Predictors of influenza a molecular viral shedding in Hutterite communities

Wang, Biao; Russell, Margaret L.; Fonseca, Kevin; Earn, David J. D.; Horsman, Gregory; Caeseele, Paul Van; Chokani, Khami; Vooght, Mark; Babiuk, Lorne A.; Walter, Stephen D.; Loeb, Mark

doi:10.1111/irv.12448

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…Given that rhinovirus causes similar upper respiratory tract symptoms as influenza, we used the same parameterization for these two pathogens for volume of fluid excretion and number of shedding events, but influenza had a higher concentration per shedding event. While viral shedding rates were similar for all age groups for both rhinovirus and norovirus, very young children (< 1 year) had higher influenza shedding rates [25][26][27]. Betweenindividual shedding rates were high among young children and we were only able to find estimates from one small study, which suggested that young children might shed up 2 orders of magnitude more than older individuals [25].…”

Section: Literature Reviewmentioning

confidence: 63%

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

et al. 2018

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BackgroundFomite mediated transmission can be an important pathway causing significant disease transmission in number of settings such as schools, daycare centers, and long-term care facilities. The importance of these pathways relative to other transmission pathways such as direct person-person or airborne will depend on the characteristics of the particular pathogen and the venue in which transmission occurs. Here we analyze fomite mediated transmission through a comparative analysis across multiple pathogens and venues.MethodsWe developed and analyzed a compartmental model that explicitly accounts for fomite transmission by including pathogen transfer between hands and surfaces. We consider two sub-types of fomite-mediated transmission: direct fomite (e.g., shedding onto fomites) and hand-fomite (e.g., shedding onto hands and then contacting fomites). We use this model to examine three pathogens with distinct environmental characteristics (influenza, rhinovirus, and norovirus) in four venue types. To parameterize the model for each pathogen we conducted a thorough literature search.ResultsBased on parameter estimates from the literature the reproductive number () for the fomite route for rhinovirus and norovirus is greater than 1 in nearly all venues considered, suggesting that this route can sustain transmission. For influenza, on the other hand, for the fomite route is smaller suggesting many conditions in which the pathway may not sustain transmission. Additionally, the direct fomite route is more relevant than the hand-fomite route for influenza and rhinovirus, compared to norovirus. The relative importance of the hand-fomite vs. direct fomite route for norovirus is strongly dependent on the fraction of pathogens initially shed to hands. Sensitivity analysis stresses the need for accurate measurements of environmental inactivation rates, transfer efficiencies, and pathogen shedding.ConclusionsFomite-mediated transmission is an important pathway for the three pathogens examined. The effectiveness of environmental interventions differs significantly both by pathogen and venue. While fomite-based interventions may be able to lower for fomites below 1 and interrupt transmission, rhinovirus and norovirus are so infectious () that single environmental interventions are unlikely to interrupt fomite transmission for these pathogens.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3425-x) contains supplementary material, which is available to authorized users.

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Section: Literature Reviewmentioning

confidence: 63%

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

et al. 2018

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“…There were more visitors and infected patients in the pediatric than the adult patient rooms which could possibly contribute to a higher viral load in the pediatric environment. Some studies postulated children may be more infectious than adults by longer duration of virus shedding 13 or increased peak viral load, but a systematic review found no difference in quantity of virus RNA in respiratory swabs by age 29,30 …”

Section: Discussionmentioning

confidence: 99%

Frequent recovery of influenza A but not influenza B virus RNA in aerosols in pediatric patient rooms

Shiu

Huang

et al. 2020

Indoor Air

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Influenza transmission occurs through the air, but the relative importance of small droplets, or aerosols, in influenza transmission especially within healthcare facilities remains uncertain. Detections of influenza virus in aerosols in cough and exhaled breath from infected patients and from the air in outpatient or inpatient healthcare facilities have been studied, but most studies were done in adults with very few data involving children. We aimed to assess the potential of influenza transmission via aerosols in pediatric patient rooms. Two‐stage cyclone (NIOSH) air samplers were used to collect the air in 5‐bed pediatric patient rooms with patients with influenza‐like illness. Influenza A virus RNA was recovered in 15/19 (79%) air sampling occasions with ≥1 patient with laboratory‐confirmed influenza A virus infections, in all air size fractions (>4 µm, 1‐4 µm and <1 µm). Influenza B virus RNA was significantly less detected (2/10 occasions, 20%). We estimated a ventilation rate of 1.46 ACH in a similar but unoccupied 5‐bed patient room. High quantities of influenza A virus RNA detected in the air in pediatric patient rooms suggests other individuals in pediatric patient rooms including other patients, visitors, caretakers and healthcare workers could be exposed to influenza A virus in aerosols while caring for infected children.

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“…This masking of gene expression biomarkers will reduce the predictive accuracy of point-of-care devices. While clinical symptoms, such as disease severity and presence of pneumonia, and demographic data, such as age and presence of comorbidities, are correlates of length of shedding (27)(28)(29)(30)(31), many of these clinical disease correlates of medically attended influenza do not manifest until many days after infection and have limited prognostic value. In contrast, significant differential PBL gene expression can be observed before 48 h postexposure just as symptoms are beginning to appear.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Influenza Virus NA, HA Head, and HA Stalk Antibodies on Peripheral Blood Leukocyte Gene Expression during Human Infection

Walters

Zhu

Welge

et al. 2019

mBio

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In this study, we examined the relationships between anti-influenza virus serum antibody titers, clinical disease, and peripheral blood leukocyte (PBL) global gene expression during presymptomatic, acute, and convalescent illness in 83 participants infected with 2009 pandemic H1N1 virus in a human influenza challenge model. Using traditional statistical and logistic regression modeling approaches, profiles of differentially expressed genes that correlated with active viral shedding, predicted length of viral shedding, and predicted illness severity were identified. These analyses further demonstrated that challenge participants fell into three peripheral blood leukocyte gene expression phenotypes that significantly correlated with different clinical outcomes and prechallenge serum titers of antibodies specific for the viral neuraminidase, hemagglutinin head, and hemagglutinin stalk. Higher prechallenge serum antibody titers were inversely correlated with leukocyte responsiveness in participants with active disease and could mask expression of peripheral blood markers of clinical disease in some participants, including viral shedding and symptom severity. Consequently, preexisting anti-influenza antibodies may modulate PBL gene expression, and this must be taken into consideration in the development and interpretation of peripheral blood diagnostic and prognostic assays of influenza infection. IMPORTANCE Influenza A viruses are significant human pathogens that caused 83,000 deaths in the United States during 2017 to 2018, and there is need to understand the molecular correlates of illness and to identify prognostic markers of viral infection, symptom severity, and disease course. Preexisting antibodies against viral neuraminidase (NA) and hemagglutinin (HA) proteins play a critical role in lessening disease severity. We performed global gene expression profiling of peripheral blood leukocytes collected during acute and convalescent phases from a large cohort of people infected with A/H1N1pdm virus. Using statistical and machine-learning approaches, populations of genes were identified early in infection that correlated with active viral shedding, predicted length of shedding, or disease severity. Finally, these gene expression responses were differentially affected by increased levels of preexisting influenza antibodies, which could mask detection of these markers of contagiousness and disease severity in people with active clinical disease.

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Predictors of influenza a molecular viral shedding in Hutterite communities

Cited by 16 publications

References 31 publications

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

Fomite-mediated transmission as a sufficient pathway: a comparative analysis across three viral pathogens

Frequent recovery of influenza A but not influenza B virus RNA in aerosols in pediatric patient rooms

Differential Effects of Influenza Virus NA, HA Head, and HA Stalk Antibodies on Peripheral Blood Leukocyte Gene Expression during Human Infection

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