The 5-point Screen for Hantavirus

1. The 5-point Screen for Hantavirus Hantavirus Conference 2019 Dine College, Tsaile Campus Aaron Kofman, MD EIS Officer, Viral Special Pathogens Branch CDC, Atlanta GA

2. Overview • Clinical review of hantavirus disease • Background on 5-point screen for hantavirus • Use of 5-point screen in the Four Corners region • Questions

3. Clinical Review of Hantavirus Disease

4. Hantavirus Pulmonary Syndrome • Incubation Period: 1-8 weeks • Febrile Prodrome: 3-6 days of flu-like illness • Cardiopulmonary Stage: 1-2 days of worsening respiratory symptoms • Roughly 30-40% of patients will die • Diuretic Stage: 3-7 days; polyuria • Convalescence: may have residual fatigue, poor exercise tolerance

6. How do we diagnose someone with Hantavirus Pulmonary Syndrome? • It is rare; even in the Four Corners region! • Many people with rodent exposure…most do not end up with hantavirus. • Most clinicians have never seen a case • It looks like other illnesses • Influenza, pneumonia, etc. • Most cases in spring/summer but can occur any time of year • Bottom line: Requires a high index of suspicion in the appropriate context.

7. Once we suspect it…how do we diagnose? • Diagnostic tests • ELISA for anti-hantavirus IgM and IgG antibodies • Problem: turnaround time • 4-6 hours to run the test • But longer to ship the specimen • Meanwhile, clock is ticking…patient may be getting more ill…

8. Once we suspect it…how do we diagnose? • Diagnostic tests • ELISA for anti-hantavirus IgM and IgG antibodies • Problem: turnaround time • 4-6 hours to run the test • But longer to ship the specimen • Meanwhile, clock is ticking…patient may be getting more ill… • What can make a difference? • Rapid referral to facilities with high-level intensive medical support and extracorporeal membrane oxygenation (ECMO) • Early identification of illness to enable #1

9. Treatment for patients with Hantavirus Pulmonary Syndrome • Supportive therapy • Blood pressure medications • Supplemental oxygen • Extracorporeal membrane oxygenation = ECMO • UNM has initiated ECMO in patients with a cardiac index of <2 L/min, PaO2/FiO2 ratio <60, and refractory shock

10. ECMO • 51 patients with hantavirus pulmonary syndrome with 100% predicted mortality were placed on venoarterial ECMO • 26 patients were intubated and then placed on ECMO once they became hemodynamically unstable • 54% survived • 25 patients were given ECMO vascular access so there was no delay to initiation of ECMO when needed • 80% survived Wernly et al. Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment. Eur J Cardio-Thor Surg 2011;40:1334-40.

11. 5-point screen

12. Laboratory results in patients with Hantavirus Pulmonary Syndrome • Platelets decrease • White blood cells increase • Immunoblasts increase • Hematocrit increases 1Koster et al. “Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review” Am J ClinPathol 2001;116:665-672

13. 5-point screen1: what is it? • Low platelet count (thrombocytopenia) • Elevated white blood cell count with left shift • Increased immunoblasts (>10% of lymphocyte population) • Enlarged lymphoid cells 2-3x greater in diameter than normal • Lack of toxic changles in neutrophils • No toxic granulations, no Dohle bodies, no cytoplasmic vacuolization • Hemoconcentration (increased hematocrit) 1Koster et al. “Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review” Am J ClinPathol 2001;116:665-672 2Dvorscak et al. “Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear.” Am J ClinPathol 2014;142:196-201.

14. Examples Normal lymphocyte https://imagebank.hematology.org/image/60511/lymphocyte

15. Examples Normal lymphocyte Immunoblasts on peripheral blood smear https://imagebank.hematology.org/image/60511/lymphocyte Kosteret al. “Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review” Am J ClinPathol 2001;116:665-672

16. Examples Mature neutrophil “Left Shift”; more cells earlier in their maturation https://www.pathpedia.com/education/eatlas/histology/blood_cells/Images.aspx?00fa6c0f-5e6c-4c1b-a8b9-dfd2e32174f3 http://www.browncoatnation.com/deepdive/inconceivable/inconceivable-the-left-shift/

17. Examples Thrombocytopenia, hemoconcentration, and left shift in granulocyticseries Kosteret al. “Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review” Am J ClinPathol 2001;116:665-672

18. Use of 5-point screen in Four Corners Region

19. 5-point screen1: how does it perform? • Studied at University of New Mexico2 • Presence of 4/5 criteria most clinically useful • 96% sensitivity, 99% specificity for hantavirus pulmonary syndrome • Retrospective review of 10-years of cases (158 patients) found 89% sensitivity, 93% specificity • Accurate 93% of the time • 31 cases met 4/5 criteria and received treatment (including ECMO if needed) 2Dvorscak et al. “Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear.” Am J ClinPathol 2014;142:196-201.

20. Use of 5-point screen in Four Corners Dvorscak et al. “Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear.” Am J ClinPathol 2014;142:196-201.

21. Use of 5-point screen in Four Corners Dvorscak et al. “Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear.” Am J ClinPathol 2014;142:196-201.

22. 5-point screen: Limitations • Not perfect • Serial evaluation is critical • Different smear interpretations may affect scores • On-call UNM infectious diseases and medical critical care physician available at 1-800-272-2000

24. Thank you