Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus

Swine flu (H1N1) virus will be making a comeback in just a few weeks.
Here is a recent update on Influenza Testing from the CDC.

IN SUMMARY

1. These results showed that, although the Rapid Influenza Diagnostic Tests ( RIDT) were capable of detecting novel A (H1N1) virus from respiratory specimens containing high levels of virus (as indicated by low cycle threshold [Ct] values), the overall sensitivity was low (40%--69%) among all specimens tested and declined substantially as virus levels decreased (and Ct values increased). These findings indicate that, although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus

2. Please place patients on isolation- Droplet and Contact Precautions with eye protection (surgical mask with eye shield, gown and gloves) when H1N1 is suspected with negative rapid test results.

Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus --- United States, 2009
The recent appearance and worldwide spread of novel influenza A (H1N1) virus (1,2) has highlighted the need to evaluate commercially available, widely used, rapid influenza diagnostic tests (RIDTs) for their ability to detect these viral antigens in respiratory clinical specimens. As an initial assessment, CDC conducted an evaluation of multiple RIDTs. Sixty-five clinical respiratory specimens collected during April--May 2009* that had previously tested positive either for novel influenza A (H1N1) or for seasonal influenza A (H1N1) or A (H3N2) viruses by real-time reverse transcription--polymerase chain reaction (rRT-PCR) assay were used in the evaluation. The results showed that, although the RIDTs were capable of detecting novel A (H1N1) virus from respiratory specimens containing high levels of virus (as indicated by low cycle threshold [Ct] values), the overall sensitivity was low (40%--69%) among all specimens tested and declined substantially as virus levels decreased (and Ct values increased). These findings indicate that, although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus. Patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness, and risk for complications. If a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed. Additional evaluations of the accuracy of RIDTs in detecting novel influenza A (H1N1) virus should be conducted.

Overall, for the 45 specimens that had tested positive for novel influenza A (H1N1) by rRT-PCR, the sensitivity of the three RIDT tests was 40% for BinaxNOW Influenza A&B, 49% for Directigen EZ Flu A+B,** and 69% for QuickVue Influenza A+B.

Sensitivity of the RIDTs was generally greater for seasonal influenza A (H1N1) and (H3N2) than for novel influenza A (H1N1), although the number of specimens tested was small, especially for seasonal influenza A (H1N1). None of the specimens had a Ct value <20. Compared with rRT-PCR, the three tests demonstrated sensitivity ranging from 60% to 80% for seasonal A (H1N1) and from 80% to 83% for seasonal A (H3N2)

Reported by: A Balish, et al. Influenza Div, National Center for Immunization and Respiratory Diseases, CDC.

Editorial Note:
The sensitivity of RIDTs to detect seasonal influenza viruses compared with virus isolation or rRT-PCR varies among commercial kits and has been shown to be low in some reports (3--5). In this evaluation, the sensitivity of three RIDTs to detect novel influenza A (H1N1) viral antigen in clinical specimens ranged from 40% to 69% and declined substantially with lower viral titers (as determined by Ct values). These findings are compatible with other recent studies, which reported that the sensitivity of some RIDTs to detect novel influenza A (H1N1) in clinical specimens ranged from 10% to 51% (6,7). Overall, the findings in this report demonstrate that these RIDTs are capable of detecting novel influenza A (H1N1) in respiratory specimens, but that many infections will be missed, especially in specimens with low viral titers.

RIDTs do not distinguish among influenza A virus subtypes, and RIDT sensitivity might vary by subtype of influenza A (4,6,8). Therefore, when using a positive RIDT result to help determine the appropriate course of clinical treatment or other action, the result should always be interpreted in the context of currently circulating strains. Conversely, as indicated by the results of this and other studies, a negative RIDT result should not be interpreted as indicating the absence of infection. In this analysis, the sensitivity of all three assays evaluated declined as the viral titer in the specimen decreased. The amount of virus found in respiratory specimens can be affected by timing of the specimen collection; viral titers are highest in the first 3 days of illness. Other factors that can affect the amount of virus in the specimen include age (e.g., children generally shed more virus and for longer periods than adults), type of specimen collected, and transportation and storage of the specimen before testing. Testing with rRT-PCR or virus isolation should be performed if a more definitive determination of the presence of influenza virus is required. In the titered cultured virus results presented in this report, all three RIDTs detected the cultured novel H1N1 influenza A/California/4/2009 virus with a lower limit of detection between 104.5 and 105.5 TCID50, slightly higher TCID50 levels than for detection of seasonal influenza viruses. These findings are consistent with the analytical sensitivities of RIDTs to detect novel influenza A (H1N1) virus described in one report (9), but higher than those described in another report (10).

The results described in this report should be viewed as preliminary. More data are needed on the clinical performance of all RIDTs to detect novel influenza A (H1N1) virus in different respiratory specimens. Because of the limitations of RIDTs and until additional data are available, all results from RIDTs, both positive and negative, when used for clinical decision-making in a patient with suspected novel influenza A (H1N1) virus infection, should be interpreted in the context of circulating influenza virus strains in the patient's community, level of clinical suspicion, severity of illness, and risk for complications. Additional CDC guidance on interpretation of RIDTs for testing of patients with suspected novel influenza A (H1N1) virus infection is available at http://www.cdc.gov/h1n1flu/guidance/rapid_testing.htm.

References
1. Dawood FS, Jain S, Finelli L, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360:2605--15.
2. CDC. Update: novel influenza A (H1N1) virus infections---worldwide May 6, 2009. MMWR 2009;58:453--8.
3. Uyeki TM. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatr Infect Dis J 2003;22:164--77.
4. Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 2007;39:132--5.
5. Uyeki TM, Prasad R, Vukotich C, et al. Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 2009;48:e89.
6. Faix DJ, Sherman SS, Waterman SH. Rapid-test sensitivity for novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; e-published ahead of print.
7. Ginocchio CC, Zhang F, Manji R, et al. Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol 2009;45:191--5.
8. Carrat F, Vergu E, Ferguson NM, et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol 2008;167:775--85.
9. Hurt AC, Baas C, Deng YM, Roberts S, Kelso A, Barr IG. Performance of influenza rapid point-of-care tests in the detection of swine lineage A (H1N1) influenza viruses. Influenza Other Respi Viruses 2009;3:171--6.
10. Chan KH, Lai ST, Poon LL, Guan Y, Yuen KY, Peiris JS. Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). J Clin Virol 2009;45:205--7.



Please remember, as with all our articles we provide information, not medical advice.
For any treatment of your own medical condition you must visit your local doctor, with or without our article[s]. These articles are not to be taken as individual medical advice.

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NEW MEDICAL CONFLICT OF INTEREST GUIDELINES

In 2007, nearly half of the $2.54 billion in income for CME providers accredited by the Accreditation Council for Continuing Medical Education (ACCME) was from commercial support (companies with a product in the marketplace); over the past decade, commercial support has quadrupled. The committee found that CME "has become far too reliant on industry funding" and that this funding "tends to promote a narrow focus on products," not "a broader education on alternative strategies for managing health conditions. It concluded "that the current system of funding is unacceptable and should not continue."

In March 2009, despite increasing pressures for reform the ACCME,announced that it would "not be taking any action to end the commercial support" of accredited CME and affirmed its systems and standards for keeping CME "free of commercial bias."

As if in response in late April 2009, the Institute of Medicine (IOM) issued a report on conflicts of interest that is notable for its breadth — it covers many aspects of medical research, education, and practice as well as both individual and institutional financial relationships.

The IOM defined a conflict of interest as "a set of circumstances that creates a risk that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest." Secondary interests "may include not only financial gain but also the desire for professional advancement, recognition for personal achievement, and favors to friends and family or to students and colleagues."

Overview of IOM Recommendations about Conflict of Interest in Medicine.
• Institutions engaged in medical research and education, clinical care, and the development of clinical practice guidelines should "adopt and implement conflict of interest policies" and "strengthen disclosure policies."
• Congress "should create a national program that requires pharmaceutical, medical device, and biotechnology companies and their foundations to publicly report payments to physicians and other prescribers, biomedical researchers, health care institutions, professional societies, patient advocacy and disease-specific groups, providers of continuing medical education, and foundations created by any of these entities." Until Congress acts, "companies should voluntarily adopt such reporting."
• Academic medical centers, research institutions, and medical researchers should "restrict participation of researchers with conflicts of interest in research with human participants." Exceptions "should be made public."
• Academic medical centers, teaching hospitals, faculty members, students, residents, and fellows should "reform relationships with industry in medical education"; these institutions and professional societies should "provide education on conflict of interest."
• The organizations that created the accrediting program for continuing medical education and other interested groups should reform the financing system so that it is "free of industry influence, enhances public trust in the integrity of the system, and provides high-quality education."
• Physicians, professional societies, hospitals, and other health care providers should reform physicians' financial relationships with industry; the same standards should apply to community physicians, medical school faculty, and trainees. Physicians should forgo all gifts and other "items of material value" from pharmaceutical, medical-device, and biotechnology companies, accepting only "payment at fair market value for a legitimate service" in specified situations. Physicians should "not make educational presentations or publish scientific articles that are controlled by industry or contain substantial portions written by someone who is not identified as an author or who is not properly acknowledged." Physicians should "not meet with pharmaceutical and medical device sales representatives except by documented appointment and at the physician's express invitation" and should "not accept drug samples except in certain situations for patients who lack financial access to medications." Until institutions change their policies, physicians and trainees "should voluntarily adopt" these recommendations "as standards for their own conduct."
• Medical companies and their foundations should reform interactions with physicians — for example, by instituting "policies and practices against providing physicians with gifts, meals, drug samples (except for use by patients who lack financial access to medications), or other similar items of material value and against asking physicians to be authors of ghostwritten materials." Consulting arrangements "should be for necessary services, documented in written contracts, and paid for at fair market value." Companies "should not involve physicians and patients in marketing projects that are presented as clinical research."
• Groups that develop clinical practice guidelines should restrict industry funding and conflicts of panel members. Various entities, including accrediting and certification bodies, formulary committees, health insurers, and public agencies should "create incentives for reducing conflicts in clinical practice guideline development."
• The governing bodies of institutions engaged in medical research, medical education, patient care, or guideline development "should establish their own standing committees on institutional conflicts of interest" that "have no members who themselves have conflicts of interest relevant to the activities of the institution."
• The National Institutes of Health should revise federal regulations to require research institutions to have policies on institutional conflicts of interest, including "the reporting of identified institutional conflicts of interest and the steps that have been taken to eliminate or manage such conflicts."
• Oversight bodies and other groups should "provide additional incentives for institutions to adopt and implement" conflict-of-interest policies, such as by publicizing the names of institutions that have instituted the recommended policies and those that have not.
• The Department of Health and Human Services and its agencies should develop and fund research agendas on conflict of interest.

Adapted from Steinbrook R. NEJM 360;21:2160

COMMENT:
On Clinical practice guidelines.
Perhaps the most dangerous of these comments are that with regard to clinical practice guidelines the IOM found that "the risk of undue industry influence . . . is significant."

Specific recommendations were made for strengthening conflict-of-interest policies.

These include a general exclusion of panel members with conflicts of interest, a prohibition on direct funding for guideline development from industry or industry-controlled foundations, and complete disclosure of any remaining financial associations or industry funding.

In exceptional circumstances "in which avoidance of panel members with conflicts of interest is impossible because of the critical need for their expertise," groups should take measures such as publicly documenting that they had made good-faith efforts to find experts without conflicts, for example, by advertising for members, appointing a chair without a conflict of interest, limiting members with conflicts to "a distinct minority," excluding participants with conflicts from "deliberating, drafting, or voting on specific recommendations," and publicly disclosing the "relevant conflicts of interest of panel members."

Please remember, as with all our articles we provide information, not medical advice.

For any treatment of your own medical condition you must visit your local doctor, with or without our article[s]. These articles are not to be taken as individual medical advice.

Swine Flu Public Health Emergency –What To Look For; What To Do.

A public health emergency was declared today in the U.S. as 20 cases of the disease were confirmed in this country. The Centers for Disease Control, in a news conference in Washington stated, “We expect to see more cases of swine flu. Homeland Security Secretary Janet Napolitano, speaking at the same news conference called the emergency declaration a “declaration of emergency preparedness.” However, experts at the WHO will wait until Tuesday before meeting to decide if it should increase its rating of the seriousness of the pandemic potential from the current level three to level four - which would indicate a "significant increase in risk of a pandemic.” Officials said they had confirmed eight cases in New York, seven in California, two in Kansas, two in Texas and one in Ohio, and that the cases looked to be similar to the deadly strain of swine flu that has killed more than 80 people in Mexico and infected 1,300 more. This was amid further reports of potential new cases from New Zealand to Hong Kong to Spain, raising concerns about the potential for a global pandemic. Canada also confirmed six cases of the flu. Swine flu was also likely in 10 New Zealand students.

WHAT TO LOOK FOR:
The symptoms of swine flu are nearly identical to the symptoms of other influenza, including high fever, aches, coughing, and congestion. It appears to spread through human-to-human contact and human contact with live pigs but not by eating pork products.

WHAT TO DO if pandemic is declared by WHO
-Interim Guidance for Swine influenza A (H1N1)
• Wash hands frequently

• stay home

• don't board airplanes, if you feel sick

• Keep sick children out of school.

• Use Facemasks

• Avoid close contact (less than about 6 feet away) with the sick person as much as possible.

• If you must have close contact with the sick person (for example, hold a sick infant), spend the least amount of time possible in close contact and try to wear a facemask (for example, surgical mask)

• An N95 respirator that fits snugly on your face can filter out small particles that can be inhaled around the edges of a facemask, but compared with a facemask it is harder to breathe through an N95 mask for long periods.

• Wear an N95 respirator if you help a sick person with respiratory treatments using a nebulizer or inhaler, as directed by their doctor.

• Respiratory treatments should be performed in a separate room away from common areas of the house when at all possible.

• Used facemasks and N95 respirators should be taken off and placed immediately in the regular trash so they do not touch anything else.

• Avoid re-using disposable facemasks and N95 respirators if possible.

• If a reusable fabric facemask is used, it should be laundered with normal laundry detergent and tumble-dried in a hot dryer.

• After you take off a facemask or N95 respirator, clean your hands with soap and water or an alcohol-based hand sanitizer.

• Ask your doctor whether you are a candidate for Tamiflu or Relenza.

• Do not take any drugs or medications prophylactic ally without your doctor’s permission.