INFLUENZA CLINICAL FINDINGS & CASE DETECTION

3. INFLUENZACLINICAL FINDINGS & CASE DETECTION مركز بهداشت استان اصفهان گروه مبارزه با بيماريها

4. Definition of flu • Definition might be different according to Flu alert status • Classic definition: 1)Fever 2)Cough or sore throat 3) 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 c 2)cough,sore throat,or dyspnea

5. 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

6. No significant risk related to eating or preparing poultryproducts or exposure to persons withinfluenzaA (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

7. Potential Modes: • Oral ingestion of contaminated water during swimming and directintranasal or conjunctival inoculation during exposure to water • Contamination of hands frominfected fomites and subsequent self-inoculation

8. 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

9. نحوه انتقال ويروس آنفلوآنزای طيور به انسان • تماس مستقيم و نزديک انسان با پرنده آلوده • انتقال ويروس آنفلوآنزا از طريق خوردن گوشت پرنده آلوده بصورت پخته ميسر نمی باشد ولی توصيه ميگردد از خوردن گوشت و تخم مرغ آلوده بصورت نيم پز اجتناب گردد.

10. پاندمیهای جهانی آنفلوآنزا در قرن بیستم Credit: US National Museum of Health and Medicine 1968: “Hong KongFlu” 1957: “Asian Flu” 1918: “Spanish Flu” 1 - 4 million deaths 1 - 4 million deaths 20 - 40 million deaths A(H3N2) A(H2N2) A(H1N1)

11. Clinical findings .1 Classic 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

12. Clinical findings .2 Uncomplicated 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

13. 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

14. COMPARISON OF FINDINGS IN ADULTS VS CHILDREN(%)

15. Animals and Highly Pathogenic Avian Influenza

16. Clinical 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

17. Post Mortem Lesions • Lesions may be absent with sudden death • Severe congestion of the musculature • Dehydration • Subcutaneous edema of head and neck area

18. Post Mortem Lesions • Nasal and oral cavity discharge • Petechiae on serosal surfaces • Kidneys severely congested • Severe congestion of the conjunctivae

19. علائم بيماري • شروع ناگهاني بيماري • تلفات بدون نشاني (حالت برق گرفتگي) • افزايش فزاينده تلفات حتي تا 100% • علائم تنفسي حاد • گسترش سريع بيماري در گله • سيانوره شدن تاج و ريش و ساق پا • ترشحات چشمي و بيني • كاهش اشتها • علائم عصبي • اسهال

20. تورم تاج و ريش

21. خونريزيهای زير جلدی

22. خونريزی نای

23. Differential Diagnosis • Virulent Newcastle disease • Avian pneumovirus • Infectious laryngotracheitis • Infectious bronchitis • Chlamydia • Mycoplasma • Acute bacterial diseases • Fowl cholera, E. coli infection

24. Diagnosis • 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

25. Diagnosis • Laboratory Tests • HP AI is usually diagnosed by virus isolation • Presence of virus confirmed by • AGID • ELISA • RT-PCR • Serology may be helpful

26. Avian Influenza in Humans

27. Avian Flu 1)Fever & 2)at least one of the following items: • Sore throat • Headache • Conjunctivitis • Dyspnea & 3)At least one of the following epidemiologic clues: • Hx of contact to dead bird during preceding 10 days • Hx of contact to confirmed human case of avian flu, during preceding 10 days • Hx of contact to suspicious environmental area during preceding 10 days • Hx of occupational contact in the lab during preceding 10 days • Positive inf A virus detection without knowing it’s subtype

28. Initial symptoms • High fever >38.c • Headache • Myalgia • Watery diarrhea • Abdominal pain • Vomiting • Cough • Sputum • Sore throat • Bleeding nose and gums • Rhinorrhea • Shortness of breath • Conjunctivitis(Rarely)

29. Clinical Stages of AI in humans Recovery in 30% of cases Exposure Incubation Period Prodromal Stage Lower Respiratory Stage 3 days, range 2-4 days 0-1 days high fever (above 38 °C), cough and shortness of Breath 1-7 days early dyspnea crackles rapid progress to respiratory distress - respiratory failure Most cases have died in spite of ventilatory support after about 10 days

30. Avian flu characteristics.1 • Lower respiratory tract manifestations • dyspnea • Respiratory distress, tachypnea, and inspiratory crackles are common. • Radiographic changes include diffuse, multifocal, or patchy infiltrates; interstitial infiltrates; and segmentalor lobular consolidation with air bronchograms. Radiographicabnormalities were present a median of 7 days after the onsetof fever in one study • Pleural effusions are uncommon. • primary viral pneumonia, usually without bacterial super infection

31. Avian flu characteristics:2 • Progression to respiratory failure • Manifestations of the acute respiratory distress syndrome (ARDS) • Multiorgan failure with signs of renal dysfunction • Ventilator-associated pneumonia, pulmonary hemorrhage, pneumothorax, pancytopenia, Reye's syndrome, and sepsis syndrome without documented bacteremia.

33. Mortality in avian flu • The fatality rate among hospitalized patients has been high • The overall rate is probably much lower in patientsolder than 13 years of age • The case fatality rate was 89 percent amongthose younger than 15 years of age in Thailand. • Death has occurredan average of 9 or 10 days after the onset of illness. • Most patients have died of progressive respiratoryfailure

34. Laboratory findings • leukopenia particulary lymphopenia • mild –to-moderate thrombocytopenia • mild-to-moderate elevated Aminotransferase levels

35. Some laboratory Findings in avian flu • Markedhyperglycemia • Elevatedcreatinine levels • Death was associated with decreased leukocyte, platelet, and particularly, lymphocyte counts at the time of admission.

36. Radiographic changes : • Diffuse ,multifocal , or patchy infiltrates interstitial infiltrates and segmental or lobular consolidation with air bronchograms • Pleural effusions are uncommon

37. Radiological Findings

38. Virologic diagnosis • Viral isolation(pharyngeal>nasal) • RT – PCR • Rapid antigen test

39. When do you suspect to flu in a case? Very important key findings: • Characteristics of fever • Toxic appearance at presentation+/- • Body pain+/- • Avian flu has many clinical similarities but the key point is the epidemiologic evidences

40. CASE DEFINITIONS • Person under investigationA person whom public health authorities have decided to investigate for possible H5N1 infection. • Suspected H5N1 caseA person presenting with unexplained acute lower respiratory illness with fever (>38 ºC ) and cough, shortness of breath or difficulty breathing. ANDOne or more of the following exposures in the 7 days prior to symptom onset: 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;b. Exposure (e.g. handling, slaughtering, defeathering, butchering, preparation 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 humans have been suspected or confirmed in the last month;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 month;d. Close contact with a confirmed H5N1 infected animal other than poultry or wild birds (e.g. cat or pig);e. Handling samples (animal or human) suspected of containing H5N1 virus in a laboratory or other setting.

41. CASE DEFINITIONS • Probable H5N1 case (notify WHO) • Probable definition 1 :A person meeting the criteria for a suspected caseAND One of the following additional criteria: a. infiltrates or evidence of an acute pneumonia on chest radiograph plus evidence of respiratory failure (hypoxemia, severe tachypnea) ORb. positive laboratory confirmation of an influenza A infection but insufficient laboratory evidence for H5N1 infection. • Probable definition 2 :A person dying of an unexplained acute respiratory illness who is considered to be epidemiologically linked by time, place, and exposure to a probable or confirmed H5N1 case.

42. CASE DEFINITIONS • Confirmed H5N1 case (notify WHO) A person meeting the criteria for a suspected or probable caseAND One of the following positive results conducted in a national, regional or international influenza laboratory whose H5N1 test results are accepted by WHO as confirmatory: a. Isolation of an H5N1 virus; b. Positive H5 PCR results from tests using two different PCR targets, e.g. primers specific for influenza A and H5 HA;c. A fourfold or greater rise in neutralization antibody titer for H5N1 based on testing of an acute serum specimen (collected 7 days or less after symptom onset) and a convalescent serum specimen. The convalescent neutralizing antibody titer must also be 1:80 or higher;d. A microneutralization antibody titer for H5N1 of 1:80 or greater in a single serum specimen collected at day 14 or later after symptom onset and a positive result using a different serological assay, for example, a horse red blood cell haemagglutination inhibition titer of 1:160 or greater or an H5-specific western blot positive result.

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