Influenza vaccination in Turkey: Prevalence of risk groups, current vaccination status, factors influencing vaccine uptake and steps taken to increase vaccination rate

Influenza infections cause considerable morbidity and mortality not only during the pandemics but also during annual epidemics. Vaccines are the most effective tools for preventing the infection. Although World Health Organization (WHO) and Ministry of Health (MoH) recommends vaccination for people at increased risk, sales data indicate that vaccination rate remains low in Turkey. Vaccine recommended groups are well defined and reimbursed in Turkey. However, the prevalence of people in risk groups, current vaccination rates and factors influencing vaccine uptake which are essential in order to develop and sustain effective strategies to increase vaccination rate are not documented. A thorough literature review was performed to determine the estimated number of people in risk groups, vaccination rates, factors influencing vaccine uptake in Turkey. Actions taken by the health authorities in order to increase the vaccine uptake among specified risk groups are also summarized. Based on the published prevalence rates, current study calculated that there are approximately 27 to 33 million people in risk groups. In addition, there are 428,000 health care providers serving in the public sector who are at increased risk for influenza infections. The lowest reported vaccination rate (5.9%) was in the elderly >= 65 years of age and the highest (27.3%) in patients with COPD. Finally, survey results indicated that leading factor negatively influencing vaccine uptake was disbelief in the effectiveness of vaccine. In order to increase vaccination coverage, vaccines are provided to health care providers free of charge and reimbursed for those in the risk groups. Realizing the fact that combating flu requires multidisciplinary collaboration, a stakeholder network, Grip Platformu, has been established in 2011 with the endorsement of the MoH to increase influenza awareness and vaccine coverage rates among risk groups in accordance with WHO recommendations. (C) 2012 Elsevier Ltd. All rights reserved

Molecular and serological investigations of the Influenza A(H1N1) 2009 pandemic virus in Turkey

Intense research has been conducted on influenza A(H1N1)pdm09 virus to determine the virulence markers. Limited information on characteristics of pandemic virus has become available in Turkey since the pandemic. In this first report from Turkey, we investigated the molecular markers that have been associated with increased virulence and oseltamivir resistance. We also conducted serological studies in people after infection, vaccination, exposure, and no-exposure controls to determine the level of protection against the pandemic H1N1 influenza virus. Thirteen rRT-PCR positive samples were analyzed for presence of mutations that have been associated with host range, virulence, and antiviral resistance: substitution D222G in the HA, E627K in the PB2, and H275Y in the neuraminidase (NA). In addition, 135 serum samples from vaccinated, recovered, asymptomatic contacts, and control individuals were tested using hemagglutination inhibition (HI) assay. D222G was detected in nasal samples from two severe cases. No specified mutations in the PB2 and NA were identified. Additional substitutions, I216V, V321I, E374K, S203T in HA, V655I in PB2, and I163V in NA, were detected. HI testing from vaccinated individuals, recovered patients, asymptomatic contacts, and control individuals showed that 97.9, 99.7, 88.2, and 44.2 % had HI titers a parts per thousand yen40, respectively. Molecular markers promoting influenza A(H1N1)pdm09 to become a pandemic virus are still under investigation. Serological results confirm that younger, un-exposed individuals are at increased risk of pandemic virus infections. Influenza A(H1N1)pdm09 viruses are still in circulation around the globe. Therefore, these viruses need to be monitored closely for development of new markers including antiviral resistance mutations

Viral etiology of influenza-like illnesses during the influenza season between December 2011 and April 2012

The aim of this study was to determine the frequency of respiratory viruses responsible for respiratory tract infections in Turkish children during the 2011-2012 influenza season. Nasal swabs were obtained from patients with symptoms suggestive of an influenza-like illness between December 2011 and April 2012. Samples were analyzed with multiplex real-time polymerase chain reaction (RT-PCR) to help identify the causative viral pathogen. A total of 200 patients were enrolled in the study. A respiratory virus was detected successfully in 102 (51%) children; influenza A (H3N2) in 39.2%, influenza B in 23.5%, RSV in 15.6%, rhinovirus in 13.7%, bocavirus in 2.9%, coronavirus in 2.9%, and metapneumovirus in 0.9% of patients. Only one patient was co-infected with bocavirus and influenza A virus. A statistically significant difference in the mean age of presentation was observed between the various viral pathogens (P < 0.001). Patients with RSV were significantly younger whereas children infected with the influenza viruses were significantly older. Comparison of symptoms revealed that fever and headache occurred more frequently with the influenza viruses than the other viruses combined (P < 0.001, <0.05). Durations of symptoms such as fever, cough, nasal congestion, and rhinorrhea were also significantly longer in the influenza group (P < 0.001, <0.005, <0.001, <0.005, respectively). Demographic analyses revealed that the school/daycare attendance was the only parameter associated with a significantly increased risk for influenza infection. With an overall viral pathogen detection rate of 51%, findings of the present study suggest other respiratory pathogens, whether viral or bacterial, may also lead to hospital visits due to influenza-like illnesses in children. J. Med. Virol. 86:865-871, 2014. (c) 2013 Wiley Periodicals, Inc

Sensitivity of rapid influenza antigen tests in the diagnosis of pandemic (H1N1)2009 compared with the standard rRT-PCR technique during the 2009 pandemic in Turkey

The real-time reverse transcription polymerase chain reaction (rRT-PCR) technique has been used as the reference technique for the diagnosis of pandemic (H1N1)2009 virus infections. However, rapid influenza diagnostics tests (RIDTs) have been considered in the diagnosis of pandemic (H1N1)2009 by some healthcare institutions in Turkey due to their ease of use and generation of fast results. Nevertheless, their low sensitivity has caused concern during the control of the pandemic. This study aimed to determine the sensitivity of 4 different rapid tests available on the market in Turkey in the diagnosis of pandemic (H1N1)2009 infections compared to the reference rRT-PCR technique. One hundred and four patient samples that tested positive and 88 samples that tested negative for pandemic (H1N1)2009 by rRT-PCR were tested with RIDTs available on the market. The sensitivity of the rapid tests ranged from 31.7% to 50% depending on the brand of RIDT. Specificity ranged from 97.7% to 100%. Currently available RIDTs are not sensitive enough and could lead physicians to delay the treatment of patients, adversely affecting control efforts to mitigate the pandemic. Therefore, these tests should only be used for screening, and negative results should not rule out influenza. More sensitive and rapid point-of-care techniques are needed to meet the demands of point-of-care testing

Influenza Surveillance in Nine Consecutive Seasons, 2003-2012: Results from National Influenza Reference Laboratory, Istanbul Faculty of Medicine, Turkey

Influenza is a public health problem that affects 5-20% of the world population annually causing high morbidity and mortality especially in risk groups. In addition to determining prevention and treatment strategies with vaccines and antivirals, surveillance data plays an important role in combat against influenza. Surveillance provides valuable data on characteristics of influenza activity, on types, sub-types, antigenic properties and antiviral resistance profile of circulating viruses in a given region. The first influenza surveillance was initiated as a pilot study in 2003 by now named National Influenza Reference Laboratory, Istanbul Faculty of Medicine. Surveillance was launced at national level by Ministry of Health in 2004 and two National Influenza Laboratories, one in Istanbul and the other in Ankara, have been conducting surveillance in Turkey. Surveillance data obtained for nine consequtive years, 2003-2012, by National Influenza Reference Laboratory in Istanbul Faculty of Medicine have been summarized in this report. During 2003-2012 influenza surveillance seasons, a total of 11.077 nasal swabs collected in viral trantport medium were sent to the National Influenza Reference Laboratory, Istanbul for analysis. Immun-capture ELISA followed by MDCK cell culture was used for detection of influenza viruses before 2009 and real-time RT-PCR was used thereafter. Antigenic characterizations were done by hemagglutination inhibition assay with the reactives supplied by World Health Organization. Analysis of the results showed that influenza B viruses have entered the circulation in 2005-2006 seasons, and have contributed to the epidemics at increasing rates every year except in the 2009 pandemic season. Influenza B Victoria and Yamagata lineages were cocirculating for two seasons. For other seasons either lineage was in circulation. Antigenic characterization revealed that circulating B viruses matched the vaccine composition either partially or totally for only three seasons. Influenza A(H1N1) and A(H3N2) subtypes were in circulation since the beginning of the surveillance in 20032004 season either alone or in cocirculation. After the 2009 pandemic, A(H1N1) viruses were replaced by A(H1N1)pdm09. A(H1N1) and A(H1N1)pdm09 viruses matched the vaccine composition for all seasons. However, A(H3N2) viruses matched the vaccine composition in only three out of eight seasons. Analysis of the data revealed that, (a) influenza season has extended in Turkey and it lasts through May; (b) influenza peaks in different age groups depending on the season; (c) every year a different influenza type and subtype dominates the season; (d) influenza B has been circulating with increasing rate especially in the past six seasons. Influenza surveillance provides valuable data that can guide policy makers in developing programmes to prevent and reduce influenza burden. Therefore, addition of hospital based surveillance to general practice based sentinel surveillance will take influenza surveillance one step ahead in meeting the need for collecting data on severe influenza cases which will allow assesment of burden of influenza more reliably

Influenza B-associated encephalopathy in two adults.

Influenza virus is associated with a variety of neurological complications, of which the most commonly encountered are seizures and encephalopathy. Acute encephalitis and postinfectious encephalopathy have been reported infrequently in association with influenza A and B virus infections. We describe two previously healthy adults who presented with encephalopathy with a virologically documented influenza B infection

Mortality Related Factors In Patients Requiring Hospitalization For Influenza Like Illness

The knowledge about the viral etiologies causing respiratory disease in adults is limited. Viral respiratory diseases may lead deterioration in certain patient populations. The aim of this study was to determine the viral etiologies of influenza-like illness among patients requiring hospitalization and to document the risk factors for mortality. This prospective study was performed in one of the 7 centers in Turkey in the context of influenza surveillance by the Global Influenza Hospital Surveillance Network. A 35-bed Adult Emergency Service and 10-bed Acute Care Unit were screened for consequent recruitment of eligible patients daily, on weekdays only. ICD-10 codes in the electronic health records and direct patient encounters were used to screen for the following eligibility diagnoses: acute respiratory tract infection, asthma, heart failure, pneumonia, influenza, chronic obstructive lung disease, dyspnea/respiratory abnormality, respiratory symptoms, cough and fever. A total of 334 patients who were admitted with the eligible ICD-10 codes within the 24th and 48th hours were screened during the study period and of those eligible ones, 106 consented and were swabbed. Nasal or nasopharyngeal swabs were collected using Virocult (Medical Wire & Equipment, UK) and sent to the central laboratory in 1-3 days. Swabs were collected and specimens were introduced to real-time polymerase chain reaction based multiplex kits, as well as, ABI 7500 platform with CDC primers and probes. A total of 106 patients were swabbed. Hospital mortality was 12.2%. More than one fourth of the patients needed a sort of mechanical ventilation support and at least one organ failure developed in one third of the patients. One or more viral pathogens were detected in 56 (52.8%) of the swabbed patients, with influenza H3N2 being the most prevalent one. Having a lower body mass index (OR, 0.845, p=0.034) was associated with mortality. Chronic lung diseases were shown to confer a survival advantage (OR, 0.127, p=0.009). Community acquired viral respiratory infections might lead to significant compromise in adult patients. Prevention of malnutrition might result in better outcomes in patients who need acute admission. The survival advantage of those with chronic lung diseases warrants further investigation.WoSScopu

Surveillance and Oseltamivir Resistance of Human Influenza A Virus in Turkey During the 2007-2008 Season

Monitoring the activity of influenza viruses is important for establishing the circulating types and for detection of the emergence of novel sub-types and antiviral resistant strains. This is the first report from Turkey on the surveillance and oseltamivir resistance of influenza viruses in 2007-2008. Five hundred twenty-four nasal swabs were tested from different geographical regions in Turkey during November 2007-April 2008. One hundred sixty-three (31%) samples were positive for influenza viruses of which 111 (68%) were influenza A, 52 (31%) influenza B using an immuno-capture ELISA. Forty isolates were selected at random from influenza A positive samples and grown in MDCK cell cultures. The supernatant of the cell cultures was used for RNA extraction followed by RT-PCR to detect the sub-types. Sub-typing revealed all samples as A/H1N1. The N1 gene segment of 30 A/H1N1 samples was sequenced in part, from the 201st to 365th residue, which included the critical region for oseltamivir resistance. Then resulting sequences were analyzed with oseltamivir sensitive and resistant strains obtained from National Center for Biotechnology Information (NCBI) GenBank by CLC Main Workbench Software. H275Y (H274Y according to N2 numbering) mutation, which is known to confer resistance to oseltamivir, was detected in 6 out of 30 (20%) H1N1 isolates from four cities (Istanbul, Bursa, Ankara, and Izmir). The D354G mutation was observed in all oseltamivir resistant H1N1 isolates but not in the oseltamivir sensitive isolates. Assay of neuraminidase activity revealed that these isolates were resistant to oseltamivir, but sensitive to zanamivir. J. Med Virol. 81:1645-1651, 2009. (C) 2009 Wiley-Liss, Inc

Active Surveillance of Influenza A and Other Respiratory Viruses in Children with Influenza-like-illness in Two Seasons

Introduction: The aim of this study was to asses the surveillance of influenza A/other respiratory viruses and risk factors in hospitalized children with the symptoms of influenza-like illness during two consecutive influenza seasons