Risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study.

OBJECTIVE: To assess the role of rhinoviruses in elderly people living in the community. DESIGN: Prospective community based surveillance of elderly people, without intervention. Subjects were telephoned weekly to identify symptomatic upper respiratory tract infections. Symptoms and impact of illnesses were monitored, and specimens were collected for diagnostic serology and human rhinovirus polymerase chain reaction. SETTING: Leicestershire, England. SUBJECTS: 533 subjects aged 60 to 90. MAIN OUTCOME MEASURES: Symptoms, restriction of activity, medical consultations, and antibiotic use during 96 rhinovirus infections. Adjusted odds ratios for lower respiratory syndromes with respect to smoking and health status. RESULTS: A viral cause was established in 211 (43%) of 497 respiratory illnesses; rhinoviruses were identified in 121 (24%) and as single pathogens in 107. The median duration of the first or only rhinovirus infection in the 96 people with 107 rhinovirus infections was 16 days; 18 of the 96 patients were confined to bed and 25 were unable to cope with routine household activities. Overall, 60 patients with rhinovirus infections had lower respiratory tract syndromes; 41 patients consulted their doctor, 31 of them (76%) receiving antibiotics. One patient died. Logistic regression analysis showed that chronic medical conditions increased the estimated probability of lower respiratory rhinovirus illness by 40% (95% confidence interval 17% to 68%) and smoking by 47% (14% to 90%). There were almost six times as many symptomatic rhinovirus infections as influenza A and B infections. CONCLUSIONS: Rhinoviruses are an important cause of debility and lower respiratory illness among elderly people in the community. Chronic ill health and smoking increase the likelihood of lower respiratory complications from such infections. The overall burden of rhinovirus infections in elderly people may approach that of influenza.     

Diurnal Variation in the Symptoms of Colds and Influenza

The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings.

Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.     

Diurnal Variation in the Symptoms of Colds and Influenza

The present research examined diurnal variation in the severity of symptoms of experimentally-induced colds and influenza. Nasal secretion was greatest in the morning, decreased over the day, and then showed a slight increase in the late evening. Colds did not change the average temperature, nor did they alter the temperature rhythm. Similar, negative results were found with alertness ratings.

Influenza B illnesses produced an increase in nasal secretion and systemic effects. The average temperature increased during this illness and subjects reported that they felt more drowsy. Diurnal variation in the severity of local and central symptoms was observed, with nasal secretion and the temperature increase being greatest in the early morning. These results have important implications for the assessment and treatment of the illnesses.     

Utility of the tourniquet test and the white blood cell count to differentiate dengue among acute febrile illnesses in the emergency room

Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm(3)) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Luke's Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2-7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue.     

Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets

Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses). The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology) correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response). Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.     

Syndromic surveillance for influenzalike illness

Emergency department data are currently being used by several syndromic surveillance systems to identify outbreaks of natural or man-made illnesses, and preliminary results suggest that regular outbreaks might be detected earlier with such data than with traditional reporting. This article summarizes a retrospective study of 5 influenza seasons in Ottawa,Canada; time-series analysis was used to look for an association between consultation to the emergency department for influenzalike illness and the isolation of influenza virus in the community. The population studied included both children and adults consulting to 3 local hospitals. In 4 seasons, visits to the emergency department involving children younger than 5 years consulting mainly for fever and for respiratory symptoms peaked 1 to 4 weeks before the isolation of influenza virus in the community. If monitored regularly for the presence of key symptoms, pediatric hospitals might be efficient and cost-effective sentinels of influenza and of other infectious diseases.     

Failures of metacognition and lack of insight in neuropsychiatric disorders

Lack of insight or unawareness of illness are the hallmarks of many psychiatric disorders, especially schizophrenia (SCZ) and other psychoses and could be conceived of as a failure in metacognition. Research in this area in the mental health field h as burgeoned with the development and widespread use of standard assessment instruments and the mapping out of the clinical and neuropsychological correlates of insight and its loss. There has been a growing appreciation of the multi-faceted nature of the concept and of the different 'objects' of insight, such as the general awareness that one is ill, to more specific metacognitive awareness of individual symptoms, impairments and performance. This in turn has led to the notion that insight may show modularity and may fractionate across different domains and disorders, supported by work that directly compares metacognition of memory deficits and illness awareness in patients with SCZ, Alzheimer's disease and brain injury. The focus of this paper will be on the varieties of metacognitive failure in psychiatry, particularly the psychoses. We explore cognitive models based on self-reflectiveness and their possible social and neurological bases, including data from structural and functional MRI. The medial frontal cortex appears to play an important role in self-appraisal in health and disease.     

Respiratory viruses and exacerbations of asthma in adults.

OBJECTIVE--To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN--Longitudinal study of 138 adults with asthma. SETTING--Leicestershire Health Authority. SUBJECTS--48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES--Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS--Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS--These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.     

Caida de Mollera among Children of Mexican Migrant Workers: Implications for the Study of Folk Illnesses

Information about the folk illness caida de mollera was collected from Mexican and Mexican American migrant mothers who had treated their children for the illness, and from physicians in a clinic that served this population. These physicians believed that the vast majority of the sets of symptoms were worthy of medical attention and could be life threatening if not treated. This research report concurs with other studies that suggest that although Mexican folk illnesses are conceptualized to have folk-social and psychological causes, they are also seen to have biological causes and physiological symptoms that can be treated by biomedical methods. This report outlines a model for understanding aspects of folk illnesses that includes folk vs. biomedical ideas about disease, causes vs. symptoms, and psychological vs. physiological aspects of sickness. It also suggests that the kinds of questions anthropologists ask about these illnesses may need to be modified—shifting away from questions about treatments of causes and refocusing on those about the treatment of physiological symptoms—if we are to more fully understand home approaches to the management of these illnesses, [folk illnesses, Mexican, Mexican American, farmworkers]     

Acute viral infections of upper respiratory tract in elderly people living in the community: comparative,prospective, population based study of disease burden.

OBJECTIVE: To evaluate the disease burden of upper respiratory infections in elderly people living at home. DESIGN: Prospective surveillance of elderly people. INTERVENTION: None. SETTING: Leicestershire, England SUBJECTS: 533 subjects 60 to 90 years of age. MAIN OUTCOME MEASURES: Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. RESULTS: 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. CONCLUSIONS: Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.     

Epidemiology of Pathogen-Specific Respiratory Infections among Three US Populations

Background

Diagnostic tests for respiratory infections can be costly and time-consuming. Improved characterization of specific respiratory pathogens by identifying frequent signs, symptoms and demographic characteristics, along with improving our understanding of coinfection rates and seasonality, may improve treatment and prevention measures.

Methods

Febrile respiratory illness (FRI) and severe acute respiratory infection (SARI) surveillance was conducted from October 2011 through March 2013 among three US populations: civilians near the US–Mexico border, Department of Defense (DoD) beneficiaries, and military recruits. Clinical and demographic questionnaire data and respiratory swabs were collected from participants, tested by PCR for nine different respiratory pathogens and summarized. Age stratified characteristics of civilians positive for influenza and recruits positive for rhinovirus were compared to other and no/unknown pathogen. Seasonality and coinfection rates were also described.

Results

A total of 1444 patients met the FRI or SARI case definition and were enrolled in this study. Influenza signs and symptoms varied across age groups of civilians. Recruits with rhinovirus had higher percentages of pneumonia, cough, shortness of breath, congestion, cough, less fever and longer time to seeking care and were more likely to be male compared to those in the no/unknown pathogen group. Coinfections were found in 6% of all FRI/SARI cases tested and were most frequently seen among children and with rhinovirus infections. Clear seasonal trends were identified for influenza, rhinovirus, and respiratory syncytial virus.

Conclusions

The age-stratified clinical characteristics associated with influenza suggest that age-specific case definitions may improve influenza surveillance and identification. Improving identification of rhinoviruses, the most frequent respiratory infection among recruits, may be useful for separating out contagious individuals, especially when larger outbreaks occur. Overall, describing the epidemiology of pathogen specific respiratory diseases can help improve clinical diagnoses, establish baselines of infection, identify outbreaks, and help prioritize the development of new vaccines and treatments.     

A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore

Introduction

Influenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection.

Methods

Personnel with FRI (defined as fever≥37.5°C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model.

Results

821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria.

Conclusions

Use of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI.     

The severity of psychiatric disorders

The issue of the severity of psychiatric disorders has great clinical importance. For example, severity influences decisions about level of care, and affects decisions to seek government assistance due to psychiatric disability. Controversy exists as to the efficacy of antidepressants across the spectrum of depression severity, and whether patients with severe depression should be preferentially treated with medication rather than psychotherapy. Measures of severity are used to evaluate outcome in treatment studies and may be used as meaningful endpoints in clinical practice. But, what does it mean to say that someone has a severe illness? Does severity refer to the number of symptoms a patient is experiencing? To the intensity of the symptoms? To symptom frequency or persistence? To the impact of symptoms on functioning or on quality of life? To the likelihood of the illness resulting in permanent disability or death? Putting aside the issue of how severity should be operationalized, another consideration is whether severity should be conceptualized similarly for all illnesses or be disorder specific. In this paper, we examine how severity is characterized in research and contemporary psychiatric diagnostic systems, with a special focus on depression and personality disorders. Our review shows that the DSM‐5 has defined the severity of various disorders in different ways, and that researchers have adopted a myriad of ways of defining severity for both depression and personality disorders, although the severity of the former was predominantly defined according to scores on symptom rating scales, whereas the severity of the latter was often linked with impairments in functioning. Because the functional impact of symptom‐defined disorders depends on factors extrinsic to those disorders, such as self‐efficacy, resilience, coping ability, social support, cultural and social expectations, as well as the responsibilities related to one's primary role function and the availability of others to assume those responsibilities, we argue that the severity of such disorders should be defined independently from functional impairment.     

Current status for influenza control

Influenza viruses are responsible for respiratory illness with significant morbidity and mortality. To curb the disease, two-pronged attack on the virus, therapeutic and prophylactic, is being actively pursued. The therapeutic use of existing anti-influenza drugs, such as amantadine and rimantadine, is limited by their significant adverse side effect, emergence of resistant viral strains, and lack of activity against influenza B virus. A new class of antiviral agents designed to inhibit influenza neuraminidase are currently under active development for use in the prophylaxis and treatment of influenza A and B virus infections. Two of these compounds, zanamivir (GG167) and GS4104 have reached clinical trials. Limitations in the effectiveness and application of inactivated vaccines have stimulated development of alternative approaches to influenza immunization. One such approach is a live, intranasally administered vaccine, attenuated by cold-adaptation of a master strain with subsequent genetic reassortment with circulating wild-type strains. Recently developed reverse-genetics techniques have made it possible to use RNA viruses as vector. Besides DNA viral vectors, live influenza virus vectors may emerge as a useful alternative for the vaccination against different pathogens.     

Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach

IntroductionNon-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness.MethodologyWe conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis.ConclusionsThis study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings.     

Neuraminidase inhibitors for treatment of human and avian strain influenza: A comparative modeling study

Treatment of seasonal influenza viral infections using antivirals such as neuraminidase inhibitors (NAIs) has been proven effective if administered within 48 h post-infection. However, there is growing evidence that antiviral treatment of infections with avian-derived strains even as late as 6 days post-infection (dpi) can significantly reduce infection severity and duration. Using a mathematical model of in-host influenza viral infections which can capture the kinetics of both a short-lived, typical, seasonal infection and a severe infection exhibiting sustained viral titer, we explore differences in the effects of NAI treatment on both types of influenza viral infections. Comparison of our model's behavior against experimental data from patients naturally infected with avian strains yields estimates for the times at which patients were infected that are consistent with those reported by the patients, and estimates of drug efficacies that are lower for patients who died than for those who recovered. In addition, our model suggests that the sustained, high, viral titers often seen in more severe influenza virus infections are the reason why antiviral treatment delayed by as much as 6 dpi will still lead to reduced viral titers and shortened illness. We conclude that NAIs may be an effective and beneficial treatment strategy against more severe strains of influenza virus characterized by high, sustained, viral titers. We believe that our mathematical model will be an effective tool in guiding treatment of severe influenza viral infections with antivirals.     

Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome

It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-alpha, IFN-gamma, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.     

Serological Assessment of Rubella During Pregnancy

In 45 patients with rubella-like illnesses during pregnancy serological tests showed that the clinical diagnosis had been accurate in only 20. Since only 16 of these patients had presented for laboratory investigations within a week of the onset of symptoms, the value of haemagglutination-inhibition tests was considerably reduced; the diagnosis in these cases was confirmed by complement-fixation and rubella-specific IgM tests.Of 172 patients exposed to a rubella-like illness, only 17 were seronegative; 105 sought advice within two weeks of exposure, and therefore the haemagglutination-inhibition antibody tests were useful in determining immunity. Since the clinical diagnosis of rubella was proved incorrect in a number of cases, these pregnancies were saved. Hence both doctors and patients should report both exposure to and rubella-like illnesses as early as possible, so that laboratory investigations may be carried out without delay.