13) Epidemiology

Epidemiology

• the study of how often diseases occur in different groups of people and why

• used to plan and evaluate strategies to prevent illness and to manage patients

• measurement of disease outcomes in relation to a population at risk

• conclusions are drawn about a target population (full target population vs study sample)

• sample size and sample selction is critical (to small -> unrepresentative, systematic samplin errors)

• may help in individual cases but primarily important for groups

• etiology comes from comparing disease rates in groups with differing levels of exposure

Monitoring or surveillance of time trends is very important in epidemiology

• show which diseases are increasing, decreasing in incidence or changing in their distribution

• is needed to identify emerging problems and also to assess effectiveness of measures to control problems

• BUT standards of diagnosis and data recording may change, and conclusions from time trends must be carefully interpreted

Standardization and quality control of investigative methods are essential (risk of biases)

Endemic: Describes the baseline level of a disease usually present in a community

Epidemic or Outbreak: An increase, often sudden, in the number of cases of a disease above normal levels in a region. An outbreak sometimes refers to an increase in a smaller geographical area

Pandemic: An epidemic that has spread across several countries or continents and usually affects a large number of people

Zoonosis: A type of infectious disease that originates in vertebrate animals and moves to people. It can be spread by direct contact or carried from animals to humans by a vector such as a biting insect

John Snow

• From the distribution of cases, and by questioning local residents, Snow concluded that the outbreak source was a public water pump

burden of disease

• is the sum of moratility and morbidity

• measured by ‘Disability Adjusted Life Years‘ (DALYs)

Communicable diseases

• significant reduction in global burden

• mostly infectious disease

• major challenge in low- and middle-income countries

Top bacterial infectious diseases (2018)

• Tuberculosis

• Malaria

• Influenza

• Diarrhoeal disease

• HIV / AIDS

• Measles

Main notifiable infectious disease is Coronavirus disease (COVID-19)

The chain of infection

• used to show how infection spreads

• infection can be stopped by breaking one or more links

  • infectious agent

  • reservoir

  • portal of exit

  • model of transmission

  • portal of entry

  • susceptible host

Model of transmission:

• general

  • abiotic (Wind, Water, inhalation, skin)

  • animal vectors (mosquitos, fleas)

• human to human

  • Direct contact

  • indirect contact

  • droplets

  • airborne

  • fecal - oral

washing hands

masks

Different Salmonella serotypes have different antigens and different phases

Phage typing:

• ability of a given phage to lyse a particular strain

• easy to perform and provides strain characterisation

• BUT usual issues with phenotypic methods, reproducibility etc.

• Salmonell has >300 phage types

Advantages of molecuar methods:

• simplify

• accelerate

• precise detection and identification

• subtypes possible (gain knowledge of old and emerging diseases)

Older: Pulsed Field Gel Electrophoresis (PFGE) and Multi-locus sequence typing (MLST)

Newer: NGS

Genomic Epidemiology

• Discipline of mapping, sequencing, analysing and comparing genomes

• microbes accumulate changes in their genomes over time

• identification of species of isolate

• clinically important features such as vaccine antigens

• identification of virulence traits and antibiotic-resistance genes

• monitoring emergence and spread of pathogens at a high resolution

Pan-genome

• entire gene set of all strains of a species

• includes core genome and variable/accessory genome

Core-genome

• genes present in all strains

• typically includes housekeeping genes for cell envelope or regulatory functions

Variable or accessory genome

• genes not present in all strains of a species

• includes genes present in two or more strains or even genes unique to a single strain only e.g. genes for strain specific adaptation such as antibiotic resistance

• the mobilome e.g. plasmids may be included in this genome

Sequencing

Quality Control

Genome assembly (de novo or reference based) of a draft genome

• annotated (gene prediction and their function)

• screened against databases

• further analysis

• look at single nucleotide variants (SNVs)

Mapping to a reference

• looking for genotypes

• looking for specific genes of interest (e.g. virulence factors, AMR)

In a short time frame e.g. outbreak, focus of variant detection is often on samll and frequent changes

• SNP approach can give very high resolution

• construction of a phylogenetic tree

• closly related reference genome is needed

Core-genome or whole-genome multilocus sequence typing (MLST)

• traditional MLST only 7-8 houskeeping genes

• cgMLST and wgMLST 100s-1000s

• definition of a scheme is central, depends on pipulation structure and diversity of species

After genome assembly, automated genome annotation tools can be used to predict gene functions

• comprehensive picture of the organism's functional capability

• based on gene ontology

• reconstruct metabolic pathways and assign gene function based on functional reconstruction

• RAST

• KEGG

Query against specialised databases

• Virulence Factors Database and antimicrobial resistant databases (e.g. CARD)

• serotype and capsule type information can also be derived from WGS data

Integrated Rapid Infectious Disease Analysis (IRIDA) project

PulseNet

C. perfringens

• WGS resolution allowed identification of a strain associated with 9 care-home outbreaks

Yersinia pestis

• cause of plague

• studied using ancient DNA analysis

• lack of diversity -> spread very quick through europe

Staphylococcus aureus

• daily surveillance

• epidemiology and phylogeny of an MRSA outbreak that affected infants on a special care baby unit (SCBU)

AMR

• WGS revealed the rapid temporal and spatial evolution of antimicrobial resistance (AMR)