1. Case Management of Suspect Human Avian Influenza Infection
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Case Management of Suspect Human Avian Influenza Infection
In this session we will talk about case management of suspect human avian influenza H5N1 infection. This is Part 1 of a three part series on this subject. Part 1 focuses on background information on clinical features and management of avian influenza infection in humans.
Part 1: Background information on clinical features and management of avian influenza

2. Learning Objectives Recognize clinical features of H5N1 in humans
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Learning Objectives
Recognize clinical features of H5N1 in humans
Understand how information about the patient before onset of illness can help you suspect infection
Know the types of treatment options available
By the end of this presentation, you should have a good understanding of the clinical features of avian influenza H5N1 infection in humans. You should also understand how additional information about your patient in the weeks before illness can help you suspect avian influenza H5N1 infection. Finally, you should know the types of treatment options available to people who are suspected to have avian influenza H5N1 infection.

3. Part 1 Session Overview Clinical features Epidemiologic information
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Part 1 Session Overview
Clinical features
Epidemiologic information
Risk for infection
Transmission
Current antiviral medications
Group exercise
Over the next hour, we will review information that will help you try to answer these very important questions. We will begin by discussing the clinical features of avian influenza H5N1 in humans. We will review signs and symptoms, laboratory findings, and complications. In addition, we will highlight differences between avian influenza H5N1 in humans and human influenza infections. Next we will review two key pieces of epidemiologic information. These include risk factors for the infection and the way in which the virus is transmitted. Finally, we will talk about current antiviral medications that you might use to treat people with suspected avian influenza H5N1.
At the end of Part 1, you will have an opportunity to participate in a group exercise.

4. Illness Scenario 5-year-old Mg Win was sick for three days Fever
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Illness Scenario
5-year-old Mg Win was sick for three days
Fever
Watery diarrhea
Headache
Cough
Short of breath
No one else sick
Mg Win and a friend play with chickens
Question: Is this avian influenza?
Before we start, imagine that it is a normal working day for you at the local health department. You see a 5 year old child .He has been sick for the past three days. He has a high fever and complains of a headache. He has watery diarrhea that began two days ago. He started coughing, is short of breath, and is very tired.
No one else in the family is sick. He plays with a friend whose family has chickens. He and his friend like to play and hold the chickens but they do not know if any of the chickens have died recently. His friend is not sick.

5. Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Clinical Features
First let’s learn about the clinical features of influenza.

6. General Information Human influenza Avian Vulnerable Age Groups
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
General Information
Human
influenza
Avian
Vulnerable
Age Groups
All ages affected
Highest rates in children < 5 years
Most complications in elderly >60 years
Children < 5 years
Healthy young adults
Adolescents
Time from exposure to illness
Mean 2 days
Range: 1 – 5 days
Mean 2 – 3 days
Range: 2 – 10 days
Human influenza virus can infect anyone of any age group, but generally has the most impact on those who are very young or very old. Attack rates tend to be higher in young children under the age of 5, and the elderly over age 60 are especially vulnerable to complications. The current avian influenza H5N1 also affects children under the age of 5. However, healthy young adults and adolescents are also vulnerable to H5N1 infection and complications.
The time from exposure to the virus to onset of illness, or the incubation period, for seasonally occurring human influenza virus is generally 1 to 3 days. For avian influenza H5N1, the incubation period has been observed to be a little longer; it can range from 2 to 8 days.

7. Signs and Symptoms Human Influenza Avian Influenza (H5N1)
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Signs and Symptoms
Human Influenza
Avian Influenza (H5N1)
Type of infection
Upper respiratory
Lower respiratory
Fever
Yes
Headache
Cough
Respiratory symptoms
Varies; sore throat to difficulty breathing
Difficulty breathing, crackles, increased respiratory rate
Gastrointestinal symptoms
Rare: Children, elderly
Rare: Variable, watery diarrhea, vomiting, abdominal pain
Recovery
2-7 days
Longer
It can be difficult to tell if a patient has influenza because the signs and symptoms for influenza are similar to those for other diseases that may cause respiratory illnesses. If you do suspect influenza, there are a few differences between human influenza and avian influenza that you can assess.
Human influenza usually leads to an upper respiratory infection. Signs and symptoms include fever, headache, cough, sore throat, muscle ache, and exhaustion. Other respiratory symptoms may appear, varying from sore throat to difficulty breathing. Children and the elderly may also have gastrointestinal symptoms like diarrhea, vomiting and nausea, but adults rarely have gastrointestinal symptoms. People generally recover anywhere from 2 to 7 days after symptoms appear. However, cough and muscle ache may last more than 14 days. Although influenza generally causes an upper respiratory infection, it can progress to pneumonia and respiratory failure in some cases.
Avian influenza seems to be slightly different from human influenza. Avian influenza leads to a lower respiratory infection with variable upper respiratory involvement. Initial symptoms are similar to human influenza. These include fever, headache, cough, sore throat, muscle ache, and exhaustion. Gastrointestinal symptoms of watery diarrhea, vomiting, and abdominal pain have been more commonly reported from H5N1 patients. Symptoms of a lower respiratory infection appear early in course of the illness. About five days after symptoms appear, patients may begin to have difficulty breathing leading to respiratory distress. A crackling sound may be heard during inhalation, and an increased respiratory rate may also be observed. By this time, sputum production may occur and may contain blood.

8. Unusual Presentations
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Unusual Presentations
Knowledge of avian influenza infection in humans changes as we learn more
Unusual symptoms
Absence of respiratory symptoms
Severe watery diarrhea
Loss of consciousness
It is important to remember that our knowledge of avian influenza infection in humans changes as we learn more about it. For example, we have recently learned that there are a few unusual symptoms that may present. These include: the absence of any respiratory symptoms; severe watery diarrhea; and loss of consciousness.

9. Complications Avian Influenza Seasonal Influenza
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Complications
Avian Influenza
Almost all develop pneumonia
Acute Respiratory Distress Syndrome (ARDS)
Multiorgan failure
Encephalitis
Seasonal Influenza
Ear infection, sinusitis
Bronchitis, bronchiolitis
Pneumonia
viral or secondary bacterial
Exacerbation of chronic conditions
Muscle inflammation
Neurologic Disease
Seizures
Brain inflammation
Reye’s syndrome
Human influenza infection can lead to serious complications including: ear infection; sinusitis; bronchitis; pneumonia due to viral or secondary bacterial infections; exacerbation of chronic conditions such as asthma; muscle inflammation; and neurologic disease. Neurologic disease includes seizure, inflammation of the brain, and Reye’s syndrome.
Almost all avian influenza cases develop pneumonia that seems to be viral rather than bacterial. Acute respiratory distress syndrome (or ARDS) was observed in patients in Thailand about 6 days after symptoms appeared. In Turkey, ARDS developed about 3 to 5 days after symptoms appeared. Multi-organ failure involving the kidneys and heart and encephalitis have also been reported.

10. Laboratory Findings Commonly associated with avian influenza:
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Laboratory Findings
Commonly associated with avian influenza:
Drop in white blood cell count (lymphocytes)
Mild to moderate drop in blood platelet count
Increased aminotransferases (Liver enzymes)
In addition to signs and symptoms, a few laboratory findings have been commonly associated with avian influenza H5N1 infection. These include:
The most important finding that has been observed is a drop in the white blood cell count, especially lymphocytes
A mild to moderate drop in the blood platelet count
An increase in aminotransferases, or liver enzymes, is also common

11. Do you think Mg Win has signs and symptoms of avian influenza?
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Question:
Do you think Mg Win has signs and symptoms of avian influenza?
Why or why not?
Let’s stop for a moment and think about the child. After everything you have just heard, do you think the child has signs and symptoms of avian influenza H5N1 infection? Why or why not?
Lecturer answer: Symptoms that may indicate avian influenza do include high fever, headache, watery diarrhea, cough, and tiredness. However, these signs and symptoms are not specific for avian influenza, so we need more information to assess whether or not the child may have avian influenza H5N1 infection.

12. Epidemiologic Information
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Epidemiologic Information
Now let’s talk about epidemiologic information that will help guide you in suspecting if someone may have avian influenza H5N1.

13. Risk for Infection from Animals
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Risk for Infection from Animals
Within 10 days before symptoms begin:
Close contact with live, sick, or dead birds
In setting with confined birds
Contact with contaminated surfaces
Ingestion of uncooked infectious poultry
Especially in countries where outbreaks in poultry and human cases have been reported, there are a few things a person may do that may put him or her at risk for avian influenza infection.
This slide presents risk posed by animals. When you collect information about a patient, a time frame within 10 days before symptoms began should be considered. A person is at risk of infection if he or she has close contact with any live, sick, or dead birds, including preparing and cooking dead birds. Close contact means being within one meter of the bird. A person may also be at risk of infection if he or she has been in settings where birds have been confined, has had contact with surfaces contaminated by sick birds, or has ingested uncooked infectious poultry.

14. Risk for Infection from Humans
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Risk for Infection from Humans
Uncertain risk of person-to-person spread
Within 10 days before symptoms begin:
Face-to-face contact
Touching or within 1 meter of suspected or diagnosed H5N1 patient without proper precautions
Touching or being within 1 meter of a person who has severe pneumonia or dies from an acute respiratory illness without proper precautions
There is an uncertain risk of person to person spread of avian influenza. Listed here are potential risks posed by humans if proper precautions, such as masks and gloves, are not used. You should learn about a patient’s actions during the 10 days before symptoms began. Face to face contact, touching, or being within one meter of a person suspected or diagnosed with avian influenza infection may be a risk of infection. Another risk is touching or being within one meter of a person who has severe pneumonia or dies from an acute respiratory illness, including being a healthcare worker or working in laboratories with the H5N1 virus.

15. Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Question:
Do you think that Mg Win is at risk for avian influenza H5N1 infection?
Why or why not?
Let’s think about the child again. Do you think the patient is at risk for avian influenza H5N1 infection? Why or why not?
Answer: Yes, The Child may be at risk for avian influenza H5N1 infection. He likes to play with his friend and his friend’s chicken. He has close contact with live birds (chickens). It is not clear if any chickens have died. Would want to learn more about his friend’s chickens.

16. Routes of Transmission
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Routes of Transmission
Another important piece of information to know about avian influenza is the possible route of transmission.

17. Risk Factors Direct contact with birds Risk Factors:
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Risk Factors
Direct contact with birds
Risk Factors:
Playing with birds
Working with birds
Preparing birds for meals
Contaminated water
Most patients diagnosed with avian influenza H5N1 infection have had direct contact with birds. This includes playing with birds, preparing sick birds for eating, and cock fighting. Since H5N1 can survive in the environment, it is also possible that ingesting contaminated recreational water could cause infection.

18. Routes of Transmission
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Routes of Transmission
Indirect contact
Infected materials, surfaces
Person-to-person rare at present
Eating undercooked or raw bird products
Meat, eggs, blood
Hands that have come in contact with infected materials may also lead to illness if they are not washed. Although no continued person-to-person transmission has been documented, there have been household clusters that suggest limited person-to-person transmission. So far, transmission to healthcare workers seems low. Finally, eating undercooked or raw bird products, such as meat or blood, may place humans at risk for avian influenza infection.

19. Question: Has Mg Win had an exposure that could lead to transmission?
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Question:
Has Mg Win had an exposure that could lead to
transmission?
Has the child had an exposure that could lead to transmission?
Answer: Yes, the child has had direct contact with live birds (chickens). He and his friend liked to hold the chickens.

20. Using All of The Information
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Using All of The Information
Let us take a moment to stop and think about what you have just learned. We discussed how the clinical features of avian influenza H5N1 are slightly different from human influenza. Based on this information, you may suspect someone has avian influenza H5N1. We also discussed how it may sometimes be difficult to suspect avian influenza H5N1 based on the symptoms alone. Epidemiologic information can help us by increasing or decreasing how much we suspect avian influenza.

21. A Clinician Should Suspect H5N1 Infection if a Patient Has:
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
A Clinician Should Suspect H5N1 Infection if a Patient Has:
Severe acute respiratory illness with
Exposure 10 days before symptoms to:
Suspect / diagnosed avian H5N1 patient
Poultry or Wild Birds OR
Direct contact with birds OR
Residence in an area with known H5N1 activity in poultry
To summarize what we have discussed thus far, you should have a suspicion of avian influenza H5N1 infection if
A patient has severe acute respiratory illness and
A patient has been exposed in the 10 days before symptoms began to birds or an individual with a suspect or diagnosed avian influenza H5N1 infection or
A patient had direct contact with birds or
If you know that a patient with a severe illness comes from an area with human or animal H5N1 activity

22. Case Scenario 5-year-old Mg Win is sick for three days Fever
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Case Scenario
5-year-old Mg Win is sick for three days
Fever
Watery diarrhea
Headache
Cough
No one else sick
The patient and a friend play with and hold chickens
Keeping the criteria for suspecting an H5N1 infection in mind, let’s revisit the information about the child’s scenario:
The patient is 5 years old and has been sick for the past three days.
He has a high fever and complains of a headache.
He has watery diarrhea that began two days ago.
He has coughing and is very tired.
No one else in the family is sick.
He plays with a friend whose family has chickens. He and his friend like to play and hold the chickens
his father does not know if any of the chickens have died recently.
his father does not think that his friend is sick.

23. Would you suspect avian influenza H5N1 infection? Why or why not?
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Question:
Would you suspect avian influenza H5N1 infection? Why or why not?
Think about all that you know about what to look for in a person suspected of having avian influenza H5N1 infection, and the information that you have about the patient.
Would you suspect avian influenza H5N1 infection? Why or why not?
Facilitator Answer: Yes, you should suspect avian influenza. The patient has symptoms that are consistent with avian influenza H5N1 infection, has had close contact with birds, and had direct contact when he held the birds.

24. Current Antiviral Treatment
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Current Antiviral Treatment
Treatments, or medications, that work against avian influenza can prevent disease or improve outcomes in those who are ill.

25. Neuraminidase Inhibitor
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Neuraminidase Inhibitor
Neuraminidase enzyme breaks bond between infected cell and newly formed virus
Inhibitor prevents enzyme from breaking bond and releasing virus
Virus particles cannot infect other cells
Since you suspect that the patient may have avian influenza H5N1 infection, what should you use to treat him? The answer is that any patient suspected of having avian influenza H5N1 infection should be treated with a neuraminidase inhibitor.
An infected cell has many virus particles on the surface of its cell, ready to infect other cells. Neuraminidase is an enzyme that breaks the bond between the infected cell and the virus particle. A neuraminidase inhibitor prevents the enzyme from breaking the bond so virus particles cannot infect other cells.

26. Neuraminidase Inhibitor
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Neuraminidase Inhibitor
Two drugs available
Oseltamivir (Tamiflu®) and Zanamivir (Relenza ®)
Should be given as soon as possible
Effective for treatment and prevention
Used for seasonal or avian influenza
The two neuraminidase inhibitor drugs currently available are Oseltamivir, with the trade name Tamiflu, and Zanamivir, with the trade name Relenza. You should not wait for laboratory diagnosis before beginning treatment; all patients should begin treatment as soon as possible. There is some suggestion that antivirals given within 48 hours of symptom onset may improve survival. Antivirals can also be given to prevent disease from developing in those who have been exposed to the virus.

27. Dosage for seasonal influenza
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Oseltamivir
Dosage for seasonal influenza
Adults:
75 mg twice a day for 5 days
Children:
<1 year, not studied adequately
< 15 kg - 30 mg twice a day for 5 day
>15 kg to <23 kg - 45 mg twice a day for 5 days
>23 kg to <40 kg - 60 mg twice a day for 5 days
>40 kg - 75 mg twice a day for 5 days
Oseltamivir is available in capsule or liquid form. It is recommended for treatment in people more than 1 year old. Current guidelines for Oseltamivir treatment of seasonal influenza are:
- Adults: 75 mg twice a day for 5 days
- Children: <1 year, not recommended
- If body weight is < 15 kg, the dose should be mg twice a day for 5 days
- If body weight is >15 kg to <23 kg, the dose should be 45 mg twice a day for 5 days
- If body weight is >23 kg to <40 kg, the dose should be 60 mg twice a day for 5 days
- If body weight is >40 kg, the dose should be mg twice a day for 5 days

28. Dosage for avian influenza
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Oseltamivir
Dosage for avian influenza
Best dosage for H5N1 unknown
Longer treatment (7 to 10 days) OR
Higher doses (150 mg)
Dosage for prevention
Once daily for 7 to 10 days after last exposure
Side Effects
Nausea and vomiting
Skin rash
Oseltamivir has been used to treat avian influenza as well. No clinical trial on the effectiveness of Oseltamivir on avian influenza H5N1 infection in humans has been conducted. Therefore, the best dosage for treatment is unknown. But it has been suggested that patients with avian influenza H5N1 infection may benefit from longer treatment (7 to 10 days) or higher doses (150 mg). The dosage for prevention of avian influenza is once daily for 7 to 10 days after last exposure.
Side effects of Oseltamivir use can include nausea, vomiting and skin rash.

29. Oseltamivir Effectiveness in seasonal influenza
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Oseltamivir
Effectiveness in seasonal influenza
Reduces influenza symptoms days
Reduces lower respiratory tract complications, pneumonia, and hospitalization
Cautions- Consider Risk versus Benefits
People with kidney disease (adjust dose)
Pregnant or nursing females
Resistance
Detected in several avian influenza H5N1 patients
Studies show that Oseltamivir can reduce seasonal influenza infection by one to three days. It has also been shown to reduce serious complications such as lower respiratory tract complications, pneumonia, and hospitalization. However, individuals with kidney disease will need to have their dosage adjusted, and pregnant and nursing females should avoid taking this drug.
Resistance to Oseltamivir has been detected in several avian influenza H5N1 patients.

30. Zanamivir Inhaled by mouth via special device
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Zanamivir
Inhaled by mouth via special device
May be used for > 5 years of age
Treatment dosage
Once in morning and night, 5 days
Side effects
Wheezing, and breathing problems
The second neuraminidase inhibitor that we want to discuss is Zanamivir. This drug is inhaled as a powder through the mouth, and requires a special device to administer. Zanamivir is recommended for the treatment of anyone greater than 7 years of age. It should be taken once in the morning and once at night for 5 days. Side effects can include wheezing and serious breathing problems.

31. Zanamivir Effectiveness in seasonal influenza
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Zanamivir
Effectiveness in seasonal influenza
Reduces influenza symptoms days
Reduces lower respiratory tract complications
Consider Risk vs. Benefit
People with chronic respiratory disease
Pregnant or nursing females
Resistance
Not identified in human H5N1 infections
Active against Oseltamivir resistant H5N1
Studies show that Zanamivir can reduce human influenza infection by one to three days. It has also been shown to reduce lower respiratory tract complications. Neither people with chronic respiratory disease such as asthma nor pregnant or nursing women should take this drug. Resistance to Zanamivir has not been identified among patients with avian influenza H5N1 infections, and Zanamivir is active against Oseltamivir resistant H5N1 virus.

32. Other Treatments? Amantadine and Rimantadine
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Other Treatments?
Amantadine and Rimantadine
H5N1 resistant in some isolates
Not as effective as
neuraminidase inhibitors
Corticosteroids
Low dose for sepsis
Unclear if high dose useful
Risk of side effects
For human influenza infections, Amantadine and Rimantadine are also used for treatment. However, avian influenza H5N1 has been shown to be resistant to these drugs in some patients. Furthermore, the drugs are not as effective as the neuraminidase inhibitors.
Corticosteroids have been used in low doses to treat sepsis – or a bacterial infection in the blood. It is unclear if a high dose is useful for treatment of avian influenza H5N1 infections, and there is a risk of side effects.

33. Question: What would you do at this stage ?
Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Question:
What would you do at this stage ?
Now that you know about some antiviral treatment options, let’s talk about the child in the case scenario one last time. “What should the doctor do?” Based on what you have learned during this presentation, what would you do?
Answer: Based on the signs and symptoms and the patient’s direct contact with chicken in the 7-14 days before symptoms, you should be suspicious that the patient may have avian influenza H5N1. It is needed to notify hospital staff so proper precautions be used to protect their health. In addition, the child should be given Oseltamivir or Zanamivir immediately. Finally, as a local health department worker, you should begin an investigation to learn more about how the child became ill and to learn if others in his neighborhood are ill.

34. Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Part 1 Summary
Ask about recent exposure and contact with humans or animals that may have had avian influenza H5N1 infection
Laboratory can confirm H5N1, but you should not wait
Individuals with avian influenza H5N1 infection may not have respiratory symptoms
In summary, there are three important points you should remember from this presentation:
1. Ask patients about recent exposure and contact with humans or animals that may have had avian influenza H5N1 infection. Clinical features of avian influenza H5N1 are similar to other diseases, so you should not suspect avian influenza H5N1 infection based on symptoms alone.
2. The laboratory can confirm H5N1 infection in a patient, but you should not wait until laboratory results come back to begin treatment and control measures.
3 Individuals with avian influenza H5N1 infection may not have respiratory symptoms. Once again, it is important to find out if your patient has had any exposure or contact with humans or animals that may have had avian influenza H5N1 infection.

35. Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Questions?

36. Module 4: Case Management of Suspect Human Avian Influenza Infection; Parts 1 & 2
Case Study Exercise
Background information on clinical features and management of avian influenza
Next we will break into groups to conduct a case study that uses the information just presented.
See Module 4 Trainee Exercises/ Facilitator guide
Module 4 part 1 Case Study.