COVID-19 associated pulmonary aspergillosis.

OBJECTIVES: Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID-19) associated invasive aspergillosis at a single centre in Cologne, Germany. METHODS: A retrospective chart review of all patients with COVID-19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. RESULTS: COVID-19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. CONCLUSION: Clinicians caring for patients with ARDS due to COVID-19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co-infection.

Respiratory pathogens and acute chest syndrome in children with sickle cell disease.

BACKGROUND: Acute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS. MATERIALS AND METHODS: An observational, prospective, single-centre cohort study with nested case-control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray). RESULTS: We included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4-8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniae was detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case-control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS. CONCLUSIONS: Viral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniae was rare in young children with SCD experiencing ACS.

Respiratory syncytial virus and human metapneumovirus after allogeneic hematopoietic stem cell transplantation: Impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes.

INTRODUCTION: Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV. PATIENTS AND METHODS: In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty-one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low-, moderate-, and high-risk groups. Twenty-two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT-PCR. RESULTS: In the cohort, as whole 11.5% suffered a virus-associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty-day mortality was significantly higher in the ISI high-risk group (log-rank P = .05). Mortality was independent of the type of virus (P = .817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log-rank P = .001). In the ISI high-risk group, treatment with ribavirin significantly reduced the risk of progression (log-rank P < .001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P = .529 and P = .141, respectively). The detection of co-pathogens in the BAL fluid was borderline significant for mortality (P = .07). CONCLUSIONS: We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus-associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV- and hMPV-infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.

Epidemiological, clinical and genotypic features of human Metapneumovirus in patients with influenza-like illness in Senegal, 2012 to 2016.

BACKGROUND: Human metapneumovirus (HMPV) is a causal agent of acute respiratory infection, especially in primarily children. At the clinical level, HMPV is associated to several diseases including bronchitis, croup, pneumonia, bronchiolitis, reactive airway disease, chronic obstructive pulmonary disease and asthma exacerbations, specifically in children less than 5 years. Here, we carried out a retrospective pilot study, based on the processing of nasopharyngeal swabs, with a focus on the epidemiology and molecular characteristics of HMPV in Senegal. METHODS: This retrospective study was conducted from January 2012 to December 2016. Briefly, all outpatients presenting to healthcare sentinel sites were screened for surveillance enrollment and included if they met criteria for ILI. Naso-oropharyngeal swabs were collected from eligible participants. For viral respiratory pathogens detection, including HMPV, the Anyplex™ II RV16 Detection kit was used. A fragment of the hMPV F gene was targeted for sequencing. RESULTS: In total, 8209 patients with ILI were enrolled. Half of them (49.7%) were children under 5 years. Fever was the most common symptom followed by cough, and rhinitis. Three hundred eight patients were positive for HMPV (3.75%). 89 (28.9%) were detected as single infection. In co-infection cases, the most common co-infecting viruses were influenza, adenovirus and rhinovirus. HMPV detection rates in the different age groups varied significantly with the children under 5 years group accounting for 71.7% of positive patients. The temporal distribution pattern for HMPV infection showed a clear seasonal pattern with a higher activity during the rainy period (July-September). Phylogenetic analyses revealed that HMPV specimens circulating in Senegal were distributed into the two main genetic lineages, A and B. We also noted a co-circulation of both genetic lineages during the whole study period except in 2014. CONCLUSION: In summary, the present study characterized the recent prevalence, seasonality and genetic diversity of HMPV in a large outpatient population presented with ILI in Senegal between 2012 and 2016. Globally our results show a clear seasonal circulation pattern of HMPV in Senegal. Our findings identified children less than 5 years as more susceptible group to HMPV infection. Molecular studies identified A2, B1 and B2 as the major genotypes circulating.

Risk Factors for Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation.

Parainfluenza virus (PIV) infection can progress from upper respiratory tract infection (URTI) to lower respiratory tract disease (LRTD) in immunocompromised hosts. Risk factors for progression to LRTD and presentation with LRTD without prior URTI are poorly defined. Hematopoietic cell transplant (HCT) recipients with PIV infection were retrospectively analyzed using standardized definitions of LRTD. PIV was detected in 540 HCT recipients; 343 had URTI alone and 197 (36%) had LRTD (possible, 76; probable, 19; proven, 102). Among 476 patients with positive nasopharyngeal samples, the cumulative incidence of progression to probable/proven LRTD by day 40 was 12%, with a median time to progression of 7 days (range, 2 to 40). In multivariable analysis monocytopenia (hazard ratio, 2.22; P = .011), steroid use ≥1mg/kg prior to diagnosis (hazard ratio, 1.89; P = .018), co-pathogen detection in blood (hazard ratio, 3.21; P = .027), and PIV type 3 (hazard ratio, 3.57; P = .032) were associated with increased progression risk. In the absence of all 4 risk factors no patients progressed to LRTD, whereas progression risk increased to >30% if 3 or more risk factors were present. Viral load or ribavirin use appeared to have no effect on progression. Among 121 patients with probable/proven LRTD, 64 (53%) presented LRTD without prior URTI, and decreased lung function before infection and lower respiratory co-pathogens were risk factors for this presentation. Mortality was unaffected by the absence of prior URTI. We conclude that the risk of progression to probable/proven LRTD exceeded 30% with ≥3 risk factors. To detect all cases of LRTD, virologic testing of lower respiratory samples is required regardless of URTI symptoms.

DAS181 for Treatment of Parainfluenza Virus Infections in Hematopoietic Stem Cell Transplant Recipients at a Single Center.

Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or a single-arm clinical trial. Of the 16 patients (clinical trial: 9; compassionate use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n = 7), 4 (n = 5), 1 (n = 3), and type 3 and 4 coinfection (n = 1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia, and 8 had a fever. Patients received 5 to 10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and 4 (25%) had a partial response. The 3 patients without a clinical response had coinfections with other pathogens. Of the 7 patients with virologic and spirometric data, 5 had >1-log reduction in nasopharyngeal swab PIV viral load and 4 had improved forced expiratory volumes by the end of treatment. Three patients (19%) died within 30 days and 2 of these deaths were related to PIV infection. Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized placebo-controlled trials are needed to better evaluate its efficacy.

Prevalence of Human metapneumovirus infection among patients with influenza-like illness: Report from a Tertiary Care Centre, Southern India.

BACKGROUND: Human metapneumovirus (HMPV), discovered in the 21st century, has emerged as an important cause of influenza-like illness in children and adults causing mild upper respiratory tract infection to severe bronchiolitis and community-associated pneumonia. The aim of this study was to determine the prevalence of HMPV in the Union Territory of Puducherry, India, as part of National Influenza Surveillance Programme. MATERIALS AND METHODS: From November 2011 to December 2013, a total of 447 nasopharyngeal samples were collected from patients with acute respiratory infections and tested for HMPV RNA by real-time polymerase chain reaction. RESULTS: HMPV was identified in 23/447 (5%) samples with 11/23 in the age group of 14-30 years. Most of the HMPV infections were mild with no fatalities. Two patients were co-infected with the respiratory syncytial virus and one with influenza B virus. The seasonal distribution showed increasing HMPV infection cases in rainy months except for a peak in summer of 2012. Phylogenetic analysis based on the sequences of the nucleoprotein gene of one HMPV strain showed a high degree of sequence identity with Indian strains obtained during 2006 and 2011. CONCLUSION: This study shows that HMPV infection is more common in adults than in children. Sequence homology suggests the circulation of closely related HMPV strains within the country.

Serious outbreak of human metapneumovirus in patients with hematologic malignancies.

Human metapneumovirus (hMPV) is an important cause of lower respiratory tract infection. In healthy subjects infections are usually mild and rarely necessitate hospitalization. However, more serious outcomes have been described for allogeneic stem cell transplant recipients. This study reports an outbreak of hMPV A2 infection in severely immunocompromised adult hematologic cancer patients in a tertiary care unit. HMPV RNA was detected in bronchoalveolar lavage or produced sputum from patients presenting with typical clinical features. A total of 15 patients were diagnosed in a period of 7 weeks. Molecular subtyping revealed infection with genotype A2a virus, implicating nosocomial transmission. Eleven patients (73%) were treated with intravenous immunoglobulins and ribavirin. Ten patients (65%) presented with severe dyspnea, five (33%) required mechanical ventilation. Four patients (26.6%) died from hMPV-associated pneumonia and consequent multi-organ failure. Thus, hMPV is a critical pathogen for patients with hematologic cancers warranting early detection.

Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review.

Parainfluenza viral infections are increasingly recognized as common causes of morbidity and mortality in cancer patients, particularly in hematopoietic cell transplant (HCT) recipients and hematologic malignancy (HM) patients because of their immunocompromised status and susceptibility to lower respiratory tract infections. Advances in diagnostic methods, including polymerase chain reaction, have led to increased identification and awareness of these infections. Lack of consensus on clinically significant endpoints and the small number of patients affected in each cancer institution every year make it difficult to assess the efficacy of new or available antiviral drugs. In this systematic review, we summarized data from all published studies on parainfluenza virus infections in HM patients and HCT recipients, focusing on incidence, risk factors, long-term outcomes, mortality, prevention, and management with available or new investigational agents. Vaccines against these viruses are lacking; thus, infection control measures remain the mainstay for preventing nosocomial spread. A multi-institutional collaborative effort is recommended to standardize and validate clinical endpoints for PIV infections, which will be essential for determining efficacy of future vaccine and antiviral therapies.

[Association between parainfluenza virus infection and climatic factors in children].

OBJECTIVE: To study the association between acute respiratory human parainfluenza virus (HPIV) infection and climatic factors in children. METHODS: A total of 2 526 throat swab samples were collected from children with acute respiratory infection who visited the Pediatric Clinic of Shanghai Jiading Nanxiang Hospital between 2011 and 2013. HPIV was detected by multiplex RT-PCR. Related meteorological data were collected, including monthly mean temperature, monthly mean humidity, and monthly total rainfall. The association between HPIV detection rate and climatic factors was analyzed by Spearman's or Pearson test. RESULTS: During the three years, the overall HPIV detection rate was 5.62% (142/2 526), and HPIV-1 was the most common type (46.5%), followed by HPIV-3 (31.0%), HPIV-2 (17.6%), and HPIV-4 (4.9%). There were significant differences in the detection rates of HPIV-1 and HPIV-2 in different seasons, and the detection rates of both were the highest in summer (P<0.05). HPIV positive rate was positively correlated with monthly mean temperature (r=0.598; P<0.01) and monthly total rainfall (rs=0.602; P<0.01). CONCLUSIONS: The activity of HPIV in children is correlated with climatic factors, particularly temperature and rainfall.

Etiology and Incidence of Viral Acute Respiratory Infections Among Refugees Aged 5 Years and Older in Hagadera Camp, Dadaab, Kenya.

We used the Centers for Disease Control and Prevention-Kenya Medical Research Institute Acute Respiratory Infection (ARI) Surveillance System data to estimate severe acute respiratory infection (SARI) hospitalization rates, viral etiology, and associated complaints of influenza-like illnesses (ILI) and SARI conditions among those aged 5 years and older in Hagadera, Dadaab refugee camp, Kenya, for 2010-2012. A total of 471 patients aged ≥ 5 years met the case definition for ILI or SARI. SARI hospitalization rates per 10,000 person-years were 14.7 (95% confidence interval [CI] = 9.1, 22.2) for those aged 5-14 years; 3.4 (95% CI = 1.6, 7.2) for those aged 15-24 year; and 3.8 (95% CI = 1.6, 7.2) for those aged ≥ 25 years. Persons between the ages of 5 and 14 years had 3.5 greater odds to have been hospitalized as a result of SARI than those aged ≥ 25 years (odds ratio [OR] = 3.5, P < 0.001). Among the 419 samples tested, 169 (40.3%) were positive for one or more virus. Of those samples having viruses, 36.9% had influenza A; 29.9% had adenovirus; 20.2% had influenza B; and 14.4% had parainfluenza 1, 2, or 3. Muscle/joint pain was associated with influenza A (P = 0.002), whereas headache was associated with influenza B (P = 0.019). ARIs were responsible for a substantial disease burden in Hagadera camp.

Role of hydrogen sulfide in paramyxovirus infections.

UNLABELLED: Hydrogen sulfide (H2S) is an endogenous gaseous mediator that has gained increasing recognition as an important player in modulating acute and chronic inflammatory diseases. However, its role in virus-induced lung inflammation is currently unknown. Respiratory syncytial virus (RSV) is a major cause of upper and lower respiratory tract infections in children for which no vaccine or effective treatment is available. Using the slow-releasing H2S donor GYY4137 and propargylglycin (PAG), an inhibitor of cystathionine-γ-lyase (CSE), a key enzyme that produces intracellular H2S, we found that RSV infection led to a reduced ability to generate and maintain intracellular H2S levels in airway epithelial cells (AECs). Inhibition of CSE with PAG resulted in increased viral replication and chemokine secretion. On the other hand, treatment of AECs with the H2S donor GYY4137 reduced proinflammatory mediator production and significantly reduced viral replication, even when administered several hours after viral absorption. GYY4137 also significantly reduced replication and inflammatory chemokine production induced by human metapneumovirus (hMPV) and Nipah virus (NiV), suggesting a broad inhibitory effect of H2S on paramyxovirus infections. GYY4137 treatment had no effect on RSV genome replication or viral mRNA and protein synthesis, but it inhibited syncytium formation and virus assembly/release. GYY4137 inhibition of proinflammatory gene expression occurred by modulation of the activation of the key transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3) at a step subsequent to their nuclear translocation. H2S antiviral and immunoregulatory properties could represent a novel treatment strategy for paramyxovirus infections. IMPORTANCE: RSV is a global health concern, causing significant morbidity and economic losses as well as mortality in developing countries. After decades of intensive research, no vaccine or effective treatment, with the exception of immunoprophylaxis, is available for this infection as well as for other important respiratory mucosal viruses. This study identifies hydrogen sulfide as a novel cellular mediator that can modulate viral replication and proinflammatory gene expression, both important determinants of lung injury in respiratory viral infections, with potential for rapid translation of such findings into novel therapeutic approaches for viral bronchiolitis and pneumonia.

Management of respiratory viral infections in hematopoietic cell transplant recipients and patients with hematologic malignancies.

Despite preventive strategies and increased awareness, a high incidence of respiratory viral infections still occur in patients with hematologic malignancies (HMs) and in recipients of hematopoietic cell transplant (HCT). Progression of these viral infections to lower respiratory tract may prove fatal, especially in HCT recipients. Increasing evidence on the successful use of ribavirin (alone or in combination with immunomodulators) for the treatment of respiratory syncytial virus infections in HM patients and HCT recipients is available from retrospective studies; however, prospective clinical trials are necessary to establish its efficacy with confidence. The impact on progression to pneumonitis and/or mortality of treating parainfluenza virus infections with available (ribavirin) or investigational (DAS181) antiviral agents still needs to be determined. Influenza infections have been successfully treated with neuraminidase inhibitors (oseltamivir or zanamivir); however, the efficacy of these agents for influenza pneumonia has not been established, and immunocompromised patients are highly susceptible to emergence of antiviral drug resistance, most probably due to prolonged viral shedding. Infection control measures and an appreciation of the complications following respiratory viral infections in immunocompromised patients remain crucial for reducing transmission. Future studies should focus on strategies to identify patients at high risk for increased morbidity and mortality from these infections and to determine the efficacy of novel or available antiviral drugs.

Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013.

BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.

Human metapneumovirus: review of an important respiratory pathogen.

Human metapneumovirus (hMPV), discovered in 2001, most commonly causes upper and lower respiratory tract infections in young children, but is also a concern for elderly subjects and immune-compromised patients. hMPV is the major etiological agent responsible for about 5% to 10% of hospitalizations of children suffering from acute respiratory tract infections. hMPV infection can cause severe bronchiolitis and pneumonia in children, and its symptoms are indistinguishable from those caused by human respiratory syncytial virus. Initial infection with hMPV usually occurs during early childhood, but re-infections are common throughout life. Due to the slow growth of the virus in cell culture, molecular methods (such as reverse transcriptase PCR (RT-PCR)) are the preferred diagnostic modality for detecting hMPV. A few vaccine candidates have been shown to be effective in preventing clinical disease, but none are yet commercially available. Our understanding of hMPV has undergone major changes in recent years and in this article we will review the currently available information on the molecular biology and epidemiology of hMPV. We will also review the current therapeutic interventions and strategies being used to control hMPV infection, with an emphasis on possible approaches that could be used to develop an effective vaccine against hMPV.

[Pathogenesis of human metapneumovirus infection and research on attenuated live vaccine].

Numerous studies have indicated that human metapneumovirus (hMPV) is an important viral pathogen in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (RSV). HMPV infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than 1 year old. Host innate immune response has been implicated in recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs). Toll like receptors (TLRs) are one of the largest class of PRRs which initiate and regulate adaptive immune responses. Some studies have indicated that TLR 3 and TLR 4 may play critical roles in hMPV infection. Construction of recombinant mutant viruses lacking one or two N-linked glycosylation sites in the F protein by using site-directed mutagenesis and reverse genetics may be helpful for developing attenuated live vaccines.

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.

Interleukin-12p40 modulates human metapneumovirus-induced pulmonary disease in an acute mouse model of infection.

The mechanisms that regulate the host immune response induced by human metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family, are largely unknown. Cytokines play an important role in modulating inflammatory responses during viral infections. IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV. In this work, we demonstrated that in mice deficient in IL-12p40, hMPV infection induced an exacerbated pulmonary inflammatory response and mucus production, altered cytokine response, and decreased lung function. However, hMPV infection in these mice does not have an effect on viral replication. These results identify an important regulatory role of IL-12p40 in hMPV infection.

Human metapneumovirus.

Respiratory tract infections (RTI) are the leading cause of death in low-income countries and the second leading cause of death worldwide in children less than 5 years old. Most RTI are viral. Human metapneumovirus (hMPV) was discovered in 2001 in routine viral cultures of respiratory specimens from children with RTI and has been implicated as a common cause of RTI in children and adults and a cause of severe disease in immunocompromised hosts. This article describes the microbiology, epidemiology, clinical presentation, pathogenesis, diagnosis, treatment, prognosis, long-term outcome, immunity and reinfection of hMPV.

Timing and severity of community acquired respiratory virus infections after myeloablative versus non-myeloablative hematopoietic stem cell transplantation.

BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality after hematopoietic cell transplantation. Their clinical course can be severe with progression to lower respiratory tract infection, co-infection with serious pulmonary co-pathogens, and high mortality. Non-myeloablative conditioning regimens achieve engraftment without eradication of host hematopoietic cells, which potentially allows for protection against infections commonly seen in hematopoietic cell transplantation patients treated with standard intensity conditioning regimens. DESIGN AND METHODS: We performed a retrospective cohort study to measure the incidence and severity of parainfluenza types 1-4, influenza (A and B), respiratory syncitial virus and human rhinovirus disease in myeloablative versus non-myeloablative versus autologous hematopoietic cell transplantation patients. RESULTS: The incidences of all respiratory virus infections were similar in the non-myeloablative and myeloablative cohorts but less in the autologous cohort (33/420 [7.9%], 150/1593 [9.4%], and 37/751 [4.9%], respectively, p<0.0001). However, respiratory virus lower tract infections were significantly less common during the first 100 days after transplantation in non-myeloablative patients compared to myeloablative and autologous patients (1/420 [0.2%], 34/1593 [2.1%] and 16/751 [2.1%], respectively, p=0.005. Respiratory virus lower tract infection had high co-infection and attributable mortality rates. CONCLUSIONS: Respiratory virus lower tract infection during the first 100 days after hematopoietic cell transplantation was less common in persons receiving non-myeloablative conditioning regimens compared to myeloablative conditioning, despite a similar overall rate of acquisition.