Concepts in Emerging Infections – Simon D.W. Frost, M.A. D.Phil.

Concepts in Emerging Infections

Simon D.W. Frost, M.A. D.Phil.

Dept. of Veterinary Medicine, University of Cambridge

Introduction

• What is an emerging infection?
• Why do pathogens emerge?
• Where do pathogens emerge?
• When do pathogens emerge?
• Zoonoses and emerging infections:
  • What are the stages through which a zoonotic pathogen emerges?
  • How might evolution play a role in this emergence?
• Surveillance of emerging infections
• Some examples

What is an emerging infectious disease?

What is a zoonosis?

What is a vector-borne disease?

• Typically defined as a disease transmitted to an animal through an intermediate arthropod vector, including ticks or insects
• Hence a vector borne disease is discriminated from a zoonosis in two ways
  • Transmission from arthropod vs. vertebrate
  • Vector is obligate part of the pathogen lifecycle
• Many diseases are both vector-borne and zoonotic

What is a reservoir?

Simple and complex reservoir systems

Rabies in Zimbabwe

• Domestic dogs are a maintenance and source population of rabies for humans
• Jackals account for >25% of all confirmed rabies cases in animals and are also an important source of infection for humans
• As rabies can be maintained in dogs without jackals, jackals are not an essential constituent population of the reservoir.

Maintenance hosts in rabies

Why do pathogens emerge or re-emerge?

Zoonoses and emerging/re-emerging pathogens

• Woolhouse and Gowtage-Sequeria (2005) conducted a literature survey and found:
  • 1407 recognized species of human pathogen
  • 58% were zoonotic
  • 177 were emerging/re-emerging
  • Zoonotic pathogens were twice as likely to be emerging/re-emerging
  • Pathogens with multiple hosts were more likely to be zoonotic

Hosts and pathogens in emerging zoonoses

Where do pathogens emerge from?

• The same human population
• Other human populations
• The environment
  • Legionella (Legionnaire's Disease)
  • Coccidiomycosis (Valley Fever)
• Animal reservoirs i.e. zoonoses

Where do emerging infections emerge?

• Jones et al. (Nature 2008) analyzed a database of 335 EID ‘events’ (origins of EIDs) between 1940 and 2004
• EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife and are increasing significantly over time

Map of EID

Discovery of new human viruses

Recently discovered viruses in animals

Zoonoses

Zoonoses and emergence

• What is the reservoir, and the dynamics of transmission in the reservoir?
• What is the nature and frequency of cross-species jumps?
• What happens when the pathogen jumps host?

Evolution and emergence

• Initially, a zoonotic infection may be poorly adapted to its new human host
• Whether emergence occurs may depend on the mutations required to infect a new host, and the impact that these mutations have in each host
• Even limited transmission within humans may be sufficient to allow further mutations

Fitness and host jumps

Evolution, emergence, and R0

Surveillance of emerging infectious diseases

• Surveillance of EID is complicated as they may be unanticipated
• Improvements in diagnostics has led to the discovery of many new viruses, but it is not clear whether these cause disease or not
• Frequently, we rely on syndromic surveillance to detect new diseases

Google Flu Trends

Here be zombies

Here be zombies

Examples of zoonoses

• Many examples covered in detail in other parts of the course (WNV, SARS, etc.)
• Brief examples here:
  • Hantavirus
  • MERS-CoV

Hantavirus

Hantaviruses

• Hantaviruses are negative-sense single-stranded RNA viruses that infect many species of rodents, shrews, moles and bats
• Reservoir hosts are typically asymptomatic
• Some rodent-borne hantaviruses also infect humans
  • Haemorrhagic fever with renal syndrome (HFRS)
  • Hantavirus (cardio)pulmonary syndrome (H(C)PS)

Haemorrhagic fever with renal syndrome

• Disease first described in Russia in 1913
• Outbreak in North and South Korea in 1951
• Associated with viruses in the hantavirus genus in the Old World, each with different primary hosts
  • Hantaan virus - Apodemus agrarius
  • Seoul virus - Rattus rattus and norvegicus
  • Puumala virus - Clethrionomys glareolus
  • Dobrava virus - Apodemus flavicollis

Hantavirus pulmonary syndrome

• Hantavirus pulmonary syndrome (HPS) is a potentially fatal disease from rodents
• Humans can contract the disease when they come into contact with infected rodents or their urine and droppings
• First recognized in May 1993 in the "Four Corners" in the SW United States
  • A number of previously healthy young adults suddenly developed acute respiratory symptoms; about half soon died
  • Thought to be due to heavy rains in 1993, leading to an increase in food supply for deer mice
• The new virus was called Muerto Canyon virus—later changed to Sin Nombre virus (SNV)

Hantaviruses and hosts

Cophylogeny of hantaviruses and hosts

MERS-CoV

MERS-CoV timeline

MERS-CoV human cases

MERS-CoV human cases

Timing of MERS-CoV

Bat viruses and MERS-CoV

Egyptian tomb bat and MERS-CoV

Camels and MERS-CoV

Conclusions

• Viruses such as MERS-CoV and hantaviruses are just two examples of emerging infectious diseases
• EID is on the rise; many factors may contribute to this
• We still understand little about pathogen diversity, especially in wildlife
• Cross-species transmissions are still relatively rare events, although with potentially great impact