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Background. The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; denned as the presence of ≥2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. Methods. From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. Results. The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2-17 years, whereas other viruses had varied patterns among age groups. Conclusions. The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

Background Little is known about laboratory capacity to routinely diagnose influenza and other respiratory viruses at clinical laboratories and hospitals. Aims We sought to assess diagnostic practices for influenza and other respiratory virus in a survey of hospitals and laboratories participating in the US Influenza Hospitalization Surveillance Network in 2012–2013. Materials and Methods All hospitals and their associated laboratories participating in the Influenza Hospitalization Surveillance Network (FluSurv‐NET) were included in this evaluation. The network covers more than 80 counties in 15 states, CA, CO, CT, GA, MD, MN, NM, NY, OR, TN, IA, MI, OH, RI, and UT, with a catchment population of ~28 million people. We administered a standardized questionnaire to key personnel, including infection control practitioners and laboratory departments, at each hospital through telephone interviews. Results Of the 240 participating laboratories, 67% relied only on commercially available rapid influenza diagnostic tests to diagnose influenza. Few reported the availability of molecular diagnostic assays for detection of influenza (26%) and other viral pathogens (≤20%) in hospitals and commercial laboratories. Conclusion Reliance on insensitive assays to detect influenza may detract from optimal clinical management of influenza infections in hospitals.

Viruses cause the majority of respiratory infections. A rapid laboratory method to accurately diagnose etiology of respiratory illness can inform physicians and guide treatment decisions. The objective of this cross-sectional, laboratory based surveillance study is to assess the sensitivity and specificity of influenza virus rapid antigen assay Quidel A+B (Quidel, San Diego, CA) and two multiplex respiratory pathogen assays [Idaho Technology FilmArray® Respiratory Panel (Idaho Technology, Inc., Salt Lake City, UT) and Qiagen ResPlex™ II (Qiagen, Germantown, MD)] compared with influenza virus polymerase chain reaction (PCR) assays. Patients seeking treatment for influenza-like-illness (ILI) in the outpatient setting were identified between October 17, 2010 and May 31, 2011. A total of 1,481 ILI patients were seen. Nasal specimens were collected and tested on all assays for 253 of these patients. Sensitivity and specificity of each influenza and multiplex respiratory assay was calculated relative to a gold standard PCR assay. The self-reported symptom profiles of each organism identified in the respiratory pathogen panels were compared. The median patient age was 12 years (range: 0-89 years); 176 (70%) had one or more viruses detected in the nasal swab specimen. Sensitivity for influenza A was 92% (95% CI: 88-99%) for FilmArray® RP, 85% (95% CI: 81-96%) for ResPlex™ II, and 38% (95% CI: 48-71%) for Rapid, with specificities of 99.5-100%. Sensitivity for influenza B was 85% (95% CI: 86-99%), 70% (95% CI: 66-90%) for ResPlex™ II, and 6% (95% CI: 0-23%) for Rapid, with specificities of 99.5-100%. A similar pattern was seen for noninfluenza viruses, with the FilmArray® RP assay being more sensitive and specific than the ResPlex™ II. The use of multiplex viral assays is becoming more common in point-of-care settings. In this study, the Idaho Technology FilmArray® Respiratory Panel was more sensitive and specific than the Qiagen ResPlex™ II assay for influenza A and B viruses, as well as other common respiratory viruses.

On July 12, 2016, the Utah Department of Health (UDOH) was notified by a clinician caring for an adult (patient A) who was evaluated for fever, rash, and conjunctivitis that began on July 1. Patient A had not traveled to an area with ongoing Zika virus transmission; had not had sexual contact with a person who recently traveled; and had not received a blood transfusion, organ transplant, or mosquito bites (1). Patient A provided care over several days to an elderly male family contact (the index patient) who contracted Zika virus abroad. The index patient developed septic shock with multiple organ failure and died in the hospital on June 25, 2016. The index patient's blood specimen obtained 2 days before his death had a level of viremia approximately 100,000 times higher than the average level reported in persons infected with Zika virus (2). Zika virus infection was diagnosed in patient A by real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing on a urine specimen collected 7 days after symptom onset. In addition, a serum specimen collected 11 days after symptom onset, after patient A's symptoms had resolved, was positive for antibodies to Zika virus by Zika immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (MAC-ELISA) and had neutralizing antibodies detected by plaque-reduction neutralization testing (PRNT). Working with Salt Lake and Davis County Health Departments, UDOH requested assistance from CDC with an investigation to determine patient A's exposures and determine a probable source of infection.

In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution. Competing Interest Statement The authors have declared no competing interest.

On Jul 12, 2016, the Utah Department of Health was notified by a clinician caring for an adult (patient A) who was evaluated for fever, rash, and conjunctivitis that began on July 1. Patient A had not traveled to an area with ongoing Zika virus transmission; had not had sexual contact with a person who recently traveled; and had not received a blood transfusion, organ transplant, or mosquito bites. Patient A provided care over several days to an elderly male family contact who contracted Zika virus abroad. The investigation consisted of four components: an epidemiologic evaluation of family contacts of the index patient, a serosurvey of health care workers who provided direct care to the index patient before his death, a community serosurvey around the locations where the index patient had resided, and active vector surveillance near the residences of the index patient and patient A.

In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.