influenza (Flu) A and B, adenovirus and parainfluenza (Paraflu) virus. Patients with RSV pneumonia or with upper RSV infection, but considered at high risk for developing RSV pneumonia received aerosolized ribavirin. Oseltamivir was given to patients with influenza. A total of 179 patients had 392 episodes of URI. In all, 68 (38%) tested positive: RSV was detected in 18 patients (26.4%), Flu B in 17 (25%), Flu A in 11 (16.2%) and Paraflu in 7 (10.3%). A total of 14 patients (20.6%) had multiple RV infections or coinfection. RSV pneumonia developed in 55.5% of the patients with RSV-URI. One of the 15 patients (6.6%) with RSV pneumonia died. Influenza pneumonia was diagnosed in three patients (7.3%). RSV and influenza infections peaked in fall-winter and winter-spring months, respectively. We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia. The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in randomized trials.

Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment.

All 456 recipients of hemopoietic stem cell transplants (SCT) at the Hammersmith Hospital, London, from January 1990 through September 1996 were reviewed for parainfluenza virus (PIV) infections. Of the 24 (5.3%) PIV type 3 (PIV3)-infected patients, 10 had upper respiratory tract infection and all survived, but 8 of 14 with pneumonia died. A same-day immunofluorescence test diagnosed PIV3 infection in 20 (83%) of the 24 cases, but virus culture diagnosed only 10 (42%) of the 24 cases after a mean delay of 12 days. Eighteen PIV3-infected patients first received ribavirin at a median of 3 days after onset of symptoms, but, nevertheless, 2 patients shed PIV3 for 4 months. Six of 10 patients with pneumonia died despite early ribavirin therapy. The cause of death was not established by autopsy; 3 patients had concurrent infections, but in 3, only PIV3 was detected. The value of immunofluorescence testing for early diagnosis and treatment of PIV3 infection after SCT is demonstrated, but the outcome was not altered.

Protective effect of passive immunization against TNF-alpha in mice infected with Sendai virus.

TNF-alpha has been reported to be induced in mice infected with Sendai virus. We evaluated the role of TNF-alpha in the virus infection. TNF-alpha was induced locally in proportion to virus titers in the lung. The activity was correlated with suppression of body weight gain. Passive immunization against TNF-alpha improved body weight gain and ameliorated pneumonic lesions in infected mice, and prevented them from lethal infection, but lung virus induced emaciation, pneumonic lesions and death were mediated by TNF-alpha.

Increased tumor necrosis factor-alpha (TNF-alpha) gene expression in parainfluenza type 1 (Sendai) virus-induced bronchiolar fibrosis.

Increased airway resistance and airway hyperresponsiveness induced in rats by infection with parainfluenza type I (Sendai) virus is associated with bronchiolar fibrosis. To determine whether increased tumor necrosis factor (TNF)-alpha gene expression is an important regulatory event in virus-induced bronchiolar fibrosis, pulmonary TNF-alpha mRNA and protein expression was assessed in rat strains that are susceptible (Brown Norway; BN) and resistant (Fischer 344; F344) to virus-induced bronchiolar fibrosis. Virus-inoculated BN rats had increased TNF-alpha pulmonary mRNA levels (P < 0.05) and increased numbers of bronchiolar macrophages and fibroblasts expressing TNF-alpha protein compared with virus-inoculated F344 rats (P < 0.05). Virus inoculation also induced elevated TNF-alpha mRNA and protein levels (P < 0.05) in cultured rat alveolar macrophages (NR8383 cells). A 55-kd soluble TNF receptor-immunoglobulin G fusion protein (sTNFR-IgG) was used to inhibit TNF-alpha bioactivity in virus-inoculated BN rats. Treated rats had fewer proliferating bronchiolar fibroblasts, as detected by bromodeoxyuridine incorporation, compared with virus-inoculated control rats (P < 0.05). There was also increased mortality in p55sTNFR-IgG-treated virus-inoculated rats associated with increased viral replication and decreased numbers of macrophages and lymphocytes in bronchoalveolar lavage fluid (P < 0.05). The results of this study indicate that 1) Sendai virus can directly up-regulate TNF-alpha mRNA and protein expression in macrophages, 2) TNF-alpha is an important mediator of virus-induced bronchiolar fibrosis, and 3) TNF-alpha has a critical role in the termination of Sendai viral replication in the lung.

Predictors of outcome of severe respiratory syncytial virus-associated respiratory failure treated with extracorporeal membrane oxygenation.

OBJECTIVE: To examine the Extracorporeal Life Support Organization registry data base for all infants and children with respiratory syncytial virus-associated respiratory failure managed with extracorporeal life support, to delineate predictors of outcome. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization data registry. PATIENTS: All pediatric patients treated in the United States with extracorporeal life support for severe pediatric respiratory syncytial virus-associated respiratory failure reported to the registry, from 1982 through June 1992. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: As of June 1992, fifty-three pediatric patients meeting study entry criteria were reported to the Pediatric Respiratory Failure Registry (n = 412) as having received extracorporeal membrane oxygenation (ECMO) for severe respiratory syncytial virus infection with pulmonary failure. Forty-nine percent (26/53) were successfully managed and survived to hospital discharge. The mean patient age was 5.0 +/- 8.6 months. Duration of mechanical ventilation before institution of extracorporeal life support was 8.1 +/- 6.2 days. Multivariate logistic regression analysis found four variables to be associated with patient nonsurvival at the p < 0.05 level: male gender, longer duration of mechanical ventilation before ECMO, higher peak inspiratory pressure, and lower ratio of arterial oxygen tension to fraction of inspired oxygen. Era of treatment was not associated with outcome. Receiver operator characteristic curve analysis of this multivariate model resulted in cutoff points of r = 0.5 and 0.1 that resulted in 92% sensitivity and 81% specificity (false-positive ratio 19%) and 96% sensitivity and 73% specificity (false-positive ratio 27%), respectively. CONCLUSIONS: Predictors of outcome of severe respiratory failure caused by respiratory syncytial virus infection managed with ECMO exist, and multivariate predictive models with high sensitivity and low false-positive risk are possible. Similar mathematical models may be helpful in establishing criteria for future trials of ECMO versus conventional respiratory support.

Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada.

PURPOSE: To determine the outcomes in children at high risk for death or complications from respiratory disease who are hospitalized with respiratory syncytial virus (RSV) infection. DESIGN: Retrospective chart review. SETTING: Twelve pediatric tertiary care centers. PATIENTS: All hospitalized children with an RSV infection diagnosed by a positive antigen detection test result or viral isolation during the study period from 1988 to 1991, encompassing three winter seasons. Charts from patients in the following high-risk groups were reviewed in detail: (1) congenital heart disease, (2) chronic lung disease, (3) immunodeficiency, (4) age less than 6 weeks, (5) gestational age less than 36 weeks, and (6) hypoxia (defined as oxygen saturation less than 90% or arterial oxygen pressure less than 60 mm Hg). MEASUREMENTS: The age of all children, the date of RSV identification, and the use of oxygen supplementation, intensive care, and ventilatory support. In addition, the duration of these treatments and the duration of hospitalization were noted. Left-to-right shunting and pulmonary hypertension before RSV infection were determined in those children with congenital heart disease. The nature of the chronic lung disease was noted. Death within 2 weeks of RSV identification was recorded, and the use of ribavirin, bronchodilators, and corticosteroids was determined. RESULTS: Significant year-to-year variation in the frequency of RSV infection was confirmed, with a peak during the 1989-1990 winter noted by the majority of centers (p = 0.0001). Of the 1584 patients in the study, 260 had underlying cardiac disease, 200 had chronic lung disease, 35 had compromised immune function, 378 had been premature, 373 were less than 6 weeks of age, and 338 had hypoxia. Seventeen patients died within 2 weeks (mortality rate 1%); significantly more patients with underlying cardiac disease (3.4%) or lung disease (3.5%) died. Immunocompromised patients had the longest hospital stay (median 39 days), followed by those patients with underlying cardiac or pulmonary disease (11 days); patients less than 6 weeks of age (5 days) and those with hypoxia (6 days) had the shortest hospital stays. Patients with underlying cardiac and pulmonary disease also required oxygen supplementation for a significantly longer period. CONCLUSION: The year-to-year variation in frequency of RSV infection was confirmed in this study. Morbidity and mortality rates associated with RSV infection in a high-risk population in Canada were significantly lower than previously reported.

An outbreak of respiratory syncytial virus in a bone marrow transplant center.

An outbreak of respiratory syncytial virus (RSV) infection occurred among 31 patients in a marrow transplant center over a 13-week period beginning in January 1990. RSV infection was also documented in 35 family members and employees. Of 18 patients with pneumonia, 14 (78%) died. None of 13 with upper respiratory infection died. Preengraftment patients tended to develop pneumonia more frequently than did engrafted patients. Early administration of ribavirin may have had a beneficial effect in patients with pneumonia. Antigenic and genomic analysis of 14 available isolates suggested that at least four different viral strains were responsible for the outbreak. One group of patients and 1 employee in spatial proximity were infected with the same strain and likely acquired their infections nosocomially. RSV infection in marrow transplant patients is a serious and life-threatening infection with a high mortality rate once pneumonia develops.