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Complementary and alternative medicine in alliance with conventional medicine for influenza therapeutics and prevention

2016; Future Medicine; Volume: 11; Issue: 10 Linguagem: Inglês

10.2217/fvl-2016-0084

1746-0808

Shailendra K. Saxena, Sai V. Chitti, Srinivasulu Gadugu,

Viral gastroenteritis research and epidemiology

Future VirologyVol. 11, No. 10 EditorialFree AccessComplementary and alternative medicine in alliance with conventional medicine for influenza therapeutics and preventionShailendra K Saxena, Sai V Chitti & Srinivasulu GaduguShailendra K Saxena*Author for correspondence: E-mail Address: shailen1@gmail.com Department of Stem Cell & Cell Culture, Centre for Advance Research (CFAR), King George's Medical University (KGMU), Lucknow 226003 (UP), India CSIR-Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500007 (TS), India, Sai V Chitti Department of Stem Cell & Cell Culture, Centre for Advance Research (CFAR), King George's Medical University (KGMU), Lucknow 226003 (UP), India CSIR-Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500007 (TS), India & Srinivasulu Gadugu Department of Stem Cell & Cell Culture, Centre for Advance Research (CFAR), King George's Medical University (KGMU), Lucknow 226003 (UP), IndiaPublished Online:6 Sep 2016https://doi.org/10.2217/fvl-2016-0084AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: CAMinfluenza virusInfluenzinuminnate immunitytherapeuticsvaccinesFirst draft submitted: 9 August 2016; Accepted for publication: 19 August 2016; Published online: 6 SeptemberInfluenzaInfluenza, otherwise called seasonal flu, is a respiratory disease caused by viruses belonging to the family Orthomyxoviridae [1]. Influenza viruses (IV) cause highly communicable acute respiratory illnesses with significant mortality. According to the WHO, influenza occurs globally with an annual attack rate estimated at 5–10% in adults and 20–30% in children, resulting in 250,000 to 500,000 deaths [2]. Influenza virion are enveloped and measure about 80–120 nm in diameter. Their genome consists of approximately 13.5-kb long, segmented, single stranded, negative sense RNA, which encodes 11 different proteins [3]. Because of the segmented nature of its genetic material, the IV is exceedingly mutagenic, bringing about incessant introduction of new antigenic strains into the population. The viral proteins include hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix (M1, M2), NS1, NS2 (NEP: nuclear export protein), PA, PB1 (polymerase basic 1), PB1-F2 and PB2. The surface of IV is coated with two proteins, HA and NA. Orthomyxoviridae family consists of four different genera: influenza A, influenza B, influenza C and influenza D. Influenza A and influenza B cause significant disease in humans. Reassortment of viral genes, such as those that code for HA and NA, serves as a major factor in the emergence of a new virus strain. Variations in proteins are due to error prone RNA dependent RNA polymerase activity [4].IV infection in humans is seasonal, pandemic and zoonotic. Seasonal influenza viruses circulate and cause disease in humans every year. A pandemic occurs when an IV that was not previously circulating among humans, and to which most people do not have immunity, emerges and transmits among humans. Zoonotic IVs routinely circulate in animals, such as avian influenza virus subtypes A(H5N1) and A(H9N2) and swine influenza virus subtypes A(H1N1) and (H3N2). Over the previous decades, there have been numerous examples of sporadic transmission of IV between animals and humans [5]. IV is thought to spread from person to person primarily through large-particle respiratory droplet transmission (when an infected person coughs or sneezes near a susceptible person) [6].Flu pandemics are unpredictable and frequent reoccurrences have costs on human health and economic well-being globally. Currently there are three families of IVs (IV A[H1N1], IV A[H3N2] and IV B) circulating in the human population in Africa, the Americas, Asia, Europe and Oceania. Among the three influenza strains, A(H1N1)pdm09 is the most frequently detected virus. The illness may be characterized by upper respiratory symptoms, specifically, common cold, high fever, sore throat, muscle pains, severe headache, coughing, bleeding from the nose, myalgia, weakness, diarrhea, abdominal pain, photophobia and general discomfort leading to life threatening complications and death [7]. Diagnostic tests include serological assays, RT-PCR, direct/indirect immunofluorescence assay, viral tissue culture, nucleic acid detection test and immunochromatography-based rapid diagnostic tests [8]. The currently available antiviral drugs for influenza are categorized into M2 ion channel inhibitors and neuraminidase inhibitor. But the available influenza vaccines have to be reformulated yearly because of occurrence of antigenic drift among viruses [9]. Complementary and alternative medicine (CAM), in alliance with conventional medicine, might be an effective preventive/therapeutic strategy against IV, considering no or low toxicity and side effects.CAM is a cluster of diverse medical and healthcare systems, practices and products that are not usually considered as a part of conventional medicine system. According to National Institute of Health – National Center for Complementary and Integrative Health (NIH-NCCIH), the use of CAM in the USA is approximately 38% in adults and 12% in children. In CAM the selection of treatment is based upon the theory of personalized symptoms [10]. The CAM mode of treatment for influenza includes Influenzinum, Oscilococcinum, herbal extracts and others. The essential goal of CAM today is, not only to treat the diseases but to address its underlying cause and individual susceptibility.Available vaccines & their limitationsProducing an influenza vaccine is very complex due to the continually evolving nature of the virus. It is important to constantly monitor and ensure continuous reformulation of available vaccines. It is essential to collect data on the epidemiology of the pandemic viruses and the local circulating seasonal viruses for the development of specific antivirals. For over five decades, WHO has been working in partnership with clinicians, scientists and policy makers globally, to move forward in influenza vaccine development and additionally to ensure their efficient use and distribution during an outbreak. Traditional influenza vaccines, termed as trivalent vaccines, are designed to protect against three IVs: influenza A (H1N1) virus, influenza A (H3N2) virus and an influenza B virus. In addition quadrivalent vaccines work against the same as the trivalent vaccine along with an additional influenza B virus [11]. Five licensed (US FDA approved) prescription influenza antiviral agents are available, which include: oral oseltamivir (Tamiflu®), inhaled zanamivir (Relenza®), intravenous peramivir (Rapivab®), amantadine and rimantadine. The antiviral drugs for influenza are categorized into two classes: the first category includes M2 ion channel inhibitors (amantadine and rimantadine) and second category includes neuraminidase inhibitor (oseltamivir, zanamivir and peramivir) [12–14]. These available antiviral drugs (neuraminidase inhibitor) reported side effects that include transient neuropsychiatric events [15], respiratory function deterioration along with nausea and vomiting.Resistance to influenza antiviral drugsThe M gene sequencing of two IVs, A(H1N1)pdm09 and A(H3N2), revealed that amino acid substitution S31N of the M2 protein confers resistance to the M2 inhibitors. Resistance to neuraminidase inhibitor in influenza A(H1N1)pdm09 viruses is due to the H275Y amino acid substitution in the NA protein. Influenza A(H3N2), which contains Q391K and K249E, neuraminidase amino acid substitutions also show resistance to neuraminidase inhibitors [16]. The single amino acid substitution at specific sites makes the available vaccine inappropriate for treatment.CAM as preventive medicine: an alternative approachVaccine production by current methods cannot be carried out with the speed required to halt the progress of a new strain of virus. Considering drug resistance, lack of specific vaccination and time required for vaccine development, it is worth considering the beneficial alternative medicines like CAM [17]. Treatment of diseases by use of CAMs is considered a competent approach for the setting up of universal healthcare. These medicines are characteristically prepared in ultra-low doses and high dilutions. Nosodes are biotherapeutic remedies that are made from the specific products of a particular disease. The nosode is characterized as medicines prepared in advance and according to traditional methods of dilution. One such nosode that might be used during IV outbreak is Influenzinum. Influenzinum is prepared in accordance with the standards of the homeopathic pharmacopoeia of the USA. One dosage of Influenzinum nosode includes three granules orally, once in every seventh day up to 28 days at the beginning of flu season and additional one dose is required 1 month later [18].In vitro studies of Influenzinum have shown its capability to induce cytokine production, such as TNF-α by the macrophage cell line (J774G8), the key cytokine regulating the innate immune response [19]. Studies have pointed out that the antiviral role of TNF-α during IV infection is mediated via expression of retinoic acid-inducible protein I (RIG-I), Toll-like receptor 3 (TLR3), MyD88, Toll/IL-1 receptor domain-containing adapter inducing IFN-β (TRIF) and interferon regulatory factor (IRF7) genes [20]. The activation of TNF-α activates various innate immune responses and provides protection against influenza. The potential of Influenzinum was also studied in a clinical survey conducted by the French society of homeopathy, over a 10-year period (1987–1998), concerning the use of Influenzinum in 453 patients for the prevention of the influenza. The results showed that in 90% of cases, there were no occurrences of the flu in all the age groups. It was additionally reported that Influenzinum showed protective role without any side effects in 97% cases [18]. Collectively it appears that Influenzinum may be a possible preventive agent against influenza. If the molecular mechanism of action of Influenzinum is understood, it will be an ideal choice during any influenza outbreak.Conclusion & future perspectiveDue to the rapid resistance of the IVs to presently available antiviral drugs and the emergence of various influenza strains as a consequence of reassortment, climatic changes and rapid globalization, there is a significant need for the proper healthcare system and the search of specific antiviral drugs. However, making progress with specific antiviral drugs is difficult because of the segmented nature of its genetic material which makes influenza virus highly mutagenic, causing frequent insertion of new antigenic strains into the community. Additionally, the development of new vaccines involves human resource, expensive equipment, special biosafety laboratories, clinical trials, manufacturing and marketing. During the progress of vaccine knowledge, influenza viruses may come up with a new strain, which may bring new challenges. Hence CAM mode of treatment may provide a substitute approach as a potential preventive and therapeutic strategy. Further research is mandatory in the alternative and preventive medicine direction.Financial & competing interests disclosureThe authors are grateful to the Vice Chancellor, King George's Medical University (KGMU), Lucknow and Director, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research (CSIR-CCMB), India for the encouragement and support for this work. SK Saxena is also supported by CCRH, Government of India, and US NIH grants: R37DA025576 and R01MH085259. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.Papers of special note have been highlighted as: • of interest; •• of considerable interestReferences1 Vemula SV, Zhao J, Liu J, Wang X, Biswas S, Hewlett I. Current approaches for diagnosis of influenza virus infections in humans. Viruses 8(4), 96 (2016).Crossref, Medline, Google Scholar2 WHO. www.who.int/influenza/surveillance_monitoring/updates/2016_06_27_surveillance_update_266.pdf Google Scholar3 TeVelthuis AJ, Fodor E. Influenza virus RNA polymerase: insights into the mechanisms of viral RNA synthesis. Nat. Rev. Microbiol. 14(8), 479–493 (2016).Crossref, Medline, CAS, Google Scholar4 Saxena SK, Mishra N, Saxena R, Saxena S. 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Rev. 1, CD002745 (2012).Medline, Google Scholar15 Anonymous. New concerns about oseltamivir. Lancet 369(9567), 1056 (2007).Crossref, Google Scholar16 WHO. www.who.int/influenza/vaccines/virus/recommendations/201602_recommendation.pdf •• Discusses about the resistance to available influenza antiviral drugs and recommendation compositions for influenza vaccines.Google Scholar17 Jonas WB. Do homeopathic nosodes protect against infection? An experimental test. Altern. Ther. Health Med. 5(5), 36–40 (1999). • Provides the evidence for partial protection of nosode.Medline, CAS, Google Scholar18 Coulamy A. Survey of the prescription habits of homeopathic doctors on the subject of a single medication: influenzinum. In: French Society of Homeopathy Conference Notes: The Prescription in Homeopathy. French Society of Homeopathy, Paris, France, 1–16 (1998). • Gives the details of Influenzinum clinical survey and dosage.Google Scholar19 Siqueira CM, Costa B, Amorim AM et al. H3N2 homeopathic influenza virus solution modifies cellular and biochemical aspects of MDCK and J774G8 cell lines. Homeopathy 102(1), 31–40 (2013). •• Discusses Influenzinum preparation and activation of innate immune responses.Crossref, Medline, Google Scholar20 Matikainen S, Sirén J, Tissari J et al. Tumor necrosis factor alpha enhances influenza A virus-induced expression of antiviral cytokines by activating RIG-I gene expression. J. Virol. 80(7), 3515–3522 (2006). • Discusses activation of various cytokines during influenza virus A infection.Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByCalcarea carbonica treatment rescues lipopolysaccharide-induced inflammatory response in human mononuclear cells via downregulation of inducible cyclooxygenase pathwayJournal of Integrative Medicine, Vol. 18, No. 5Complementary and Alternative Medicine Treatments of Water-Associated Infectious Diseases in Alliance with Conventional Medicine Treatments22 November 2019Introductory Chapter: Human Influenza A Virus Infection - Global Prevalence, Prevention, Therapeutics, and Challenges19 September 2018Complementary and alternative medicine in alliance with conventional medicine for dengue therapeutics and preventionShailendra K Saxena, Amrita Haikerwal, Srinivasulu Gadugu & Madan LB Bhatt18 August 2017 | Future Virology, Vol. 12, No. 8Vision for the prevention of infections using HomoeopathyIndian Journal of Research in Homoeopathy, Vol. 10, No. 4 Vol. 11, No. 10 Follow us on social media for the latest updates Metrics History Published online 6 September 2016 Published in print October 2016 Information© Future Medicine LtdKeywordsCAMinfluenza virusInfluenzinuminnate immunitytherapeuticsvaccinesFinancial & competing interests disclosureThe authors are grateful to the Vice Chancellor, King George's Medical University (KGMU), Lucknow and Director, Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research (CSIR-CCMB), India for the encouragement and support for this work. SK Saxena is also supported by CCRH, Government of India, and US NIH grants: R37DA025576 and R01MH085259. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download