107 terms

Micro Chapter 21

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Spirochetes Characteristics. Morphology?
- Gram negative human pathogens
-Representation of the general spirochete morphology with a pair of endoflagella inserted in the opposite poles, lying beneath the outer membrane and within the periplasmic space.
Treponema Pallidum. What do they look like? Where are they cultured? Who is the natural host? Can it survive outside the host? What does it cause?
Thin, regular, coiled cells
Pathogens are strict parasites that can only be cultured in live cells
Human is the sole natural host
Extremely fastidious & sensitive; cannot survive long outside of the host
Causes syphilis
When is syphilis most contagious?
- Most contagious to sex partners during the primary and secondary stages
What are the risk populations for syphilis?
- Men who have sex with both men and women
- Secondary to increased likelihood of co-infection with HIV
- African American/black population
Pathogenesis of T. pallidum.
T. pallidum enters the body via skin and mucous membranes through abrasions during sexual contact

Binds to mucous membranes or damaged skin using its hooked endoflagellum

Travels via the circulatory system (including the lymphatic system and regional lymph nodes) throughout the body

Invasion of the central nervous system (CNS) can occur during any stage of syphilis
What are T. pallidum virulence factors?
Outer membrane proteins (surface proteins)
Primary Syphilis
represents first stage of infection, localized; painless** chancre
Secondary syphilis
weeks to few months later, 25% of untreated patients will develop a systemic illness that represents the dissemination of T. pallidum; manifests with a generalized, diffuse, maculopapular rash and/or anorectal involvement (condylomata lata)
Tertiary syphilis
months to years later, untreated patients can develop neurologic symptoms (neurosyphilis) and gummas (tender tumors that can be erosive)
Congenital syphilis
(via placenta) causes nasal discharge ("the snuffles"), skin eruptions, bone deformation, nervous system abnormalities
Where does the lesion develop in primary syphilis?
Primary lesion or "chancre" develops at the site of inoculation.
Characteristics of the chancre in primary syphilis?
- Progresses from macule to papule to ulcer;
- Typically painless, indurated, and has a clean base;
- Highly infectious;
- Heals spontaneously within 3 to 6 weeks; and
- Multiple lesions can occur.
What other symptoms can you see in primary syphilis?
Regional lymphadenopathy: classically rubbery, painless
Clinical Manifestations of secondary syphilis
Rash (75%-100%)
Lymphadenopathy (50%-86%)
Malaise
Condylomata lata (10%-20%)
Alopecia (5%)
Liver and kidney involvement can occur
Splenomegaly is occasionally present
When do secondary lesions occur? Which lesions are the most common?
- Secondary lesions occur several weeks after the primary chancre appears; and may persist for weeks to months.
- Mucocutaneous lesions most common
Serological test of primary and secondary syphilis.
- Serologic tests for syphilis may not be positive during early primary syphilis.

- Serologic tests are usually highest in titer during this stage (2nd)
Describe the secondary syphilis rash.
The skin rash in secondary syphilis is typically reddish to brownish, diffuse, and maculopapular. *Affects the palms and soles. The rash does not hurt or itch and can persist for months.
Latent syphilis. What is the only evidence? When can it occur? What are the 2 different categories?
- Host suppresses infection, but no lesions are clinically apparent
- Only evidence is a positive serologic test
- May occur between primary and secondary stages, between secondary relapses, and after secondary stage
- Categories:
~Early latent: <1 year duration
~Late latent: >1 year duration
When does neurosyphilis occur? What stage of syphilis does it occur?
- Occurs when T. pallidum invades the central nervous system (CNS); Spirochetes destroy the blood vessels in the brain, cranial nerves, and dorsal roots of the spinal cord

- May occur at any stage of syphilis, but is typically associated with tertiary stage
Clinical manifestations of neurosyphilis?
- Clinical manifestations can include acute syphilitic meningitis, ocular involvement
Patients develop headaches, seizures, altered mental status, blindness
- Can be asymptomatic
What is the sign of ocular involvement in neurosyphilis?
- Ocular involvement can occur in early or late neurosyphilis
- Argyll Robertson pupil -- pupil becomes misshapen, indicating damage to the nerves that control the iris, and will not react to light. Pupil still accommodates.
Tertiary syphilis.
- 30% of untreated infections enter tertiary syphilis, which can follow a period of latency up to 20 years or longer
- Rare because of the widespread availability and use of antibiotics
What is the hallmark sign of tertiary syphilis?
- Hallmark of this stage = Gummas
~Gummas are granulomatous lesions that destroy soft tissue, cartilage, and bone
~Can occur in skeletal, spinal, and mucosal areas; the eyes, and viscera (lung, stomach, liver, genitals, breast, brain, and heart)
Cardiovascular syphilis.
- Results from damage by the spirochete
- Presents as ascending aortic aneurysm, aortic valve insufficiency and/or heart failure
When does congenital syphilis occur? What can it lead to? What stage of syphilis is it transmitted?
- Occurs when T. pallidum is transmitted from a pregnant woman to her fetus
- May lead to stillbirth, neonatal death, and infant disorders such as deafness, neurologic impairment, and bone deformities
- Transmission can occur during any stage of syphilis; risk is much higher during primary and secondary syphilis
What is an early sign of congenital syphilis? What is a common characteristic?
- An early sign is "snuffles", a profuse nasal discharge that obstructs breathing.
- A common characteristic of late congenital syphilis is notched, barrel-shaped incisors (Hutchinson's teeth)
Lab dx of early syphilis
- Identification of Treponema pallidum in lesion exudate or tissue (antibodies may not be present)
- Darkfield microscopy
Serology test for secondary, latent, and tertiary syphilis
Nontreponemal tests
Treponemal tests
Principles of Nontreponemal Serologic Tests. What tests does it include?
- Principles:
~Measure antibody directed against a cardiolipin-lecithin-cholesterol antigen
~Not specific for T. pallidum
~Titers usually correlate with disease activity and results are reported quantitatively
~May be reactive for life, referred to as "serofast"
- Nontreponemal tests include VDRL, RPR
Advantages of Nontreponemal serologic tests
- Rapid and inexpensive
- Easy to perform and can be done in clinic or office
- Quantitative
- Used to follow response to therapy****
- Can be used to evaluate possible reinfection
Disadvantages of nontreponemal serologic tests
- May be insensitive in certain stages
- False-positive reactions may occur
Principles of Treponemal serologic tests. What tests does it include?
- Principles:
~Measure antibody directed against T. pallidum antigens
~Qualitative
~Usually reactive for life
~Titers should not be used to assess treatment response**
- Treponemal tests include FTA-ABS, EIA, and Treponemal Agglutination test
Treatment of syphilis. What is second line?
- Primary, Secondary, and Early Latent Syphilis = Benzathine penicillin G 2.4 million units intramuscularly in a single dose (Bicillin L-A)
- If penicillin allergic, patient is given an oral course of doxycycline
- Late latent and tertiary syphilis require higher dosage and multiple doses
What causes the most widespread zoonosis in the world? Characteristics of the bacteria.
- Leptospirosis
- Tight, regular individual coils with a bend or hook at one or both ends
How is L. interrogans transmitted?
- Transmitted to humans from dogs, cattle, skunks, raccoons, foxes, rats, mice, guinea pigs, gerbils, rabbits, hamsters and reptiles
- No human-to-human transmission
Pathogenesis of L. interrogans. What symptoms present?
- Bacteria shed in urine**; infection occurs by contact - often during handling affected animals, cleaning cages, and swimming in waters with infected animals
- Organism enters through skin abrasions or through the conjunctiva; targets kidneys, liver, brain, eyes
- Infection usually produces no symptoms
- Moderate to severe disease - patients present with s/sx of meningitis (sudden high fever, chills, headache, nausea, vomiting) as well as conjunctivitis and a petechial rash
~Can develop jaundice and anemia; death can occur due to hepatic and renal failure
How is dx of L. interrogans made?
Diagnosis usually by darkfield examination of blood or urine; culture should be done but takes several weeks
How do you treat L. interrogans? is there a vaccine?
- Severe disease - early treatment with Penicillin G or ampicillin
- Doxycycline used for mild disease
- Vaccine for dogs to eliminate reservoir; vaccine also available for livestock workers and military personnel
What does the Borrelia species have an abundance of?
periplasmic flagella
How is Borrelioses transmitted?
arthropod vector
What does B. hermsii cause?
relapsing fever
What does B. burgdorferi cause?
Lyme dz
How does B. hermsii develop? What symptoms are seen? What is the treatment?
- Mammalian reservoirs - squirrels, chipmunks, wild rodents. Vector is a tick.
- After 2-15 day incubation, patients have high fever, shaking, chills, headache, & fatigue
- Then nausea, vomiting, muscle aches, abdominal pain; extensive damage to liver, spleen, heart, kidneys, & cranial nerves.
- Parasite changes & immune system tries to control it - recurrent relapses
- Treatment of choice is tetracycline
How is lyme dz transmitted? Is it common? Describe the syndrome.
- Transmitted by the Ixodes tick - black-legged deer ticks
- Most common vector-borne disease in the US
- Nonfatal, slowly progressive syndrome that mimics neuromuscular & rheumatoid conditions
Cycle of Lyme dz
1. Newly hatched larvae become infected when they feed on small animals such as mice, which harbor the spirorochete. The larvae continue development through this year
2. In the second year the larvae molt into the nymph, an aggressive feeding stage
3. the nymph takes blood from a number of hosts, including deer and humans
4. On deer, the nymph matures into adult male and female ticks which mate. The females lays eggs in plant litter, where they hatch and once again begin the cycle
S/S of Lye dz
- 70% get a bull's-eye rash called erythema migrans
- Fever, headache, stiff neck, & dizziness
If untreated what can lyme dz progress to?
If untreated can progress to cardiac damage, neurological symptoms and polyarthritis
What is the treatment and prevention of Lyme dz?
- Treatment: doxycycline for 8 years and above; amoxicillin for those younger than 8
- Insect repellant containing DEET to control ticks is recommended as prevention.
Describe the lesion of lyme dz.
Note the flat, reddened rings in the form of a bull's eye.
Primary lesions often give rise to large numbers of secondary lesions in other locations.
How to remove a tick.
- Use fine-tipped tweezers to grasp the tick as close to the skin's surface as possible.
- Pull upward with steady, even pressure. Don't twist or jerk the tick; this can cause the mouth-parts to break off and remain in the skin. If this happens, remove the mouth-parts with tweezers. If you are unable to remove the mouth easily with clean tweezers, leave it alone and let the skin heal.
- Dispose of a live tick by submersing it in alcohol, placing it in a sealed bag/container
Curved, gram neg rods
Curviform bacteria
What generally causes enteric dz? and what are their characteristics?
Vibrio - comma-shaped rods, single polar flagellum
Campylobacter - short spirals or curved rods; one flagellum
Helicobacter - curved rods with several polar flagella
What are the three pathogens of the vibrio species? Where are they found and when do infections usually occur? How are they transmitted ?
- Three pathogens - Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus
- All three are found in saltwater and infections usually occur during the spring and summer
- Transmission is either by consumption of contaminated shellfish or traumatic injury associated with infected water
What is cholera caused by? How is it contracted? Where does it infect?
- The disease cholera is caused by toxigenic strains of V. cholerae (01 and 0139 serotypes)
- Ingested via contaminated food or water
- Infects surface of small intestine, non-invasive
What is the hallmark sign of cholera? What does it result in? How is it treated?
- Hallmark of cholera is severe, watery diarrhea with mild to severe dehydration due to toxin production
- Cholera toxin causes electrolyte & water loss through secretory diarrhea ("rice water" stools)
- Resulting dehydration leads to muscle, circulatory, & neurological symptoms
- Treatment: oral or IV rehydration, tetracycline
What does Vibrio parahaemolyticus cause? What do patients present with?
- Causes a gastroenteritis from raw seafood, shrimp, tuna, squid, crabs and others
- Disease is usually self-limited; dehydration is not as severe as with V. cholerae
- Patients present with explosive, watery diarrhea, abdominal pain, fever
What does Vibrio vulnificus cause?
- Gastroenteritis usually from raw oysters; poor outcome in patients with diabetes, liver disease, and alcohol abuse
- Also causes wound infections, e.g. cellulitis, in the setting of contaminated saltwater that carry a high mortality rate if not treated early
What is the tx for Vibrio parahaemolyticus
and Vibrio vulnificus?
tetracycline and rehydration
What is an important cause of bacterial gasteroenteritis worldwide? What is the incubation period? What is it ingested from?
- Campylobacter jejuni
- Incubation period of 1-7 days
- Ingested via contaminated chicken, water, other meats
Where does the C. jejuni attack? What are the symptoms?
- Reach mucosa at the ileum near colon; adhere, burrow through mucus and multiply
- Symptoms of headache, fever, abdominal pain, and bloody diarrhea
- Heat-labile enterotoxin CJT causes most of the symptoms.
What is a serious sequlae of C. jejuni? What are most cases due to? What is the treatment?
- Serious sequelae following C. jejuni infection include Guillian-Barré syndrome
- Antigenic similarities between the LPS of some serotypes of C. jejuni and human myelin proteins are thought to be responsible
- Most cases due to consumption of undercooked poultry, though contaminated milk, water, and other meats have been implicated
- Treatment - erythromycin and fluid replacement
What does chloramphenicol cause? What does it treat?
- Agranulocytosis.
- Treats brain abscess and typhus
What does H.pylori cause? How is it transmitted? What is it resistant to?
- Causes 90% of stomach & duodenal ulcers, also a factor in gastric adenocarcinomas
- Probably transmitted from person to person via fecal-oral route.
- Able to inhabit the human stomach (resistant to gastric acid)
What test is used for H. pylori?
Produces large amounts of urease which can be measured (urea breath test)
How is a dx made for H. pylori? What is the tx?
- Diagnosis by biopsy, breath test or antibody test of serum.
- Treatment by triple therapy provides a 95% cure rate (in areas where H. pylori is not resistant to clarithromycin)
- Proton pump inhibitor + amoxicillin + clarithromycin - all BID for 10 to 14 days
Rickettsia. What are involved in its life cycle? How is it treated?
- Obligate intracellular parasites with a gram negative cell wall
- Non-motile pleomorphic rods or coccobacilli
- Ticks, fleas & louse are involved in their life cycle
- ALL species of this genus have a tropism for endothelial cells - enter endothelial cells & cause necrosis of the vascular lining - vasculitis, vascular leakage & thrombosis
- Treated with tetracyclines such as doxycycline
What are groups of Rickettsioses?
Typhus group - epidemic and endemic typhus
Rocky Mountain Spotted Fever
Ehrlichiosis
Anaplasmosis
Epidemic typhus
- Rickettsia prowazekii
- Harbored by human body lice
- Rare in US
Endemic or murine typhus. How is it transmitted? What are the symptoms?
- Rickettsia typhi
- Harbored by mice & rats
- Transmitted to humans via flea bites
- Symptoms include fever, headache, muscle aches, malaise and rash.
- Endemic in the US in the Southeast, Gulf coast and Southwest
Rocky mountain spotted fever. What is it carried by?
Rocky Mountain spotted fever - R. rickettsii

Zoonosis carried by dog & wood ticks
The transmission cycle in Rocky mountain spotted fever?
- Dog and wood ticks are the principal vectors. Ticks are infected from a mammalian reservoir during a blood meal.
- Transovarial passage of Rickettsia rickettisii to tick eggs serves as a continual source of infection within the tick population
- A tick attaches to a human, embeds its head in the skin, feeds and sheds rickettsias into the bite.
Pathogenesis of R. rickettsii
- R. rickettsii is engulfed by endothelial cells via endocytosis and takes over the cell's machinery
- Spreads through the bloodstream or the lymphatics and causes widespread damage to the small blood vessels (vasculitis)
- Leads to hemorrhage, increased vascular permeability, edema, and the activation of inflammatory and coagulation mechanisms
S/S of rocky mountain spotted fever. What is the hallmark?
Signs/Symptoms:
- Onset usually between 2 and 7 days of exposure
- Fever, chills, headache, N/V, myalgias
- Distinct spotted rash occurs within 2-5 days of onset of fever
~Hallmark of RMSF is a blanching erythematous rash with macules (1 to 4 mm in size) that become petechial over time
~Rash begins on the ankles and wrists and spreads to the trunk
~Inclusion of palms and soles is highly characteristic of RMSF, but usually occurs in later-stage disease
Ehrlichiosis
Caused by E. chaffeensis, which is transmitted by the Lone Star tick
Occurs in the southeastern and south central US
Anaplasmosis
Caused by Anaplasma phagocytophilum, which is transmitted by the Ixodes tick
Most cases occur in Wisconsin, Minnesota, Connecticut and New York
What do both Ehrlichiosis and Anaplasmosis cause? how do they present? How is it treated?
- Both diseases cause acute, febrile, systemic illnesses similar to Rocky Mountain spotted fever but also have leukopenia, anemia, hepatitis
- Both disease forms have similar presentations - fever, headache, muscle aches, nausea, vomiting; both can progress to pneumonia, meningitis, renal failure and death
- Human monocytic ehrlichiosis occasionally manifests with a rash and also carries a higher mortality rate
- Both usually last 1 to 2 weeks; treated with doxycycline to prevent complications
What does Coxiella burnetii cause? How is it transmitted?
- Pleomorphic gram negative rod, causes Q fever
- Commonly causes pneumonia, hepatitis
- Obligate intracellular parasite but produces an unusually resistant spore
- Q fever is a zoonosis transmitted to humans most commonly via cattle, sheep, goats, and dogs bitten by ticks harboring C. burnetii.
- Transmission is via inhalation of C. burnetii from products of conception, manure, or living along a road used for sheep or cattle drive; can also be transmitted via milk, cheese, or wool from infected animals
What is unique about Coxiella burnetti?
The vegetative cells of Coxiella burnetii produce unique endospores that are released when the cell disintegrates. Free spores survive outside the host and are important in transmission.
What does lack of treatment of C. burnetii lead to? how do you dx it? How is it treated? Is there a vaccine?
- Lack of treatment results in chronic form of disease, which leads to endocarditis
- Diagnosis via IFA, ELISA, or antibody titers
- Treated with Doxycycline x 2 weeks
- A vaccine is available.
Trench fever
Caused by Bartonella quintana; spread by human body lice
Cat- scratch dz
caused by Bartonella henselae; a lymphatic infection associated with a clawing injury by cats
Carrion's dz
endemic in South America, caused by Bartonella bacilliformis, spread by biting sand flies
How does cat scratch dz start? What is the tx?
- Starts as a small patch of papules or pustules, then progresses to tender, regional lymphadenopathy
- Most cases of cat scratch disease resolve without treatment, but azithromycin has been shown to decrease lymph node volume more rapidly than no treatment at all
Chlamydia trachomatis.
- STD, neonatal and ocular disease
Chlamydophila pneumoniae
atypical pneumonia
Chlamydophila psittaci
zoonotic atypical pneumonia usually transmitted from parrots, macaws, cockatiels, or parakeets, but has been isolated in over 100 different species of birds
What is a trachoma? Ocular trachoma?
- Attacks the mucous membranes of the eyes, genitourinary tract
- Ocular trachoma - severe infection of the epithelial cells of the eye, causing deformity of eyelids & cornea, can cause blindness
When does Inclusion Conjunctivitis occur?
occurs as babies pass through birth canal; prevented by prophylaxis
What can result from an untreated Chlamydial STD?
urethritis, cervicitis, salpingitis (PID), infertility, scarring
Where does lymphogranuloma verereum invade? What does it lead to?
- Invades the lymphatic tissue of the genitalia
- Leads to disfiguring disease of the external genitalia & pelvic lymphatics
The pathology of primary ocular chlamydial infection.
- Ocular trachoma, an early pebble like inflammation of the conjunctiva and inner lid in a child
- Inclusion conjunctivitis in a newborn. Within 5-6 days, an abundant , watery exudate collects around the conjunctival sac. This is currently the most common cause of ophthalmia neonatorum
Describe the clinical appearance of advanced lymphogranuloma venereum.
A chronic local inflammation blocks the lymph channels, causing swelling and distortion of the external genitalia.
What is the most commonly transmitted STD in both men and women?
Chlamydia trachomatis
How do males present with Chlamydia trachomatis?
Males - nongonococcal urethritis (NGU) - can cause dysuria, mild discharge but up to 40% are asymptomatic
How do females present with Chlamydia trachomatis?
Females - cervicitis or urethritis - can elicit a yellowish-whitish discharge and/or dysuria but up to 90% are asymptomatic
How do you identify Chlamydia trachomatis? How do you treat it?
- Identification methods include direct nucleic acid antigen testing (NAAT) from patient swab samples
~Male - urethral swab or urine
~Female - cervical swab
~Sensitivity of 80-90% and specificity of 95-100%
~Direct immunofluorescent testing, ELISA testing
- Treatment with azithromycin (first line) or doxycycline
The direct dx of chlamydial infection.
- A specimen stained with monoclonal antibodies bearing a fluorescent dye. Infected cells glow a bright apple green.

- Direct Giemsa stain of an eyelid scraping in inclusion conjunctivitis. Large inclusion body represents a phagosome packed with chlamydia in various stages of development
Chlamydophila pnemoniae. What are the symptoms? How do you dx it? Treatment?
- Causes an atypical pneumonia that is serious in asthma patients
- Symptoms are similar to infection with Mycoplasma pneumoniae (fever, dry cough, sore throat) but C. pneumoniae also causes hoarseness/laryngitis
- Diagnosis: culture, complement fixation, IgM antibody titers
- Treatment: doxycycline x 2 weeks for adults; azithromycin for children and pregnant women
Chlamydophila psittaci. What can it lead to? How is it transmitted? Dx and Tx?
- Causes atypical pneumonia in humans
- Can lead to endocarditis, myocarditis, encephalitis
- Transmitted to humans from bird vectors
~Via bird feces, bird bites, or mouth-to-beak contact
- Diagnosis and Treatment are same as for C. pneumoniae
What is unique to the Mycoplasma species?
Naturally lack cell walls, highly pleomorphic
M. pneumoniae
primary atypical pneumonia
M. genitalum & Ureaplasma urealyticum
historically regarded to be weak sexually transmitted pathogens but M. genitalum now linked to PID in women and urethritis in men.
Ureaplasma urealyticum
also implicated in urethritis, prostatitis, and as an opportunistic pathogen of the fetus, causing cases of miscarriages and stillbirths
How do you dx the mycoplasma species?
Diagnosis of all via serology - EIA, immunofluorescence, complement fixation
Most common cause of atypical community-acquired pneumonia especially in healthy patients younger than 40. What is it known as?
Mycoplasma pneumoniae

Known as walking pneumonia
Symptoms of Mycoplasma pneumoniae? CXR? Treatment?
- The disease usually has a prolonged, gradual onset with:
~Fever; malaise; a persistent, slowly worsening dry cough; headache; chills, and sore throat
~Chest XR usually shows patchy bilateral infiltrates
- Treated with doxycycline or azithromycin
The morphology of mycoplasmas
- A scanning electron micrograph of Mycoplasma peumoniae
(bar= 0.5um). Note pleomorphic shape and elongate attachment tip (arrow). The cells use this to anchor themselves to host cells.

- M. pneumoniae becomes a membrane parasite that adheres tightly and fuses with the host cell surface. This fusion makes destruction and removal of the pathogen very difficult.