Update on Human Rhinovirus and Coronavirus Infections.

Human rhinovirus (HRV) and coronavirus (HCoV) infections are associated with both upper respiratory tract illness ("the common cold") and lower respiratory tract illness (pneumonia). New species of HRVs and HCoVs have been diagnosed in the past decade. More sensitive diagnostic tests such as reverse transcription-polymerase chain reaction have expanded our understanding of the role these viruses play in both immunocompetent and immunosuppressed hosts. Recent identification of severe acute respiratory syndrome and Middle East respiratory syndrome viruses causing serious respiratory illnesses has led to renewed efforts for vaccine development. The role these viruses play in patients with chronic lung disease such as asthma makes the search for antiviral agents of increased importance.

Picornavirus, the most common respiratory virus causing infection among patients of all ages hospitalized with acute respiratory illness.

We evaluated the prevalence of respiratory virus infection (RVI) in 403 illnesses of 364 persons hospitalized over a 2-year period with acute respiratory conditions using virus-specific reverse transcription-PCR (RT-PCR) assays in addition to cell culture and serology. RVIs were identified in >75% of children under 5 years of age and 25 to 37% of adults. The molecular assays doubled the number of infections identified; picornaviruses were the most frequent in patients of all ages, followed by respiratory syncytial virus and influenza viruses.

Update on rhinovirus and coronavirus infections.

Rhinoviruses and coronaviruses cause significant morbidity in immunocompetent people of all ages and in patients with underlying chronic medical or immunosuppressed conditions. Newer diagnostic tests, such as polymerase chain reaction (PCR), have expanded our understanding of these respiratory viruses in clinical infections. These sensitive diagnostic tests have been used to describe new members of these virus families, such as human rhinovirus C (HRVC) and human coronavirus NL-63 (HCoV-NL63). The epidemiology of these newly described viruses will help us develop better intervention strategies.

Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide. Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease. OBJECTIVE: We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors. METHODS: Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103). We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions. We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice. RESULTS: HRVs are isolated from nasal and lung fluid from subjects with AE-COPD. Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a T(H)1 and T(H)2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong T(H)1 and T(H)2 immune responses from CD4 T cells. Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-gamma production from CD4 T cells. CONCLUSION: Our findings suggest that patients with severe COPD show T(H)1- and T(H)2-biased responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a T(H)1- and T(H)2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD. Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD.

The Changing Epidemiology and Microbiology of Patients With Prostate Abscess: Increase in Staphylococcal Infection.

BACKGROUND: Prostatic abscesses are rare and have been most commonly associated with gram-negative bacteria; however, Staphylococcus aureus has emerged as a leading cause, particularly in persons who are immunocompromised. METHODS: We conducted a retrospective chart review of all patients discharged from Ben Taub Hospital with a diagnosis of prostatic abscess during January 2011-January 2019. Demographic, clinical, microbiologic, and radiographic data were abstracted from the patients' charts and analyzed for comorbidities, causative organisms, clinical course, and outcomes. RESULTS: We identified 32 patients with a prostatic abscess during the study period. S. aureus was the most common causative organism (18/32, 56%). Most patients (24/32, 75%) were admitted to a general medicine service, and the median length of stay was 9 days. Twenty-one patients (66%) were treated with a combination of surgical drainage and antibiotic therapy; 11 (34%) were treated with antibiotics alone. All patients treated with antibiotics alone had full clinical recovery. Two patients (6.3%) died, both of whom had septic shock secondary to disseminated S. aureus infection. CONCLUSIONS: Prostatic abscesses are rare and can be difficult to diagnose, leading to significant morbidity and mortality. S. aureus is a frequent causative organism especially in persons with diabetes mellitus or other immunocompromising conditions. Hematogenous spread of S. aureus infection to the prostate appears common. Prostatic abscesses can serve as the nidus of disseminated S. aureus infection.

Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons.

BACKGROUND: Immune responses after influenza immunization are reduced in elderly individuals, the group at greatest risk for complications and death after influenza. Improved vaccines are needed to address this problem. METHODS: Ambulatory individuals 65 years and older (N = 202) were assigned randomly to receive a single intramuscular injection of the 2001-2002 formulation of trivalent inactivated influenza vaccine containing 15, 30, or 60 microg of hemagglutinin per strain (up to 180 microg total per dose) or placebo. Clinical and serologic responses were assessed during the month after immunization. RESULTS: Increasing dosages of vaccine elicited significantly higher serum antibody levels, frequencies of antibody responses, and putative protective titers after vaccination. Mean serum hemagglutination inhibition antibody titers 1 month after immunization in groups given 0-, 15-, 30-, and 60-microg dosages were 23, 37, 50, and 61 against influenza A/H1N1; 43, 86, 91, and 125 against influenza A/H3N2; and 10, 14, 18, and 24 against influenza B, respectively. Mean serum hemagglutination inhibition and neutralizing antibody levels against the 3 vaccine antigens in participants given the 60-microg dosage were 44% to 71% and 54% to 79%, respectively, higher than those in participants given the standard 15-microg dosage, and the 60-microg dosage level nearly doubled the frequency of antibody responses in those whose preimmunization antibody titers were in the lower half of the antibody range. Dose-related increases in the occurrence of injection site reactions were observed (P<.001), but all dosages were well tolerated. CONCLUSION: The improved immunogenicity of high-dose influenza vaccine among elderly persons should lead to enhanced protection against naturally occurring influenza.

The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy.

This study of human immunodeficiency virus (HIV)-infected patients coinfected with Cryptococcus neoformans found that 30% of patients who initiated highly active antiretroviral therapy developed immune reconstitution inflammatory syndrome (IRIS). Patients with C. neoformans-related IRIS had higher cerebrospinal fluid opening pressures, glucose levels, and white blood cell counts, compared with patients with typical HIV-associated C. neoformans meningitis.

Bacteraemia in the elderly: predictors of outcome in an urban teaching hospital.

OBJECTIVES: To analyze the underlying factors of mortality in elderly adults with bacteraemia. METHODS: The study included 238 episodes of bacteraemia in an urban public teaching hospital. Retrospective chart review recorded demographic information, comorbid conditions, length of stay, source of infection, and physiologic and laboratory data on admission. RESULTS: Of the 238 episodes of bacteraemia, 128 patients were 65-74 years of age and 110 patients were > or =75 years of age. Eighty-one percent came from home. Fifty-four percent had Gram positive cocci detected in blood cultures and 36% had Gram negative bacilli. Factors associated with increased odds of mortality included underlying renal disease, admission to MICU, hypotension and hypoalbuminemia. Decreased odds of mortality were associated with being admitted from home and receiving appropriate antibiotics. CONCLUSIONS: Bacteraemia in the elderly has a high mortality rate, but is not significantly increased in those >or =75 years of age. The recent microbiology has shifted from Gram negative bacilli to Gram positive cocci. Physiologic abnormalities on admission predict worse outcomes in the elderly bacteraemic patient. Hypoalbuminemia on admission is associated with higher mortality rates in the elderly.

Respiratory viral infections in patients with chronic, obstructive pulmonary disease.

OBJECTIVES: The purpose of the present study was to apply reverse transcription-PCR (RT-PCR) assays to clinical specimens collected from patients with acute respiratory illness and chronic obstructive pulmonary disease (COPD). METHODS: One hundred and ninety-four samples from two different study cohorts were analysed using RT-PCR assays for picornaviruses, coronaviruses 229E and OC43, influenza A and B viruses, respiratory syncytial virus, parainfluenza types 1-3 viruses, and human metapneumovirus and a PCR assay for adenoviruses. The results were added to results obtained previously using cell culture and serologic methods. RESULTS: RT-PCR assays identified an additional 35 respiratory virus-associated illnesses not identified previously by cell culture or serology (n=46). Picornaviruses and coronaviruses were the most common viral infections identified only by RT-PCR. Overall, 41.8% of the acute respiratory illnesses evaluated were associated with a respiratory virus infection, with picornaviruses, coronaviruses and influenza viruses being the most common infections recognized. No human metapneumovirus infections were identified by RT-PCR assay. CONCLUSIONS: Respiratory viral infections are commonly associated with acute respiratory illness in COPD patients, and the use of RT-PCR assays significantly increases the ability to diagnose these infections.

Respiratory consequences of rhinovirus infection.

Rhinoviruses, a genus of the family Picornaviridae, are the cause of more than 50% of respiratory tract infections. Complications of rhinovirus infections, which include otitis media, sinusitis, exacerbations of asthma, and other pulmonary diseases, can be significant in certain populations. Reverse transcriptase-polymerase chain reaction has allowed the identification of rhinoviruses and led to a greater appreciation of the role of this pathogen in upper and lower respiratory tract disease. Furthermore, antiviral agents with broad activity against rhinoviruses have recently been developed, have undergone clinical trials, but have not been approved for clinical use. By altering the clinical course of picornavirus infections, it may be possible to minimize their potential adverse consequences.

Comparison of the instructional efficacy of Internet-based CME with live interactive CME workshops: a randomized controlled trial.

CONTEXT: Despite evidence that a variety of continuing medical education (CME) techniques can foster physician behavioral change, there have been no randomized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective. OBJECTIVE: To determine if Internet-based CME can produce changes comparable to those produced via live, small-group, interactive CME with respect to physician knowledge and behaviors that have an impact on patient care. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted from August 2001 to July 2002. Participants were 97 primary care physicians drawn from 21 practice sites in Houston, Tex, including 7 community health centers and 14 private group practices. A control group of 18 physicians from these same sites received no intervention. INTERVENTIONS: Physicians were randomly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks, or to a single live, small-group, interactive CME workshop. Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live settings. Content was based on the National Institutes of Health National Cholesterol Education Program--Adult Treatment Panel III guidelines. MAIN OUTCOME MEASURES: Knowledge was assessed immediately before the intervention, immediately after the intervention, and 12 weeks later. The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention. RESULTS: Both interventions produced similar and significant immediate and 12-week knowledge gains, representing large increases in percentage of items correct (pretest to posttest: 31.0% [95% confidence interval {CI}, 27.0%-35.0%]; pretest to 12 weeks: 36.4% [95% CI, 32.2%-40.6%]; P<.001 for all comparisons). Chart audits revealed high baseline screening rates in all study groups (> or =93%) with no significant postintervention change. However, the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines (preintervention, 85.3%; postintervention, 90.3%; P = .04). CONCLUSIONS: Appropriately designed, evidence-based online CME can produce objectively measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities.

Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy.

OBJECTIVE: To evaluate HIV-1 reverse transcriptase (RT) drug resistance in patients receiving abacavir, lamivudine and zidovudine therapy. METHODS: In a randomized, double-blind study, 173 antiretroviral treatment-naive HIV-1-infected adults received abacavir/lamivudine/zidovudine or lamivudine/zidovudine for up to 48 weeks. After week 16, patients could switch to open-label abacavir/lamivudine/zidovudine, and those with plasma HIV-1 RNA (vRNA) > 400 copies/ml could add other antiretrovirals. From weeks 11 to 48, samples with vRNA > 400 copies/ml were collected for genotyping and phenotyping. RESULTS: At baseline, 90% of isolates were wild-type (WT). At week 16, vRNA was > 400 copies/ml in seven of 72 (10% patients receiving abacavir/lamivudine/zidovudine and in 41 of 66 (62%) receiving lamivudine/ zidovudine. At week 16, the genotypes in isolates from the abacavir/lamivudine/zidovudine group were M184V alone (n = 3 cases), WT (n = 3) and M184V plus thymidine analogue mutations (TAMs) (n = 1). The genotypes in isolates from the lamivudine/zidovudine group were M184V alone (n = 37), WT ( n= 1) and M184V plus TAMs (n = 3). In the four cases where M184V plus TAMs were detected some mutations were present at baseline. Despite detectable M184V in 74% of patients on lamivudine/zidovudine, addition of abacavir with or without another antiretroviral therapy resulted in a reduction in vRNA, with 42 of 65 (65%) patients having week 48 vRNA < 400 copies/ml (intent-to-treat with missing = failure). At week 48, the most common genotype was M184V alone in the abacavir/ lamivudine/zidovudine group (median vRNA 1-2 log,10 below baseline), and M184V with or without TAMs in patients originally assigned to lamivudine/zidovudine. At week 48, phenotypic results were obtained for 11 isolates for patients from both arms, and all had reduced susceptibility to lamivudine but all remained sensitive to stavudine, all protease inhibitors and all non-nucleoside reverse transcriptase inhibitors. Three, three and two isolates had reduced susceptibility to abacavir, didanosine and zidovudine, respectively. CONCLUSIONS: Abacavir retained efficacy against isolates with the M184V genotype alone. TAMs did not develop during 48 weeks of abacavir/lamivudine/zidovudine therapy and were uncommon when abacavir was added after 16 weeks of lamivudine/zidovudine therapy. Limited mutations upon rebound on this triple nucleoside combination allows for several subsequent treatment options.

Viral respiratory infections in elderly patients and patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) and elderly individuals are prone to the development of significant lower respiratory tract symptoms from colds caused by viral respiratory pathogens. Longitudinal surveillance studies conducted to assess the impact of viral respiratory tract pathogens on morbidity and mortality in each of these at-risk populations demonstrate that there is a substantial burden of disease from viral respiratory infection (VRI), including rhinovirus infections, with respect to utilization of health-care resources. Despite a similar rate of occurrence of VRI among subjects with COPD and the control group, a cohort with moderate to severe COPD had a 2-fold increase in medical resource utilization, including clinician visits, emergency center visits, and hospitalizations. In surveillance studies of respiratory viruses in the elderly, regular seasonal infections with rhinoviruses cause substantial morbidity, which has been largely underappreciated and underreported.

Infectious exacerbations of chronic obstructive pulmonary disease associated with respiratory viruses and non-typeable Haemophilus influenzae.

Infectious exacerbations of chronic obstructive pulmonary disease (COPD) have been reported to occur with both viral and bacterial pathogens. In this study, 35 exacerbations associated with the isolation of non-typeable Haemophilus influenzae from sputum were identified as part of a prospective longitudinal study. Samples from these patients were subjected to immunoassays to identify a new immune response to the homologous isolate of non-typeable H. influenzae to more accurately assess a bacterial etiology. These patients also were studied carefully for evidence of viral infection using viral culture, serology and polymerase chain reaction-based assays. Sixteen of 35 exacerbations (45.7%) were associated with evidence of acute viral infection and 11 of the 35 exacerbations (31.4%) were associated with the development of new serum IgG to homologous non-typeable H. influenzae. Overall, evidence of infection with a respiratory virus or non-typeable H. influenzae was seen in 24 of 35 exacerbations (68.6%). No association between viral infection and immune response to non-typeable H. influenzae was observed, although a trend toward an immune response to non-typeable H. influenzae and absence of viral infection was seen. The results show that exacerbations in adults with COPD were associated with infection caused by virus alone, non-typeable H. influenzae alone, or virus and non-typeable H. influenzae simultaneously.

Infections in the immunocompromised rheumatologic patient.

Immunocompromised patients with rheumatic diseases have an increased risk of infections. A major risk factor for infection seems to be the immunosuppressive therapy used. Newer therapies for RA may lead to increased rates of infection by opportunistic pathogens such as Mycobacteria tuberculosis. Because disease manifestation may mimic signs and symptoms of infection, prompt diagnosis may be difficult. Familiarity with the likely infections and their causes should aid in obtaining the appropriate culture specimens.

Rethinking CME: an imperative for academic medicine and faculty development.

To help address the clinical care gap, a working group discussed the future of faculty development in academic medicine, explored problems within the large, current enterprise devoted to continuing medical education (CME), and described four domains core to its revitalization and reformation. These domains are (1) preparing and supporting an engaged clinician-learner, (2) improving the quality of knowledge or evidence shared, (3) enhancing the means by which to disseminate and implement that knowledge and evidence, and (4) reforming the patient, health care, and regulatory systems in and for which the process of CME exists. Reshaping these domains requires the consideration of a more seamless, evidence-based, and patient-oriented continuum of medical education. Revitalizing CME also requires the full engagement of the academic medical community and its faculty. To achieve the goal of creating a new, more effective, seamless process of CME, the working group recommended an active faculty development process to develop strong clinician-learners, strong involvement of academic health center leaders, the development of an educational home for clinician-learners, and a meaningful national conversation on the subject of CME.

Rhinovirus and coronavirus infections.

Rhinoviruses and coronaviruses cause the majority of common colds and play a part in more serious respiratory illnesses that lead to increased morbidity and mortality. Patients who are infants or elderly, have asthma or chronic obstructive pulmonary disease (COPD), or are immunosuppressed have increased frequency of rhinovirus-related respiratory complications. Newer diagnostic tests such as reverse transcriptase polymerase chain reaction (RT-PCR) have greatly expanded our understanding of the importance of these respiratory viruses. Although there are no currently approved antiviral agents for clinical use, our increased understanding of the virus-host interaction should lead to new intervention strategies.