Virus Infection In Adults Research Articles

Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis.

Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate-quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate-quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low-quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen-positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen-negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low-level viremia. Most of the current literature focuses on the immune active phases of chronic HBV infection; decision-making in other commonly encountered and challenging clinical settings depends on indirect evidence.

Should clinical case definitions of influenza in hospitalized older adults include fever?

IntroductionInfluenza is a major cause of morbidity and mortality in elderly persons. Fever is included in all standard definitions of influenza-like illness (ILI), yet older patients may have diminished febrile response to infection. Therefore, we examined the utility of various thresholds to define fever for case definitions of influenza in persons ≥65 years of age.MethodsData from two prospective surveillance studies for respiratory viral infection in adults hospitalized with acute cardiopulmonary illnesses with or without fever were examined. The highest temperature reported prior to admission or measured during the first 24 h after admission was recorded. The diagnosis of influenza was made by a combination of viral culture, reverse-transcription polymerase chain reaction, antigen testing, and serology.ResultsA total of 2410 subjects (66% ≥65 years of age) were enrolled; 281 had influenza (261 influenza A, 19 influenza B, and one mixed influenza A and B). The commonly used definition of ILI (fever ≥37·8°C and cough) resulted in 57% sensitivity and 71% specificity in older adults. Receiver operating characteristic curves examining the various temperature thresholds combined with cough and/or sore throat showed the optimal balance between sensitivity and specificity to be 37·9°C (AUC 0·71) and 37·3°C (AUC 0·66), in younger and older persons, respectively.ConclusionClinical decision rules using the presence of cough and fever may be helpful when screening for influenza or empiric antiviral treatment when rapid influenza testing is not available; however, lower fever thresholds may be considered for elderly subjects.

Primary oropharyngeal herpes simplex virus infection in adults: a profile of thirty-two immunoserologically confirmed cases.

Primary oropharyngeal herpes simplex virus infection in adults: a profile of thirty-two immunoserologically confirmed cases.

The Role of Viral Infection in Pulmonary Exacerbations of Bronchiectasis in Adults: A Prospective Study

BACKGROUNDAlthough viral infections are a major cause of exacerbations in patients with chronic airway diseases, their roles in triggering bronchiectasis exacerbations in adults remain unclear. Therefore, we prospectively investigated the incidence and clinical impacts of viral infection in adults with bronchiectasis exacerbations.METHODSThe study cohort of 119 adults with bronchiectasis was followed up prospectively for 12 months. Nasopharyngeal swabs and sputum samples were assayed for 16 respiratory viruses, using polymerase chain reaction assays. Symptoms, spirometry, quality of life, bacterial cultures, and inflammatory markers were assessed during steady-state bronchiectasis and exacerbations.RESULTSA total of 100 exacerbations were captured from 58 patients during 1-year follow-up. Respiratory viruses were found more frequently in nasopharyngeal swabs and sputum during bronchiectasis exacerbations (49 of 100, 49.0') than during steady state (11 of 58, 18.9'; P < .001). The most common viruses found in patients experiencing exacerbations were coronavirus (19 of 65, 39.2'), rhinovirus (16 of 65, 24.6'), and influenza A/B viruses (16 of 65, 24.6'). Virus-positive exacerbations were associated with a greater increase in markers of systemic and airway inflammation (serum IL-6 and tumor necrosis factor-α; sputum IL-1β and tumor necrosis factor-α) compared with virus-negative exacerbations, but the differences in spirometric indexes, quality of life, and bacterial density were unremarkable. In receiver operating characteristics analysis, serum interferon-γ-induced protein 10 yielded an area under curve of 0.67 (95' CI, 0.53-0.77; P = .018). Furthermore, a greater proportion of patients with virus-positive exacerbations received IV antibiotics.CONCLUSIONSPrevalence of viral infections, detected by polymerase chain reaction assay, is higher in cases of bronchiectasis exacerbations than in steady-state bronchiectasis, suggesting that respiratory viruses play crucial roles in triggering bronchiectasis exacerbations. The potential mechanisms of virus-induced bronchiectasis exacerbations merit further investigations.TRIAL REGISTRYClinicalTrials.gov; No.: NCT01801657; www.clinicaltrials.gov

ETIOLOGICAL STRUCTURE OF VIRAL RESPIRATORY DISEASES IN ADULT PATIENTS WITH BRONCHIAL ASTHMA EXACERBATION AND CHRONICAL BRONCHIOLITIS OBLITERANS

Exacerbation of bronchial asthma (BA) and common deterioration of health during chronic bronchiolitis obliterans (ChBO) are associated with viral infections in adults in 64 and 83% respectively. Mixed virus-viral associations were shown in 21–25% of cases. Respiratory syncytial infections were diagnosed with the highest frequency (50%) in patients with BA. Influenza A(H1N1)pdm09 and adenoviral infections dominated in persons with ChBO in 50 and 42% of cases, respectively. Response of virus-specific IgG in patients with BA and ChBO indicates the acute course of influenza A(H1N1)pdm09 (63% of seroconversions). There were no reactions of IgG which is specific to respiratory syncytial virus in 75% of cases and to adenovirus in 83% of cases, that is the risk factor for occurrence of latent/persistent infection. Presence of structural components of respiratory syncytial virus in the upper respiratory tract had been revealed in three patients with asthma within at least 21–28 days. Respiratory syncytial viral infections and pandemic influenza A(H1N1) pdm09 in patients with BA and ChBO are characterized by the presence of an allergic component, which is indicated by the high levels of virus-specific IgE in blood. An adenoviral infection, in contrast, has no such peculiarity.

2014 UK national guideline for the management of anogenital herpes.

These guidelines concern the management of anogenital herpes simplex virus infections in adults and give advice on diagnosis, management, and counselling of patients. This guideline replaces the 2007 BASHH herpes guidelines and includes new sections on herpes proctitis, key points to cover with patients regarding transmission and removal of advice on the management of HSV in pregnancy which now has a separate joint BASHH/RCOG guideline.

Quantitative polymerase chain reaction for detection of human herpesvirus-7 infection in umbilical cord blood donors.

Umbilical cord blood (UCB) has been a reasonable alternative to granulocyte colony-stimulating factor-mobilized peripheral blood or bone marrow, as a source of hematopoietic stem cells with a lower risk of graft-versus-host disease. In immunocompromised hosts after transplantation, the risk of viral infection in adults, especially with beta-herpesviruses such as human herpesvirus-7 (HHV-7), may be increased. This virus in immunocompromised patients can be reactivated from latency and converted to an active phase. Therefore, light-upon-extension real-time polymerase chain reaction (PCR) was developed to assess the prevalence and load of HHV-7 in the plasma and buffy coat of donors. About 825 UCB samples under standard protocol from donors were collected. Then, DNA from plasma and buffy coat was extracted and quantitative real-time PCR was performed with light-upon-extension primers. Overall, HHV-7 was detected in 3.64% (30/825) of UCB donors. HHV-7 DNA was detected in 26 (3.2%) buffy coat samples (latent infection), and only 4 (0.48%) of them were positive for HHV-7 DNA in plasma samples (active infection); the mean HHV-7 viral load was 1.31×10(1) copies/mL in latent infection, and 1.94×10(5) copies/mL in active infection. We suggest that real-time PCR in plasma and buffy coat could be a useful method to detect active and latent HHV-7 infection in UCB donors and determine its role in subsequent transmission events.

Increased PGD2 is associated with delayed dendritic cell maturation in neonates during respiratory viral infection (VIR2P.1031)

Abstract During respiratory viral infection in adults, inflammatory cytokines stimulate conventional dendritic cells (cDC) to increase expression of MHC class II molecules, co-stimulatory molecules, and chemokine receptors. Activated cDC then migrate from the lung to the draining lymph nodes where they present antigen to T cells. Our previous studies demonstrated that neonatal mice exhibit reduced inflammation and inflammatory cytokine expression during paramyxoviral infection. Thymic stromal lymphopoietin (TSLP), a cytokine known to participate in cDC activation, is expressed at significantly lower levels in neonatal mice during respiratory viral infection compared to adults. Thus, we hypothesized that cDC maturation and migration to lymph nodes may be delayed or impaired in neonates. Adult and two-day old neonatal C57BL/6 mice were inoculated intranasally with Sendai virus (500 pfu/g body weight). Adult cDC had increased expression of MHC Class II and CCR7 and had migrated to the lymph nodes on post-infection days 1 and 3. However, these events were delayed in neonates and did not reach adult levels until post-infection day 7. Interestingly, studies in geriatric mice suggest that high levels of Prostaglandin D2 (PGD2) may inhibit cDC maturation and migration to lymph nodes. We also observed higher PGD2 expression in neonatal bronchoalveolar lavage fluid compared to adults during paramyxoviral infection, and this may contribute to the impairment of DC maturation in neonates.

Therapeutic perspectives of recurrent respiratory infections

Viruses can cause interferon imbalance and inhibit cellular and phagocytic responses. Persistent viral and bacterial infections, such as Mycoplasma, Chlamydia, etc., can stimulate atopy and cause exacerbations of chronic respiratory diseases. A high efficacy of inosine pranobex (Groprinosin) has been demonstrated for treatment and prevention (immunological rehabilitation) of recurrent respiratory viral infections in adults and children.

Diagnostic pitfalls of varicella virus infection in adults

Case report We present three cases of previously healthy adult patients diagnosed with varicella in December 2012 with uncommon onsets, but with mild evolution of the disease. Patient 1: female, age 45, had an atypical onset with very few vesicles only one on the trunk, and then on the head after five days, but with inflammatory occipital lymph nodes. From day 6, our patient had typical dermatological lesions, mild pruritus and only two days of mild fever. Patient 2: male, age 38, had a typical onset, with high fever in the first week. With another episode of varicella in his childhood, this was considered as a varicella virus recurrent infection. Patient 3: male, age 80, was admitted to the hospital for extremely painful cutaneous eruptions on the thorax, initially diagnosed as zona zoster. In the next days, the lesions, in different stages of development, extended all over the body, with typical evolution of chickenpox. All patients were treated with supportive therapy: antipruritic and anti-inflammatory drug mouthwashes, soothing topical lotions and anesthetic gels. They had self-limited evolution, with no complications and with complete remission of lesions.

Medically Attended Respiratory Syncytial Virus Infections in Adults Aged &gt;=50 Years: Clinical Characteristics and Outcomes

Few studies have examined respiratory syncytial virus (RSV) infections in adults. We assessed the characteristics and outcomes of RSV relative to other viral infections. Patients ≥ 50 years old with acute respiratory illness were recruited for studies of influenza vaccine effectiveness from 2004 through 2010. Nasopharyngeal swabs from enrollees were analyzed for the presence of RSV and other respiratory viruses by multiplex reverse transcription polymerase chain reaction. Clinical data were obtained from interview and medical records. A total of 2225 samples were tested across all seasons. The mean age was 64.2 (SD, 10.7) years; the mean interval from illness onset to sample collection was 4 (SD, 2.2) days. One or more viruses were detected in 1202 (54%) participants. In a multivariable logistic regression model, RSV was associated with ages 65-79 years (vs 50-64 years), symptoms of cough, nasal congestion and wheezing, and longer interval from illness onset to clinical encounter. RSV was not associated with the presence of chronic obstructive pulmonary disease or congestive heart failure in univariate analyses. Hospital admission within 30 days after illness onset was less common among patients with RSV compared to those with influenza (unadjusted odds ratio = 0.54 [95% confidence interval, .29-1.01], P = .06). RSV is a common cause of acute respiratory illness in adults aged ≥ 50 years; the risk of infection increases with age. Delays in healthcare seeking and reduced risk of hospital admission in patients with RSV suggest a milder course of illness relative to influenza.

Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement

Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement

Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement

Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement

Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement

Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for and treatment of hepatitis C virus (HCV) infection in asymptomatic adults. The Agency for Healthcare Research and Quality commissioned 2 systematic reviews on screening for and treatment of HCV infection in asymptomatic adults, focusing on evidence gaps identified in the previous USPSTF recommendation and new studies published since 2004. The evidence on screening for HCV in pregnant women was also considered. This recommendation applies to all asymptomatic adults without known liver disease or functional abnormalities. The USPSTF recommends screening for HCV infection in persons at high risk for infection. The USPSTF also recommends offering 1-time screening for HCV infection to adults born between 1945 and 1965. (B recommendation).

Evaluation of nevirapine dosing recommendations in HIV‐infected children

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used for chronic human immunodeficiency virus infections in adults and children. The aims of this study were to investigate the population pharmacokinetics of NVP in children, establish factors that influence NVP pharmacokinetics and evaluate the current dosing recommendations. Concentrations were measured on a routine basis in 94 children aged from 2 months to 17 years. A total of 390 NVP plasma concentrations were retrospectively collected, and a population pharmacokinetic model was developed with Monolix 4.0. Nevirapine pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. After standardization to a 70 kg adult using allometry, postmenstrual age had a significant effect on the bioavailability. Estimates of apparent clearance and volume of distribution were 3.9 l h(-1) (70 kg)(-1) and 140 l (70 kg)(-1) , respectively. Based on simulations of European Medicines Agency (EMA) and World Health Organization (WHO) dosing recommendations, the probability of observing minimal concentrations below the efficacy target of 3 mg l(-1) is higher following the EMA recommendations than the WHO recommendations. However, NVP underdosing persists for the 3-6 and 6-10 kg weight ranges following the WHO recommendations. It is suggested to increase doses to 75 and 100 mg twice daily for the 3-6 and 6-10 kg weight ranges, respectively, in order to obtain more than 95% of children with concentrations above 3 mg l(-1) .

Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates

Preterm and small-for-gestational-age (SGA) neonates are vulnerable groups that are susceptible to various microbial infections. Vγ9Vδ2-T cells are critical components of the host immune system and have been demonstrated to play an important role in the defense against viral infection in adults. However, the characteristics of Vγ9Vδ2-T cells in children, especially the preterm and SGA populations, are poorly understood. Here, we examined the frequency and antiviral function of Vγ9Vδ2-T cells in neonates, including preterm, SGA and full-term babies. When compared to adults, neonates had a significantly lower percentage of Vγ9Vδ2-T cells in the blood. Upon influenza virus stimulation, neonatal Vγ9Vδ2-T cells, especially from preterm and SGA babies, showed markedly decreased and delayed antiviral cytokine responses than those of adults. In addition, the antiviral responses of neonatal Vγ9Vδ2-T cells were positively correlated with gestational age and birth weight. Finally, a weaker expansion of Vγ9Vδ2-T cells by isopentenyl pyrophosphate (IPP) was shown in neonates than the expansion in adults. Our data suggest that the depressed antiviral activity and decreased frequency of Vγ9Vδ2-T cells may likely account for the high susceptibility to microbial infection in neonates, particularly in preterm and SGA babies. Improving Vγ9Vδ2-T-cell function of neonates may provide a new way to defend against virus infection.

Increased regulatory T cells and impaired functions of circulating CD8 T lymphocytes is associated with viral persistence in Hepatitis B virus‐positive newborns

Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.

Screening for Hepatitis C Virus Infection in Adults: A Systematic Review for the U.S. Preventive Services Task Force

Identification of hepatitis C virus (HCV)-infected persons through screening could lead to interventions that improve clinical outcomes. To review evidence about potential benefits and harms of HCV screening in asymptomatic adults without known liver enzyme abnormalities. English-language publications identified from MEDLINE (1947 to May 2012), the Cochrane Library Database, clinical trial registries, and reference lists. Randomized trials and cohort, case-control, and cross-sectional studies that assessed yield or clinical outcomes of screening; studies reporting harms from HCV screening; and large series reporting harms of diagnostic liver biopsies. Multiple investigators abstracted and checked study details and quality by using predefined criteria. No study evaluated clinical outcomes associated with screening compared with no screening or of different risk- or prevalence-based strategies. Three cross-sectional studies in higher prevalence populations found that screening strategies that targeted multiple risk factors were associated with sensitivities greater than 90% and numbers needed to screen to identify 1 case of HCV infection of less than 20. Data on direct harms of screening were sparse. A large study of percutaneous liver biopsies (n = 2740) in HCV-infected patients with compensated cirrhosis reported no deaths and a 1.1% rate of serious adverse events (primarily bleeding and severe pain). Modeling studies were not examined. High or unreported proportions of potentially eligible patients in the observational studies were not included in calculations of screening yield because of unknown HCV status. Although screening tests can accurately identify adults with chronic HCV infection, targeted screening strategies based on the presence of risk factors misses some patients with HCV infection. Well-designed prospective studies are needed to better understand the effects of different HCV screening strategies on diagnostic yield and clinical outcomes. Agency for Healthcare Research and Quality.

Comparative Effectiveness of Antiviral Treatment for Hepatitis C Virus Infection in Adults: A Systematic Review

Multiple treatments are available for chronic hepatitis C virus (HCV) infection. To compare benefits and harms of antiviral regimens for chronic HCV infection in treatment-naive adults. English-language literature from MEDLINE (1947 to August 2012), the Cochrane Library Database, Embase, Scopus, PsychINFO, and clinical trial registries. Randomized trials of antiviral treatments and cohort studies examining associations between sustained virologic response (SVR) after therapy and clinical outcomes. Several investigators abstracted study details and quality by using predefined criteria. No trial evaluated effectiveness of treatment on long-term clinical outcomes. Dual therapy with pegylated interferon alfa-2b plus ribavirin was associated with a lower likelihood of SVR than was pegylated interferon alfa-2a plus ribavirin (absolute difference, 8 percentage points [95% CI, 3 to 14 percentage points]) on the basis of 7 poor- to fair-quality trials. For genotype 2 or 3 infection, dual therapy for 12 to 16 weeks was associated with a lower likelihood of SVR than was therapy for 24 weeks, and lower doses of pegylated interferon alfa-2b were less effective than standard doses (2 to 4 fair-quality trials). For genotype 1 infection, fair-quality trials found that triple therapy with pegylated interferon, ribavirin, and either boceprevir (2 trials) or telaprevir (4 trials) was associated with a higher likelihood of SVR than was dual therapy (absolute difference, 22 to 31 percentage points). Compared with dual therapy, boceprevir triple therapy increased risk for hematologic adverse events and telaprevir triple therapy increased risk for anemia and rash. A large well-designed cohort study and 18 smaller cohort studies found that an SVR after antiviral therapy was associated with lower risk for all-cause mortality than was no SVR. Trials involved highly selected populations. Observational studies did not always adequately control for confounders. SVR rates for genotype 1 infection are higher with triple therapy that includes a protease inhibitor than with standard dual therapy. An SVR after antiviral therapy appears associated with improved clinical outcomes. Agency for Healthcare Research and Quality.

EICOSANOIDS MEDIATE CELLULAR IMMUNE RESPONSE AND PHENOLOXIDASE REACTION TO VIRAL INFECTION IN ADULT Pimpla turionellae

Nodulation is the predominant insect cellular immune response to microbial infections. We posed the hypothesis that parasitoid insects in their adulthood express melanotic nodulation reactions to viral challenge and that eicosanoids mediate nodulation reactions and phenoloxidase (PO) activation in response to viral challenge. To test this idea, we injected Pimpla turionellae adults with indomethacin, a nonsteroidal anti-inflammatory drug, immediately prior to intrahemocoelic injection of Bovine herpes simplex virus-1 (BHSV-1). Treating newly emerged adults of P. turionellae with BHSV-1 induced nodulation reactions, and decreased PO activity at high viral doses. Relative to vehicle-treated controls, indomethacin-treated adults produced significantly reduced numbers of nodules following viral infection (down from approximately 21 nodules per adult to less than six nodules per adult). In addition to injection treatments, increasing dietary indomethacin dosages (from 0.01% to 0.1%) were associated with decreasing nodulation (by six-fold) and PO (by about three-fold) reactions to BHSV-1 injection. Wasp adults orally fed with the lowest dietary indomethacin concentration (0.001%) expressed significantly increased PO activity (1.45 unit/min/mg protein) while nodulation reaction was not affected in response to viral challenge compared to control adults. We infer from these findings that cyclooxygenase (COX) products, at least prostaglandins, mediate nodulation response and PO action to viral infection in adults of these highly specialized insects.