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**Chapter 7**

Provisional chapter

**Therapeutic Approach for Seasonal Influenza and**

DOI: 10.5772/intechopen.76473

Influenza infection is usually a self-limiting and suddenly life-threatening disease. Seasonal influenza causes severe clinical symptoms and almost subsides within 7 days in patients without severe illness, following no complications of pneumonia and encephalitis. Influenza A (H1N1) pdm09 brought the disaster including many deaths. We cannot make differential diagnosis between seasonal and pandemic influenza adequately in a pre-pandemic state. Seasonal influenza displaces suddenly pandemic, and we necessarily establish a standard treatment for influenza viral infection in routine work. If antiviral therapy would not be effective for patients with influenza viruses in an early period of illness, further investigations would be proceeded concerning three points: mutations of influenza viruses resistant to neuraminidase inhibitors (NAIs), concomitant diseases of patients, and a new pandemic virus. If the systemic procedure would be functioned, we are able to reduce individually burden of patients with severe clinical symptoms and leading complications and socially delay widespread of pandemic and plan for the

Keywords: antiviral therapy, seasonal epidemic, pandemic, streamline surveillance,

Influenza viruses spread seasonally and cause infection of the airway tract in humans following severe symptoms. Influenza viruses grow and multiply among in human, swine, and avian bodies. Influenza viruses escape human immunological protective system against influenza viruses by changing their epitope detected by human immune cells. Annual seasonal influenza epidemic often happened under no antiviral procedure by easy infection of influenza viruses.

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Therapeutic Approach for Seasonal Influenza and

Additional information is available at the end of the chapter

streamline management of pandemic documents.

the systemic procedure

1. Introduction

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76473

**Pandemic**

Pandemic

Yuji Takemoto

Abstract

Yuji Takemoto

#### **Therapeutic Approach for Seasonal Influenza and Pandemic** Therapeutic Approach for Seasonal Influenza and Pandemic

DOI: 10.5772/intechopen.76473

#### Yuji Takemoto Yuji Takemoto

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76473

#### Abstract

Influenza infection is usually a self-limiting and suddenly life-threatening disease. Seasonal influenza causes severe clinical symptoms and almost subsides within 7 days in patients without severe illness, following no complications of pneumonia and encephalitis. Influenza A (H1N1) pdm09 brought the disaster including many deaths. We cannot make differential diagnosis between seasonal and pandemic influenza adequately in a pre-pandemic state. Seasonal influenza displaces suddenly pandemic, and we necessarily establish a standard treatment for influenza viral infection in routine work. If antiviral therapy would not be effective for patients with influenza viruses in an early period of illness, further investigations would be proceeded concerning three points: mutations of influenza viruses resistant to neuraminidase inhibitors (NAIs), concomitant diseases of patients, and a new pandemic virus. If the systemic procedure would be functioned, we are able to reduce individually burden of patients with severe clinical symptoms and leading complications and socially delay widespread of pandemic and plan for the streamline management of pandemic documents.

Keywords: antiviral therapy, seasonal epidemic, pandemic, streamline surveillance, the systemic procedure

#### 1. Introduction

Influenza viruses spread seasonally and cause infection of the airway tract in humans following severe symptoms. Influenza viruses grow and multiply among in human, swine, and avian bodies. Influenza viruses escape human immunological protective system against influenza viruses by changing their epitope detected by human immune cells. Annual seasonal influenza epidemic often happened under no antiviral procedure by easy infection of influenza viruses.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Seasonal influenza viruses affect 10–20% of human population in epidemics each year [1] and worldwide, cause an estimated 3.5 million cases of severe illness and 250,000–500,000 death each year [2]. Although almost infected patients with seasonal influenza viruses recover from the disease in less than 2 weeks. On the other hand, some group of people containing young children, adults being elder than 65 years old and compromised hosts with severe illness had complications of influenza infection leading hospital admission [3]. Influenza viruses mutate and change the disease severity in host when transferring from avian to swine or from avian to human or from swine to human. A new mutant of influenza viruses is defined at the site of a mutation and called as influenza A (H5N1), A (H7N9), and A (H1N1) pdm09 each, causing severe affected people following many deaths [4]. Three influenza pandemics happened in the twentieth century: in 1918–1919, 1957, and 1968 and were called as Spanish flu, Asian flu, and Hong-Kong flu each and caused the severe disaster [4]. Especially Spanish flu brought estimated 20–50 million mortality [4]. We have the inability to predict and testify the appearance of dangerous influenza viruses to human health by the lack of rapid, affordable, highly sensitive, and specific diagnostic tests. The appearance of a new mutation of influenza viruses was noticed as unsuccessful treatment cases leading to life-threatening complications of influenza infection in the treatment of seasonal influenza [4]. The expansion of disaster by both the delayed use and little sharing of pre-pandemic information makes difficult in minimizing a widespread of a new mutant infection of influenza virus [4]. So it is necessary to establish a systemic procedure of diagnosis and treatment for patients with seasonal influenza and pandemic viruses in early phase of pandemic. In a first step of diagnosis of influenza virus infection, we can use rapid diagnostic kits for influenza A/B virus and we diagnose easily seasonal influenza infection in the outpatients. But rapid immune-chromatographic kits cannot show the mutation of influenza virus subtypes, we cannot make a differential diagnosis between seasonal and pandemic influenza virus by it [5]. A mutation of influenza virus subtypes is evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR) and direct sequence of a recognition site of influenza virus subtypes [5]. This method is expensive and time-consuming. We cannot apply this method to all outpatients with influenza virus. On the course of clinical treatment, we need to discriminate patients with suspicious pandemic influenza virus from the other patients with seasonal influenza effectively and economically. We would discuss the feasibility and execution of this trial in the following chapters.

influenza vaccine. Recently, WHO has been recommending QIV in 2013 and QIV has been adopted in several countries. QIV is estimated cost-effective and cost saving to reduce the burden of outpatient visit for influenza but 1.62 hospitalizations and 0.078 deaths per 100,000 individuals were estimated in Japan [9]. VE is often influenced by the timing between vaccination and influenza epidemic. Early epidemic occurs seasonally before administration of vaccine against seasonal influenza infection in people and VE is low. A mismatch of influenza viral strains between vaccination and epidemic makes VE low. It is very difficult to overcome influenza infection only by vaccination because of current VE and variability of influenza virus. We need the adequate diagnosis and treatment systematically after the procedure of

Therapeutic Approach for Seasonal Influenza and Pandemic

http://dx.doi.org/10.5772/intechopen.76473

135

Adoption of neuraminidase inhibitors (NAIs) for treating patients with influenza virus improves clinical incidences of outpatients leading hospitalization. Influenza infection is typical symptoms such as fever, headache, sore throat, cough, joints lasting, and sometimes diarrhea and nausea. On the first step of the treatment for influenza, concomitant use of antipyretic and mild analgesic drugs such as acetaminophen, are applied to the patients with influenza viruses as symptomatic treatment. It is very difficult to suppress widespread of influenza viruses without the isolation of patients within 1 or 2 weeks. On the next step of the treatment for influenza, amantadine and rimantadine were administered to patients with influenza A, and ribavirin was used to treat immunosuppressed patients with severe influenza conditions [10]. These are limited in operating only against influenza A viruses and adverse effect and resistance of virus to drugs lead to less use. On the use of these drugs, antiviral effectiveness for alleviation of severe symptoms of patients with seasonal influenza viruses was limited and not enough to suppress the widespread of those? On the third step of the treatment for influenza, NAIs are administered to the patients with influenza viruses. The NA protein is a homotetrameric glycoprotein with a stalk region and enzymatically active head. The NA active site cleaves sialic acid at the glycol-sialic bond on the host cell as well as in respiratory mucus, leading to spread of the virus [11–13]. NAIs act to inhibit the release of progeny viral particles from infected host cells and have more effectiveness and less adverse effects than amantadine and rimantadine when administered to patients with influenza viral infection [14]. Administration of NAIs to patients is recommended within 48 h from the onset of infection [14]. NAIs alleviate symptoms and shorten its duration bothered from typical symptoms of influenza, especially high fever and headache without using antipyretic agents. Four NAIs, namely oseltamivir, zanamivir, laninavir, and peramivir are available in various countries and three measures of administration, namely oral intake, inhalation, and infusion to vein are used [14]. Zanamivir was the first NAI to be developed and was licensed in 1999. Its feature is poor absorption and an inhaled agent and is available in an intravenous form for compassionate use [15]. Oseltamivir is a prodrug being developed on the basis of the structure

adequate vaccination.

3.1. Antiviral therapy

3. Therapy for patients with influenza viruses

#### 2. Prevention

It is not too enough to exaggerate that prevention is the most effective therapy for infectious disease. It is desirable to establish universal most effective vaccine against influenza virus. Vaccine effectiveness (VE) is influenced by viral subtype/lineage as well as the timing of vaccination (early or late epidemic in a season). VE of trivalent influenza vaccine (TIV) is assessed as from 20 to 50% in vaccine programs of several countries [6, 7]. The population rate of people was over 80% in the Korean national immunization program but VE remains low in the elderly adults [8]. They addressed the improvement of influenza vaccine including the adoption of quadrivalent influenza vaccine (QIV), adjuvanted influenza vaccine, and high-dose influenza vaccine. Recently, WHO has been recommending QIV in 2013 and QIV has been adopted in several countries. QIV is estimated cost-effective and cost saving to reduce the burden of outpatient visit for influenza but 1.62 hospitalizations and 0.078 deaths per 100,000 individuals were estimated in Japan [9]. VE is often influenced by the timing between vaccination and influenza epidemic. Early epidemic occurs seasonally before administration of vaccine against seasonal influenza infection in people and VE is low. A mismatch of influenza viral strains between vaccination and epidemic makes VE low. It is very difficult to overcome influenza infection only by vaccination because of current VE and variability of influenza virus. We need the adequate diagnosis and treatment systematically after the procedure of adequate vaccination.
