Update I had a little bird, It s name was Enza, I opened up the window, And In Flu Enza.

Transcription

1 I had a little bird, It s name was Enza, I opened up the window, And In Flu Enza. Update Timothy R. Cassity, Ph.D. Microbiologist Southern Ohio Medical Center January 16, 2015

2 The opinions expressed in this presentation are those of the presenter. The material presented here does not necessarily reflect the views of Southern Ohio Medical Center.

3 The author/presenter has no relevant financial relationships with any of the companies that produce or distribute any of the products that may be mentioned in this presentation.

4 The references for the information included in this presentation are available upon request. Most of the information has come from Morbidity and Mortality, and Emerging Infectious Diseases published by CDC.

5 Understand the current status of influenza virus infections locally and nationwide

6 Understand the role of the laboratory, and laboratory testing options for the diagnosis of influenza

7 Understand the treatment and prevention options available for patients with influenza

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9 A single-stranded RNA genome is closely associated with a helical nucleoprotein (NP), and is present in eight separate segments of ribonucleoprotein (RNP)

10 All 8 have to be present for successful replication. Influenza viruses change genetically quite easily. This causes antigenic drift Permits persistence of the virus and prevents its extinction

11 The envelope carries two types of protruding spikes. One is a box-shaped protein, called the neuraminidase (NA), There are nine major antigenic types neuraminidase (N types).

12 The other type of envelope spike is the hemagglutinin (HA) There are 15 major antigenic types (H types).

13 The hemagglutinin functions during attachment of the virus particle to the cell membrane

14 Because the genome is small, changes in one or a few bases in a RNA segment can result in an antigenically distinct virus Permits re-infection with influenza virus Makes vaccine design and production difficult

15 Most of the influenza viruses this season have been drifted A/H3N2 strains. H3N2-predominant seasons have been associated with more severe illness and mortality, especially in older people and young children compared to A/H1N1 predominant seasons.

16 Primarily 3 natural hosts that involve human infection. Humans Swine Birds Some strains have jumped from one host to another.

17 First classified based on the Matrix protein (A or B)

18 Second - classed by hemagglutinin and neuraminidase types. H type (1 to 15) N type (1 to 9)

19 Further classed by city/country initially isolated from, number of isolates, and year of isolation. This information is not helpful clinically More important to vaccine developers and epidemiologists

20 Example: A/Panama/2007/99 (H3N2) Type A matrix protein, isolated from Panama 99 times in Hemagglutinin type 3, neuraminidase type 2.

21 It is difficult to determine an exact number of cases. Estimates 100, ,000 hospital admissions annually 3,000 36,000 deaths annually Financial impact huge Study done in 2003 at NIH calculated the annual cost of influenza in the U.S. as $87.1 billion.

22 With typical influenza, most mortality is due to secondary bacteria pneumonia Influenza predisposes some individuals to a rapidly developing bacterial pneumonia. Pneumonia due to Staphylococcus aureus and Haemophilus influenza are the most common, even though many also get pneumonia with Streptococcus pneumonia.

23 Influenza virus is transmitted via aerosols and infects cells of the respiratory tract. The time from infection until occurrence of symptoms (incubation period) is usually 1-3 days.

24 Adults "shed" influenza virus for approximately 7 days following infection During this time they can spread the infection to others. High viral titers more contagious early in infection Children can shed virus longer.

25 Number Pos LOCALLY NATIONALLY Number of Viral Cultures positive for influenza A and B virus Week ending Influenza A Influenza B

26 Data from SOMC Microbiology RT- PCR Testing data are not accurate as far as actual numbers Most of the data comes from specimens that tested as negative using a rapid influenza test. Actual numbers are approximately 4 5 times higher. Data includes only those presenting to SOMC facilities.

27 10/4/ /18/ /1/ /15/ /29/ /13/ /27/2014 1/10/2015 Number Number of Viral cultures performed per week Week ending

28 Number Pos Number of RT-PCR positive tests for influenza A & B Week ending Influenza A Influenza B

29 60.0% Percent Pos Influenza A & B versus Patient Age 50.0% 40.0% 30.0% Flu B Flu A 20.0% 10.0% 0.0% <

30 120 Positive Influenza RT-PCR Pos Influenza OPT UCC INPAT ED

31 63 y/o male with COPD exacerbation. This patient was morbidly obese, a diabetic, and had several other comorbidities. 92 y/o female admitted because of weakness with a diagnosis of influenza. She improved with hydration and oseltamivir and was discharged to home in 3 days.

32 79 y/o male with a mental status change - this patient had Alzheimer's and Parkinson's as well as several other co-morbidities. His admitting diagnosis was encephalopathy. 80 y/o female with COPD exacerbation and severe dyspnea.

33 A 85 y/o female who fell in the night and broke her hip. She had surgery to repair the hip fracture. 76 y/o male with end stage COPD, diabetes, and multiple comorbidities.

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41 Patients Influenza A Prevalence by Fiscal Year H1N1 H3N Week Ending Date

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45 Abrupt onset Fever ( F) Chills Chilly feeling, not shaking chills) Weakness Myalgia Headache Lumbosacral backache Sore throat and dry cough

46 Children may present with vomiting and diarrhea Vomiting and diarrhea usually not found in adults

47 Laboratory diagnosis or confirmation of influenza is generally not necessary for most outpatients once influenza is known to be circulating in the community Clinical diagnosis sufficient unless patient is being admitted to the hospital or antiviral therapy is being considered.

48 Laboratory diagnosis or confirmation of influenza is beneficial for inpatients Specific diagnosis and documentation is needed for infection control purposes as well as treatment on hospitalized patients. Most influenza positive inpatients receive anti-viral therapy.

49 Test Method Rapid Enzyme Immunoassay Viral Culture Limit of Detection 50,000 PFU/ml 1,000 PFU/ml RT-PCR (reverse transcriptase polymerase chain reaction) <100 PFU/ml

50 For admitted patients, submit specimen for influenza RT-PCR (in season) or virus culture (out of season). Preferred Specimens - nasal wash, nasopharyngeal swab, bronch wash, or BAL. Not as good Nasal swabs or throat swabs

51 Rapid enzyme immunoassays lack sensitivity and specificity! 10 to 70% for A/H1N1, average 65% when compared to real time RT-PCR. Negative predictive value around 32% Cannot be used to rule out influenza if negative. Cannot be used to make any treatment or infection control decisions.

52 Rapid enzyme immunoassays lack sensitivity and specificity Specificity 80% in non-symptomatic patients (20% false positive) Specificity around 90% in symptomatic patients. (10% false positive) Can be used to confirm influenza in a symptomatic patient, but is generally unnecessary.

53 Rapid enzyme immunoassays lack sensitivity and specificity Because of poor sensitivity, patients with negative results must have an influenza culture or RT-PCR to confirm EIA result, particularly during times of high influenza prevalence.

54 Rapid enzyme immunoassays lack sensitivity and specificity Because of poor specificity, patients with positive results should have an influenza culture or RT-PCR to confirm EIA result when influenza is not widely circulating.

55 When can you believe the results of a rapid influenza EIA? When the patient has a typical presentation and influenza is known to be widely circulating, you can believe a positive test result.

56 Rapid enzyme immunoassays In general, these are more risk than value. Many horror stories of patients with influenza who were misdiagnosed by these. ASM recommends NOT using these, and if they are used to include disclaimers that you cannot rely on the results.

57 Rapid enzyme immunoassays - My biased opinion WORTHLESS. Nothing worse than a lying lab test!

58 Real-time reverse transcriptase polymerase chain reaction (RT-PCR) Gold standard Done at SOMC when influenza is prevalent. Sensitivity approximately 10X higher than viral culture and 500X EIA Turnaround 5 24 hours.

59 Viral culture reliable Past gold standard, now co-gold standard with RT-PCR Done at SOMC when influenza prevalence is low Turnaround hours

60 Viral culture reliable Sensitivity >90% when compared to RT- PCR Sensitivity 50X that of a rapid EIA Specificity 100%

61 Specific Typing (such as for A/H1N1) Do we need it? NO, not for clinical management of the patient. Useful for public health and curiosity (takes about a month to get a result back).

62 Replace rapid EIA testing with a more sensitive method. Method that does require back-up PCR testing. Rapid molecular test that can be done point of care. Rapid immunofluorescent detection done point of care.

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64 Decision to treat with antiviral should be made on the basis of severity of illness and underlying patient conditions. Most outpatients with mild illness receive little clinical benefit from antiviral treatment. Symptomatic relief and comfort measures are preferable to antivirals

65 Decision to treat with antiviral should be made on the basis of severity of illness and underlying patient conditions. Patients with symptoms >= 3 days duration receive no benefit from antivirals. Symptomatic relief important with or without antiviral

66 High Risk of Severe Illness Children < 2 years Adults > 65 years persons with chronic pulmonary, cardiovascular, renal, hepatic, hematological, and metabolic disorders persons with immunosuppression women who are pregnant persons who are morbidly obese residents of nursing homes and other chronic care facilities.

67 Antiviral treatment is recommended as soon as possible for all persons with suspected or confirmed influenza requiring hospitalization or who have progressive, severe or complicated illness regardless of previous health or vaccination status.

68 Those with illness severe enough for hospitalization: Should receive antiviral treatment (Typically oseltamivir or peramivir) Should receive prophylactic antibiotics for bacterial pneumonia, including S. aureus? Aggressive supportive therapy

69 Neuraminidase Inhibitor Resistance Testing Results on Samples Collected Since October 1, 2014 Strain No. Tested Percent Susceptible Oseltamivir Zanamivir Peramivir Influenza A (H3N2) % 100% 100% Influenza B % 100% 100% Influenza A (H1N1)pdm % 100% 100% Note: Amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A (or B) viruses. > 99% of current influenza A strains are resistant.

70 In both adults and children, treatment with oseltamivir had no significant effect on whether they were admitted to hospital.

71 Studies on patients with mild illness in outpatient settings showed oseltamivir can reduce the duration of uncomplicated influenza by approximately 1 day compared with placebo when administered within 48 hours of illness onset.

72 Minimal or no benefit was reported in healthy children and adults when antiviral treatment was initiated more than 2 days after onset of uncomplicated influenza.

73 In adults, zanamivir reduced the time until the first alleviation of symptoms in adults by 0.60 days

74 Cochrane Review Both oseltamivir and zanamivir both shorten the symptoms of illness by about half a day in adults (but not in asthmatic children), compared to a placebo.

75 In adults, oseltamivir reduced the time it took to first alleviate symptoms by 16.8 hours. There was no effect in asthmatic children but in otherwise healthy children, there was an average reduction in the time it took to first alleviate symptoms of 29 hours.

76 Wholesale cost to a Pharmacy is about $115 for ten 75 mg tablets. Retail costs per script range from $155 ($139 with coupon) to $240.

77 Peramivir was approved by the FDA 12/19/14. It is a single dose, IV neuraminidase inhibitor. In available studies, peramivir shortened duration of symptoms by 1 day, on average.

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79 Vaccinate! Vaccination by no means totally prevents influenza, but it is still the best method of preventing it.

80 Multi-Year vaccine? Research has been underway for years to develop a vaccine against conserved antigens so that the vaccine that doesn t have to be produced and administered annually. To date there has not been good success with these vaccines.

81 Vaccinate! Cell culture based vaccine instead of eggbased vaccines is available! Will eventually replace egg-based vaccines??

82 The current injectible flu vaccines contain no live or dead whole virus, only viral proteins. You cannot get influenza from the vaccine.

83 Trivalent vaccine A/California/7/2009 (H1N1)pdm09 A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 Quadrivalent vaccine Same as Trivalent, plus B/Brisbane/60/2008

84 All persons aged 6 months should receive influenza vaccine annually. LAIV should be used for healthy children aged 2 through 8 years who have no contraindications.

85 Antibody levels induced by vaccine develop in days in most patients. Antibody levels induced by vaccine decline post-vaccination Vaccine effectiveness significantly diminished after 6 months post-vaccination. Titers may decrease more rapidly in patients >65 y/o.

86 Standard influenza vaccine is less immunogenic in patients > 65 years old. High dose recommended for those > 65 y/o. Fluzone makes a high-dose vaccine for patients >65 y/o

87 Flumist is a nasal vaccine that does contain a live attenuated virus. Works better in children 2 8 years old than adults

88 LAIV should not be used in the following populations: Persons aged <2 years or >49 years; Those with contraindications listed in the package insert: Children aged 2 through 17 years who are receiving aspirin or aspirin-containing products; Persons who have experienced severe allergic reactions to the vaccine or any of its components, or to a previous dose of any influenza vaccine; Pregnant women; Immunosuppressed persons

89 LAIV should not be used in the following populations: Persons with a history of egg allergy; Children aged 2 through 4 years who have asthma or who have had a wheezing episode noted in the medical record within the past 12 months Persons who have taken influenza antiviral medications within the previous 48 hours.

90 October early November through the end of the season is preferable. Most seasons occur in Dec Feb. Antibodies are produced in 10 days post vaccination. Influenza vaccine good for 6 months.

91 Depends on the immune competence of the patient The "match" between the strains in the flu vaccine and the flu viruses circulating in the community. The better the match the better the protection

92 Protection against getting influenza Good match 60-70% effective Prevents spread of influenza 77% reduction in hospitalizations among adults 50 years old

93 Strains have matched 16 of the last 20 years Even if not perfect match, vaccination minimizes severity and duration of influenza

94 Meticulous hand hygiene is important Other good hygienic practices Masks and aerosol prevention A popular public-health slogan in was: Obey the laws, And wear the gauze, Protect yourself, From septic paws.

95 Neuraminidase inhibitors are approximately 70% to 90% effective in preventing influenza and are adjuncts to influenza vaccination. Routine chemoprophylaxis is not recommended. May promote development of resistance

96 Antiviral chemoprophylaxis is not indicated if more than 48 hours have elapsed since the first exposure to an infectious person. Antiviral chemoprophylaxis is expensive. $350 - $700 per person Used only in specific situations

97 Examples of situations where chemoprophylaxis is indicated: People with severe immune deficiencies after exposure to an infectious person. People at high risk for complications from influenza who cannot receive influenza vaccine after exposure to an infectious person.

98 Examples of situations where chemoprophylaxis is indicated: Residents of institutions, such as longterm care facilities, during influenza outbreaks in the institution. Chemoprophylaxis may also be considered for employees if the outbreak is caused by a strain of influenza virus that is not wellmatched by the vaccine.

99 Antiviral chemoprophylaxis should be administered for a minimum of two weeks, and continue for at least seven days after the last known case was identified.

100 Maybe to most likely Influenza outbreaks depend on the immunity of the community to circulating viruses!

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