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The role of the public health laboratory (PHL) in support of public health response has expanded beyond testing to include a number of other core functions, such as emergency response, training and outreach, communications, laboratory-based surveillance, and laboratory data management. These functions can only be accomplished by a network that includes public health and other agency laboratories and clinical laboratories. It is a primary responsibility of the PHL to develop and maintain such a network. In this article, we pre- sent practical recommendations-based on 17 years of network development experience-for the development of statewide laboratory networks. These recommendations, and examples of current laboratory networks, are provided to facilitate laboratory network development in other states. The development of laboratory networks will enhance each state's public health system and is critical to the development of a robust national Laboratory Response Network. [ABSTRACT FROM AUTHOR]

Describes the epidemiology of and clinical findings associated with a rhinovirus outbreak that occurred among institutionalized elderly persons. Number of illnesses and rhinovirus isolates; Demographic information and underlying conditions; Comparison of illness in persons with and without lung disease.

To assess whether the use of rapid influenza diagnostic tests (RIDTs) for long-term care facility (LTCF) residents with acute respiratory infection is associated with increased antiviral use and decreased health care utilization. Nonblinded, pragmatic, randomized controlled trial evaluating a 2-part intervention with modified case identification criteria and nursing staff–initiated collection of nasal swab specimen for on-site RIDT. Residents of 20 LTCFs in Wisconsin matched by bed capacity and geographic location and then randomized. Primary outcome measures, expressed as events per 1000 resident-weeks, included antiviral treatment courses, antiviral prophylaxis courses, total emergency department (ED) visits, ED visits for respiratory illness, total hospitalizations, hospitalizations for respiratory illness, hospital length of stay, total deaths, and deaths due to respiratory illness over 3 influenza seasons. Oseltamivir use for prophylaxis was higher at intervention LTCFs [2.6 vs 1.9 courses per 1000 person-weeks; rate ratio (RR) 1.38, 95% CI 1.24-1.54; P <.001]; rates of oseltamivir use for influenza treatment were not different. Rates of total ED visits (7.6 vs 9.8/1000 person-weeks; RR 0.78, 95% CI 0.64-0.92; P =.004), total hospitalizations (8.6 vs 11.0/1000 person-weeks; RR 0.79, 95% CI 0.67-0.93; P =.004), and hospital length of stay (35.6 days vs 55.5 days/1000 person-weeks; RR 0.64, 95% CI 0.0.59-0.69; P <.001) were lower at intervention as compared to control LTCFs. No significant differences were noted for respiratory-related ED visits or hospitalizations or in rates for all-cause or respiratory-associated mortality. The use of low threshold criteria to trigger nursing staff–initiated testing for influenza with RIDT resulted in increased prophylactic use of oseltamivir. There were significant reductions in the rates of all-cause ED visits (22% decline), hospitalizations (21% decline), and hospital length of stay (36% decline) across 3 combined influenza seasons. No significant differences were noted in respiratory-associated and all-cause deaths between intervention and control sites. [ABSTRACT FROM AUTHOR]

Residents of long-term care facilities (LCTFs) have high morbidity and mortality associated with acute respiratory infections (ARIs). Limited information exists on the virology of ARI in LTCFs, where virological testing is reactive. We report on findings of a surveillance feasibility substudy from a larger prospective trial of introducing rapid influenza diagnostic testing (RIDT) at 10 Wisconsin LTCFs. Any resident with symptoms consistent with ARI had a nasal swab specimen collected for RIDT by staff. Following RIDT, the residual swab was placed into viral transport medium and tested for influenza using Reverse transcription polymerase chain reaction, and for 20 pathogens using a multiplex polymerase chain reaction respiratory pathogen panel. Numbers of viruses in each of 7 categories (influenza A, influenza B, coronaviruses, human metapneumovirus, parainfluenza, respiratory syncytial virus, and rhinovirus/enterovirus) across the 3 years were compared using χ2. Totals of 160, 215, and 122 specimens were collected during 2016‒2017, 2017‒2018, and 2018‒2019, respectively. Respiratory pathogen panel identified viruses in 54.8% of tested specimens. Influenza A (19.2%), influenza B (12.6%), respiratory syncytial virus (15.9%), and human metapneumovirus (20.9%) accounted for 69% of all detections, whereas coronaviruses (17.2%), rhinovirus/enterovirus (10.5%) and parainfluenza (3.8%) were less common. The distribution of viruses varied significantly across the 3 years (χ2 = 71.663; df = 12; P <.001). Surveillance in LTCFs using nasal swabs collected for RIDT is highly feasible and yields high virus identification rates. Significant differences in virus composition occurred across the 3 study years. Simple approaches to surveillance may provide a more comprehensive assessment of respiratory viruses in LTCF settings. [ABSTRACT FROM AUTHOR]

Background: Seasonal influenza leads to an increase in outpatient clinic visits. Timely, accurate, and affordable testing could facilitate improved treatment outcomes. Rapid influenza diagnostic tests (RIDTs) provide results in as little as 15 minutes and are relatively inexpensive, but have reduced sensitivity when compared to RT-PCR. The contributions of multiple factors related to test performance are not well defined for ambulatory care settings. We assessed clinical and laboratory factors that may affect the sensitivity and specificity of Sofia Influenza A+B Fluorescence Immunoassay. Study design: We performed a post-hoc assessment of surveillance data amassed over seven years from five primary care clinics. We analyzed 4,475 paired RIDT and RT-PCR results from specimens collected from patients presenting with respiratory symptoms and examined eleven potential factors with additional sub-categories that could affect RIDT sensitivity. Results: In an unadjusted analysis, greater sensitivity was associated with the presence of an influenza-like illness (ILI), no other virus detected, no seasonal influenza vaccination, younger age, lower cycle threshold value, fewer days since illness onset, nasal discharge, stuffy nose, and fever. After adjustment, presence of an ILI, younger age, fewer days from onset, no co-detection, and presence of a nasal discharge maintained significance. Conclusion: Clinical and laboratory factors may affect RIDT sensitivity. Identifying potential factors during point-of-care testing could aid clinicians in appropriately interpreting negative influenza RIDT results. [ABSTRACT FROM AUTHOR]

Background: Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community. Materials and methods: Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining the OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis. Findings: Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53–0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44–0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21–0.33), following MAI by six days. Discussion: Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts. [ABSTRACT FROM AUTHOR]

Background: Influenza viruses pose significant disease burdens through seasonal outbreaks and unpredictable pandemics. Existing surveillance programs rely heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause‐specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school‐based monitoring of influenza‐like illness‐specific student absenteeism (a‐ILI) in kindergarten through Grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Methods: Starting in September 2014, ORCHARDS combines automated reporting of daily absenteeism within six schools and home visits to school children with acute respiratory infection (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre‐existing and highly effective influenza surveillance program, based on MAI at five family medicine clinics in the same geographical area. Results: Over the first 5 years, a‐ILI occurred on 6634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of 1728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Conclusion: ORCHARDS uses a community‐based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. [ABSTRACT FROM AUTHOR]

Human-to-swine transmission of seasonal influenza viruses has led to sustained human-like influenza viruses circulating in the U.S. swine population. While some reverse zoonotic-origin viruses adapt and become enzootic in swine, nascent reverse zoonoses may result in virus detections that are difficult to classify as "swine-origin" or "human-origin" due to the genetic similarity of circulating viruses. This is the case for human-origin influenza A(H1N1) pandemic 2009 (pdm09) viruses detected in pigs following numerous reverse zoonosis events since the 2009 pandemic. We report the identification of two human infections with A(H1N1)pdm09 viruses originating from swine hosts and classify them as "swine-origin" variant influenza viruses based on phylogenetic analysis and sequence comparison methods. Phylogenetic analyses of viral genomes from two cases revealed these viruses were reassortants containing A(H1N1)pdm09 hemagglutinin (HA) and neuraminidase (NA) genes with genetic combinations derived from the triple reassortant internal gene cassette. Follow-up investigations determined that one individual had direct exposure to swine in the week preceding illness onset, while another did not report swine exposure. The swine-origin A(H1N1) variant cases were resolved by full genome sequence comparison of the variant viruses to swine influenza genomes. However, if reassortment does not result in the acquisition of swine-associated genes and swine virus genomic sequences are not available from the exposure source, future cases may not be discernible. We have developed a pipeline that performs maximum likelihood analyses, a k-mer-based set difference algorithm, and random forest algorithms to identify swine-associated sequences in the hemagglutinin gene to differentiate between human-origin and swine-origin A(H1N1)pdm09 viruses. [ABSTRACT FROM AUTHOR]

Influenza virus isolation from clinical samples is critical for the identification and characterization of circulating and emerging viruses. Yet efficient isolation can be difficult. In these studies, we isolated primary swine nasal and tracheal respiratory epithelial cells and immortalized swine nasal epithelial cells (siNEC) and tracheal epithelial cells (siTEC) that retained the abilities to form tight junctions and cilia and to differentiate at the air-liquid interface like primary cells. Critically, both human and swine influenza viruses replicated in the immortalized cells, which generally yielded higher-titer viral isolates from human and swine nasal swabs, supported the replication of isolates that failed to grow in Madin-Darby canine kidney (MDCK) cells, and resulted in fewer dominating mutations during viral passaging than MDCK cells. [ABSTRACT FROM AUTHOR]

We analyzed 4,352 participant- and staff-collected respiratory specimens from 2,796 subjects in the Oregon Child Absenteeism due to Respiratory Disease Study. Trained staff collected oropharyngeal specimens from school-aged children with acute respiratory illness while household participants of all ages collected their own midturbinate nasal specimens in year one and anterior nasal specimens in year two. Human ribonuclease P levels were measured using RT-PCR for all staff- and participant-collected specimens to determine adequacy, defined as Cycle threshold less than 38. Overall, staff- and participant-collected specimens were 99.9% and 96.4% adequate, respectively. Participant-collected midturbinate specimens were 95.2% adequate in year one, increasing to 97.2% in year two with anterior nasal collection. The mean human ribonuclease P Cycle threshold for participant-collected specimens was 31.18 in year one and 28.48 in year two. The results from this study suggest that community-based participant collection of respiratory specimens is comparable to staff-collected oropharyngeal specimens, is feasible, and may be optimal with anterior nasal collection. [ABSTRACT FROM AUTHOR]

Cocirculation of varying influenza types, strains, and lineages allows coinfection and intra‐season sequential infection, although a same‐strain sequential infection has not been previously described. This case report describes the first known case of sequential laboratory‐confirmed influenza A (H3N2) infections in a child within one season. [ABSTRACT FROM AUTHOR]

Background: Antiviral chemoprophylaxis effectiveness for influenza control has not been prospectively established for unvaccinated residents of long-term care facilities. This study evaluated the efficacy and tolerability of zanamivir against the standard of care (no intervention, ie, placebo) for influenza outbreak control in a largely unvaccinated institutionalized population. Objective: To evaluate the efficacy and tolerability of zanamivir versus placebo for influenza outbreak control in long-term care facilities. Methods: This double-blind, randomized, placebo-controlled study prospectively enrolled/followed residents of long-term care facilities (LTCF) at 12 centers for 1 to 3 influenza seasons (1997 to 2000). Following influenza outbreak declaration, asymptomatic subjects were randomized for prophylaxis to inhaled zanamivir 10 mg or inhaled placebo given once daily for 14 days. The proportion of randomized subjects who during prophylaxis developed symptomatic, laboratory-confirmed influenza (SLCI) was the primary end point. Results: Influenza outbreaks were explosive. The attack rates varied from 9.5 to 14.8 per 100 residents. Of 1763 consents given and resulting in 494 randomizations, 49% received zanamivir and 51% placebo; 66% were elderly and 9% were vaccinated. SLCI occurred in 6% of zanamivir and 9% of placebo subjects (P = .355; protective efficacy for zanamivir = 29%, 95% confidence interval 31% to 62%), and symptomatic influenza confirmed by culture in 2% and 6%, respectively (P = .052; protective efficacy = 65%, 95% confidence interval 8.5% to 86%). Zanamivir use was also associated with a 70% (95% confidence interval 13% to 89%) reduction in laboratory-confirmed influenza with fever (2% vs 6%, P = .043). Influenza B was not detected. Zanamivir was well tolerated. No virus isolate demonstrated zanamivir resistance. Conclusions: The protective efficacy of zanamivir versus placebo for SLCI was marginal, for all laboratory confirmed illnesses, but significant against culture proven and febrile influenza, suggesting zanamivir can be effective for outbreak control and symptom reduction of unvaccinated institutionalized residents. Zanamivir had an acceptable safety profile in elderly, high-risk LTCF residents and was not associated with the emergence of resistant strains. [Copyright &y& Elsevier]

Background: Despite vaccination, influenza commonly causes morbidity and mortality in institutional settings. Influenza control with rimantadine and amantadine is limited by emergence and transmission of drug-resistant influenza A variants, ineffectiveness against influenza B, and toxicity. This study evaluated the efficacy and tolerability of zanamivir versus rimantadine for influenza outbreak control in long-term care facilities. Methods: This double-blind, randomized, controlled study prospectively enrolled nursing home residents for 3 influenza seasons (1997 to 2000). Vaccine was offered to all subjects. Following influenza outbreak declaration, subjects were randomized to inhaled zanamivir 10 mg or standard of care (rimantadine 100 mg for influenza A or placebo for influenza B) once daily for 14 days. The proportion of randomized subjects developing symptomatic, laboratory-confirmed influenza during prophylaxis was the primary endpoint. Results: Of 482 randomizations (238 zanamivir, 231 rimantadine, 13 placebo), 96% of subjects were elderly or had high-risk conditions; over 90% were vaccinated. Symptomatic, laboratory-confirmed influenza occurred in 3% of zanamivir subjects and 8% of rimantadine subjects during chemoprophylaxis (P = .038; additional protective efficacy for zanamivir over rimantadine = 61%). Since only 25 subjects were randomized during 2 influenza B outbreaks and none developed influenza, the influenza B data were excluded from further analysis. Zanamivir was well tolerated and unassociated with emergence of resistant virus; rimantadine-resistant variants were common. Conclusions: This is the first prospective, controlled study demonstrating effectiveness of chemoprophylaxis for influenza outbreak control. Zanamivir prevents symptomatic, laboratory-confirmed influenza more effectively than rimantadine, is unassociated with resistant virus, and has a favorable safety profile. Zanamivir is an appropriate alternative for influenza outbreak control among institutionalized vaccinated elderly. [Copyright &y& Elsevier]

Asthma is a common disease that results from both genetic and environmental risk factors. Children attending day care in the 1st year of life have lower risks for developing asthma, although the mechanism for this ‘day care’ effect is largely unknown. We investigated the interactions between day care exposure in the 1st 6 mo of life and genotypes for 72 polymorphisms at 45 candidate loci and their effects on cytokine response profiles and on the development of atopic phenotypes in the 1st year of life in the Childhood Onset of Asthma (COAST) cohort of children. Six interactions (at four polymorphisms in three loci) with ‘day care’ that had an effect on early-life immune phenotypes were significant at . The estimated false-discovery rate was 33%, indicating that an P< .001 estimated four P values correspond to true associations. Moreover, the "day care" effect at some loci was accounted for by the increased number of viral infections among COAST children attending day care, whereas interactions at other loci were independent of the number of viral infections, indicating the presence of additional risk factors associated with day care environment. This study identified significant gene-environment interactions influencing the early patterning of the immune system and the subsequent development of asthma and highlights the importance of considering environmental risk factors in genetic analyses. [ABSTRACT FROM AUTHOR]

To prospectively detect amantadine-resistant influenza when amantadine was used for influenza A outbreak control.Prospective clinical surveillance and viral culture of all new respiratory illnesses during the course of amantadine prophylaxis.A 721-bed, 14-ward nursing home for veterans and spouses during an influenza A outbreak (1993–94).Residents of a veterans hospital and their spouses.Nasopharyngeal and throat viral culture. All residents with positive cultures who developed new respiratory symptoms while receiving or residing on a unit receiving amantadine prophylaxis had antiviral-resistance testing and polymerase chain reaction restriction analyses performed.Amantadine prophylaxis was administered sequentially on nine of 14 wards to all well residents for 14 to 31 days/ward to control influenza outbreaks between December 9, 1993, and January 28, 1994. Amantadine treatment was simultaneously provided to 29 ill residents. Between December 3, 1993, and January 22, 1994, 68 culture-positive cases of influenza A were detected. Twenty subjects were receiving or residing on units receiving amantadine prophylaxis. Amantadine sensitivity testing could be performed on 16 residents; 12 residents had amantadine resistant strains. Four of the 12 had not received any antiviral treatment. Illness onset ranged from 1 to 22 days after amantadine prophylaxis was begun on the individual's unit. Two ribonucleic acid (RNA) mutations in the gene coding the M2 protein transmembrane region were observed that were clustered in time and space. Isolates from two roommates, one receiving amantadine for 18 days and one on no antiviral, had identical RNA sequences.Antiviral resistance may be responsible for failure of prophylaxis in nursing home outbreaks. Strategies that use different classes of antivirals for prophylaxis and treatment may limit emergence and transmission of resistant virus. [ABSTRACT FROM AUTHOR]

Both virus-mediated damage to airway tissues and induction of pro-inflammatory cytokines such as interleukin-8 (IL-8) could contribute to symptom severity during viral respiratory infections in children. To test the hypothesis that IL-8 contributes to the pathogenesis of respiratory symptoms during naturally acquired respiratory viral infections in children, nasal wash samples collected from infants with acute viral infections (n = 198) or from healthy uninfected infants (n = 31) were analysed for IL-8. Nasal wash IL-8 was positively related to age in uninfected children (r s = 0.36, p < 0.05). Respiratory syncytial virus (RSV) infection caused more severe respiratory symptoms compared to infections with influenza A, parainfluenza viruses, or rhinoviruses. In addition, RSV, parainfluenza and rhinovirus infections increased levels of IL-8 in nasal lavage fluid, and there were some differences in the ability of the viruses to induce IL-8 production (RSV>influenza, p < 0.05). Finally, there were significant correlations between nasal wash IL-8 levels and symptom scores during infections with rhinovirus (r s = 0.56, p < 0.001) or influenza A (r s = 0.45, p < 0.05), but not with parainfluenza virus or RSV. These findings provide evidence of a close relationship between the generation of IL-8 and symptoms during acute community-acquired infections with rhinovirus or influenza A. In contrast, for RSV and parainfluenza infections, factors in addition to IL-8 production appear to contribute to the generation of clinical symptoms. [ABSTRACT FROM AUTHOR]

Focuses on the functions and capabilities of State Public Health Laboratories (SPHL) in the U.S. Role of SPHL in developing health policies; Importance of high quality laboratory services to health care systems; Information on the funding of SPHL; Details on the National Laboratory System.

BACKGROUND. Large outbreaks of influenza A and B may occur in nursing homes despite high resident vaccination rates, even when the vaccine strain is matched to the circulating strain. This study reports the occurrence of separate influenza A and B outbreaks in a nursing home where more than 85% of residents were vaccinated. METHODS. Prospective surveillance was used to identify symptomatic residents in a rural Wisconsin nursing home with 680 residents. Viral cultures were obtained from all consenting residents identified with new respiratory symptoms even in the absence of temperature elevation. A "case" refers to a resident with a respiratory illness and an influenza isolate. RESULTS. During the 1992-93 season, 86% of 670 total residents were vaccinated, 104 (15.5%) were cases with influenza B. During the 1993-94 season, 89% of 690 total residents were vaccinated, 68 (9.8%) were cases with influenza A. The antigenic matches between vaccine and epidemic strains were characterized as "identical or minimal difference" by the Centers for Disease Control and Prevention. CONCLUSIONS. There is still a need to protect residents from infectious secretions and for contingency plans to permit the rapid use of antiviral agents. Future efforts are needed to develop vaccines that provide greater protection and to improve staff vaccination rates. [ABSTRACT FROM AUTHOR]

• From 2015–2017 greater than 13,800 cases of mumps were reported in the United States. • In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. • Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was lo. Most sequences (98.7 %) were genotype G. • Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. Despite high coverage with measles, mumps, and rubella vaccine in the United States, outbreaks of mumps occur in close contact settings such as schools, colleges, and camps. Starting in late 2015, outbreaks were reported from several universities, and by the end of 2017, greater than 13,800 cases had been reported nation-wide. In 2013, the CDC and the Association of Public Health Laboratories contracted four Vaccine Preventable Diseases Reference Centers (VPD-RCs) to perform real-time reverse transcription PCR (RT-qPCR) to detect mumps RNA in clinical samples and to determine the genotype. Twelve genotypes of mumps virus are currently recognized by the World Health Organization, and the standard protocol for genotyping requires sequencing the entire gene coding for the small hydrophobic (SH) protein. Phylogenetic analysis of the 1862 mumps samples genotyped from 2015 through 2017 showed that the overall diversity of genotypes detected was low. Only 0.8 % of the sequences were identified as genotypes C, H, J, or K, and 0.5 % were identified as vaccine strains in genotypes A or N, while most sequences (98.7 %) were genotype G. The majority of the genotype G sequences could be included into one of two large groups with identical SH sequences. Within genotype G, a small number of phylogenetically significant outlier sequences were associated with epidemiologically distinct chains of transmission. These results demonstrate that molecular and epidemiologic data can be used to track transmission pathways of mumps virus; however, the limited diversity of the SH sequences may be insufficient for resolving transmission in all outbreaks. [ABSTRACT FROM AUTHOR]