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?

Diseases of infectious origin whose incidence in humans has increased within the last two decades or threatens to increase in the near future.
CDC (1994)

An infectious disease whose incidence is increasing following its first introduction into a defined host population, or an infectious disease whose incidence is increasing in a defined host population as a result of long term changes in its epidemiology.
Woolhouse and Dye (2001)

What is a zoonosis?

Any disease which can be transmitted to humans from animals.
Oxford English Dictionary

Diseases or infections which are naturally transmitted between vertebrate animals and humans.
WHO (1959)

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?

A population which is chronically infested with the causative agent of a disease and can infect other populations.
Oxford English Dictionary

An ecological system in which the infectious agent survives indefinitely.
Ashford, R.W. (1997) Belgian J Zoology 127:85

One or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population.
Haydon et al. (2002)

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

←  →

Maintenance=Jackals+wild carnivores

Maintenance=Jackals only

Maintenance=Dogs

Why do pathogens emerge or re-emerge?

1. Changes in land use or agricultural practices
2. Changes in human demographics and society
3. Poor population health (e.g. HIV, malnutrition)
4. Hospitals and medical procedures
5. Pathogen evolution
6. Contamination of food or water
7. International travel
8. Failure of public health programs
9. International trade
10. Climate change

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