Download Outcomes of Infection

The Iceberg Concept: As Applied to Virus Infections
Examples of Encounters and Disease Prevention
Type of
contact
Example
Type of
Agent
Source
Strategy for
Prevention
Preventive Aim
Inhalation
Common cold
Virus
None
Difficult to avoid
contact
Ingestion
Coccidiodomycosis
Typhoid fever
Salmonella food
poisoning
Gonorrhea
Fungus
Aerosol from
infected
persons
Soil
None
Bacterium
Bacterium
Water, food
Food
Sanitation
Sanitation
Hard to avoid
contact
Lower infecting
dose
Bacterium
Person
Social
Behavior
Wound
Surgical
infections
Bacterium
Normal flora
surroundings
Aseptic
Avoid contact
techniques
Insect Bite
Malaria
Protozoan
Mosquito
Insect
control
Sexual
contact
Avoid contact
Eliminate vector
Constitutive Defenses: Physical Barriers to Infection
System or Organ
Skin
Mucous
membranes
Cell Type
Squamous
Columnar nonciliated
(e.g., gastrointestinal tract)
Columnar ciliated
(e.g., trachea)
Cuboidal ciliated
(e.g., nasopharynx)
Secretory
Clearing Mechanism
Desquamation
Perstalsis
Mucociliary movement
Tears, saliva, mucus,
sweat
Flow of liquids
Constitutive Defenses: Chemical Barriers to Infection
System or Organ
Source
Skin
Mucous membranes
Sweat, sebaceous glands
Parietal cells of stomach
Secretions
Neutrophils
Lung
A cells
Salivary glands
Neutrophils
Small bowel and below
Liver via biliary tree
Gut flora
Substances
Organic acids
Hydrochloric acid, Low pH
Antimicrobial compounds
Lysozyme, peroxidase,
lactoferrin
Pulmonary surfactant
Thiocyanate
Myeloperoxidase
Cationic proteins
Lactoferrin
Lysozyme
Bile acids
Low molecular weight fatty
acids
Some Important Pathogens of Aquatic
and Terrestrial Environments
• The Microbial Agents:
– Most are from feces or other excreta (urine,
respiratory exudates, etc.) of humans and/or other
animals
– Some are of natural origin
• either exclusively or in addition to fecal
contamination
• Enteric Microbial Agents:
– Infect the human and/or animal gastrointestinal (GI)
tract
• Some enteric microbes also infect or invade other
sites in the body
IMPORTANT HUMAN ENTERIC VIRUSES
Viruses/Groups
Enteroviruses:
(polios, echos, coxsackies, etc.)
Hepatitis A virus*
Hepatitis E virus
Reoviruses
Rotaviruses
Adenoviruses*
Caliciviruses*:
Animal Feces
no
no
pigs, rats
yes
yes**
yes**
no
Norwalk, Snow Mountain, etc.
*On EPA’s candidate contaminants list (CCL).
**humans & animals usually infected by different ones; not always.
IMPORTANT HUMAN ENTERIC BACTERIAL
PATHOGENS AND OTHER SOURCES OF THEM
Bacterium/Group
Salmonella spp.
(except S. typhi)
Campylobacter spp.
Escherichia coli
yes
Helicobacter pylori*
Aeromonas hydrophila*
yes
Yersinia enterocolitica
Vibrio cholerae; other Vibrio spp. yes
Leptospira
Mycobacteria spp. (non-tubercular)
Shigella spp.
AnimalsOther Sources
yes
no
no
no
yes
yes
no
unknown
unknown
yes
yes
yes
yes
yes
no
very rare
yes
no
no
*On EPA’s candidate contaminants list (CCL).
IMPORTANT HUMAN ENTERIC
PROTOZOAN PATHOGENS
Parasite
Animal Feces
Cryptosporidium parvum
yes
Cyclospora cayatenensis*
unknown
Giardia lamblia
yes
Entamoeba histolytica
rare
Balantidium coli
yes (pigs)
Microsporidia*
yes
(Enterocytozoon and Septata)
Toxoplasma gondii*
*On EPA’s candidate contaminants list (CCL).
unknown
yes
Helminths (Worms):
Some of the Important Ones
Most acquired from ingestion of or contact with fecescontaminated soil or food
• Nematodes (Roundworms):
– Ascaris lumbricoides
1
GI illness; pneumonitis
– Trichuris trichuria
1
chronic GI
• Hookworms:
– Ancylostoma duodenale
1
chronic anemia
– Necator americanus
1
chronic anemia
– Strongyloides stercoralis 1
chronic anemia
• Cestodes (tapeworms):
– Hymenolepis nana
1
GI illness
Some Non-fecal Bacterial Pathogens
Bacteria:
Legionella spp.
>20
Pneumonia; febrile illness
L. pneumophila, etc.
Mycobacterium spp.
M. tuberculosis
1
M. avium-intracellulare
Other bacteria
Legionnaires’ disease
many Upper respiratory illness
tuberculosis
several Upper respiratory illness
many Variable; "opportunistic"
or "conditional pathogens
Some Non-fecal Protozoan Pathogens
Free living amebas:
Naegleria fowleri
Acanthamoeba spp.
1
Primary amebic meninoencephalitis
few
eye infections; encephalitis
Some Non-fecal Helminths
Agent:
• Dracunculus medenensis (N) 1
• Schistosoma (T; blood fluke) 3
S. haematobium, S. mansoni
and S. japonicum
• Schistosoma spp. (T).
birds and fish
No.
Illness and Sites
Tissue infections
(subcutaneous & deep;
esp. foot and/or leg
Liver, intestine, colon
bladder & rectum from
colonization of venous
vessels.
few
swimmers itch: larvae
penetrate skin; not in
bloodstream; no
maturation in human
Occurrence of Microbial Pathogens in Humans
• Microbial pathogens usually are not “normal flora” of
humans; opportunities for pathogenicity are possible
– Some are “normal flora” of animals:
• Salmonella enteriditis and Campylobacter jejuni in poultry
– “Normal flora” for local populations may be pathogenic
for visitors and transient populations:
• “Traveller’s diarrhea” due to local strains of E. coli
– “Some “normal flora” are pathogenic for sensitive
populations, such as immunocompromised persons:
• Example: Pneumocystis carinii (a protozoan or fungus)
– causes fatal pneumonia in AIDS patients
– immunocompetent people get asymptomatic infections
Occurrence of Enteric Microbial Pathogens in
Humans and Pathogen Shedding
• Enteric (gastrointestinal) illnesses are second only to respiratory
illnesses in the population
• Most people get 1 enteric illness per year:
– Annual illness rates are even higher in infants, children, the
elderly, child caregivers, health professionals, the poor, male
homosexuals and other high risk groups
• Not all enteric infections produce illness (asymptomatic or sub-clinical
infections)
– So, rates of infection are even higher (by perhaps 2 to 100 times)
• People (and animals) with enteric infections fecally excrete high
concentrations of pathogens for days, weeks, months or longer.
• Pathogen concentrations can be >106 to >109 per gram of feces.
• Community pathogen shedding is often 1-10% at any time.
Disease Due to Some Important Waterborne
Enteric Virus Pathogens
Norwalk Virus Gastroenteritis: A Localized Infection
• Fecal-oral transmission
• Localized infection of small intestine
• Damage to microvilli of intestinal epithelium
– “blunting” of the microvilli
• Incubation period 1-3 days
• Illness 1-3 days
• Major symptoms: diarrhea, vomiting, nausea, abdominal pain and
low grade fever
• Fecal shedding from onset of illness for several days.
– Virus concentration in feces as high as 109/gram
• Low infectious dose; perhaps as few as 10-100 virus particles
– Virus has not been cultured in laboratory animals or cell cultures
Response of Human Volunteers to Norwalk Virus Infection
via the Oral Route
Disease Due to Some Important Waterborne
Enteric Virus Pathogens
Hepatitis A Virus and Infectious Hepatitis: A Systemic Infection
• Fecal-oral transmission
• Systemic (generalized; disseminated) infection
• Liver as "target organ"
• Incubation period 2-6 weeks; average 4 weeks
• Illness for several weeks or months
• Destruction of liver hepatocytes
• Jaundice (in some but not all cases) and severe "flu-like"
symptoms, including gastrointestinal symptoms.
• Virus shed fecally from 2 weeks before to a few weeks after
onset of symptoms.
Disease Due to Some Important Waterborne
Enteric Bacterial Pathogens
Salmonella gastroenteritis: (S. enteriditis): localized infection
• Fecal-oral transmission
• Localized infection of intestines
• Damage and inflammation to lamina propria
• 0.5-2 day incubation period
• Watery diarrhea, nausea, vomiting, abdominal cramps,
low grade fever, lasting several days
• Bacteria shed fecally at billions per gram
• Infectious dose is relatively high: >103 ID50
Disease Due to Some Important Waterborne
Enteric Bacterial Pathogens
Typhoid fever: (S. typhi and S. paratyphi): Systemic Infection
• Fecal-oral transmission
• Systemic infection:
– Macrophages, reticuloendothelial system (esp. liver, spleen and
bone marrow), gallbladder and intestines as major sites of damage
• 1.5-2 week incubation period
• Symptoms: fever, headache, malaise, anorexia, then bloody
diarrhea
• Mortality rate 10%, if untreated
• Carrier state possible
– "Typhoid Mary”: infamous food handler; infected hundreds
• Fecally shed at billions/gram by ill persons and carriers
Disease Due to Some Important Waterborne
Enteric Protozoan Pathogens
Giardiasis (Giardia lamblia): localized enteric infection
• Fecal-oral transmission; hardy cyst ~10 m diameter
• Human and numerous non-human animal reserviors
• Infectious dose: low: ID50 ~10 cysts
• Infection: cysts excyst in small intestine; trophozoites attach to
microvilli of intestinal epithelium, tissue damage and
• interference with transport processes
• Profuse watery to semi-solid, greasy, bulky, malodorous diarrhea;
abdominal cramps,nausea, vomiting, anorexia, low grade fever,
headache
• 1-1.5week incubation period
• Duration of Illness: few days to months
• Subchronic infection possible
Disease Due to Some Important Waterborne
Enteric Protozoan Pathogens
Cryptosporidium and cryptosporidiosis
• Cryptosporidium parvum: coccidian (sporozoan) parasite
• Numerous animal reservoirs: feral, domestic and agricultural
• Fecal-oral transmission of hardy oocyst, ~5 m diameter
• Infectious at low dose: ID50 ~10 oocysts for some strains
• Excysts in small intestine; trophozoites attach to epithelial cells
• Complex life cycle; 6 major stages, some asexual, other sexual
• Infection and illness in immunocompetent hosts: similar to giardiasis:
diarrhea, nausea, vomiting, anorexia, fever, malaise
– Incubation period ~1 week; duration ~1.5 weeks, range 1-4 weeks
• Infection in immunocompromised hosts (ex, persons with AIDS):
– Life threatening, excessive fluid loss, chronic, no drug therapy
– ISpread to extra-intestinal sites: respiratory tract; pneumonia.