Identifying new modes of transmission by new generation technique

Practices of molecular epidemiology Lecture 7: Unmasking new modes of transmission National Institute of Infectious Disease January 17, 2017 Infectious disease epidemiological problems addressed by molecular biology techniques             Tracking strains across time and geography Distinguishing endemic from epidemic disease occurrence Stratification of data to refine study designs Distinguishing pathovars vs commensal flora or saprophytes Identifying new modes of transmission Studying microorganisms associated with healthcare or institutional infections Surveillance and monitoring response to intervention Characterizing population distribution and determinants of distribution of parasitic organisms Identifying genetic basis for disease transmission Analysis of microbiomes to study non-infectious disease epidemiology Identifying direction and chain of transmission Identifying hidden social networks to unmask transmission links Example 1: Drug‐resistant urinary tract infection in  a college community: Epidemiologic question: How is community‐ acquired urinary tract infection (UTI) transmitted? UTI—public health problem  In the US, million office visits a year  >1 million emergency room visits a year  >100,000 hospitalizations a year  $1.6 billion in medical expenditure  Most common bacterial infectious disease of women Urinary tract infection (UTI) drug susceptibility study, UC Berkeley October 11, 1999 to January 31, 2000 University Health Services, Tang Health Center, Berkeley, California 505 consecutive urine samples 255 total E coli isolates, 228 women Results of antibiotic susceptibility tests, UC Berkeley (n=255)  Trimethoprim-sulfamethoxazole:  Ciprofloxacin  Cephalothin  Nitrofurantoin 55 (22%) (0.8%) (3.5%) ERIC2 PCR Fingerprints of selected E coli Isolates California university community University Health Services, Berkeley 255 total E coli isolates, 228 women Collected October 11, 1999 to January 31, 2000 Case community Minnesota University of Minnesota Health Services, Minneapolis 82 total E coli isolates Collected June 1998 to August 1999 Michigan University of Michigan Health Services, Ann Arbor 67 total TMP-SMZ resistant E coli isolates Collected 1996 to 1999 Comparison community ERIC2 PCR Patterns of E coli Isolates SF Bay Area MW BP Michigan 102 203 283 Minnesota 10 11 12 4072 1000 CFT073 T10F2 T367F2 T338F2 26 80 153 Neg Isolation of E coli from animal sources by year, ST69 UTI Study 200 150 100 50 1971- 1976- 1965- 1971- 1976- 1981- 1986- 1991- 19961975 1980 1970 1975 1980 1985 1990 1995 2001 Total # of Isolates ST69 TMP-SMZ resistant PFGE analysis of TMP-SMZ-resistant E coli isolates with ERIC CgA pattern, UTI Study (Ramchandani et al, Clin Infect Dis 2005) # animal isolate 10 MLST analysis of uropathogenic E coli (Tartof et al, J Clin Micro 2005) Cg A E coli PFGE analysis of ST69 Distribution of ST69 E coli Johnson et al, EID 2005 What happened to ST69? Drug-resistant UTI, Berkeley, CA(S Smith et al Clin Infect Dis 2008 )  6-year cross-sectional study (Oct-Jan, 1999-2000; 2000-01; 2003- 04; 2004-05)  780 E coli isolates from 1667 women with UTI attending the university student health service  ERIC PCR performed on all the isolates Drug-resistant UTI, Berkeley, CA (S Smith et al, Clin Infect Dis., 2008)—cont  Results: Period  Number of isolates studied:  TMP-SZX resistance (%):  Ciprofloxacin (%):  Nitrofurantoin (%):  Ampicillin (%):  Multidrug resistance (%): *significant decrease 228 24 NA NA 206 18 NA NA 230 16 1 35 36 116 16 24* 24 Major clonal group distribution over the study periods Period Clonal group CgA # CgA (%) CgC # CgC (%) CgH # CgH (%) 25 (26) (7) 0 (5) (3) 17 (12) 30 (13) 31 (13) 24 (10) 10 (9) 18 (16) (8) 35 30 25 20 CgA 15 CgC 10 CgH 1999-2000 2000-01 2003-04 2004-05 Summary of results, UTI study, Berkeley, 1999-2005  There was no evidence of increasing prevalence of drug resistance at the university community  Ampicillin resistance decreased significantly between 20032005  One clone (CgC) accounted for 75% of this decrease  largest clonal groups (CgA, CgC, CgH, and Cg3) accounted for 41% of all UTI cases and 52% of TMP-SZX-resistant UTI  No initially pan-susceptible clonal group strains gained resistance over time Example 2: Unmasking new modes of viral transmission Newly discovered modes of transmission of viruses that cause epidemic disease  Filovirus (Ebola, Marburg)  Transmitted by direct contact with blood or eating bush meat  Ebola virus disease (EVD) reported in woman 30 days after last case of EVD in Liberia (MMWR, 2015, 64(17):479-481)  Woman had unprotected sex with survivor of EVD  Ebola virus shown to remain in semen 82 days after onset of symptoms  Ebola virus RNA detected in semen up to 284 days and in vaginal secretions 33 days after symptoms onset  Genome sequencing of woman and man’s viruses shared substitutions not found in any West African EV during the epidemic (Mate, SE et al, NEJM, 2015)  Possible transmission of Marburg virus reported in 1968 Viral persistence in semen after onset of symptoms Thorson A et al, BMJ Open,2016 Newly discovered modes of transmission of viruses that cause epidemic disease  Zika virus  Transmitted by Aedes mosquitoes Alternet  Sexual transmission in 2008 in Colorado, USA (Foy BD et al, EID, 2011)  American scientist acquired ZIKV in Senegal from mosquito bite  Wife in Colorado, who had no travel history, developed ZIKV infection  Male-to-female and female-to-male transmission documented by genome sequence analysis ArboNET, CDC: as of December 21, 2016: US Locally acquired mosquitoborne cases reported: • 215 Travel-associated cases reported: • 4,541 Laboratory acquired cases reported: •1 Total: 4,756 • Sexually transmitted: 38 • Guillain-Barré syndrome: 13 https://www.cdc.gov/zika/geo/united-states.html ... Example 2: Unmasking new modes of viral transmission Newly discovered modes of transmission of viruses that cause epidemic disease  Filovirus (Ebola, Marburg)  Transmitted by direct contact with... onset of symptoms Thorson A et al, BMJ Open,2016 Newly discovered modes of transmission of viruses that cause epidemic disease  Zika virus  Transmitted by Aedes mosquitoes Alternet  Sexual transmission. .. and determinants of distribution of parasitic organisms Identifying genetic basis for disease transmission Analysis of microbiomes to study non-infectious disease epidemiology Identifying direction