Post Exposure Prophylaxis

Post-Exposure Work Up: What happen in reality? Anucha Apisarnthanarak, M.D. Division of Infectious Diseases Thammasart University Hospital Pratumthani, Thailand

Situation 1 • 45 year-old, Thai woman, with a history of pulmonary fibrosis has been on prednisone and endoxan for 6 months admitted to Thammasart Hospital ICU because of CAP • She was doing well on 10-days cefoperazone- sulbactam and was subsequently extubated • On HD day-11, she develop rash

Varicella Expose in ICU HCWs (Epidemiology) 100,000-200,000 cases/yr post vaccine introduction (1995) -4 million cases/yr pre-vaccine -Cases in adult (>20 yr) <7% Zoster 300,000 cases/yr -Generally in patients >50 yr or immunocompromised Mortality has been reduced post vaccine introduction Atypical presentation could occur in patients who receive vaccine Nguyen, et al. Decline in mortality due to varicella after implementation of varicella vaccination in United States, N Engl J Med, 2005 Vazquez, et al. Varicella vaccine and infection with varicella zoter, N Engl J Med, 2005

Atypical presentation

What should be the most appropriate management? • A) Put the patient on airborne and contact isolation • B) All exposed HCWs in ICU should off work from day 5 to 21 after exposure • C) Offer vaccine for all exposed HCWs • D) Offer VZIG for all exposed HCWs • E) All are correct

Varicella Exposure Among ICU HCW • Transmission Airborne and direct contact with lesions • Transmission can occur from 2 days before to 5 days after rash appears • Lesion non-infectious when crusted Incubation period 10-16 days (range, 10-21 days) Secondary attack rate ~90% in susceptible contacts

Post-exposure management • Establish susceptibility of HCWs • Negative history of known susceptible • Exclude from patient contact form day 10th-21st after last exposure or if compatible symptom develop • Offer VZV vaccine (2 doses separate by 4-8 wks) -Effective in preventing illness or modifying severity, if use within 3-5 days after post-exposure -Vaccine contraindicated for pregnant female or those who become pregnant • Previous vaccinated HCWs • Retest for antibodies • If negative, retest in 5-6 days to determine anamestic response • If negative by 7 days post exposure, then furlough from work or monitor • Risk of transmission of vaccine virus negligible unless vaccinee develop rash

Case Scinario (cont)

Who should be the candidate for vaccine? • A) All HCWs in ICU • B) All exposed HCWs in ICU • C) All HCWs who reported previous history of VZV • D) All HCWs who reported no history of VZV • E) All are correct

Candidate for VZV vaccine • Seroprevalence • >90% adult seropositive (in general) • History of varicella 97-99% predictive of antibodies • Negative or uncertain history 79-93% seropositive

Exposed to Varicella zoster case N = 140 HCWs N = 18 ICU patients Active disease No disease N = 130 HCWs N = 18 patients N = 10 HCWs Cost: ACV to patients Costs : Furlough HCWs occupational health protocol for continuing varicella risk: ACV - Self-reported history - IgG screen - Counsel & vaccinate Occupational health surveillance No reported history of chicken pox Reported history of chicken pox N = 77 N = 53 N Serology Vaccination 30 IgG+ NA Serologic testing Drop out 30 IgG- Yes 23/23 IgG+ N = 30 17 IgG- Declined

IgG + - + 23 0 Hx - 30 47 Sensitivity = 23 / 53 = 43% Specificity = 17 / 17 = 100% PPV = 23 / 23 = 100% NPV = 47 / 77 = 61%

Post-exposure management Chemoprophylaxis • No role for antivirus Varicella-zoster immunoglobulin • 400-500$ for maximum adult doses • No role for routine use in post-exposure in susceptible HCWs, unless HCWs were know to be high risk for complications or HCWs is not a candidate for, or refuses vaccination

Will VZV vaccine be cost-effective to provide for all HCWs in the hospital? • A) Yes • B) No • C) Not sure

Cost Analysis • Investment in future surveillance & immunization next 300 HCWs (cost 857,094.40 bath for ACV & furloughs) NB: Attack rate = 21.1% Seroprevalence = 55% Apisarnthanarak A, et al. A Varicella zoster outbreak among Thai HCWs. Infect Control Hosp Epidemiol, 06

Outbreak Investigation Steps 1. Confirm the outbreak 7. Formulate hypothesis 2. Prepare for 8. Execute additional investigation studies 3. Initiate emergency 9. Implement control measures measures 4. Create a case- 10. Share results definition 11. Evaluate outbreak 5. Search for additional process cases 6. Characterize outbreak

Quiz: A Thai student present with fever, malaise and rash

What is the most appropriate action? 1. Start this patient on droplet isolation during the whole admission period 2. Start this patient on droplet isolation during the first 24 hours 3. Start this patient on airborne isolation during the first 24 hours 4. Start this patient on airborne isolation during the whole admission period 5. Provide ciprofloxacin to all HCWs for post-exposure prophylaxis

Meningococcemia: Definition of Close Contact • “Person who has had prolonged contact (>8 hours), while in close proximity (<3 ft) to index patient or has been directly exposed to patient secretion (intubation, mouth to mouth CPR) within 1 week before onset until 24 hours after received appropriate therapy” • Classmate or coworkers who did not met the close contact criteria were not included in prophylaxis. Garden P. Prevention of meningococcal disease. NEJM, 2006

Case 2 • On March 9, 2004 a 35 yo woman with no underlying disease was transferred to Thammasat University Hospital with rapidly progressive pneumonia. At presentation to OSH, she reported 1 week of fever, N/V/D; no respiratory symptoms. She received one dose of ceftazidime and gentamicin prior to transfer. • Social history: Lives in rural area of Ayudhaya with family. Works in a factory; no travel history.

Additional data • WBC 2,200 cells – Neu 65% – Lym 25% – Mono 10% • Hct 35% • Plt 330,000 u/L • BUN/Cr= 11/1.6 • AST/ALT = 474/106 • Alkaline phos = 546 • PT/PTT= 35/11.9 • LDH = 1,830

What should you do next? • A) Obtain contact history • B) Start broad spectrum antibiotics • C) Perform rapid influenza test • D) A-C • E) A-B

Initial evaluation • IC team notified and contact & air-borne precautions initiated • Rapid influenza test performed (negative) • Local health department & hospital administration notified • Additional negative studies: – HIV ELISA – Chalmydia and mycoplasma titers – Leptospira, melioid titer, dengue titer

What should be the diagnosis? • A) Bacterial sepsis • B) Avian influenza • C) PCP • D) SARS • E) Influenza pneumonia H1N1

RT-PCR results 2 RT-PCR primers and 1 real-time RT-PCR positive for H5 band and viral culture was negative. Neighborhood chicken tested positive for H5N1.

Case outcome • Exposures: Several recent chicken deaths in the neighborhood. • Given limited access to antiviral medication, neuraminidase inhibitor was not prescribed; prednisone was initiated. • The patient died from severe ARDS with multi- organ failure within 48 hours. • All patient family members are well without influenza-like illness. Apisarnthanarak A, et al. Atypical avian influenza, 2004

Lesson Learned I • Ask about occupation and exposure to ill humans/animals during outbreaks. Inquire about exposure history from multiple sources. • Diff dx: Avian influenza in differential dx of patients with only GI symptoms, especially if there is exposure to poulty • Design and coordinate a dynamic interdisciplinary preparedness plan. • A high index of suspicion will facilitate prompt diagnosis and proper management. Apisarnthanarak A, et al. Atypical avian influenza. Emerg Infect Dis 2004;10:1321-4.

• Clinical spectrum of H5N1 broader than we thought. • Surveillance definition should be adjusted to include these presentations. • Isolation of H5N1 from stool may have implications for infection control. deJong MD, et al. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. New Engl J Med 2005.

Avian influenza (H5N1) replication sites. Auewarakul P, et al. Emerg Infect Dis, 2005

Lesson Learned II • The rapid influenza test is not the most sensitive test, which may limit its usefulness in correctly identifying H5N1, esp. when patients present late in clinical course. • Thus, clinical findings and history of occupational exposure may be most helpful in identifying patients with H5N1.

48 hours post-transfer... • Infectious disease consultation requested. • 30 ICU HCWs exposed to the index case without using appropriate personal protective equipment.

Setting • Level III, 8-bed MICU equipped with central air conditioning • Two isolation rooms • No negative pressure room • No special ventilation system • One Hospital Epidemiologist • Two ICNs

Personal Protective Equipment AFTER CASE RECOGNITION: • All HCWs wore surgical mask, gown, and gloves. • HCWs who were assigned for aerosol producing procedures wore N95 mask, cap/hood, and goggles.

IC protocol for HCWs at TU Hospital • All exposed HCWs monitored for 2 wks for temperature and influenza-like illness (ILI) • If any developed ILI, rapid influenza test done. • If rapid test positive: – Neuraminidase inhibitor prescribed. – Influenza vaccine offered. Role?? • Paired acute and convalescent sera for anti-H5 antibody (microneutralization assay) collected.

Healthcare Workers and Avian Influenza: Lesson Learned III • Healthcare workers are at low risk of H5N1 acquisition, even unprotected. • Continued precautions and monitoring are essential in case viral mutations evolve to a more virulent and readily-transmissible virus. Apisarnthanarak A, et al. Seroprevalence of Anti-H5 antibody among Thai HCWs after exposure to H5N1 in a tertiary care center. Clin Infect Dis, 2005

Avian Influenza (H5N1) Clinical Presentation • Severe viral pneumonia • Mild influenza-like syndrome Hong Kong: Yuen, et al Lancet 98 Yuen, et al. Lancet 98 Kandun, et al NEJM 06 Perris, et al. Lancet 04 Vietnam: • Difficulty for rapid diagnostic Hien, et al. NEJM 04 Hong Kong: Thailand: Yuen, et al. Lancet 98 (82%) Chotepitayasunondh, et al. EID 05 Vietnam: Turkey: De Jong, et al. Unpublished (20%) Oner, et al. NEJM 06 Turkey: Oner, et al. NEJM 06 (0%) • Atypical presentation Indonesia: De Jong, et al NEJM 05 Kandun, et al. NEJM 06 (0%) Apisarnthanarak, et al EID 04 Thailand: Apisarnthanarak, et al. CID 07 (29%)

Post Exposure Prophylaxis

by Society of Thai Emergency Physicians

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