2. This Guide on the clinical management of pandemic (H1N1) virus infection
Prof. AHMED ABDELRAHMAN
DEPARTMENT OF CHEST MENUFYIA UNIVERSITY HOSPITAL

3. INFLUENZA
Acute respiratory illness caused by infection with influenza viruses.
Affects the upper and/or lower respiratory tract and is often accompanied by systemic signs and symptoms:
fever - headache
myalgia - weakness

4. H1 – H16 N1 – N9 N H

5. Three types: A, B, C A epidemic flu, severe disease
Surface proteins determine subtype
H (hemagglutinin) H1 – H16
N (neuraminidase) N1 – N9
Influenza A viruses infect multiple species depending on subtype
Humans
Birds
Pigs

6. What is the Influenza A (H1N1)?
Influenza A virus Subtypes
16 different HA antigens (H1 to H16)
9 different NA antigens (N1 to N9)
3 subtypes of HA (H1, H2, and H3) &
2 subtypes of NA (N1 and N2) – caused human disease.
found in birds & pigs

7. H3N2 ("swine flu") is endemic in pigs in China, and in Vietnam
H3N2 ("swine flu") is endemic in pigs in China, and in Vietnam. The dominant strain of annual flu virus in January 2006 was H3N2, which is now resistant to the standard antiviral drugs amantadine and rimantadine.
The possibility of H5N1 and H3N2 exchanging genes is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2did when it evolved into the Hong Kong Flu strain of H3N2

8. H5N1
 Influenza A virus  subtype it might mutate into a form that transmits easily from person to person.
If such a mutation occurs, it might remain an H5N1 subtype or could shift subtypes as didH2N2 when it evolved into the Hong Kong Flu strain of H3N2.

9. SARS coronavirus
The SARS coronavirus, sometimes shortened to SARS-CoV, is the RNA virus virus that causes severe acute respiratory syndrome (SARS)

10. Influenza - Case Definition
Fever ≥ C with cough &/or sore throat in the absence of a known cause other than influenza

11. Estimated incubation period 1-7 days, (likely 1-4 days).
Infectious period
for a confirmed case of influenza A (H1N1) virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset.

12. CLINICAL FEATURES

13. Clinical Features of Influenza A/H1N1
Uncomplicated disease manifest with
fever
headache
upper respiratory tract symptoms (cough, sore throat, rhinorrhea),
myalgia, fatigue, vomiting, or diarrhea.

14. Complications
Clinical syndromes have ranged from mild respiratory illness, to lower respiratory tract illness, dehydration, or pneumonia.
URTIs (sinusitis, otitis media, croup)
LRT disease (pneumonia, bronchiolitis, status asthmaticus),
cardiac (myocarditis, pericarditis),
musculoskeletal (myositis, rhabdomyolysis),
neurologic ( encephalopathy, encephalitis, febrile seizures, status epilepticus),
In children,risk of REYE Syndrome (therefore, NSAIDS contraindicated)

15. Symptom (%) Fever* (93%) Cough (83%) Shortness of breath (54%)
Fatigue/Weakness (40%)
Chills (37%)
Myalgias (36%)
Rhinorrhea (36%)
Sore Throat (31%)
Headache (31%)
Vomiting (29%)
Wheezing (24%)
Diarrhea (24%)

16. Influenza A/H1N1 Infections in Children
Majority are mild & self limiting
Most common are
fever(100%) , cough(100%) , sore throat(66%) , myalgia(44%) , vomiting & diarrhea(25%)
Uncommon: altered conscious level (10%) , hypotension

17. Suspected case of pandemic (H1N1)
A suspected case of H1N1 infection is defined as an individual with acute respiratory illness and fever and one of the followings; cough, sore throat, shortness of breath, difficulty in breathing or chest pains with onset:
Within 7 days of close contact with a person who is probable or confirmed case of H1N1infection, OR
Within 7 days of travel to a country/community where there has been one or more confirmed cases of H1N1 infection; OR
Resident in a community where there is one or more confirmed cases of H1N1 infection.

18. Probable case of (H1N1)
A probable case of H1N1 infection is defined as an individual with an influenza-like illness who is positive for influenza A that is confirmed by real-time PCR, OR
an individual with a clinically compatible illness or died of an acute respiratory illness who is linked to a probable or confirmed case.

19. Case Definitions Confirmed Case of pandemic (H1N1)
A confirmed case of H1N1 infection is defined as an individual with an influenza-like illness with laboratory confirmed pandemic (H1N1) 2009 virus infection by one or more of the following test:
Real-time RT-PCR
Viral culture

20. Influenza like illness (ILI)
A person with sudden onset of fever of >38 °C and at-least one of the following two respiratory symptoms in the absence of other known causes:
dry cough & sore throat 

21. Severe acute respiratory illness (SARI)
A person meeting the case definition of influenza-like illness (sudden onset of fever > 38 0C with at-least one of the following two respiratory symptoms- dry cough, sore throat in the absence of other diagnosis)
AND shortness of breath OR difficulty in breathing requiring hospital admission

22. Acute Respiratory Infection (ARI)
For the purposes of this interim guidance, Acute Respiratory Infection (ARI) is defined as an acute respiratory tract illness that is caused by an infectious agent transmitted from person to person. The onset of symptoms is typically rapid, over a period of hours to several days. Symptoms include fever, cough, and often sore throat, coryza, shortness of breath, wheezing, or difficulty breathing.

23. Complications of Influenza:
Respiratory complications are the most common ones (esp secondary infections).
At times these complications, eg. an exacerbation of COPD, may be the presenting symptom.
Cardiac events are not uncommon.
Complications of influenza Major clinical category
Respiratory Pneumonia: primary viral, secondary bacterial, combined
Upper respiratory: otitis media, sinusitis, conjunctivitis
Acute laryngotracheo-bronchitis (croup)
Bronchiolitis
Complication of pre-existing disease

24. Cardiovascular
Myocarditis & Pericarditis
Muscular Rhabdomyositis
Rhabdomyolysis with myoglobinuria and renal failure
Neurological Encephalitis
Reye’s syndrome
Guillain-Barré syndrome
Transverse myelitis
Systemic Toxic shock syndrome
Sudden death

25. DIAGNOSIS

26. The CXR shows bilateral alveolar opacities in the base of both lungs.
The specimen (H&E stain) shows
necrosis of bronchiolar walls,
neutrophilic infiltrate and diffuse alveolar damage with prominent hyaline membranes.
Bacterial cultures were negative on admission, and no evidence of bacterial infection of the lungs.

27. The CXR shows bilateral alveolar opacities in the base of both lungs.

28. The specimen (H&E stain) shows necrosis of bronchiolar walls, neutrophilic infiltrate and diffuse alveolar damage.

29. Real-Time Reverse Transcription-Polymerase Chain Reaction (rRT-PCR) Detection
Qualitative for Influenza A, B, H1, and H3
positive for influenza A and negative for H1 and H3
If reactivity of real-time RT-PCR for influenza A is strong (eg, Ct <30), it is more suggestive of a novel influenza A virus.

30. Risk factors in adults include the following:
Chronic respiratory conditions, eg asthma, COPD, OSA
Pregnant women, esp. in second or third trimester
Obesity (BMI > 30)
Other predisposing conditions, such cardiac disease and diabetes mellitus, renal failure, immunosuppression.
Adults > 65 years of age esp.

31. Risk factor for children with ILI
Cardiac disease : congenital heart dis.
Chr. resp. disease : asthma
Chronic renal failure
Diabetes mellitus or other metabolic diseases
Chr. neurological disease : ms. Dystrophy
Impaired immunity:HIV,malignancy
Malnutrition or obesity
Children < 5 yrs : Higher risk of severe disease & mortality

32. Recognition of deterioration of Pts with moderate / severe illness need to be admitted and provided with antiviral therapy.
Severe illness following influenza occurs in at least 3 ways:
1. severe viral infection with ARDS occurring relatively early in illness related to viral pneumonia (within 1st 4 days)
2. bacterial pneumonia, complicating initial bronchitis caused by influenza, or following apparent recovery from initial illness

33. Abnormal pulse oximetry – Significant ↓in SpO2 (<92%)
low SpO2 can detect severe or complicated influenza in some cases.
In people with normal pre-existing respiratory and cardiac function, SpO2 < mid 90’s is abnormal and < low 90s is very abnormal and indicates severe disease.

34. Severe Disease in Children
Apnea
Tachypnea
Dyspnea
Cyanosis
Dehydration
Altered mental status
Extreme irritability

35. Lower chest wall indrawing
Sternal recession
Grunting
Noisy breathing when calm
Increased Respiratory Rate in Children
≥ 50 breaths per min if under 1 yr old
≥ 40 breaths per min if ≥ 1 year old
Severe Clinical Dehydration or Clinical Shock in children
Reduced skin turgor
Sunken eyes or fontanelle

36. CNS Involvement in children
Irritable
Unconscious
Drowsiness
Confusion
Seizures
Weakness or paralysis
Floppy infant

37. Patients to be hospitalized:
All patients fulfilling criteria of ILI with any of the parameters for moderate to severe influenza

38. Patient Home Assessment
Respiratory Difficulties: Shortness of breath, rapid breathing & blue discoloration of lips
2 Coughing of blood or blood streaked sputum
3 Persistent chest pains
4 Persistent diarrhea and / or vomiting
5 Fever persisting beyond 2 days or recurring after 2 days
6 Abnormal behavior , confusion, less responsive , convulsion
7 Dizziness when standing and/or reduced urine production

39. Home Assessment Tool for pediatric
Lethargy or poor oral intake
Change in mental status
Signs of dehydration
Signs of respiratory distress
Fits
Cyanosis
Persistent fever > 2 days

40. Confirmed Case of Influenza A/H1N1 Infection
Individuals with ILI and +ve laboratory test , either by
a) PCR
b) Viral culture

41. Antiviral Treatment for Influenza A / H1N1 RECOMMENDATION:
All hospitalized patients (ie. those with moderate to severe disease) with confirmed or suspected novel influenza A H1N1.
Empirical therapy for suspected patients with severe disease should be considered if the time for H1N1 confirmation is prolonged. The antiviral treatment may be stopped if the results are negative.
All individual with co-morbid factors whether they are admitted or not.

42. Antiviral Therapy Oseltamivir (Tamiflu) dosage: Duration 5 days
Adults & adolescents > 13 yrs: 75 mg bd
(in severe cases, dosage can be doubled to 150 mg bd)
For children (according to weight):
<15kg: 30mg bd
15-23kg: 45mg bd
23-40kg: 60mg bd
> 40kg: 75mg bd
Renal adjustments: patients with a serum creatinine clearance between ml/min: treated with 75 mg daily for 5 days

43. Oseltamivir Side Effects
Gastrointestinal(40%) : nausea , vomiting , abd. pain/cramps, diarrhea
Neuropsychiatric(18%) : sleep problems , insomnia , poor concentration , delirium , feeling confused , hallucinations , bad dreams , nightmares , abnormal behavior

44. Zanamivir (Relenza) dosage:
10mg (2 puffs) bd for 5days (Adults & children)
In patients with bronchospasm: Zanamivir is not recommended for the treatment of patients with underlying airways disease (eg. asthma or COPD). Patients with pulmonary dysfunction should always have a fast-acting bronchodilator available and discontinue zanamivir if respiratory difficulty develops.
No dosage adjustment is required in patients with renal impairment

45. Conclusions
Careful clinical assessment of the individual with ILI in primary healthcare setting is important
Admission is needed for individual with moderate to severe diseases of any age.
Treatment with antiviral is needed only for admitted individuals and those with co-morbid factors whether admitted or not.

46. The single best way to protect against the flu is to get vaccinated each year.
flu shot
— an inactivated vaccine (containing killed virus). - for use in people older than 6 months, including healthy people and people with chronic medical conditions.
The nasal-spray flu vaccine
—made with live, weakened flu viruses that do not cause the flu .
- approved for use in healthy people, y.o. who are not pregnant.

47. Thank You !