Shopping Cart

Influenza (flu) is on the nation's radar currently as we experience an influenza season that has produced more cases and influenza-related hospitalizations than recent years. This highly contagious respiratory illness is now considered epidemic. In fact, during the week ending January 27, 2018, the National Center for Health Statistics indicates that 9.8% of deaths were due to either pneumonia or influenza.¹ Additionally, Americans are currently hospitalized for influenza at a rate of 67.9 cases per 100,000 population.¹ These facts underscore that influenza is epidemic, and have pharmacists scurrying to find information and tools that can assist them with the influx of influenza-infected patients.

HISTORY

Influenza has been an ongoing seasonal concern for hundreds of years. It periodically occurs as a pandemic (a global epidemic). Most healthcare providers are aware of the most lethal influenza pandemic, which occurred between June 1918 and December 1920, a period that coincides with the end of World War I. Modest estimates indicate that 50 million people or more died from the Spanish flu, so- called because Spain, a neutral country during World War I, did not censor the news and reported openly about widespread influenza.² Allied and central power nations did not, believing that public discussion of an influenza pandemic would quash morale. People in nations that had media block outs obtained most of their information from Spanish news media outlets, and dubbed this flu "Spanish flu." (The Spaniards, however, called it "French Flu.")^2-4

Researchers did not isolate actual viral particles until the 1930s, with influenza A virus isolated from ferrets in 1933, and influenza B virus in 1936. This led to the discovery that culturing the virus in fertilized hens' eggs diminished its virulence, and eventually the development of inactivated vaccines in the 1950s.⁵

Vaccination became and continues to be the most effective way to limit spread of influenza, but has not eliminated periodic pandemics.⁵ Since the influenza vaccination's introduction, several global epidemics have occurred. These include a 1957 Asian flu pandemic that killed approximately 1.5 million people, a 1968 pandemic of Hong Kong flu that killed 1 million, and a 2009 pandemic of swine flu resulting in approximately 575,000 deaths. In the 2009 epidemic, a new influenza A (H1N1) virus emerged that was very different from previous circulating human influenza A (H1N1) viruses. The new virus has now replaced earlier H1N1 subtype that infected humans. (CDC, 2017a) (CDC, 2016b)(WHO, 2017).⁵

In the current epidemic, activity began to increase in early November 2017 and remains elevated at this time (February 2018). Patients most often have influenza A(H3N2) viruses, but A(H1N1)pdm09 and B viruses are also circulating. All indicators suggest flu activity will be as high as or higher than the 2014- 2015 season, which public health officials determined to be a high severity A(H3N2)-predominant season.⁶

INFLUENZA VIRUSES

Pharmacists field many questions from patients and hear many comments. This year, many patients wonder why the flu shot doesn't appear to be is as effective as it could be, and why they need annual influenza immunizations. Pharmacists and pharmacy technicians need a basic understanding of influenza viruses to address these concerns appropriately.

Influenza viruses are RNA viruses belonging the Orthomyxoviridae family. Influenza viruses come in four types – A, B, C, and D – with human influenza viruses A and B responsible for seasonal influenza epidemics that occur almost every winter (although flu infection is possible year-round). In general, influenza A virus are usually responsible for influenza pandemics.⁵

Type A viruses are the most virulent, producing the most severe symptoms. They infect humans and many different animals (e.g. cats, chickens, ducks, horses, pigs, seals, whales). Influenza A's 2 surface glycoprotein antigens, hemagglutinin (H) and neuraminidase (N), explain its virulence. The H antigen allows the virus to enter cells, and the N antigen facilitates cell-to-cell transmission. Various influenza A viruses have different hemagglutinin and neuraminidase subtypes, with hemagglutinin occurring as types H1 through H18 and neuraminidase occurring as types N1 through N11. The circulating virus's nomenclature incorporates these designators, and currently influenza A (H1N1) and influenza A (H3N2) viruses are problematic.^5,7

Type B viruses, which are unique to humans, tend to cause milder influenza than type A, and primarily infect children. They are more stable than influenza A, and are differentiated not by subtypes, but by lineages and strains. Currently, the circulating influenza B viruses belong to one of two lineages: B/Yamagata or B/Victoria.⁵

Although Type C viruses infect humans and pigs, they are relatively uncommon and most cases are mild and asymptomatic. Type D influenza viruses affect cattle primarily, not humans.⁵

Antigen Drift and Shift

Influenza viruses change constantly using 2 mechanisms: antigenic drift and antigenic shift (see Table 1). Antigenic drift is expected; health policy makers anticipate antigenic drift and plan for it.^5,8 Antigenic shift is a much more serious development, and leads to new and potentially more virulent viruses. An example of antigenic shift might be when an avian virus and a human virus simultaneously infect a cell in another species, for example a pig. This creates the potential for their genetic materials to be mixed creating a new and hybrid-type virus with increased virulence in humans.⁸

Table 1. Antigenic Shift and Antigenic Drift
Antigenic drift	Antigenic shift
A predictable slow accumulation of multiple small mutations in hemagglutinin (H) and neuraminidase (N) genes Occurs in all types of influenza May lead to a loss of immunity or vaccine mismatch Precipitates the need for annual vaccination with predicted circulating strains Rarely associated with pandemic	An unexpected event in which at least two different viral strains or viruses from different species combine to form a new subtype Occurs only in influenza A viruses Precipitates a need for a new vaccine entirely Often associated with epidemic or pandemic
Source: Reference 5,8

Seasonal Vaccine

Due to the mercerial nature of the virus a need is created to predict which strains will circulate in the next flu season. This need is filled by the World Health Organization (WHO), which monitors viral changes globally. Each year, the WHO Global Influenza Surveillance and Response System chooses 3 strains for inclusion in the next year's flu vaccination. They select the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Starting with the 2012–2013 Northern Hemisphere influenza season, WHO has also recommended a second B-strain for use in quadrivalent vaccines.⁹

CDC recommends annual vaccination against seasonal influenza for everyone starting at 6 months of age.¹⁰ Despite early speculation that the current flu vaccine had low effectiveness, CDC released updated data on February 16, 2018. It indicates that between November 2, 2017 and February 3, 2018, the overall adjusted vaccine effectiveness against influenza A and influenza B virus infection was 36%. Influenza A(H3N2) viruses caused 69% of influenza infections, and the vaccine's effectiveness was approximately 25%. Its effectiveness was 67% and 42% against influenza A (H1N1)pdm09 and influenza B viruses, respectively.¹¹

This stands repeating: The best way to protect oneself from the flu is to receive an annual flu shot.^10,11

TRANSMISSION

Viral disease results from specific interactions between the virus, susceptible host, and environment, a process called the chain of infection.⁸ Influenza viruses spread by droplet infection (exhalation, coughing, sneezing, etc).^5,8

If virus-containing droplets reach others' mucous membranes, recipients may develop the flu. Virus- containing droplets may also land on an intermediate surface where they can survive for 24 hours.^5,12 If individuals inhale the virus or touch a contaminated surface and self-inoculate themselves by touching their noses, eyes, or mouths, they may develop symptoms 1 to 4 days later. Sick adults are contagious beginning 1 day before symptoms appear, peaking on the first day of clinical illness, and for 5 to 7 days after symptoms develop. Children and immunocompromised individuals can be contagious for longer. Patients are most contagious within 3 days of illness onset.¹²

Taking action to break any link in the chain of infection—that is taking preventive measures—can stop the spread of influenza (see Resources).^5,12

Resources: Influenza Prevention Based on Chain Of Infection
Link in Chain of Infection	Influenza Implications	Notes for pharmacy staff
Infectious agent	Present in environment during flu season	□ Be aware of current strains and case reporting requirements □ Watch the CDC website https://www.cdc.gov/flu/index.htm
Reservoir	Potentially everyone, some higher risk	□ Promote annual vaccination in everyone age 6 months or older
Portal of exit	Droplets	Tell patients to… □  Limit contact with people who appear to be sick □  Isolate themselves if they have the flu and stay home for at least 24 hours or until the fever resolves □  Wash sheets, pillow cases and blankets weekly and hot water and separate each household members personal items (e.g. toothbrushes, razors) □ Remind all household members to use disposable tissues, cover their mouths when sneezing or blowing their noses, and wash their hands immediately afterward. □ Ensure infected family members have trash cans nearby to dispose of tissues and wipes; educate each household member to avoid placing soiled tissues on the ground or nearby surfaces □ Remind people to keep their hands away from the face and mouth.
Transmission	Organism can remain active on environmental surfaces	□ Remind patients to disinfect objects and surfaces such as telephones, computer keyboards, light switches, door knobs, remotes, and children's toys □ The Environmental Protection Agency only allows manufacturers to use words like "sanitize" or "disinfect" on products that have proven ability to kill germs; look for these products. The most commonly used products are Pine Sol, Clorox, and Lysol Lemon juice, lavender, and tea tree oil or natural products that have disinfectant properties A mixture of 1/4 cup chlorine bleach to 1 gallon hot water will also disinfect □  Consider using washing machine or the dishwasher to clean communal items; many items can be washed in these appliances, and using hot settings and soap can disinfect
Portal of entry	Nose/mouth	□ Advise frequent handwashing (BEST PREVENTIVE METHOD) with soap and water, especially before eating and after using the bathroom. □ If soap is unavailable, alcohol-based hand rubs with at least 60% alcohol are recommended □ Evidence that facemasks prevent influenza transmission is lacking but CDC recommends facemasks when Healthcare personnel enter a room belonging to a patient with suspected or confirmed influenza Patients with suspected influenza leave their rooms, must leave home, or enter a healthcare facility
Vulnerable hosts	Everyone; some people at greater risk	Promote annual influenza immunization, especially among high-risk groups Children younger than five, especially those younger than 2 Adults 65 years of age and older Pregnant women and women up to 2 weeks postpartum Residents of nursing homes and other long-term care facilities Native Americans and Alaska Natives
Sources: 10, 12-14

Numerous populations are at high risk for influenza and should be vaccinated annually. In addition to causing its own symptoms (which can be severe), influenza can worsen chronic health problems. People who have certain medical conditions are more vulnerable to serious influenza-related complications. In particular, pharmacists should advocate for patients who have asthma and chronic lung diseases, heart disease, diabetes, immunosuppression due to underlying conditions or drug therapy, organ impairment, or any condition in children requiring aspirin to be vaccinated.^5,12

RECOGNIZING INFLUENZA

Influenza's signs and symptoms can vary by age, immune status, and presence of underlying medical conditions. Uncomplicated influenza can cause mild to severe illness and may include any or all of these signs and symptoms^5,8:

• Fever (usually high, however, not everyone with the flu has a fever, especially elderly persons)
• Dry cough
• Sore throat
• Runny or stuffy nose
• Muscle or body aches
• Headache
• Fatigue, malaise or weakness
• Conjunctivitis, rhinitis, and gastrointestinal symptoms (more common in infants and young children than adults)

Once influenza virus infects the respiratory tract, it stimulates a host immune response. Some people can experience an exaggerated inflammatory responses; these patients may develop pro-inflammatory effects, cytokine dysregulation (cytokine storm) that causes tissue inflammation and damage, or pulmonary and extra-pulmonary injury. (Note that healthy young adults may be especially susceptible to cytokine storm pursuant to some virus variants because of their strong immune systems. This was the case in the 1918 influenza pandemic.^2,3) In addition, bacterial co-infection can progress every quickly and often leads to pneumonia and severe disease including septicemia and meningitis. Patients with severe symptoms may need emergency care.⁸

Diagnosis

Clinicians diagnose most influenza cases based on presenting symptoms, and most individuals with flu symptoms do not require special testing, especially if influenza is well documented in the community, because test results usually will not change treatment. Clinicians should only consider testing if patients are hospitalized or have high risk conditions, or the test results would have implications for other patients.^12,15

Several tests are available that require a mucus specimen collected from the back of the patient's throat or nose. Rapid influenza diagnostic tests (RIDT) for antigen detection yield positive/negative results in 15 minutes or fewer, but are less likely to detect type B influenza. False-negative results are more likely during periods of high influenza activity; and false positive results occur more often during periods of low influenza activity.^12,15 Clinicians can also order viral tissue cell cultures, which take up to 10 days for results; rapid cell cultures, which take 1 to 3 days; or reverse transcription-polymerase chain reaction assays in hospitalized patients if an upper respiratory tract specimen is negative and if positive testing would change clinical management. Immunofluorescence yields results in one to four hours, and rapid molecular essay takes about 20 minutes.^12,16

TREATMENT

Influenza is a self-limiting infection that lasts approximately 1 week and occasionally 2. Standard of care for influenza infection begins with rest, comfort, sleep, and extra fluids. Clinicians should advise patients to take analgesics and antipyretic medications (unless a contraindication exists) such as ibuprofen, naproxen, or acetaminophen for muscle or body aches and fever. They should also advise patients to stay home for at least 24 hours, possibly more. A critical point to remember is that youths younger than 18 years of age should not be given salicylate containing medication (aspirin) because it has been linked to Reye's syndrome. Reye's syndrome is rare but potentially fatal.¹⁷

Antiviral Medications

Antiviral medications can be used to treat influenza, and they are 70% to 90% effective in preventing influenza following exposure in specific populations.¹⁸ Patients treated appropriately with antiviral medications may experience a shorter illness duration, fewer complications from influenza, and earlier discharge if hospitalized. CDC does not recommend widespread, routine use of antiviral medications for chemoprophylaxis; they make this recommendation to limit the possibility of antiviral-resistant viruses.¹⁷

CDC recommends initiating antivirals ideally within 48 hours of illness onset as early as possible in patients who have confirmed or suspected influenza and¹⁹:

• are hospitalized
• have severe, complicated, or progressive illness
• are at higher risk for influenza complications, including:
  • Children younger than 2 years of age
  • Adults 65 years and older
  • Women who are pregnant or postpartum within 2 weeks of delivery
  • Children and adolescents younger than 19 years who take long-term aspirin therapy
  • People with certain chronic medical conditions, including chronic pulmonary, cardiovascular, renal, hepatic, hematological, and metabolic disorders, or neurologic and neurodevelopment conditions
  • Immunosuppressed individuals
  • Native Americans/Alaska Natives
  • Individuals with body mass index above 40
  • Residents of nursing homes and other chronic care facilities

RECOMMENDED ANTIVIRAL DRUGS

The U. S. Food and Drug Administration has approved 3 antiviral neuraminidase inhibitors for influenza (see Table 2). Each of these products is labeled with the warning that they are not a substitute for annual influenza vaccination.

Table 2. Antiviral Neuraminidase Inhibitors for Influenza
Neuraminidase Inhibitor	Indication	Side Effects	Key points
Oral oseltamivir (Tamiflu capsule or suspension)	□ Flu prevention following exposure in people 3 months of age and older □ Flu treatment in people of any age Adults and adolescents 13 years of age and older: one 75 mg capsule or 12.5 mL of oral suspension twice daily for 5 days. Infants 2 week through 1 year of age: 3 mg/kg twice daily Pediatric patients aged 1 to 12 years is weight-based: <15 kg = 30 mg BID 15.1 to 23 kg = 45 mg BID 23.1 to 40 kg = 60 mg BID > 40.1 kg = 75 mg BID	Common: Nausea, vomiting, pain, fever, chills, arthralgia Other: Bronchospasm, skin/hypersensitivity reactions, neuropsychiatric events (self injury, delirium)	□ Monitor closely for signs of unusual behavior □ Avoid administration of live attenuated influenza vaccine within 2 weeks before or 48 hours after oseltamivir use, unless medically indicated □ Inform patients with hereditary fructose intolerance that one dose of 75 mg oseltamivir oral suspension delivers 2 grams of sorbitol and may cause dyspepsia and diarrhea
Inhaled zanamivir (Relenza) 10 mg inhaled q12hr for 5 days; may consider longer treatment for patients severely ill after 5 days	□ Flu prevention in people 5 years of age and older Household outbreak: initiate 10 mg inhaled qd for 10 days within 36 hours of exposure Community outbreaks: Begin within 5 days of outbreak; may administer for up to 28 days □ Flu treatment in people 7 years of age and older Start within 2 days of symptom onset; administer 2 doses on day 1, at least 2 hours apart . Then 10 mg inhaled q12hr for 5 days; consider extending  treatment for severely ill patients after 5 days	Common: Diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, here/nose/throat infection Allergic: Oropharyngeal or facial edema	□ Contraindicated in underlying respiratory disease (asthma, COPD) or history of allergy to milk protein □ Not approved for prophylaxis in nursing home residents □ Patients scheduled to use an inhaled bronchodilator at the same time as zanamivir should use their bronchodilator before taking
Intravenous peramivir (Rapivab)	□ Treatment in Pediatric patients 2 to 12 years of age: 12 mg/kg up to 600 mg □ Treatment in adults 13 years of age and older A single 600 mg dose, administered via intravenous infusion over 15 to 30 minutes	Common: Diarrhea Other: Serious skin reactions, sporadic transient neuropsychiatric events	□ Monitor for signs of unusual behavior
Sources: 12, 19, 20, 21, 22

Oral and inhaled antivirals work best when initiated within 48 hours of symptom onset, but hospitalized patients may benefit even if the drug is started more than 48 hours after symptoms began. Clinicians should not wait for influenza testing results. Patient should continue oseltamivir and zanamivir for at least 5 days. Intravenous peramivir is given as one dose over 15 minutes. Patients should receive one of these drugs; concurrent administration of more than one is contraindicated. Consult the full prescribing information for appropriate dosing.¹⁹

Note that amantadine and rimantadine, FDA-approved for type A influenza, are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses because of high levels of resistance.¹⁹

Some reports of oseltamivir shortages are circulating. CDC indicates that at this time, there is no national shortage of neuraminidase inhibitors, although local shortages may exist. If a local shortage develops, pharmacists should contact multiple distributors or manufacturers for availability. If these drugs are not available, clinicians will need to prioritize oseltamivir for treatment of hospitalized patients, high-risk outpatients, and those with severe or progressive illness not requiring hospitalization.¹²

Finally, Americans love complementary and alternative medicines(CAM). More than 90,000 individual vitamin and mineral supplementation products are marketed. Studies indicate that one of every two patients is taking at least one supplement.²³ Patients may turn to CAM because of cultural influences or because it is available and affordable. Evidence supporting the use of CAM is growing, and pharmacists should be aware of these substances.²⁵ Table 3 lists a handful of substances that have some evidence of effectiveness, although most of it is in vitro or in animal models. Researchers are looking at these substances, which are generally inexpensive, as potentially helpful if a pandemic occurs.²³ Little information is available about their potential adverse events or drug interactions. Each product will differ, and patients should consult the product information. Here, too, pharmacists should emphasize that none of these CAMs replace vaccination.

Table 3. Complementary and Alternative Medicines Used in Influenza
Substance	Source	Possible evidence of effectiveness in influenza
Antiwei	A traditional Chinese herbal	• May reduce influenza severity and duration
Bifidobacterium longum Lactobacillus acidophilus	Probiotics	• Increases natural killer cell activities in the lungs and spleen and  significantly increases pulmonary gene expression of natural killer cell activators • May be used as an influenza prevention intervention if given chronically
Clinacanthus siamensis	Traditional herb from a leafy green plant	• Produced higher anti-influenza virus IgG and IgA antibodies compared with oseltamivir in mice
Echinacea	Extract from the purple cone flower with a diverse chemical composition	• Has antiviral activity against influenza viruses in vitro • Inhibits cytochrome P450 3a4 substrates (e.g. atorvastatin, simvastatin, amlodipine, verapamil)
Sambucus nigra	Elderberry	• Extracts of berries containing polyphenol inhibit influenza virus infection in vitro Flavonoids and anthocyanins seem to be the primary biologically active compounds
Epimedium koreanum Nakai	Traditional Korean and Chinese medicine	• Effective against different influenza A subtypes by significant reduction in viral replication
Garlic extract	A member of the Allium genus	• May enhance immune function • Rich in sulfur compounds that can cause halitosis and body odor • May interact with warfarin, antiplatlet agents, and quinolone antibiotics
Glycyrrhizin	Licorice root	• Stimulates of interferon-gamma production by T cells, promotes immunomodulation, decreases inflammation, reduces viral uptake by host cells
Korean red ginseng	A root containing ginsenosides and gintonin	• Clinical studies show mixed results in influenza; may reduce incidence or duration
Maoto	Traditional Japanese herbal containing Ephedrae Herba, Cinnamomi Cortex, Armeniacae Semen, and Glycyrrhizae Radix	• Equivalent clinical and virologic efficacy to neuraminidase inhibitors • Exerts antipyretic activity in influenza virus–infected mice
Paeonia lactiflora	Also called Bai Shao; a common Chinese herb	• Inhibits viral RNA and viral protein
Psidium guajava	Guava tea prepared by the infusion method	• Inhibits viral hemagglutination and sialidase activity
Punica granatum	Pomegranate polyphenol extract	• Has shown anti-influenza properties in vitro • May be synergistic with oseltamivir
Scutellaria baicalensis Georgi (baicalin)	Chinese herbal	• Antiviral activity that increases in a dose-dependent manner, working at virus budding • May be a natural neuraminidase inhibitor
Thuja orientalis	From trees belonging to the cypress family	• Dose-dependent anti-influenza activity in mice
Source: References 24-30

CONCLUSION

The 2017-2018 influenza season has been a rough ride for Americans and the healthcare providers who care for them. Pharmacists are at the forefront in this epidemic, armed with flu shots and antiviral neuraminidase inhibitors. Armed with accurate information, pharmacists can encourage vaccination, coach patients on preventive measures, and dispense medications likely to ease discomfort.

References

1. Centers for Disease Control and Prevention. Weekly US influenza surveillance report. Accessed at https://www.cdc.gov/flu/weekly/index.htm#S2, February 17, 2018
2. [No author.] 1918 flu pandemic. Accessed at http://www.history.com/topics/1918-flu-pandemic, February 17, 2018.
3. Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis 2006;12(1):15-22  Accessed at https://wwwnc.cdc.gov/eid/article/12/1/pdfs/05-0979.pdf, February 17, 2018.
4. Andrews E. Why was it called the "Spanish Flu?" January 15, 2016. Accessed at http://www.history.com/news/ask-history/why-was-it-called-the-spanish-flu, February 17, 2018.
5. Centers for Disease Control and Prevention. Influenza. Pinkbook. Accessed at https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/flu.pdf, February 17, 2018.
6. Centers for Disease Control and Prevention. Update on the 2017-2018 Influenza Season for Clinicians. February 8, 2018. Accessed at https://emergency.cdc.gov/coca/ppt/2018/slides_020818_2017-2018influenzaSeasonUpdate.pdf, February 17, 2018.
7. National Pork Board, Understanding influenza naming. 2012. Accessed at https://www.cdfa.ca.gov/ahfss/Animal_Health/pdfs/UnderstandingInfluenzaNaming.pdf, February 17, 2018.
8. Talaro KP, Chess B. Foundation in Microbiology, 10th ed. New York, NY: McGraw-Hill Education; 2017: 760-765.
9. World Health Organization Global Influenza Surveillance and Response System (GISRS). Accessed at http://www.who.int/influenza/gisrs_laboratory/en/, February 17, 2018.
10. Centers for Disease Control and Prevention. Prevention and control of seasonal influenza with vaccines, 2017-18. Accessed at https://www.cdc.gov/flu/professionals/acip/index.htm, February 17, 2018.
11. Flannery B, Chung JR, Belongia EA, et al. Interim estimates of 2017-18 seasonal influenza vaccine effectiveness - United States, February 2018. MMWR 2018;67(6):180-185.
12. Budd AP, Uyeki T. Update on the 2017-2018 influenza season for clinicians. February 8, 2018. Accessed at https://emergency.cdc.gov/coca/ppt/2018/slides_020818_2017-2018influenzaSeasonUpdate.pdf, February 17, 2018.
13. Centers for Disease Control and Prevention. CDC Says "Take 3" Actions to Fight the Flu. Accessed at https://www.cdc.gov/flu/protect/preventing.htm, February 17, 2018.
14. New York State Department of Health. When someone at home has the flu. Accessed at https://www.health.ny.gov/publications/7114.pdf, February 17, 2018.
15. Centers for Disease Control and Prevention. Rapid diagnostic testing for influenza: information for clinical laboratory directors. Accessed at https://www.cdc.gov/flu/professionals/diagnosis/rapidlab.htm, February 17, 2018.
16. Centers for Disease Control and Prevention. Guidance for clinicians on the use of RT-PCR and other molecular assays for diagnosis of influenza virus infection. Accessed at https://www.cdc.gov/flu/professionals/diagnosis/molecular-assays.htm, February 17, 2018.
17. Centers for Disease Control and Prevention. Influenza: treatment. Accessed at https://www.cdc.gov/flu/treatment/index.html, February 17, 2018.
18. Baum SG, Carey J. Preventing and treating influenza. Infect Med. 2007;24(1):13-20.
19. Centers for Disease Control and Prevention. Influenza Antiviral medications: summary for clinicians. Accessed at https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm, February 17, 2018.
20. Rapivab (peramivir injection) prescribing information. Durham, NC: BioCryst Pharmaceuticals, Inc.; 2017.
21. Relenza (zanamivir injection) prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2016.
22. Tamiflu (oseltamivir injection) prescribing information. South San Francisco, CA: Genentech, Inc.; 2016.
23. Manson JE, Bassuk SS. Vitamin and mineral supplements: what clinicians need to know. JAMA. 2018 Feb 5. doi: 10.1001/jama.2017.21012. [Epub ahead of print]
24. Mousa HA. Prevention and treatment of influenza, influenza-like illness, and common cold by herbal, complementary, and natural therapies. J Evid Based Complementary Altern Med. 2017;22(1):166-174.
25. Tao Z, Yang Y, Shi W, et al. Complementary and alternative medicine is expected to make greater contribution in controlling the prevalence of influenza. Biosci Trends. 2013;7(5):253-256.
26. Ross SM. Echinacea Formula (Echinaforce® Hotdrink): Effects of a proprietary echinacea formula compared with oseltamivir in the early treatment of influenza. Holist Nurs Pract. 2016;30(2):122-5.
    
27. Wirotesangthong M, Nagai T, Yamada H, Amnuoypol S, Mungmee C. Effects of Clinacanthus siamensis leaf extract on influenza virus infection. Microbiol Immunol. 2009;53(2):66-74.
28. Im K, Kim J, Min H. Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection. J Ginseng Res. 2016;40(4):309-314.
29. Wang L, Zhang RM, Liu GY, et al. Chinese herbs in treatment of influenza: a randomized, double-blind, placebo-controlled trial. Respir Med. 2010;104(9):1362-9.
30. Asher GN, Corbett AH, Hawke RL. Common herbal dietary supplement-drug interactions. Am Fam Physician. 2017 Jul 15;96(2):101-107.
    

Back to Top