1. TM Centers for Disease Control and Prevention National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention National Center on Birth Defects and Developmental Disabilities Investigation of Fetal Loss Due to Maternal Dengue Infection During a Outbreak in Puerto Rico, 2005-2006 Investigation of Fetal Loss Due to Maternal Dengue Infection During a Dengue Outbreak in Puerto Rico, 2005-2006 Carrie Lazarus M.S., Ph.D., Sherry Farr MSPH., Ph.D., Mark Beatty MD., MPH Mirna Perez-Rodriguez MSW., Aidsa Rivera MS., Mary Ramos MD., MPH.

2. TM Aedes aegypti Aedes aegypti Mosquito

3. TM Transmission of Dengue Virus by Aedes aegypti Viremia Extrinsic incubation period DAYS 0581216 20 2428 Human #1 Human #2 Illness Mosquito feeds / acquires virus Mosquito refeeds / transmits virus Intrinsic incubation period Illness

4. TM Aedes aegypti Dengue transmitted by infected female mosquito Primarily a daytime feeder Lives around human habitation Lays eggs and produces larvae preferentially in artificial containers

5. TM Dengue Clinical Syndromes Classic dengue fever (“breakbone fever”) Dengue hemorrhagic fever Severe Body Pain Acute Illness w/ High Fever Headache Retro-orbital Eye Pain Rash Hemorrhagic manifestations ↑Capillary Permeability Haemostatic Changes Mortality 10-20% w/o early treatment Mortality 0.2% w/ experienced hospitals

6. TM Dengue Clinical Syndromes Dengue shock syndrome, includes symptoms of DHF + “Unusual presentations” Sustained Abdominal Pain ∆ level of consciousness Sudden decrease in platelet count Gastrointestinal Hemorrhage Hepatic Fever Cardiomyopathy

7. TM Undifferentiated Fever May be the most common manifestation of dengue Prospective study found that 87% of students infected were either asymptomatic or only mildly symptomatic

8. TM Laboratory Methods for Dengue Diagnosis, CDC Dengue Branch Virus isolation to determine serotype of the infecting virus IgM ELISA to test for antibodies to the virus

9. TM Temperature, Virus Positivity and Anti-Dengue IgM, by Fever Day Dengue IgMMean Max. TemperatureVirus Adapted from Figure 1 in Vaughn et al., J Infect Dis, 1997; 176:322-30. Fever Day 0 20 40 60 80 100 Percent Virus Positive -4-3-20123456 39.5 39.0 38.5 38.0 37.5 37.0 Temperature (degrees Celsius) Dengue IgM (EIA units) 300 150 0 75 225

10. TM Infection and Pregnancy 10-25% of fetal loss caused by maternal or fetal infection Due to: – High maternal fever – Reduced blood flow from infected placenta – Fetal infection and damage of vital organs

11. TM Dengue Infection in Pregnancy Limited information Vertical transmission 1,2 Dengue infection may be associated with: – Spontaneous abortion and fetal death 3,4 – Premature births 3 1. Chye, 1997; 2. Boussemart, 2001; 1. Chye, 1997; 2. Boussemart, 2001; 3. Carles, 1999; 4. 2000

12. TM Objectives 1)Investigate the risk of fetal loss due to maternal dengue infection during a current dengue outbreak in San Juan 2)Develop recommendations and health messages to inform the public about the risks of dengue infection during pregnancy

13. TM Suspected Dengue Cases by Week Specimen Received ─ Puerto Rico, 2005 Epidemiologic Week Number of CasesAverage Number of Cases Cases Reported

14. TM Design and Recruitment Case-control model Cases: when presenting at ob/gyn for medical care for fetal loss – Physician/resident interviews patient Controls: at prenatal care visit – Interview and self-administered Recruitment criteria – >16 years of age – Singleton pregnancies

15. TM Participating Hospitals UPR Carolina San Juan Municipal Hospital Divisions involved: – Ob/gyn – Prenatal care – Laboratory – Pathology – Epidemiology

16. TM Data Collection Short questionnaire – Medical and pregnancy history – Demographic characteristics – History of dengue symptoms Information from: – Medical record – Patient interview 90 days of data collection

17. TM Specimen Collection Blood (4mL) – Initial visit – Follow-up 7-30 days later – Dengue Case Report form Products of Conception – Fetal tissue, cord, placenta Specimens picked up weekly by CDC staff

18. TM

19. Results Between December 14th, 2005, and March 13th, 2006, – 39 case-patients and – 111 controls were recruited. Mean gestational age: case-patients (10 weeks) controls (16 weeks), p<0.01. No differences in past fetal loss or self-reported past dengue infection. IgM tests for dengue infection: – positive for 0 case-patient and 2 controls.

20. TM Conclusions Outbreak peaked earlier than expected, the incidence of confirmed dengue infection during this investigation was low among recruited women. Replicate the investigation at the first signs of a future dengue outbreak in Puerto Rico. The foundation has been laid for further public health responses to the dengue virus.

21. TM Recommendations Public health message: – Limit risk of transmission among pregnant women – Encourage pregnant women to seek immediate care – Heighten awareness among healthcare providers

22. TM Limitations Level of dengue peaked before investigation. 90 day data collection period. Reliance on an already burdened hospital staff

23. TM Accomplishments Education of healthcare professionals Hospital staff monitor the prenatal care of over 210 women per month Increased awareness

24. TM Acknowledgements NCBDDD – Developmental Disabilities Branch – Birth Defects Branch NCCDPHP – Women’s Health and Fertility Branch NCID – Dengue Branch Hospital Federico Trilla (UPR, Carolina) – Clínica de Cuidado Prenatal – Sala de Partos – Laboratorio Clínico – Area de Patología – Oficina de Control de Infecciones San Juan Municipal Hospital – Departamento de Obstetricia y Ginecología – Clínica de Cuidado Prenatal – Sala de Urgencias de Obstetricia y Ginecología – Laboratorio Clínico – Area de Patología – Programas Institucionales-Área de Control de Infecciones The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention

25. TM Dengue BranchSan Juan, Puerto Rico