Water

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Water- Soil-Borne Diseases
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Recent UN Development Program Report

• 2.6B people lack proper toilets
• At least 1B get water from sources polluted with
  human or animal feces
• 10B estimate to halve the above numbers
• Beyond Scarcity Power, Poverty and the Global
  Water Crisis

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Shigellosis Dysentery

• Infection can trigger fever 12 hours after
  ingestion
• Shigella sonnei (mild), S.flexneri, S.dysenteriae
  (severe), S.boydii
• Shiga toxin
• Cells survive stomach acid and grow in small
  intestine
• Severe cases are often treated with
  fluoroquinolones (i.e. Cipro)

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Cholera

• Vibrio cholerae
• Survive in estuaries (high salt) and fresh water
  tolerant of alkalinity
• Spore-like state not culturable, but infectious
• Two known serotypes (other serotypes cause milder
  disease)
• Grow in small intestine

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Cholera

• Host cells lose chlorides, bicarbonates and water
• 3-5 gallons can be lost per day massive diarrhea
• Blood becomes viscous
• Rehydration is best therapy

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Vibrio cholerae along Brush border of rabbit villi
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Virstatin inhibits virulence expression in V.
cholerae
Virstatin turns off transcription of an exotoxin
and a pilus Exotoxin (Cholera toxin) is an
enzyme that elevates cAMP in host cells leads
to fluid loss (gene is part of prophage) Pilus
is for attachment
Virstatin can inhibit cholera infection in mice
D. T. Hung et al., Science 310, 670 -674
(2005)
Published by AAAS
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Unusual Quorum Sensing

• In some strains of V. cholerae, QS works the
  opposite of expectations.
• High concentration of autoinducer inhibits toxin
  production!

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Cholera Epidemic in Iraq

• 1217 cases in Northern Iraq from August
  December, 2007.
• Sulaymaniya province.
• Meeting 27.5 of water demand.
• SF Chronicle. 12/10/07.
• (16,000?)

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Protozoan Diseases

• Giardiasis
• Cryptosporidiosis
• Amoebic Dysentery
• Often ingested as cysts, which is analagous to a
  bacterial spore.
• Trophozoite form is analagous to vegetative cells
  of bacteria.

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Giardiasis

• Giardia lamblia
• Flagellated
• Attaches to intestinal wall can interfere with
  nutrient absorption
• Diarrhea, H2S odor in breath and stool

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Giardia trophozoite, 15um
Giardia cyst, 11um
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Giardiasis

• 7 of U.S. population carry the cysts in feces.
• Cysts are sensitive to boiling, but not chlorine.
• Testing of stool ELISA .
• String test 140 cm of string tied to gelatin
  capsule.

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Will enter duodenum
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Cryptosporidiosis

• Cryptospridium parvum.
• Oocysts release sporozoites in small intestine.
• latter enter epithelial cells.
• Oocysts are released in feces.

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Cryptosporidium oocysts in feces
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Cryptosporidiosis

• Diarrhea for up to 2 weeks
• Rehydration therapy
• Prevented by proper filtration
• 10 oocysts (at right) can be infective

4.2 µm - 5.4 µm in diameter
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Amoebic Dysentery

• Entamoeba histolytica
• Cysts can survive stomach acid
• Trophozoites multiply in large intestine
  epithelium
• Blood and mucus in feces
• Can infect liver
• 10 of worldwide population are carriers

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Entamoeba histolytica
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Viral Hepatitis

• Liver inflammation
• 5 main viruses A E (F G too)
• HAV fecal-oral
• HBV parenteral, sex
• HCV parenteral
• HDV parenteral
• HEV fecal-oral

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Hepatitis A Virus

• Non-enveloped, ss RNA
• Multiplies in intestinal lining
• Then enters blood and spreads to liver (kidneys
  and spleen too)
• Detected in blood, urine, feces
• Can survive for days on fomites
• Resistant to typical chlorine concentrations

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Hepatitis A

• Most infections show no obvious symptoms
• Low appetite, fever, chills, diarrhea, jaundice,
  dark urine, yellow stool
• Symptoms last up to 3 weeks
• 4 week (avg.) incubation
• Anti-HAV IgM detected for diagnosis

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Hepatitis B

• Enveloped dsDNA pararetrovirus
• Three types of particles only 1 is complete
  virus
• Incomplete particles also have a surface protein
  which serves as an antigen to stimulate immune
  response
• 12 week (avg.) incubation period

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Hepatitis B

• Health care workers usually vaccinated
• Subunit vaccine
• Can be passed from mother to baby during birth
• Newborn is treated with antibody and vaccine

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Acute HBV Hepatitis

• Symptoms are similar to Hep A
• Recovery is typical liver function can return to
  normal

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Chronic HBV Hepatitis

• Detection of surface antigen for more than 6
  months
• Can develop into cirrhosis
• Higher incidence of liver cancer (due to
  integrated viral DNA)

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Hepatitis C

• Enveloped ss RNA
• Rapid antigenic variation no vaccine
• Detection of antibodies in 2-3 months (PCR
  detection within 2 weeks)
• Can take up to 20 years for symptoms are
  observable
• Very likely to develop chronic hepatitis

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Hepatitis C

• Major reason for liver transplant
• Pharmaceutical therapies are not very effective
• Crisis may be on its way (recognition of this
  disease was in 1975)
• High incidence in Egypt (10-20)
• Non-sterile needles used in 50s-70s for
  Schistosomiasis treatment

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Hepatitis D

• Circular ss RNA, requires HepB surface antigen
  for packaging (and infectivity)
• RNA is not infectious on its own
• Thus, there is no Hep D without Hep B infection
• More serious disease than Hep B (if chronic)

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Hepatitis E

• Non-enveloped ss RNA
• Disease is similar to Hep A, but lower
  transmission rate
• First recognized in 1980
• Determined to be cause of a water-borne epidemic
  in India in 1950s

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Poliomyelitis

• Causes paralysis in lt1 of cases
• Most cases are asymptomatic
• Oral-fecal route for most cases
• Infects throat area, then moves into lymphatic
  system and blood
• Persistent infection can get into CNS
• Motor neurons in spinal cord are infected not
  peripheral nerves or muscles

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Polio in U.S.

• Last case reported due to a wild-type virus was
  in 1979
• 142 cases from 1980 2002 mostly due to
  vaccination
• Three serotypes of virus

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Polio Vaccines

• Salk vaccine (1954) virus inactivated by
  formalin, requires boosters
• Sabin vaccine (1963) 3 live attenuated viruses,
  oral, more common in U.S.
• Rarely (or occasionally?), the virus in the
  vaccine reverts and causes disease in a contact
  of the recipient of the vaccine

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Tetanus

• Clostridium tetani
• Obligate anaerobe, gram positive, endospores
• Found in soils with animal feces
• No inflammation, bacteria do not spread
• Release tetanospasmin, which enters CSF
• Blocks relaxation pathway in neuromuscular
  junction
• Toxin is a protein
• Toxoid vaccine

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Clostridium difficile

• Fecal-oral route Normal microbiota.
• Problem for the immuno-compromised (primarily
  elderly hospital patients).
• New antibiotic-resistant strains.
• New hypervirulent strains.
• Diarrhea, abdominal pain.
• 82K cases in 1996 to 178K in 2003.

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Anthrax

• Bacillus anthracis
• Aerobic, gram-positive rod, endospores
• Can grow slowly in soil
• Spores can survive in soil
• Ingested by grazing animals

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B.anthracis
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ground glass B.anthracis colonies on blood agar
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Anthrax

• Endospores enter body
• Macrophage ingests
• Organism reproduces in and kills macrophage
• Capsule is composed of amino acids
• No immune response against capsule!
• B.anthracis can multiply in blood and cause shock

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Anthrax toxins

• 2 exotoxins each has a protein component that
  binds to host cell surface (protective antigen)
• Both toxins can enter target cells
• Edema toxin causes local swelling, interferes
  with phagocytosis
• Lethal toxin kills macrophages

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Cutaneous Anthrax

• Endospore enters through wound in skin
• Pustule forms
• Recovery is routine if infection stays local
• If it enters bloodstream, fatal sepsis is possible

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Cutaneous anthrax, 2cm on forearm
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Pulmonary Anthrax

• Endospores are inhaled
• High probability of entering bloodstream
• Most dangerous form
• Early symptoms mild fever, cough, chest pain
  (antibiotics effective at this stage)
• Fatal septic shock occurs 2 -3 days later

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Hemorrhagic meningitis due to inhalation anthrax
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Treating Anthrax

• Ciproflaxacin is most common antibiotic
• But inhaled endospores may take up to 2 months
  before they germinate
• Live, attenuated vaccine for animals only
• Human vaccine toxoid form of protective antigen
  (several shots boosters)

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Anthrax

• An effective biological weapon
• or -
• fulfillment of a suicidal fantasy?