L'influenza A/ H1N1 Tra rischi reali e allarmismi Ruolo dell'Ospedale e del territorio La clinica,la stratificazione del rischio e la terapia ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
ASL 8
CAGLIARI L’influenza A/ H1N1
Tra rischi reali e allarmismi
Ruolo dell’Ospedale e del territorio
La clinica,la stratificazione del rischio e la terapia
Giuseppe Angioni
Cagliari 21 dicembre 2009
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, N Engl J Med 361, 2009
Virus dell’influenza A
2009 H1N1 Influenza
• Illness resulted from triple reassortment virus of
human, avian and swine influenza virus genes
• Viruses susceptible to oseltamivir and zanamivir,
resistant to amantadine and rimantadine
• Median age – 20 years, range 3 months
to 81 years; 60% were 18 years or
younger (based on 642 confirmed cases reported
4/15-5/5/2009)
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, N Engl J Med 361, 2009
CDC, MMWR Morb Mortal Wkly Rep 58:536-41, 2009 and 58:497-500, 20092009 H1N1 Influenza Distribuzione dell’eta’ in 3152 casi confermati di influenza H1N1
2009 H1N1 Influenza
2009 H1N1 Influenza
Stratificazione del rischio
Ricovero ospedaliero in 3152 casi di H1N1 confermati per classi d’eta’
CMAJ 20092009 H1N1 Influenza
(continued)
• In the US, most confirmed cases
characterized by self-limited,
uncomplicated febrile respiratory
illness: similar to seasonal influenza
(cough, sore throat, rhinorrhea,
headache, and myalgia) – 38% with
vomiting or diarrhea (based on 642
confirmed cases reported 4/15-
5/5/2009)
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, N Engl J Med 361, 2009
CDC, MMWR Morb Mortal Wkly Rep 58:536-41, 2009 and 58:497-500, 2009How does novel H1N1
Influenza spread?
• This virus is thought to spread the
same way seasonal flu spreads
• Primarily through respiratory
droplets
– Coughing
– Sneezing
– Touching respiratory droplets
on yourself, another person,
or an object, then touching
mucus membranes (e.g.,
mouth, nose, eyes) without
washing hands• Symptoms of infection with 2009 H1N1 influenza are generally the same as for seasonal influenza: fever, cough, sore throat, runny or stuffy nose, headache, body aches (muscle aches or joint pain), chills and fatigue. Some people have reported diarrhea and vomiting associated with 2009 H1N1 flu. Not everyone who has flu will have a fever.
Signs and symptoms
Symptoms of novel H1N1 flu in people are similar to those
associated with seasonal flu.
• Fever
• Cough
• Sore throat
• Runny or stuffy nose
• Body aches
• Headache
• Chills
• Fatigue
• In addition, vomiting (25%) and diarrhea (25%) have
been reported. (Higher rate than for seasonal flu.)• The symptoms of pandemic H1N1 influenza of 2009 are essentially the same as the seasonal flu, although some have noted an increased frequency of gastrointestinal symptoms, including vomiting and diarrhea, and others have noted the absence of fever in a significant number with virologically proven cases.
• Patients with 2009 influenza A H1N1 infections have higher rates of gastrointestinal symptoms and lack of fever compared with those who have seasonal flu • CDC epidemiologist Tim Uyeki notes that about 12% do not have fever and that many report diarrhea and vomiting
• Most patients have mild symptoms, but a small subset of previously healthy young adults have severe pulmonary disease that progresses to acute respiratory distress syndrome (ARDS);
Symptoms in viroloconfirmed cases.
During an outbreak of H1N1 in high school, a sample of New York City
school students (median age, 15 years)
• Cough (98%);
• Subjective fever (96%);
• Fatigue (89%);
• Headache (82%);
• Sore throat (82%);
• Abdominal pain (50%);
• Diarrhea (48%);
• Dyspnea (48%); and
• Joint pain (46%)
• The measured mean peak fever in this group was
102.2°• La sintomatologia clinica della influenza pandemica H1N1 e’ essenzialmente la medesima dell’influenza stagionale; talune osservazioni hanno evidenziato una maggiore frequenza di sintomi a carico dell’apparato gastro intestinale,in particolare vomito e diarrea,ed in un significativo numero di casi ,virologicamente accertati,e’ stata osservata l’assenza di febbre.
• La sintomatologia piu’ rilevante e’ a carico dell’apparto respiratorio con comparsa di tosse,mal di gola,modica dispnea,toracalgia e rinorrea,all’esame obiettivo si rilena una iperemia delle mucose delle vie respiratorie superiori,la presenza di essudato sieroso nel faringe,nessun ulteriore reperto patologico viene riscontrato a carico dell’apparato respiratorio che nelle forme ad evoluzione favorevole – che son di gran lunga le piu’ frequenti – appare del tutto normale.
• In taluni rari casi –quelli ad evoluzione meno favorevole – gia’ nelle fasi iniziali viene obiettivata una compromissione dell’apparato respiratorio che presenta un quadro di polmonite interstiziale diffusa dovuta all’azione diretta del virus influenzale,che puo’ accompagnare verso una sfavorevoloe evoluzione per la comparsa di alterazioni anche gravi della funzione respiratoria.
• Tale quadro assume rilievo particolare nelle eta’ estreme della vita,ove l’immaturita’ immunologia o il deficit immunitario presente,trovano nella particolarita’ anatomo-fisiologica un elemento prognostico sfavorevole. Ed anche un terreno adatto per eventuali sovra infezioni batteriche
Complications of H1N1 Influenza • Exacerbation of underlying chronic disease; • Complications related to the upper airways, including sinusitis or otitis; • Pulmonary complications, including bronchitis, asthma (sometimes with status asthmaticus), and acute exacerbations of chronic bronchitis; Miscellaneous conditions, including cardiac (myocarditis and pericarditis), myositis, rhabdomyolysis, central nervous system complications (encephalopathy, encephalitis, seizures), toxic shock syndrome, and secondary bacterial pneumonia.
• Bacterial coinfections. CDC investigators reviewed clinical records and pathology reports from 77 lethal cases of pandemic H1N1 infection. (CDC. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - US, May - August 2009. MMWR Morb Mortal Wkly Rep. 2009;58: early release) The tissue specimens were examined by tissue Gram stain, Warthin-Starry silver stain, various microbe- specific immunohistochemical assays, and PCR that targeted the 16S ribosomal DNA in tissue blocks. Bacteria were detected in 22 of 77 cases (29%). Major pathogens were Streptococcus pneumoniae (10), Staphylococcus aureus (7), Streptococcus pyogenes (6), Streptococcus mitis (2), and Haemophilus influenzae (1); 4 cases had more than 1 pathogen.
• Bacterial coinfections • CDC investigators reviewed clinical records and pathology reports from 77 lethal cases of pandemic H1N1 infection. • Bacteria were detected in 22 of 77 cases (29%). Major pathogens were Streptococcus pneumoniae (10), Staphylococcus aureus (7), Streptococcus pyogenes (6), Streptococcus mitis (2), and Haemophilus influenzae (1); 4 cases had more than 1 pathogen. CDC. Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - US, May - August 2009. MMWR Morb Mortal Wkly Rep. 2009;58: early release)
• Severe complications of H1N1 Influenza. • In June 2009, the University of Michigan reported severe pulmonary complications of 2009 H1N1 influenza infection in 10 patients with a median age of 49 years. All 10 patients were referred for severe hypoxemia, ARDS, and inability to oxygenate with conventional ventilation methods. All had severe multilobar pneumonia on x-ray, none had evidence of bacterial pneumonia, and 4 had CT scan-confirmed pulmonary embolism. Lab findings included leukocytosis in 5 (median WBC 9500/mm3), elevated AST levels (41-109 IU/L) in all 10, and elevated CPK levels (51-6572 IU/L) in 6; none had evidence of disseminated intravascular coagulation
• The major risk factor was obesity in 9 and morbid obesity (BMI>40)
in 7 oscillatory or bilevel ventilation with mean airway pressures of
32-55 The major risk factor was obesity in 9 and morbid obesity
(BMI > 40) in 7. All 10 required advanced mechanical ventilation .
Two required veno-venous extracorporeal membrane oxygenation
(ECMO) support and 6 required dialysis. At the time of the report, 3
had died, 1 was still on ECMO, 1 was still on mechanical ventilation,
and 5 had been transferred back to referring institutions.*
• * (CDC. Intensive care patients with severe novel influenza A
(H1N1) virus infection -- Michigan, June, 2009. MMWR Morb Mortal
Wkly Rep. 2009;58:749-752.)• Neurologic complications.
• Neurologic complications were reported in 4 children ages 7-17
years with 2009 H1N1 influenza A. Findings included seizures in 2
children, encephalitis in 2, and ataxia in 1. All recovered without
neurologic sequelae. The editorial comment in this report noted that
the neurologic disease in these 4 patients was less severe than
what has been described in previous reports of seasonal flu. *
*(CDC. Neurological complications associated with novel influenza A (H1N1) infection in
children -- Dallas, Texas, May 2009. MMWR Morb Mortal Wkly Rep. 2009;58:773-778.;
Maricich SM, Neuf JL, Lotze TE, et al. Neurologic complications association with
influenza A in children during the 2003-2004 influenza season in Houston, Texas.
Pediatrics. 2004;114:e626-e633.; Morishima T, Togashi T, Yokota S, et al. Encephalitis
and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis.
2002;35:512-517.)Terapia • Treatment with influenza antiviral drugs is generally not needed for people who are not at higher risk for complications or do not have severe influenza, such as those requiring hospitalization. However, any suspected influenza patient who presents with emergency warning signs (for example, difficulty breathing or shortness of breath) or signs of lower respiratory tract illness or worsening illness should seek medical care promptly receive antiviral therapy when indicated.
• 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); hiv??
– 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.
• Pregnant women.
• Young children (especially those under two years).Terapia • At this time, treatment with oseltamivir (trade name Tamiflu®) or zanamivir (trade name Relenza®) is recommended for all people with suspected or confirmed influenza who require hospitalization.
Terapia • Once the decision to administer antiviral treatment is made, treatment with zanamivir or oseltamivir should be initiated as soon as possible after the onset of symptoms. Evidence for benefits from antiviral treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours of illness onset.
Terapia • However, some studies of oseltamivir treatment of hospitalized patients with seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset.
Terapia • When treatment is indicated, health care providers generally should not wait for laboratory confirmation of influenza to begin treatment with antiviral drugs because laboratory testing can delay treatment and because a negative rapid test for influenza does not rule out influenza. The sensitivity of rapid influenza diagnostic tests can range from 10-70% for 2009 H1N1 virus.
Terapia • The recommended duration of treatment is five days. However, hospitalized patients with severe infections might require longer treatment courses.
Terapia • Antiviral chemoprophylaxis generally should be reserved for people at higher risk for influenza- related complications who have had contact with someone likely to have been infected with influenza. As an alternative to chemoprophylaxis, clinicians can also choose to counsel people at higher risk for influenza- related complications about the early signs and symptoms of influenza and advise them to immediately contact a health care provider for evaluation and possible early treatment if clinical signs or symptoms develop.
Terapia • Post-exposure antiviral chemoprophylaxis with either oseltamivir or zanamivir can be considered for health care personnel, public health workers, or first responders who have had a recognized, unprotected close contact exposure to a person with confirmed, probable, or suspected 2009 H1N1 or seasonal influenza during that person’s infectious period.
Terapia • For antiviral chemoprophylaxis of 2009 H1N1 influenza virus infection, either oseltamivir or zanamivir are recommended. Currently, circulating 2009 H1N1 viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine • Duration of antiviral chemoprophylaxis post- exposure is 10 days after the last known exposure
Terapia • Zanamivir • Limited data are available about the safety or efficacy of zanamivir for persons with underlying respiratory disease or for persons with complications of acute influenza, and zanamivir is licensed only for use in persons without underlying respiratory or cardiac disease.
Terapia • Oseltamivir • Nausea and vomiting were reported more frequently among adults receiving oseltamivir for treatment (nausea without vomiting, approximately 10%; vomiting, approximately 9%) than among persons receiving placebo (nausea without vomiting, approximately 6%; vomiting, approximately 3%). Nausea and vomiting might be less severe if oseltamivir is taken with food
Terapia • Oseltamivir, zanamivir, amantadine and rimantadine are both "Pregnancy Category C" medications.
Terapia • Limited clinical data are available regarding drug interactions with oseltamivir. Because oseltamivir and oseltamivir carboxylate are excreted in the urine by glomerular filtration and tubular secretion via the anionic pathway, a potential exists for interaction with other agents excreted by this pathway. For example, coadministration of oseltamivir and probenecid resulted in reduced clearance of oseltamivir carboxylate by approximately 50% and a corresponding approximate twofold increase in the plasma levels of oseltamivir carboxylate
Terapia • Peramivir • Peramivir is a novel neuraminidase inhibitor. It is an unapproved drug that may be effective in certain patients who are severely ill with influenza. Peramivir is supplied in 200 mg/20 mL (10 mg per mL) single-use vials. Intravenous (IV) peramivir is the only available formulation and the only authorized product at this time. • Peramivir authorized for emergency use in hospitalized patients
Terapia • Criteria for use: It is authorized for use in adult and pediatric patients who (1) are not responding to oral or inhaled antiviral therapy or (2) need drug delivery by a route other than oral or inhaled, and in whom the IV route is expected to be dependable or the clinician judges IV therapy to be appropriate for other reasons. • Efficacy: In phase 2 trials, peramivir reduced the duration of symptoms by 21 hours compared with placebo • $2250/patient
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).You can also read
