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INFLUENZACLINICAL FINDINGS &

CASE DETECTION

مركز بهداشت استان اصفهانگروه مبارزه با بيماريها

Definition of flu• Definition might be different according to Flu alert status

• Classic definition:1)Fever2)Cough or sore throat3) One of the following items:• malaise( ill appearance?)• Neck pain (calf tenderness?) (muscle pain)• Shivering• Mucosal irritation• Hx of contact to suspicious flu case

• Definition during pandemic:Illness with both of the following:1)T>38 c2)cough,sore throat,or dyspnea

Transmission

• Human influenza is transmitted by inhalation of infectious droplets and droplet nuclei, by direct contact, and perhaps, by indirect (fomite) contact, with self-inoculation onto the upper respiratory tract or conjunctival mucosa

• Evidence is consistent with bird-to-human, possibly environment-to-human, and limited, nonsustained human-to-human transmission

• No significant risk related to eating or preparing poultry products or exposure to persons with influenza A (H5N1) disease

• Exposure to ill poultry and butchering of birds were associated with seropositivity for influenza A (H5N1).

• Most patients have had a history of direct contact with poultry, although not those who were involved in mass culling of poultry

Potential Modes:

• Oral ingestion of contaminated water during swimming and direct intranasal or conjunctival inoculation during exposure to water

• Contamination of hands from infected fomites and subsequent self-inoculation

How do humans get “bird flu? ”

Through close contact with infected birdse.g. breathing in particles from their droppings

Rare for bird flu to infect humans Limited evidence of human-to-

human transmission to dateaccording to WHO

با انسان نزديک و مستقيم با تماس انسان نزديک و مستقيم تماسآلوده آلوده پرنده پرنده

طر از آنفلوآنزا ويروس طر انتقال از آنفلوآنزا ويروس ق ق ييانتقالبصورت آلوده پرنده گوشت بصورت خوردن آلوده پرنده گوشت خوردن

توصيه ولی باشد نمی ميسر توصيه پخته ولی باشد نمی ميسر پختهمرغ تخم و گوشت خوردن از مرغ ميگردد تخم و گوشت خوردن از ميگردد

اجتناب پز نيم بصورت اجتناب آلوده پز نيم بصورت .آلوده .گردد گردد

نحوه انتقال ويروس آنفلوآنزای طيور به نحوه انتقال ويروس آنفلوآنزای طيور به انسانانسان

A(H1N1) A(H2N2) A(H3N2)

1918:

“Spanish Flu”

1957:

“Asian Flu”

1968:

“Hong Kong Flu”

20 - 40 million deaths 1 - 4 million deaths 1 - 4 million deaths

Credit: US National Museum of Health and Medicine

در آنفلوآنزا جهانی پاندمیهایبیستم قرن

Clinical findings .1Classic signs

&symptoms :• Sudden onset• Incubation:1-2 days• Dominancy of

systemic s&s at the onset: fever, headache,chilly sens. ,shaking chills ,myalgia, anorexia,perspiration

• Eye s&s• URI s&s

Clinical findings .2Uncomplicated course:• Persistence of

systemic s&S FOR 3 DAYS

• Cough become more prominent & can continue for a few days after stopping the fever

• A few wks convalescence

Differences of findings in pediatric age group

More common features in pediatric patients:• More sudden onset• Anorexia• Abd. Pain & GI s&s• Very high fever• Cervical LNP• Specially in younger kids: non obvious

respiratory s&s• Newborn period: like sepsis• Febrile convulsion

COMPARISON OF FINDINGS IN ADULTS VS CHILDREN(%)

SYMPTOMSCHLDRENADULTS

Sudden onset6646

Myalgia33 62

Nasal discharge 67 82

Sneezing 38 67

Abd pain310

Vomiting 267

Cervical LNP388

Animals and Highly Pathogenic Avian Influenza

Clinical SignsClinical Signs

• Incubation period: 3-14 days • Birds found dead• Drop in egg production• Neurological signs• Depression, anorexia,

ruffled feathers• Combs swollen, cyanotic• Conjunctivitis and respiratory signs

Post Mortem LesionsPost Mortem Lesions

• Lesions may be absent with sudden death

• Severe congestion of the musculature

• Dehydration• Subcutaneous

edema of head and neck area

Post Mortem LesionsPost Mortem Lesions

• Nasal and oral cavity discharge• Petechiae on serosal surfaces• Kidneys severely congested• Severe congestion of

the conjunctivae

عالئم بيماريعالئم بيماري بيماري ناگهاني بيماري شروع ناگهاني شروع( گرفتگي ( برق حالت نشاني بدون )تلفات گرفتگي ( برق حالت نشاني بدون تلفات تا حتي تلفات فزاينده تا افزايش حتي تلفات فزاينده %%100100افزايش حاد تنفسي حاد عالئم تنفسي عالئم گله در بيماري سريع گله گسترش در بيماري سريع گسترش پا ساق و ريش و تاج شدن پا سيانوره ساق و ريش و تاج شدن سيانوره بيني و چشمي بيني ترشحات و چشمي ترشحات اشتها اشتها كاهش كاهش عصبي عصبي عالئم عالئماسهال

ر و تاج ر تورم و تاج ششييتورم

ز يزيخونر جلدی يهای ر

نای يخونر زی

Differential DiagnosisDifferential Diagnosis

• Virulent Newcastle disease• Avian pneumovirus• Infectious laryngotracheitis• Infectious bronchitis• Chlamydia• Mycoplasma• Acute bacterial diseases

−Fowl cholera, E. coli infection

DiagnosisDiagnosis

• Clinically indistinguishable from virulent Newcastle Disease

• Suspect with:−Sudden death−Drop in egg production−Facial edema, cyanotic combs

and wattles−Petechial hemorrhages

• Virology and serology necessary for definitive diagnoses

DiagnosisDiagnosis

• Laboratory Tests−HP AI is usually diagnosed by

virus isolation• Presence of virus confirmed by

−AGID−ELISA−RT-PCR

• Serology may be helpful

Avian Influenza in Humans

Avian FluAvian Flu1)Fever 1)Fever

&&2)at least one of the following items:2)at least one of the following items: Sore throatSore throat HeadacheHeadache ConjunctivitisConjunctivitis DyspneaDyspnea

&&3)At least one of the following epidemiologic clues:3)At least one of the following epidemiologic clues: Hx of contact to dead bird during preceding 10 daysHx of contact to dead bird during preceding 10 days Hx of contact to confirmed human case of avian flu, during Hx of contact to confirmed human case of avian flu, during

preceding 10 dayspreceding 10 days Hx of contact to suspicious environmental area during Hx of contact to suspicious environmental area during

preceding 10 dayspreceding 10 days Hx of occupational contact in the lab during preceding 10 Hx of occupational contact in the lab during preceding 10

daysdays Positive inf A virus detection without knowing it’s subtypePositive inf A virus detection without knowing it’s subtype

Initial symptomsInitial symptoms High fever >38.cHigh fever >38.c HeadacheHeadache MyalgiaMyalgia Watery diarrheaWatery diarrhea Abdominal painAbdominal pain Vomiting Vomiting CoughCough SputumSputum Sore throatSore throat Bleeding nose and gumsBleeding nose and gums RhinorrheaRhinorrhea Shortness of breathShortness of breath Conjunctivitis(Rarely)Conjunctivitis(Rarely)

0-1 days high fever (above 38 °C), cough and shortness ofBreath

1-7 daysearly dyspnea crackles rapid progress to respiratorydistress - respiratory failure

Incubation Period

Prodromal Stage

Lower Respiratory Stage

Recovery in 30% of cases

Mostcases have died in spite of ventilatory support after about 10 days

Exposure

Clinical Stages of AI in humans

3 days, range 2-4 days

Avian flu characteristics.1Avian flu characteristics.1

Lower respiratory tract manifestations Lower respiratory tract manifestations dyspneadyspnea Respiratory distress, tachypnea, and Respiratory distress, tachypnea, and

inspiratory crackles are common. inspiratory crackles are common. Radiographic changes include diffuse, multifocal, Radiographic changes include diffuse, multifocal,

or patchy infiltrates; interstitial infiltrates; and or patchy infiltrates; interstitial infiltrates; and segmental or lobular consolidation with air segmental or lobular consolidation with air bronchograms. Radiographic abnormalities were bronchograms. Radiographic abnormalities were present a median of 7 days after the onset of present a median of 7 days after the onset of fever in one study fever in one study

Pleural effusions are uncommon. Pleural effusions are uncommon. primary viral pneumonia, usually without primary viral pneumonia, usually without

bacterial super infectionbacterial super infection

Avian flu characteristics:2Avian flu characteristics:2

Progression to respiratory failure Progression to respiratory failure Manifestations of the acute respiratory Manifestations of the acute respiratory

distress syndrome (ARDS)distress syndrome (ARDS) Multiorgan failure with signs of renal Multiorgan failure with signs of renal

dysfunction dysfunction Ventilator-associated pneumonia, Ventilator-associated pneumonia,

pulmonary hemorrhage, pneumothorax, pulmonary hemorrhage, pneumothorax, pancytopenia, Reye's syndrome, and sepsis pancytopenia, Reye's syndrome, and sepsis syndrome without documented bacteremia. syndrome without documented bacteremia.

Mortality in avian fluMortality in avian flu

The fatality rate among hospitalized patients The fatality rate among hospitalized patients has been high has been high

The overall rate is probably much lower inThe overall rate is probably much lower in patients older than 13 years of agepatients older than 13 years of age The case fatality rate was 89 percent among The case fatality rate was 89 percent among

those younger than 15 years of age in Thailand. those younger than 15 years of age in Thailand. Death has occurred an average of 9 or 10 days Death has occurred an average of 9 or 10 days

after the onset of illness. after the onset of illness. Most patients have died of progressive Most patients have died of progressive

respiratory failurerespiratory failure

Laboratory findingsLaboratory findings

1.1. leukopenia particulary lymphopenialeukopenia particulary lymphopenia

2.2. mild –to-moderate thrombocytopeniamild –to-moderate thrombocytopenia

3.3. mild-to-moderate elevated mild-to-moderate elevated

Aminotransferase levelsAminotransferase levels

Some laboratory Findings in Some laboratory Findings in avian fluavian flu

Marked hyperglycemiaMarked hyperglycemia

Elevated creatinine levelsElevated creatinine levels Death was associated with decreased Death was associated with decreased

leukocyte, platelet, and particularly, leukocyte, platelet, and particularly, lymphocyte counts at the time of lymphocyte counts at the time of admission. admission.

Radiographic changes :Radiographic changes :

Diffuse ,multifocal , or patchy Diffuse ,multifocal , or patchy

infiltrates interstitial infiltrates infiltrates interstitial infiltrates

and segmental or lobular and segmental or lobular

consolidation with air consolidation with air

bronchograms bronchograms

Pleural effusions are uncommon Pleural effusions are uncommon

Radiological FindingsRadiological Findings

Virologic diagnosisVirologic diagnosis

1.1. Viral Viral

isolation(pharyngeal>nasal)isolation(pharyngeal>nasal)

2.2. RT – PCRRT – PCR

3.3. Rapid antigen testRapid antigen test

When do you suspect to flu in a When do you suspect to flu in a case?case?

Very important key findings:Very important key findings: Characteristics of feverCharacteristics of fever Toxic appearance at presentation+/-Toxic appearance at presentation+/- Body pain+/-Body pain+/-

Avian flu has many clinical Avian flu has many clinical similarities but the key point is the similarities but the key point is the epidemiologic evidencesepidemiologic evidences

CASE DEFINITIONSCASE DEFINITIONS Person under investigationPerson under investigation

A person whom public health authorities have decided to investigate for possible H5N1 A person whom public health authorities have decided to investigate for possible H5N1 infection. infection.

Suspected H5N1 caseSuspected H5N1 case

A person presenting with unexplained acute lower respiratory illness with fever (>38 ºC ) A person presenting with unexplained acute lower respiratory illness with fever (>38 ºC ) and cough, shortness of breath or difficulty breathingand cough, shortness of breath or difficulty breathing. .

ANDAND

One or more of the following exposures in the 7 days prior to symptom One or more of the following exposures in the 7 days prior to symptom onset:onset:

a. Close contact (within 1 meter) with a person (e.g. caring for, speaking with, a. Close contact (within 1 meter) with a person (e.g. caring for, speaking with, or touching) who is a suspected, probable, or confirmed H5N1 case;or touching) who is a suspected, probable, or confirmed H5N1 case;

b. Exposure (e.g. handling, slaughtering, defeathering, butchering, preparation b. Exposure (e.g. handling, slaughtering, defeathering, butchering, preparation for consumption) to poultry or wild birds or their remains or to environments for consumption) to poultry or wild birds or their remains or to environments contaminated by their faeces in an area where H5N1 infections in animals or contaminated by their faeces in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month;humans have been suspected or confirmed in the last month;

c. Consumption of raw or undercooked poultry products in an area where H5N1 c. Consumption of raw or undercooked poultry products in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last infections in animals or humans have been suspected or confirmed in the last month;month;

d. Close contact with a confirmed H5N1 infected animal other than poultry or d. Close contact with a confirmed H5N1 infected animal other than poultry or wild birds (e.g. cat or pig);wild birds (e.g. cat or pig);

e. Handling samples (animal or human) suspected of containing H5N1 virus in a e. Handling samples (animal or human) suspected of containing H5N1 virus in a laboratory or other setting. laboratory or other setting.

CASE DEFINITIONSCASE DEFINITIONS Probable H5N1 case Probable H5N1 case ((notify WHOnotify WHO)) Probable definition 1 Probable definition 1 ::

A person meeting the criteria for a suspected caseA person meeting the criteria for a suspected case

AND AND

One of the following additional criteria: One of the following additional criteria: a. infiltrates or evidence of an acute pneumonia on chest a. infiltrates or evidence of an acute pneumonia on chest

radiograph plus evidence of respiratory failure (hypoxemia, radiograph plus evidence of respiratory failure (hypoxemia, severe tachypneasevere tachypnea) )

OROR

b. positive laboratory confirmation of an influenza A b. positive laboratory confirmation of an influenza A infection but insufficient laboratory evidence for H5N1 infection but insufficient laboratory evidence for H5N1 infection. infection.

Probable definition 2 Probable definition 2 ::A person dying of an unexplained acute respiratory illness A person dying of an unexplained acute respiratory illness who is considered to be epidemiologically linked by time, who is considered to be epidemiologically linked by time, place, and exposure to a probable or confirmed H5N1 case.place, and exposure to a probable or confirmed H5N1 case.

CASE DEFINITIONSCASE DEFINITIONS Confirmed H5N1 case (notify WHO)Confirmed H5N1 case (notify WHO)

A person meeting the criteria for a suspected or probable A person meeting the criteria for a suspected or probable casecase

AND AND

One of the following positive results conducted in a national, One of the following positive results conducted in a national, regional or international influenza laboratory whose H5N1 test regional or international influenza laboratory whose H5N1 test results are accepted by WHO as confirmatory: results are accepted by WHO as confirmatory:

a. Isolation of an H5N1 virus; a. Isolation of an H5N1 virus;

b. Positive H5 PCR results from tests using two different PCR b. Positive H5 PCR results from tests using two different PCR targets, e.g. primers specific for influenza A and H5 HA;targets, e.g. primers specific for influenza A and H5 HA;

c. A fourfold or greater rise in neutralization antibody titer for c. A fourfold or greater rise in neutralization antibody titer for H5N1 based on testing of an acute serum specimen (collected 7 H5N1 based on testing of an acute serum specimen (collected 7 days or less after symptom onset) and a convalescent serum days or less after symptom onset) and a convalescent serum specimen. The convalescent neutralizing antibody titer must also specimen. The convalescent neutralizing antibody titer must also be 1:80 or higher;be 1:80 or higher;

d. A microneutralization antibody titer for H5N1 of 1:80 or greater d. A microneutralization antibody titer for H5N1 of 1:80 or greater in a single serum specimen collected at day 14 or later after in a single serum specimen collected at day 14 or later after symptom onset and a positive result using a different serological symptom onset and a positive result using a different serological assay, for example, a horse red blood cell haemagglutination assay, for example, a horse red blood cell haemagglutination inhibition titer of 1:160 or greater or an H5-specific western blot inhibition titer of 1:160 or greater or an H5-specific western blot positive result. positive result.

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