What is it?

What can I do?

An Indian perspective! Dr. T.R.Chandrashekar

Director critical care

Dr. N.K. RAGHURAM

Fellow in CCM

K.R HOSPITAL

Bengaluru, India

What do we do?• We have recorded 24 deaths • We have no Medical guidelines of do’s and

don'ts• Young people are dying-is their a pattern • Can we pick them early before they turn sick?• Testing in few center’s-takes 4 days to get

results• Do we start Tamiflu in all suspected cases?• Deterioration is occurring on 4th day and death

on 7th or 8th day• Where do we stand?

CHALLENGES WE FACE

• Recognition of disease

• Not to forget chikungunya & dengue

• Difficulty in Confirmation of disease

• Self protection

• Protection of people around us

• Notification

• To know more ; Are we facing the pandemic?

Scenario

• Admitted suspected Patient (symptoms+ travel history)

• Sample sent for PCR• Reported positive

H1N1• What to do for patient

relatives& hosp staff

who are exposed

Patient with hemodynamic compromise & respiratory difficulty

Need for intubation-To proceed & then send sample for PCR

What to do meanwhile

Is it necessary to test all doctors & staff

Enigmatic questions

• Should we close the hospital & fumigate?

• What to do for other patients next to the case

• Should we send all suspected cases to referral hospital

Subsequent challenges• Recognising in OPD- identify flu symptoms,

travel history, clinical signs of hemodynamic derangement &pneumonia/ALI/ARDS

• Proper referral to institutions handling cases

• Isolation rooms, Use of masks Hand wash

• Ventilatory management

Influenza At A Glance

• Influenza, commonly called "the flu," is caused by viruses that infect the respiratory tract.

• Influenza viruses are divided into three types, designated A, B, and C.

INFLUENZA VIRUS

ELECTRON MICROSCOPY

TYPES

PIG THE CREATOR

VIRAL VARIANTS

• INFLUENZA A VIRUS

• Swine Human Avian

•

• H1N2 H1N1(pandemics) H5N1

• H3N1 H3N2 (rare)

• H3N2

QUADRUPLE REASSORTMENT GENETICS • Human swine

• Avian swine

H1N1

EARTH LIVING SPACE FOR ALL

Epidemic: An increase in disease above what is normally expected

Pandemic: A worldwide epidemic

A pandemic begins when: there is person-to-person sustained transmission on multiple continents

HISTORY

• In the 20th century there have been three influenza pandemics in 1918, 1957 and 1968.

Emergency hospital, Camp Funston, Kansas 1918

WHO• April 24: H1N1 first disease outbreak notice.

• April 25: WHO Director General declares a formal “Public health emergency of international concern”

• April 27: “containment of the outbreak is not feasible” pandemic alert raised from phase 3 to phase 4.

• April 29: phase 4 to phase 5.

• June 11: phase 5 to phase 6.

• The World Health Organization uses a six stage phase for alerting the general public to an outbreak

• Phase 1 – animal to animal transmission.

• Phase 2 – an animal influenza virus is capable of human infection.

• Phase 3 - small outbreaks among close populations but not through human to

human contact.

• Phase 4 - Human to human transmission

• Phase 5 - spread across two countries or more in one of the WHO regions (continents).

• Phase 6 – spread across two countries or more in one of the WHO regions plus spread to another WHO region.

Global pandemic

• W.H.O. identifies the following six epidemiological sub-regions.

• - African Region

• - Eastern Mediterranean Region

• - European Region

• - Region of the Americas

• - South-East Asian Region

• - Western Pacific Region

Global pandemic

EPIDEMIOLOGY• Incubation period- 1-7 days

• Transmission

PRIMARY CASE –direct contact with pigs

SECONDARY CASES

sneezing, coughing

resp droplets

body fluids(diarroeal stool) contact surfaces

Transmission

• This virus is not transmitted from eating pork or pork products

• Contagiousness:

1 day onset of symptoms

7 days

Children are contagious for longer periods.

. Majority of pts were previously healthy.

Clinical course mild in PCR negative influenza.

• Majority of pts were previously healthy.

• Clinical course mild in PCR negative influenza.

• Pregnant women — Increased rates of spontaneous abortion and preterm birth

• Patients with swine flu were found to have increased incidence of cardiovascular & cerebrovascular events.

Can I get infected with this new H1N1 virus from eating or preparing pork?

• No. H1N1 viruses are not spread by food. You cannot get this new HIN1 virus from eating pork or pork products. Eating properly handled and cooked pork products is safe.

Is there a risk from drinking water?

• Recent studies have demonstrated that free chlorine levels typically used in drinking water treatment are adequate to inactivate highly pathogenic H5N1 avian influenza. It is likely that other influenza viruses such as novel H1N1 would also be similarly inactivated by chlorination.

What kills influenza virus?

• Influenza virus is destroyed by heat (167-212°F [75-100°C]). In addition, several chemical germicides, including chlorine, hydrogen peroxide, detergents (soap), iodophors (iodine-based antiseptics), and alcohols

Risk factors

• COPD

• Immunocompromised state

• DM

• Pregnancy

• Cardiac disease

• Obesity

DEFINITIONS

• Influenza-like illness (ILI) is defined as fever (temperature of 100ºF [37.8ºC] or greater) with cough or sore throat in the absence of a known cause other than influenza

Case Definitions By CDC

• A confirmed case acute febrile respiratory illness with laboratory-confirmed H1N1 influenza A virus detection by real-time reverse transcriptase (RT)-PCR or culture.

• A probable case acute febrile respiratory illness who is positive for influenza A, but negative for H1 and H3 by RT-PCR

A suspected case acute febrile respiratory illness who:

•       - Develops symptoms within seven days of close contact with a person who is a confirmed case of H1N1 influenza A virus infection or

•       - Develops symptoms within seven days of travel or resides in a community where there are one or more confirmed H1N1 influenza A cases

Close contacts• Having cared for or lived with a person

• setting where there was a high likelihood of contact with respiratory droplets and/or bodily fluids

• Having had close contact (kissing, embracing, sharing eating or drinking utensils, physical examination, or any other contact likely to result in exposure to respiratory droplets)

Mexican data

• Influenza-like illness or respiratory symptoms developed in 22 of 190 health care workers

• These 22 workers received oseltamivir

• for 5 days and were sent home for 3 to 7 days. They had mild-to-moderate disease, and none required hospitalization

nejm.org august 13, 2009

Preventive measures taken in Mexican hospitals

• After infection-control measures were strictly enforced — with patients confined and isolated in three hospital areas and N95 masks

• Separate respirators used in addition to goggles, gowns, and gloves, as well as liberal use of gel-alcohol hand sanitizer — no more health care workers had influenza-like illness,

nejm.org august 13, 2009

COMPARISION

SEASONAL INFLUENZA

H1N1 INFLUENZA

AGE <5 YRS >60 YRS YOUNG & MIDDLE AGE

SEVERITY LESS SEVERE PNEUMONIA ARDS

MORBIDITY LESS MORE BUT >60 YRS LESS LIKELY TO HAVE SEVERE PNEUMONIA

contd

SEASONAL INFLUENZA

H1N1 INFLUENZA

SYMPTOMS RESPIRATORY RESPIRATORY & GASTROINTESTINAL

SECONDARY ATTACK RATE

5-15 % 22-33 %

VACCINE PROTECTIVE UNDER DEVELOPMENT

AGE SHIFTS IN MORTALITY

• Concept of “original antigenic sin,”by Francis - immune response is greatest to antigens to which first exposure occurred in childhood.

• Persons born before 1957 who were exposed in childhood to influenza A (H1N1) viruses might be better protected against this viral subtype than those who were first exposed to other influenza A subtypes, H2N2 and H3N2, at a later date .

• During the early phase of this epidemic, the rapid identification of persons who are likely to have severe disease, as

compared with those who are likely to have mild disease, can guide epidemic or pandemic response strategies.

Specimens • Nasopharyngeal swab, nasal swab, throat

swab, combined oropharyngeal/ nasopharyngeal swab, or nasal aspirate

• Swabs with a synthetic tip (eg, polyester or Dacron) and an aluminum or plastic shaft should be used. Swabs with cotton tips and wooden shafts are not recommended.

• The collection vial in which the swab is placed should contain 1 to 3 mL of viral transport media.

• Respiratory specimen should be collected within 4 to 5 days of illness.

• Specimens should be placed in viral transport media and placed on ice (4ºC) or refrigerated immediately for transportation to the laboratory

DIAGNOSTIC TESTS

RT PCRRT PCR

QUIDELQUIDEL

CULTURECULTURE

DFA/IFADFA/IFA

LAB TESTS• Real time RT PCR-confirmatory

• culture is usually too slow to help guide clinical management. A negative viral culture does not exclude pandemic H1N1 influenza A infection.

• Rapid antigen tests — evaluation of patients suspected of having influenza, but results should be interpreted with caution the QuickVue Influenza A+B (Quidel) assay (sensitivity 51 percent specificity 99 percent)

• Rapid influenza antigen tests & Direct or indirect immunofluorescent antibody testing (DFA or IFA) can distinguish between influenza A and B but negative test does not exclude infection.

Whom to test

• Testing for pandemic H1N1 influenza A should be considered in individuals with an acute febrile respiratory illness ( temperature of 100ºF or higher and recent onset of at least one of the following: rhinorrhea, nasal congestion, sore throat, or cough) or sepsis-like syndrome

Priority for testing should be given to :

Those who require hospitalization and

Those who are at high risk for severe complications

No testing if illness is mild or the person resides in an area with confirmed cases

Recommended test for suspected cases is real-time reverse transcriptase (RT)-PCR for influenza A, B, H1, and H3

CLINICAL FEATURES

Vomiting or diarrhea (not typical for influenza but reported by recent cases of swine influenza infection)

Mexican data in MV patients

Mexican data in MV patients

Younger people at risk

10-50 yrs

Severe Respiratory Disease Concurrentwith the Circulation of H1N1 InfluenzaGerardo Chowell, Ph.D., Stefano M. Bertozzi, M.D., Ph.D., NEJM August 2009

Can we make a broad clinical check list

• History of contact

• Younger age, sudden onset

• Fever, cough, breathlessness

• Leucopenia, raised LDH and CPK

• Should all such patients be isolated and given Tamiflu?

Other Manifestations:

• Tachycardia

• Tachypnoea

• Low O2 sat.

• Hypotension

• Cyanosis

• Acute myocarditis

• Cardiopulmonary arrest

Children Clinical Presentation

• Infants may present with fever and lethargy, and may not have cough or other respiratory symptoms.

• Apnea, tachypnea, dyspnea, cyanosis, dehydration, altered mental status, and extreme irritability.

Children Emergency Warning Signs

• Fast breathing or trouble breathing

• Bluish or gray skin color

• Not drinking enough fluids

• Severe or persistent vomiting

• 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

In adults, emergency warning signs

• Difficulty breathing or shortness of breath

• Pain or pressure in the chest or abdomen

• Sudden dizziness

• Confusion

• Severe or persistent vomiting

• Flu-like symptoms improve but then return with fever and worse cough

Why Complications In young (Cytokine storm)

• It is the systemic expression of a healthy and vigorous immune system resulting in the release of more than 150 inflammatory mediators . Both pro and anti-inflammatory cytokines are elevated in serum with lethal interplay of these cytokines is referred to as a "Cytokine Storm".

• The primary contributors to the cytokine storm are TNF-a and IL-6 .

• It is inappropriate (exaggerated) immune response that is caused by rapidly proliferating and highly activated T-cells or natural killer (NK) cells.

• Bird flu patients die from acute respiratory distress syndrome (ARDS) caused by the cytokine storm, and not directly from the virus

SYMPTOMS OF THE CYTOKINE STORM

The final result, of cytokine storm (SIRS) or sepsis is multiple organ dysfunction syndrome (MODS)

• hypotension ( Myocarditis)

• tachycardia

• ARDS acute respiratory failure

• Ischemia, or insufficient tissue perfusion

• uncontrollable haemorrhage

• Multisystem organ failure

Cytokine Storm Treatment

• Steroids

• ACE Inhibitors & ARBs

• Anti-CD28 Monoclonal Antibody

• TNF-alpha blockers

HISTOPATHOLOGY LUNG FINDINGS

• . The specimen shows necrosis of bronchiolar walls (top arrow),

• a neutrophilic infiltrate (middle arrow), and diffuse

• alveolar damage with prominent hyaline membranes (bottom arrow).

Diagnosis

• Laboratory Tests– Viral culture

• Presence of virus confirmed by– ELISA( 4 fold rise )– RT-PCR

• Rapid antigen tests  (distinguish between influenza A and B

LABORATORY FINDINGS

• CBC- leucocytosis/leucopenia

lymphopenia

• Elevated CPK, LDH

• Elevated UREA,CREATININE

• Elevated AST,ALT

• CHEST RADIOGRAPH-bilateral patchy pneumonia.

H1 N1 Pneumonia

COMPLICATIONS

Similar to those of seasonal influenza• Exacerbation of underlying chronic medical

conditions • Upper respiratory tract disease (sinusitis, otitis

media, croup) • Lower respiratory tract disease (pneumonia,

bronchiolitis, status asthmaticus)

•

• Cardiac (myocarditis, pericarditis)

• Neurologic (Acute and post-infectious encephalopathy, encephalitis, febrile seizures, status epilepticus)

• Toxic shock syndrome

• Secondary bacterial pneumonia with or without sepsis

DD H1N1 PNEUMONIA

• OTHER VIRAL pneumonia

influenza A,B adenovirus RSV para influenza rhinovirus humanmetapneumonia

• Legionella,Chlamydia,Mycoplasma

TREATMENT• Only neuraminidase inhibitors

ORALTamiflu (oseltamivir) and Relenza( zanamivir) are approved to cure the viral infection.

• H1N1 is resistant to Amantadine Rimantadine

• Antiviral drugs can be given to treat those who become severely ill with influenza.

Tamiflu (Oseltamivir )

• Block the active site of the influenza viral enzyme neuraminidase

• This effect results in viral aggregation at the host cell surface and reduces the number of viruses released from the infected cell

http://en.wikipedia.org/wiki/Image:Tamiflu.JPG

Tamiflu

Tamiflu

Tamiflu(contd)

• If one dose missed?

take as soon as you remember unless it is within 2 hours of next dose

do not take two doses at a time

. With other medications?

minimal drug interaction

no intranasal flu vaccine(Flu Mist) within 2weeks before or 48 after taking tamiflu

Tamiflu (Contd)

• With kidney disease

Flu treatment :one 75mg dose OD for 5 days

Flu prevention:one 75 mg dose alternate day or 30 mg dose OD

. Storage:

capsules- <25 degree C

liquid - 2 to 8 degree C

Zanamivir ( Relenza)

– It is not recommended for people with underlying respiratory disease such as asthma or chronic obstructive pulmonary disease or lactose intolerance

– Treatment of 7 year & older patients 10mg (2puffs)BID 5d

– Prophylaxis of 5 year & older patients 10mg OD 10d-28 days

Mild Cases

• Supportive: Paracetamol, flds…

*NO SALICYLATES IN CHILDREN/ YOUNG ADULTS: REYE'S SYNDROME

• Antivirals : *best within first 48 hours

*Early administration in at-risk pts ie those with comorbidities/ pregnancy…

• control precautions: cough etiquette• Hand hygiene & Natural ventilation

Hospitalized pts:

• Antivirals

• Pneumonia management like avian (antibiotics)

• Resp. Support: early detection

Correction of hypoxia with supplemental O2 or mech. Vent as necessary

Supportive care• When Mech. vent is indicated:

low volume low pressure lung protective vent.

• Steroids:

• Avoid routine use, no benefit was reported . Higher doses associated with serious SE:o evidence of increased viral replication in

SARS and other resp. viral infections. o Increased mortality in Avian

It is highly contagious!

• Can we have separate wards ,ICU’s and staffing

• We require separate OPD and testing facilities for suspected cases

• Can we spare separate equipment

• Can we organise all this in a running hospital?

prevention

N95 Mask

What should I do to keep from getting the flu?

• First and most important: wash your hands

• Get plenty of sleep

• Drink plenty of fluids

• Try not to touch surfaces that may be contaminated with the flu virus.

• Avoid close contact with people who are sick.

Avoid close contact

• Avoid close contact with people who are sick. When you are sick, keep your distance ( > 1 meter )from others to protect them from getting sick too.

• Aerosols spread the virus in any environment

Prevention

• management of the outbreak such as closure of schools, advising avoidance of mass gatherings and distribution of antivirals

• Avoiding close contact• Staying home from work, school• Covering mouth and nose with a tissue or

N95 mask (three layered) when coughing or sneezing. Change the mask every 6 to 8 hours

• Washing your hands

Is Negative Pressure Room Must ?

Place patients in a single-patient room with the door kept closed & droplet and contact isolation

Is BIA ready?

Why do we need vaccine

COST EFFECTIVETARGET AT RISKPEOPLE

VACCINE

WINTER SEASONTO COME(LOW HUMIDITY,TEMP)

RAPID GLOBALSPREAD

SEASONAL VACCINEPROTECTION?

• Transport of deceased persons in a transport bag.

• Hand hygiene should be performed after completing transport.

• For deceased persons with confirmed, probable, or suspect novel influenza A (H1N1):o limit contact with the body in health care settings to close family

memberso Direct contact with the body is discouragedo Necessary contact may occur as long as hands are washed

immediately with soap and water.

Dealing with the Deceased

Conclusion

• Be cautious but no need to panic

• Need for further guidelines beyond diagnosis & management.

• Judicious use of diagnostic tests

• Early suspecting and treating cytokine storm is very important

• Not to forget universal precautions

THANK YOU

Department of critical care medicine