Chapter 22 - Pathogens
Objectives
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Be able to describe the difference between a frank and opportunistic
pathogen
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Be able to list the five modes of transmission of pathogens
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For each of the major groups of pathogens (virus, bacteria, protozoa)
be able to discuss relative minimum infective dose, survival in the
environment, and sensitivity to disinfection
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Be able to discuss an example of each of the major groups of
pathogens from the perspective of why it has been an important
pathogen, what its mode of transmission is, what its lifestyle is
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Be able to give an example of an emerging pathogen
Pathogens in the Environment
Outbreaks of water-, air-, or foodborne disease have engendered study of
pathogens and ways to protect ourselves from them:
– filtration/chlorination of drinking water sources
– treatment/disposal of wastewater
– food processing/preparation
– air handling, esp. hospitals/buildings
Terminology:
• Infection is the invasion and growth of an organism within a host organism
• Pathogens are infectious organisms that harm their host
- Frank pathogens can cause disease in otherwise healthy
individuals
- Opportunistic pathogens can only cause disease in compromised
individuals (burn victims, AIDS patients, the young or
elderly, pregnant women, transplant patients)
- Human pathogens include bacteria, viruses, and protozoa
(amoebas,
flagellates, and apicomplexans)
• Virulence is the degree of pathogenicity of a parasite determined in part by
minimal infective dose, the number of organisms needed to cause an
infection bacteria > viruses > parasites
Five Modes of Transmission
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Waterborne transmission
- drinking water or swimming (usually via ingestion)
- fecal-oral route
- fecal contamination of drinking water from municipal wastewater sources or
animal feedlots
Foodborne transmission
– ingestion of infectious agents in food
– poor sanitation, hygiene (fecal-oral route)
– insufficiently cooked fish and shellfish
– in US there are 76 million cases/yr with 325,000 hospitalizations and
5000 deaths
• Person to person transmission
–requires direct physical contact between hosts
–sexually-transmitted diseases
–respiratory infections (coughing, sneezing)
Modes of Transmission (cont.)
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Airborne Transmission
– inhalation of pathogens in aerosols
– aerosols created at wastewater treatment plants, land application of
sludge, showers
– legionellosis, fungal infections
• Vector-borne transmission
–transmission by the bite of an animal host
–malaria, sleeping sickness, yellow fever
Bacterial Pathogens
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High minimal infective dose
– 104-109
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Bacterial pathogens do not remain infectious in the environment very long
– typical half-life less than 24 hours
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Outbreaks can be prevented with proper sanitation and chlorination of
drinking water, proper food handling and preparation
Enteric bacteria
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Inhabit intestines of animals
Gram – rods, facultative, aerobes
non-sporulating
nonmotile, or motile with peritrichous flagella
mixed-acid fermentation
– ferment sugars to acetic, lactic, and succinic acids
Enteric bacteria -- Salmonella
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Found in particularly high numbers in the intestines of birds and reptiles
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Over 2000 serotypes can cause disease in humans
– serotypes differentiated by O-antigen, a cell wall antigen
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Serotypes Typhimurium, Enteriditis, Typhi, and Paratyphi cause human disease
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Genome ~ 50% homologous with E. coli
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Salmonellosis
– caused primarily by serotypes Typhimurium and Enteriditis
– fever, abdominal cramps, and diarrhea (sometimes bloody), 5-7 days
– disease due to cell lysis in stomach and release of endotoxin (LPS)
– may lead to septicemia or Reiter’s syndrome (e.g., chronic arthritis)
– minimal infective dose: 104 – 107
– 40,000 confirmed and 1.4 million estimated cases in US/yr, ~ 500 fatalities
– 2% develop chronic arthritis
– Usually a foodborne disease (food poisoning), but may also be waterborne
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Typhoid fever
– infection of intestines and blood caused by serotype Typhi
– fever, headache, constipation, malaise, chills, myalgia for 3-4 weeks
– Rare in industrialized nations (400 cases per year in the U.S. most from
international travel). ~16 million cases and 600,000 deaths occur
worldwide each year
– In 5% of cases, victims become carriers, and shed S. typhi for at least a
year in feces
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Paratyphoid fever
– Caused by serotype Paratyphimurium
– Similar to typhoid fever, but milder
Enteric bacteria - Escherichia coli
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Commensal enteric bacterium, but some strains are pathogenic
– enteropathogenic E. coli
• watery diarrhea with mucus, fever, dehydration
• common in infants in less developed countries (50% mortality rate)
• high minimal infective dose: 106-109
– enterotoxigenic E. coli
• cramping, vomiting, profuse diarrhea, dehydration
• disease caused by the production of two toxins
• common in travellers (traveller’s diarrhea) and children in less
developed countries
– enteroinvasive E. coli
•severe cramping, watery diarrhea, fever
•disease caused by invasion of epithelium of intestine by the bacterium,
much like Shigella
•common in less developed countries
– enterohemorrhagic E. coli (e.g. O157:H7)
• severe cramping and very, very bloody diarrhea, 5-10 days
• very young and elderly can develop hemolytic anemia and acute renal
failure (HUS, 2-7% incidence)
• disease due to the production of two prophage-encoded toxins shared
with Shigella dysenteriae
• occurs in North and South America, Europe
• 73,000 cases of infection and 61 deaths each year in the U.S.
• There have been multiple outbreaks of E. coli 0157:H7 since 2003
affecting from 3 to 24 people each.
• waterborne outbreaks occur, but usually due to contaminated meat
(especially hamburger), milk, fruit juice, leafy veggies
Enteric bacteria - Shigella
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Four species cause shigellosis: S. sonnei, S. flexneri, S. boydii, S.
dysenteriae
– Most severe symptoms due to S. dysenteriae.
– S. sonnei most common in U.S.
Shigellosis: watery or bloody diarrhea, cramps, fever, malaise
– due to invasion and destruction of intestinal epithelium
– can cause Reiter’s syndrome, hemolytic-uremic syndrome (HUS),
convulsions in children
Estimated 440,000 cases per year in U.S.
Epidemics in Africa and Central America have 5-15% fatality rate
Second most common source of waterborne disease outbreaks in U.S. from
1972-1985 (also foodborne)
Infective dose: 10-200 organisms !
On August 20, 1995, 82 cases of shigellosis occurred at resort in Island Park,
Idaho due to high water tables and leaky sewage lines
Enteric bacteria - Vibrio cholerae
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Gram (-) oxidase (+) fermentative facultative aerobes
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first waterborne disease whose epidemiology was determined (John Snow,
1854)
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native marine microbe
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infection is usually asymptomatic or mild. One in 20 develop cholera Cholera:
profuse watery diarrhea (and rapid dehydration), vomiting, leg cramps, shock
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20-50% fatality rate within a couple of hours if untreated (with antibiotics) due to
dehydration
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disease due to production of enterotoxin
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only 5 cases per year in U.S., but pandemic in India, sub-Saharan Africa, and
Latin America
1991: A cholera epidemic began in Peru, spread to Central and
South America affecting 1,041,400 people with 9640 deaths.
Waterborne Viral Pathogens
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Viruses are the leading cause of gastroenteritis (GE)
– inflammation of the mucous membrane of the intestine, usually
accompanied by cramps and diarrhea (and dehydration)
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Half of all waterborne gastroenteritis outbreaks have no known etiology
(cause). It is thought that viruses are the responsible agents
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Viruses last longer in the environment and have a lower minimal infective
dose than bacteria
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Although many of these viruses infect animals, infection is usually speciesspecific (only human viruses infect humans)
Viruses That Cause Gastroenteritis
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Astrovirus – first described in 1975 by EM following a diarrhea outbreak in a
Scottish hospital maternity ward
– 28 nm diameter
– ssRNA genome
– mild GE in 1-3 year old children. Seroprevalence studies show that more
than 80% of children between 5 and 10 years old have antibodies to
astroviruses
– rare in infants, young adults, adults, elderly
most common cause of GE in the immuno-compromised
Rotavirus
– 70 nm diameter
– segmented dsRNA genome (11 segs.)
– 2-layered protein capsid
– vomiting, watery diarrhea, mild fever for 4-8 days
– usually spread person-to-person, but can also be waterborne
– Rotavirus A is endemic worldwide, and is the leading cause of infantile GE and
diarrhea. Adults can be infected, but disease is usually subclinical
– Rotavirus B can cause severe disease in adults and has caused epidemics in
China involving millions of victims
– 2.7 million cases per year in U.S., including > 49,000 hospitalizations and 150
deaths
Almost 1 million infants die worldwide from rotavirus (mainly by
dehydration from diarrhea)
Norwalk virus
– 26-35 nm diameter
– ssRNA genome
– unable to be propagated in cell culture, so not much is known
about it
– identifiable with EM of stool samples
most common cause of waterborne viral gastroenteritis
Adenovirus
- 70 nm diameter
- dsDNA genome
- 49 serotypes cause human disease
- primarily cause respiratory disease
- also cause waterborne GE and conjunctivitis
- Resistant to drying, inactivation in tap water and seawater, heat, and UV
dsDNA genome uses host cell DNA repair mechanisms to repair itself
- serotypes 40 and 41 (enteric adenovirus) are second most common
causes of GE in children
- serotypes 3 and 4 cause most outbreaks of waterborne viral conjunctivitis
Enteroviruses
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27-32 nm diameter
ssRNA genome
includes polioviruses, coxsackieviruses, echoviruses, and enteroviruses
May be waterborne or spread person-to-person (airborne) Some groups
cause gastroenteritis, but mainly responsible for causing meningitis, paralysis,
conjunctivitis, and respiratory diseases
Waterborne oubreaks difficult to establish, since infection is usually subclinical
(no symptoms)
Aggressive vaccination worldwide has nearly eliminated paralytic polio
Hepatitis A Virus (HAV)
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Closely related to Enteroviruses (and morphologically identical)
Most common viral waterborne disease from 1946-1994
In the late 1990s, hepatitis A vaccine was more widely used and the number of
cases reached historic lows.
10-50 day incubation period, during which viruses are shed in feces
fever, malaise, nausea, anorexia (loss of appetite) abdominal discomfort, followed
by jaundice
Almost asymptomatic in children, with symptoms increasing in severity with
age
Epidemics occur both nationally and within communities
One-third of Americans have evidence of past infection (immunity).
Not a chronic disease, like Hepatitis B
– in fact, HAV and HBV are not related
Very stable in environment, heat stable, and resistant to chlorine disinfection
Waterborne Protozoan Parasites
Giardia lamblia (G. intestinalis, G. duodenalis)
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Phylum Zoomastigina, Order Diplomonadida, Family Hexamitidae
– i.e. a flagellate
Trophozoites (active, feeding stage)
– 14 m long
– teardrop shaped
– 4 pairs of flagella
– ventral sucking disk
– two nuclei
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Very primitive
– no mitochondria, nucleoli, peroxisomes
– anaerobic!
– rRNA more like prokaryotes’ in size
– replicates by binary fission
– Giardia has 5 chromosomes, with 4-10 copies of each in each nucleus
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Giardiasis, “Beaver Fever”
– Attaches to the epithelium of the duodenum (where it’s anaerobic) with
sucker disk
• absorbs bile and other intestinal goodies
– Exudes enzymes and other substances that damage Na+ and K+ pumps
in the epithelium, allowing salt, and then water to leak into the lumen,
causing diarrhea, 1-4 weeks
– Infection can be asymptomatic, particularly in previously infected hosts but
hosts still shed cysts
Most common agent of waterborne disease outbreaks 1972-1985
Endemic worldwide
– CO, OR -- incidence is high as 13%
Infects many other warm-blooded animals
– Animals may infect humans, but this isn’t proven
Repeat infections are possible, but some immunity is acquired
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Cysts
– victims suffering from diarrhea pass
trophozoites in feces, which quickly die
in environment
– when stools are more well-formed,
trophozoites encyst when they reach the
lower intestine
The signal to encyst is cholesterol starvation
cysts are 12-15m, oval shaped, containing 4 nuclei
last over a month in the environment, esp. in cold watersheds
resistant to chlorine disinfection, but easily removed by settling and filtration
when swallowed, cysts excyst in the duodenum, releasing 2 trophozoites
Readily detectable in stool and environmental samples with fluorescent
monoclonal antibody
minimal infective dose only 10 cysts!
Many animals especially beavers
are reservoirs of infection.
When swallowed by the host,
cysts pass through the stomach
and excyst in the duodenum.
Consumption of
contaminated water
or fecal-oral
transmission are
common routes
of infection
Excysting
Waterborne transmission
is a common route of
infection
Cyst formation
Dividing
In the colon as feces
begin to dehydrate, Giardia
begin to encyst. The cysts
are then passed into the
environment.
Giardia divide by binary fission and
can swim rapidly using multiple
flagella. In severe infections nearly
every intestinal cell is covered by
parasites.
Giardia lamblia live in the
duodenum, jejunum and
upper ileum of humans.
They attach to the surface
of epithelial cells using their
adhesive disc.
Cryptosporidium parvum
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Phylum Apicomplexa, Class Sporozoea, Order Eucocciida, Suborder Eimeriina,
Family Cryptosporiidae
– i.e. apicomplexan, or coccidian
Several life stages including oocyst/sporozoites/merozoites/zygote
Oocyst is the most hardy, resistant life stage
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oocysts are 3 to 6 um in diameter
survive for weeks in surface waters
resistant to chlorine disinfection
oocyst contains 4 naked sporozoites which are
released upon excystation
• 20% of oocysts are thin-walled and excyst within
original host
• oocysts pass from host in feces
Many animals especially cattle
are reservoirs of infection.
Consumption of
contaminated water
or fecal-oral
transmission are
common routes
of infection
Excystation
of oocysts
Attachment of
sporozoites to
epithelial cells
Oocyst is expelled
from cell surface
Oocyst can sporulate
in the intestines and
reinfect the host.
merozoite
A micro and macrogamete
join to form a zygote, which
differentiates into a new
oocyst.
Type I meront
(schizont)
Gametocytes
Merozoites released
from type II meront
attach and form either
micro or macrogametocytes.
Type II meront
(schizont)
Four second generation
merozoites formed.
Sporozoite is enveloped by
microvilli and matures into
type I meront. Asexual
reproduction results in the
formation of eight merozoites
which can reinfect or move
into sexual reproduction.
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Cryptosporidiosis/Coccidiosis
– 3-10 day incubation period
– 10-14 days profuse watery diarrhea, stomach cramps, slight fever
– after symptoms cease, may pass cysts in feces up to 2 months
– autoinfective (thin-walled cysts can excyst within and reinfect original
host)
immunocompromised may not be able to clear infection; mortality rate is 1015% in AIDS patients
Infects all mammals, especially cattle
Oocysts persist 6-12 months in the environment!
Highly resistant to chlorination
minimal infective dose: 15-100 oocysts
Outbreak in Milwaukee, 1993 affected 400,000 people
Emerging Waterborne Pathogens
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Pathogens that we are only now becoming aware of and linking to disease
Many emerging pathogens were discovered due to the AIDS epidemic
Helicobacter pylori
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Binds to epithelium in stomach and duodenum
produces urease that locally lowers pH, disrupting mucous layer and causing
peptic and gastric ulcers
– 90% of duodenal and 80% of gastric ulcers caused by H. pylori infection, not
spicy food, acid, or stress
~2/3 of the world’s population is infected
Most likely a waterborne disease
In 1996, the FDA approved the use of antibiotics to treat (and cure!) peptic
ulcers
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Phylum Microspora
– Enterocytozoan bieneusi, E. hellem, E. cunniculi, E. intestinalis, Pleistophora
spp., and Nosema corneum cause disease in humans
no mitochondria!
may be closer to fungi than protozoa!
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Spores are only 1.5 m in diameter!
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Contain coiled polar filament
– under certain conditions, filament explodes from cyst and pierces host cell
– sporoplast (contents of cyst) are injected into host cell cytoplasm
– reproduces asexually (merogony), but not sexually
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E. bieneusi causes diarrhea, and is a very common infection of AIDS patients
E. intestinalis can infect macrophage and can disseminate through body.
Cysts shed in feces and urine
E. cunniculi causes hepatitis, and is shed in the urine
E. hellem causes conjunctivitis, uretitis, and pneumonia, and is shed in the
urine
If cysts are shed in the feces and urine, then waterborne transmission is
likely. . .
The Microsporidia are all obligate intracellular parasites and spores appear to
be nearly ubiquitous. There are currently approximately 150 described genera
of Microsporidia. Microsporidia parasitize animals from virtually all groups,
however, the vast majority of Microsporidia attack insects and other
arthropods.
One microsporidian, Nosema locustae, is even commercially marketed (as
NoLo Bait) for biological control of grasshoppers, locusts and
crickets. However, a related species, Nosema apis, is a serious problem for
bee keepers.