Recent advances in Recent advances in H1N1H1N1

Dr. Vaibhav Yawalkar

What is Swine FluWhat is Swine Flu

Swine influenza virus (referred to as SIV) refers to influenza cases that are caused by Orthomyxovirus endemic to pig populations. SIV strains isolated to date have been classified either as Influenza(virus C or one of the various subtypes of the genus Influenza virus A)

Different Strains circulate Different Strains circulate PeriodicallyiPeriodicallyi

In the United States the H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages.

MAP of H1 N1 Swine FluMAP of H1 N1 Swine Flu

Swine Influenza (Flu)Swine Influenza (Flu)

Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza that regularly cause outbreaks of influenza among pigs. Swine flu viruses do not normally infect humans, however, human infections with swine flu do occur, and cases of human-to-human spread of swine flu viruses has been documented.

Pigs can harbour influenza viruses Pigs can harbour influenza viruses can be adapted to Humanscan be adapted to Humans

Swine Flu 2009Swine Flu 2009

In late March and early April 2009, cases of human infection with swine influenza A (H1N1) viruses were first reported in Southern California and near San Antonio, Texas. Other U.S. states have reported cases of swine flu infection in humans and cases have been reported internationally as well.

Swine flu in IndiaSwine flu in India

India reported its first case on 13th May, 2008. Most of the cases reported subsequently were travel related cases among those traveling to India from affected countries. Number of cases now being reported from Maharashtra (Mumbai and Pune), Karnataka (Bangalore) and Tamil Nadu (Chennai) are indigenous cases.

There have been 132 deaths and 708 cases of swine flu across the country during the current year. The worst hit state has been Rajasthan with 236 cases and 65 deaths, followed by Haryana.

Since 2009 there have been a reported 53,943 cases and 3,315 deaths due to the virus. 

Swine Flu and VirusSwine Flu and Virus

Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza virus that regularly causes outbreaks of influenza in pigs. Swine flu viruses cause high levels of illness and low death rates in pigs. Swine influenza viruses may circulate among swine throughout the year, but most outbreaks occur during the late fall and winter months similar to outbreaks in humans. The classical swine flu virus (an influenza type A H1N1 virus) was first isolated from a pig in 1930.

Cause by Reassortment of Cause by Reassortment of different strainsdifferent strainsLike all influenza

viruses, swine flu viruses change constantly. Pigs can be infected by avian influenza and human influenza viruses as well as swine influenza viruses. When influenza viruses from different species infect pigs, the viruses can reassort (i.e. swap genes) and new viruses that are a mix of swine, human and/or avian influenza viruses can emerge

Swine Flu differs from Human Swine Flu differs from Human FluFluThe H1N1 swine flu

viruses are antigenically very different from human H1N1 viruses and, therefore, vaccines for human seasonal flu would not provide protection from H1N1 swine flu viruses

Out breaks among PigsOut breaks among PigsOutbreaks among pigs

normally occur in colder weather months (late fall and winter) and sometimes with the introduction of new pigs into susceptible herds. Studies have shown that the swine flu H1N1 is common throughout pig populations worldwide, with 25 percent of animals showing antibody evidence of infection.

Present Swine Flu strainsPresent Swine Flu strainsAt this time, there are

four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1. However, most of the recently isolated influenza viruses from pigs have been H1N1 viruses.

How man is exposedHow man is exposedMost commonly, these

cases occur in persons with direct exposure to pigs (e.g. children near pigs at a fair or workers in the swine industry). In addition, there have been documented cases of one person spreading swine flu to others.

From 1 day before to 7 days after the onset of symptoms. If illness persist for more than 7 days, chances of communicability may persist till resolution of illness. Children may spread the virus for a longer period.

Communicability

Is the eating Pork infects ?Is the eating Pork infects ?No. Swine influenza

viruses are not transmitted by food. You can not get swine influenza from eating pork or pork products. Eating properly handled and cooked pork and pork products is safe. Cooking pork to an internal temperature of 160°F kills the swine flu virus as it does other bacteria and viruses

What are the signs and symptoms What are the signs and symptoms of swine flu in people?of swine flu in people?

FeverCoughSore throatBody achesHeadacheChillsFatigueDiarrheaVomiting.Lack of appetite

In children emergency warning signs that need urgent medical attention include:

Fast breathing or trouble breathing Bluish skin color.Not drinking enough fluids

Not waking up or not interacting Being so irritable that the child does not

want to be held Flu-like symptoms improve but then

return with fever and worse cough Fever with a rash

Childrens Need attention if Childrens Need attention if Present withPresent with

Adults Need attention if Adults Need attention if Present withPresent with

Difficulty breathing or shortness of breath Pain or pressure in the chest or abdomen Sudden dizziness Confusion Severe or persistent vomiting

Categorization of Influenza A Categorization of Influenza A H1N1 casesH1N1 cases

Category- A

Patients with mild fever plus cough / sore throatwith or without body ache, headache, diarrhoea and vomiting will be categorized as Category-A. They do not require Oseltamivir and should be treated for the symptoms mentioned above.

The patients should be monitored for their progress and reassessed at 24 to 48 hours by the doctor.

No testing of the patient for H1N1 is required. Patients should confine themselves at home and avoid

mixing up with public and high risk members in the family.

Category-B(i) In addition to all the signs and symptoms mentioned under Category-A, if the patient has high grade fever and severe sore throat, may require home isolation and Oseltamivir.(ii) In addition to all the signs and symptoms mentioned under Category-A, individuals having one or more of the following high risk conditions shall be treated with Oseltamivir: Children with mild illness but with predisposing risk factors. Pregnant women; Persons aged 65 years or older; Patients with lung diseases, heart disease, liver disease, kidney disease, blood disorders, diabetes, neurological disorders, cancer and HIV/AIDS; Patients on long term cortisone therapy. No tests for H1N1 is required for Category-B (i) and (ii). All patients of Category-B (i) and (ii) should confine themselves at home and avoid mixing with public and high risk members in the family

Category-C

In addition to the above signs and symptoms of Category-A and B, if the patient has one or more of the following:

Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discolouration of nails.

Children with influenza like illness who had a severe disease as manifested by the red flag signs (Somnolence, high and persistent fever, inability to feed well,convulsions, shortness of breath, difficulty in breathing, etc).

Worsening of underlying chronic conditions.

All these patients mentioned above in Category-C require testing, immediate hospitalization and treatment.

Complications:Complications:Clinicians should expect complications to be similar to seasonal influenza: Sinusitis,otitis media, croup, pneumonia,

bronchiolitis, status asthamaticus, myocarditis, pericarditis, myositis, rhabdomyolysis, encephalitis, seizures, toxic shock syndrome and secondary bacterial pneumonia with or without

sepsis. Individuals at extremes of age and with preexisting

medical conditions are at higher risk of complications and exacerbation of the underlying conditions.

Investigations:Investigations: Routine investigations required for evaluation and management

of a patient with symptoms as described above will be required. These may include haematological, biochemical, radiological and microbiological tests as necessary.

Confirmation of Pandemic influenza A(H1N1) infection is through: ” Real time RT PCR or ” Isolation of the virus in culture or ” Four-fold rise in virus specific neutralizing antibodies.

For confirmation of diagnosis, clinical specimens such as nasopharyngeal swab, throat swab, nasal swab, wash or aspirate, and tracheal aspirate (for intubated patients) are to be obtained.

The sample should be collected by a trained physician / microbiologist preferably before administration of the anti-viral drug. Keep specimens at 4°C in viral transport media until transported for testing. The samples should be transported to designated laboratories with in 24 hours.

If they cannot be transported then it needs to be stored at

-70°C. Paired blood samples at an interval of 14days for serological testing should also be collected.

The apex laboratories are:

National Institute of Communicable Diseases, 22, Sham Nath Marg, Delhi

National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune-411001

There is a network of 16 other laboratories that can test for Influenza A H1N1. This network is being expanded to include private laboratories.

An H1N1 detection kit developed by the Defence Research and Development Organisation (DRDO) that will give test reports in an hour and will come at a low cost will be available in the market soon. 

At present, the real time polymerase chain reaction kits approved by the WHO and recommended by the Centre for Disease Control (CDC) take 24 hours to get the result and the test costs Rs 4,500 for a patient. 

The kit was developed in the Defence R&D Establishment (DRDE) labs in Gwalior. The technology has been transferred to a private company, bigtec Labs', Bangalore.

Chest X-Ray Features:Chest X-Ray Features:

CDC helps in DiagnosisCDC helps in Diagnosis

Requires sending the specimen to CDC for laboratory testing as many laboratories in Developing world do not have facilities

Guidelines on Infection control Guidelines on Infection control MeasuresMeasuresDuring Pre Hospital Care o Standard precautions are to be followed while transporting patient to a

health-care facility. The patient should also wear a three layer surgical mask.

o Aerosol generating procedures should be avoided during transportation as far as possible.

o The personnel in the patient’s cabin of the ambulance should wear full complement of PPE including N95 masks, the driver should wear three layered surgical mask.o Once the patient is admitted to the hospital, the interior and exterior of the

ambulance and reusable patient care equipment needs to be sanitized using sodium hypochlorite / quaternary ammonium compounds.

o Recommended procedures for disposal of waste (including PPE used by personnel) generated in the ambulance while transporting the patient should be followed.

During Hospital Care

o The patient should be admitted directly to the isolation facility and continue to wear a three layer surgical mask. o The identified medical, nursing and paramedical personnel attending the suspect/ probable / confirmed case should wear full complement of PPE . If splashing with blood or other body fluids is anticipated, a water proof apron should be worn over the PPE. o Aerosol-generating procedures such as endotracheal intubation, nebulized medication administration, induction and aspiration of sputum or other respiratory secretions, airway suction, chest physiotherapy and positive pressure ventilation should be performed by the treating physician/ nurse wearing full complement of PPE with N95 respirator on. o Sample collection and packing should be done under full cover of PPE with N-95 respirator . o Perform hand hygiene before and after patient contact and following contact with contaminated items, whether or not gloves are worn.

o Until further evidence is available, infection control precautions should continue in an adult patient for 7 days after resolution of symptoms and 14 days after resolution of symptoms for children younger than 12 years because of longer period of viral shedding expected in children.

o The virus can survive in the environment for variable periods of time (hours to days). Survival period of virus outside the host varies with

temperature, at 40 C it survives for about 200 days and with temperature around 350 C it survives for 24 hours. Hence outbreaks occur during winter seasons.

o The virus is inactivated by a number of disinfectants such as 70% ethanol, 5% benzalkonium chloride (Lysol) and 10% sodium hypochlorite. Patient rooms/areas should be cleaned at least daily and finally after discharge of patient. In addition to daily cleaning of floors and other horizontal surfaces, special attention should be given to cleaning and disinfecting frequently touched surfaces.

Personal Protection Equipments Personal Protection Equipments (PPE)(PPE)PPE reduces the risk of infection if used correctly.It includes: • Gloves (nonsterile), • Mask (high-efficiency mask) / Three layered

surgical mask• Long-sleeved cuffed gown • Protective eyewear (goggles/visors/face shields)• Cap (may be used in high risk situations where

there may be increased aerosols), • Plastic apron if splashing of blood, body fluids,

excretions and secretions is anticipated.

Correct procedure for applying PPE in the following order:

1. Follow thorough hand wash 2. Wear the coverall. 3. Wear the goggles/ shoe cover/and head

cover in that order. 4. Wear face mask 5. Wear gloves The masks should be changed after every

six to eight hours.

Remove PPE in the following order:

• Remove gown (place in rubbish bin). • Remove gloves (peel from hand and discard into rubbish

bin). • Use alcohol-based hand-rub or wash hands with soap and

water. • Remove cap and face shield (place cap in bin and if

reusable place face shield in container for decontamination).

• Remove mask - by grasping elastic behind ears – do not touch front of mask

• Use alcohol-based hand-rub or wash hands with soap and water.

• Leave the room. • Once outside room use alcohol hand-rub again or wash

hands with soap and water.

Guidelines for waste DisposalGuidelines for waste Disposal

• All the waste has to be treated as infectious waste and decontaminated as per standard procedures

• Articles like swabs/gauges etc are to be discarded in the Yellow coloured autoclavable biosafety bags after use, the bags are to be autoclaved followed by incineration of the contents of the bag.

• Waste like used gloves, face masks and disposable syringes etc are to be discarded in Blue/White autoclavable biosafety bags which should be autocalaved/microwaved before disposal.

• All hospitals and laboratory personnel should follow the standard guidelines (Biomedical waste management and handling rules, 1998) for waste management.

Treatment:Treatment:The guiding principles are:

” Early implementation of infection control precautions to minimize nosocomical / household spread of disease

” Prompt treatment to prevent severe illness & death.

” Early identification and follow up of persons at risk.

Oseltamavir Medication:Oseltamavir Medication: Oseltamivir is the recommended drug both for prophylaxis and

treatment. In the current phase, if a person conforms to the case definition

of suspect case, then he would be provided Oseltamivir. for treatment is as follows: Dose By Weight: ‐ For weight <15kg 30 mg BD for 5 days ‐ 15-23kg 45 mg BD for 5 days ‐ 24-<40kg 60 mg BD for 5 days ‐ >40kg 75 mg BD for 5 days • For infants: ‐ < 3 months 12 mg BD for 5 days ‐ 3-5 months 20 mg BD for 5 days ‐ 6-11 months 25 mg BD for 5 days ‐ It is also available as syrup (12mg per ml )

Adverse Reactions of Oseltamavir:Adverse Reactions of Oseltamavir: Gastrointestinal side effects (transient nausea, vomiting) may increase with increasing

doses, particularly above 300 mg/day. Bronchitis, insomnia and vertigo. Less commonly angina, pseudo membranous colitis

and peritonsillar abscess have also been reported. Rare reports of anaphylaxis and skin rashes. In children, most frequentlyreported side effect is

vomiting. There is no recommendation for dose reduction in

patients with hepatic disease.

Important points to consider:Important points to consider: Patients with severe pneumonia and acute respiratory

failure (SpO2 < 90% and PaO2 <60 mmHg with oxygen therapy) must be supported with mechanical ventilation. Invasive mechanical ventilation is preferred choice.

If the laboratory reports are negative, the patient would be discharged after giving full course of oseltamivir. Even if the test results are negative, all cases with strong epidemiological criteria need to be followed up.

Immunomodulating drugs has not been found to be beneficial in treatment of ARDS or sepsis associated multi organ failure. High dose corticosteroids in particular have no evidence of benefit and there is potential for harm. Low dose corticosteroids (Hydrocortisone 200-400 mg/ day) may be useful in persisting septic shock (SBP < 90).

Discharge Policy:Discharge Policy: Patients who responded to treatment after two to three days

and become totally asymptomatic should be discharged after 5 days of treatment. There is no need for a repeat test.

Patients who continue to have symptoms of fever, sore throat etc. even on the 5th day should continue treatment for 5 more days. If the patient become asymptomatic during the course of treatment there is no need to test further.

For patients who continue to be symptomatic even after 10 days of treatment or those cases with respiratory distress and in whomsecondary infection is taken care of, and if patient continue to shed virus, then resistance of the patients to anti viral would be tested. The dose of anti viral may be adjusted on case to case basis.

Chemoprophylaxis:Chemoprophylaxis: Oseltamivir is the drug of choice. Prophylaxis should be provided till 10 days after last

exposure (maximum period of 6 weeks) By Weight: ‐ <15kg 30 mg OD ‐ 15-23kg 45 mg OD ‐ 24-<40kg 60 mg OD ‐ >40kg 75 mg OD For infants: ‐ < 3 months not recommended unless situation judged

critical due to limited data on use in this age group ‐ 3-5 months 20 mg OD ‐ 6-11 months 25 mg OD

Swine flu in Pregnancy:Swine flu in Pregnancy:Pregnant women are at greater risk from swine flu

because their immune system is suppressed during pregnancy.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has given a clear recommendation that the GlaxoSmithKline vaccine Pandemrix can be given safely to all pregnant women.

Zanamavir is recommended as a first choice.Zanamavir is inhaled using a disk-shaped inhaler. It

is recommended for pregnant women because it easily reaches the throat and lungs, where it is needed, and does not reach significant levels in the blood or placenta.

Is there a vaccine for Pandemic Flu?Is there a vaccine for Pandemic Flu?

Seasonal flu vaccine or past flu immunization will not provide protection.

‘‘Made in India’ H1N1 vaccineMade in India’ H1N1 vaccine

Swine flu vaccine in India was launched by Health minister Gulam Nabi Azad. Given by I/M or intranasal route. Vaccines manufactured by Zydus Cadila Serum institute of india Panacea biotech Bharat biotech

The flu vaccine is available by shot or nasal spray.

Sr. Type of H1N1 Vaccine

Manufacturer Date of Result

Cost Per Vial INR

1 Whole Virion Inactivated

Serum institute of India

18/1/2010 Not Decided

2 Human live attenuated and freeze dried

Serum institute of India(Nasovac)

17/12/2009 790

3 Whole virion inactivated

Zydus Cadila Health Care Ltd.(Vaxiflu S)

17/11/2009 3910

There are two different types of flu vaccines, trivalent and quadrivalent. Trivalent vaccines protect against 3 strains of the flu, A/H3N2, A/H1N1, and

influenza B. Trivalent vaccines are available in: Traditional flu shots, approved for anyone 6 months and older Intradermal shots, which use a shorter needle, approved for anyone 18-64 High dose shots approved for people over 65 Cell based shots created using viruses grown in animal cells and approved for

anyone over 18 Recombinant shots created using DNA technology, approved for people 18-49

with severe egg allergies Quadrivalent vaccines protect against 4 strains of the flu, A/H3N2, A/H1N1,

and 2 strains of influenza B. Quadrivalent vaccines are available in: Traditional flu shots, approved for anyone 6 months and older Nasal spray, approved for healthy people from 2-49, except pregnant women.

Side effects:Side effects: Mild side effects usually begin soon after you get the vaccine and last one to

two days. Possible mild side effects of the flu shot include: Soreness, redness, and swelling at the injection site Fainting, mainly in adolescents Headaches Fever NauseaPossible mild side effects of the nasal spray include: Runny nose Wheezing Headache Vomiting Muscle aches Fever

Serious side effects:Serious side effects: Serious side effects usually begin within a few minutes to a

few hours after receiving the shot. Possible serious side effects of vaccination include:

Difficulty breathingHoarsenessSwelling around the eyes or lipsHivesPalenessWeaknessRacing heartDizzinessBehavior changesHigh fever

Contraindications:Contraindications:A severe allergy to chicken eggsA history of severe reaction to a flu

vaccinationA moderate-to-severe illness with a fever

(you should wait until you are better to get the vaccine)

A history of Guillain Barre Syndrome (a severe paralytic illness, also called GBS)

IV Medication for swine flu:IV Medication for swine flu:Peramivir is an investigational neuraminidase

inhibitor medication that has variable activity against influenza A and B viruses as reported in human and animal studies with small sample sizes.

In October 2009, the FDA issued an Emergency Use Authorization (EUA) for the use of peramivir based on safety data from Phase 1, Phase 2, and limited Phase 3 trial data. The emergency use authorisation for peramivir expired in June 2010.