Chapter 21 and 22

Microbial Diseases of the Skin and Eyes

Microbial Diseases of the Nervous System

Skin• Epidermis - the outer portion of the skin

– Keratins - a waterproof coating– Hair follicles– Oil glands

• Dermis - the inner portion of the skin– Sweat ducts– Provide passageways for microorganisms.

• Sebum and perspiration are secretions of the skin – Can inhibit the growth of microorganisms

• Salt inhibits microbes• Lysozyme hydrolyzes peptidoglycan• Fatty acids inhibit some pathogens

– Provide nutrients for some microorganisms.Figure 21.1

Mucous Membranes

• Line body cavities

• Epithelial cells attached to an extracellular matrix

• Cells secrete mucus ( often acidic)

• Some have cilia

Figure 16.4 (3 of 3)

Normal Microbiota of the Skin

• Gram-positive, salt-tolerant bacteria– Staphylococcus

– Micrococcus

– Members of the genus Propionibacterium • metabolize oil from the oil glands

• colonize hair follicles.

– Malassezia furfur yeast • grows on oily secretions and may be the cause of dandruff.

• The normal skin microbiota are not completely removed by washing

• Bacterial pathogens– Staphilococcus aureus

– Streptococcus pyogenes

– Pseudomonas aeruginosa

– Propionibacterium acnes

Figure 14.1a

Microbial Diseases of the Skin• Many diseases manifested by skin lesions are actually systemic

diseases affecting internal organs

– Exanthem (from Greek "exanthema", a breaking out)

• Skin rash arising from another focus of infection

– Enanthem (ulcerative lesions on oropharyngeal mucosa)

• Mucous membrane rash arising from another focus of infection

Figure 21.2

Vesicles are small fluid-filled lesions Bullae are vesicles larger than 1 cm

Macules are flat, reddened lesions Pustules are raised lesions containing pus

1. Staphylococcal Skin Infections• Gram-positive bacteria in irregular grape like clusters

1. Coagulase-negative

• Staphylococcus epidermidis

-make up 90% of normal flora on skin

-can cause severe infections in those with venous catheters and

• immune-suppressed patients.

2. Coagulase-positive

• Staphylococcus aureus

- resident of nasal passage

- can survive on dry surfaces for months

- often evade host defenses

• Almost all pathogenic strains of S. aureus produce: – Coagulase positive ( form fibrin clots, protected from phagocytosis),

Enterotoxins, affect the GIT, Leukocidins ,Exfoliative toxin

– Lysozyme resistant, Superantigen, Penicillinase

– these are treated with vancomycin.

Staphylococcal Skin Infections

• Can cause…

- folliculitis, furuncle, carbuncle, impetigo

- scalded skin syndrome

- life threatening sepsis

- toxic shock syndrome

2. Streptococcal Skin Infections

• Streptococcus are gram-positive cocci classified according to their hemolytic enzymes and cell wall antigens.

• Group A beta-hemolytic streptococci (including Streptococcus pyogenes) are the pathogens most important to humans.

• Produce a number of virulence factors:– Hemolysins

– Deoxyribonuclease

– Streptokinases

– Hyaluronidase

– M protein

Figure 21.5

Streptococcal Skin Infections• Erysipelas

– infects the dermal layer

– reddish patches

– Can progress to local tissue destruction

– Enter the bloodstream

• Impetigo– isolated pustules

• Streptococcal toxic shock syndrome– M proteins

– Complex with fibrinogen

– Binds to neutrophils

– Activates neutrophils

– Release of damaging enzymes

– Shock and organ damage

Figure 21.6, 7

3. Infections by Pseudomonads

• Pseudomonads are gram-negative rods.

• Aerobes found primarily in soil and water that are

• Resistant to many disinfectants and antibiotics

• Pseudomonas aeruginosa produces an endotoxin and several exotoxins.

– Cause:

• dermatitis

• otitis externa

• burn infections

• respiratory infections

• Infections have a characteristic blue-green pus caused by the pigment pyocyanin.

• Quinolones are useful in treating P. aeruginosa infections.

What was the mostly likely source of this outbreak of Pseudmonas

dermatitis?

Exposure Relative Risk

Restaurant 1.24

Arcade 1.04

Swimming pool 6.14

Exercise room 1.29

Hot tub 9.90

Acne• Comedonal (mild) acne

– Occurs when sebum channels are blocked with shed cells• Inflammatory (moderate) acne

– The microorganism responsible for acne is Propionibacterium. • Gram positive• Obligate anaerobic• Slow growing• Rod shaped or branched• Produce lactic acid propionic acid and acetic acid from glucose

– Treatment• over the counter products (mild soaps, sulfur, benzyl peroxide)• prescription topical (topical antibiotics, topical retinoid, acanya, benzaclin, differin)• oral medications (oral contraceptives, minocycline, doxycycline)• -professional procedures (microdermabrasion, blue light therapy, facials, chemical peels)

• Nodular cystic (severe) acne– Treatment: isotretinoin

Viral Diseases of the Skin 

1. Papillomaviruses cause skin cells to proliferate and produce a benign growth called a wart or papilloma.

– dsDNA viruses– Productive infections only in the stratified epithelium of the skin or mucous membranes– Warts are spread by direct contact with the virus– Warts may regress spontaneously or be removed chemically or physically.– Interferon gamma

3. Poxviruses – Smallpox (Variola) virus causes two types of skin infections: variola major and

variola minor.– Very high infectious nature; 10-100 virus particles needed.– Smallpox is transmitted by the respiratory route, and the virus is moved to the skin via the bloodstream.– The only host for smallpox is humans.

• Symptoms - flu like symptoms; fever, body aches, headache, chills, backache, confusion.– Virus infects internal organs, bloodstream, and epidermal layer of the skin. – 30% of patients die within two weeks. Smallpox lives scarred skin. blindness,

arthritis, bone infection, lethal to a fetus.• Treatment- no cure. • Smallpox has been eradicated as a result of a vaccination effort by the WHO. popular

in 1970s – Vaccination is a life variola virus administered under the skin, leaves a scar and can

spread while it heals.– Possible damage of the vaccine and death.

3. Herpesviruses:

3.1. Chicken Pox and Shingles•Varicella zoster virus (Human Herpervirus 3 )

– Belongs to a group of eight herpes viruses that infect humans

– Very susceptible to disinfectants

– Infection originally occurs via droplet transmission and

incubates in respiratory epithelium for 10-20 days

– After primary infection, Varicella zoster virus remains dormant in sensory nerve roots latent for a long period of time.

– Can be reactivated as Herpes zoster to cause shingles later in

life if the immune system is compromised.•Symptoms:

– Red itchy rash of blisters filled with fluid, Mild fever, Backache, Headache, Sore throat

•Treatment:

– Live attenuated Varicella vaccine is available and suggested.

– Antiviral medication may be prescribed for high risk cases. Usually just pain medication and/or anti-histamines for itching and time is all that is necessary. (aspirin should not be taken as it can lead to Reye’s Syndrome)

3.2. Herpes simplex 1 and Herpes simplex 2 – Herpes simplex infection of mucosal cells results in cold sores and

occasionally encephalitis.– HSV-1 is transmitted primarily by oral and respiratory routes.– The virus remains latent in nerve cells, and cold sores can recur when the virus

is activated.– Herpes encephalitis occurs when herpes simplex viruses infect the brain.– Acyclovir has proven successful in treating herpes encephalitis.

4. Measles (Rubeola)

• Caused by measles virus

• Transmitted by the respiratory route.

• Extremely contagious viral disease spread by the respiratory route

• Koplik’s spots

– Small red spots with central blue-white specks

– Diagnostic indicator of disease

• MMR vaccine

• Vaccine is 95% effective

• Children under 1 are at risk

• Complications of measles include middle ear infections, pneumonia, encephalitis, and secondary bacterial infections.

5. Rubella (German Measles) – The rubella viruses transmitted by the respiratory route.

– A red rash and light fever might occur in an infected individual; the disease can be asymptomatic.

– Congenital rubella syndrome can affect a fetus when a woman contracts rubella during the first trimester of her pregnancy.

• Damage from congenital rubella syndrome includes stillbirth, deafness, eye cataracts, heart defects, and mental retardation.

– Vaccination with live rubella virus provides immunity of unknown duration.

Fungal Diseases of the Skin and Nails 

1. Cutaneous Mycoses– Fungi that colonize the outer layer of the epidermis cause dermatomycoses

called ringworm, or tinea– Microsporum,

– Trichophyton,

– Epidermophyton cause dermatomycoses.

– These fungi grow on keratin-containing epidermis, such as hair, skin, and nails.

– Ringworm and athlete’s foot are usually treated with topical antifungal chemicals.

– Diagnosis is based on the microscopic examination of skin scrapings or fungal culture.

– Treatment

• Oral griseofulvin

• Topical miconazole

2. Subcutaneous Mycoses– More serious than cutaneous mycoses

– Sporotrichosis• Results from a soil fungus that penetrates the skin through a wound.

• The fungi grow and produce subcutaneous nodules along the lymphatic vessels.

• Most common U.S. disease of this type– Sporothrix schenchii enters puncture wound

– Treated with potassium iodide (KI)

3. Candidiasis– Candida albicans is an opportunistic pathogen that may proliferate when the

normal bacterial microbiota are suppressed.

– C. albicans (yeast) causes infections of mucous membranes and is a common cause of thrush (in oral mucosa) and vaginitis.

– Topical antifungal chemicals may be used to treat candidiasis.

• miconazole or nystatin

Eyes• Conjunctiva (Mucous membrane)

– Lines the inside of the eyelids and covers the sclera (white part of the eye)

– Composed of non-keratinized epithelium

– Secrete mucus and the aqueous portion of tears

– Contains blood vessels, fibrous tissue, and lymphatic channels

• Lacrimal apparatus – – Tear production and drainage

– Anti-microbial compounds

– Lysozyme

– Secretory antibodies (IgA).

Microbial Diseases of the Eye

1. Conjunctivitis (pinkeye)– The mucous membrane lining the eyelid and covering the eyeball is the

conjunctiva.

– Inflammation of the Eye Membranes: Conjunctivitis 

– Conjunctivitis is caused by several bacteria and can be transmitted by improperly disinfected contact lenses.

• Haemophilus influenzae

• Various microbes

• Associated with unsanitary contact lenses

Microbial Diseases of the Eye2. Neonatal gonorrheal ophthalmia

– Neisseria gonorrhoeae– Transmitted to newborn's eyes during passage through the birth canal– Prevented by treatment newborn's eyes with antibiotics

3. Trachoma (caused by certain serotypes of Chlamydia trachomatis)– Inclusion conjunctivitis

• Transmitted to newborn's eyes during passage through the birth canal• Spread through swimming pool water• Treated with tetracycline

– Greatest cause of blindness worldwide• Infection causes permanent scarring; scars abrade the cornea leading to

blindness

4. Herpetic Keratitis– Herpes simplex virus 1 (HHV-1)– Infects cornea, may cause blindness– Treated with trifluridine

5. Acanthamoeba keratitis– Transmitted from water– Associated with unsanitary contact lenses

Learning objectives• Describe the structure of the skin and mucous membranes and the ways

pathogens can invade the skin.• Provide examples of normal skin microbiota, and state their locations and

ecological roles of its members.• Differentiate staphylococci from streptococci, and name several skin infections

caused by each.• List the causative agent, method of transmission, and clinical symptoms of

Pseudomonas, dermatitis, otitis externa, acne.• List the causative agent, method of transmission, and clinical symptoms of

these skin infections: warts, smallpox, chickenpox, shingles, cold sores, measles, rubella.

• Differentiate cutaneous from subcutaneous mycoses, and provide an example of each.

• List the causative agent of and predisposing factors for candidiasis.• Define conjunctivitis.• List the causative agent, method of transmission, and clinical symptoms of

these eye infections: neonatal gonorrheal ophthalmia, inclusion conjunctivitis, trachoma.

• List the causative agent, method of transmission, and clinical symptoms of these eye infections: herpetic keratitis, Acanthamoeba keratitis.

• The central nervous system (CNS) – the brain, which is protected by the skull bones– the spinal cord, which is protected by the backbone

• The peripheral nervous system (PNS) consists of the nerves that branch from the CNS.

• The CNS is covered by three layers of membranes called meninges: – dura mater, – arachnoid mater– pia mater.

• Cerebrospinal fluid (CSF) circulates between the arachnoid mater and the pia mater in the subarachnoid space.

The Nervous System

Structure and Function of the Nervous System

• The blood–brain barrier normally prevents many substances, including antibiotics, from entering the brain.

• Microorganisms can enter the CNS through:– Trauma – Along peripheral nerves – Through the bloodstream and lymphatic system.

• Meningitis -An infection of the meninges.– Meningitis can be caused by viruses, bacteria, fungi, and protozoa.

• Encephalitis - An infection of the brain.– Primary encephalitis - caused by a bacterial infection such as bacterial meningitis spreading directly to the brain– Secondary encephalitis - a complication of a current infectious disease (syphilis)

Bacterial Meningitis • Nearly 50 species of opportunistic bacteria can cause meningitis.

• Symptoms-fever, headache and stiff neck, nausea and vomiting, neurological damage, may progress to convulsions, coma , death.

• The three major causes of bacterial meningitis are:1. Haemophilus influenzae

• Part of the normal throat microbiota. • Requires blood factors for growth; • A conjugated vaccine directed against the capsular polysaccharide antigen is available.

2. Neisseria meningitidis• This bacterium is found in the throats of healthy carriers. • Symptoms are due to endotoxin. • The bacteria probably gain access to the meninges through the bloodstream. • Purified capsular polysaccharide vaccine against serotypes A, C, Y, and W-135 is

available.

3. Streptococcus pneumoniae • commonly found in the nasopharynx. • It is rare disease but has a high mortality rate. • A conjugated vaccine is available.

Bacterial Meningitis

• Diagnosis is based on Gram stain and serological tests of the bacteria in CSF.

• Cultures are usually made on blood agar and incubated in an atmosphere containing reduced oxygen levels.

• Cephalosporins may be administered before identification of the pathogen.

 Genus Clostridium1. Tetanus

• Clostridium tetani– Obligate anaerobe

– Endospore-forming

– Produces the neurotoxin tetanospasmin,

– Tetanus bacilli live in the soil, so the most dangerous kind of injury involves possible contamination with dirt, animal feces, and manure, self-piercing

– Tetanus is not spread from person to person.

– Causes localized infection of a wound ( grow in deep, unclean wounds and wounds with little bleeding)

• Symptoms: spasms, contraction of muscles controlling the jaw, and death resulting from spasms of respiratory muscles.– Acquired immunity results from DPT immunization (tetanus toxoid)

• Following an injury:– An immunized person may receive a booster of tetanus toxoid

– An unimmunized person may receive (human) tetanus immune globulin.

– Debridement (removal of tissue) and antibiotics may be used to control the infection.

2. Botulism - Clostridium botulinum

– Anaerobe– Growing in foods.– Produced a neurotoxin that inhibits the transmission of nerve impulses.

• Symptoms: Blurred vision occurs in 1 to 2 days; progressive flaccid paralysis follows for 1 to 10 days, possibly resulting in death from respiratory and cardiac failure.

• Several serological types of botulinal toxin - differed in their virulence – The toxin is heat labile and is destroyed by boiling (100°C) for 5 minutes.– Endospore-forming

• Killed by proper canning. • The addition of nitrites to foods inhibits growth after endospore germination.• C. botulinum will not grow in acidic foods or in an aerobic environment.

• Infant botulism results from the growth of C. botulinum in an infant’s intestines.

• Wound botulism occurs when C. botulinum grows in anaerobic wounds.• For diagnosis, mice protected with antitoxin are inoculated with toxin from

the patient or foods.

Leprosy

• Causative agent - Mycobacterium leprae– Acid-fast rod that grows best at 30°C

– Grows in peripheral nerves and skin cells

• Tuberculoid (neural) form: • Loss of sensation in skin areas;

• Positive lepromin test

• Lepromatous (progressive) form: • Disfiguring nodules over body;

• Negative lepromin test

• Transmission requires prolonged contact with an infected person

• Untreated individuals often die of secondary bacterial complications, such as tuberculosis.

• Patients with leprosy are made noncontagious within 4 to 5 days with sulfa drugs and then treated as outpatient.

Viral disease of the Nervous System

1. Rabies - Rabies virus (Rhabdovirus)– Transmitted by animal bite (zoonotic)

• Virus multiplies in skeletal muscles,

then brain cells causing encephalitis

• An acute, usually fatal encephalitis

• Occurs when the virus moves

along peripheral nerves to the CNS.

– Initial symptoms may include muscle spasms of the mouth and pharynx and hydrophobia

– Furious rabies: animals are restless then highly excitable

– Paralytic rabies: animals seem unaware of surroundings

– Pre exposure prophylaxis: Infection of human diploid cells vaccine

– Post exposure treatment: Vaccine + immune globulin

2. Poliomyelitis - Poliovirus– Transmitted by ingestion

• Initial symptoms: sore throat and nausea

• Viremia (presence of a virus in the blood) may occur;

• If persistent, virus can enter the CNS; destruction of motor cells and paralysis occurs in <1% of cases

– Diagnostics of polio is based on isolation of the virus and measured of cytopatic effect on the cells.

– Prevention is by vaccination (enhanced-inactivated polio vaccine)

3. Arboviral Encephalitis - Arboviruses are arthropod-borne viruses that belong to several families transmitted by mosquitoes cause encephalitis.– Symptoms of encephalitis are chills, headache, fever, and eventually coma.

– The incidence of arboviral encephalitis increases in the summer months, when mosquitoes are most numerous.

– Diagnosis is based on serological tests.

– Control of the mosquito vector is the most effective way to control encephalitis.

Fungal Disease of the Nervous System

• Cryptococcus neoformans meningitis • an encapsulated yeast like fungus that causes cryptococcosis

• The disease may be contracted by inhalation of dried infected pigeon or chicken droppings.

• The disease begins as a lung infection and may spread to the brain and meninges.• Immunosuppressed individuals are most susceptible to Cryptococcus neoformans

meningitis.• Diagnosis is based on latex agglutination tests for cryptococcal antigens in serum or

CSF.

Protozoan Diseases of the Nervous System

1. African Trypanosomiasis  – Causative agent - Trypanosoma brucei gambiense and T. b. rhodesiense

– Transmitted by the bite of the tsetse fly.

– The disease affects the nervous system of the human host, causing lethargy and eventually coma. It is commonly called sleeping sickness.

– Vaccine development is hindered by the protozoan’s ability to change its surface antigens.

2. Amebic Meningoencephalitis – Encephalitis caused by the protozoan Naegleria fowleri is almost always fatal.

3. Granulomatous amebic encephalitis – Caused by Acanthamoeba spp. and Balamuthia mandrillaris, is a chronic disease.

Transmissible Spongiform Encephalopathies

• Causative agent – prions• Tiny holes appear in the cortex causing it to appear like a sponge (hence 'spongiform') when brain tissue obtained at autopsy is examined under a microscope

• A group of progressive conditions that affect the brain and nervous system of animals and also humans. – The disorders cause impairment of brain function, including

memory changes, personality changes and problems with movement that worsen over time.

– Prion diseases of humans include classic • Mad cow disease, Sheep scrapie and bovine spongiform

encephalopathy (BSE) are transferable from one animal to another• Creutzfeldt-Jakob disease and kuru are human diseases similar to

scrapie. They are transmitted between humans.

Figure 22.17a

Learning objectives• Define central nervous system and blood-brain barrier.• Differentiate meningitis from encephalitis.• Discuss the epidemiology of meningitis caused by H. influenzae, S. pneumoniae, N.

meningitidis, and L. monocytogenes.• Explain how bacterial meningitis is diagnosed and treated.• Discuss the epidemiology of tetanus, including mode of transmission, etiology, disease

symptoms, and preventive measures.• State the causative agent, symptoms, suspect foods, and treatment for botulism.• Discuss the epidemiology of leprosy, including mode of transmission, etiology, disease

symptoms, and preventive measures.• Discuss the epidemiology of poliomyelitis, rabies, and arboviral encephalitis, including mode of

transmission, etiology, and disease symptoms.• Compare preexposure and postexposure treatments for rabies.• Explain how arboviral encephalitis can be prevented.• Identify the causative agent, reservoir, symptoms, and treatment for cryptococcosis.• Identify the causative agent, vector, symptoms, and treatment for African trypanosomiasis and

amebic meningoencephalitis.• List the characteristics of diseases caused by prions.