Information for Healthcare Providers

Clinicians

Influenza is characterized by the abrupt onset of fever, myalgia, headaches, malaise, non-productive cough, sore throat and rhinitis. Children may experience gastrointestinal symptoms
including nausea and vomiting, as well as otitis media.

Clinical manifestation of influenza may resemble that of other respiratory viruses including enterovirus, adenovirus, parainfluenza virus, respiratory syncitial virus, and echovirus. Laboratory analysis and careful diagnostic evaluation can distinguish influenza from other
respiratory illnesses including the common cold.

Amongst special populations, including the elderly, the very young, severely immunocompromised patients, and those with chronic heart, lung or other metabolic disease, influenza infection may develop secondary complications including pneumonia, febrile seizures, myositis, myocarditis, and pericarditisis. Infants administered with Aspirin while infected with influenza may develop Reye’s syndrome.

Transmissibility

Influenza is transmitted via respiratory droplets of infected persons. The incubation period prior to onset of illness is typically 2 days. Patients are infectious at least a day prior to onset of symptoms, and continue to be infectious for several days. In general, the weaker the immune response to the virus, the longer the patient remains infectious. Therefore, severely immunocompromised patients shed virus for the longest duration lasting up to several months, whereas healthy vaccinated adults mount a strong immune response to the virus and remain infectious for short periods of time following onset (approximately 5 days).

Laboratory Diagnosis

Several laboratory tests are available for influenza testing, each of which has advantages and limitations.

Rapid Influenza Antigen Tests

Rapid influenza tests use antibody to detect the presence of influenza A and/or influenza B antigen in a visually read
format, usually within about 30 minutes. Commercial laboratories in Hawaii generally provide this rapid testing to clinicians.
There are many products that have varying performance characteristics, so providers are advised to consult with their
supporting laboratory. The main advantage of rapid testing is the short turnaround time, which is quite valuable in
remote areas or urgent medical circumstances; however, false positives occur and low test sensitivity means about half
of true infections are missed if this is the only test used.

Real-Time Reverse Transcriptase Polymerase Chain Reaction (rti RT-PCR)

Real-time RT-PCR detects specific influenza genomic RNA, and is a very high quality testing approach with a reasonable
turn-around-time. Testing is available commercially in Hawaii, and depending on the laboratory and test volume, results
are often available same or next day. In addition to distinguishing between influenza A and B, rti RT-PCR testing can
also identify some common hemagglutinin (H) subtypes such as H1 and H3. Some PCR panels are designed to detect multiple
respiratory viruses in the specimen, so consult with your supporting laboratory for options. Real-time RT-PCR is the best
overall testing strategy commonly available to Hawaii’s healthcare providers.

Viral Culture
Viral culture involves growing viruses in cell culture. This testing is available at the Hawaii Department of Health
State Laboratories Division and at some other laboratories on a limited scale. This is the “gold standard” for virus
detection and characterization, and is critical for epidemiological and vaccine development efforts at the state, national
and global levels. This technique is limited in clinical laboratories because it is very labor and supply intensive, and
viruses may take several days to weeks before the grow. Tests conducted on viral isolates can distinguish between further
between various subtypes of influenza The State Laboratories Division sends influenza isolates to CDC for strain-typing
twice a month year round.

Genomic Sequence Analysis

Genomic sequencing is used by the State Laboratories Division and CDC to detect known mutations associated with resistance
to antiviral drugs. This is useful in monitoring the emergence of resistance and explaining treatment failures. Clinicians
should report potential treatment failures to the Disease Investigation Branch, who can coordinate with SLD for this testing.

Submitting Specimens for Influenza Testing

Physicians interested in testing specimens for influenza must contact the diagnostic laboratory they usually work with for
collection kits. You will be provided with collection materials, a laboratory order form, and a state form that requests
demographic and epidemiological information on the client. Please complete both forms, as specimens will be selected for
more detailed testing by SLD based on the epidemiological information provided.

Treatment

Although a flu shot is the best way to prevent the flu, antiviral drugs are other tools that can be used to help prevent and treat influenza. The four available drugs are amantadine, rimantadine, zanamivir and oseltamivir

Comparison of Antiviral Drugs for Influenza

Drug

Trade Name

Influenza Virus Type

Approved Use

Treatment Age

Prevention Age

amantadine

Symmetrel®

A

Treatment and Prevention

>1 year

>1 year

rimantadine

Flumadine®

A

Treatment and Prevention

Adults

>1 year

zanamivir

Relenza®

A and B

Treatment

>7 years

n/a

oseltamivir

Tamiflu®

A and B

Treatment and Prevention

>1 year

>13 years

These drugs can be divided into two groups based upon how they work. Amantadine and rimantadine can be used to treat and prevent influenza A infections. These drugs do not work against influenza B viruses. The CDC released a Health Alert Notice on January 14, 2006 recommending that neither amantadine nor rimantadine be used for treatment or prophylaxis of influenza A.

The second group of drugs includes zanamivir and oseltamivir, which can be used to treat influenza A and B infections. Oseltamivir can also be used as prophylactically to protect the patient from developing influenza A or B. Studies show that treatment with any of these drugs can shorten the time a person infected with influenza feels ill by approximately 1 day, if treatment is started during the first 2 days of illness. Because of growing antiviral resistance, antivirals should be used prudently. For current recommendations on the use of antivirals, please click here.

Side Effects

Amantadine and Rimantadine
Among some healthy adults and children, central nervous system (CNS) side effects such as anxiety, difficulty concentrating, lightheadedness, and gastrointestinal side effects like nausea and loss of appetite may occur. CNS side effects are more frequent amongst those taking amantadine than among persons taking rimantadine. In persons with long-term illnesses, more serious side effects, such as delirium, hallucinations, agitation and seizures, can occur. Side effects are generally not long-lasting.

Zanamivir
This drug is inhaled and can cause side effects, especially in those with asthma or other chronic lung disease. Decreased respiratory function and bronchospasm have been reported with use of zanamivir. Zanamivir is generally not recommended for use in persons with underlying lung disease such as asthma and chronic obstructive pulmonary disease. Other side effects reported by less than 5% of those who have used this drug are diarrhea, nausea, sinusitis, nasal infections, bronchitis, cough, headache, and dizziness.

Oseltamivir
Gastrointestinal side effects occur most commonly. Nausea and vomiting may be less severe if oseltamivir is taken with food.

Sentinel (ILINet) Providers

Healthcare providers interested in voluntarily providing influenza-like illness (ILI) data from their practices may be
enrolled in a CDC program called ILINet. ILINet providers may be physicians (MD or DO), or advanced practice nurses,
who work in primary care settings, and can commit to reporting weekly numbers of patients seen for influenza-like illness
in their practice. Sufficient flexibility is built into the reporting program to extract data manually, use ICD codes for
data extraction, or use other equally robust methods to extract case counts of persons presenting with ILI by age group.
Providers must also be able to extract baseline counts of total patients seen. For additional details, or to sign-up,
please click here.

Because ILINet providers use consistent criteria to define ILI, specimens collected in their practices are very useful for
surveillance purposes. Therefore, all specimens collected by ILINet providers receive confirmatory testing for influenza,
and may be forwarded to DOH for further testing at no cost to the provider. Results for specimens tested at DOH will be
made available to the provider through the network laboratory to which the specimen was submitted. Please refer to the
“Submitting Specimens for Influenza Testing” section above for more information on how to collect and submit specimens for
testing. Your ILINet provider ID MUST be placed on the form in the appropriate field. ILINet providers may be able to
submit requisitions directly to DOH online, using our web portal; when specimens are submitted online, all results from
DOH can be retrieved directly using the same system. Please visit our online portal
for more details, and to sign-up.

Medical Advisories

2009-10-19
Medical Advisory: Update on 2009 Influenza A(H1N1) Pandemic and Hawaiʻi Response

2009-09-28
Medical Advisory: Update on 2009 Influenza A(H1N1) Pandemic and Hawaiʻi Response

2009-09-03
Update on 2009 Novel Influenza A(H1N1) Vaccination and Extending Deadline to Pre-register as a Pandemic Vaccination Provider

2009-08-14
Medical Advisory: Distribution Plans for Anticipated Novel Influenza A (H1N1) Vaccine

2009-08-13
Medical Advisory: Clarification of Isolation Recommendations for Influenza-like Illness

2009-08-03
Medical Advisory: Focused Influenza Testing and Update to Isolation Recommendation

2009-07-23
Medical Advisory: Management of Patients with Influenza-like Illness

2009-06-29
Medical Advisory: Focused Novel H1N1 Case Investigations and Community Mitigation