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Slide 1 Lecture outline Framework • Individual, species specific, environmental factors influencing transmission Three cases to consider • Typhoid • Cholera • Clostridium difficile _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________ __________

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Page 1: g on ork er omoodle.kpsahs.edu/pluginfile.php/145843/mod_resource... · 2020-01-22 · 8) & ]l]v oX^^Z} } W } Á ZÇ ]v Z}v ( ] v> l }u} Z}o }µ l M_u X:Xd } XD ,ÇPXîìíìXôï~î

Slide 1

Lecture outline

Framework

• Individual, species specific, environmental factors influencing transmission

Three cases to consider

• Typhoid

• Cholera

• Clostridium difficile

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Slide 2

Individual transmission variability• Contact rates with non-immune

hosts• Disease associated behaviors

• Social behaviors across species

• Shedding and infectious potential in injected host

• Age, sex, body and immune system condition

• Genetic differences in host resistance

• Infectious particle virulence• Duration and intensity of

infectiousness

• Ease of transmission

• Genotype-environmental interactions

Pauli et al. Superspreaders to disease hotspots. 2012.

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Slide 3

Species-level transmission variability

Species host susceptibility and contact rates with vectors or other hosts

Host competence (efficiency with which a host produces and transmits a pathogen)

-Ex: Pig is very infectious. Porcupine is infected, but not infectious.

Amplification hosts and “superspreading species”

-Ex: Species that can rapidly replicate and often interact with very susceptible species

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Slide 4

Environmental transmission variability

• High pathogen prevalence

• High intensity • Many pathogens per infected host

• High transmission rates due to environmental conditions allowing for• Elevated pathogen survival

• Greater density of amplification hosts

Pauli et al. Superspreaders to disease hotspots. 2012.

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Slide 5

Typhoid fever-Salmonella typhi

• Aerobic gram negative rod

• Fecal oral transmission

• Minimum effective dose ~100 cells

• Hygiene and proper disposal of feces

• 15% mortality

• Clinical disease: Fever, headache, abdominal pain, “rose-colored” spots

• Incubation period 5-21 days

• Diarrhea symptoms may pause and then recur

• Carrier state: 2-5% affected are asymptomatic, chronically shed organisms with inconsistent eradication of shedding even with antibiotic

Gunn et al. Salmonella chronic carriage. 2014.

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Slide 6

Historical outbreaks of epic

proportions in military camps

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Typhoid Mary

Individual

• Carrier state is asymptomatic and common in older women

• Poor hygiene in food preparer major source of transmission

• Symptoms resolve and recur

• Low bacterial load needed for effective transmission

Amplification species

• Flies breed in human feces, unaffected by bacteria

• Feet carry enough bacteria to spread disease to food left open to air

• Synanthropic flies attracted to foul breath and open mouths of sick and under nourished humans

Environmental

• Poor sanitation allows contamination of water supply

• Large groups of non-immune hosts combine with asymptomatic carriers

• Heat and humidity makes feces more fragrant→ Flies with larger breeding grounds

Citations 3-5

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Slide 7

Cholera-Vibrio cholerae

• Aerobic, gram negative curved rod invades small bowel

• Spread by ingestion of contaminated food or water

• 1 ml stool → ~hundred million viable vibrio

• Several million bacteria must be ingested

• Dose reduced in persons with reduce gastric acid

• Children ages 2-4 and Type O blood more susceptible to infection

• Most infections mild-moderate

• Clinical disease: Abrupt onset painless, high volume watery diarrhea >250ml/kg in first 24 hours

• Incubation period 18h-40 hours

• Vomiting, muscle cramps with severe dehydration to shock, renal failure and metabolic acidosis

• Carrier states x 2

• Convalescent carriers- shed for weeks-months after symptoms gone

• Chronic carriers- shed asymptomatically for years

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Slide 8

Outbreaks rapidly outstrip available

resources

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Haiti

Individual

• Asymptomatic and convalescent carrier states

• May be rapidly fatal, but most infections mild-moderate

• High inoculum needed for infection easily present in massive efflux of stool in new infections

• Antibiotics decrease vibrio concentration in stool

Species

• Shellfish and plankton (blooms) can be infected and then ingested improperly cooked.

• Water hyacinth plants may help sustain vibrio/mosquito populations.

• Toxic and non-toxigenic strains bacteriophages transfer toxicity genes for human infection and vibrio motile

Environmental

•Upstream sanitation breakdown spreads through pre-existing water channels

•Large groups of non-immune hosts may share a limited resources for rehydration

•Vibrio in high concentrations in fresh and brackish water.

• Rain may worsen risk of infection with overflow of brown/black waste water.

Citations 6-8

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Slide 9

C. diff-Clostridium difficile

• Anaerobic gram positive spore forming rod • ~20% of antibiotic associated diarrhea• Toxin production causes colitis

• Clinical disease: Acute or chronic diarrhea, stomach cramps, and occasional fever.

• Adult gut has colonization resistance • Gut microbiota depletion post-antibiotic

allows C. diff to overgrow • Antibiotic exposure remains major risk for

clinical disease• PO vancomycin or fecal transplant for

treatment

• Normal commensal in infants– carrier state identification is laborious• 3% of non-hospitalized adults estimated to be

colonized vs 20-40% of hospitalized adults.

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Slide 10

Larger influences on the human gut microbiome

Trihn et al. One Health Microbiome mini-review. 2018

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Slide 11

Rising incidence in developed world

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Antibiotic stewardship/Fecal

transplant

Individual

• Normal commensal with adult gut with colonization/overgrowth resistance with questionable “infective dose”

• Affected individuals sporadic

• “Hypervirulent strain” may be responsible for increased mortality.

Species

• Antibiotic exposure ubiquitous –depletes normal human gut microbiome

• Bi-directional spread of C. diff between human and farm animals (cows, pigs, vegetables, compost material) and service animals/pets.

Environmental

•Spores remain dormant until human gut microbiome suitable for growth

•Spores difficult to kill with heat or antiseptic/antibiotic

•Concentrated vulnerable persons in hospitals get antibiotics over extended periods of time

Citations 9-10

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Slide 12

Brief citations1) Pauli et al. “From super spreaders to disease hotspots: linking transmission across hosts and

space.” Front Ecol Environ. 2012 10(2): 75-82.

2) Gunn et al. “Salmonella Chronic carriage: epidemiology, diagnosis and gallbladder persistence.” Trends Microbiol. 2014 22(11): 648-655.

3) Gradmann, Harrison and Rasmussen. “Typhoid and the military in the early 20th century.” CID. 2019 69 (S5): S385-S387.

4) Cirillo. “’Winged Sponges’ houseflies as carriers of typhoid fever in 19th and early 20th –century military camps.” Perspectives in Biology and Medicine. 2006 Winter: 52-63.

5) Kim et al. “Spatial and temporal patterns of typhoid and paratyphoid fever outbreaks: A worldwide review 1990-2018.” CID. 2019 69(S6): S499-S509.

6) “Cholera: Something old, Something new.” Sigman and Luchette. Surgical infections. 2012 13(4): 216-222.

7) Lantagne et al. “The cholera outbreak in Haiti: Where and how did it begin?” Cur. Top. in microbiology and immunology. 2013.

8) Feikin et al. “Short report: Does water hyacinth on East African Lakes promote cholera outbreaks?” Am. J. Trop. Med Hyg. 2010. 83(2): 370-373.

9) Trinh et al. One health relationships between human, animal and environmental microbiomes: A mini-Review.” Frontiers in Public health. 2018 6(235).

10) Lim et al. “Clostridium difficile and One health.” Clinical microbiology and infection. 2019. CMI 1820.


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