Sağlık Çalışanlarında Kırım Kongo Kanamalı Ateşi. Önder Ergönül İlayda Arjen Kara Melis Çeldir Şiran Keske

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1 Sağlık Çalışanlarında Kırım Kongo Kanamalı Ateşi Önder Ergönül İlayda Arjen Kara Melis Çeldir Şiran Keske

2 Sağlık Çalışanlarında Kırım Kongo Kanamalı Ateşi Ergonul O, In Emerging Infections, 2014, Elsevier

3 Amaç Olgular veya olgu serileri olarak bildirilen raporların bir araya getirilmesi ve tartışmalı olduğu iddia edilen ribavirin kullanımına açıklık getirilmesi

4 Yöntem PubMED, Google, Ulakbim, ProMED Anahtar kelimeler: Crimean Congo Hemorrhagic Fever Nosocomial Health care worker, health care personnel Ribavirin

5 1099 rapora ulaşıldı Bulgular Uygun olan 30 makale çalışmaya dahil edildi. Yeni bir veri tabanı oluşturuldu. Veri tabanına, demografik, epidemiyolojik, klinik, profilaksi ve tedaviye dair veriler girildi. STATA 14v (ABD) kullanıldı Ki kare, t test ve logistik regresyon kullanıldı

6 Sağlık Çalışanlarında Kırım Kongo Kanamalı Ateşi Riski: İran 5 sağlık çalışanından 3 ü (%) öldü 10 yıl önce İran da ribavirin kullanımı yok. Mardani, et al. Am J Trop Med 2009

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9 Emerg Infect Dis 2014

10 Emerg Infect Dis 2014

11 the HCPs, aside from a few physicians, who spent the most time directly caring for the patient. The remaining 72 per- le exposure risk and were instructed to have their temperatures taken twice daily for 15 d and to contact the infectious diseases physician for any febrile illness within this same time period (Table 3). An oral ribavirin PEP regimen of 600 mg twice daily for 7 d was recommended initially; this dosage was based on drug availability, drug tolerance, and dosage regimens reported in the literature (3). Seventy-two hours later, a more oral ribavirin became available, and the 16 HCPs sonnel had unlikely/no b identifia Health Care Response to CCHF in US Soldier and Nosocom ial Transm ission to Health Care Providers, Germ any, risk for exposure and were offered oral ribavirin PEP (offlabel use); 16 of the 18 accepted treatment (Table 3). Most of the 18 HCPs were present during bronchoscopies or ventilation procedures that used a bag-valve-mask device and had reported blood splashes on their gowns. Although there were no known percutaneous exposures, 2 HCPs reported blood on intact skin. Also, some HCPs wore only a surgical mask as PPE during the initial bronchoscopies and/or were unsure if they had always maintained a properly t fited N95 respirator during subsequent bronchoscopies. The group of 16 HCPs who accepted ribavirin PEP included a medic Nicholas G. Conger, Kristopher M. Paolino, Erik C. Osborn, Janice M. Rusnak, Stephan Günther, Jane Pool, Pierre E. Rollin, Patrick F. Allan, Jonas Schmidt-Chanasit, Toni Rieger, and Mark G. i Kortepeter Table 3. Surveillance criteria and PEP, by exposure risk, for contacts of US soldier with fatal Crimean Congo hemorrhagic fever, Germany, 2009* Group No In 2009, a lethal case of Crimean Congo hemorrhagic fever blood or body i fluds of infected animals (1 3). The disease no. persons (CCHF), acquired by a US soldier in Risk Afghanistan, was treated at a medical Contact center in of Germany skin or and mucous resulted membranes in nosocomi- with ally 2 7 Oral d (range ribavirin 2 14) PEP after offered; exposure baseline to the virus and at and least by weekly is characterized by the abrupt PEP onset and of monitoring a febrile illness usu al transmission contaminated to 2 health blood care providers or body fluids; (HCPs). present After his during subsequent chemistries severe changes and CBC; in mental CCHF status, acute/convalescent-phase hemorrhagic arrival at the bronchoscopy medical center or (day during 6 of illness) use of bag-valve-mask by aeromedical evacuation, ventilation the patient device required (risk of repetitive aerosolization bronchosco- of infectious symptoms and medication side effects (for 15 d in clinic) manifestations, titers ; and monitoring hepatorenal for fever failure (twice (1,4). daily) Case-fatality and for CCHF rates vary by region but are 30% 50% (range 1% 73%) in pies to control blood/body severe fluids pulmonary likely) hemorrhage and without and proper renal PPE most regions; death generally occurs 5 14 d after symptom 2 31 and hepatic Present dialysis during for bronchoscopy hepatorenal failure. or during After use showing of bag-valvemask ventilation the patient device died (even suddenly with proper on day PPE) ; 11 of known onset and is observation most commonly and reporting a result of of multi-organ signs or symptoms failure, e.g., Monitoring for fever twice daily for 15 d (in clinic); self- clinical improvement, illness from contact cerebellar with contaminated tonsil herniation blood caused or body by cerebral/ fluids but wore shock, severe anemia, cerebral fever) hemorrhage, for 15 d and/or pulmonary edema (1,5). cerebellar proper edema. PPE The and 2 infected without HCPs PPE breaches were among (no 16 known HCPs who mucosal received ribavirin or skin contact postexposure with infectious prophylaxis. blood/body The We report a fatal case of CCHF in a US soldier deployed to Afghanistan, who was aero-evacuated to Ger- infected HCPs fluids); had laboratory mild no workers CCHF symptoms. who performed Transmission may specimens have occurred (removed during bag-valve-mask specimens from ventilation, container) and many for treatment, and the documented nosocomial infec- tests on breaches in personal protective wore equipment proper PPE during resuscitations, or Persons bronchoscopies in patient s generating room who infectious wore proper aerosols. PPE and exposure No and active had received monitoring; ribavirin self-observation postexposure and prophy- reporting of tion of 2 health care providers (HCPs) who were at risk for 3 41 This case without highlights PPE the breaches critical care and and no contact infection with control infectious laxis (PEP). We also signs review or symptoms infection (e.g., control fever) interventions for 15 d challenges blood/body presented by fluids ; severe laboratory CCHF cases, workers including who the handled and contact surveillance, both of which were required because of the patient s severe bleeding and the risk for aero- need for experience laboratory specimens with ribavirin (but treatment did not and remove postexposure prophylaxis. from container) and wore proper PPE specimens sol production. Research on human subjects was conducted Proper PPE for aerosol exposure included gown, gloves, N95 respirator, and protective in compliance eyewear; with powered US Department air-purifying Conger, respirators of Defense, and EID, federal, full biohazard 2015

12 IJID, 2015

13 Yüksek riskli maruziyet 13 Ülkeden çalışma Toplam n=130 (100) Ölen n=31 (24%) Sağ kalan n=99 (76%) Turkey 2, 4, 14, (7) 26 (93) Pakistan 7, (17) 25 (83) Iran 5, (27) 8 (73) South Africa (33) 6 (66) Russia (0) 8 (100) Tajikistan (29) 5 (71) UAE (40) 3 (60) Mauritania (100) 0 (0) India 29, (100) 0 (0) Kazakhstan (100) 0 (0) Sudan 15, (66) 1 (33) Germany (0) 2 Albania (0) 1

14 Cinsiyet (51 sağlık çalışanı için bildirilmiş) Toplam n=130 (100) Ölen n=31 (24%) Sağ kalan n=99 (76%) Kadın 21 9 (43) 12 (57) Erkek (33) 20 (67) Ortalama Yaş(48 sağlık çalışanı için bildirilmiş) Meslek Hemşire (30) 30 (70) Doktor (28) 29 (72) İndex olgunun ölmesi (n=115) Ölen (24) 76 (76) Sağ kalan 15 2 (13) 13 (87)

15 Toplam n=130 (100) Ölen n=31 (24%) Sağ kalan n=99 (76%) Maruziyet Gruplaması (30) 54 (70) Birinci Grup Tanımlanmış kan ve vücut sıvıları ile doğrudan temas (iğne batması, sıçrama gibi) İkinci Grup Tanımlanmış kan ve vücut sıvıları ile doğrudan temas yok ama hastayla 1 m den daha yakın temas (entübasyon, bronkoskopi, muayene, resüsitasyon gibi) Üçüncü Grup 44 7 (16) 37 (84) 4 1 (25) 3 (75) Yakın temas yok (aynı odada bulunmak gibi)

16 Kişisel Koruyucu Malzeme Kullanımı Toplam n=130 (100) Ölen n=31 (24%) Sağ Kalan n=99 (76%) Kişisel koruyucu malzeme kullanımı (n=84) Uygunsuz (37) 31 (63) <0.001 Uygun 35 0 (0) 35 (100)

17 Sağlık Çalışanlarında Kırım Kongo Kanamalı Ateşi Maruziyeti: Profilaksi ve Tedavi High risk exposure n=130 PEP Ribavirin n=44 (34%) no PEP n=86 (66%) Infected Not infected Infected Not infected n=11 (25%) n=33 (75%) n=86 (100%) n=0 (0%) symptomatic n=10 (90%) symptomatic n=85 (99%) Fatal n=0 (0%) Ribavirin <48 hrs after symptoms n=17 No ribavirin <48 hours after symptoms n=59 Fatal n=0 (0%) Fatal n=27 (46%) P<0.001 Ergonul, et al, in press

18 Ölümü Belirleyen En Önemli Faktörler (Çok değişkenli analiz) Semptomların başlamasından sonra ribavirin başlanmasında gecikme (gün) Odds Oranı Güven aralığı p Birinci riskli grup

19 Erken Ribavirin Kullanımı EARLY PHASE LATE PHASE CYTOKINES viremia PLTs Disseminated Intravascular Coagulation AST and ALT Fatality Incubation 3-7 days Prehemorrhagic period 1-7 days 7 d 10 d days Hemorrhagic period 2-3 days Convelescence Ribavirin erken dönemde başlanırsa etkilidir Ergonul O. Treatment of CCHF, Antivir Res 2008

20 Sonuçlar Maruziyet sonrası yüksek riskli gruplarda ribavirin mutlaka başlanmalıdır. Tedavi amaçlı olarak semptomlar başladıktan sonra 48 saat içinde ribavirin başlanmalıdır. Profilaksi süresi ve ribavirin dozu farklılık göstermektedir.

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