Application of molecular epidemiologic methods to infectious disease surveillance

Practices of Molecular Epidemiology Lecture 11: Application of molecular epidemiologic methods to infectious disease surveillance National Institute of Infectious Disease January 18, 2017 Learning objectives  Describe how surveillance systems contribute to molecular epidemiology investigations  Give examples of how the application of molecular epidemiologic methods contributed to solving an infectious disease epidemiologic problem that could not be solved by conventional methods 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 Surveillance definition  A continuous and systematic process of collection, analysis interpretation and dissemination of descriptive information for monitoring health problems  This information ideally is linked to specific actions in the decision-making process General functions of surveillance:  Measures disease burden  Facilitates initiation of outbreak investigations  Generates hypotheses concerning risk factors and provides a source of cases to test these hypotheses  Guides prevention, control or treatment strategies  Evaluates effects of interventions and confirms findings from outbreak investigations that lead to control measures  Provides public health officials with information (and the ability to anticipate future health service demands) required to make policy decisions and allocate resources appropriately Types of surveillance systems • • • • Passive, provider-based Passive, laboratory-based Active, provider or laboratory-based Sentinel: provider, hospital, or laboratory Choice of surveillance system • Depends on the question that needs to be addressed by the surveillance system:  Completeness (sensitivity or % cases identified), specificity  Representativeness  Acceptability and ease of implementing the system  Timeliness  Cost and resources Infectious disease surveillance timeline (Lipkin WI Nat Rev Micro 2013) Function of surveillance in molecular epidemiology  Helps to validate new strain typing tests  Provides reference for pattern analysis  Identifies outbreaks not previously recognized  Provides opportunity to perform type of analysis not possible to by conventional methods  Monitors clonal group distribution over time and place  Identifies new modes and reservoir of transmission  Identifies clones that may have distinct biologic properties responsible for their predominance in a community  Identifies new pathogens or variants of recognized pathogens—provides evidence for a causal relationship Validation of new typing methods—premises that need to be considered What is the specific public health question to be answered?  Geographical target population for surveillance?  Global  National  State or Local  Duration of the surveillance system?  Outbreaks/epidemics in a discrete time period  e.g., influenza, SARS,  Long-term (hospital, national, global)  MRSA, Salmonella, Shigella, E coli O157;H7, HIV, etc Providing reference for pattern analysis  PFGE analysis: Tenover’s criteria can be satisfied if a reference PFGE pattern exists  Sequence-based tests: Constructing trees based on nucleic sequences—which sequence to root the other sequences Identifying outbreaks not previously recognized  Examples:  Salmonellosis in Pennsylvania  Identification of a new clonal group E coli ST69 during a local UTI surveillance study  Drug-resistant pneumococcal meningitis in Salvador, Brazil  Salmonellosis and E coli O157:H7 infections in Minnesota Surveillance for E coli 0157:H7 infections, Minnesota: 1994 1995 Surveillance for E coli 0157:H7 infections, Minnesota: Are strains identified during surveillance related according to their typing patterns? Surveillance for E coli 0157:H7 infections, Minnesota: Genotyping pathogens for surveillance provides opportunity to perform type of analysis/research not possible to by conventional methods  Redefine cases according to strain type to conduct a case-control study  Make stochastic inferences based on sample size smaller than what would be required for a conventional epidemiologic study  Identify new biologic tests (e.g., diagnostic) that may not have been considered otherwise Monitoring clonal group distribution over time and place  Uropathogenic E coli ST69 over years at UC Berkeley  Global spread of ST131 E coli  International spread of drug-resistant pneumococcus, Salmonella, M tuberculosis, HIV  Spread of CA-MRSA  Introduction of enterovirus 71 in China in 2008  Serotype replacement after vaccine introduction (19A Pneumococcus) Changes in incidence of invasive pneumococcal disease, USA, since introduction of PCV7 in 2000 Hospital-based surveillance before and after the introduction of Hib conjugate vaccines, Salvador, Brazil, 1996-2000 (Ko et al, Clin Infect Dis 2000)  In the one-year period following Hib immunization, 29 cases of H influenzae meningitis were identified vs 308 cases in the previous 3½ year period  However, (16%) of the 29 cases were due to H influenzae type a, whereas only (0.7%) of the 308 cases during the pre-vaccine period were due to this serotype 1996 1997 1998 Date of hospitalization 1999 2000 Aug Jul Jun May Apr Mar Feb Jan Dec Nov Oct Sep Aug Jul Jun May Apr Mar Feb Jan Dec Nov Oct Sep Aug Jul Jun May Apr Mar Feb Jan Dec Nov Oct Sep Aug Jul Jun May Apr Mar Feb Jan Dec Nov Oct Sep Aug Jul Jun May Apr Mar NúmerodeCasos 25 20 Isolado não-tipado Não-Capsulado Tipo f Tipo a Tipo b 15 Campanha de Vacina 10 PFGE Typing of H influenzae Type a isolates from Salvador and other cities in Brazil ATCC A Clone USA Salvador PN SP Pre Post B Clone Pre Salvador Post SP PE SP Identifying new modes and reservoir of transmission-examples  UTI as a possible foodborne disease  Produce as new vehicles of transmission of Salmonella and E coli O157:H7  Bats as a reservoir of SARS-coronavirus  Camel as a reservoir of MERS-coronavirus Surveillance: providing evidence for causality  Outbreaks or epidemics of a disease recognized by a conventional surveillance system can be used to show causal relationship of a detected organism with the disease  Clusters of a disease unrecognized as an outbreak can be unmasked by genotyping methods to provide new information that can be used to find a causal relationship  Sporadic illnesses (e.g., bloody diarrhea) may be unmasked as parts of an epidemic by molecular biology tools Once shown as an outbreak, the same methods can be used to show a causal relationship References  Lipkin WI The changing face of pathogen discovery and surveillance Nat Rev Microbiol 2013;11:133-141 ... how surveillance systems contribute to molecular epidemiology investigations  Give examples of how the application of molecular epidemiologic methods contributed to solving an infectious disease. .. Outbreaks or epidemics of a disease recognized by a conventional surveillance system can be used to show causal relationship of a detected organism with the disease  Clusters of a disease unrecognized... Acceptability and ease of implementing the system  Timeliness  Cost and resources Infectious disease surveillance timeline (Lipkin WI Nat Rev Micro 2013) Function of surveillance in molecular epidemiology