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Purpose: Receiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined., Results: We compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46-0.51)., Conclusions: Receipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections., (Published by Elsevier Ltd.)

The immunocompromised patient with an acute respiratory illness (ARI) may present with fever, chills, weight loss, cough, shortness of breath, or chest pain. The number of immunocompromised patients continues to rise with medical advances including solid organ and stem cell transplantation, chemotherapy, and immunomodulatory therapy, along with the continued presence of human immunodeficiency virus and acquired immunodeficiency syndrome. Given the myriad of pathogens that can infect immunocompromised individuals, identifying the specific organism or organisms causing the lung disease can be elusive. Moreover, immunocompromised patients often receive prophylactic or empiric antimicrobial therapy, further complicating diagnostic evaluation. Noninfectious causes for ARI should also be considered, including pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, pulmonary hemorrhage, diffuse alveolar damage, organizing pneumonia, lung transplant rejection, and pulmonary thromboembolic disease. As many immunocompromised patients with ARI progress along a rapid and potentially fatal course, timely selection of appropriate imaging is of great importance in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking, or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to conduct a prospective analysis of the association between negative life events (NLEs) and respiratory infections in children genetically at risk for islet autoimmunity (IA) and type 1 diabetes (T1D). Long- and short-term temporal associations between NLEs and rate of respiratory infection episodes (RIEs) in 5,618 children in The Environmental Determinants of Diabetes in the Young study for at least 1 up to 4 years were analysed. All models were adjusted for demographic, day care, season of infection, and psychosocial factors associated with the rate of child RIEs between study visits. The rate of child RIEs was 26% higher in Europe (Sweden, Finland, Germany) than in the United States (rate ratio [RR] = 1.26, p < 0.001). However, the percentage of child NLEs (odds ratio [OR] = 1.18, p < 0.001) and mother NLEs (OR = 1.83, p < 0.001) was higher in the United States compared with Europe. In both continents (Europe, RR = 1.12, p < 0.001; United States, RR = 1.07, p = 0.006), high child cumulative NLEs (>1 NLE per year since study inception) was significantly associated with an increased rate of child RIEs. This large-scale prospective study confirms observations that stress may increase the susceptibility for infections in paediatric populations and suggests at least one mechanism by which stress could increase risk for IA and T1D in genetically at risk children., (© 2019 John Wiley & Sons, Ltd.)

Background: FebriDx is a 10-minute disposable point-of-care test designed to identify clinically significant systemic host immune responses and aid in the differentiation of bacterial and viral respiratory infection by simultaneously detecting C-reactive protein (CRP) and myxovirus resistance protein A (MxA) from a fingerstick blood sample. FebriDx diagnostic accuracy was evaluated in the emergency room and urgent care setting., Methods: A prospective, multicentre, observational cohort study of acute upper respiratory tract infections (URIs), with and without a confirmed fever at the time of enrolment, was performed to evaluate the diagnostic accuracy of FebriDx to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference method consisted of an algorithm with physician override that included bacterial cell culture, respiratory PCR panels for viral and atypical pathogens, procalcitonin, and white blood cell count., Results: Among 220 patients enrolled, 100% reported fever 100.5°F within the last 72 hours while 55% had a measured hyperthermia (T > 100.4) at the time of enrolment. FebriDx demonstrated a sensitivity of 95% (95% CI: 77-100%), specificity of 94% (88-98%), PPV of 76% (59-87%), and a NPV of 99% (93-100%)., Conclusion: FebriDx may identify clinically significant bacterial URI's and supports outpatient antibiotic decisions. Key messages FebriDx is an outpatient POC test designed to identify a clinically significant systemic host immune response and aid in the differentiation of viral and bacterial infection through rapid measurement of MxA and CRP from a fingerstick blood sample. FebriDx test was determined to be an accurate test, with a 85% sensitivity, 93% specificity and 97% NPV to rule out bacterial infection for any patient presenting with symptoms and reported fever within the prior 3 days, and when confirming fever (hyperthermia) at the time of testing, the test was even more sensitive (95%) and specific (94%) with a 99% NPV. FebriDx may support antibiotic stewardship by rapidly identifying clinically significant bacterial URIs.

Background: Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a chronic disease caused by human papillomavirus types 6 and 11. It is associated with significant morbidity that places intense physical, psychological, and financial strain on patients and their families. Few studies have assessed the incidence and prevalence of JORRP in the United States., Methods: This retrospective, longitudinal cohort study was performed using data from a pair of large insurance claims databases in the United States. The Optum Clinformatics and Truven MarketScan Medicaid databases represent a sample of privately and publicly insured children, respectively. Cohorts of children aged 0 to 17 years were created within each database to estimate the incidence and prevalence of JORRP in 2006. Claims-based algorithms were designed to capture as many potential cases as possible. To improve the accuracy of the incidence and prevalence estimates, chart validation was performed to estimate the positive predictive value (PPV) of the claims-based algorithms., Results: The overall PPV-adjusted incidence of JORRP in 2006 was 0.51 per 100,000 in Optum and 1.03 per 100,000 in the MarketScan Medicaid population. Peak incidence was observed among 0- to 4-year-olds in both databases. The PPV-adjusted prevalence of JORRP in 2006 was 1.45 and 2.93 per 100,000 in the Optum and MarketScan Medicaid cohorts, respectively., Conclusions: Although relatively uncommon, JORRP represents a disease with significant morbidity. The incidence and prevalence of JORRP in publicly insured children were consistently higher than those covered by private insurance plans, suggesting an increased burden of illness among those with lower socioeconomic status.

After a 12-year hiatus, military recruit training centers resumed administration of adenovirus type 4 and type 7 vaccine, live, oral (adenovirus vaccine) to trainees beginning in October of 2011. Subsequently, rates of febrile respiratory illnesses (FRI) and adenovirus isolations markedly declined. These findings are consistent with those of a placebo-controlled efficacy trial conducted prior to the vaccine's licensure by the U.S. Food and Drug Administration. Continued surveillance will clarify the longer term impact of vaccine use.

Outbreaks of influenza A viruses continue to cause morbidity and mortality worldwide. The global disease burden of influenza is substantial. While antiviral therapies are available, influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated influenza vaccines have been available since the 1940s, with live attenuated, cold-adapted vaccines becoming available in the United States in 2003. In spite of the successes, more research is needed to develop more effective seasonal influenza vaccines that provide long-lasting immunity and broad protection against strains that differ antigenically from vaccine viruses. This review introduces the virus and its disease, the current state of seasonal and pandemic influenza vaccines, and the challenges we face in the future., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Acute otitis media (AOM) is the most frequent diagnosis in physician offices among children 1-4 years of age. Viruses that cause upper respiratory tract infections (i.e., respiratory syncytial virus [RSV], influenza virus, parainfluenza virus [PIV], and others) play an important role in the development of AOM. Prevention of infections with these viral pathogens likely would reduce the incidence of AOM. In three previous studies, influenza virus vaccines showed 30-36% efficacy against the development of AOM. Vaccines to prevent infections with RSV and PIV type 3 are undergoing clinical testing at this time. The three major bacterial pathogens causing AOM are Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis. Pneumococcal conjugate vaccine, licensed in the United States in 2000, was shown in two pivotal trials to reduce the incidence of all causes of AOM by 6%, pneumococcal AOM by 34%, and pneumococcal AOM caused by serotypes contained in the vaccine by 57%. Currently, vaccines against NTHi and M. catarrhalis are under development.

In order to determine the suitability of vaccine strains established in the 1960s for a new vaccine, a comprehensive study of strain variation of adenovirus serotype 4 (AV 4) and AV 7 was undertaken. A 1,500-bp region of the hexon gene containing the AV neutralization epitopes from prototype, vaccine, and community-acquired strains and from wild-type strains from military personnel that cause acute respiratory disease (ARD) was sequenced and analyzed. The whole hexon gene from prototype strains, vaccine strains, and selected isolates was sequenced. AV 7 and AV 7a were found to have distinct genotypes, and all vaccine and wild-type strains recovered from 1963 to 1997 had the AV 7a genotype. There was no significant strain variation in the neutralization epitopes of the AV 7a genotype over a 42-year period. The evolution of AV 4 was more complex, with continuous genetic drift punctuated by replacement with a new strain. The current strain of AV 4, which has been in circulation since 1995, is significantly different from the AV 4 prototype and the vaccine strains. Genetic differences were confirmed to be antigenic differences by neutralization tests, which define the new strain as an AV 4 variant. A type-specific PCR for AV 4, AV 7/7a, and AV 21 was developed, and this PCR facilitated the rapid identification of isolates from outbreaks of ARD.

The acute respiratory illnesses are the most common type of acute illness in the United States today. The respiratory viruses--which include influenza viruses, parainfluenza viruses, respiratory syncytial virus (RSV), rhinoviruses, coronaviruses, and adenoviruses--cause the majority of these illnesses. Some of these viruses cause illness throughout the year, whereas others are most common in winter. All population groups experience these infections and illnesses. As the number of elderly persons and those with underlying disease increases, awareness is growing that these common infections can have serious consequences. This has recently been emphasized for immunocompromised persons. At the M.D. Anderson Cancer Center (MDACC), infection surveillance of mostly hospitalized adults with leukemia or a recent bone marrow transplant yielded a respiratory virus from 181 of 668 (27.1%) respiratory illness episodes. In descending order of frequency, infections with RSV, rhinoviruses, influenza viruses, parainfluenza viruses, and adenoviruses were detected in each of three surveillance years. High frequencies of nosocomial acquisition occurred, as has been noted in prior reports. Similarly, persistence of infection and high frequencies of pneumonia and death among infected patients occurred, which have also been noted earlier. At MDACC, pneumonia occurred in 58-78% of infected patients, and 22-44% died. The role of the virus infection in many cases of pneumonia is uncertain, but death from pure viral pneumonia is well documented. A number of immune deficiencies in this patient population and options for control of these infections have been described that can, respectively, account for the medical problem and provide ways to approach prevention and treatment.

Natural dissemination of viral respiratory illness to susceptible men may occur with surprising difficulty. This was especially evident during a 1977 outbreak of adenovirus type 21 (Ad-21) at McMurdo Station, a US research base in Antarctica. The unique circumstances at McMurdo allowed 125 men from the US to join and intermingle with 75 men who had wintered for 6 months in complete isolation. For an additional 5-week (September 2 to October 4, 1977) isolation period, respiratory illness etiology and transmission were monitored in the combined population. A total of 89% of the population was susceptible (neutralizing antibody titer, less than 1:3) to Ad-21 but only 15.0% were infected. Illness spread very slowly (1.5 cases/100 persons/week) with no epidemic peak and was much less severe than Ad-21 outbreaks in other settings. The incidence of infection (17.3%) and illness (9.6%) was low even in men who had wintered over, with values very similar to those of the newcomers (13.9% and 8.9%, respectively). Thus, despite a harsh environment and frequent prolonged gatherings of susceptible personnel, even a respiratory virus type with known epidemic potential was surprisingly difficult to transmit.