Κλινική διάγνωση και πορεία νόσου “ΛΟΙΜΩΞΗ ΑΠΟ ΤΟΝ ΙΟ ΓΡΙΠΗΣ A H1N1 ΝΕΩΤΕΡΑ ΔΕΔΟΜΕΝΑ” 22/09/2009, Δώμα, ΓΝΑ «Ευαγγελισμός» Κλινική διάγνωση και πορεία νόσου Kαθ. Αθ.Σκουτέλης Ε΄Παθολογική Κλινική & Μονάδα Λοιμώξεων ΓΝΑ «Ευαγγελισμός»

The Normal Burden of Disease Influenza The Normal Burden of Disease Seasonal Influenza Globally: 250,000 to 500,000 deaths per year In the US (per year) ~35,000 deaths >200,000 Hospitalizations $37.5 billion in economic cost (influenza & pneumonia) >$10 billion in lost productivity Pandemic Influenza An ever present threat

The situation could be a lot worse for Europe The situation could be a lot worse for Europe! (Situation circa summer 2009) Contrast with what might have happened — and might still happen! A pandemic emerging in SE Asia A pandemic strain emerging in the Americas. Immediate virus sharing so rapid diagnostic and vaccines. Pandemic (H1N1) currently not that pathogenic. Some seeming residual immunity in a major large risk group (older people). No known pathogenicity markers. Initially susceptible to oseltamivir. Good data and information coming out of North America. Arriving in Europe in the summer. Mild presentation in most. Delayed virus sharing Based on a more pathogenic strain, e.g. A(H5N1) No residual immunity Heightened pathogenicity Inbuilt antiviral resistance Minimal data until transmission reached Europe Pandemics come in all shapes and sizes and are highly unpredictable. This slide should be looked at with a later one – on Known Knowns and Known Unknowns – this slide in particular shows how fortunate we have been so far with this pandemic Arriving in the late autumn or winter Severe presentation immediately

Η1Ν1-ΧΑΡΑΚΤΗΡΙΣΤΙΚΑ Μεγαλη μεταδοτικοτητα (>100Χ εποχικης) Ηπια κλινικη εικονα Μικρη θνητοτητα

ΓΙΑΤΙ ΑΝΗΣΥΧΟΥΜΕ;

H1N1 Πανδημια Προσβαλλει νεα/ανοσοεπαρκη ατομα Μπορει να προκαλεσει αιφνιδια πνευμονια ή/και ταχεια εξελιξη σε ARDS

Η1Ν1-ΧΑΡΑΚΤΗΡΙΣΤΙΚΑ Οι περισσοτερες περιπτωσεις:παιδια,νεοι ενηλικες Φασμα κλινικων εκδηλωσεων:απο ηπια συμπτωματα ανωτερου αναπνευστικου χωρις πυρετο, εως βαρεια θανατηφορο πνευμονια Συχνοτερα συμπτωματα: βηχας, πυρετος,κυναγχη,κακουχια,πονοκεφαλος Προσβολη κατωτερου αναπνευστικου σε νοσηλευομενους ασθενεις Αλλες επιπλοκες:ραβδομυολυση με νεφρ.ανεπαρκεια, μυοκαρδιτις, επιδεινωση υποκειμενων νοσηματων

Requiring hospitalisation Seasonal influenza compared to pandemic — proportions of types of cases Deaths Requiring hospitalisation Clinical symptoms Deaths Asymptomatic Clinical symptoms Requiring hospitalisation But remember this is idealised – and in 2009 in North America this is not putting as many people into Hospital as you would expect from the above. In the 2009 pandemic it is not clear yet what percentage are asymptomatic. Two reasonable estimates are 33% and 50% of the total infected. [Note to Uwe – can you increase the asymptomatic fraction in both to make them look about 33% of the total] Asymptomatic Seasonal influenza Pandemic

Laboratory findings   Both leukocytosis and leukopenia have been observed among hospitalized patients. In Mexico, many hospitalized patients have had leukopenia, elevated aminotransferases, elevated lactate dehydrogenase, and elevated creatinine phosphokinase. Some patients have also had renal insufficiency. World Health Organization. Human infection with new influenza A (H1N1) virus: clinical observations from Mexico and other affected countries, May 2009. Weekly epidemiological record 2009; 84:185.

ΔΙΑΓΝΩΣΗ Η κλινικη διαγνωση εχει αυξημενη προγνωστικη αξια, οσο αυξανεται η επιπτωση της νοσου Εργαστηριακη διαγνωση χρειαζεται για: - διαχειριση κρούσματος - αντιιικη θεραπεια - αποφυγη ασκοπης χρησης αντιβιοτικων WHO, Aug. 9, 2009

Rapid antigen tests sensitivity 51-63% specificity 99 % Clinicians may consider using rapid influenza antigen tests as part of their evaluation of patients suspected of having pandemic H1N1 influenza A, but results should be interpreted with caution [70]. Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase (RT)-PCR or culture. sensitivity 51-63% specificity 99 %

Recommended tests  RT-PCR

Swine Influenza A(H1N1) US Case Definitions A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests: real-time RT-PCR viral culture A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is: positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or within 7 days of travel to community either within the United States or internationally where there are one or more confirmed swine influenza A(H1N1) cases, or resides in a community where there are one or more confirmed swine influenza cases. Source: CDC

Η1Ν1 Οι ομαδες υψηλου κινδυνου χρειαζονται ιδιαιτερη προσοχη/χειρισμο

Risk groups for the A(H1N1) pandemic 2009 The following groups are considered more at risk of experiencing severe disease than the general population should they become infected with the pandemic A(H1N1) virus 2009: People with chronic conditions in the following categories: chronic respiratory diseases; chronic cardiovascular diseases (though not isolated mild hypertension); chronic metabolic disorders (notably diabetes); chronic renal and hepatic diseases; persons with deficient immunity (congenital or acquired); chronic neurological or neuromuscular conditions; and any other condition that impairs a person’s immunity or prejudices their respiratory (breathing) function, including severe or morbid obesity. Note: These categories will be subject to amendment and development as more data become available. These are very similar underlying conditions that serve as risk factors for seasonal influenza. What is especially different from seasonal influenza is that the older age groups (over the age of 60 years) without underlying conditions are relatively unaffected by the pandemic strain. Pregnant women. Young children (especially those under two years). ECDC Pandemic 2009 Risk Assessment. Available from: http://www.ecdc.europa.eu/en/Health_topics/novel_influenza_virus/2009_Outbreak Finelli L. CDC Influenza Surveillance. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jun09/15-2-inf.pdf Nicoll A et al. Eurosurveillance, Volume 13, Issue 43, 23 October 2008. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19018 Jamieson D et al. Lancet 2009; July 29, 2009 DOI:10.1016/S0140-6736(09)61304-0 CDC 2009 ACIP Meeting, 31 July 2009. Novel influenza A(H1N1) epidemiology update. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jul09-flu/02-Flu-Fiore.pdf CDC 2009 ACIP Meeting, 31 July 2009. Vaccine workgroup considerations. Available from: http://www.cdc.gov/vaccines/recs/ACIP/downloads/mtg-slides-jul09-flu/11-Flu-Fiore.pdf

ΕΠΙΠΛΟΚΕΣ/ΝΟΣΗΛΕΙΑ Πνευμονια/ARDS σε υγιεις νεους Επιδεινωση υποκειμενων νοσων Αφυδατωση ΚΝΣ, εγκεφαλιτις Μικροβιακη επιλοιμωξη Επιπλοκες: 15% των κλινικων περιστατικων Νοσηλεια: 2-5% (?0.3%) Θνητοτης (case fatality rate): 0.1-0.2 (0.35) %

Οξείες εγκεφαλίτιδες – εγκεφαλοπάθειες σε παιδιά 5% σχετίζονται με επιπλοκές γρίπη Σύσταση για test γρίπης σε περιπτώσεις αναπνευστικής νόσου και συμπτωμάτων από το ΚΝΣ Reye syndrome

Swine Influenza A(H1N1) Mexico Confirmed Cases & Death, by Age Groups As of June 09, 2009 Total Number of Confirmed Cases = 6,241* Deaths = 108 71.3% Deaths Highest % Case-Fatality (77.5%) was observed in the 20-54 year age group. *NOTE: 43 confirmed cases not included Source: Secretaria de Salud, Mexico

10 περιπτώσεις σε ICU 3/10 με προβλήματα υγείας ↑ ↑ BMI ARDS median WBC 9500 c/mm3 (4000-10000) 10/10 ↑AST median 83 IU/l (41-109) 6/10 ↑ CPK median 999IU/L (51-6571) Πνευμονικές εμβολές 4 (5)/10 Θεραπευτική δόση oseltamivire (έως 150mg X2 /24h)

...the 1918 H1N1 influenza virus pandemic…

Severe cases of H1N1 linked to low IgG2 levels ICAAC Sep. 2009

ΝΟΣΟΚΟΜΕΙΑΚΗ ΠΕΡΙΘΑΛΨΗ ΑΥΞΗΜΕΝΗ ΘΝΗΤΟΤΗΤΑ ΑΥΞΗΜΕΝΗ ΔΙΑΣΠΟΡΑ

Ορισμός ύποπτου κρούσματος για νέα γρίπη Α (Η1Ν1) σε ασθενείς που εισάγονται στο Νοσοκομείο για διερεύνηση ή αντιμετώπιση. Οξύ εμπύρετο (>37,7 o C) χωρίς εστία λοίμωξης από την αντικειμενική εξέταση και τα πρώτα εργαστηριακά. Ασθενείς με συμπτωματολογία από το γαστρεντερικό και εμπύρετο θεωρούνται ύποπτα κρούσματα. Η κλινική κρίση του θεράποντος βαραίνει κατά περίπτωση. Στους παραπάνω κρίνεται σκόπιμη η λήψη δείγματος για τον αποκλεισμό της νόσου και τη μείωση του κινδύνου της ενδονοσοκομειακής διασποράς

BAΡΕΙΑ ΠΕΡΙΣΤΑΤΙΚΑ ΚΑΤΑ ΚΑΝΟΝΑ ΓΙΑΤΙ ΟΙ ΝΟΣΗΛΕΥΟΜΕΝΟΙ ΑΠΟΤΕΛΟΥΝ ΠΡΟΚΛΗΣΗ ΣΤΗΝ ΑΣΚΗΣΗ ΜΕΤΡΩΝ ΠΡΟΣΤΑΣΙΑΣ; ΑΠΟΦΥΓΗ ΕΝΔΟΝΟΣΟΚΟΜΕΙΑΚΗΣ ΔΙΑΣΠΟΡΑΣ ΠΟΥ ΜΠΟΡΕΙ ΝΑ ΕΧΕΙ ΤΡΑΓΙΚΕΣ ΣΥΝΕΠΕΙΕΣ BAΡΕΙΑ ΠΕΡΙΣΤΑΤΙΚΑ ΚΑΤΑ ΚΑΝΟΝΑ

Πλάγια όψη εξαώροφου Νοσοκομείου = Ασθενής με Η1Ν1 = “Πανικόβλητος πληθυσμός” Σταθμός Νοσηλείας Γραφεία Ιατρών ΜΕΘ Θάλαμοι ασθενών Κάτοψη ορόφου Πλάγια όψη εξαώροφου Νοσοκομείου

O H1N1 AΛΛΑΖΕΙ, ΕΜΕΙΣ ΠΡΟΣΑΡΜΟΖΟΜΑΣΤΕ!

Ε Υ Χ Α Ρ Ι Σ Τ Ω !