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

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. cruzi in 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 documented potential T. cruzi vectors ~ 11 potential vector species in the U.S.

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

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

12. Vector-borne transmission in the U.S. Seven autochthonous human cases published YearStatePatient 1955Texasinfant 1955Texasinfant 1982California56 year old woman 1983Texasinfant 1998Tennesseeinfant 2006Louisiana74 year old woman 2006Texasinfant

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 YearRecipient residenceCountry of donor 1987CaliforniaMexico 1989New York CityBolivia 1989ManitobaParaguay 1993Houstonunknown 1999MiamiChile 2000ManitobaParaguay 2002Rhode IslandBolivia

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. Clinical patient releases Blood donor releases Blood donor screening starts * as of March 25, 2009 CDC Nifurtimox releases by year 1997 – 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.