Emerging Infectious Diseases Flashcards
Emerging infectious disease definition?
- infectious disease whose incidence is increasing:
- following its first introduction into a new host population
- in an existing population as a result of long term changes in its underlying epidemiology - changes in emerging pathogen
- expanding its geographic range
- changing its virulence
- changing its host range
Classification of emerging infectious disease?
- newly emerging
- not previously recognized in humans
- could be just newly recognized - reemerging
- has existed in the past but now demonstrates an increasing incidence
- may involve new host or geographic range
- new outbreaks of a known pathogen - deliberately emerging
- bioterrorism
most common EID?
- Zoonoses
- transmission from animal to human host
- develop ability to cross species barrier - vector borne
- mosquitos, ticks, are intermediate hosts
- transmit pathogen from animal reservoir to a human host
- humans are often dead end hosts
- some vector borne pathogens have been able to be spread human to human via vectors (dengue, yellow fever, chikungya, zika)
Most likely infectious agents to emerge?
- RNA viruses
- high mutation rate
- ability to generate quasi species
- segmented genome (dsRNA) allows reassortment - bacteria that can acquire genes via horizontal gene transfer
- virulence factors transferred between bacteria via plasmids or bacteriophages
- anitbiotic resistance
- other factors (toxins, adhesins) - pathogens with a broad host range
- easier to develop ability to infect a new host
common animal reservoirs?
- bats
- SARS, MERS, Nipah, Ebola
- adapt to intermediate host before transmission to humans - Rodents
- hantaviruses - Birds
- West nile, influenza - Swine
- infleunza, Nipah - non human primates
- HIV, Ebola
Categories of EID?
- pathogens infect a novel host
- many EID are zoonoses that jump species and evolve to infect humans - pathogens develop novel traits within the same host
- antibiotic resistance
- immune escape mutants
- increased virulence - pathogen extends its range into a new geographical area
- range expansion of animal reservoir or vector :
- pathogen evolves to infect new vector prevalent at a new site
- long distant jump (pathogen or vector):
- air travel, cargo ships
Stages involved in adapting to human hosts leading to pandemic? (13)
- pathogen is transmitted among animal hosts
- no human infections
- wild animals to domesticated animals- more likely to infect people - animal to human transmission
- animal reservoir with occasional human infections
- animal to human transmission with limited human to human transmission- transmission among close contacts - sustained human to human transmission
- animal to human not necessary for spread
- potential for pandemic, most people will not have prior immunity
Factors influencing transition from stage 1 to stage 2? (13)
- ecological, social or socioeconomic changes affect pathogen transmission between non human hosts
- overlapping habitats for humans, livestock, wildlife
- expanded transmission among established host
- spread to a new region (migration)
- introduction into a different non human host - spillover to humans aided by:
- handling wildlife
- open markets
- farming- mass production of livestock
Emergence of Ebola?
- ebola strain previously seen in central africa
- evidence suggests bats may be an animal reservoir
- bars carry virus without getting sick
- migration- introduces virus to new area
- moved from central to west africa
Ebola stage 1 to stage 2? (16)
- zoonotic virus
- bats the most likely reservoir, species unknown - spillover event from infected wild animals (fruit, bats, monkey, duiker) to humans, followed by human to human
Ebola transmission among animals to sustained human to human transmission? (17)
- healthcare workers commonly infected
- occurs during stage 2 (localized emergence)
- required to enter stage 3 (pandemic emergence)
Factors influencing pandemic emergence (stage 3)? (18)
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Ebola transition to stage 3? (19)
- travel creates potential to spread beyond africa
- in the past, ebola was confined to a small village, people were quarantined
- current outbreak, people infected have ended up on buses, taxis, airplanes, so it spreads
Current status of ebola?
- march 2016, WHO terminated the PHEIC for the ebola outbreak of west africa
- total deaths- 11,325
- june 2016, WHO declares end of ebola transmission in republic of guinea and liberia
- 42 days (21 day incubation cycles of virus) after last patient tests negative
- 90 day heightened surveillance
Preventing a pandemic?
- public health measures limit transmission
- early case identification, isolation, treatment - development of vaccine or antiviral would help stop outbreak and prevent future outbreaks
- some outbreaks are from survivors that spread weeks later
SARS and MERS?
- coronaviruses that recently acquired the ability to infect humans
- SARS- sudden acute respiratory syndrome (2003)
- MERS- middle east respiratory syndrome (2012) - both related to bat coronaviruses
- SARS- thought to have evolved in civets (felines) and other species before gaining ability to infect humans
- intermediate host for MERS sill under investigation
- evidence that camels may be at least 1 type of intermediate host
SARS stages of adaptation?
- stage 1- virus in bats spill over to civets
- stage 2- virus transmitted from civets to humans
- stage 3- virus is transmitted person to person
- does not need intermediate host for continued infection to people
- travel spread SARS globally
MERS stages of adaptation?
- virus in bats spill over to camels
- at least a subset of cases result from exposure to infected camels
- limited person to person transmission
- sustained person to person not yet established
Categories of EID?
- pathogen infects a novel host
- pathogen develops novel traits within same host
- pathogen extends its range into new geographic area
Adaptation of viruses to new host?
- virus evolves ability to bind new receptor in new host
- virus uses homologue of existing receptor in new host
- ability to bind to target cells of a new host is necessary but may not be sufficient to allow a virus to infect a novel host
- viral polymerase, transcription factors may need to evolve to adapt to a different species
Viral receptors SARS?
- develops ability to bind to new receptor
- receptor= angiotensin converting enzyme 2
- bat coronavirus strains use different receptor that SARS
- once SARS became adapted to replicate human cells it lost ability to infect bat cells
Viral receptors for MERS?
- binds to homologous receptor in different hosts
- receptor= dipeptidyl peptidase 4
- MERS can infect both bat and human cells
- transmission from bats is possible but an intermediate host is more likely
Flu- adaptation to human receptor?
- Avian influenza (H5N1, H7N9)
- avian to human, limited human to human transmission
- adaptation for human to human transmission requires increased affinity for alpha 2,6 linked sialic acid - H1N1 pdm09
- pre adapted in swine to readily infect humans:
- more easily transmitted human to human than seasonal flu
Evolve novel traits within the same host?
- bacterial pathogens often have clusters of genes encoding virulence factors
- pathogenicity islands or virulence cassettes
- can be transferred among related bacteria:
- plasmids or bacteriophages may be involved in transferring genes between organisms - antibiotic resistance genes often encoded on plasmids
- can be transferred between different families of organisms - frequent antimicrobial use will select for resistant organisms
MRSA?
- antibiotic resistance in staph aureus
- resistance to sulfa drugs, penicillin, methicillin, vancomycin
- transfer of plasmids from enterococcus faecalis - initially considered nosocomial pathogen (hospital acquired) but new strains are emerging that are community acquired
- HA and CA strains have different virulence properties determined by type of plasmid they have
E coli outbreak may to june 2011? (O104:H4)
- 18 deaths from hemorrhagic enteritis
- 32 deaths from hemolytic uremic syndrome
- reported to euro CDC
- foodborne outbreak- contaminated sprouts
- altered virulence:
- outbreak strain has properties from 2 types of e coli (shiga toxin- STEC, EAggEC)
Shiga toxin producing e coli (STEC)?
-associated with dysentary (diarrhea with blood and mucus)
Enteroaggregative e coli? (EAggEC)?
- attaches via aggregative adherence fimbriae
- associated with watery diarrhea
- developing countries
E coli virulence (O104:H4)
- thought to be an EAggEC that acquired the bacteriophage encoding stx2a (shiga toxin gene)
- characteristics of both STEC and EAggEC:
- shiga toxin
- aggregative adherence fimbriae
- increased adherence to intestinal epithelial cells may enhance absorption of shiga toxin - antibiotic resistance (additional virulence factor)
- resistance plasmid (CTX-M-15)- present in different types of enterbacteriaceae acquired by outbreak strain
Pathogens emerging at a new site?
- pathogens introduced to a new geographic area will encounter a large population of susceptible hosts
- facilitates spread
- example- west nile (1999) - some pathogens emerging in a new area may just be newly detected
- example- hantavirus pulmonary syndrome (1993)
- once identified, hantavirus was recognized as causing previous unexplained deaths due to respiratory tracts infections
West nile virus?
- 1999- unexplained cases of encephalitis in NYC
- simultaneously, birds were dying at bronx zoo
- etiologic agent was identified as WNV
- flavivirus- transmitted via mosquito vector
- brought to US with importation of infected bird (or mosquito) - easily disseminated throughout US
- never seen in US before
- population was susceptible
- mosquito vector already in place
Hantavirus?
- 1993 outbreak of acute respiratory illness on navajo indian reservation
- identified as hantavirus (pulmonary syndrome)
- mouse- animal reservoir
- asian and euro strains associated with hemorrhagic fever with renal syndrome - different strains of hantavirus associated with different species of mice in US
- newly identified at time of outbreak, but has been present in US for many years
Factors influencing emergence?
- microbial adaptation
- ability to evolve rapidly - economic development and agricultural practices
- population growth, urban sprawl
- land use, deforestation
- mass rearing of food animals
- mass production, distribution of food - international travel and commerce
- widens exposure range - climate and weather
- change in animal habitats, vector range
Influence of economic development on EID?
- deforestation
- increases contact between animal reservoirs and humans
- limits range of natural predators for rodents and insect vectors - urbanization (poverty stricken in inner cities)
- crowding leads to person to person transmission
- poor hygiene, malnutrition, limited access to healthcare all increase susceptibility to infectious agents - moving to suburbs
- increases exposure to ticks vectors (lyme resurgence) - ebola crisis
Influence of animal food production on EID?
- mass rearing animals
- crowded pens favor transmission between animals
- increased infection of livestock allows for spillover infection on animal handlers
- antibiotic use in animal feed, selection pressure for resistant organisms
- shipping of livestock provides risk for dissemination of pathogens
Nipah virus 1998?
- encephalitis in malaysia (265 cases, 40% mortality)
- pigs kept in pens near orchards
- fruit bats in orchards
- habitat destroyed by deforestation
- bat droppings contained a new type of paramyxovirus
- virus spread to pigs - overcrowding in pens facilitated transmission among pigs
- spillover infection of pig handlers
Other influence of food production on EID?
- open markets
- favor spread of pathogens among poultry and to people
- example (avian influenza H5N1, H7N9) - contamination of food
- contamination of meat during slaughter
- contamination of fruits and veggies:
- contaminated fertilizer
- irrigation with contaminated water - mass distribution of contaminated food
- multistate or multi country outbreaks - consumption of contaminated food leads to food borne outbreaks
- E coli O104:H4 outbreak: contaminated sprouts in farm in germany
- contaminated sprouts in france
Factors influencing emergence at new geographic area? (travel)
- international trade or travel
- air travel leads to potential dissemination of pathogens between countries within hours
- transport of animals or foods
- allows long distance jumps to new area - migrating birds
- important factor in dissemination of avian influenza (H5N1)
- spread followed the migration path of water fowl from china - SARS spread, MERS
MERS outbreak in Korea?
- largest outbreak outside of middle east
- transmission strongly associated with health care settings (person to person)
- lack of awareness of health care workers and public about MERS
- suboptimal infection prevention and control measures in hospitals
- close and prolonged contact of infected MERS in patients in crowded rooms
- practice of seeking care at multiple hospitals (doctor shopping)
- visitors staying with infected patients
Factors influencing emergence (climate)?
- climate, global warming
- natural disasters (floods, earthquakes) favors disease outbreaks:
- developing countries with poor water sanitation facilities
- more likely to cause reemerging than newly emerging infectious disease
- may be associated with flare up or outbreak of established disease - environmental condition favoring expansion of animal reservoirs
- expansion of mosquito or tick vector range
expansion of animal reservoirs due to climate change, hantavirus? (58)
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expansion of mosquito vectors- dengue and chikungunya viruses? (59)
- dengue and chikungunya viruses- endemic in tropics and subtropics
- jumped monkeys to humans
- dengue virus- global disease (not EID)
- sporadic outbreaks have occurred in US - 2013- 1st local transmission of CHIKV in western hemisphere
- newly emergent infectious disease in west
- spread parallels dengue - both viruses can now be transmitted by 2 mosquito vectors
- aedes aegypti and aides albopictus
chikungunya? (60)
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zika virus transmission (61)
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expansion of mosquito vectors- role in EID?
- primary vector = aedes aegypti
- tropical and subtropical worldwide distribution
- adapted to urban areas, lives both indoors and outdoors - secondary vector = aedes albopictus
- becoming adapted to cooler temps (broaden vector range)
- more outdoors, water is further removed from households - secondary vector present in US- why not more cases?
- mosquito vectors and susceptible human hosts leads to potential for human mosquito human transmission - chikungunya
- human mosquito human transmission is US is not sustained
- limited contact between human hosts and mosquito vectors
- low housing density, use of air conditioning and screens - zika
- human mosquito human transmission occurred in florida- only state with locally acquired infections
- too soon to see how far and how quickly zika might spread in US
mosquito map? (63)
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zika transmission (65)
- recent global increase in incidence and spread, with the same vector, globalization and urbanization
- why GBS?
Limiting emergence of pathogens?
- surveillance/detection
- reported globally - contain, quarantine, isolation
- identify infectious agents and understand pathogenicity
- how it causes disease
- how it spreads
- how to treat
- how to prevent spread, clinical disease - treatment
- antimicrobials, vaccines
Public health measures to limit MERS transmission (Korea)?
- approach:
- improve contact tracing
- ensure that cases and contacts are:
- isolated or quarantined
- monitored
- do not travel - resulted in decline in incidence in cases
- conclusions:
- countries should be aware of and prepared for potential outbreaks
- communication and collaboration between health and other sectors (aviation) is crucial
Surveillance and reporting?
- US (center for disease control and prevention- CDC)
- Globally (world health organization- WHO)
- other countries have their own reporting systems
- ProMed- established to disseminated information on EID and outbreaks via internet
- rapid identification of pathogens
- amplification of nucleic acid sequences (PCR)
- technology allows for more rapid sequencing
- simultaneous screening for multiple pathogens
Importance of sequencing pathogens?
- e coli O104:H4 outbreak sequencing enabled:
- development of specific diagnostic test
- determination of source of pathogen
- information on origin and virulence of pathogen - identification of antibiotic resistance genes enables more effective use of antibiotics
- assessment of organisms relatedness
- identify common source (foodborned illness)
- identify animal reservoir, track route of transmission