Rapid Viral Testing Research Articles

Virological failure, HIV-1 drug resistance, and early mortality in adults admitted to hospital in Malawi: an observational cohort study

SummaryBackgroundAntiretroviral therapy (ART) scale-up in sub-Saharan Africa combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance, and early mortality among patients with HIV admitted to hospital in Malawi.MethodsThis observational cohort study was nested within the rapid urine-based screening for tuberculosis to reduce AIDS-related mortality in hospitalised patients in Africa (STAMP) trial, which recruited unselected (ie, irrespective of clinical presentation) adult (aged ≥18 years) patients with HIV-1 at admission to medical wards. Patients were included in our observational cohort study if they were enrolled at the Malawi site (Zomba Central Hospital) and were taking ART for at least 6 months at admission. Patients who met inclusion criteria had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA of at least 1000 copies per mL had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR program. Mortality risk was calculated 56 days from enrolment. Patients were censored at death, at 56 days, or at last contact if lost to follow-up. The modelling strategy addressed the causal association between HIV multidrug resistance and mortality, excluding factors on the causal pathway (most notably, CD4 cell count, clinical signs of advanced HIV, and poor functional and nutritional status).FindingsOf 1316 patients with HIV enrolled in the STAMP trial at the Malawi site between Oct 26, 2015, and Sept 19, 2017, 786 had taken ART for at least 6 months. 252 (32%) of 786 patients had virological failure (viral load ≥1000 copies per mL). Mean age was 41·5 years (SD 11·4) and 528 (67%) of 786 were women. Of 237 patients with HIV drug resistance results available, 195 (82%) had resistance to lamivudine, 128 (54%) to tenofovir, and 219 (92%) to efavirenz. Resistance to at least two drugs was common (196, 83%), and this was associated with increased mortality (adjusted hazard ratio 1·7, 95% CI 1·2–2·4; p=0·0042).InterpretationInterventions are urgently needed and should target ART clinic, hospital, and post-hospital care, including differentiated care focusing on patients with advanced HIV, rapid viral load testing, and routine access to drug resistance testing. Prompt diagnosis and switching to alternative ART could reduce early mortality among inpatients with HIV.FundingJoint Global Health Trials Scheme of the Medical Research Council, UK Department for International Development, and Wellcome Trust.

A fully automated centrifugal microfluidic system for sample-to-answer viral nucleic acid testing.

The outbreak of virus-induced infectious diseases poses a global public-health challenge. Nucleic acid amplification testing (NAAT) enables early detection of pandemic viruses and plays a vital role in preventing onward transmission. However, the requirement of skilled operators, expensive instrumentation, and biosafety laboratories has hindered the use of NAAT for screening and diagnosis of suspected patients. Here we report development of a fully automated centrifugal microfluidic system with sample-in-answer-out capability for sensitive, specific, and rapid viral nucleic acid testing. The release of nucleic acids and the subsequent reverse transcription loop-mediated isothermal amplification (RT-LAMP) were integrated into the reaction units of a microfluidic disc. The whole processing steps such as injection of reagents, fluid actuation by rotation, heating and temperature control, and detection of fluorescence signals were carried out automatically by a customized instrument. We validate the centrifugal microfluidic system using oropharyngeal swab samples spiked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) armored RNA particles. The estimated limit of detection for armored RNA particles is 2 copies per reaction, the throughput is 21 reactions per disc, and the assay sample-to-answer time is approximately 70 min. This enclosed and automated microfluidic system efficiently avoids viral contamination of aerosol, and can be readily adapted for virus detection outside the diagnostic laboratory. Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/s11426-020-9800-6 and is accessible for authorized users.

False Negative Human Immunodeficiency Virus Rapid Test: Lessons to Remember

False Negative Human Immunodeficiency Virus Rapid Test: Lessons to Remember

Considerable distance to reach 90-90-90 targets among female sex workers, men who have sex with men and transgender women in Port Moresby, Papua New Guinea: findings from a cross-sectional respondent-driven sampling survey

ObjectiveTo characterise the Joint United Nations Programme on HIV/AIDS 90-90-90 cascade among female sex workers (FSW) and men who have sex with men (MSM)/transgender women (TGW) in Port Moresby, Papua...

Virological Failure, HIV-1 Drug Resistance and Early Mortality in Adults Admitted to Hospital in Malawi: A Nested Observational Cohort Study

Background: Antiretroviral therapy (ART) scale-up in sub-Saharan Africa (SSA) combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance and early mortality among hospital inpatients in Malawi. Methods: An observational cohort study nested in a trial of urine-based TB screening in unselected HIV-positive adults followed up for 2 months. Patients taking ART for ≥6 months at hospital admission had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA ≥1000 copies/ml had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR Algorithm Findings: Of 1316 patients recruited in the Malawi trial site between October 2015 and September 2017, 786 had taken ART for ≥6 months of whom 252/786 (32.1%) patients had viral load ≥1000 copies/ml (virological failure). Mean age was 38 years, 61.5% were female and median CD4 count was 60 cells/µL. Of 237 (94.0%) patients with HIV drug resistance results available, 195 (82.3%) had resistance to lamivudine, 128 (54.0%) to tenofovir and 219 (92.4%) to efavirenz. Resistance to at least 2 drugs was common (196/237, 82.7%) and this was associated with increased 2-month mortality (adjusted hazard ratio 1.7, 95% CI 1.2-2.4, p=0.004). Interpretation: HIV virological failure and HIV multidrug resistance were common in HIV-positive inpatients, and associated with increased early mortality. Targeted interventions including adherence support, rapid viral load testing and routine access to drug resistance testing are urgently needed. Enabling prompt diagnosis and switching to alternative ART could reduce early mortality among HIV-positive inpatients. Funding Statement: The Screening for TB to Reduce AIDS Related Mortality in Hospitalised Patients (STAMP) trial was funded by the Joint Global Health Trials Scheme of the UK Department of Health and Social Care, the Department for International Development, the Global Challenges Research Fund, the Medical Research Council and Wellcome Trust (MR/M007375/1). AGW has received a Royal College of Physicians London James Maxwell Grant Prophit Fellowship, and ELC has received a Wellcome Trust Fellowship (WT200901/Z/16/Z). Declaration of Interests: The authors declare no conflicts of interest exist. Ethics Approval Statement: All patients provided informed written consent for participation and sample storage. Retrospective HIV viral load and drug resistance testing was approved by the research ethics committee of the London School of Hygiene and Tropical Medicine, and the University of Malawi College of Medicine Research and Ethics Committee (COMREC).

Combining Procalcitonin and Rapid Multiplex Respiratory Virus Testing for Antibiotic Stewardship in Older Adult Patients With Severe Acute Respiratory Infection

ObjectivesVirus infection is underevaluated in older adults with severe acute respiratory infections (SARIs). We aimed to evaluate the clinical impact of combining point-of-care molecular viral test and serum procalcitonin (PCT) level for antibiotic stewardship in the emergency department (ED). DesignA prospective twin-center cohort study was conducted between January 2017 and March 2018. Setting and ParticipantsOlder adult patients who presented to the ED with SARIs received a rapid molecular test for 17 respiratory viruses and a PCT test. MeasuresTo evaluate the clinical impact, we compared the outcomes of SARI patients between the experimental cohort and a propensity score–matched historical cohort. The primary outcome was the proportion of antibiotics discontinuation or de-escalation in the ED. The secondary outcomes included duration of intravenous antibiotics, length of hospital stay, and mortality. ResultsA total of 676 patients were included, of which 169 patients were in the experimental group and 507 patients were in the control group. More than one-fourth (27.9%) of the patients in the experimental group tested positive for virus. Compared with controls, the experimental group had a significantly higher proportion of antibiotics discontinuation or de-escalation in the ED (26.0% vs 16.1%, P = .007), neuraminidase inhibitor uses (8.9% vs 0.6%, P < .001), and shorter duration of intravenous antibiotics (10.0 vs 14.5 days, P < .001). Conclusions and ImplicationsCombining rapid viral surveillance and PCT test is a useful strategy for early detection of potential viral epidemics and antibiotic stewardship. Clustered viral respiratory infections in a nursing home is common. Patients transferred from nursing homes to ED may benefit from this approach.

Rapid Multiplex Testing for Upper Respiratory Pathogens in the Emergency Department: A Randomized Controlled Trial.

BackgroundAcute upper respiratory tract infections are a common cause of emergency department (ED) visits and often result in unnecessary antibiotic treatment.MethodsWe conducted a randomized clinical trial to evaluate the impact of a rapid, multipathogen respiratory panel (RP) test vs usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza-like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136).ResultsOf 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (P = .0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (–12%; 95% confidence interval, –25% to 0.4%; P = .06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (–19%) vs adults (–9%, post hoc analysis). There was no difference in antiviral use, length of stay, or disposition.ConclusionsRapid RP testing was associated with a trend toward decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate the relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.

Prevalence and Risk Factors for HIV Infection in a Population of Homosexual, Bisexual, and Other Men Who Have Sex with Men in the Metropolitan Region of Chile: A Re-emerging Health Problem.

According to the most recent UNAIDS report, the number of new HIV infections has increased by 34% since 2010 in Chile, representing the largest increase in the Americas. The objective of this study was to identify factors associated with HIV prevalence among men who have sex with men (MSM) in the metropolitan region (MR) of Santiago, Chile. Cross-sectional study of MSM living in the MR, recruited using respondent-driven sampling (RDS). Participants were tested using Human Immunodeficiency virus rapid test, and reactive cases were confirmed withELISA. Participants were interviewed using a questionnaire adapted for the Chilean population. Descriptive and logistic regression analyses were then performed. All applicable ethical norms were followed in the execution of this study. The total sample consisted of 375 individuals. HIV prevalence among MSM was 17.6% overall. Among the HIV-negative men, most (71.5%) had not been tested for sexually-transmitted diseases (STIs) other than HIV in the past 12months, and 24.1% had never been tested for HIV. Participants who had been tested for an STI other than HIV in the past 12months had a 3.56-fold greater OR for HIV-positive status than those who had not. Conversely, having had an HIV test in the past 12months was a protective factor against positive HIV status (OR = 0.09). The high prevalence of HIV among MSM suggests a re-emergence of the disease in Chile, and cases are specifically concentrated among young MSM. Access to sexual health care and STI testing in Chile is insufficient. Targeted prevention efforts are urgently needed as part of the Chilean national strategy to combat the spread of HIV, including community-based testing programs.

Length of Stay and Complications Associated With Febrile Infants

It is not known how changes in the epidemiology of serious bacterial infection (SBI) and greater availability of rapid viral diagnostic tests have impacted the hospital length of stay (LOS) and associated complications among young infants with suspected SBI. We used national administrative data from the Healthcare Cost and Utilization Project Kids' Inpatient Database and other state-specific data to identify febrile infants <90 days of age hospitalized in 2000, 2003, 2006, 2009, and 2012. We used multivariate analysis to determine LOS, risk factors for prolonged LOS, and complications of care among infants with isolated fever or viral respiratory disease, without concomitant serious infection. We identified 44 875 infants. LOS for each clinical group did not change over time in a clinically significant way. Mean LOS was ≤2 days for approximately two-thirds of all infants and ≥4 days for 11% in each clinical group. Factors associated with longer LOS included age <31 days, critical clinical status, concomitant chronic disease, and the presence of complications (P < .05). We identified 289 (0.8%) infants with 351 complications of care, 18 (6%) of whom had >1. These infants had longer LOS (P < .001), and those with chronic disease and older age were at increased risk (P < .01). Despite the changing epidemiology of SBI and increased availability of viral diagnostic testing, we did not detect a clinically significant change in LOS for febrile infants with suspected SBI. Complications associated with hospitalization of these infants was associated with increased LOS.

Diagnosis and Management of Pediatric Influenza in the Era of Rapid Diagnostics.

Influenza is a significant cause of childhood morbidity and death; it contributes to up to 16% of hospitalizations for respiratory illnesses worldwide. Novel rapid viral diagnostic tests, including molecular diagnostic tests, have the potential to significantly affect both time to diagnosis and selection of optimal anti-infective therapy. However, little is known about current treatment algorithms used in US hospitals. In this study, for hospitalized children in the United States, we aimed to define the current approaches to influenza diagnosis and treatment and to explore reasons for their potential variation. In this study, we aimed to define the current approaches to pediatric influenza diagnosis and treatment in US hospitals, and to explore reasons for their potential variation. Our results suggest a rise in the availability and use of rapid molecular diagnostic testing in addition to continued variability in anti-infective management, particularly with regard to antiviral use.

Using a novel rapid viral test to improve triage of emergency department patients with acute respiratory illness during flu season

BackgroundAcute respiratory illnesses (ARI) are mostly viral in etiology and cause significant morbidity and mortality. Point of care PCR (POC-PCR) is a promising new technology for rapid virus identification but utility in the Emergency Department (ED) is not yet defined. ObjectivesPrimarily, to investigate the value of POC-PCR in rapidly identifying RSV and influenza in the setting of ED triage. Additionally, to assess whether rapid knowledge of accurate test results would improve patient management by preventing nosocomial transmission and optimizing the prescription of antimicrobials for ARIs. Study DesignA prospective cohort study of consecutive ED patients with ARI symptoms during peak flu season was conducted. Patient nasopharyngeal swabs were collected and tested using a POC-PCR device; physicians and patients were blinded to results. Virus positive and negative groups were compared by ED patient room placement and antimicrobial therapy ordered. Specificity and sensitivity were calculated using laboratory-PCR as the gold standard. ResultsOf 119 participants, 52.9% were POC-PCR positive - Influenza A (42.9%), RSV (41.3%), influenza B (15.9%). Nearly 70% of virus positive patients were placed rooms shared with non-ARI patients. Antibiotics were prescribed for 27.3% of virus positive patients, and 77.8% of oseltamivir-eligible patients did not receive therapy. POC-PCR was 100% sensitive (95% CI, 80.5–100.0%) and 95.2% specific (95% CI, 76.2–99.9%). ConclusionsRapid POC-PCR for influenza and RSV in ED triage has excellent sensitivity and specificity and the potential to improve social distancing practices through better triage and increase appropriate prescription of antimicrobials.

Host Cell Mimic Polymersomes for Rapid Detection of Highly Pathogenic Influenza Virus via a Viral Fusion and Cell Entry Mechanism.

Highly pathogenic avian influenza virus (HPAIV) infections have occurred continuously and crossed the species barrier to humans, leading to fatalities. A polymerase chain reaction based molecular test is currently the most sensitive diagnostic tool for HPAIV; however, the results must be analyzed in centralized diagnosis systems by a trained individual. This requirement leads to delays in quarantine and isolation. To control the spread of HPAIV, rapid and accurate diagnostics suitable for field testing are needed, and the tests must facilitate a differential diagnosis between HPAIV and low pathogenic avian influenza virus (LPAIV), which undergo cleavage specifically by trypsin‐ or furin‐like proteases, respectively. In this study, a differential avian influenza virus rapid test kit is developed and evaluated in vitro and using clinical specimens from HPAIV H5N1‐infected animals. It is demonstrated that this rapid test kit provides highly sensitive and specific detection of HPAIV and LPAIV and is thus a useful field diagnostic tool for H5N1 HPAIV outbreaks and for rapid quarantine control of the disease.

Community-Acquired Pneumonia in Children-An Update

Community-acquired pneumonia (CAP) is a potentially serious infection in children and often results in hospitalization.CAP symptoms are nonspecific in younger infants, but cough and tachypnea are usually present in older children. The diagnosis can be based on the history and physical examination results in children with fever plus respiratory signs and symptoms. Chest radiography and rapid viral testing may be helpful when the diagnosis is unclear. The most likely etiology depends on the age of the child. Viral and Streptococcus pneumonia infections are most common in preschoolaged children, whereas Mycoplasmapneumoniaeis common in older children.Most children can be managed empirically with oral antibiotics as outpatients without specific laboratory investigations.The decision to treat with antibiotics is challenging, especially with the increasing prevalence of viral and bacterial coinfections. Those with severe infections or with persistent or worsening symptoms need more intensive investigations and may need admission to hospital. The choice and dosage of antibiotics should be based on the age of the patient, severity of the pneumonia and knowledge of local antimicrobial resistance patterns.Bangladesh J Child Health 2018; VOL 42 (1) :38-42

Enterovirus D-68 in children presenting for acute care in the hospital setting.

BackgroundSevere respiratory disease associated with enterovirus D68 (EV‐D68) has been reported in hospitalized pediatric patients. Virologic and clinical characteristics of EV‐D68 infections exclusively in patients presenting to a hospital Emergency Department (ED) or urgent care have not been well defined.MethodsMid‐nasal swabs from pediatric patients with respiratory symptoms presenting to the ED or urgent care were evaluated using a commercial multiplex PCR platform. Specimens positive for rhinovirus/enterovirus (HRV/EV) were subsequently tested using real‐time reverse‐transcriptase PCR for EV‐D68. The PCR cycle threshold (CT) was used as a viral load proxy. Clinical outcomes were compared between patients with EV‐D68 and patients without EV‐D68 who tested positive for HRV/EV.ResultsFrom August to December 2014, 511 swabs from patients with HRV/EV were available. EV‐D68 was detected in 170 (33%) HRV/EV‐positive samples. In multivariable models adjusted for age and underlying asthma, patients with EV‐D68 were more likely to require hospitalization for respiratory reasons (odds ratio (OR): 3.11, CI: 1.85‐5.25), require respiratory support (OR: 1.69, CI: 1.09‐2.62), have confirmed/probable lower respiratory tract infection (LRTI; OR: 3.78, CI: 2.03‐7.04), and require continuous albuterol or steroids (OR: 3.91, CI: 2.22‐6.88 and OR: 4.73, CI: 2.65‐8.46, respectively). Higher EV‐D68 viral load was associated with need for respiratory support and LRTI in multivariate models.ConclusionsAmong pediatric patients presenting to the ED or urgent care, EV‐D68 causes more severe disease than non‐EV‐D68 HRV/EV independent of underlying asthma. High viral load was associated with worse clinical outcomes. Rapid and quantitative viral testing may help identify and risk stratify patients.

Multiplex Respiratory Virus Testing for Antimicrobial Stewardship: A Prospective Assessment of Antimicrobial Use and Clinical Outcomes Among Hospitalized Adults.

Respiratory tract infections are frequent causes of hospitalization and initiation of empirical antimicrobial therapy. Testing for a broad panel of respiratory viruses has been advocated as a useful tool for antibiotic stewardship. We conducted a prospective observational study to assess the impact of rapid viral test results on antimicrobial prescriptions and clinical outcomes among hospitalized adults. Eight hundred patients admitted with respiratory symptoms were tested by a 12-virus respiratory panel (RVP) during 3 consecutive winters in Montreal, Canada. The primary outcome measure was change in antimicrobial prescriptions (ie, de-escalation of empirical antimicrobial therapy or commencement of new antimicrobial therapy) after RVP results were available. Clinical outcomes were also assessed. Influenza virus was identified in 53% of individuals in the study population, and other viruses were identified in 10%. Influenza virus positivity was associated with shorter duration of hospitalization and appropriate antiviral management. Antibiotic management was most significantly correlated with radiographic suspicion of pneumonia and less so with results of the RVP. Positivity for viruses other than influenza virus was not correlated with significantly different outcomes. Physicians respond to results of testing for influenza virus when managing hospitalized adult patients but respond less to test results for other viruses. These data can inform the design of stewardship interventions and the selection of viral testing panels for hospitalized patients.

Analysis of False-Negative Human Immunodeficiency Virus Rapid Tests Performed on Oral Fluid in 3 International Clinical Research Studies.

The OraQuick Advance Rapid HIV-1/2 Test is a point-of-care test capable of detecting human immunodeficiency virus (HIV)-specific antibodies in blood and oral fluid. To understand test performance and factors contributing to false-negative results in longitudinal studies, we examined results of participants enrolled in the Botswana TDF/FTC Oral HIV Prophylaxis Trial, the Bangkok Tenofovir Study, and the Bangkok MSM Cohort Study, 3 separate clinical studies of high-risk, HIV-negative persons conducted in Botswana and Thailand. In a retrospective observational analysis, we compared oral fluid OraQuick (OFOQ) results among participants becoming HIV infected to results obtained retrospectively using enzyme immunoassay and nucleic acid amplification tests on stored specimens. We categorized negative OFOQ results as true-negative or false-negative relative to nucleic acid amplification test and/or enzyme immunoassay, and determined the delay in OFOQ conversion relative to the estimated time of infection. We used log-binomial regression and generalized estimating equations to examine the association between false-negative results and participant, clinical, and testing-site factors. Two-hundred thirty-three false-negative OFOQ results occurred in 80 of 287 seroconverting individuals. Estimated OFOQ conversion delay ranged from 14.5 to 547.5 (median, 98.5) days. Delayed OFOQ conversion was associated with clinical site and test operator (P < .05), preexposure prophylaxis (P = .01), low plasma viral load (P < .02), and time to kit expiration (P < .01). Participant age, sex, and HIV subtype were not associated with false-negative results. Long OFOQ conversion delay time was associated with antiretroviral exposure and low plasma viral load. Failure of OFOQ to detect HIV-1 infection was frequent and multifactorial in origin. In longitudinal trials, negative oral fluid results should be confirmed via testing of blood samples.

The association between substance use and sub-optimal HIV treatment engagement among HIV-infected female sex workers in Lilongwe, Malawi

ABSTRACTFemale sex workers (FSW) have a high prevalence of substance use and HIV, but the impact of substance use on HIV treatment engagement is not well established. We evaluated the association between alcohol and marijuana use and sub-optimal HIV treatment engagement outcomes among HIV-infected FSW in Lilongwe, Malawi. We enroled FSW using venue-based recruitment into a cross-sectional evaluation assessing substance use and HIV treatment engagement. Seropositive FSW, identified through HIV rapid testing, received rapid CD4 count and viral load testing. We used Poisson regression with robust variance estimates to ascertain associations of alcohol and marijuana use with sub-optimal HIV treatment outcomes: (1) lack of ART use among previously diagnosed, ART-eligible FSW and (2) viral nonsuppression among FSW on ART. Of previously diagnosed, ART-eligible FSW (n = 96), 29% were not using ART. Patterns of hazardous drinking were identified in 30%, harmful drinking in 10%, and alcohol dependence in 12%. ART-eligible FSW with harmful drinking or alcohol dependency were 1.9 (95% CI: 1.0, 3.8) times as likely to not use ART compared to FSW without harmful or dependent drinking. Among those on ART, 14% were virally nonsuppressed. The prevalence ratio for viral nonsuppression was 2.0 (95% CI: 0.6, 6.5) for harmful drinkers and alcohol-dependent FSW. Over 30% of ART-eligible FSW reported using marijuana. Marijuana-using FSW were 1.9 (95% CI: 0.8, 4.6) times as likely to not use ART compared to FSW who were not using marijuana. Given the high prevalence of alcohol use and its association with lack of ART use, ART uptake and alcohol reduction strategies should be tailored for alcohol-using FSW in Malawi.

Optimizing Virus Identification in Critically Ill Children Suspected of Having an Acute Severe Viral Infection.

Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection. Prospective cohort study. PICUs at 21 tertiary pediatric referral centers in the United States. During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection. We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients. Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups. Standardized specimen collection and sensitive diagnostic testing with a reverse transcription-polymerase chain reaction increased the identification of influenza in critically ill children. For most pathogenic viruses identified, results from nasopharyngeal flocked swabs agreed with those from nasopharyngeal or endotracheal aspirates.

‘Presenting CXR phenotype of H1N1’ flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks’

AimsTo review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). MethodsWe retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were ‘blinded’ to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. ResultsPatients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p=0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p=0.001). H1N1 radiographs were more likely to be ‘patchy’ versus ‘confluent’ changes of non-H1N1 CAP (p=0.03) and more often demonstrated peripheral distribution (p=0.01). H1N1 patients tended to stay in hospital longer (not significant; p=0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p=0.02). The findings were the same for the two evaluated seasons. ConclusionH1N1 patients demonstrated more extensive disease, which was more likely bilateral, ‘patchy’, and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients, particularly where rapid viral testing is not available.

Rapid viral diagnosis for acute febrile respiratory illness in children in the Emergency Department.

Pediatric acute respiratory infections (ARIs) represent a significant burden on pediatric Emergency Departments (EDs) and families. Most of these illnesses are due to viruses. However, investigations (radiography, blood, and urine testing) to rule out bacterial infections and antibiotics are often ordered because of diagnostic uncertainties. This results in prolonged ED visits and unnecessary antibiotic use. The risk of concurrent bacterial infection has been reported to be negligible in children over three months of age with a confirmed viral infection.Rapid viral testing in the ED may alleviate the need for precautionary testing and antibiotic use. To determine if the use of a rapid viral detection test for children with an acute respiratory infection (ARI) in Emergency Departments (EDs) changes patient management and resource use in the ED, compared to not using a rapid viral detection test. We hypothesized that rapid viral testing reduces antibiotic use in the ED as well as reduces the rate of ancillary testing and length of ED visits. We searched CENTRAL (2014, Issue 6), MEDLINE (1950 to July week 1, 2014), MEDLINE In-Process & Other Non-Indexed Citations (15 July 2014), EMBASE.com (1988 to July 2014), HealthStar (1966 to 2009), BIOSIS Previews (1969 to July 2014), CAB Abstracts (1973 to July 2014), CBCA Reference (1970 to 2007) and ProQuest Dissertations and Theses (1861 to 2009). Randomized controlled trials (RCTs) of rapid viral testing for children with ARIs in the ED. Two review authors used the inclusion criteria to select trials, evaluate their quality, and extract data. We obtained missing data from trial authors. We expressed differences in rate of investigations and antibiotic use as risk ratios (RRs), and expressed difference in ED length of visits as mean differences (MDs), with 95% confidence intervals (CIs). No new trials were identified in this 2014 update. We included four trials (three RCTs and one quazi-RCT), with 759 children in the rapid viral testing group and 829 in the control group. Three out of the four studies were comparable in terms of young age of participants, with one study increasing the age of inclusion up to five years of age. All studies included either fever or respiratory symptoms as inclusion criteria (two required both, one required fever or respiratory symptoms, and one required only fever). All studies were comparable in terms of exclusion criteria, intervention, and outcome data. In terms of risk of bias, one study failed to utilize a random sequence generator, one study did not comment on completeness of outcome data, and only one of four studies included allocation concealment as part of the study design. None of the studies definitively blinded participants.Rapid viral testing resulted in a trend toward decreased antibiotic use in the ED, but this was not statistically significant. We found lower rates of chest radiography (RR 0.77, 95% CI 0.65 to 0.91) in the rapid viral testing group, but no effect on length of ED visits, or blood or urine testing in the ED. No study made mention of any adverse effects related to viral testing. There is insufficient evidence to support routine rapid viral testing to reduce antibiotic use in pediatric EDs. Rapid viral testing may or may not reduce rates of antibiotic use, and other investigations (urine and blood testing); these studies do not provide enough power to resolve this question. However, rapid viral testing does reduce the rate of chest X-rays in the ED. An adequately powered trial with antibiotic use as an outcome is needed.