Chagas Disease in the United States

1. Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease Control and Prevention Atlanta, GA

2. Trypanosoma cruzi • Protozoan parasite only found in the Americas, causes Chagas disease • Vector-borne zoonosis, humans not necessary to cycle • Infects >100 domestic and wild mammals • Typical hosts: opossums, wood rats, raccoons, dogs, cats • Infection of host and vector is life-long • Enormous domestic and sylvatic reservoirs

3. Distribution of vectors and disease • Endemic for human Chagas disease • Infected vectors, nonhuman mammals

4. Chagas disease worldwide • Programs in Latin America focus on controlling transmission • Vector control • Blood safety • WHO Global Network for Chagas disease formed in 2007 • Drug donation (nifurtimox) to WHO • Unique situation in the U.S.

5. Acute phase of Chagas disease T. cruzi infection 4 - 8 weeks Asymptomatic: > 90% Symptomatic: <10% Infection remains life-long if untreated Chronic phase Indeterminate form (asymptomatic, normal H&P, ECG) 20 - 40% progress over years - decades 60 - 80% remain in indeterminate form throughout life Can reactivate if immunosuppressed Clinically manifest Chagas disease Chagas heart disease Chagas gastrointestinal disease

6. Clinical testing challenges • No gold standard test for diagnosis • Serological testing limited availability and varied sensitivity and specificity • Specific skill necessary for parasitological diagnosis (acute infection, reactivation disease) • No test to identify which patients will progress from indeterminate form to clinical disease • No test to determine cure with antiparasitic treatment

7. Risk of infection in the U.S. • Estimated 300,000 infected immigrants in U.S.* • Who is at risk of infection in the U.S. • People exposed to infected vectors and/ or reservoirs • Children of infected mothers • Transplant recipients • Transfusion recipients • Laboratory staff working with vectors, reservoir species, or parasite *Bern and Montgomery, manuscript submitted

8. History of bugs and T. cruziin the United States • 1855 – Vector bugs identified in Georgia • 1860’s / 70’s – Vector bugs identified in six more states • 1909 – Discovery of parasite and disease (Brazil) • 1916 – Parasite first observed in California • 1930’s – Reservoir host infections studied in U.S. • 1955 – First autochthonous cases of Chagas disease reported

9. States with documentedpotential T. cruzi vectors ~ 11 potential vector species in the U.S.

10. States with documented mammalian reservoirs * * * * * Published human vector-associated cases > 18 infected reservoir species identified

11. 30 mm Vector and Chagas disease in Texas* Overall, 50% of tested bugs positive for T. cruzi Female Triatoma gerstaekeri Male Triatoma sanguisuga *Kjos et al. VBZD 2009 Photo courtesy of Sonia Kjos

12. Vector-borne transmissionin the U.S. • Seven autochthonous human cases published

13. Published U.S. autochthonous cases:Acute infections • Age range 2 weeks to 84 years, 4 male • 4 presented with acute symptoms • Non-specific febrile illness • Myocarditis, pericardial effusion • 2 primary complaint of bug bites • Fever within 48 hours of bug identification • 1 unclear clinical history • Triatomines on property in 5 cases; infected reservoir animals on property in 4 cases

14. Autochthonous infections in U.S. blood donors • 2007 Investigation of two blood donors in Mississippi • Ongoing study to investigate potentially autochthonous cases, U.S.– Derived T. cruzi Infection Study (USTC) • Designed in collaboration with American Red Cross and Blood Systems Laboratories • Participants will be tested with blood center and CDC tests

15. Travel-associated infection • 26yo Canadian woman returned from 6 months in rural Mexico with acute Chagas disease (Romana’s sign) • 56yo Californian man asymptomatic positive blood donor, three international trips each < 2 wks • Two trips to Mexico, one to non-endemic area of South America

16. Congenital transmission in the U.S. • No confirmed cases in U.S. • 3 possible cases reported • Case reports from other non-endemic areas • Congenital transmission 1 – 10% in endemic areas • Usually asymptomatic or non-specific findings • Low birth weight, hepatosplenogmegaly, respiratory distress, anemia, fever • Estimate 63 – 315 infected infants per year in U.S.* *Bern and Montgomery, manuscript submitted

17. Transplant transmission in the U.S. • Five published cases • 24 recipients of solid organs from seropositive donors in U.S. • Heart • Liver • Kidney • Pancreas/ kidney, liver/ kidney, pancreatic islet • 7 (41 %) of 19 recipients became infected

18. Transfusion transmission in the U.S. and Canada • 7 transfusion transmission cases reported in U.S. and Canada • Likely under-recognized and under-reported

19. Laboratory-associated transmission in the U.S. • Possible exposures • Feces of infected triatomenes • Handling cultures from infected persons or animals • Routes of entry • Needlesticks • Existing micro-abrasions on skin • Mucus membranes • Inhaling aerosolized organisms? • 8 cases reported in the U.S. • 3 needlesticks • 3 contact with infectious material and break in skin • 2 unknown

20. Chagas disease may not be recognized in the U.S. • Most physicians not familiar with Chagas disease • Recent ACOG survey • Medscape surveys • Community-based organization focus groups • Even clinical Chagas disease is not diagnosed • Up to 14% of Hispanic cardiac patients found to be positive for Chagas disease (screened for typical EKG changes)

21. U.S. public health and Chagas disease • Not nationally notifiable • Reportable only in AZ, soon in MA • No systematic public health surveillance • AABB Biovigilance system • Competing priorities at public health departments • Lack of public health testing capacity for Chagas disease

22. 2007 – 2008 CDC consultations and drug releases for Chagas-positive blood donors 45 drug releases 115 consultations (19 suspected autochthonous infections) Total of 765 RIPA-positive blood donors* * AABB Chagas Biovigilance reporting system

23. CDC Nifurtimox releases by year1997 – 2009* Clinical patient releases Blood donor releases * Blood donor screening starts * as of March 25, 2009

24. Challenges to be addressed • Improve healthcare provider awareness of Chagas disease • Diagnose clinical disease • Recognize transfusion transmission • Screen for transplant transmission risk • Quantify burden of clinical disease in U.S. • Cardiac disease burden • Gastrointestinal disease burden

25. Risk of Trypanosoma cruzi infection in the U.S. • No estimates because insufficient data • Requires studies to investigate risk of T. cruzi infection by mode of transmission • Autochthonously • During travel • Transfusion-associated • Congenitally

26. Thanks to • Sonia Kjos, CDC and TX DSHS • Paul Cantey, CDC • Caryn Bern, CDC The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention.