Cross-reactive immunity potentially drives global oscillation and opposed alternation patterns of seasonal influenza A viruses.

Several human pathogens exhibit distinct patterns of seasonality and circulate as pairs. For instance, influenza A virus subtypes oscillate and peak during winter seasons of the world's temperate climate zones. Alternation of dominant strains in successive influenza seasons makes epidemic forecasting a major challenge.

Secondary substitutions in the hemagglutinin and neuraminidase genes associated with neuraminidase inhibitor resistance are rare in the Influenza Resistance Information Study (IRIS).

Amino acid substitutions in influenza virus neuraminidase (NA) that cause resistance to neuraminidase inhibitors (NAI) generally result in virus attenuation. However, influenza viruses may acquire secondary substitutions in the NA and hemagglutinin (HA) proteins that can restore viral fitness. To assess to which extent this happens, the emergence of NAI resistance substitutions and secondary - potentially compensatory - substitutions was quantified in influenza viruses of immunocompetent individuals included in the Influenza Resistance Information Study (IRIS; NCT00884117).

Viral Kinetics and Resistance Development in Children Treated with Neuraminidase Inhibitors: The Influenza Resistance Information Study (IRIS).

Background: We studied the effect of age, baseline viral load, vaccination status, antiviral therapy, and emergence of drug resistance on viral shedding in children infected with influenza A or B virus.

Methods: Samples from children (aged ≤13 years) enrolled during the 7 years of the prospective Influenza Resistance Information Study were analyzed using polymerase chain reaction to determine the influenza virus (sub-)type, viral load, and resistance mutations. Disease severity was assessed; clinical symptoms were recorded.

Influenza A/H3N2 virus infection in immunocompromised ferrets and emergence of antiviral resistance.

Influenza viruses can cause severe life threatening infections in high-risk patients, including young children, the elderly and patients with compromised immunity due to underlying medical conditions or immunosuppressive treatment. The impaired immunity of these patients causes prolonged virus infection and combined with antiviral treatment facilitates the emergence of viruses with resistance mutations. The diverse nature of their immune status makes them a challenging group to study the impact of influenza virus infection and the efficacy of antiviral therapy.

An analysis of the predictive value of the HIV Ag/Ab screening assay within the performance characteristics of the DiaSorin LIAISON XL for the detection of blood-borne viruses.

Background: Correct identification of blood borne viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is crucial in detection and follow up of infection in patients.

Objectives: We evaluated the diagnostic performance of the DiaSorin LIAISON XL (LIAISON XL) for screening of HBV, HCV and HIV infection. In addition, we investigated the variability of the signal-to-cuttoff ratio (S/CO) of the LIAISON XL HIV Ag/Ab assay and it's predictive value in subsequent confirmation of HIV-1 infection.

Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study.

Background And Objectives: The Influenza Resistance Information Study (IRIS) was initiated in 2008 to study the emergence of neuraminidase inhibitor (NAI) resistance and the clinical course of influenza in immunocompetent treated and untreated patients.

Methods: Patients had throat/nose swabs collected on days 1, 3, 6 and 10 for analyses of influenza type, subtype and virus susceptibility to NAIs. RT-PCR-positive samples were cultured and tested for NAI resistance by specific RT-PCR and phenotypic testing.

Discordant detection of avian influenza virus subtypes in time and space between poultry and wild birds; Towards improvement of surveillance programs.

Avian influenza viruses from wild birds can cause outbreaks in poultry, and occasionally infect humans upon exposure to infected poultry. Identification and characterization of viral reservoirs and transmission routes is important to develop strategies that prevent infection of poultry, and subsequently virus transmission between poultry holdings and to humans. Based on spatial, temporal and phylogenetic analyses of data generated as part of intense and large-scale influenza surveillance programs in wild birds and poultry in the Netherlands from 2006 to 2011, we demonstrate that LPAIV subtype distribution differed between wild birds and poultry, suggestive of host-range restrictions.

Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes.

Human cytomegalovirus (HCMV) infects most of the population worldwide, persisting throughout the host's life in a latent state with periodic episodes of reactivation. While typically asymptomatic, HCMV can cause fatal disease among congenitally infected infants and immunocompromised patients. These clinical issues are compounded by the emergence of antiviral resistance and the absence of an effective vaccine, the development of which is likely complicated by the numerous immune evasins encoded by HCMV to counter the host's adaptive immune responses, a feature that facilitates frequent super-infections.

Outcomes and Susceptibility to Neuraminidase Inhibitors in Individuals Infected With Different Influenza B Lineages: The Influenza Resistance Information Study.

Background: Little is known about how influenza infections caused by B/Victoria and B/Yamagata virus lineages compare with respect to disease course and susceptibility to antiviral therapy.

Methods: Data from patients with influenza B infections from the first 5 years (2009-2013) of the prospective Influenza Resistance Information Study (IRIS, NCT00884117) were evaluated. Cultured viruses were phenotypically tested for neuraminidase inhibitor (NAI) sensitivity, and sequenced to determine virus lineage (B/Victoria or B/Yamagata).

Viral shedding and susceptibility to oseltamivir in hospitalized immunocompromised patients with influenza in the Influenza Resistance Information Study (IRIS).

Background: Immunocompromised patients are at greater risk of complicated influenza and may be more likely to develop antiviral resistance. This observational substudy of the Influenza Resistance Information Study (NCT00884117) aimed to study antiviral resistance in immunocompromised patients with influenza and characterize its effect on clinical and virological outcomes.

Methods: Eligible immunocompromised patients were aged ≥1 year with a local rapid diagnostic or PCR test positive for influenza ≤96 h after diagnosis and with influenza symptoms.

More virological failure with lamivudine than emtricitabine in efavirenz and nevirapine regimens in the Dutch nationwide HIV Cohort.

Introduction: Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable by HIV-1 guidelines in first-line tenofovir/efavirenz (TDF/EFV) and TDF/nevirapine (NVP) combination antiretroviral therapy (cART). Data from trials on equivalence of 3TC and FTC are inconsistent. We examined the effectiveness of 3TC and FTC in the national HIV cohort in the Netherlands.

Increased virological failure in naive HIV-1-infected patients taking lamivudine compared with emtricitabine in combination with tenofovir and efavirenz or nevirapine in the Dutch nationwide ATHENA cohort.

Background: Guidelines for treatment of human immunodeficiency virus type 1 (HIV-1) infection consider lamivudine and emtricitabine to be interchangeable components in first-line combination antiretroviral therapy (cART). The evidence for their clinical equivalence in cART is inconsistent. The primary aim of this study was to evaluate the virological responses to lamivudine and emtricitabine in recommended cART.

A 5-year study of adenoviruses causing conjunctivitis in Izmir, Turkey.

Adenoviruses are a common cause of conjunctivitis. Genotypes are diverse and differ according to population and geographical distribution of the virus. There is limited data regarding ocular adenoviral infections and genotype distribution in Turkey.

Hepatitis B virus prevalence, risk factors and genotype distribution in HIV infected patients from West Java, Indonesia.

Background: Indonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden.

Objective: The objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia.

Study Design: A cross sectional study was conducted among a cohort of HIV infected patients in 2008.

HIV-1 evolution in patients undergoing immunotherapy with Tat, Rev, and Nef expressing dendritic cells followed by treatment interruption.

Objectives: This study aimed to evaluate HIV sequence evolution in whole genes and in CD8 T-cell epitope regions following immunotherapy and subsequent analytical treatment interruption (ATI). A second objective of this study was to analyze associations between vaccine-specific immune responses and epitope mutation rates.

Design: HIV-1-infected patients on combined antiretroviral therapy (cART) were subjected to immunotherapy by the administration of an autologous dendritic cell-based therapeutic vaccine expressing Tat, Rev, and Nef and subsequent ATI.

Influenza virus resistance to antiviral therapy.

Antiviral drugs for influenza therapy and prophylaxis are either of the adamantane or neuraminidase inhibitor (NAI) class. However, the NAIs are mainly prescribed nowadays, because of widespread adamantane resistance among influenza A viruses and ineffectiveness of adamantanes against influenza B. Emergence and spread of NAI resistance would further limit our therapeutic options.

Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia.

The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug-resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months.

Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic.

Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study.

Background: Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT).

Molecular assays for quantitative and qualitative detection of influenza virus and oseltamivir resistance mutations.

Sensitive and reproducible molecular assays are essential for influenza virus diagnostics. This manuscript describes the design, validation, and evaluation of a set of real-time RT-PCR assays for quantification and subtyping of human influenza viruses from patient respiratory material. Four assays are included for detection of oseltamivir resistance mutations H275Y in prepandemic and pandemic influenza A/H1N1 and E119V and R292K in influenza A/H3N2 neuraminidase.

Global assessment of resistance to neuraminidase inhibitors, 2008-2011: the Influenza Resistance Information Study (IRIS).

Background: Following emergence of naturally occurring oseltamivir-resistant influenza A(H1N1) viruses, a global observational investigation, the Influenza Resistance Information Study (IRIS; NCT00884117), was initiated in 2008 to study neuraminidase inhibitor (NAI) resistance and clinical outcome.

Methods: Patients with influenza-like illness and/or positive rapid test results agreed to swabs of the posterior nares that were assessed by semiquantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) for influenza type and subtype and NAI resistance. RT-qPCR-positive specimens were cultured, sequenced, and phenotypically tested for NAI resistance.

Long-term response rates of successful hepatitis B vaccination in HIV-infected patients.

Background: Data on long-term response rates after successful primary hepatitis B (HBV) vaccination in HIV-infected patients are scarce.

Objective: To evaluate the durability of an effective anti-HBs titer up to 5 years after primary vaccination in a cohort of 155 HIV-infected adults.

Methods: From a previous multicenter HBV vaccination trial we selected patients with an anti-HBs titer of ≥10 IU/l 28 weeks after the first vaccination.

H1N1 2009 pandemic influenza virus: resistance of the I223R neuraminidase mutant explained by kinetic and structural analysis.

Two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that antiviral resistant viruses emerge and spread in the human population. The 2009 pandemic H1N1 virus is already resistant to adamantanes.

Therapy failure resulting from superinfection by a drug-resistant HIV variant.

Background: HIV-1-infected patients can be superinfected with additional HIV-1 variants. Therapy failure can be the consequence of an infection with a resistant strain.

Methods: A patient was diagnosed with a recent HIV-1 infection in April 2005 and subsequently clinically monitored.