Modeling the transmission mitigation impact of testing for infectious diseases.

A fundamental question of any program focused on the testing and timely diagnosis of a communicable disease is its effectiveness in reducing transmission. Here, we introduce testing effectiveness (TE)-the fraction by which testing and post-diagnosis isolation reduce transmission at the population scale-and a model that incorporates test specifications and usage, within-host pathogen dynamics, and human behaviors to estimate TE. Using TE to guide recommendations, we show that today's rapid diagnostics should be used immediately upon symptom onset to control influenza A and respiratory syncytial virus but delayed by up to two days to control omicron-era severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, while rapid tests are superior to reverse transcription quantitative polymerase chain reaction (RT-qPCR) to control founder-strain SARS-CoV-2, omicron-era changes in viral kinetics and rapid test sensitivity cause a reversal, with higher TE for RT-qPCR despite longer turnaround times. Last, we illustrate the model's flexibility by quantifying trade-offs in the use of post-diagnosis testing to shorten isolation times.

Identifying the impact of non-pharmaceutical interventions on RSV transmission in a single-centre observational study.

During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory syncytial virus (RSV), the predominant cause of bronchiolitis. As NPIs were eased, it was speculated that RSV transmission would return with an increase in the severity of bronchiolitis. In a large tertiary hospital, a dramatic reduction in the incidence of bronchiolitis was seen during the COVID-19 pandemic. The easing of NPIs correlated with an increase in RSV transmission particularly in the community; however, there was no evidence of an increase in the severity of bronchiolitis.

School holidays and respiratory syncytial virus transmission in Sweden: An interrupted time series analysis.

AIM: Respiratory syncytial virus (RSV) represents a significant cause of morbidity for children worldwide, especially for newborns. As RSV vaccines are not routinely used for children yet, non-pharmaceutical interventions (NPIs) represent the main strategy for prevention. The objective of this study was to investigate the correlation between school holidays and RSV transmission. METHODS: Data were collected from the weekly reports on RSV incidence for the 2021/2022 and 2022/2023 seasons in Sweden. The 7-day cumulative incidence of RSV was compared before and after the designated school holidays (Fall, Christmas, and Winter holidays). RESULTS: Our findings reveal an immediate (-1.7%, p < 0.001, 95% CI [-3.1%, -0.4%]) and gradual (-1.4%/week, p < 0.001, 95%CI [-1.8, -1.0]) reduction in RSV incidence following the Fall holiday in 2021, especially among children under 1 year of age, both immediately (-107.6%, p < 0.05, 95% CI [-203.7, -11.5]) and gradually afterwards (-58.5%/week, p < 0.001, 95% CI [-72.7, -44.3]). Mixed results were obtained for the Fall in 2022/2023 and for the Winter and holidays in both the studied years. CONCLUSIONS: While the Fall holiday in 2021/2022 was associated with a decrease in RSV incidence in Sweden, our results do not support a universal effect of school holidays on reducing RSV transmission.

Respiratory syncytial virus seasonality, transmission zones, and implications for seasonal prevention strategy in China: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy. METHODS: We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993. FINDINGS: A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces). INTERPRETATION: Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions. FUNDING: Nanjing Medical University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Risk of Transmission and Viral Shedding From the Time of Infection for Respiratory Syncytial Virus in Households.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide, but reports of temporal changes in the risk of transmission among close contacts has been scarce. This study aimed to examine an association between the viral load trajectory and transmission risk to develop a better control strategy for the disease spread. We conducted a household-based prospective cohort study in Biliran Province, the Philippines, and enrolled 451 participants to observe the development of acute respiratory infection. Including the cases found at the health-care facility, we analyzed the data of viral loads with symptom records obtained from 172 followed participants who had household member positive for RSV with a rapid test during an RSV outbreak in 2018-2019. We developed a model estimating a temporal change in the viral shedding from the infection and evaluated transmission dynamics. We found that most transmission events occurred within approximately 7 days of the household exposure, including potential presymptomatic transmissions. The inferred risk of infection among those younger than 5 years was 3.5 times higher than that of those older than 5 years. This finding suggested that the initial week after the household exposure is particularly important for preventing RSV spread.

Absence of detection of RSV and influenza during the COVID-19 pandemic in a Brazilian cohort: Likely role of lower transmission in the community.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are prevalent seasonal community viruses. Although not completely understood, SARS-CoV-2 may have the same means of transmission. Preventive social measures aimed at preventing SARS-CoV-2 spread could impact transmission of other respiratory viruses as well. The aim of this study is to report the detection of RSV and influenza during the period of social distancing due to COVID-19 pandemic in a heavily affected community. METHODS: Prospective study with pediatric and adult populations seeking care for COVID-19-like symptoms during the fall and winter of 2020 at two hospitals in Southern Brazil. RT-PCR tests for SARS-CoV-2, influenza A (Flu A), influenza B (Flu B) and respiratory syncytial virus (RSV) was performed for all participants. RESULTS: 1435 suspected COVID-19 participants (1137 adults, and 298 children). were included between May and August. Median age was 37.7 years (IQR = 29.6-47.7), and 4.92 years (IQR = 1.96-9.53), for the adult and child cohorts, respectively. SARS-CoV-2 was positive in 469 (32.7%) while influenza and RSV were not detected at all. CONCLUSIONS: Measures to reduce SARS-CoV-2 transmission likely exerted a huge impact in the spread of alternate respiratory pathogens. These findings contribute to the knowledge about the dynamics of virus spread. Further, it may be considered for guiding therapeutic choices for these other viruses.

Extracellular amoebal-vesicles: potential transmission vehicles for respiratory viruses.

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and immunocompromised adults worldwide. Here we report that amoebae-release respirable-sized vesicles containing high concentrations of infectious RSV that persisted for the duration of the experiment. Given the ubiquity of amoebae in moist environments, our results suggest that extracellular amoebal-vesicles could contribute to the environmental persistence of respiratory viruses, including potential resistance to disinfection processes and thereby offering novel pathways for viral dissemination and transmission.

Integrating epidemiological and genetic data with different sampling intensities into a dynamic model of respiratory syncytial virus transmission.

Respiratory syncytial virus (RSV) is responsible for a significant burden of severe acute lower respiratory tract illness in children under 5 years old; particularly infants. Prior to rolling out any vaccination program, identification of the source of infant infections could further guide vaccination strategies. We extended a dynamic model calibrated at the individual host level initially fit to social-temporal data on shedding patterns to include whole genome sequencing data available at a lower sampling intensity. The study population was 493 individuals (55 aged < 1 year) distributed across 47 households, observed through one RSV season in coastal Kenya. We found that 58/97 (60%) of RSV-A and 65/125 (52%) of RSV-B cases arose from infection probably occurring within the household. Nineteen (45%) infant infections appeared to be the result of infection by other household members, of which 13 (68%) were a result of transmission from a household co-occupant aged between 2 and 13 years. The applicability of genomic data in studies of transmission dynamics is highly context specific; influenced by the question, data collection protocols and pathogen under investigation. The results further highlight the importance of pre-school and school-aged children in RSV transmission, particularly the role they play in directly infecting the household infant. These age groups are a potential RSV vaccination target group.

Absence of nosocomial influenza and respiratory syncytial virus infection in the coronavirus disease 2019 (COVID-19) era: Implication of universal masking in hospitals.

Universal masking for healthcare workers and patients in hospitals was adopted to combat coronavirus disease 2019 (COVID-19), with compliance rates of 100% and 75.9%, respectively. Zero rates of nosocomial influenza A, influenza B, and respiratory syncytial virus infection were achieved from February to April 2020, which was significantly lower than the corresponding months in 2017-2019.

Meteorological drivers of respiratory syncytial virus infections in Singapore.

Meteorological drivers are known to affect transmissibility of respiratory viruses including respiratory syncytial virus (RSV), but there are few studies quantifying the role of these drivers. We used daily RSV hospitalization data to estimate the daily effective reproduction number (Rt), a real-time measure of transmissibility, and examined its relationship with environmental drivers in Singapore from 2005 through 2015. We used multivariable regression models to quantify the proportion of the variance in Rt explained by each meteorological driver. After constructing a basic model for RSV seasonality, we found that by adding meteorological variables into this model we were able to explain a further 15% of the variance in RSV transmissibility. Lower and higher value of mean temperature, diurnal temperature range (DTR), precipitation and relative humidity were associated with increased RSV transmissibility, while higher value of maximum wind speed was correlated with decreased RSV transmissibility. We found that a number of meteorological drivers were associated with RSV transmissibility. While indoor conditions may differ from ambient outdoor conditions, our findings are indicative of a role of ambient temperature, humidity and wind speed in affecting RSV transmission that could be biological or could reflect indirect effects via the consequences on time spent indoors.

Estimating Transmission Parameters for Respiratory Syncytial Virus and Predicting the Impact of Maternal and Pediatric Vaccination.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. METHODS: Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012-2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. RESULTS: Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20-64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. CONCLUSIONS: Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0-5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits.

Respiratory Syncytial Virus and Human Metapneumovirus Infections in Three-Dimensional Human Airway Tissues Expose an Interesting Dichotomy in Viral Replication, Spread, and Inhibition by Neutralizing Antibodies.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two of the leading causes of respiratory infections in children and elderly and immunocompromised patients worldwide. There is no approved treatment for HMPV and only one prophylactic treatment against RSV, palivizumab, for high-risk infants. Better understanding of the viral lifecycles in a more relevant model system may help identify novel therapeutic targets. By utilizing three-dimensional (3-D) human airway tissues to examine viral infection in a physiologically relevant model system, we showed that RSV infects and spreads more efficiently than HMPV, with the latter requiring higher multiplicities of infection (MOIs) to yield similar levels of infection. Apical ciliated cells were the target for both viruses, but RSV apical release was significantly more efficient than HMPV. In RSV- or HMPV-infected cells, cytosolic inclusion bodies containing the nucleoprotein, phosphoprotein, and respective viral genomic RNA were clearly observed in human airway epithelial (HAE) culture. In HMPV-infected cells, actin-based filamentous extensions were more common (35.8%) than those found in RSV-infected cells (4.4%). Interestingly, neither RSV nor HMPV formed syncytia in HAE tissues. Palivizumab and nirsevimab effectively inhibited entry and spread of RSV in HAE tissues, with nirsevimab displaying significantly higher potency than palivizumab. In contrast, 54G10 completely inhibited HMPV entry but only modestly reduced viral spread, suggesting HMPV may use alternative mechanisms for spread. These results represent the first comparative analysis of infection by the two pneumoviruses in a physiologically relevant model, demonstrating an interesting dichotomy in the mechanisms of infection, spread, and consequent inhibition of the viral lifecycles by neutralizing monoclonal antibodies.IMPORTANCE Respiratory syncytial virus and human metapneumovirus are leading causes of respiratory illness worldwide, but limited treatment options are available. To better target these viruses, we examined key aspects of the viral life cycle in three-dimensional (3-D) human airway tissues. Both viruses establish efficient infection through the apical surface, but efficient spread and apical release were seen for respiratory syncytial virus (RSV) but not human metapneumovirus (HMPV). Both viruses form inclusion bodies, minimally composed of nucleoprotein (N), phosphoprotein (P), and viral RNA (vRNA), indicating that these structures are critical for replication in this more physiological model. HMPV formed significantly more long, filamentous actin-based extensions in human airway epithelial (HAE) tissues than RSV, suggesting HMPV may promote cell-to-cell spread via these extensions. Lastly, RSV entry and spread were fully inhibited by neutralizing antibodies palivizumab and the novel nirsevimab. In contrast, while HMPV entry was fully inhibited by 54G10, a neutralizing antibody, spread was only modestly reduced, further supporting a cell-to-cell spread mechanism.

Reducing respiratory syncytial virus (RSV) hospitalization in a lower-income country by vaccinating mothers-to-be and their households.

Respiratory syncytial virus is the leading cause of lower respiratory tract infection among infants. RSV is a priority for vaccine development. In this study, we investigate the potential effectiveness of a two-vaccine strategy aimed at mothers-to-be, thereby boosting maternally acquired antibodies of infants, and their household cohabitants, further cocooning infants against infection. We use a dynamic RSV transmission model which captures transmission both within households and communities, adapted to the changing demographics and RSV seasonality of a low-income country. Model parameters were inferred from past RSV hospitalisations, and forecasts made over a 10-year horizon. We find that a 50% reduction in RSV hospitalisations is possible if the maternal vaccine effectiveness can achieve 75 days of additional protection for newborns combined with a 75% coverage of their birth household co-inhabitants (~7.5% population coverage).

Epidemic dynamics of respiratory syncytial virus in current and future climates.

A key question for infectious disease dynamics is the impact of the climate on future burden. Here, we evaluate the climate drivers of respiratory syncytial virus (RSV), an important determinant of disease in young children. We combine a dataset of county-level observations from the US with state-level observations from Mexico, spanning much of the global range of climatological conditions. Using a combination of nonlinear epidemic models with statistical techniques, we find consistent patterns of climate drivers at a continental scale explaining latitudinal differences in the dynamics and timing of local epidemics. Strikingly, estimated effects of precipitation and humidity on transmission mirror prior results for influenza. We couple our model with projections for future climate, to show that temperature-driven increases to humidity may lead to a northward shift in the dynamic patterns observed and that the likelihood of severe outbreaks of RSV hinges on projections for extreme rainfall.

Transmission dynamics of acute respiratory diseases in a population structured by age.

Determining the role of age on the transmission of an infection is a topic that has received significant attention. In this work, a dataset of acute respiratory infections structured by age from San Luis Potosí, Mexico, is analyzed to understand the age impact on this class of diseases. To do that, a compartmental SEIRS multigroup model is proposed to describe the infection dynamics among age groups. Then, a Bayesian inference approach is used to estimate relevant parameters in the model such as the probability of infection, the average time that one individual remains infectious, the average time that one individual remains immune, and the force of infection, among others. Based on those estimates, our analysis leads us to conclude that children less than 5 years old are the primary spreaders of respiratory infections in San Luis Potosí's population from 2000 to 2008 since they are more prone to get sick, remain infectious for longer periods and they are reinfected more rapidly. On the other hand, the group of young adults (20-59) is the one that differs the most from the little children's group because it does not get sick often, it remains infectious only a few days and it stays healthy for longer periods. These observations allow us to infer that the group of young adults is the one that, on average, less contributed to the spread of this class of infections during the years represented in our database.

Respiratory Syncytial Virus: Spectrum of Clinical Manifestations and Complications in Children.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children. Despite its substantial disease burden, no effective vaccine is available. Clinical manifestations of RSV encompass the spectrum of acute upper and lower respiratory tract infection. Hallmarks of the virus are its propensity to progress to lower respiratory disease and to cause disproportionate disease severity at extremes of ages. Acute RSV infection may be complicated by secondary bacterial infections and respiratory failure requiring mechanical ventilation and prolonged hospitalization. In the developed world, most RSV infections are self-limited; however, globally, RSV is a significant cause of mortality in children younger than age 5 years. Severe RSV infection in infancy has also been associated with the development of childhood asthma. Thus, the extensive disease burden of RSV and its attributable mortality portend the urgency of vaccine development targeted toward populations disproportionately affected by severe disease. [Pediatr Ann. 2019;48(9):e349-e353.].

Genomic analysis of respiratory syncytial virus infections in households and utility in inferring who infects the infant.

Infants (under 1-year-old) are at most risk of life threatening respiratory syncytial virus (RSV) disease. RSV epidemiological data alone has been insufficient in defining who acquires infection from whom (WAIFW) within households. We investigated RSV genomic variation within and between infected individuals and assessed its potential utility in tracking transmission in households. Over an entire single RSV season in coastal Kenya, nasal swabs were collected from members of 20 households every 3-4 days regardless of symptom status and screened for RSV nucleic acid. Next generation sequencing was used to generate >90% RSV full-length genomes for 51.1% of positive samples (191/374). Single nucleotide polymorphisms (SNPs) observed during household infection outbreaks ranged from 0-21 (median: 3) while SNPs observed during single-host infection episodes ranged from 0-17 (median: 1). Using the viral genomic data alone there was insufficient resolution to fully reconstruct within-household transmission chains. For households with clear index cases, the most likely source of infant infection was via a toddler (aged 1 to <3 years-old) or school-aged (aged 6 to <12 years-old) co-occupant. However, for best resolution of WAIFW within households, we suggest an integrated analysis of RSV genomic and epidemiological data.

Modeling household dynamics on Respiratory Syncytial Virus (RSV).

Respiratory Syncytial Virus (RSV) is the most common cause of respiratory tract infection in infants and children and shows increasing trend among elderly people worldwide. In many developing country settings, population and household structures have gone through some significant changes in the past decades, namely fewer births, more elderly population, and smaller household size but more RSV high-risk individuals. These dynamics have been captured in a mathematical model with RSV transmission dynamics to predict the disease burden on the detailed population for future targeted interventions. The population and disease dynamics model was constructed and tested against the hospitalization data for Acute Lower Respiratory Tract Infection due to RSV in rural Thai settings between 2005 and 2011. The proportion of extended families is predicted to increase by about 10% from 2005 to 2020, especially for those with elderly population, while the classic nuclear family type (with adults and children) will decline by about 10%. For RSV, infections from extended family type (approximately 60% of all household types) have majorly contributed to the force of infection (FOI). While the model predicted the increase of FOI from the extended family by 15% from 2005 to 2020, the FOI contributed by other household types would be either stable or decrease in the same time period. RSV incidence rate is predominantly high among babies (92.2%) and has been predicted to decrease slightly over time (from 940 to 864 cases per 100,000 population by 2020), while the incidence rates among children and elderly people may remain steadily low over the same period. However, the estimated incidence rates among elderly people were twice than those in children. The model predicts that approximately 60% of FOI for RSV will come from members of the extended family type. The incidence rate of RSV among children and elderly in extended families was about 20 times lower than that in infants and the trend is steady. Targeted intervention strategies, such as health education in some specific groups and targeted vaccination, may be considered, with the focus on extended family type. Target interventions on babies can lessen the transmission to children and elderly especially when transmission within households of extended family type is high.

Bovine respiratory syncytial virus in experimentally exposed and rechallenged calves; viral shedding related to clinical signs and the potential for transmission.

BACKGROUND: Bovine respiratory syncytial virus (BRSV) is an important respiratory pathogen worldwide, detrimentally affecting the economy and animal welfare. To prevent and control BRSV infection, further knowledge on virus shedding and transmission potential in individual animals is required. This study aimed to detect viral RNA and infective virions during BRSV infection to evaluate duration of the transmission period and correlation with clinical signs of disease. The outcome of BRSV re-exposure on calves, their housing environment and effect of introduction of sentinel calves was also investigated. A live animal experiment including 10 calves was conducted over 61 days. Initially, two calves were inoculated with a non-passaged BRSV field isolate. Two days later, six naïve calves (EG: Exposed group) were introduced for commingling and four weeks later, another two naïve calves (SG: Sentinel group) were introduced. Seven weeks after commingling, EG animals were re-inoculated. Clinical examination was performed daily. Nasal swabs were collected regularly and analysed for viral RNA by RT-ddPCR, while virus isolation was performed in cell culture. BRSV serology was performed with ELISA. RESULTS: All the EG calves seroconverted and showed clinical signs of respiratory disease. Viral RNA was detected from days 1-27 after exposure, while the infective virus was isolated on day 6 and 13. On day 19, all animals were seropositive and virus could not be isolated. Total clinical score for respiratory signs corresponded well with the shedding of viral RNA. The SG animals, introduced 27 days after exposure, remained negative for BRSV RNA and stayed seronegative throughout the study. Inoculation of the EG calves seven weeks after primary infection did not lead to new shedding of viral RNA or clinical signs of disease. CONCLUSION: Viral RNA was detected in nasal swabs from the calves up to four weeks after exposure. The detection and amount of viral RNA corresponded well with the degree of respiratory signs. The calves were shedding infective virions for a considerable shorter period, and naïve calves introduced after four weeks were not infected. Infected calves were protected from reinfection for at least seven weeks. This knowledge is useful to prevent spread of BRSV.