Mode of parainfluenza virus transmission determines the dynamics of primary infection and protection from reinfection.

Little is known about how the mode of respiratory virus transmission determines the dynamics of primary infection and protection from reinfection. Using non-invasive imaging of murine parainfluenza virus 1 (Sendai virus) in living mice, we determined the frequency, timing, dynamics, and virulence of primary infection after contact and airborne transmission, as well as the tropism and magnitude of reinfection after subsequent challenge. Contact transmission of Sendai virus was 100% efficient, phenotypically uniform, initiated and grew to robust levels in the upper respiratory tract (URT), later spread to the lungs, grew to a lower level in the lungs than the URT, and protected from reinfection completely in the URT yet only partially in the lungs. Airborne transmission through 7.6-cm and 15.2-cm separations between donor and recipient mice was 86%-100% efficient. The dynamics of primary infection after airborne transmission varied between individual mice and included the following categories: (a) non-productive transmission, (b) tracheal dominant, (c) tracheal initiated yet respiratory disseminated, and (d) nasopharyngeal initiated yet respiratory disseminated. Any previous exposure to Sendai virus infection protected from mortality and severe morbidity after lethal challenge. Furthermore, a higher level of primary infection in a given respiratory tissue (nasopharynx, trachea, or lungs) was inversely correlated with the level of reinfection in that same tissue. Overall, the mode of transmission determined the dynamics and tropism of primary infection, which in turn governed the level of seroconversion and protection from reinfection. These data are the first description of the dynamics of respiratory virus infection and protection from reinfection throughout the respiratory tracts of living animals after airborne transmission. This work provides a basis for understanding parainfluenza virus transmission and protective immunity and for developing novel vaccines and non-pharmaceutical interventions.

Prolonged respiratory viral shedding in transplant patients.

Respiratory viral infections are frequent causes of morbidity in transplant patients. We screened symptomatic adult transplant recipients for respiratory viruses in a cohort of patients attending a referral medical center in Brazil. The duration of viral shedding and the prevalence of viral codetections were also determined. During a 1-year period (2011-2012), swabs were obtained from 50 patients. An in-house polymerase chain reaction panel designed to detect 10 viruses was used. Viruses were identified in 19 (38%) patients, particularly parainfluenza III (32%) and the respiratory syncytial virus (20%); multiple viruses were identified in 26% of patients. Prolonged viral shedding was observed with 60% of individuals excreting viruses for >10 days. The clinical and epidemiologic relevance of prolonged viral shedding remains to be determined.

Illumination of parainfluenza virus infection and transmission in living animals reveals a tissue-specific dichotomy.

The parainfluenza viruses (PIVs) are highly contagious respiratory paramyxoviruses and a leading cause of lower respiratory tract (LRT) disease. Since no vaccines or antivirals exist, non-pharmaceutical interventions are the only means of control for these pathogens. Here we used bioluminescence imaging to visualize the spatial and temporal progression of murine PIV1 (Sendai virus) infection in living mice after intranasal inoculation or exposure by contact. A non-attenuated luciferase reporter virus (rSeV-luc(M-F*)) that expressed high levels of luciferase yet was phenotypically similar to wild-type Sendai virus in vitro and in vivo was generated to allow visualization. After direct intranasal inoculation, we unexpectedly observed that the upper respiratory tract (URT) and trachea supported robust infection under conditions that result in little infection or pathology in the lungs including a low inoculum of virus, an attenuated virus, and strains of mice genetically resistant to lung infection. The high permissivity of the URT and trachea to infection resulted in 100% transmission to naïve contact recipients, even after low-dose (70 PFU) inoculation of genetically resistant BALB/c donor mice. The timing of transmission was consistent with the timing of high viral titers in the URT and trachea of donor animals but was independent of the levels of infection in the lungs of donors. The data therefore reveals a disconnect between transmissibility, which is associated with infection in the URT, and pathogenesis, which arises from infection in the lungs and the immune response. Natural infection after transmission was universally robust in the URT and trachea yet limited in the lungs, inducing protective immunity without weight loss even in genetically susceptible 129/SvJ mice. Overall, these results reveal a dichotomy between PIV infection in the URT and trachea versus the lungs and define a new model for studies of pathogenesis, development of live virus vaccines, and testing of antiviral therapies.

Nosocomial transmission of parainfluenza 3 virus in hematological patients characterized by molecular epidemiology.

We report an outbreak of parainfluenza 3 virus involving 17 hematology-oncology patients on 2 hospital wards. Sequence analysis of clinical samples confirmed homology of strains for 16/17 patients and 1 healthcare worker. Epidemiological analysis of the outbreak supported the molecular data with nosocomial transmission of the same genetic strain as the cause of the outbreak.

Dynamics of nosocomial parainfluenza virus type 3 and influenza virus infections at a large German University Hospital between 2012 and 2019.

Nosocomial virus infections cause significant morbidity and mortality. Besides influenza viruses, the disease burden of parainfluenza virus type 3 (PIV-3) is comparatively high among hospitalized patients and severe disease courses can occur. PIV-3 showed the highest rates of nosocomial infections of a panel of respiratory viruses. Therefore, a retrospective observational study was conducted among patients with either PIV-3 or influenza viruses, which served as reference pathogen. The aim was to compare the seasonal dynamics and clinical characteristics of nosocomial infections with these highly transmittable viruses. Nosocomial infection occurred in 15.8% (n = 177) of all influenza cases, mainly in the first half of a season. About 24.3% (n = 104) of the PIV-3 cases were nosocomial and occurred mainly in the second half of a season. Both nosocomial rates of influenza and nosocomial rates of PIV-3 varied between the seasons. Community acquired and nosocomial cases differed in underlying medical conditions and immunosuppression. Knowledge of the baseline rates of nosocomial infections could contribute to the implementation of appropriate infection control measures.

Molecular epidemiology of an outbreak of human parainfluenza virus 3 among oncology patients.

A hospital outbreak of human parainfluenza virus type 3 (HPIV-3) in haematologic oncology patients is described in 12 patients over a four-week period. Exposure histories and molecular analysis of HPIV-3 isolates suggest that both community-acquired and nosocomially transmitted infections occurred during this outbreak. Molecular analysis of HPIV-3 isolates indicated that a chain of transmission occurred among multiple patients in an oncology ward. This transmission was later determined to be associated with the movement of fomites, visitors, and activities in the unit. The infection prevention team stopped nosocomial spread of HPIV-3 through interventions including advanced cleaning procedures.

Prevalence of Human Parainfluenza Viruses and Noroviruses Genomes on Office Fomites.

The aim of this study was to evaluate the potential role of office fomites in respiratory (human parainfluenza virus 1-HPIV1, human parainfluenza virus 3-HPIV3) and enteric (norovirus GI-NoV GI, norovirus GII-NoV GII) viruses transmission by assessing the occurrence of these viruses on surfaces in office buildings. Between 2016 and 2017, a total of 130 surfaces from open-space and non-open-space rooms in office buildings located in one city were evaluated for HPIV1, HPIV3, NoV GI, and NoV GII viral RNA presence. Detection of viruses was performed by RT-qPCR method. Study revealed 27 positive samples, among them 59.3% were HPIV3-positive, 25.9% HPIV1-positive, and 14.8% NoV GII-positive. All tested surfaces were NoV GI-negative. Statistical analysis of obtained data showed that the surfaces of office equipment including computer keyboards and mice, telephones, and desktops were significantly more contaminated with respiratory viruses than the surfaces of building equipment elements such as door handles, light switches, or ventilation tracts (χ 2 p = 0.006; Fisher's Exact p = 0.004). All examined surfaces were significantly more contaminated with HPIVs than NoVs (χ 2 p = 0.002; Fisher's Exact p = 0.003). Office fomites in open-space rooms were more often contaminated with HPIVs than with NoVs (χ 2 p = 0.016; Fisher's Exact p = 0.013). The highest average concentration of HPIVs RNA copies was observed on telephones (1.66 × 102 copies/100 cm2), while NoVs on the light switches (1.40 × 102 copies/100 cm2). However, the Kruskal-Wallis test did not show statistically significant differences in concentration levels of viral RNA copies on surfaces between the all tested samples. This study unequivocally showed that individuals in office environment may have contact with both respiratory and enteric viral particles present on frequently touched surfaces.

The role of next generation sequencing in infection prevention in human parainfluenza virus 3 infections in immunocompromised patients.

BACKGROUND: Respiratory viral infections are a significant problem in patients with hematologic malignancies. We report a cluster of HPIV 3 infections in our myeloma patients, and describe the utility of next generation sequencing (NGS) to identify transmission linkages which can assist in infection prevention. OBJECTIVES: To evaluate the utility of NGS to track respiratory viral infection outbreaks and delineate between community acquired and nosocomial infections in our cancer units. STUDY DESIGN: Retrospective chart review conducted at a single site. All patients diagnosed with multiple myeloma who developed symptoms suggestive of upper respiratory tract infection (URTI) or lower respiratory tract infection (LRTI) along with a respiratory viral panel (RVP) test positive for HPIV 3 between April 1, 2016, to June 30, 2016, were included. Sequencing was performed on the Illumina MiSeq™. To gain understanding regarding community strains of HPIV 3 during the same season, we also performed NGS on HPIV3 strains isolated from pediatric cases. RESULTS: We saw a cluster of 13 cases of HPIV3 infections in the myeloma unit. Using standard epidemiologic criteria, 3 cases were considered community acquired, 7 cases developed infection during treatment in the cancer infusion center, while an additional 3 developed infections during hospital stay. Seven patients required hospitalization for a median duration of 20days. NGS enabled sensitive discrimination of the relatedness of the isolates obtained during the outbreak and provided evidence for source of transmission. Two hospital onset infections could be tracked to an index case; the genome sequences of HPIV 3 strains from these 3 patients only differed by a single nucleotide. CONCLUSIONS: NGS offers a significantly higher discriminatory value as an epidemiologic tool, and can be used to gather real-time information and identification of transmission linkages to assist in infection prevention in immunocompromised patients.

Exposure to human respiratory viruses among urban performing monkeys in Indonesia.

Performing monkeys, a common phenomena in Asia, occupy a unique urban niche that comprises a number of factors influencing the likelihood of cross-species transmission of pathogens. Here we present the first documented evidence of exposure to measles, rubella, and parainfluenza in a population of performing monkeys. Evidence of exposure to these endemic human respiratory viruses in the performing monkeys confirms human-to-primate transmission and suggests the possibility of primate-to-human transmission. Urban animal markets, the likely source of these performing monkeys, may represent an environment conducive to the mixing of animals and pathogens, making these monkeys a potential conduit for infectious agents passing from a variety of animals found in animal markets to humans. The potential significance of these results to human public health and the unique contexts of disease transmission associated with the urban ecology of the performance monkeys are discussed. Given the level of overseas travel, this potential threat is not confined solely to Asia.

Exogenous porcine viruses.

Porcine organs, cells and tissues provide a viable source of transplants in humans, though there is some concern of public health risk from adaptation of swine infectious agents in humans. Limited information is available on the public health risk of many exogenous swine viruses, and reliable and rapid diagnostic tests are available for only a few of these. The ability of several porcine viruses to cause transplacental fetal infection (parvoviruses, circoviruses, and arteriviruses), emergence or recognition of several new porcine viruses during the last two decades (porcine circovirus, arterivirus, paramyxoviruses, herpesviruses, and porcine respiratory coronavirus) and the immunosuppressed state of the transplant recipients increases the xenozoonoses risk of humans to porcine viruses through transplantation. Much of this risk can be eliminated with vigilance and sustained monitoring along with a better understanding of pathogenesis and development of better diagnostic tests. In this review we present information on selected exogenous viruses, highlighting their characteristics, pathogenesis of viral infections in swine, methods for their detection, and the potential xenozoonoses risk they present. Emphasis has been given in this review to swine influenza virus, paramyxovirus (Nipah virus, Menagle virus, LaPiedad paramyxovirus, porcine paramyxovirus), arterivirus (porcine reproductive and respiratory syndrome virus) and circovirus as either they represent new swine viruses or present the greatest risk. We have also presented information on porcine parvovirus, Japanese encephalitis virus, encephalomyocarditis virus, herpesviruses (pseudorabies virus, porcine lymphotropic herpesvirus, porcine cytomegalovirus), coronaviruses (TGEV, PRCV, HEV, PEDV) and adenovirus. The potential of swine viruses to infect humans needs to be assessed in vitro and in vivo and rapid and more reliable diagnostic methods need to be developed to assure safe supply of porcine tissues and cells for xenotransplantation.

Update: outbreak of Nipah virus--Malaysia and Singapore, 1999.

During March 1999, health officials in Malaysia and Singapore, in collaboration with Australian researchers and CDC, investigated reports of febrile encephalitic and respiratory illnesses among workers who had exposure to pigs. A previously unrecognized paramyxovirus (formerly known as Hendra-like virus), now called Nipah virus, was implicated by laboratory testing in many of these cases. Febrile encephalitis continues to be reported in Malaysia but has decreased coincident with mass culling of pigs in outbreak areas. No new cases of febrile illness associated with Nipah virus infection have been identified in Singapore since March 19, 1999, when abattoirs were closed. This report summarizes interim findings from ongoing epidemiologic and laboratory investigations in Malaysia and Singapore.

Outbreak of Hendra-like virus--Malaysia and Singapore, 1998-1999.

During September 29, 1998-April 4, 1999, 229 cases of febrile encephalitis (111 [48%] fatal) were reported to the Malaysian Ministry of Health (MOH). During March 13-19, 1999, nine cases of similar encephalitic illnesses (one fatal) and two cases of respiratory illness occurred among abattoir workers in Singapore. Tissue culture isolation identified a previously unknown infectious agent from ill patients. This report summarizes the preliminary epidemiologic and laboratory investigations of these cases, which indicate that a previously unrecognized paramyxovirus related to, but distinct from, the Australian Hendra virus is associated with this outbreak.

Emerging perspectives in management and prevention of infections of the respiratory tract in infants and children.

New products, new procedures, new information, and new legislation will have a significant impact on management and prevention of respiratory infections in children. Current areas of investigation include the changing epidemiology (increased number of children in day care), concern about morbidity of common infections (hearing impairment and effect on development of speech and language due to otitis media), and new modes of microbiologic diagnosis (antigen detection). New antimicrobial agents have wider spectrums of activity, increased concentrations in body fluids, and lesser toxicity than available drugs. New uses of old drugs are identified (value of erythromycin for Legionella pneumophila, Chlamydia trachomatis, and Mycoplasma pneumoniae). Increased usage of chemoprophylaxis for prevention of recurrences of acute otitis media follows publication of impressive results of recent studies. New conjugate polysaccharide vaccines are immunogenic in young infants. Finally, and of major importance to children, physicians, and manufacturers, is vaccine liability legislation, now in congressional committee.

Day-care center attendance and hospitalization for lower respiratory tract illness.

To identify risk factors associated with hospitalization for acute lower respiratory tract illness, 102 children less than 2 years of age admitted to four Atlanta metropolitan area hospitals between December 1984 and June 1985 with the diagnosis of lower respiratory tract illness were studied. The most common causative agent associated with illness was respiratory syncytial virus, followed by other respiratory viruses, Haemophilus influenzae, and Streptococcus pneumoniae. The 102 case-patients were compared with 199 age- and sex-matched controls. A parent or guardian for each patient and control was interviewed by telephone regarding demographic data, care outside the home, breast-feeding, previous medical history, allergies, and smoking and illness in household members. Five factors were associated with lower respiratory tract illness in both a univariate analysis and a multiple logistic regression model (P less than .05). These factors were the number of people sleeping in the same room with the child, a lack of immunization the month before the patient was hospitalized, prematurity, a history of allergy, and regular attendance in a day-care center (more than six children in attendance). Care received outside of the home in a day-care home (less than or equal to six children in attendance) was not associated with lower respiratory tract illness. The suggestion made by our study and other studies was that for children less than 2 years of age, care outside of the home is an important risk factor for acquiring lower respiratory tract illness, as well as other infectious diseases, and that this risk can be reduced by using a day-care home instead of a day-care center.

Control of nosocomial respiratory syncytial viral infections.

We evaluated methods to control the spread of respiratory syncytial virus (RSV) on our infants' ward during a community outbreak of RSV infection. Methods included isolation and cohorting of infected infants, strict handwashing, use of gowns, and the cohorting of staff to the ill infants. Of 123 infants studied, 36 were admitted with RSV infections. Of the remaining 87 contact infants, eight (19%) acquired nosocomial RSV disease. Three of the eight developed pneumonia and one died. Of the 43 staff members, 24 (56%) became infected and 82% were symptomatic. Four acquired repeated infections within weeks of the initial infection. Studies a year previously had revealed that 45% of contact infants and 42% of the staff had acquired nosocomial RSV infections. Thus, the employed procedures appeared to have decreased the transmission of RSV to infants but not to the staff. Staff may continue to be infected by large droplets from close contact with ill infants or by self-inoculation of contaminated secretions.

Severe respiratory syncytial virus pneumonia after autologous bone marrow transplantation: a report of three cases and review.

Three patients with acute leukemia who underwent autologous bone marrow transplantation (BMT) in complete remission, developed a severe respiratory syncytial virus (RSV) pneumonia, which was fatal in two. Identification of RSV was made on the products of bronchoalveolar lavage by direct immunofluorescence. As already described by others, the initial course of RSV infection varies, depending on whether it occurs sooner or later after BMT with a better prognosis in the latter situation. Treatment consists of aerosolized ribavirin. Infection by RSV is caused by manual contact with infected persons and contaminated surfaces. The severity of lung RSV infection in the course of BMT suggests the need for prophylactic measures in addition to standard isolation precautions.

Epidemiology and control of nosocomial viral infections.

The impact of nosocomial viral disease, in terms of morbidity, mortality, and health care expenditures, should not be underestimated. Respiratory viruses, in particular, account for a substantial proportion of all nosocomial infections, especially among pediatric patients and the institutionalized elderly. The immunocompromised, very young, and chronically ill patients in hospitals are unusually vulnerable to serious viral illness. The emerging technology of rapid viral diagnosis will allow more timely and accurate recognition of viral infections, even in the smaller hospital with limited laboratory resources. Early recognition of viral diseases should, in turn, permit us to institute, and further evaluate, specific measures for their control. Appreciation of the epidemiology and transmission of these viruses will provide the framework for successful infection control strategies.

Isolation of avian paramyxovirus-2 from domestic and wild birds in Costa Rica.

A survey for Newcastle disease virus (NDV) in wild birds of Costa Rica was conducted by swabbing wild-caught pet birds, backyard chickens, and wild birds captured in Japanese mist nets in tropical rain forests and agricultural areas. Cloacal swabs were collected from 876 birds of approximately 132 species representing 24 taxonomic families. Hemagglutinating agents were isolated from 18.7% of the birds. Paramyxovirus type 2(PMV-2) (Yucaipa-like), unreported in free-flying passerines in the Americas, was recovered from a finch, wren, and chicken, each from a different location. Pathogenicity trials with infected turkey poults and newly hatched chicks did not result in growth impairment or significant clinical signs of disease. Attempts to isolate NDV were negative.

Isolation of avian paramyxoviruses from sentinel ducks and turkeys in Minnesota.

In a 4-year study (1980-1983) involving the use of sentinel ducks that intermingled with wild ducks, a total of 98 paramyxovirus (PMV) isolates (84 Newcastle disease virus, 14 PMV-6) were obtained from 3652 sentinel duck cloacal samples (2.7% isolation rate) collected between June and mid-November each year. PMV infection of sentinel ducks appeared to be seasonal, with the onset of infection occurring between mid-July and mid-August. PMV was not isolated from sentinel turkeys that co-mingled with sentinel ducks during the last 2 years of the study. However, there was serological evidence that the sentinel turkeys were infected with PMV. These findings indicate that wild waterfowl are a natural reservoir of PMV and suggest that interspecies transmission of certain PMV serotypes may occur between waterfowl and turkeys.