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Flashcards in Emerging Infectious Diseases Deck (51):
1

Emerging infectious disease definition?

1. 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

2. changes in emerging pathogen

-expanding its geographic range

-changing its virulence

-changing its host range

2

Classification of emerging infectious disease?

1. newly emerging

-not previously recognized in humans

-could be just newly recognized

2. 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

3. deliberately emerging

-bioterrorism

3

most common EID?

1. Zoonoses

-transmission from animal to human host

-develop ability to cross species barrier

2. 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)

4

Most likely infectious agents to emerge?

1. RNA viruses

-high mutation rate

-ability to generate quasi species

-segmented genome (dsRNA) allows reassortment

2. bacteria that can acquire genes via horizontal gene transfer

-virulence factors transferred between bacteria via plasmids or bacteriophages

-anitbiotic resistance

-other factors (toxins, adhesins)

3. pathogens with a broad host range

-easier to develop ability to infect a new host

5

common animal reservoirs?

1. bats

-SARS, MERS, Nipah, Ebola

-adapt to intermediate host before transmission to humans

2. Rodents

-hantaviruses

3. Birds

-West nile, influenza

4. Swine

-infleunza, Nipah

5. non human primates

-HIV, Ebola

6

Categories of EID?

1. pathogens infect a novel host

-many EID are zoonoses that jump species and evolve to infect humans

2. pathogens develop novel traits within the same host

-antibiotic resistance

-immune escape mutants

-increased virulence

3. 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

7

Stages involved in adapting to human hosts leading to pandemic? (13)

1. pathogen is transmitted among animal hosts

-no human infections

-wild animals to domesticated animals- more likely to infect people

2. animal to human transmission

-animal reservoir with occasional human infections

-animal to human transmission with limited human to human transmission- transmission among close contacts

3. sustained human to human transmission

-animal to human not necessary for spread

-potential for pandemic, most people will not have prior immunity

8

Factors influencing transition from stage 1 to stage 2? (13)

1. 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

2. spillover to humans aided by:

-handling wildlife

-open markets

-farming- mass production of livestock

9

Emergence of Ebola?

1. ebola strain previously seen in central africa

2. 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

10

Ebola stage 1 to stage 2? (16)

1. zoonotic virus

-bats the most likely reservoir, species unknown

2. spillover event from infected wild animals (fruit, bats, monkey, duiker) to humans, followed by human to human

11

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)

12

Factors influencing pandemic emergence (stage 3)? (18)

pic

13

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

14

Current status of ebola?

1. march 2016, WHO terminated the PHEIC for the ebola outbreak of west africa

2. total deaths- 11,325

3. 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

15

Preventing a pandemic?

1. public health measures limit transmission

-early case identification, isolation, treatment

2. development of vaccine or antiviral would help stop outbreak and prevent future outbreaks

-some outbreaks are from survivors that spread weeks later

16

SARS and MERS?

1. coronaviruses that recently acquired the ability to infect humans

-SARS- sudden acute respiratory syndrome (2003)

-MERS- middle east respiratory syndrome (2012)

2. both related to bat coronaviruses

3. SARS- thought to have evolved in civets (felines) and other species before gaining ability to infect humans

4. intermediate host for MERS sill under investigation

-evidence that camels may be at least 1 type of intermediate host

17

SARS stages of adaptation?

1. stage 1- virus in bats spill over to civets

2. stage 2- virus transmitted from civets to humans

3. stage 3- virus is transmitted person to person

-does not need intermediate host for continued infection to people

-travel spread SARS globally

18

MERS stages of adaptation?

1. virus in bats spill over to camels

2. at least a subset of cases result from exposure to infected camels

3. limited person to person transmission

-sustained person to person not yet established

19

Categories of EID?

1. pathogen infects a novel host

2. pathogen develops novel traits within same host

3. pathogen extends its range into new geographic area

20

Adaptation of viruses to new host?

1. virus evolves ability to bind new receptor in new host

2. virus uses homologue of existing receptor in new host

3. 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

21

Viral receptors SARS?

1. develops ability to bind to new receptor

2. receptor= angiotensin converting enzyme 2

3. bat coronavirus strains use different receptor that SARS

4. once SARS became adapted to replicate human cells it lost ability to infect bat cells

22

Viral receptors for MERS?

1. binds to homologous receptor in different hosts

2. receptor= dipeptidyl peptidase 4

3. MERS can infect both bat and human cells

4. transmission from bats is possible but an intermediate host is more likely

23

Flu- adaptation to human receptor?

1. 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

2. H1N1 pdm09

-pre adapted in swine to readily infect humans:

-more easily transmitted human to human than seasonal flu

24

Evolve novel traits within the same host?

1. 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

2. antibiotic resistance genes often encoded on plasmids

-can be transferred between different families of organisms

3. frequent antimicrobial use will select for resistant organisms

25

MRSA?

1. antibiotic resistance in staph aureus

-resistance to sulfa drugs, penicillin, methicillin, vancomycin

-transfer of plasmids from enterococcus faecalis

2. initially considered nosocomial pathogen (hospital acquired) but new strains are emerging that are community acquired

3. HA and CA strains have different virulence properties determined by type of plasmid they have

26

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)

27

Shiga toxin producing e coli (STEC)?

-associated with dysentary (diarrhea with blood and mucus)

28

Enteroaggregative e coli? (EAggEC)?

-attaches via aggregative adherence fimbriae

-associated with watery diarrhea

-developing countries

29

E coli virulence (O104:H4)

1. 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

2. antibiotic resistance (additional virulence factor)

-resistance plasmid (CTX-M-15)- present in different types of enterbacteriaceae acquired by outbreak strain

30

Pathogens emerging at a new site?

1. pathogens introduced to a new geographic area will encounter a large population of susceptible hosts

-facilitates spread

-example- west nile (1999)

2. 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

31

West nile virus?

1. 1999- unexplained cases of encephalitis in NYC

2. simultaneously, birds were dying at bronx zoo

3. etiologic agent was identified as WNV

-flavivirus- transmitted via mosquito vector

-brought to US with importation of infected bird (or mosquito)

4. easily disseminated throughout US

-never seen in US before

-population was susceptible

-mosquito vector already in place

32

Hantavirus?

1. 1993 outbreak of acute respiratory illness on navajo indian reservation

2. identified as hantavirus (pulmonary syndrome)

-mouse- animal reservoir

-asian and euro strains associated with hemorrhagic fever with renal syndrome

3. different strains of hantavirus associated with different species of mice in US

4. newly identified at time of outbreak, but has been present in US for many years

33

Factors influencing emergence?

1. microbial adaptation

-ability to evolve rapidly

2. economic development and agricultural practices

-population growth, urban sprawl

-land use, deforestation

-mass rearing of food animals

-mass production, distribution of food

3. international travel and commerce

-widens exposure range

4. climate and weather

-change in animal habitats, vector range

34

Influence of economic development on EID?

1. deforestation

-increases contact between animal reservoirs and humans

-limits range of natural predators for rodents and insect vectors

2. 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

3. moving to suburbs

-increases exposure to ticks vectors (lyme resurgence)

4. ebola crisis

35

Influence of animal food production on EID?

1. 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

36

Nipah virus 1998?

1. encephalitis in malaysia (265 cases, 40% mortality)

2. pigs kept in pens near orchards

3. fruit bats in orchards

-habitat destroyed by deforestation

-bat droppings contained a new type of paramyxovirus

-virus spread to pigs

4. overcrowding in pens facilitated transmission among pigs

5. spillover infection of pig handlers

37

Other influence of food production on EID?

1. open markets

-favor spread of pathogens among poultry and to people

-example (avian influenza H5N1, H7N9)

2. contamination of food

-contamination of meat during slaughter

-contamination of fruits and veggies:

-contaminated fertilizer

-irrigation with contaminated water

3. mass distribution of contaminated food

-multistate or multi country outbreaks

4. consumption of contaminated food leads to food borne outbreaks

-E coli O104:H4 outbreak: contaminated sprouts in farm in germany

-contaminated sprouts in france

38

Factors influencing emergence at new geographic area? (travel)

1. 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

2. migrating birds

-important factor in dissemination of avian influenza (H5N1)

-spread followed the migration path of water fowl from china

3. SARS spread, MERS

39

MERS outbreak in Korea?

1. largest outbreak outside of middle east

2. 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

40

Factors influencing emergence (climate)?

1. 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

2. environmental condition favoring expansion of animal reservoirs

3. expansion of mosquito or tick vector range

41

expansion of animal reservoirs due to climate change, hantavirus? (58)

pic

42

expansion of mosquito vectors- dengue and chikungunya viruses? (59)

1. dengue and chikungunya viruses- endemic in tropics and subtropics

2. jumped monkeys to humans

3. dengue virus- global disease (not EID)

-sporadic outbreaks have occurred in US

4. 2013- 1st local transmission of CHIKV in western hemisphere

-newly emergent infectious disease in west

-spread parallels dengue

5. both viruses can now be transmitted by 2 mosquito vectors

-aedes aegypti and aides albopictus

43

chikungunya? (60)

pic

44

zika virus transmission (61)

pic

45

expansion of mosquito vectors- role in EID?

1. primary vector = aedes aegypti

-tropical and subtropical worldwide distribution

-adapted to urban areas, lives both indoors and outdoors

2. secondary vector = aedes albopictus

-becoming adapted to cooler temps (broaden vector range)

-more outdoors, water is further removed from households

3. secondary vector present in US- why not more cases?

-mosquito vectors and susceptible human hosts leads to potential for human mosquito human transmission

4. 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

5. 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

46

mosquito map? (63)

pic

47

zika transmission (65)

-recent global increase in incidence and spread, with the same vector, globalization and urbanization

-why GBS?

48

Limiting emergence of pathogens?

1. surveillance/detection

-reported globally

2. contain, quarantine, isolation

3. identify infectious agents and understand pathogenicity

-how it causes disease

-how it spreads

-how to treat

-how to prevent spread, clinical disease

4. treatment

-antimicrobials, vaccines

49

Public health measures to limit MERS transmission (Korea)?

1. approach:

-improve contact tracing

-ensure that cases and contacts are:

-isolated or quarantined

-monitored

-do not travel

2. resulted in decline in incidence in cases

3. conclusions:

-countries should be aware of and prepared for potential outbreaks

-communication and collaboration between health and other sectors (aviation) is crucial

50

Surveillance and reporting?

1. US (center for disease control and prevention- CDC)

2. Globally (world health organization- WHO)

3. other countries have their own reporting systems

4. ProMed- established to disseminated information on EID and outbreaks via internet

5. rapid identification of pathogens

-amplification of nucleic acid sequences (PCR)

-technology allows for more rapid sequencing

-simultaneous screening for multiple pathogens

51

Importance of sequencing pathogens?

1. e coli O104:H4 outbreak sequencing enabled:

-development of specific diagnostic test

-determination of source of pathogen

-information on origin and virulence of pathogen

2. identification of antibiotic resistance genes enables more effective use of antibiotics

3. assessment of organisms relatedness

-identify common source (foodborned illness)

-identify animal reservoir, track route of transmission