Human Diseases

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Human Diseases

• Pathogenicity and Transmission

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Pathogenic Determinants

• Genetic factors of pathogen and host
• Environmental factors
• Infectious dose
• Route of infection
• Host resistance factors

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Stages in Pathogenesis

• Entry into host
• Spread within the host
• Cell and tissue tropism
• Cell injury
• Persistence

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Mode of entry into host
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Patterns of Viral Disease

• Inapparent infection
• Acute disease
• Chronic disease, productive vs. unproductive
• Latent disease
• Late disease

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Examples of human viral disease

• Airborne diseases
• Arthropod-borne diseases
• Direct contact diseases
• Food and water-borne diseases
• Unconventional agents

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Airborne diseases

• Varicella zoster
• Influenza
• Measles, mumps, rubella
• Respiratory syncytial virus
• Smallpox
• Metapneumovirus ??

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Chicken pox
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Recurrence of chickenpox
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Measles
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Mumps
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Smallpox
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Arthropod-borne and vector diseases

• Invertebrate (and occasionally vertebrate)
  intermediate hosts
• Requirement for replication in intermediate host
• Incidence influenced by ecological/population
  factors

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Vector diseases

• Ebola hemorrhagic fever (vector unknown)
• Hantavirus pulmonary and renal syndromes
  (rodents, airborne?)
• Yellow fever (mosquito Aedes aegypti)
• West Nile encephalitis (mosquito many)
• Rabies (vertebrate, direct contact required)

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Direct Contact Diseases

• AIDS
• Herpes simplex I and II
• Mononucleosis
• Hepatitis B and C
• Papilloma/condyloma (warts)

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HIV AIDS

• Envelope with virus-encoded glycoproteins
• gag proteins form virion core
• Diploid, ssRNA genome
• Enzymes
• Reverse transcriptase
• Integrase
• Protease

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HIV Life Cycle

• Cell binding
• Entry membrane fusion
• Reverse transcription
• Integration
• Gene expression
• Budding through plasma membrane

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The Nucleus and Beyond

• No site specificity on host genome
• Integrated copy flanked by long terminal repeats
• Host transcription factors and RNA polymerase
  carry out expression
• RNA splicing generates several mRNAs
• RNA exported from nucleus
• Assembly and Budding

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Time Course of Human Infection
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Why do CD4 T cells Die?

• Apoptosis
• Syncytium formation (multinucleated cell due to
  fusion)
• Attack by cytotoxic cells
• Cell lysis

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What Makes HIV People Sick?

• CD4 T cell count below 200/ml
• Inability to resist opportunistic infections
• Pneumocystis carnii
• Oral candidiasis
• Kaposis sarcoma (HSV-8)
• Cervical cancer (HPV-11,16,18,38)
• AIDS dementia complex

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What can be done?

• Prevention
• Safer sex
• Protective equipment (gloves, eyewear,
  mouthpieces)
• Drug treatments
• RT inhibitors
• Protease inhibitors
• Novel approaches

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Testing for HIV infection

• Primary ELISA
• Repeat ELISA if positive
• Western blot analysis
• Direct detection of viral RNA by PCR

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What are the Major Problems?

• Presymptomatic individuals spread virus
• Drug therapies are expensive, difficult to
  tolerate long term
• HIV has extremely high mutation rate
• No effective vaccine

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Portals of entry for bacteria Mucous
membranes respiratory, GI, GU, conjunctiva

air food, water, objects Skin
pores (sweat glands), hair follicles
Parenteral damage to barrier punctures, insect
bites, cuts, drying Adherence - attachment
to tissue adhesins capsules fimbriae (S.
mutans, Actinomyces, N. gonorrhea)
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Bacterial infections classified on tissue
involvement skin infections skin, sweat
glands, hair follicles respiratory system
infections gastrointestinal system
infections genitourinary infections
nervous system infections wound infections
blood and lymphatic infections
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Skin infections Lyme disease
Staphylococcus hair follicles
Staphylococcus boils scalded skin syndrome
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Wound infections gas gangrene tetanus
neurotoxin necrotizing fasciitis S.
pyogenes burn infections P. aeruginosa
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Respiratory tract infections strep throat
diphtheria tuberculosis pneumonia
Legionaires disease anthrax
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Digestive tract infections upper digestive
tract periodontal disease - spirochetes trench
mouth spirochetes ulcers H. pylori
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Digestive system infections lower digestive
tract cholera Salmonella Shigella E. coli
O157H7
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Genitourinary tract toxic shock syndrome
gonorrhea Chlamydia
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Genitourinary tract syphilis
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Nervous system meningitis botulism
tetanus listeriosis
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Listeriosis bacteria in food Outbreak 1 34
perinatal infections 9 stillbirths 23
infected infants 1/3 nearly died 2
healthy infants 77 non-pregnant adult
infections 30 died Coleslaw prepared with
cabbage from farmer who had 2 sheep die of
listeriosis. Fertilized fields with sheep
manure
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Outbreak 2 142 people with symptoms
93 perinatal 30 stillborn or died shortly after
birth 49 adults 48 immunocompromised 18
died suspect pasteurization equipment failed
raw milk mixed with pasteurized cheese
contaminated
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In 1985, an outbreak of Listeriosis, due to
Mexican-style cheese, led to 18 deaths and
numerous stillbirths. As a result of this
episode, FDA has been monitoring domestic and
imported cheeses and has taken numerous actions
to remove these products from the market when L.
monocytogenes is found. The Center for Disease
Control has established an epidemiological link
between consumption of raw hot dogs or under
cooked chicken in approximately 20 of the
sporadic cases under study. Source U.S.
Department of Agriculture, Food and Safety
Inspection Service, Food and Drug Administration,
Background Document, March, April 1992.
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In 2002, an outbreak of Listeriosis, due to deli
meats from a plant in Pennsylvania, led to 8
deaths. The organism was found in the drains in
the plant. The processing plant was closed until
the problem had been remedied.
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blood infections endocarditis
septicemia multiplication of bacteria
in blood plague involves lymph
nodes and spleen