Treatment of influenza

Last updated

Treatments for influenza include a range of medications and therapies that are used in response to disease influenza. Treatments may either directly target the influenza virus itself; or instead they may just offer relief to symptoms of the disease, while the body's own immune system works to recover from infection. [1]

Contents

The main classes of antiviral drugs used against influenza are neuraminidase inhibitors, such as zanamivir and oseltamivir, polymerase acidic endonuclease inhibitors such as baloxavir marboxil, or inhibitors of the viral M2 protein, such as amantadine and rimantadine. These drugs can reduce the severity of symptoms if taken soon after infection and can also be taken to decrease the risk of infection. However, virus strains have emerged that show drug resistance to some classes of drug.

Symptomatic treatment

The United States authority on disease prevention, the Centers for Disease Control and Prevention (CDC), recommends that people with influenza infections:

Warning signs are symptoms that indicate that the disease is becoming serious and needs immediate medical attention. These include:[ citation needed ]

In children other warning signs include irritability, failing to wake up and interact, rapid breathing, and a blueish skin color. Another warning sign in children is if the flu symptoms appear to resolve, but then reappear with fever and a bad cough. [2]

Antiviral drugs

Antiviral drugs directly target the viruses responsible for influenza infections. Generally, anti-viral drugs work optimally when taken within a few days of the onset of symptoms. [3] Certain drugs are used prophylactically, that is they are used in uninfected individuals to guard against infection.[ medical citation needed ]

Four licensed influenza antiviral agents are available in the United States: zanamivir, oseltamivir phosphate, peramivir, and baloxavir marboxil. [4] They are available through prescription only. [4]

Antiviral drugs to treat influenza [4]
ClassEffective AgainstDrug Name (INN)Brand NameYear ApprovedManufacturer
Neuraminidase inhibitors Influenza A & B zanamivir Relenza1999 GlaxoSmithKline
oseltamivir Tamiflu1999 Hoffmann-La Roche
peramivir Rapivab2014 BioCryst Pharmaceuticals
Cap-dependent endonuclease inhibitorInfluenza A & B baloxavir marboxil Xofluza2018 Shionogi Pharma Co., Ltd.

In Russia and China a drug called arbidol is also used as a treatment. Testing of the drug has predominantly occurred in these countries and, although no clinical trials have been published demonstrating this is an effective drug, some data suggest that this could be a useful treatment for influenza. [5] [6]

Interferons

Interferons are cellular signalling factors produced in response to viral infection. Research into the use of interferons to combat influenza began in the 1960s in the Soviet Union, culminating in a trial of 14,000 subjects at the height of the Hong Kong Flu of 1969, in which those treated prophylactically with interferon were more than 50% less likely to suffer symptoms, though evidence of latent infection was present. [7] In these early studies leukocytes were collected from donated blood and exposed to a high dose of Newcastle disease, causing them to release interferons. Although interferon therapies became widespread in the Soviet Union, the method was doubted in the United States after high doses of interferon proved ineffective in trials. Though the 1969 study used 256 units of interferon, subsequent studies used up to 8.4 million units. It has since been proposed that activity of interferon is highest at low concentrations. [8] Phase III trials in Australia are planned for 2010, and initial trials are planned in the U.S. for late 2009. [9]

Interferons have also been investigated as adjuvants to enhance to effectiveness of influenza vaccines. This work was based on experiments in mice that suggested that type I interferons could enhance the effectiveness of influenza vaccines in mice. [10] However, a clinical trial in 2008 found that oral dosing of elderly patients with interferon-alpha actually reduced their immune response to an influenza vaccine. [11]

Viferon is a suppository of (non-pegylated [12] ) interferon alpha-2b, ascorbic acid (vitamin C), and tocopherol (vitamin E) which was reported in two small studies to be as effective as arbidol. [13] [14] Another interferon alfa-2b medicine, "Grippferon", nasal drops, is used for treatment and emergency prevention of Influenza and cold. [15] Its manufacturers have appealed to the WHO to consider its use against avian influenza and H1N1 Influenza 09 (Human Swine Flu), stating that it was used successfully in Russia for eight years, but that "the medical profession in Europe and the USA is not informed about this medicine". [16]

Drug resistance

Influenza viruses can show resistance to anti-viral drugs. Like the development of bacterial antibiotic resistance, this can result from over-use of these drugs. For example, a study published in the June 2009 Issue of Nature Biotechnology emphasized the urgent need for augmentation of oseltamivir (Tamiflu) stockpiles with additional antiviral drugs including zanamivir (Relenza) based on an evaluation of the performance of these drugs in the scenario that the 2009 H1N1 'Swine Flu' neuraminidase (NA) were to acquire the tamiflu-resistance (His274Tyr) mutation which is currently widespread in seasonal H1N1 strains. [17] Yet another example is in the case of the amantadines treatment may lead to the rapid production of resistant viruses, and over-use of these drugs has probably contributed to the spread of resistance. [18] In particular, this high-level of resistance may be due to the easy availability of amantadines as part of over-the-counter cold remedies in countries such as China and Russia, [19] and their use to prevent outbreaks of influenza in farmed poultry. [20] [21]

On the other hand, a few strains resistant to neuraminidase inhibitors have emerged and circulated in the absence of much use of the drugs involved, and the frequency with which drug resistant strains appears shows little correlation with the level of use of these drugs. [22] However, laboratory studies have shown that it is possible for the use of sub-optimal doses of these drugs as a prophylactic measure might contribute to the development of drug resistance. [22]

During the United States 2005–2006 influenza season, increasing incidence of drug resistance by strain H3N2 to amantadine and rimantadine led the CDC to recommend oseltamivir as a prophylactic drug, and the use of either oseltamivir or zanamivir as treatment. [23] [24]

Over-the-counter medication

Antiviral drugs are prescription-only medication in the United States. Readily available over-the-counter medications do not directly affect the disease, but they do provide relief from influenza symptoms, as illustrated in the table below.

OTC medicines provide relief for 'flu symptoms [25]
Symptom(s)OTC Medicine
fever, aches, pains, sinus pressure, sore throat analgesics
nasal congestion, sinus pressure decongestants
sinus pressure, runny nose, watery eyes, cough antihistamines
cough cough suppressant
sore throat local anesthetics

Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin as taking aspirin in the presence of influenza infection (especially Influenzavirus B) can lead to Reye syndrome, a rare but potentially fatal disease of the brain. [26]

Off-label uses of other drugs

Several generic prescription medications might prove useful to treat a potential H5N1 avian flu outbreak, including statins, fibrates, and chloroquine. [27] [28] [29]

Nutritional supplements and herbal medicines

Malnutrition can reduce the ability of the body to resist infections and is a common cause of immunodeficiency in the developing world. [30] For instance, in a study in Ecuador, micronutrient deficiencies were found to be common in the elderly, especially for vitamin C, vitamin D, vitamin B-6, vitamin B-12, folic acid, and zinc, and these are thought to weaken the immune system or cause anemia and thus place people at greater risk of respiratory infections such as influenza. [31] Seasonal variation in sunlight exposure, which is required for vitamin D synthesis within the body, has been proposed as one of the factors accounting for the seasonality of influenza. [32] A meta-analysis of 13 studies indicated some support for adjunctive vitamin D therapy for influenza, but called for more rigorous clinical trials to settle the issue conclusively. [33]

A recent review discussing herbal and alternative medicines in influenza treatment details evidence suggesting that N-acetylcysteine, elderberry, or a combination of Eleutherococcus senticosus and Andrographis paniculata may help to shorten the course of influenza infection. The article cites more limited evidence including animal or in vitro studies to suggest possible benefit from vitamin C, DHEA, high lactoferrin whey protein, Echinacea spp., Panax quinquefolium , Larix occidentalis arabinogalactans, elenolic acid (a constituent of olive leaf extract), Astragalus membranaceus , and Isatis tinctoria or Isatis indigotica . [34] Another review assessed the quality of evidence for alternative influenza treatments, it concluded that there was "no compelling evidence" that any of these treatments were effective and that the available data on these products is particularly weak, with trials in this area suffering from many shortcomings, such as being small and poorly-designed and not testing for adverse effects. [35]

N-Acetylcysteine

The activity of N-acetylcysteine (NAC) against influenza was first suggested in 1966. [36] In 1997 a randomized clinical trial found that volunteers taking 1.2 grams of N-acetylcysteine daily for six months were as likely as those taking placebo to be infected by influenza, but only 25% of them experienced clinical symptoms, as contrasted with 67% of the control group. The authors concluded that resistance to flu symptoms was associated with a shift in cell mediated immunity from anergy toward normoergy, as measured by the degree of skin reactivity to seven common antigens such as tetanus and Candida albicans. [37]

Several animal studies found that in a mouse model of lethal infection with a high dose of influenza, oral supplementation with one gram of N-acetylcysteine per kilogram of body weight daily increased the rate of survival, either when administered alone or in combination with the antiviral drugs ribavirin or oseltamivir. [38] [39] [40] NAC was shown to block or reduce cytopathic effects in influenza-infected macrophages, [41] to reduce DNA fragmentation (apoptosis) in equine influenza-infected canine kidney cells, [42] and to reduce RANTES production in cultured airway cells in response to influenza virus by 18%. [43] The compound has been proposed for treatment of influenza. [44]

Elderberry

A few news reports have suggested the use of an elderberry (Sambucus nigra) extract as a potential preventative against the 2009 flu pandemic. [45] [46] [47] [48] The preparation has been reported to reduce the duration of influenza symptoms by raising levels of cytokines. [49] [50] [51] However, the use of the preparation has been described as "imprudent" when an influenza strain causes death in healthy adults by cytokine storm leading to primary viral pneumonia. [52] The manufacturer cites a lack of evidence for cytokine-related risks, but labels the product only as an antioxidant and food supplement. [53]

"Kan Jang"

The mixture of Eleutherococcus senticosus ("Siberian ginseng") and Andrographis paniculata, sold under the trade name Kan Jang, was reported in the Journal of Herbal Pharmacotherapy to outperform amantadine in reducing influenza-related sick time and complications in a Volgograd pilot study of 71 patients in 2003. [54] Prior to this, an extract of Eleutherococcus senticosus was shown to inhibit replication of RNA but not DNA viruses in vitro. [55] Among nine Chinese medicinal herbs tested, Andrographis paniculata was shown to be most effective in inhibiting RANTES secretion by H1N1 influenza infected cells in cell culture, with an IC50 for the ethanol extract of 1.2 milligrams per liter. [56]

Green Tea

High dietary intake of green tea (specifically, catechins and theanine that is found in tea products) has been correlated with reduced risk of contracting influenza, as well as having an antiviral effect upon types A and B. [57] [58] [59] Specifically, the high levels of epigallocatechin gallate, epicatechin gallate, and epigallocatechin present in green tea were found to inhibit influenza virus replication. [60] Additionally, topical application has been suggested to possibly act as a mild disinfectant. [61] Regular dietary intake of green tea has been associated with stronger immune response to infection, through the enhancement of T-Cell function. [62]

Passive immunity

Transfused antibodies

An alternative to vaccination used in the 1918 flu pandemic was the direct transfusion of blood, plasma, or serum from recovered patients. Though medical experiments of the era lacked some procedural refinements, eight publications from 1918 to 1925 reported that the treatment could approximately halve the mortality in hospitalized severe cases with an average case-fatality rate of 37% when untreated. [63] [64]

Bovine colostrum might also serve as a source of antibodies for some applications. [65]

Ex vivo culture of T lymphocytes

Human T lymphocytes can be expanded in vitro using beads holding specific antigens to activate the cells and stimulate growth. Clonal populations of CD8+ cytotoxic T cells have been grown which carry T cell receptors specific to influenza. These work much like antibodies but are permanently bound to these cells. (See cellular immunity). High concentrations of N-acetylcysteine have been used to enhance growth of these cells. This method is still in early research. [66] [67]

Related Research Articles

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

<i>Influenza A virus</i> Species of virus

Influenza A virus (IAV) is the only species of the genus Alphainfluenzavirus of the virus family Orthomyxoviridae. It is a pathogen with strains that infect birds and some mammals, as well as causing seasonal flu in humans. Mammals in which different strains of IAV circulate with sustained transmission are bats, pigs, horses and dogs; other mammals can occasionally become infected.

<i>Orthomyxoviridae</i> Family of RNA viruses including the influenza viruses

Orthomyxoviridae is a family of negative-sense RNA viruses. It includes seven genera: Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in birds and mammals, including humans. Isaviruses infect salmon; the thogotoviruses are arboviruses, infecting vertebrates and invertebrates. The Quaranjaviruses are also arboviruses, infecting vertebrates (birds) and invertebrates (arthropods).

<span class="mw-page-title-main">Zanamivir</span> Influenza medication

Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and approved in the US in 1999, only for use as a treatment for influenza. In 2006, it was approved for prevention of influenza A and B. Zanamivir was the first neuraminidase inhibitor commercially developed. It is marketed by GlaxoSmithKline under the trade name Relenza as a powder for oral inhalation.

<span class="mw-page-title-main">Oseltamivir</span> Antiviral medication used against influenza: winners drink Tamiflu

Oseltamivir, sold under the brand name Tamiflu among others, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid.

<span class="mw-page-title-main">Rimantadine</span> Drug used to treat influenzavirus A infection

Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Rimantadine can mitigate symptoms, including fever. Both rimantadine and the similar drug amantadine are derivates of adamantane. Rimantadine is found to be more effective than amantadine because when used the patient displays fewer symptoms. Rimantadine was approved by the Food and Drug Administration (FDA) in 1994.

<span class="mw-page-title-main">Amantadine</span> Medication used to treat dyskinesia

Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended because of widespread drug resistance. It is also used for a variety of other uses. The drug is taken by mouth.

<span class="mw-page-title-main">Swine influenza</span> Infection caused by influenza viruses endemic to pigs

Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As of 2009, identified SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3.

Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are a commonly used antiviral drug type against influenza. Viral neuraminidases are essential for influenza reproduction, facilitating viral budding from the host cell. Oseltamivir (Tamiflu), zanamivir (Relenza), laninamivir (Inavir), and peramivir belong to this class. Unlike the M2 inhibitors, which work only against the influenza A virus, NAIs act against both influenza A and influenza B.

<span class="mw-page-title-main">Influenza A virus subtype H1N1</span> Subtype of Influenza A virus

Influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus (IAV). Some human-adapted strains of H1N1 are endemic in humans and are one cause of seasonal influenza (flu). Other strains of H1N1 are endemic in pigs and in birds. Subtypes of IAV are defined by the combination of the antigenic H and N proteins in the viral envelope; for example, "H1N1" designates an IAV subtype that has a type-1 hemagglutinin (H) protein and a type-1 neuraminidase (N) protein.

<span class="mw-page-title-main">Influenza pandemic</span> Pandemic involving influenza

An influenza pandemic is an epidemic of an influenza virus that spreads across a large region and infects a large proportion of the population. There have been five major influenza pandemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The 2009 swine flu pandemic resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.

<span class="mw-page-title-main">Peramivir</span> Antiviral drug targeting influenza

Peramivir is an antiviral drug developed by BioCryst Pharmaceuticals for the treatment of influenza. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells. It is approved for intravenous administration.

<span class="mw-page-title-main">Transmission and infection of H5N1</span> Spread of an influenza virus

Transmission and infection of H5N1 from infected avian sources to humans has been a concern since the first documented case of human infection in 1997, due to the global spread of H5N1 that constitutes a pandemic threat.

<span class="mw-page-title-main">H5N1 genetic structure</span> Genetic structure of Influenza A virus

The genetic structure of H5N1, a highly pathogenic avian influenza virus, is characterized by a segmented RNA genome consisting of eight gene segments that encode for various viral proteins essential for replication, host adaptation, and immune evasion.

<span class="mw-page-title-main">Umifenovir</span> Chemical compound

Umifenovir, sold under the brand name Arbidol, is sold and used as an antiviral medication for influenza in Russia and China. The drug is manufactured by Pharmstandard. It is not approved by the U.S. Food and Drug Administration (FDA) for the treatment or prevention of influenza.

<span class="mw-page-title-main">Nitazoxanide</span> Broad-spectrum antiparasitic and antiviral medication

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Pandemrix</span> Flu vaccine

Pandemrix is an influenza vaccine for influenza pandemics, such as the 2009 flu pandemic. The vaccine was developed by GlaxoSmithKline (GSK) and patented in September 2006.

<span class="mw-page-title-main">Influenza</span> Infectious disease

Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin one to four days after exposure to the virus and last for about two to eight days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia from the virus or a subsequent bacterial infection. Other complications include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<span class="mw-page-title-main">2009 swine flu pandemic</span> 2009–2010 pandemic of swine influenza caused by H1N1 influenza virus

The 2009 swine flu pandemic, caused by the H1N1/swine flu/influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, was the third recent flu pandemic involving the H1N1 virus. The first identified human case was in La Gloria, Mexico, a rural town in Veracruz. The virus appeared to be a new strain of H1N1 that resulted from a previous triple reassortment of bird, swine, and human flu viruses which further combined with a Eurasian pig flu virus, leading to the term "swine flu".

<span class="mw-page-title-main">Pandemic H1N1/09 virus</span> Virus responsible for the 2009 swine flu pandemic

The pandemic H1N1/09 virus is a swine origin influenza A virus subtype H1N1 strain that was responsible for the 2009 swine flu pandemic. This strain is often called swine flu by the public media due to the prevailing belief that it originated in pigs. The virus is believed to have originated around September 2008 in central Mexico.

References

  1. ↑ Montalto NJ, Gum KD, Ashley JV (December 2000). "Updated treatment for influenza A and B". Am Fam Physician. 62 (11): 2467–76. PMID   11130232. Archived from the original on 2011-06-06. Retrieved 2009-04-29.
  2. 1 2 "Taking Care of Yourself: What to Do if You Get Sick with Flu". Disease and Conditions: Seasonal Flu. CDC. 2008-02-06. Archived from the original on 2019-01-04. Retrieved 2008-10-24.
  3. ↑ Stiver, Grant (2003). "The treatment of influenza with antiviral drugs". Canadian Medical Association Journal. 168 (1): 49–57. PMC   139319 . PMID   12515786 – via Pub Med.
  4. 1 2 3 Centers for Disease Control and Prevention (3 September 2020). "What You Should Know about Flu Antiviral Drugs". Centers for Disease Control and Prevention (CDC). Retrieved 26 November 2020.
  5. ↑ Leneva, IA; Fediakina, IT; Gus'kova, TA; Glushkov, RG (2005). "[Sensitivity of various influenza virus strains to arbidol. Influence of arbidol combination with different antiviral drugs on reproduction of influenza virus A]". Терапевтический Архив (Therapeutic Archive). 77 (8). Moscow, Russia: ИЗДАТЕЛЬСТВО "МЕДИЦИНА": 84–88. PMID   16206613 . Retrieved 2008-10-24.
  6. ↑ Shi L, Xiong H, He J, et al. (2007). "Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo". Arch. Virol. 152 (8): 1447–55. doi:10.1007/s00705-007-0974-5. PMID   17497238. S2CID   13595688.
  7. ↑ V.D. Solov'ev (1969). "The results of controlled observations on the prophylaxis of influenza with interferon" (PDF). Bulletin of the World Health Organization. 41 (3): 683–688. PMC   2427762 . PMID   5309493. Archived from the original (PDF) on June 4, 2011.
  8. ↑ Joseph M. Cummins, DVM, Chad G. Thompson, BA (December 2004). "Low Dose Interferon, Immune Modulation and Emergency Influenza Prophylaxis". Pathobiologics International.{{cite web}}: CS1 maint: multiple names: authors list (link) – see also Cummins, Joseph M.; Krakowka, G. Steven; Thompson, Chad G. (January 2005). "Systemic effects of interferons after oral administration in animals and humans" (PDF). American Journal of Veterinary Research. 66 (1): 164–176. doi:10.2460/ajvr.2005.66.164. PMID   15691053.
  9. ↑ "Amarillo Biosciences Selects Accelovance for Its Next Influenza Study". MarketWire. 2009-05-20. Archived from the original on 2020-04-03. Retrieved 2009-06-15.
  10. ↑ Bracci L, Canini I, Venditti M, et al. (April 2006). "Type I IFN as a vaccine adjuvant for both systemic and mucosal vaccination against influenza virus". Vaccine. 24 (Suppl 2): S56–7. doi:10.1016/j.vaccine.2005.01.121. PMID   16823927.
  11. ↑ Launay O, Grabar S, Bloch F, et al. (July 2008). "Effect of sublingual administration of interferon-alpha on the immune response to influenza vaccination in institutionalized elderly individuals". Vaccine. 26 (32): 4073–9. doi:10.1016/j.vaccine.2008.05.035. PMID   18602725.
  12. ↑ "Russia through the prism of the world biopharmaceutical market" (PDF). Archived from the original (PDF) on 2012-02-24. Retrieved 2009-06-14.
  13. ↑ Gatich RZ, Kolobukhina LV, Vasil'ev AN, Isaeva EI, Burtseva EI, Orlova TG, Voronina FV, Kol'tsov VD, Malinovskaia VV (2008). "Viferon suppositories in the treatment of influenza in adults (article in Russian)". Antibiot Khimioter. 53 (3–4): 13–7. PMID   18942420.
  14. ↑ Kolobukhina LV, Malinovskaia VV, Gatich RZ, et al. (2008). "[Evaluation of the efficacy of wiferon and arbidol in adult influenza]". Vopr. Virusol. 53 (1): 31–3. PMID   18318133.
  15. ↑ "Clinical Investigations of Grippferon". Archived from the original on 2011-07-06. Retrieved 2009-07-04.
  16. ↑ "OPEN LETTER to: Director-General's office of the World Health Organization". February 2006. Archived from the original on 2011-07-06. Retrieved 2009-06-15.
  17. ↑ Venkataramanan Soundararajan; Kannan Tharakaraman; Rahul Raman; S. Raguram; Zachary Shriver; V. Sasisekharan; Ram Sasisekharan (9 June 2009). "Extrapolating from sequence — the 2009 H1N1 'swine' influenza virus". Nature Biotechnology. 27 (6): 510–3. doi:10.1038/nbt0609-510. PMID   19513050. S2CID   22710439.
  18. ↑ Lynch JP, Walsh EE (April 2007). "Influenza: evolving strategies in treatment and prevention". Semin Respir Crit Care Med. 28 (2): 144–58. doi:10.1055/s-2007-976487. PMID   17458769. S2CID   260316848.
  19. ↑ Bright RA, Medina MJ, Xu X, et al. (October 2005). "Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern". Lancet. 366 (9492): 1175–81. doi:10.1016/S0140-6736(05)67338-2. PMID   16198766. S2CID   7386999.
  20. ↑ Ilyushina NA, Govorkova EA, Webster RG (October 2005). "Detection of amantadine-resistant variants among avian influenza viruses isolated in North America and Asia". Virology. 341 (1): 102–6. doi:10.1016/j.virol.2005.07.003. PMID   16081121.
  21. ↑ Parry J (July 2005). "Use of antiviral drug in poultry is blamed for drug resistant strains of avian flu". BMJ. 331 (7507): 10. doi:10.1136/bmj.331.7507.10. PMC   558527 . PMID   15994677.
  22. 1 2 Lackenby A, Thompson CI, Democratis J (December 2008). "The potential impact of neuraminidase inhibitor resistant influenza". Curr. Opin. Infect. Dis. 21 (6): 626–38. doi:10.1097/QCO.0b013e3283199797. PMID   18978531. S2CID   26989985.
  23. ↑ Smith NM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA (July 2006). "Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR Recomm Rep. 55 (RR-10). Centers for Disease Control and Prevention: 1–42. PMID   16874296.
  24. ↑ Altman LK (2006-01-15). "This Season's Flu Virus Is Resistant to 2 Standard Drugs". The New York Times .
  25. ↑ "Cold and Flu Guidelines: Influenza". American Lung Association. Archived from the original on April 1, 2007. Retrieved 2007-09-16.
  26. ↑ Molotsky I (1986-02-15). "Consumer Saturday – Warning on Flu and Aspirin". The New York Times .
  27. ↑ D.S. Fedson (September 2008). "Confronting an influenza pandemic with inexpensive generic agents: can it be done?". The Lancet Infectious Diseases. 8 (9): 571–6. doi:10.1016/S1473-3099(08)70070-7. PMC   7128266 . PMID   18420459.
  28. ↑ Fedson DS (July 2006). "Pandemic influenza: a potential role for statins in treatment and prophylaxis". Clin. Infect. Dis. 43 (2): 199–205. doi: 10.1086/505116 . PMC   7107836 . PMID   16779747.
  29. ↑ Fedson DS, Dunnill P (2007). "Commentary: From scarcity to abundance: pandemic vaccines and other agents for "have not" countries". J Public Health Policy. 28 (3): 322–40. doi: 10.1057/palgrave.jphp.3200147 . PMID   17717543. S2CID   8373109.
  30. ↑ Katona P, Katona-Apte J (May 2008). "The interaction between nutrition and infection". Clin. Infect. Dis. 46 (10): 1582–8. doi: 10.1086/587658 . PMID   18419494.
  31. ↑ Hamer DH, Sempértegui F, Estrella B, et al. (January 2009). "Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians". J. Nutr. 139 (1): 113–9. doi:10.3945/jn.108.095091. PMC   2646211 . PMID   19056665.
  32. ↑ Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E (2008). "On the epidemiology of influenza". Virol. J. 5: 29. doi: 10.1186/1743-422X-5-29 . PMC   2279112 . PMID   18298852.
  33. ↑ Yamshchikov AV, Desai NS, Blumberg HM, Ziegler TR, Tangpricha V (2009). "Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials". Endocr Pract. 15 (5): 438–49. doi:10.4158/EP09101.ORR. PMC   2855046 . PMID   19491064.
  34. ↑ Mario Roxas, ND and Julie Jurenka, MT (ASCP) (2007). "Colds and Influenza: A Review of Diagnosis and Conventional, Botanical, and Nutritional Considerations" (PDF). Alternative Medicine Review. 12 (1): 25–48. PMID   17397266. Archived from the original (PDF) on 2011-07-28. Retrieved 2009-06-13.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ↑ Guo R, Pittler MH, Ernst E (November 2007). "Complementary medicine for treating or preventing influenza or influenza-like illness". Am. J. Med. 120 (11): 923–929.e3. doi:10.1016/j.amjmed.2007.06.031. PMID   17976414.
  36. ↑ Streightoff F, Redman CE, DeLong DC (1966). "In vivo antiviral chemotherapy. II. Anti-influenza action of compounds affecting mucous secretions". Antimicrob Agents Chemother. 6: 503–8. PMID   5985279.
  37. ↑ S. De Flora; C. Grassi; L. Carati (1997). "Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment" (PDF). Eur Respir J. 10 (7): 1535–1541. doi: 10.1183/09031936.97.10071535 . PMID   9230243.(Open access article)
  38. ↑ Ungheri D, Pisani C, Sanson G, et al. (2000). "Protective effect of n-acetylcysteine in a model of influenza infection in mice". Int J Immunopathol Pharmacol. 13 (3): 123–128. PMID   12657201.
  39. ↑ Ghezzi P, Ungheri D (2004). "Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model". Int J Immunopathol Pharmacol. 17 (1): 99–102. doi: 10.1177/039463200401700114 . PMID   15000873.
  40. ↑ Garozzo A, Tempera G, Ungheri D, Timpanaro R, Castro A (2007). "N-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection". Int J Immunopathol Pharmacol. 20 (2): 349–54. doi:10.1177/039463200702000215. PMID   17624247. S2CID   10510588.
  41. ↑ Lowy RJ, Dimitrov DS (August 1997). "Characterization of influenza virus-induced death of J774.1 macrophages". Exp. Cell Res. 234 (2): 249–58. doi:10.1006/excr.1997.3602. PMID   9260892.
  42. ↑ Saito T, Tanaka M, Yamaguchi I (November 1996). "Effect of brefeldin A on influenza A virus-induced apoptosis in vitro". J. Vet. Med. Sci. 58 (11): 1137–9. doi: 10.1292/jvms.58.11_1137 . PMID   8959666.
  43. ↑ Mugnier A, Manoha E, Drapier M (1976). "[Relation between the orofacial musculature and vertebral statics]". Orthod Fr. 47: 69–73. PMID   1070671.
  44. ↑ "N-acetylcysteine". Altern Med Rev. 5 (5): 467–71. October 2000. PMID   11056417.
  45. ↑ Kristin Chambers (2009-05-02). "2 flu cases found in state". Archived from the original on 2012-07-16. Retrieved 2009-06-13.
  46. ↑ La'Tasha Givens (2009-05-05). "Thomasville Residents Concerned About H1N1". WCTV News. Archived from the original on 2020-04-03. Retrieved 2009-06-13.
  47. ↑ Louis Cooper (2009-04-28). "No swine flu cases in state; officials on alert". Pensacola News-Journal. Archived from the original on 2020-04-03. Retrieved 2009-06-13.
  48. ↑ Matthew Stein (2009-04-28). "When a Super-Bug Strikes Close to Home, How Will You Deal With it?". Huffington Post.
  49. ↑ Barak, V; Halperin, T; Kalickman, I (June 2001). "The effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines: I. Inflammatory cytokines". European Cytokine Network. 12 (2): 290–296. PMID   11399518.
  50. ↑ Barak V, Birkenfeld S, Halperin T, Kalickman I (November 2002). "The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines". Isr Med Assoc J. 4 (11 Suppl): 919–922. PMID   12455180.
  51. ↑ "Elderberry Fights Flu Symptoms". WebMD. 2003-12-22.
  52. ↑ Jeffrey R. Ryan (2008). Pandemic Influenza. CRC Press. ISBN   978-1-4200-6087-4.
  53. ↑ "Sambucol FAQs". Manufacturer Web site. Archived from the original on 2009-07-25. Retrieved 2009-06-13.
  54. ↑ Kulichenko LL, Kireyeva LV, Malyshkina EN, Wikman G (2003). "A randomized, controlled study of Kan Jang versus amantadine in the treatment of influenza in Volgograd". J Herb Pharmacother. 3 (1): 77–93. doi:10.1080/j157v03n01_04. PMID   15277072. S2CID   36307129.
  55. ↑ Glatthaar-Saalmüller B, Sacher F, Esperester A (June 2001). "Antiviral activity of an extract derived from roots of Eleutherococcus senticosus". Antiviral Res. 50 (3): 223–8. doi:10.1016/S0166-3542(01)00143-7. PMID   11397509.
  56. ↑ Ko HC, Wei BL, Chiou WF (September 2006). "The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus-infected human epithelial cells". J Ethnopharmacol. 107 (2): 205–10. doi:10.1016/j.jep.2006.03.004. PMID   16621378.
  57. ↑ Matsumoto, K; Yamada, H; Takuma, N; Niino, H; Sagesaka, YM (2005). "Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial". BMC Complement Altern Med. 11: 15. doi: 10.1186/1472-6882-11-15 . PMC   3049752 . PMID   21338496.
  58. ↑ Park, M; Yamada, H; Matsushita, K; Kaji, S; Goto, T; Okada, Y; Kosuge, K; Kitagawa, T (2011). "Green tea consumption is inversely associated with the incidence of influenza infection among schoolchildren in a tea plantation area of Japan". J. Nutr. 141 (10): 1862–70. doi: 10.3945/jn.110.137547 . PMID   21832025.
  59. ↑ Imanishi, N; Tuji, Y; Katada, Y; Maruhashi, M; Konosu, S; Mantani, N; Terasawa, K; Ochiai, H (2002). "Additional inhibitory effect of tea extract on the growth of influenza A and B viruses in MDCK cells". Microbiol. Immunol. 46 (7): 491–4. doi: 10.1111/j.1348-0421.2002.tb02724.x . PMID   12222936. S2CID   24102910.
  60. ↑ Song, JM; Lee, KH; Seong, BL (2005). "Antiviral effect of catechins in green tea on influenza virus". Antiviral Research. 68 (2): 66–74. doi:10.1016/j.antiviral.2005.06.010. PMID   16137775.
  61. ↑ Shin, WJ; Kim, YK; Lee, KH; Seong, BL (2012). "Evaluation of the antiviral activity of a green tea solution as a hand-wash disinfectant". Biosci. Biotechnol. Biochem. 76 (3): 581–4. doi: 10.1271/bbb.110764 . PMID   22451404.
  62. ↑ Rowe, CA; Nantz, MP; Bukowski, JF; Percival, SS (2007). "Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances gamma, delta T cell function: a randomized, double-blind, placebo-controlled study". J Am Coll Nutr. 26 (5): 445–52. doi:10.1080/07315724.2007.10719634. PMID   17914132. S2CID   71265877.
  63. ↑ Thomas C. Luke, MD, MTMH; Edward M. Kilbane, MD, MPH; Jeffrey L. Jackson, MD, MPH; and Stephen L. Hoffman, MD, DTMH (2006-10-17). "Meta-Analysis: Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?". Annals of Internal Medicine. 145 (8): 599–609. doi:10.7326/0003-4819-145-8-200610170-00139. PMID   16940336. S2CID   2929898.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  64. ↑ Jeffrey R. Ryan (2008). Pandemic Influenza. CRC Press. ISBN   978-1-4200-6087-4.
  65. ↑ Korhonen H, Marnila P, Gill HS (November 2000). "Bovine milk antibodies for health". Br. J. Nutr. 84 (Suppl 1): S135–46. doi:10.1017/s0007114500002361. PMID   11242458. S2CID   12874865.
  66. ↑ Kalamasz D, Long SA, Taniguchi R, Buckner JH, Berenson RJ, Bonyhadi M (2004). "Optimization of human T-cell expansion ex vivo using magnetic beads conjugated with anti-CD3 and Anti-CD28 antibodies". J. Immunother. 27 (5): 405–18. doi:10.1097/00002371-200409000-00010. PMID   15314550. S2CID   19278587.
  67. ↑ Boon AC, Vos AP, Graus YM, Rimmelzwaan GF, Osterhaus AD (January 2002). "In vitro effect of bioactive compounds on influenza virus specific B- and T-cell responses". Scand. J. Immunol. 55 (1): 24–32. doi: 10.1046/j.1365-3083.2002.01014.x . PMID   11841689. S2CID   43746920.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.