Hantavirus Pulmonary Syndrome: Diagnosis and Clinical Review

 
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
 
Overview
 
Clinical review of hantavirus disease
Background on 5-point screen for hantavirus
Use of 5-point screen in the Four Corners region
Questions
 
Clinical Review of Hantavirus Disease
 
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
 
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.
 
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…
 
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?
1.
Rapid referral to facilities with high-level intensive medical support
and 
extracorporeal membrane oxygenation (ECMO)
2.
Early identification of illness to enable #1
 
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
 
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.
 
5-point screen
 
Laboratory results in patients with
Hantavirus Pulmonary Syndrome
 
1.
Platelets decrease
2.
White blood cells increase
3.
Immunoblasts increase
4.
Hematocrit increases
 
1
Koster et al. “Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary
Syndrome by Peripheral Blood Smear Review” 
Am J Clin Pathol
2001;116:665-672
 
5-point screen
1
: what is it?
 
1.
Low platelet count (thrombocytopenia)
2.
Elevated white blood cell count with left shift
3.
Increased immunoblasts (>10% of lymphocyte population)
Enlarged lymphoid cells 2-3x greater in diameter than normal
4.
Lack of toxic changles in neutrophils
No toxic granulations, no Dohle bodies, no cytoplasmic vacuolization
5.
Hemoconcentration (increased hematocrit)
 
1
Koster et al. “Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary
Syndrome by Peripheral Blood Smear Review” 
Am J Clin Pathol
2001;116:665-672
2
Dvorscak et al. “Successful Triage of Suspected Hantavirus
Cardiopulmonary Syndrome by Peripheral Blood Smear.” 
Am J Clin Pathol
2014;142:196-201.
 
Normal lymphocyte
 
https://imagebank.hematology.org/image/60511/lymphocyte
 
Examples
 
Normal lymphocyte
 
https://imagebank.hematology.org/image/60511/lymphocyte
 
Immunoblasts on peripheral blood smear
 
Examples
 
Koster et al. “Rapid Presumptive Diagnosis of Hantavirus
Cardiopulmonary Syndrome by Peripheral Blood Smear
Review” 
Am J Clin Pathol
 2001;116:665-672
 
“Left Shift”; more cells earlier in their
maturation
 
Mature neutrophil
 
https://www.pathpedia.com/education/eatlas/histology/blood_ce
lls/Images.aspx?00fa6c0f-5e6c-4c1b-a8b9-dfd2e32174f3
http://www.browncoatnation.com/deepdive/inconceivable/incon
ceivable-the-left-shift/
 
Examples
 
Examples
 
Thrombocytopenia, hemoconcentration, and left
shift in granulocytic series
 
Koster et al. “Rapid Presumptive Diagnosis of Hantavirus
Cardiopulmonary Syndrome by Peripheral Blood Smear
Review” 
Am J Clin Pathol
 2001;116:665-672
 
Use of 5-point screen in Four Corners
Region
 
5-point screen
1
: how does it perform?
 
Studied at University of New Mexico
2
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)
 
 
2
Dvorscak et al. “Successful Triage of Suspected Hantavirus
Cardiopulmonary Syndrome by Peripheral Blood Smear.” 
Am J Clin Pathol
2014;142:196-201.
 
Use of 5-point screen in Four Corners
 
Dvorscak et al. “Successful Triage of Suspected Hantavirus
Cardiopulmonary Syndrome by Peripheral Blood Smear.” 
Am J Clin Pathol
2014;142:196-201.
 
Use of 5-point screen in Four Corners
 
Dvorscak et al. “Successful Triage of Suspected Hantavirus
Cardiopulmonary Syndrome by Peripheral Blood Smear.” 
Am J Clin Pathol
2014;142:196-201.
 
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
 
 
 
 
Thank you
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This content provides an in-depth overview of Hantavirus Pulmonary Syndrome, including its clinical presentation, diagnosis, and management. It covers key points such as incubation periods, symptoms, and diagnostic tests like ELISA. The information emphasizes the need for a high index of suspicion due to the rarity and similarity of symptoms to other illnesses.

  • Hantavirus
  • Pulmonary Syndrome
  • Diagnosis
  • Clinical Review
  • ELISA

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

  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 Overview

  3. Clinical Review of Hantavirus Disease Clinical Review of Hantavirus Disease

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

  5. 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. How do we diagnose someone with Hantavirus Pulmonary Syndrome? It is rare; even in the Four Corners region! It looks like other illnesses Bottom line: Requires a high index of suspicion in the appropriate context.

  6. Once we suspect ithow 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 Once we suspect it how do we diagnose? Diagnostic tests

  7. Once we suspect ithow 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? 1. Rapid referral to facilities with high-level intensive medical support and extracorporeal membrane oxygenation (ECMO) 2. Early identification of illness to enable #1 Once we suspect it how do we diagnose? Diagnostic tests What can make a difference? extracorporeal membrane oxygenation (ECMO)

  8. 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 Treatment for patients with Hantavirus Pulmonary Syndrome Supportive therapy Extracorporeal membrane oxygenation = ECMO

  9. ECMO 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 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.

  10. 5 5- -point screen point screen

  11. Laboratory results in patients with Hantavirus Pulmonary Syndrome 1. Platelets decrease 2. White blood cells increase 3. Immunoblasts increase 4. Hematocrit increases Laboratory results in patients with Hantavirus Pulmonary Syndrome 1Koster et al. Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review Am J Clin Pathol 2001;116:665-672

  12. 5 5- -point screen 1. 1. Low platelet count (thrombocytopenia) 2. 2. Elevated white blood cell count with left shift 3. 3. Increased Enlarged lymphoid cells 2-3x greater in diameter than normal 4. 4. Lack of toxic No toxic granulations, no Dohle bodies, no cytoplasmic vacuolization 5. 5. Hemoconcentration point screen1 1: what is it? Low platelet count (thrombocytopenia) Elevated white blood cell count with left shift Increased immunoblasts Lack of toxic changles Hemoconcentration (increased hematocrit) : what is it? immunoblasts (>10% of lymphocyte population) changles in neutrophils (increased hematocrit) (>10% of lymphocyte population) in neutrophils 1Koster et al. Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review Am J Clin Pathol 2001;116:665-672 2Dvorscak et al. Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear. Am J Clin Pathol 2014;142:196-201.

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

  14. Examples Examples Normal lymphocyte Normal lymphocyte Immunoblasts on peripheral blood smear Immunoblasts on peripheral blood smear https://imagebank.hematology.org/image/60511/lymphocyte Koster et al. Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review Am J Clin Pathol 2001;116:665-672

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

  16. Examples Examples Thrombocytopenia shift in Thrombocytopenia, hemoconcentration, and shift in granulocytic , hemoconcentration, and left granulocytic series left series Koster et al. Rapid Presumptive Diagnosis of Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review Am J Clin Pathol 2001;116:665-672

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

  18. 5 5- -point screen Studied at University of New Mexico 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) point screen1 1: how does it perform? Studied at University of New Mexico2 2 Presence of 4/5 criteria most clinically useful : how does it perform? 2Dvorscak et al. Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear. Am J Clin Pathol 2014;142:196-201.

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

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

  21. 5 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 point screen: Limitations

  22. Thank you Thank you

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