What are some sources of novel infectious agents?

Why do they spread?

zoonotic-evolution from an animal pathogen to be able to spread amongst humans

some old IDs that have reappeared with antibiotic resistance traits

human population must be sufficient to maintain spread of disease

Can spread due to environmental factors such as climate change, poverty, malnutrition, sociopolitical causes

extended contact with animals (i.e. livestock, habitat encroachment)

Protection from pathogenic microorganisms

energy production-breaks down complex carbs

makes vitamins

modulates immune system

Koch-Henle postulates

Bradford Hill criteria

Evan's Immunological Proof of Disease Causation

Epidemiologic evidence of causality

1. organism cannot be cultured in vitro

2. no animal model exists

3. the organism cannot be cultured period.

The presence of antibody does not always confer resistance to a disease (and lack of antibody does not necessarily confer suceptibility)

You can mount an antibody response without becoming ill (meaning that antibody doesn't appear during an overt disease)

1. Identify the organism associated with disease in an outbreak

2. identify organism in multiple outbreaks of same disease in different locations/times

3. study endemic manifestations of the same disease and show that the same organism is associated with the disease

4. Show that there is a common risk factor associated with infection with the organism in question

Secretory diarrhea (cholera)

Invasive/inflammatory diarrhea (salmonellosis)

Persistent diarrhea

Attatching/effacing lesion producing diarrhea (eg EPEC)

Disruption in net fluid output or absorption along GI tract

more fluid going into the intestine can be a factor

poor reabsorption can also be a factor

Humans are sole reservoir

nonhuman animal reservoir

non-animal and non-human reservoir

Developing nations-Poverty, poor sanitation, poor nutrition

endemicity of diarrhea causing pathogens

Developed nations-food animal reservoir, centralization of food production, food distribution networks

What are the classic agents of:

1. Secretory diarrhea

2. invasive/inflammatory diarrhea

3. persistent diarrhea

4. attaching/effacing leision producing diarrhea (disruption of the mucosal surface)

1. Cholera!

2. Salmonella typhimurium, enteriditis; Shigella; Bacillary dysentery (Salmonella dysenteriae)

2. Enteroaggregative E. coli (EaggEC)

4. Enteropathogenic E. coli (EPEC)

Antibiotics: made by bacteria/fungi that suppress growth or kill other microorganisms

Antimicrobial agents: anti-infective drugs made from ANY source including synthetics (used to treat bacterial and fungal infections)

Anti-infectives: treat any kind of infection (fungal, viral, bacterial, protozoan/helminths)

Antiseptics: disifect contaminated objects in the environment

1. Alter drug target (eg penicillin binding proteins)
2. inactivate/modify the drug (beta-lactamases)
3. Induction of proteins that remove drug from organism (efflux pumps)
4. Inativation/mutation of enzymes that activate the drug (M. tuberculosis catalases that activate isoniazid)

What are 5 major categories of antimicrobial agents?

Beta-lactams (Cephalosporins/Carbapenams)

Aminoglycosides

Fluoroquinolones

Tetracyclines

Macrolides

Ant TB drugs

Inhibitory-stops bacterial growth

bacteriocidal-actively kills bacteria

MDR Acinetobacter (G+)

Drug resistant Campylobacter (G+)

Vancomycin Resistant enterococcus (GRAM -)

MDR Pseudomonas aeruginosa

DR Salmonella (non typhi), S. typhi

DR Shigella

MRSA

DR Strep pneumonia

DR tuberculosis

C. difficile

Carbapenem resistant enterobacteriaceae (CRE)

Drug resistant Neisseria gonorrhoeae

Hospitals/healthcare centers

Community

Agricultural settings (i.e. food animal production)

International travel and "medical tourism"

global food trade

Extrachromasomal elements:

plasmids

transposons

integrons/cassettes

movements from sp. to sp

Intraorganism:

point mutations/deletions

efflux pump gene expression

Altering drug target

inactivating drug

induction of proteins that remove the drug

inactivation/mutation of enzymes that activate the drug

What are 3 pathogens associated with hospital/healthcare accquired infections?

What are 3 pathogens associated with community infections?

Hospital: 

Gram positives-MRSA, VRE, C. difficile (also appearing in community settings)

Gram neg: many sp. Enterobacteriaceae, glucose non fermenters (Pseudomonas, Acinetobacter)

Community:

E. coli, Salmonella, Shigella, Yersinia, V. cholerae, Campy

E. coli UTIs, BSIs

E. coli

Klebsiella pneumonia

Enterobacter

Salmonella

Innate vs. Adaptive

Adaptive: humoral vs cell mediated

Cell mediated: CD8+ (cytotoxic T cells) vs CD4+ T helper cells

Th1 helper cells vs Th2 helper cells

Antigen presenting cells (APCs): dendritic cells, macrophages

Need to know which molecules will elicit the strongest innate immune response (i.e. which polysaccharide or hapten will activate PRRs)

which antigens should be made available to APC's to elicit a strong humoral response from adaptive immune system?

Selects for gram positive vs. gram negative bacteria (gram negative grows on McConkey Agar)

Also differentiates between lactose fermenters and non lactose fermenters

SMAC (Sorbitol McConkey Agar culturing)

Infection-an organism establishes a relationship us (mutual, commensal, or parasitic)

Colonization: an organism not usually part of our normal flora becomes part of it (often transiently)

What are the definitions of:

Parasitism

Mutualism

Commensalism

Parasitism (+/-) symbiotic relationship where the host is harmed and the colonizing organism benefits

Mutualism (+/_) colonizing organism benefits, host is neither harmed not helped

Commensalism (+/+) both host and colonizing organism benefit from the relationship

Latent

Chronic

Convalescent

host immunity/immune suppression

host genetics, age, sex

living conditions (poverty/slums)

Define:

Exotoxin

Enterotoxin

Endotoxin

Exotoxin: secreted by bacteria; includes preformed toxins like Staphylotoxin A, TSS toxin, C. botulinum toxin

Enterotoxin: protein secreted by bacteria in vivo during infection (cholerotoxin, HS or HL toxin of E. coli)

Endotoxin: LPS (not a true toxin)

• IgG-protects against bacteria, viruses, toxins, increases phagocytosis, crosses placenta
• IgA-protects against infection on mucous membranes
• IgM-protects against early phase infection (innate)
• IgD-receptors for activation of Bcells
• IgE-allergic response, triggers histamine release

A-Picornaviridae

B-Hepadnaviridae

C-Flaviviridae

D-Deltaviridae

E-Hepeviridae

A-RNA

B-DNA (partially circular)

C-RNA

D-circular RNA!

E-RNA

95% of babies become carriers, increased risk of liver damage and cancer

3-5% remain chronically infected if they get it as adults

Hepatitis A

initially replicates in oropharynx and circulates before entering liver

Prodrome: HBsAf, HBcIgM Ab

Acute infection: HBcIgM Ab, HBsAg, HBeAg (correlates with high titer of HBV and high infectivity)

early: HBcIgM Ab

Late: HBcIgM Ab, HBcAb IgG, HBsAb IgG

Those with natural infection have HBsAb IgG AND HBcAb IgG

Those who have been vaccinated only have HBsAb IgG