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Infectious disease epidemiological problems addressed by molecular biology techniques (2016) 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 Validating microdiversity genotyping methods applied to epidemiology Virus quasispecies population structure analysis Identifying direction and chain of transmission Identifying hidden social networks and transmission links Analyzing microbiomes to study non-infectious disease epidemiology Practices of molecular epidemiology Lecture 4: Differentiating endemic from epidemic occurrence of infectious disease National Institute of Infectious Disease January 17, 2017 Epidemic vs endemic disease occurrence 20 19 18 17 16 15 14 13 12 11 10 1901- 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 19811970 2010 2500 2000 Shigellosis in New Delhi, India, 1985-1995 2500 2000 1500 1500 1000 1000 500 500 Shigellosis in New Delhi, India, 1985-1995 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 Molecular epidemiology: Application in outbreak investigations • Outbreaks provide an opportunity to validate new strain typing methods • Once validated, the same method can be applied to investigate other outbreaks and sporadic diseases • With some infectious diseases, strain typing methods themselves provide evidence for occurrence of an outbreak Use of molecular techniques in outbreak investigations • To identify unrecognized outbreaks among what looks like sporadic (endemic) cases of disease. • To identify vehicles of infection in which conventional methods are not useful • To monitor the impact of an intervention measure Molecular techniques used to study sporadic cases of an infectious disease: Rationale • A small fraction of reported cases come from recognized outbreaks (7% in salmonellosis in the US) • Identifying risk factors for sporadic infections is difficult • May provide information about attributable risk • May provide information about the dynamics of disease transmission in a community • transmission by a food vehicle • transmission by person‐to‐person contact • geographic and temporal distribution of a clone Examples: Multi‐drug resistant bacterial infections in the United States • Drug‐resistant human salmonellosis in the U.S., 1970‐1990s—animal or human source? • Drug‐resistant salmonellosis in Brazil—hospital or community‐ acquired? • Sources of drug‐resistant human uropathogenic E. coli in the United States—humans or animals? • Sources of drug resistance genes—hospitals or community? Example 1: Measuring drug‐resistance prevalence: Drug‐ resistant salmonellosis in the U.S., 1970‐1990s Epidemiological question: What is the main source of drug‐resistant Salmonella‐‐animals or humans? Drug‐resistant salmonellosis‐‐conclusions • Human infections with drug‐resistant Salmonella have animal origin • Measures of incidence and prevalence of drug resistance in a community is dependent on the number of drug‐resistant clones that happen to be circulating in that community at the time of the study • It is meaningless to discuss increasing or decreasing prevalence of drug‐resistance without specifying the clonal composition of the isolates tested for antimicrobial susceptibility Quantifying attributable risks in sporadic (endemic) infections Example 2: Investigation of sporadic cases of salmonellosis in New Jersey and Pennsylvania: Epidemiological question: What proportion of sporadic salmonellosis in a community can be attributed to a single contaminated food product? Salmonellosis in New Jersey and Pennsylvania, June-Aug, 1981 Background: Salmonellosis outbreak at a wedding in New Jersey across the river from Philadelphia, Pennsylvania Salmonellosis outbreak in a Eye Hospital in Philadelphia Precooked roast beef implicated as the vehicle for both outbreaks Precooked roast beef prepared at a meat processing plant in Philadelphia Question: How many cases of salmonellosis caused by precooked roast beef occurred among those not part of these outbreaks? Comparison S newport isolates from sporadic infections analyzed Period of isolation Place Number of isolates analyzed Jan-March, 1981 Pennsylvania 14 June-August, 1981* Pennsylvania, New Jersey 33 Nov 1981-Jan 1982 Pennsylvania, New Jersey 12 June 1981-Feb 1982 Georgia, Michigan, Texas 45 Total 104 *outbreak period Proportion of S newport infections associated with roast beef (RB)-associated plasmid profile, Pennsylvania and New Jersey, Jan 1981-Jan 1982 Period Total number reported* Jan-March 68 1981 June-Aug 1981 49 Nov 1981Jan 1982 14 Number analyzed (%) RB associated plasmid profile 14 (21%) 33 (67%) 42% 12 (86%) 25% *excludes known outbreak cases Salmonellosis in New Jersey and Pennsylvania conclusions Contaminated food product was introduced into a community Increased prevalence of salmonellosis was found to be associated with one predominant strain of Salmonella A single food product was found to be responsible for nearly 40% of sporadic salmonellosis cases in NJ and PA in the summer of 1981 After recall of the implicated food item, salmonellosis caused by the epidemic clone continued in the community by person-toperson transmission
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