Challenges and Opportunities in Dengue Clinical Management

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1 Challenges and Opportunities in Dengue Clinical Management George Han, MD, MPH Medical Epidemiologist Dengue Branch San Juan, Puerto Rico CKLN/CARPHA Dengue Symposium June 12, 2014 National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-Borne Diseases Dengue Branch

2 Prevention of Dengue Morbidity and Mortality Primary prevention Vaccine Vector control programs Education (mosquito breeding areas, screens, and repellent) Secondary prevention Clinical management and clinician education Antivirals Improved diagnostics Education about warning signs and when to seek care

3 Natural History of DENV Infections Infection Incidence ~5% per year Asymptomatic 75% Symptomatic 25% Dengue 95 99% Severe dengue 1 5% Adapted from Vaccine 2004; 22: Survive % Die 0.5 5%

4 Natural History of DENV Infections Symptom onset 1 to 2 days Death or recovery 2 to 7 days Critical Phase 3 to 5 days Febrile Phase Convalescence Incubation Viremia Not viremic Days Mosquito bite

5 Complications During Clinical Course Shock End Organ Damage Hemorrhage Encephalopathy Dehydration Hyponatremia Febrile Seizures * Critical Phase Fluid Overload Pulmonary Edema Nosocomial Infections Febrile Phase Convalescence Incubation Viremia Not viremic Days *Note: manifestations of neuroinvasive disease including encephalitis and meningitis may present early in the febrile phase

6 Causes of Death in Dengue Lack of or late diagnosis of dengue Unrecognized shock or prolonged shock Unrecognized occult hemorrhage Fluid overload Nosocomial sepsis especially in elderly

7 1997 WHO Classification Dengue virus infection Asymptomatic Symptomatic Undifferentiated Fever Dengue Fever (DF) Dengue Hemorrhagic Fever (DHF) No hemorrhage Hemorrhage DHF I & II Dengue Shock Syndrome (DSS) Modified from Dengue hemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. Geneva; World Health Organization

8 2009 WHO Classification Dengue ± warning signs Severe dengue Without with warning signs 1.Severe plasma leakage 2.Severe hemorrhage 3.Severe organ impairment Criteria for dengue ± warning signs Probable dengue Live in/travel to dengue endemic area. Fever and 2 of the following criteria: Nausea, vomiting Rash Aches and pains Tourniquet test positive Leucopenia Any warning sign Laboratory confirmed dengue (important when no sign of plasma leakage) Warning signs* Abdominal pain or tenderness Persistent vomiting Clinical fluid accumulation Mucosal bleed Lethargy; restlessness Liver enlargement >2cm Laboratory: Increase in HCT concurrent with rapid decrease in platelet count * Requiring strict observation and medical intervention Criteria for severe dengue 1. Severe plasma leakage leading to: Shock (DSS) Fluid accumulation with respiratory distress 2. Severe bleeding as evaluated by clinician 3. Severe organ involvement Liver: AST or ALT>=1000 CNS: Impaired consciousness Heart and other organs Adapted from World Health Organizaiton (WHO), Dengue: Guideline for Diagnosis, Treatment, Prevention and Control. Geneva, Switzerland. WHO/TDR 2009

9 Clinical Practice in Puerto Rico Fatal case review for 2007 dengue outbreak Identified poor clinical practices such as the use of corticosteroids or the use of hypotonic saline while in shock Physician survey performed in Identified clinical practices consistent with fatal case review Found gaps in knowledge regarding diagnosis & management of dengue, and the recognition of early signs of shock

10 Clinical Management Issues Intravenous fluid (indications, type/amount, and when to change to colloid) Blood products (indications, type/amount) Monitoring (vital signs, intake and output) Practices not recommended: Steroids Hypotonic saline solutions Prophylactic platelet transfusions

11 Other Clinical Management Issues Prolonged shock leading to metabolic acidosis, encephalopathy and end organ failure, and severe GI bleeding Too much or incorrect fluid given leading to worsening effusions and dyspnea, pulmonary edema, ARDS Secondary infections in infants and elderly Abdominal compartment syndrome especially in infants and young children given hypotonic saline

12 CDC Dengue Clinical Management Course Objective: increase physician knowledge about dengue clinical management Trained Master Trainers who gave the course in >50 sessions to >8,000 physicians In 2010, Puerto Rico Secretary of Health issued an administrative order requiring all physicians to take the 4-hour course Evaluation of 1500 inpatient charts showed improvements in physician management of dengue

13 CDC Dengue Clinical Management Course Now Online Five modules, including case studies Contains videos to illustrate concepts and case studies Available on-demand when doctors see dengue patients 4 hours of free CME offered for physicians

14 CDC Dengue Course for Clinicians

15 CDC Clinical Management Pocket Guide Convenient pocket guide developed for easy reference for clinicians Currently two versions: 8-page web version which can be printed by anyone Pocket version which can be professionally printed and folded to fit in a white coat pocket Electronic mobile app under development

16 Opportunities for Research Admission criteria and timing of admission More operational research needed to test new referral and admission recommendations Colloids vs. crystalloids early in the course of illness Which are the best colloids to use? Utility of platelet transfusions (especially prophylactically) and fresh frozen plasma

17 Opportunities for Research Validate noninvasive hematocrit monitoring methods Develop rapid that predicts who will develop severe dengue Perform clinical evaluation of the warning signs to see how accurate they are in predicting severe dengue

18 Prevention of Dengue Morbidity and Mortality Primary prevention Vaccine Vector control programs Education (mosquito breeding areas, screens, and repellent) Secondary prevention Clinical management and clinician education Antivirals Improved diagnostics Education about warning signs and when to seek care

19 Acknowledgments Kay M. Tomashek, MD, MPH Epidemiology Team Lead Eunice Soto, MPHE Health Educator Chris Gregory, MD Medical Epidemiologist Hal Margolis, MD Dengue Branch Chief For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA Telephone, CDC-INFO ( )/TTY: Web: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-Borne Diseases Dengue Branch

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