Pandemic influenza-focus on inpatient issues

1. Pandemic influenza-focus on inpatient issues Susan M. Kellie, MD, MPH Associate Professor of Medicine Division of Infectious Diseases Hospital Epidemiologist, UNMHSC and NMVAHCS

2. Talk outline • Current epidemiology • Potential surge for inpatient care • Spectrum of disease and complications • Testing and treatment • Infection control in the hospital • Healthcare worker health issues • Contingency planning

6. Number of isolates Influenza A by week 2009-Tricore lab, NM

7. Case rate by age group-US data on around 35k confirmed cases

8. Hospitalization rates by age group

9. Deaths-numbers by age group

10. Age distribution of current cases-NM • Tricore requests for virus detection 9/5-9/11/09 • 536 requests, 80 positives • 3 adenovirus • 77 Influenza A-all from previous week confirmed as H1N1 • Age # of isolates • 0-2: 3 • 3-5: 12 • 6-11: 22 • 12-18: 21 • 19-64: 15 • >65: 4

11. FluSurge 2.0 assumptions • No. 1 Average length of non-ICU hospital stay for influenza-related illness is 5 days. • No. 2 Average length of ICU stay for influenza-related illness is 10 days. • No. 3 Average length of ventilator usage for influenza-related illness is 10 days. • No. 4 Average proportion of admitted influenza patients will need ICU care is 15%. • No. 5 Average proportion of admitted influenza patients will need ventilators is 7.5%. • No. 6 Average proportion of influenza deaths assumed to be hospitalized is 70%. • No. 7 Daily percentage increase in cases arriving compared to previous day is 3%. • 4

16. Disease spectrum • Most disease is mild and does not require medical attention • Patients should be educated to do self-care at home • All persons should be aware of the “danger signs” • shortness of breath, either during physical activity or while resting • difficulty in breathing • turning blue • bloody or coloured sputum • chest pain • altered mental status • high fever that persists beyond 3 days • low blood pressure.

17. Clinical course of more severe disease • WHO states 40% of patients with severe manifestations of pandemic influenza do not have underlying risk factors • Rapid progression to viral pneumonia at the onset of symptoms • Deterioration at day 4-5 of symptoms with viral pneumonia and MODS • Bacterial superinfection not described in US severe cases • Some descriptions of bloody mucus plugging requiring therapeutic bronchoscopy

18. Groups at risk of severe disease • Pregnant women and those in the immediate post-partum period • Children under 4 • Immunocompromised and those with underlying cardiopulmonary, metabolic, liver, renal conditions • Older children with neurodevelopmental delay-only group described so far with substantial rates of bacterial superinfection • Obesity may be a risk factor? Due to other underlying conditions

19. MMWR Dispatch July 10, 2009/58(Dispatch):1-4 • Intensive Care patients with Severe Novel Influenza A (H1N1) Virus Infection-Michigan, June 2009 • 10 patients with H1N1 and ARDS • 9 had BMI >30, 7 had BMI>40 • Other RF: asthma, asthma plus smoking, granulomatous chronic lung disease • 5 had PE, 9 had MODS • 3 died • DFA for influenza was negative in all 10, viral culture was positive in 2 • 10 were confirmed by PCR of respiratory specimens

20. Complicated or severe influenza • Presentations: • clinical and/or radiological signs of pneumonia, • CNS findings (e.g. encephalopathy), • severe dehydration or secondary complications such as renal failure, • multi‐organ failure, and septic shock. • Other complications can include musculoskeletal (rhabdomyolysis) and cardiac (myocarditis). • Exacerbation of underlying chronic disease • Any condition requiring hospital admission for clinical management.

21. Signs and symptoms of progressive disease • Patients who present initially with uncomplicated influenza may progress to more severe disease. Progression can be rapid. • Indicators include respiratory, CNS deterioration or indicators of severe dehydration, hypotension • i.e. meet criteria for sepsis, SIRS, MODS

22. Preventing bacterial pneumonia • Pneumovax is now indicated for all asthmatics and current smokers age 19 and up • Be aware of MRSA/ MSSA necrotizing pneumonia following or concurrent with influenza • Presents with severe pleuritic chest pain, purulent bloody sputum, toxic patients

24. Neuro manifestations of influenza in adults-per Dr. Larry Davis • Most common is severe headache, fever,  and meningismus mimicking an acute meningitis.  However, the CSF is normal with no cells.  It is self limited.  Myalgias of the posterior neck muscles simulate the meningismus. • Second most common is pt with high fever, headache, myalgias, and confusion looking like an acute encephalopathy.  MRI is normal. Self limited, improves quickly • The third most common is seizures.  Any high fever can trigger a seizure and influenza can.  In those from Mexico, consider underlying neurocysticercosis. • Uncommon but does occur are patients with Reye’s syndrome • Another group is the influenza ADEM where the encephalopathy has focal neurologic signs, and the MRI shows patchy white matter lesions.   • Finally is the influenza patient with focal myositis.  The muscle is painful and biopsies have shown actual fiber necrosis and inflammation. CPK is elevated

25. H1N1 2009 influenza virus during pregnancy in the USA-Lancet online July 29, 2009 • From April 15-May 18, 2009, 34 confirmed or probable cases of H1N1 in pregnant women were reported to CDC from 13 states. 11 (32%) were admitted to hospital. • Rate of admission was 0.32 per 100,000 pregnant women at risk vs 0.076 per 100,000 general population • 6 of 45 deaths from April 15 to June 16 were in pregnant women. As more deaths accrued over the following week, this ratio dropped to 7 out of 87 deaths.

26. Recent case at UNM • 21 year old woman with only PMHx recent pregnancy and C-section-not within last month • 4 days of coryza, cough and fever • Presented to another ED hypotensive and hypoxemic • Intubated, flown to UNMH. • Died after 11 days in ICU with refractory ARDS

27. Emerging complications • Pulmonary embolisms in non-hospitalized and hospitalized patients • Respiratory decompensation in ventilated patients due to plugging with bloody mucus • Myositis

28. Influenza causes GBS Figure 3. Distribution of Guillain-Barre syndrome episodes in 90-day intervals around the date of influenza-like illness, UK 1990-2005. Stowe et al. Am J Epidemiol 2009; 169: 382-8

29. Testing/surveillance • As disease activity increases, it is 30-70% likely that influenza-like illness (i.e. fever plus sore throat and/or cough) is influenza-more sensitive the younger the patient is. • Influenza H1N1 is almost 100% of circulating strains • Testing should be limited to hospitalized patients • Specific PCR testing for “H1N1” will be performed at state lab on admitted patients for epidemiologic purposes

30. Exact mechanics of testing still to be decided • Currently Tricore forwards all positives to SLD for PCR-requires extensive form to be filled out • State now wants all negative swabs also-will match to admission list for respiratory diseases (?) • No feedback loop to infection control on previously unidentified cases (rapid neg, PCR positive)-these are called to provider/patient • Tricore now validating independent PCR with SLD

31. Test all patients admitted with or developing while in hospital… • NMDOH:  All hospitalized patients meeting any of the following criteria are considered by NMDOH to be possible influenza cases and should have a specimen sent to SLD for influenza PCR testing, regardless of whether other influenza testing has been ordered (e.g., a rapid influenza diagnostic test):*Influenza or rule-out influenza*Influenza-like illness (i.e., fever 100º degrees Fahrenheit or higher, and cough, and/or sore throat) *Pneumonia or rule-out pneumonia*Bronchiolitis*Exacerbation of underlying pulmonary disease (e.g., asthma, cystic fibrosis, COPD)*Fever of unknown origin*Cough*Dyspnea/shortness of breath/respiratory distress*CHF, or CHF exacerbation, associated with fever or with unclear etiology • Added by SK_ARDS, respiratory failure*Any of the following testing/treatment events:*Any influenza test ordered on an inpatient*Any influenza antiviral medication/s {e.g., Tamiflu (oseltamavir), Relenza (zanamavir), Symmetrel (amantadine), Flumadine (rimantadine)} ordered for an inpatient

32. Oseltamivir • New Mexico has 350,000 courses • Enough to treat 1/3 to 1/2 of those who might become ill • Prioritize those admitted to hospital with severe/complicated influenza • Persons at high risk of complications of influenza-young children, pregnant women and those with underlying conditions • Prophylax persons at high risk post-exposure

33. WHO classification • Uncomplicated influenza • – Influenza‐like illness symptoms: fever, cough, sore throat, rhinorrhea, headache, muscle pain, malaise, but no shortness of breath, no dyspnoea. Patients may present with some or all of these symptoms. • – Gastrointestinal illness may also be present, such as diarrhoea and/or vomiting, especially in children, but without evidence of dehydration.

34. Signs and symptoms of progressive disease • Patients who present initially with uncomplicated influenza may progress to more severe disease. Progression can be rapid. • Indicators include respiratory, CNS deterioration or indicators of severe dehydration, hypotension • i.e. meet criteria for sepsis, SIRS, MODS

35. Treatment • Treat serious /hospitalized cases immediately • Oseltamivir can significantly reduce the risk of pneumonia (a leading cause of death for both pandemic and seasonal influenza) and the need for hospitalization. (usual dose 75mg po bid for 5 days, reduce by 50% for creatinine clearance under 30ml/min) • For patients with severe or deteriorating illness, treatment should be provided even if started later. Where oseltamivir is unavailable or cannot be used for any reason, zanamivir may be given. • Patients with underlying medical conditions that increase the risk of more severe disease, should also receive treatment as soon as possible after symptom onset, without waiting for the results of laboratory tests. • Children under4 • Pregnant women or those in the immediate post-partum period • All patients with underlying conditions • ALSO PROPHYLAX THIS GROUP AND EXPOSED HCWs • Prophylaxis dose –oseltamivir 75mg poqd for 10 d

36. Treatment in severe disease • In ventilated patients, some clinicians have used double dose oseltamivir 150mg po bid • Based on H5N1 experience and fear that diarrhea will interfere with absorption • Duration of treatment can be longer-no data in severely ill patients • Investigational drug: peramivir-Dr. Goade is PI, Intravenous neuraminidase inhibitor, final criteria for study pending, open label

37. Employee health • Employees with influenza-like illness must call supervisor and stay off work for either 7 days or 24 hours afebrile off all antipyretics, whichever is longer • Doctor’s note will not be required • Vacation time will not be taken • Treatment will be dispensed to employees at higher risk of complications-send in family with your ID. • Lobocare clinic will be site of care for sick UNM employees and referral site for UH employees • No work restrictions are advised for employees at higher risk e.g. pregnant workers

38. Infection control-see WHO checklist • HICPAC recommendations: • Standard and droplet (surgical mask) precautions will be used. • N95 masks will be reserved for the following aerosol-generating procedures on patients with ILI: • Intubation/extubation • CPR with emergency intubation and/or chest compressions • Open suction • Bronchoscopy

39. Infection control in 1918 Basic respiratory hygiene and droplet precaution measures “None of my classmates died and very few became ill. Perhaps the masks, gowns and handwashing did more to protect us than we had a right to expect. Certainly, with death all around us, we had every encouragement to be as careful as we could, but we were so busy and so tired that we forgot about precautions, and patient after patient coughed into our faces as we tended to their needs.” Starr. Influenza in 1918: recollections of the epidemic in Philadelphia. Ann Intern Med 2006: 145:138-40.

40. Before entering the room: Hand Hygiene Don Surgical Mask Don Gown, Gloves and Eye Protection depending on task and risk of exposure to body fluids Expanded Precautions indicated for aerosol generating procedures – turn sign over On exit from room: Remove and Discard PPE Hand Hygiene Disinfect all shared equipment. Visitors: Some restrictions apply Please see a nurse for instructions before entering the room. Surgical mask required with hand hygiene on entry and exit. Protective equipment is not available for children <12 years. Droplet Precautions Alternatives: Cone-style surgical mask or ear-loop procedure mask (N-95 respirators are NOT required)

41. Use Expanded Precautions: Visitors are restricted for 1 hour Essential Healthcare Workers ONLY Don N-95 Respirator Mask or PAPR Don Gown, Gloves and Eye Protection Keep Door Closed (Negative Pressure Room preferred) On exit from room: Remove and Discard PPE Hand Hygiene Disinfect all shared equipment. Discontinue Expanded Precautions1 hour after aerosol generating procedure is completed Aerosol Generating Procedure in Progress

42. Other measures • Restriction of visitation • Screening of all visitors • Immunization of healthcare workers-walk-in starting October 8. • One seasonal, one (?) pandemic injection

43. Emergency coordination • UNM, UNMHSC and VA have all activated their emergency operations centers • Frees up resources and communication to create greater flexibility and responsiveness • Homeland Security will be running Joint Information Center for State to coordinate all public and healthcare communication

44. Surge capacity/limitations to services • Early on, employee and employee family illness may be major cause of absenteeism and interfere with usual delivery of care • VA/UNM are prepared to open alternate site of care near ED to render care to overflow ILI patients and if necessary, employees • Supervisors/division chiefs need to consider continuation of operations plans with significant staff absenteeism

45. Other critical infrastructure • Ethics training at state and facility level for allocation of scarce resources • ECMO • Vents • Daily reporting of all beds, oseltamivir, masks etc now being monitored by DOH

46. Essential resources • www.flu.gov link from CDC-patient education, personal preparedness • CDC website www.cdc.gov , current recs • NMDOH website, DOH symposium Oct 2-at UNM CE • Free materials on www.idsociety.org www.nejm.com, www.thelancet.com