Emerging Mycotic Diseases in Washington: Partnerships in the Investigation of Fungal Pathogens

Transcription

1 Emerging Mycotic Diseases in Washington: Partnerships in the Investigation of Fungal Pathogens Nicola Marsden-Haug, MPH Office of Communicable Disease Epidemiology Washington State Department of Health Cross Border Conference, May 2014 Overview Coccidioidomycosis (Valley Fever) Disease background Investigation of cases acquired in Washington Next steps Cryptococcus gattii Symptoms and transmission Global occurrence and emergence in the Pacific Northwest Epidemiologic differences Environmental factors Summary 1

2 COCCIDIOIDES Coccidioidomycosis Valley Fever Soil-dwelling fungus: Coccidioides immitis & C. posadasii Hot, arid climates; low rainfall (SW U.S., Mexico, S/C America) Transmission by inhalation of spores Incubation period: 1-4 weeks Spectrum of disease: asymptomatic to disseminated Most often mild; typically ILI or pneumonia Higher risk groups: immunosuppressed, African-American or Filipino descent, pregnant in 3 rd trimester Can treat with antifungals Images courtesy of CDC Mycotic Diseases Branch 2

3 Three unusual case reports Most Valley fever cases in U.S. reported from AZ and CA Washington State cases typically report travel to a known endemic area In 2010 and 2011 received reports of 3 acute cases among Benton, Franklin, and Walla Walla residents without any recent travel Remote histories of travel to CA or AZ Clinical and serologic evidence indicated acute infection Graphic courtesy of CDC Mycotic Diseases Branch Epidemiologic investigation Case #1: digging & building forts in dirt Case #2: ATV crash on dirt track Case #3: Soil excavator No recent travel Serology IgM IgG Absence of pulmonary nodules Geographically clustered Favorable growth parameters Rain shadow; semi-arid; low elevation Previous animal cases without travel* * M. Davis and T. Besser, Washington State Animal Disease Diagnostic Laboratory Pictures by N. Marsden-Haug & K. Stigi (WA DOH) 3

4 Soil sampling Interviews with case-patients helped identify suspected exposure sites for 2 of 3 cases Specimens collected from 2 locations in Benton Co. Surface and 6-inch depth collections Soil tested positive for C. immitis by PCR and culture DNA from soil isolates matched DNA of a clinical isolate from a case-patient Pictures by N. Marsden-Haug & K. Stigi (WA DOH); Heather Hill (Benton-Franklin Health District) Conclusions and questions C. immitis was isolated outside of the endemic range Novel PCR assay was able to detect C. immitis in soil Clinical and environmental strains had identical genomes: infections were acquired locally How widespread is cocci in WA? Is this a new expansion or has it been here for long time? What was the mechanism of expansion? Is it present in Oregon and neighboring states? 4

5 Cocci awareness Healthcare providers and veterinarians should be aware of potential for WA acquired cases Consider the diagnosis in clinically compatible cases who have spent time in south-central WA or an endemic area Delays in appropriate therapy can lead to substantial clinical complications Now explicitly notifiable in tri-county area; reportable as a rare disease statewide Clinicians and labs asked to report Graphic courtesy of CDC Mycotic Diseases Branch CRYPTOCOCCUS GATTII 5

6 Cryptococcus gattii Environmental fungi Unicellular encapsulated yeast (asexual); filaments (sexual) Causes mild to severe disease People: meningitis, pneumonia, cryptococcomas (masses) Symptoms: fever, chest pain,cough, shortness of breath, weight loss, headache, confusion/disorientation), night sweats Animals: nasal/sinus infection, skin ulcerations/nodules, enlarged lymph nodes, respiratory tract infections, ocular disease, nervous system involvement (incoordination, seizures, paralysis) brain cryptococcoma neurocases/may01/fig1.jpg C. gattii transmission Inhalation of spores from environment Colonization of nasal cavity, sinuses Conditions for propagation not well defined Disseminates from lungs to tissues (most commonly CNS) Not spread from animal to human A few maternal-fetus transmissions reported in marine mammals Incubation period: ~6 months (range: 2-13 mo.) May depend on host immunity and intensity of exposure Sources: Harris CID 2011; MacDougall EID 2011; Dixit, Interdisc Persp Inf Dis, 2009; preliminary US and BC surveillance data (unpublished). 6

7 Global occurrence Previously only seen in tropical/subtropical climates Emerged in Pacific Northwest in 1999 Before onwards Emergence in the Pacific Northwest Began appearing in animals and humans in British Columbia (BC); Vancouver Island then mainland Outbreak expanded into Washington and Oregon Initial cases with travel to BC; now in-state (no travel) * Sources: (1) Datta Interdisc. Perspect. Inf Dis. 2008; 2) Galanis, Can J. Inf Dis Med Microbiol., 2008; (3) Datta EID 2009; (4) Galanis, EID

8 Number of Cases Surveillance in Washington State Reportable as rare disease Historically voluntary isolate submission 2011: clinical and veterinary labs required to submit isolates of C. gattii and non-neoformans Cryptococcus Goal is to track cases and identify risk factors and exposures Animal cases also valuable sentinel indicators Standardized reporting; describe clinical features & genetic variety Outreach to increase awareness Infectious disease, neurologists, pulmonologists, and veterinarians Environmental detection Collaborate with BCCDC & US PNW working groups C. gattii human cases in Washington, Human cases (21) Animal cases (38) Year of Onset 8

9 Human cases of C. gattii in the U.S. by year of illness onset (n=114*) *Onset year is missing for 5 cases; reporting incomplete for 2011 (typically lagged by several months). Includes data as of 4/2012. Genetic similarity of isolates, WA and OR VGIIb VGI VGIII Neighbor-joining tree of C. gattii isolates shows conservation of 7 loci in major sequence types VGIIc VGIIa Washington Oregon 9

10 Outbreak-strain infections occur in association with PNW (OR, WA), Outbreakstrain genotypes * Includes data as of 4/2012. Genotype WA, ORassociated Not associated with WA, OR VGI 4 11 VGIIa 59 0 VGIIb 6 1 VGIIc 25 0 VGII (other) 0 1 VGIII 1* 10 VGIV 0 0 Total *VGIII patient moved from CA during year before illness Epidemiologic differences in human cases Strain-specific comparisons among U.S. cases Patient characteristic VGIIa/b/c outbreak strains Other genotypes Respiratory symptoms 76% 43% CNS (neurologic) symptoms 34% 100% Pre-existing condition 78% 43% Died of or with C. gattii 33% 20% Geographic comparisons between countries* Patient characteristic U.S. B.C. Australia Male 53% 56% 70-77% Predominant infecting strain genotype VGIIa & VGIIc VGIIa Mostly VGI Age (years): median (range) 56 (15-95) 62 (2-92) Early/mid-40s Clinical presentation Respiratory > CNS CNS > Respiratory Mostly CNS Pre-existing condition 73%** 38% 0-13% Hospitalized 91% 46% no data Died from or with C. gattii 32% 9% 0% * Galanis, 2010; Speed, 1995; Chen, 2000; Harris 2011.; US & BC surveillance data (unpublished). ** When limited to conditions considered in BC, only 61%. 10

11 Evaluating epidemiologic differences International study with Australia, British Columbia, and U.S. Chart review of case-patients to: Determine the relationships between host factors, therapy, C. gattii genotype, clinical presentation, and outcome Provide better clinical guidance Data use agreement recently signed Initial investigation phase in WA & OR Collaboration between both states and CDC In-state collaboration with local health jurisdictions Retrospective review of culture-confirmed cases with onset of symptoms between 1/ /2011 Medical records reviewed using standardized chart abstraction form Collected clinical data from initial visit and 2, 6, 12, 24, 52 week follow-ups; inpatient & outpatient records 11

12 Key findings from OR and WA study Most patients immunosuppressed; only 14% healthy Immunosuppressed patients more likely to die within 6 months Primary presentation of C. gattii is respiratory Pulmonary cases more likely to be immunosuppressed than CNS cases Long delay to diagnosis; especially among pulmonary patients Treatment is highly variable; not necessarily adherent to IDSA Success is partially dependent on site of infection and immune status Case-fatality rate is 16.5%; double reported rate in BC Differences in hospitalization and case ascertainment Unique genotype (VGIIc) accounts for 25% cases in U.S. No differences in clinical presentation or outcome by VG type Contradicts animal model studies of virulence; but small n studied here Next phases of epi investigation Comparison of US cases with BC and Australia Data use agreement signed Reviewing variables and data cleaning Evaluate differences between cases in different regions Comparison of C. gattii cases with C. neoformans cases Collaboration with academic medical centers 12

13 A stable ecological niche? Emergence in a temperate climate is new and surprising Documented presence in the Pacific Northwest Environmental detections in BC, WA, OR Vancouver Island: isolated from >10 native tree species, soil, and air samples WA: fence posts, parking lots Most early human and animal cases had contact with trees and the Coastal Douglas fir climatic zone Now many cases without travel to Vancouver Island * Sources: Kidd S, EID 2007; MacDougall L, EID 2007; Bartlett KH, Curr Inf Dis Rep 2008; Datta K, Interdisc. Perspectives on ID, Many questions Has C. gattii always been here or recently introduced? Has the organism adapted? How does that change pathogenesis, clinical presentation, ecological preferences? What are preferred ecological characteristics? Have environmental conditions become more favorable? Why was Vancouver Island colonized so well? Do ecological preferences differ by strain (genotype)? 13

14 Ecological niche modeling of Cryptococcus gattii in the U.S. Pacific Northwest Likelihood of species occurrence, as per the ENM: % 81-90% 71-80% 61-70% 51-60% 41-50% 31-40% 21-30% 11-20% 1-10% 0% Model based on 32 domestic veterinary cases in the US, Data applied against seven environmental layers: January min/max temperatures, temperature seasonality, min temperature of coldest month, annual temperature range, and mean temperature of coldest quarter. Preferences: -Low elevations - Temp above freezing - Coastal Douglas fir and Western Hemlock zones British Columbia Washington Oregon Idaho California Nevada Map created November 23, 2010 by Julie Harris, CDC, with assistance from Sunny Mak, BC CDC. Mak, et al, Env. Health Perspectives, Human cases, Washington, San Juan (1) Island (1) Whatcom (18) Skagit (2) Snohomish Jefferson (1) King (4) Thurston (1) Lewis (1) Clark (4) Yakima (1) Benton (2) Mapped by county of residence. 14

15 More questions Additional physical, ecological niches than currently known? Limited detections in U.S. but more clonal diversity Is the organism being distributed/spread? Animals (migratory birds); ships/ferries (imported trees, passengers); vehicles; people (shoes, clothes, camping gear); wind or water currents Do activities that promote aerosolization contribute to exposure and/or distribution? Commercial (large scale) logging, excavation, and forestry Small scale gardening, landscaping, vehicle travel on dirt roads, chopping trees or making wood chips Some studies of tree cutting, air concentrations Sources: Bartlett KH, Curr Inf Dis Rep 2008; Kidd S, EID 2007; Duncan C, JAVMA 2006.; Taylor (unpublished); Datta EID 2009; MacDougall EID 2010 C. gattii: limitations and considerations Cryptococcus infections not routinely speciated Underestimate of true burden of C. gattii is likely Reporting likely over-represents most severe cases Risk factors still unclear Unsure of environmental presence, exposure sources Just beginning to characterize how infections differ by genotype and geographic locations Small numbers of VGI / VGIII cases might obscure (or artificially enhance) true epidemiologic associations between exposures and outcomes Review of treatment guidance may be warranted 15

16 CONCLUSIONS Both cocci and C. gattii were recently and surprisingly discovered in the PNW Clinical awareness to support diagnosis and appropriate treatment Much to learn about these emerging diseases Clinical and epidemiological Genetic and ecological investigations to study origin of infections and try to predict future path Fungi are environmentally sensitive; role of new climate influence on organisms? Impact for human and animal infections? Benefits us all in partnering with neighboring jurisdictions Research, outreach, messaging ACKNOWLEDGEMENTS Valley fever investigation Benton-Franklin Health District: Heather Hill, Cindy Ralston Walla Walla Health Department: Harvey Crowder, Larry Jecha CDC: Tom Chiller, Anastasia Litvintseva, Ben Park, Mary Brandt, Steve Hurst, Lalitha Gade WA DOH: Marcia Goldoft, Ron Wohrle UC Davis: George Thompson T-Gen: David Engelthaler, Elizabeth Driebe, Chandler Roe, Paul Keim Cryptococcus gattii investigations and study CDC: Julie Harris, Shawn Lockhart, Rachel Smith, Adamma Mba-Jones, Mathieu Tourdjman, Ben Park, Tom Chiller Greg Stern and other local health investigators and health officers Oregon: Emilio DeBess, Paul Cieslak WA DOH: Marcia Goldoft, Ron Wohrle, Cyndi Free, Katie Stigi Pacific Northwest C. gattii work group (BCCDC, UBC) 16

17 Questions? 17