11. Emerging Infectious Diseases

What infectious agents are most likely to be a big deal? Why?

- RNA viruses: High mutation rate
- Bacteria that do horizontal gene transfer: Plasmids, abx resistance, virulence factors (toxins, adhesins)
- Pathogens w/ broad host range: Easier to develop infectious ability

What are the (4) most common animal reservoirs of zoonotic diseases?

- Bats: SARS, MERS, Nipah
- Rodents: Hantavirus
- Swine: Flus, Nipah
- Primates: HIV, ebola

What are the categories of emerging infectious disease (i.e. how they emerge)?

- Pathogens infect NEW HOST: "Jump" species
- Pathogen develops NOVEL TRAIT w/in same host: ABX resistance, escape mutants, increased virulence.
- Pathogen EXTENDS its geographic RANGE:

What are the 3 stages of emergence?

Stage 1 - Pre-emergence: Encroachment into wildlife habitat, change in land use
Stage 2 - Localized emergence: Expansion of wildlife-human interface (Nipah, ebola)
Stage 3 - Pandemic emergence: International travel/trade (HIV, SARS)

Summarize SARS and MERS.

- Coronavirusis (enveloped), related to bat coronaviruses
- SARS evolved from civets, MERS evolution being investigated

Outline stages 1-3 of SARS transmission.

Stage 1: Bats ==> civets
Stage 2: Civets ==> humans
Stage 3: Person ==> person

Outline stages 1-3 of MERS transmission.

Stage 1: Bats ==> unknown
Stage 2: Limited person to person spread
Stage 3: Potential for sustained person to person transmission

What are the mechanisms by which viruses can attach to a new host?

- Virus evolves to bind human receptor
- Virus uses homologue of existing receptor in new host
- (Simply binding host usually not sufficient, need polymerase and TF's to evolve too)

Describe the SARS receptor.

SARS:
- Develops ability to bind new receptor ==> angiotensin converting enzyme 2
- Bat viruses use different receptor than SARS
- Once SARS evolved to replicate in humans, no longer infects bats

Describe the MERS receptor.

MERS:
- Binds to homologous receptor in different hosts ==> dipeptidyl peptidase 4
- MERS infects both bats and humans
- Transmission from bats is possible, probably uses intermediate host

What were the differences between the avian flu (H5N1; H7N9) and 2009 H1N1 pandemic?

Avian flu:
- Avian to human, not really human to human
- Adaptation to human requires increased affinity for alpha-2,6-sialic acid
H1N1:
- Pre-adapted to swine to readily infect humans
- More easily transmitted from human to human than seasonal flu

How do novel traits of bacterial infection w/in the same host develop?

- Gene clusters encoding virulence factors: Pathogenicity islands or virulence cassettes
- ABX resistance genes encoded on plasmids (can be transferred between different organisms)
- Frequent ABX use selects for resistant organisms

What is the deal w/ ABX resistance among enterobacteria family?

- Plasmid gene for carbapenem is being transferred among familly
- Common pathogenic Gram (-) rods
- Klebsiella pneumoniae carbapenumase and New Delhi metallo-B-lactamase
- Interacts w/ E coli
- Resistant to most ABX, if it mutates more we're F'd

How did MRSA become resistant to vancomycin in 2002?

Plasmid transfer Enterococcus fecalis

What is the genetic feature that confers resistance to both HA and CA MRSA?

mecA gene on SCCmec chromosome encodes for PBP2a that doesn't bind methicillin

What is the difference between resistance in HA and CA MRSA?

SSCmec I-III==>HA MRSA:
- II and III carry methicilin and non-beta-lactam resistance
- HA MRSA is multi-drug resistant
SSCmec IV==>CA MRSA:
- Carries only methicillin resistance
- Usually sensitive to non-beta-lactams (clinda, trimethroprim, tetracyclines

What are 2 examples of gene transfer via plasmid/phage encoding toxins?

- Enterotoxigenic E coli and Vibrio cholera express same toxin ==> Watery diarrhea
- Shiga toxin-producing E coli and Shigella dysenteriae express same toxin ==> Bloody diarrhea

What was the source of the 2011 E. coli 0104:H4 outbreak? What were major sources of death?

- Sprouts
- Hemmorrhagic enteritis and hemolytic uremic syndrome

What properties from different E coli strains did this E coli express?

- Shigella toxin E coli (STEC)
- Enteroaggretive E coli (EAggEC): Attaches via fimbriae and expresses shigella (not shiga) enterotoxin
- Epidemic d/t EAggEC that acquired the phage encoding STX2a (Shiga toxin gene) ==> had shiga toxin, fimbriae, and shige

What kind of virus causes West Nile? Why was it easily disseminated?

- Flavivirus
- Never seen in US, susceptible population, mosquito vector already in place

What is the difference between US and Europe/Asia strains of hantavirus?

US strain ==> Pulmonary
Europe/Asia strain ==> Hemorrhagic fever, renal syndrome

What does Nipah virus cause? What led to 1998 outbreak?

- Encephalitis
- Pigs in pens near orchards, fruit bats in orchards
- Habitat destroyed by deforestation, bat droppings contained novel paramyxovirus
- Overcrowding in pig pens facilitated transmission
- Spillover transmission to pig farmers occurred

What weather and wildlife patterns led to hantavirus outbreak?

- Long drought in 1990's decreased number of predators for mice
- 1993 heavy rainfall ==> pinon nuts, food for mice ==> mouse population increased

Why might dengue occur in US now? Why is malaria re-emerging?

- Dengue carried by 2nd species of mosquito
- Decreased DDT use leading to more malaria
- Drug-resistant malaria becoming more common

What was pneumocystis jirovecii seen in before AIDS?

Malnourished children

What are risk factors for legionnaire's disease?

COPD, smoking