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- Brittain-Long, Robin, 1969, et al.
(författare)
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Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial.
- 2011
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Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. METHODS: Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit) and after 10 days (follow-up visit). Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days). The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. RESULTS: A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202) of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204) (P = 0.005) of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202) in the rapid result group and 17.2% (35 of 204) in the delayed result group (P = 0.359), respectively. CONCLUSIONS: Access to a rapid method for etiologic diagnosis of ARTIs may reduce antibiotic prescription rates at the initial visit in an outpatient setting. To sustain this effect, however, it seems necessary to better define how to follow and manage the patient according to the result of the test, which warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01133782.
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| 3. |
- Brittain-Long, Robin, 1969
(författare)
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On the Diagnosis and Management of Viral Respiratory Infections
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute respiratory tract infections (ARTIs), are the most common infections in man, and represent a major global health burden. Viruses, most often causing a mild and self-limiting disease, yet with substantial morbidity and high costs for society, mainly cause upper respiratory tract infections. 70% of all infections in primary care in Sweden are due to ARTIs. Lower respiratory infections on the other hand constitute the third leading cause of death worldwide, mainly in children <5 years of age in resource poor settings. Distinguishing virus from bacteria can be difficult, and often lead to an over-prescription of antibiotics. Modern molecular based diagnostic methods have increased the possibility of an etiologic diagnosis of ARTIs significantly. This thesis aims to evaluate the use of a multiplex real time PCR assay targeting 13 respiratory viruses and two bacteria, from a clinical perspective. In paper I, a retrospective study of 954 nasopharyngeal samples, the PCR assay, which is based on automated specimen extraction and multiplex amplification, is described. Detection rate was 48%. Streamlined testing and cost limitation (€ 33 per sample) along with high accuracy and prompt result delivery, is key to successful implementation of broad molecular testing. Paper II evaluates in a prospective study of 209 adults with ARTI in primary care, and 100 asymptomatic controls, the impact duration of symptoms have on detection rate. Overall positive yield was 43% in patients and 2% in controls, with a significantly higher detection rate in patients with < 6 days duration of symptoms (51%) compared to ≥ 7 days (30%, p<0.01). Having access to the PCR assay reduced antibiotic prescription rates by 50%, in a prospective study (paper III) of 426 adults with ARTI. Patients receiving a result within 48 hours were prescribed antibiotics in 6,8% (n=14) compared to 15.1% (n=33, p<0.01) in the delayed result group. The diagnostic yield in paper IV, a retrospective study of 8753 patients of all ages during 36 consecutive months, was significantly higher during winter (54.7%) than in summer (31.1%, p<0.001), and in children (61.5%) compared with adults (30.5%, p<0.001). Rhinovirus was the most frequently found virus (32.5%), independent of season, and displayed a high genetic variability across seasons. The findings of this thesis support the implementation of similar methods in routine clinical care.
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| 5. |
- Brittain-Long, Robin, 1969, et al.
(författare)
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Seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay.
- 2011
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Nucleic acid amplification tests are increasingly being used to diagnose viral and bacterial respiratory tract infections. The high sensitivity of these tests affects our understanding of the epidemiology of respiratory tract infections. We have assessed the detection rate of a multiplex real-time polymerase chain reaction (PCR) test, with emphasis on epidemiology and seasonal distribution of the most common respiratory tract infections. Methods: Seven thousand eight hundred and fifty-three nasopharyngeal samples from 7220 patients (age range 0-98 y, median 22 y) obtained during 36 consecutive months (November 2006-October 2009), were analyzed with a multiplex PCR panel including influenza A (IfA) and B (IfB) virus, parainfluenza virus (PIV) 1-3, respiratory syncytial virus (RSV), human rhinovirus (HRV), human coronavirus (CoV) OC43, NL63, and 229E, human metapneumovirus (HMPV), adenovirus (AdV), enterovirus (EV), and 2 bacteria - Mycoplasma pneumoniae and Chlamydophila pneumoniae. Results: Of the total samples, 44.5% (n = 3496) were positive for at least 1 agent, with HRV being the most common (n = 1482, 38.0%), followed by RSV (n = 526, 13.5%) and IfA (n = 403, 10.3%). The diagnostic yield was significantly higher during the winter and early spring compared to the summer (n = 2439 of 4458 samples, 54.7% and n = 1057 of 3395 samples, 31.1%, respectively; p < 0.001). Conclusions: The diagnostic yield was highly dependent on the month of sampling and the age of the patient. However, the overall detection rate per month was above 30%, apart for August and September. Our findings support the use of similar tests in routine clinical care all year round. HRV was the most common finding in the respiratory tract, independent of season.
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| 6. |
- Magnusson, Jesper, et al.
(författare)
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The Impact of Viral Respiratory Tract Infections on Long-Term Morbidity and Mortality following Lung Transplantation: A Retrospective Cohort Study Using a Multiplex PCR Panel.
- 2013
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Ingår i: Transplantation. - 1534-6080. ; 95:2, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The major factor affecting morbidity and mortality after lung transplantation (LTX) is bronchiolitis obliterans syndrome. Earlier studies have suggested a connection between the presence of viral agents and morbidity in this patient group, but data are somewhat conflicting. The objective of this study was to investigate the development of bronchiolitis obliterans syndrome and graft loss after LTX in relation to the presence of respiratory viruses during the first year after LTX. METHOD: The study is a retrospective cohort study of 39 LTX recipients 11-13 years after surgery. Patients were operated between January 1, 1998 and December 31, 2000 at Sahlgrenska University Hospital. The presence of virus in bronchoalveolar lavage (BAL) fluids from patients during the first year after surgery was analyzed retrospectively using a multiplex polymerase chain reaction test capable of detecting 15 respiratory agents. The time to BOS or graft loss was analyzed in relation to the positive findings in BAL during the first year after LTX. RESULTS: Patients with one or more viruses detected in BAL during the first year after transplantation demonstrated a significantly faster development of BOS (P=0.005) compared with patients with no virus detected. No significant difference in graft survival was found. CONCLUSION: Our results suggest that the long-term prognosis after LTX may be negatively affected by viral respiratory tract infections during the first year after LTX.
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| 7. |
- Nilsson, Anna, et al.
(författare)
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Frequent detection of respiratory agents by multiplex PCR on oropharyngeal samples in Swedish school-attending adolescents
- 2012
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44, s. 393-397
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Tidskriftsartikel (refereegranskat)abstract
- Background: Respiratory agents may be detected in the oropharynx of healthy individuals. The extent of this condition and the reasons behind it are largely unknown. The objective of this study was to determine the factors associated with the presence of respiratory agents in the oropharynx of adolescents healthy enough to attend school activities. Methods: On a single day in December, samples from the posterior wall of the oropharynx of adolescents aged 1015 y were obtained using cotton-tipped swabs. The samples were analyzed by real-time polymerase chain reaction (PCR) for the presence of 13 respiratory viruses and 2 bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae). Results: Out of the 232 adolescents sampled, 67 (29%) had any respiratory symptom. A positive PCR result was found in 50 individuals (22%). Human rhinovirus was the most commonly found agent. Respiratory agents were significantly more frequent in the younger age group (1013 y) than in the older age group (1415 y): 26% (38/148) vs 14% (12/84), respectively; p = 0.04. Cough was the only symptom that was more common among individuals with a positive PCR test than among those with a negative PCR test: 8/50 (16%) vs 11/182 (6%); p = 0.02. Family size and class size were not associated with the likelihood of a positive PCR test. Conclusions: The presence of respiratory agents in the oropharynx is a frequent finding among adolescents healthy enough to attend school activities. The high prevalence was found to be associated with young age, but not with the size of the family or class. © 2012 Informa Healthcare.
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| 8. |
- Olofsson, Sigvard, 1948, et al.
(författare)
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PCR for detection of respiratory viruses: seasonal variations of virus infections
- 2011
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Ingår i: EXPERT REVIEW OF ANTI-INFECTIVE THERAPY. - 1478-7210. ; 9:8, s. 615-626
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Forskningsöversikt (refereegranskat)abstract
- Real-time PCR and related methods have revolutionized the laboratory diagnosis of viral respiratory infections because of their high detection sensitivity, rapidness and potential for simultaneous detection of 15 or more respiratory agents. Results from studies with this diagnostic modality have significantly expanded our knowledge about the seasonality of viral respiratory diseases, pinpointed the difficulties to make a reliable etiologic diagnosis without the aid of an unbiased multiplex molecular assay for respiratory viruses, and revealed previously unknown details as to possible infections with multiple agents as aggravating factors. The scope of this article is to review and discuss this new knowledge and its implications for diagnostic strategies and other measures essential for the clinical management of respiratory viral infections and for epidemiological surveillance of seasonal respiratory infections.
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| 10. |
- Sundell, Nicklas, et al.
(författare)
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PCR detection of respiratory pathogens in asymptomatic and symptomatic adults.
- 2019
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Ingår i: Journal of clinical microbiology. - 1098-660X. ; 57:1
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Tidskriftsartikel (refereegranskat)abstract
- The frequency of viral respiratory pathogens in asymptomatic subjects is poorly defined. The aim of this study was to explore the prevalence of respiratory pathogens in the upper airways of asymptomatic adults, as compared with a reference population of symptomatic patients sampled in the same centres during the same period. Nasopharyngeal (NP) swab samples were prospectively collected from adults with and without ongoing symptoms of respiratory tract infection (RTI) during 12 consecutive months, in primary care centres as well as hospital emergency departments, and analysed for respiratory pathogens by a PCR panel detecting 16 viruses and four bacteria. Altogether, 444 asymptomatic and 75 symptomatic subjects completed sampling as well as follow-up (FU) at day 7. In the asymptomatic subjects the detection rate of viruses was low (4.3%) and the most common virus detected was rhinovirus (3.2%). Streptococcus pneumoniae was found in 5.6% of the asymptomatic subjects and Haemophilus influenzae in 1.4%. The only factor independently associated with low viral detection rate in asymptomatic subjects was age ≥65 (p=0.04). An increased detection rate of bacteria was seen in asymptomatic subjects who were currently smoking (p<0.01) and who had any chronical condition (p<0.01). We conclude that detection of respiratory viruses in asymptomatic adults is uncommon, suggesting that a positive PCR result from a symptomatic patient likely is relevant for ongoing respiratory symptoms. Age influences the likelihood of virus detection among asymptomatic adults and smoking as well as co-morbidity may increase the prevalence of bacterial pathogens in the upper airways.
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| 11. |
- Westin, Johan, 1965, et al.
(författare)
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Multiplex real-time PCR for detection of respiratory tract infections
- 2008
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 41:1, s. 53-56
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Tidskriftsartikel (refereegranskat)abstract
- Background Broad diagnostics of respiratoryinfection by molecular assays has not yet won acceptance due to technical difficulties and high costs. Objectives To evaluate clinical applicability of multiplexreal-timePCR. Study design An assay targeting influenza virus A (IfA) and B (IfB), parainfluenza 1-3 (PIV), human metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RV), enterovirus (EV), adenovirus (AdV), human coronaviruses (229E, OC43, NL63), M. pneumoniae and Ch. pneumoniae was developed and run daily on consecutive clinical nasopharyngeal swab samples. Results An etiology was identified in 48% of the 954 samples, with IfA in 25%, RV in 20%, MPV in 10% and M. pneumoniae in 10% of the positive. By a rational procedure costs could be reduced and the customer price set relatively low (€33 per sample). Conclusion Streamlined testing and cost limitation is achievable and probably critical for implementation of a broad molecular diagnostics of respiratoryinfections.
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