INTRODUCTION:

Swine flu is causing a massive havoc among the common people of India and has created fear across they various strata of the society. In April 2009, a new strain of influenza virus- A/H1N1, commonly referred to as "Swine to human led the World Health Organization to quickly raise the risk level to Phase6, indicating that a full global pandemic was under way. The outbreak of human infection due to the novel swine-origin influenza A (H1N1) virus began in Mexico in March 2009. Because clinical symptoms of infection with the novel influenza virus do not differ from those of seasonal human influenza, there is a continued need for sub typing and laboratory confirmation^[1].

According to WHO estimates, 1/3rd of the world’s population will be affected with H1N1flu within two years and India is no exception. It ranked 3rd most affected country for cases and deaths of swine flu globally. The no. of cases in various countries in subsequent three years has well established the reason why it is being considered as a major threat in emerging disease in global scenario. In context to India, the highest number was reported in 2009 (27,236), followed by 2010 (20,604) and 2012 (5,054 cases).

The highest number of swine flu deaths took place in 2011(1,763), followed by 2009 (981) and 2012 (405). The recommendations include using tissues when sneezing, washing hands regularly with soap and water and setting up a network of “flu friends” to provide mutual assistance should someone become ill^[2]. Sheer volume of cases could easily overstretch already fragile and Overburdened health services, especially in the developing countries, and cause considerable in human populations around the world^[3].Swine flu has killed 261 people in India in the first 3 months of 2013, with most deaths reported from Rajasthan and Gujarat. A total of 2,329 people tested positive for the Influenza A (H1N1) virus, which causes Swine flu, in 35states and union territories. The most common cause of death from the virus is respiratory failure, but other causes of mortality include sepsis, dehydration and electrolyte imbalance^[4]. In a northern state of India, Punjab, total no. of confirmed cases was 182 and 42 deaths. In the Patiala district where this study has been done, 17confirmed cases were found with 7 deaths. This death sinitiated chain of media reports and local physician’s articles on measures to prevent Swine flu being published in the newspaper dailies. All hospitalized patients with novel influenza A (H1N1) infection should be monitored carefully and treated with antiviral therapy, including patients who seek care >48 h after the onset of illness^[5]. At the same time Swine Flu cases in the National Capital Region also led to Swine Flu coverage in maj or news channels. When levels of worry are generally low, acting to increase the volume of mass media and advertising coverage is likely to increase the perceived efficacy of recommended behaviors, which, in turn, is likely to increase their uptake.Trust in government/mediation formation was more strongly associated with greater self efficacy and hand washing; whereas trust in formalin formation was strongly associated with perceived health threat and avoidance behavior.

The Government has been successful in providing information to people on swine flu. Even television channels have played a major role in educating people by inviting doctors and experts in their studios every day to provide information about the deadly virus," Information &Broadcasting minister, Govt. of India said ^[6]. The best we citizens can do is to keep ourselves informed about the happenings and the steps we can take to prevent the spread of the flu^[7]. Prevention is the most appropriate measure to control H1N1 flu pandemic and awareness of H1N1 flu is ranked very high in preventive measures. The distribution of proper information to the public on the status of them H1N1.Virus pandemic will be important to achieve awareness of the potential risks and the optimum code of behavior during the pandemic. District Health authorities in Patiala has distributed 2500 pamphlets and installed flex banners at Community health centers in the district as IEC activities. State health department has published mass media messages in daily newspapers through State nodal officer during Jan –March 2013 (as per information from District Civil Surgeon office).

History:

Swine influenza was first proposed to be a disease related to human influenza during the 1918 flu pandemic, when pigs became sick at the same time as humans. The first identification of an influenza virus as a cause of disease in pigs occurred about ten years later, in 1930.4 For the following 60 years, swine influenza strains were almost exclusively H1N1. Then, between 1997 and 2002, new strains of three different subtypes and five different genotypes emerged as causes of influenza among pigs in North America. In 1997-1998, H3N2 strains emerged^[8,9]. These strains, which include genes derived by re assortment from human, swine and avian viruses, have become a major cause of swine H1N2. In 1999 in Canada, a strain of H4N6 crossed the species barrier from influenza in North America. Reassortment between H1N1 and H3N2 produced birds to pigs, but was contained on a single farm. The H1N1 form of swine flu is one of the descendants of the strain that caused the 1918 flu pandemic. 5-6 As well as persisting in pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century, contributing to the normal seasonal epidemics of influenza. However, direct transmission from pigs to humans is rare, with only 12 cases in the U.S. since 2005.7 The H1N1 viral strain implicated in the 2009 flu pandemic among humans often is called "swine flu" because initial testing showed many of the genes in the virus were similar to influenza viruses normally occurring in North American swine.8 But further research has shown that the outbreak is due to a new strain of H1N1 not previously reported in pigs. In late April, Margaret Chan, the World Health Organization's director-general, declared a "public health emergency of international concern" under the rules of the WHO's new International Health Regulations when the first cases of the H1N1 virus were reported in the United States. 9-10 Following the outbreak, on May 2, 2009, it was reported in pigs at a farm in Alberta, Canada, with a link to the outbreak in Mexico. The pigs are suspected to have caught this new strain of virus from a farm worker who recently returned from Mexico, then showed symptoms of an influenza-like illness. These are probable cases, pending confirmation by laboratory testing.

The new strain was initially described as an apparent reassortment of at least four strains of influenza A virus subtype H1N1, including one strain endemic in humans, one endemic in birds, and two endemic in swine. Subsequent analysis suggested it was a reassortment of just two strains, both found in swine.12 Although initial reports identified the new strain as swine influenza (i.e. zoonosis originating in swine), its origin is unknown. Several countries took precautionary measures to reduce the chances for a global pandemic of the disease13. The Swine flu has been compared to other similar types of influenza virus in terms of mortality: "in the US it appears that for every 1000 people who get infected, about 40 people need admission to hospital and about one person dies. There are fears that swine flu will become a major global pandemic in the winter months, with many countries planning major vaccination campaigns^[10].

PATHOPHISIOLOGY:

Influenza (the “flu”) is a seasonal respiratory illness caused by flu viruses. The viruses can cause mild to severe illness sometimes resulting in death. It is important to note that the flu is different from a common cold or seasonal allergies. Generally, the onset of the flu is sudden and symptoms include fever (usually high), headache, chills, sore throat, runny or stuffy nose, dry cough, severe exhaustion, muscle aches and stomach symptoms, such as nausea, vomiting and diarrhea. The flu season typically starts in late November and lasts through early spring. The flu affects about 30-50 million Americans each year. The flu differs from the common cold in that it lasts longer (about two weeks) and can be temporarily debilitating even in healthy individuals. There are three types of Influenza viruses – A, B, and C. Influenza A is further categorized into subtypes based on the type of two surface proteins – he agglutinin (H)and neuraminidase.

Fig no 1. Influenza virus

About Influenza Epidemic and Pandemic:

Epidemic refers to the onset of a disease that occurs in an unusually high number of individuals in a community at the same time and is clearly in excess of normal expectancy in a defined community, geographical area or season. The U.S. Centers for Disease Control (CDC) says “that to epidemiologists the terms ‘epidemic’ and ‘outbreak’ basically mean the same thing. “Pandemic refers to a widespread, usually global spread of a disease, while an epidemic is localized to geographic region. According to the World Health Organization, “an influenza pandemic occurs when anew influenza virus appears against which the human population has no immunity, resulting in epidemics worldwide with enormous numbers of deaths and illness. “The World Health Organization (WHO) is coordinating the global response to human cases of swine influenza A (H1N1) and monitoring the corresponding threat of an influenza pandemic.

WHO revised the phase descriptions in 2009 and has retained the use of six phases in regards to pandemics to allow for the incorporation of new recommendations and approaches into existing national preparedness and response plans. Currently the pandemic threat is at Phase 5, which means that a pandemic is imminent. One way for a new pandemic flu strain to arise is through the mixing of different types of influenza A viruses. For instance, the influenza viruses that caused the Avian Flu and the Hong Kong Flu pandemics are believed to have come from the mixing of human influenza and avian (bird) influenza viruses in another animal such as a pig. The new strain was then able to cause a much more severe illness in humans. The Spanish Flu pandemic, on the other hand, is thought to have started from an avian flu that directly infected humans; the mixing of the avian influenza with the human influenza within a human led to the new deadly strain of influenza a virus. The current influenza outbreak of swine flu is a result of an influenza virus species that infected pigs, then reassert (swap genes) and the new virus emerging. Currently there are four main influenza types a virus subtypes, but the most recent influenza virus from pigs causing the outbreak have been H1N1 viruses. This new virus that has emerged is a mixture of swine, human and avian influenza viruses. During the 20th century, new strains of Influenza A viruses resulted in three influenza pandemics:

Spanish Flu (1918-1919):

Influenza H1N1 caused an estimated 20-50 million deaths worldwide and accounted for 675,000 deaths in the United States. The most striking characteristics of the1918 pandemic were the unusually high death rate among the otherwise healthy age group of 15-34 year olds. Healthy people, as well as those in frail condition, were equally affected, and many died within the first few days after infection.

Asian Flu (1957-58):

Influenza H2N2 started in China in February 1957; by June 1957 it spread to United States, causing 70,000 deaths. The initial outbreak occurred during the summer of1957 and again during January/February 1958. This is an example of a second wave of infections that can develop during a pandemic.

Hong Kong Flu (1968-1969):

Influenza H3N2 started in Hong Kong in early 1968. Later in the year, it spread to the United States and caused 34,000 deaths. The Hong Kong Flu was the mildest pandemic of the 20th century. The U.S. Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada (PHAC) and the World Health Organization (WHO) have a large surveillance system for detecting possible pandemic flu strains around the world. The CDC has activated its emergency operations center to coordinate the agency’s emergency response. The goals of the CDC are to reduce transmission and illness severity, and to provide information to health care providers, public health officials and the public to address the current outbreak of the swine influenza virus. WHO is coordinating the global response to the influenza A virus can mutate in two different ways; antigenic drift, in which existing antigens are subtly altered, and antigenic shift, in which two or more strains combine. Antigenic drift causes slight flu mutations year on year, from which humans have partial, but not complete, immunity. By contrast, the new strain of H1N1 appears to have originated via antigenic shift in Mexican pigs human cases of swine influenza A and is also monitoring the corresponding threat of a pandemic. PHAC is currently working with federal, provincial and international governments to address the swine influenza outbreak.

Tests for Influenza (Diagnosis):

The most common method for diagnosing influenza is the Rapid flu Test. Depending on the type of test used, it can identify influenza A and B. Proper sample collection is critical for testing. Because the tests rely on detecting the virus shed in there aspiratory secretions of the infected person, the test must be done during the first few days of illness when there is viral shedding. The best sample is a nasal aspirate, but nasopharyngeal swabs are most frequently used. With the patient's head tilted back, a Dacron swab (like a very long Q-tip) is inserted into a nostril until there’s resistance (1-2 inches) and then rotated several times. The major advantages of the Rapid Flu Test are that it can be done in an outpatient setting and the results return within 30 minutes to two hours. The major disadvantages are that true influenza cases will be missed up to 30 percent of the time (false negative result) and some without influenza will be misdiagnosed as having influenza (false positive result).The gold standard for diagnosing influenza is a viral culture. The virus from the nasal secretion is grown and identified in the laboratory. The advantage of a viral culture is that the specific viral strain and type can be identified. Such detailed information is critical in detecting influenza outbreaks (including surveillance for the pandemic strain) and for developing vaccines. The major disadvantages are that there sults take about three to ten days and not all labs are equipped to perform a viral culture. In response to the current outbreak of swine influenza, the U.S. Food and Drug Administration (FDA) have issued Emergency Use Authorizations (EUAs) at the request of the CDC.

The FDA will make available to public health and medical personnel important diagnostic and therapeutic tools to identify and respond to the swine flu virus under certain circumstances. The EUAs are for the use with certain Relenza and Tami flu antiviral products and for the rR T-PCR Swine Flu Panel diagnostic test. In authorizing an EUA for the rRT-PCR Swine Flu Panel diagnostic test, the FDA has determined that it may be effective in testing samples from individuals diagnosed with influenza A infections and whose virus subtypes cannot be identified by test that are currently available. This EUA will allow the CDC to distribute the swine flu test to public health and other qualified laboratories that have personnel and equipment trained to perform and interpret the results,

Transmission:

Influenza is spread from person-to-person by contact with respiratory secretions from an infected person. When an infected person coughs or sneezes, the viruses are carried in large droplets which settle on the surfaces of the upper respiratory tracts of persons who are nearby (i.e. within three feet of the infected person). The viruses can also spread by direct or indirect contact with respiratory secretions-touching contaminated surfaces and then touching the eyes, nose or mouth. Influenza is more infectious than SARS. Infected adults can spread the virus from the day before exhibiting symptoms to five days after symptoms start (two days on average); whereas, the transmission timeline for SARS is six to eight days. Infected children can spread the virus for 10 days or longer. Due to the highly contagious nature of influenza virus, first responders who may be exposed to or are taking care of persons suspected of influenza should wear appropriate protection (discussed later in this article). The swine influenza A (H1N1) virus is likely to be transmitted in the same manner as the seasonal flu spreads.

The main transmission of flu viruses from person to person is through coughing or sneezing. Transmission can also occur by touching something with flu viruses on it and then touching the mouth or nose. Persons with swine flu should be considered potentially contagious as long as they are symptomatic and possibly for up to seven days following illness onset. Children, especially younger children, can potentially be contagious for a longer period. People infected with the swine flu may be able to infect others on day one before symptoms develop and up to seven or more days after becoming sick. This means that you may be able to pass on the flu to someone else before you know you are sick. Viruses and bacteria can live up to two hours or longer on surfaces such as cafeteria tables, doorknobs and desks. Washing hands frequently will help reduce the chance of getting contamination from common surfaces One concern with this recent strain of swine influenza A (H1N1) virus is that there is a real threat to persons with seemingly healthy immune systems. The danger is that healthy people have no defenses built up to this influenza virus and causing a healthy immune system to overreact and attack the body’s healthy organs and systems – this makes a healthy 15-60 year old individual more likely to succumb to this new virus^[11].

Fig no 2. Influenza (Diagnosis)

Signs and symptoms:

In swine.

In pigs influenza infection produces fever, lethargy, sneezing, coughing, difficulty breathing and decreased appetite. In some cases the infection can cause abortion. Although mortality is usually low (around 1-4present;)the virus can produce weight loss and poor growth, causing economic loss to farmers. Infected pigs can lose up to 12 pounds of body weight over a 3 to 4 week period.

In humans:

Main symptoms of swine flu in humans:

Direct transmission of a swine flu virus from pigs to humans is occasionally possible (called zoonotic swine flu). In all, 50 cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection may be higher, since most cases only cause a very mild disease, and will probably never be reported or diagnosed. According to the Centre’s for Disease Control and Prevention (CDC), in humans the symptoms of the 2009 "swine flu" H1N1 virus are similar to those of influenza and of influenza-like illness in general. Symptoms include fever, cough, sore throat, body aches, headache, chills and fatigue. The 2009 outbreak has shown an increased percentage of patients reporting diarrhea and vomiting. The 2009 H1N1 virus is not zoonotic swine flu, as it is not transmitted from pigs to humans, but from person to person.

Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms but also a high likelihood of swine flu due to the person's recent history. For example, during the 2009 swine flu outbreak in the United States, CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the 7 days preceding their illness onset. “A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab). The most common cause of death is respiratory failure, other causes of death are pneumonia (leading to sepsis), high fever (leading to neurological problems), dehydration (from excessive vomiting and diarrhea) and electrolyte imbalance.

Fig no 3.Symptoms of swine influenzas

Diagnosis

Swine flu is diagnosed by following five steps:

Step1: The first symptoms of swine flu include coughing, lack of appetite and lethargy. Fever over 100 degrees Fahrenheit is typical.

Step2: Watch for the advanced signs of Swine Flu. As the infection advances, some people will experience sore throat, body aches, runny nose, vomiting, nausea and diarrhea. Apart from the above symptoms caution should be taken in children showing the following symptoms.

· Flu symptoms appear to get better but then return with worse cough and fever

· Bluish colour of the skin

· Troubled, Fast Breathing

· Does not want to drink fluids

· Fever and a rash

· refusing to be held because of irritability

· Difficulty waking up or little interaction.

Urgent medical attention is required for adults who show signs of Symptoms listed in Steps 1, 2 and any of the following:

(a) Sudden confusion or dizziness.

(b) Shortness of breath or difficult breathing.

(d) Pressure or pain the abdomen or chest

Step3: Call your Doctor. If you are experiencing many of the symptoms listed in Steps 1 and 2, contact your doctor to discuss if influenza treatment or testing is recommended.

Step4: Final Diagnosis by a Doctor. Only a Doctor can diagnose swine flu by running tests. There are two tests that are conducted to aid in the confirmation of a diagnosis. Both tests require a sample of secretions from the nose and mouth (known as a nose and throat swab) and must be tested in the first 24-72 hours after the first symptoms appear.

Prevention:

Prevention of transmission from pig to human:

Swine can be infected by both avian and human influenza strains of influenza, and therefore are hosts where the antigenic shifts can occur that create new influenza strains .The transmission from swine to human is believed to occur mainly in swine farms where farmers are in close contact with live pigs. Although strains of swine influenza are usually not able to infect humans this may occasionally happen, so farmers and veterinarians are encouraged to use a face mask when dealing with infected animals. The use of vaccines on swine to prevent their infection is a major method of limiting swine to human transmission. Risk factors that may contribute to swine-to-human transmission include smoking and not wearing gloves when working with sick animals.

Prevention of transmission form human to human:

Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The swine flu in humans is most contagious during the first five days of the illness although some people, most commonly children, can remain contagious for up to ten days. Diagnosis can be made by sending a specimen; collected during the first five days for analysis. Recommendations to prevent spread of the virus among humans include using standard infection control against influenza. This includes frequent washing of hands with soap and water or with alcohol-based and sanitizers, especially after being out in public. Chance of transmission is also reduced by disinfecting household surfaces, which can be done effectively with a diluted chlorine bleach solution. Experts agree that hand-washing can help prevent viral infections, including ordinary influenza and the swine flu virus. Also avoiding touching eyes, nose and mouth with hands prevents flu.

Influenza can spread in coughs or sneezes, but an increasing body of evidence shows small droplets containing the virus can linger on table tops, telephones and other surfaces and be transferred via the fingers to the mouth, nose or eyes. Alcohol-based gel or foam hand sanitizers work well to destroy viruses and bacteria. Anyone with flu-like symptoms such as a sudden fever, cough or muscle aches should stay away from work or public transportation and should contact a doctor for advice.

Vaccination:

Fig no 4. H1N1 Flu Vaccine

Vaccines are available for different kinds of Swine Flu. Avoid close contact that is, being within 6 feet with people who have flu like symptoms. Minimize touching your mouth, nose, or eyes. Since this is not easy, keep those hands clean. If you have flu like symptoms fever plus at least cough or sore throat or other flu symptoms stay home for seven days after symptoms begin or until you've been symptom-free for 24 hours whichever is longer. Wear an N95 respirator if helping a sick person with a nebulizer, inhaler, or other respiratory treatment. Since there is no definitive proof that a face mask prevents flu transmission, do not rely solely on a face mask to prevent infection. People who have or are suspected of having swine flu should wear a face mask, if available and tolerable, when sharing common spaces with other household members, when outside the home, or when near children or infants. Breastfeeding mothers with swine flu symptoms should express their breast milk, and the child should be fed by someone else.

Dosage recommendations:

Children Age Nine and Under:

Currently available data suggest that children six months to nine years of age have little or no evidence of protective antibodies to the H1N1 2009 virus1. Based on these data, children nine years of age and younger should be administered two doses of the monovalent pandemic (H1N1) 2009 virus vaccine.

Adults and Children 10 Years of Age and Older:

Adults should be administered one dose, as should children and adolescents 10 years of age and older, as they are expected to respond similarly to adults. Clinical studies are underway and will provide additional information about the optimal number of doses.

1. TAMIFLU^®(Oseltamivir phosphate)

Fig no 5. TAMIFLU Capsule

30-mg capsules (30 mg free base equivalent of the phosphate salt): light yellow hard gelatin capsules. "ROCHE" is printed in blue ink on the light yellow body and "30 mg" is printed in blue ink on the light yellow cap. Available in blister packages of 10 (NDC 0004-0802-85).

Mechanism of Action:

Oseltamivir phosphate is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. Oseltamivir carboxylate is an inhibitor of influenza virus neuraminidase affecting release of viral particles.

2. RELENZA (Zanamivir) dry powder for inhalation:

Zanamivir is indicated for treatment of influenza in adults and children (>5 years). The recommended dose for treatment of adults and children from the age of 5 years (based on data from studies in typical uncomplicated influenza) is two inhalations (2 x 5mg) twice daily for 5 days.

Fig no 6. RELENZA (Zanamivir) dry powder for inhalation

Drug-Drug Interactions:

Zanamivir is less than 15% protein bound. There is no evidence of hepatic metabolism, and zanamivir is not a substrate nor does it affect cytochrome P450 (CYP) isoenzymes (CYP1A1/2, 2A6, 2C9, 2C18, 2D6, 2E1, and 3A4) in human liver microsomes. Therefore, based on data from in vitro studies, clinically significant drug interactions are unlikely. RELENZA® (zanamivir), when given for 28 days (10 mg once daily), did not impair the immune response to the influenza vaccine.

Drug-Food Interactions:

Interactions with food have not been established.

Drug-Herb Interactions:

Interactions with herbal products have not been established.

CONCLUSION:

H1N1 influenza or swine flu is a contagious disease that is caused by the influenza virus. Infection with the H1N1 influenza virus can result in severe illness and life- threatening complications. Symptoms of H1N1 flu are similar to those of the common flu and scientists are actively studying the situation to better understand its range of symptoms and how it is spread. For healthy people, resting and drinking plenty of fluids usually allows infected people to recover from the flu. For people at high risk of developing flu complications, medications and hospitalization may be needed. The flu can be prevented by avoiding close contact with sick people and by washing your hands frequently.

ACKNOWLEDGEMENT:

Authors are highly Acknowledge the help of teaching staff of Rajarambapu College of Pharmacy, Kasegaon. For providing necessary information required for research work. Also we are highly Acknowledge the help and guidance of Dr M. M. Nitalikar.

REFERENCE:

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5. Centers for Disease Control and Prevention (CDC). Hospitalized patients with novel influenza A (H1N1) virus infection - California, April-May, 2009. MMWR Morb Mortal Wkly Rep. 2009; 58:536–41.

6. http://www.reuters.com/article/latestCrisis/idUSN26488473.

7. http://www.nytimes.com/2009/04/29/world/asia/29swine.html.

8. http://www.reuters.com/article/latestCrisis/idUSN26488473.

9. http://www.nytimes.com/2009/04/29/world/asia/29swine.html.

10. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0430a2.htm.

11. Knobler S., Mack A., Mahmoud A. and Lemon S. (2005). The Threat of Pandemic Influenza: Are We Ready, Washington, D.C., The National Academies Press.

Received on 31.12.2018 Accepted on 31.01.2019

Asian J. Pharm. Ana. 2019; 9(1):30-36.

DOI: 10.5958/2231-5675.2019.00008.5