February 22, 2010 — The rapid influenza diagnostic test (RIDT) for swine-origin 2009 A (H1N1) influenza virus (S-OIV) in children may be most useful in young children who present early after symptom onset, according to the results of a large pediatric cohort study reported online February 15 in Pediatrics.
“Data on the test performance of the RIDT for S-OIV have been limited,” write Michael Hawkes, MD, from the University of Toronto in Ontario, Canada, and colleagues. “The few available reports in mixed adult-pediatric populations have shown variable sensitivity between 11% and 69%…. The rapidly evolving pandemic of novel 2009 [S-OIV] demands that accurate and practical diagnostics be urgently evaluated for their potential clinical utility.”
The goal of this study was to assess the diagnostic accuracy of RIDT and direct fluorescent antibody (DFA) assay for S-OIV, using reverse-transcription polymerase chain reaction (RT-PCR) as the reference standard. Between May 22 and July 25, 2009, the investigators prospectively recruited 820 children from birth to age 17 years who were evaluated for influenza-like illness in the emergency department of a pediatric referral hospital (n = 651) and a community pediatric clinic (n = 169).
To examine the sensitivity and specificity for S-OIV of RIDT (performed on-site) and of DFA, these tests were compared with the sensitivity and specificity of RT-PCR. In addition, the sensitivity of RIDT for S-OIV was compared with sensitivity for seasonal influenza during 2 preceding seasons.
For RIDT, sensitivity for S-OIV was 62% (95% confidence interval [CI], 52% – 70%), and specificity was 99% (95% CI, 92% – 100%). Sensitivity of DFA was 83% (95% CI, 75% – 89%), which was significantly higher than that of RIDT (P < .001). When using DFA supplemented with culture as the reference standard, RIDT sensitivity for S-OIV was similar to that for seasonal influenza. Sensitivity of RIDT for influenza viruses was significantly higher in children not older than 5 years of age (P =.003) and in those evaluated not longer than 2 days after onset of symptoms (P < .001).
“The sensitivity of RIDT for detection of S-OIV is higher than recently reported in mixed adult-pediatric populations but remains suboptimal,” the study authors write. “Nonetheless, RIDTs may have a role in clinical practice for diagnosis of S-OIV in young children who present early after symptom onset, for whom the test sensitivity is superior.”
Limitations of this study include lack of generalizability to children with preexisting medical comorbidities and possible variation in test collection methods.
“Our findings support a recent Centers for Disease Control and Prevention interim guidance statement that, when influenza viruses are circulating in a community, a positive RIDT result indicates that influenza infection is likely present; however, a negative test result does not rule out infection,” the study authors conclude. “In the face of a negative test result, a diagnosis of influenza should still be considered, empiric therapy and appropriate infection-control measures should be instituted if indicated, and confirmatory testing should be sought if necessary. Future studies are warranted to examine the clinical utility and cost-effectiveness of RIDTs in the context of the current S-OIV pandemic.”
The Canadian Institutes of Health Research/SickKids Foundation, the Canadian Institutes of Health Research, and the University of Toronto supported this study. The study authors have disclosed no relevant financial relationships.
Pediatrics. Published online February 15, 2010.
Clinical Context
RT-PCR is the diagnostic test of choice for the detection of S-OIV, but it is limited by the longer turnaround for results, and commercially available RIDTs have been developed for the diagnosis of influenza A and B and S-OIV.
This is a study of the diagnostic accuracy of the RIDT and DFA tests compared with the gold standard of the RT-PCR, conducted during 2 consecutive influenza seasons in children with influenza-like illnesses.
Study Highlights
- The sample consisted of patients aged 0 to 17 years who were prospectively enrolled during 2 influenza seasons (2007 – 2008 and 2008 – 2009) in the Toronto, Ontario, Canada, community.
- Children were recruited from a pediatric hospital and a community general pediatrics practice.
- Inclusion criteria included 2 or more symptoms of influenza-like illnesses (fever for 1 or more weeks, myalgia, cough, headache, and fatigue) and age 17 years and younger.
- Excluded were children with underlying conditions predisposing to serious influenza.
- Specimens were collected using flocked nasopharyngeal swabs at the point of care.
- Testing was performed within 1 hour, using standardized procedures.
- During the 2007 to 2008 season, RIDT, DFA, viral isolation, and RT-PCR tests were routinely performed on all suspected influenza cases.
- In the 2008 to 2009 season, viral culture was performed only on DFA-negative specimens.
- Sensitivity and specificity were calculated using standard formulae.
- A total of 820 children with influenza-like illnesses were tested for respiratory viruses during the 2 seasons (n = 194 for 2007 – 2008).
- There were 651 samples from the pediatric hospital and 169 from the clinic.
- Median age was 3.4 years.
- 9.7% were younger than 1 year, 37% were aged 1 to 5 years, and 53% were older than 5 years.
- 63% of specimens tested were positive.
- 13% tested positive by RT-PCR (S-OIV); seasonal influenza A was detected in 13%, and influenza B in 9.4%.
- Test performance of the RIDT was compared with DFA and DFA with viral culture.
- The sensitivity of RIDT for detecting S-OIV was 72% when compared with DFA alone and 69% compared with DFA with viral culture. Sensitivity of DFA was 83% and superior to that of RIDT.
- Specificity of RIDT for S-OIV was 99%.
- Thus, a positive result for RIDT indicated that influenza infection was likely, but a negative result did not rule out influenza infection.
- RIDT performed better (more sensitive) in children younger than 5 years for all 3 influenza strains.
- RIDT was more sensitive in those tested within 2 days of symptom onset.
- The independent predictive value of RIDT for the 3 strains was 2.8 in those participants who were 5 years or younger vs those 5 years or older (P = .003), and the adjusted odds for symptom duration 2 days or less vs longer than 2 days was 2.9 (P = .024).
- The sensitivity did not vary by site (hospital vs outpatient).
- The authors concluded that although RIDT performed reasonably in children younger than 5 years, it was still suboptimal compared with DFA and RT-PCR.
Clinical Implications
- DFA is superior to RIDT for sensitivity to detect S-OIV in children.
- RIDT has a higher sensitivity in children younger than 5 years with symptom duration of 2 or fewer days.
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