15 - Multisystem Infections

Question 1

What is a multisystem infection?

Answer 1

An infection caused by an agent that can:

1: Disseminate (spread) to infect multiple tissues, usally via blood or lymphatics
2. Replicate and/or persist in mult. tissues.
3. Cause disease (symptoms/pathology) in multiple tissues.

Question 2

What are opportunistic bacteria that cause multisystem infections?

Answer 2

Bugs that are artifically introduced into places where they don’t normally go (eg CSF a normally sterile site), spread and survive, often in compromised hosts.

Often are commensal flora or environmental bacteria.

MAY disseminate and cause multisystem infections if the host is compromised.

Question 3

What is the role of “professional” multisystem pathogens?

Answer 3

All disseminate and cause multisystem infections in immunocompetent hosts.

This ability is often a key feature of the lifestyle (some are transmitted by an arthropod vector).

Question 4

What are the routes of entry that opportunistic multi-system bacterial pathogens can use?

Answer 4

Disruptions to physical barriers: constituting a first line of host defense (indwelling lines, IV drug use, surgery, ventilators).

Systemic disruptions to host defenses: may be due to chemotherapy, irradiation, immunosuppressive therapies.

Not essential to lifestyle of these bacteria.

Question 5

Describe the routes of entry and disruptions to host defenses that can lead to multi-system bacterial infections by “professional” multi-system pathogens?

Answer 5

Overcoming physical barriers and dissemination are often ESSENTIAL to the biology of the organism.

Multi-system infections in previously healthy people are usually caused by bacteria that by nature evade defenses and disseminate.

Question 6

What are some mechanisms used by professional multisystem bacteria that contribute to its virulence?

Answer 6

Immune evasion or disruption: antigenic variation or absence, serum resistance (resist complement), cloaking themselves with host protein to avoid recognition.

Invasiveness: cell invasion and dissemination/tissue invasion

Question 7

What are the vector-borne PROFESSIONAL multi-system bacterial infections frequently seen in the US? What about non-vector-borne?

Answer 7

Vector borne:

• Anaplasmosis (human granulocytic anaplasmosis)
• Ehrlichiosis (human monocytic ehrlichiosis)
• Rocky mountain spotted fever
• Lyme disease

Non-vector-borne: syphilis

Question 8

Where can vector-borne infections occur?

Answer 8

Pretty much everywhere; BUT specific vectors and therefore diseases vary with geographic location.

Question 9

What is biological transmission? What is vector competence?

Answer 9

When a pathogen has a specific life stage in a vector (ie colonizes a specific site and alters its gene expression in the vector).

The ability of a vector to transmit a pathogen: reflects ability to acquire, maintain, and transmit a pathogen which are three distinct processes.

Question 10

What is transstadial transmission? What are examples of disease in which this occurs?

Answer 10

When a pathogen is transmitted or maintained in the different life stages of the same individual vector

Lyme disease, anaplasmosis, ehrlichiosis

Question 11

What is transovarial transmission? What are examples of diseases in which this occurs?

Answer 11

When a pathogen is transmitted from one vector generation to the next

Rocky mountain spotted fever rickettsiosis.

Question 12

What agent causes Rocky Mountain Spotted Fever? What are its characteristics? What is the vector and reservoir?

Answer 12

Rickettsia ricketsii -

Ticks are the vector and reservoir

Tiny gram-negative intracellular coccobacilli - replicates in the cytoplasm.

Question 13

What is the agent that causes anaplasmosis? What are its characteristics? What are the endemic regions for this disease? What is the vector?

Answer 13

Anaplasmosis caused by anaplasma phagocytophilum - gram negative intracellular bacilli.

Endemic in north america, europe, and asia.

Ixodes ticks

Question 14

What is the classic presentation of anaplasmosis? What is the treatment?

Answer 14

Fever, chills, headache, myalgias, malaise.

Treat with doxycycline (even kids).

Question 15

What are the key virulence factors associated with anaplasmosis?

Answer 15

Cell invasion and absence of PAMPS recognized by TLRs.

Type IV secretion system, intracellular replication in vacuole in PMNs, no LPS or peptidoglycan.

Question 16

How would you diagnose anaplasmosis in the lab?

Answer 16

Thick or thin blood smear, serology.

Culture is difficult so it’s not done in clinical labs.

Question 17

What is the agent that causes Ehrlichiosis? What are its characteristics? Where is this diseases endemic? What are the vectors?

Answer 17

Several Ehrlichia species: tiny gram negative intracellular coccobacilli.

Endemic in north america, europe, and asia.

Vectors: dermacentor, amblyomma, and ixodes ticks.

Question 18

What is the classic presentation of Ehrlichiosis? How is it treated?

Answer 18

Fever, chills, headache, myalgias, and malaise.

Treat with doxycycline (even kids or pregnant).

Question 19

What are the key virulence determinants of Ehrlichiosis? How is it tested in lab?

Answer 19

Type IV secretion system, obligate intracellular bacteria that replicate in vacuoles in monocytes; no LPS or peptidoglycan.

Cell invasion and absence of PAMPS recognized by TLRs.

Thick or thin blood smear in which you see morulae (intracell colonies) in PMNs or monocytes. Serology. Culture is difficult so not done.

Question 20

What is the agent responsible for Lyme disease? Where is this disease endemic? What is the vector?

Answer 20

Borrelia burgdorferi, B. garinii, B. afzelii - gram negative extracellular spirochetes that replicate outside of the host cell.

Endemic in north america, europe, and asia.

Vector are ticks.

Question 21

What is the classic presentation of Lyme disease? What can this sometimes be confused with?

Answer 21

Non-itchy, non-tender erythema migrans lesion (usually bullseye but not always), facial palsy, oligoarticular arthritis, heart block.

This contrasts from STARI (Southern Tick Associated Rash Illness) which may be a borrelia infection that cannot disseminate in humans.

Question 22

What are key virulence factors associated with lyme disease (borrelia)?

Answer 22

Antigenic variation, tissue invasion, complement resistance, adhesions, do NOT reach high titers in blood, no LPS.

Absence of PAMP recognized by TLR. Flagella hidden.

Question 23

What is the treatment for lyme disease?

Answer 23

Doxycycline, amoxicillin, ceftriaxone if CNS involvement is suspected.

Question 24

How would you diagnose Lyme disease in lab?

Answer 24

Clear erythema migrans and history of likely or known tick attachment.

Lesion, can be confirmed by serology with two steps:

• ELISA screen followed by immunoblot confirmation of positive ELISA
• IgM should be positive within 2-3 weeks, IgG within 3-4 weeks.

Culture difficult so not done.

Question 25

All vector-borne bacteria are gram _______. What is critical to remember when assessing a patient that may have a vector borne illness?

Answer 25

Gram Negative!!!

Endemic regions are critical to consider, as many vector-borne infections are only seen in endemic foci.

Question 26

What agent causes syphilis and what are it’s characteristics? What encounter results in syphilis?

Answer 26

Treponema pallidum subspecies pallidum - gram negative spirochete.

Human to human, STD or congenital.

Question 27

What is the multiphasic presentation of syphilis? What happens if this is untreated?

Answer 27

Initial painless lesion (chancre) at the site of inoculation, regional lymphadenopathy.

If untreated, goes to secondary infection: diffuse, non-itchy rash all over, including palms and soles, myalgias, arthralgias, fever, condyloma latum (wart-like lesion).

Question 28

What happens when secondary syphilis is left untreated?

Answer 28

Latency.

Then tertiary (tabes dorsalis): loss of sensory and motor neuron function, intense pain, personality changes, dementia, ataxia, optic nerve deterioration causing blindness, incontinence, degeneration of joints, gummas (non-infectious fibrous granulomas), aortic aneurism, aortic valve insuff., and tissue destruction.

Question 29

What are the key virulence factors associated with syphilis? Does it have peptidoglycan?

Answer 29

Antigenic variation, tissue invasion, few surface-exposed proteins, can bind human plasma proteins (maybe “cloaks”), proteases that degrade human proteins, and latency.

Syphilis DOES have PG.

Question 30

What is the treatment for syphilis?

Answer 30

Long half-life (long-acting) penicillins preferred (used in pregnancy too).

Doxycycline is alternative early.
Ceftriaxone in the 2nd and 3rd stage

Question 31

How is syphilis diagnosed in the lab?

Answer 31

Serology: RPR and VDRL are non-specific and anti-cardiolipin screening tests but fast and cheap. + results must be confiredwith fluorescent Ab absorbed test (FTA-ABS) or T. pallidum hemagglutanin assay (MHA-TP).

Sometimes these tests give false +.

These bacteria are not culturable.

Question 32

What are the different presentations of anthrax?

Answer 32

Cuteaneous: most common and least lethal, lesion becomes necrotic/hemmorhagic.

Inhalational and meningeal have high fatality rates and can cause fever, malaise, nausea, chest pain, headache, mediatinal widening on xray, meningitis.

Question 33

What are the intracellular bacteria that cause multi-system infections?

Answer 33

Anaplasma, Ehrlichia, Ricketsia

Question 34

What are the extracellular bacteria that cause multi-system infections?

Answer 34

Borrelia, Treponema

Question 35

What virulence is associated with rocky mountain spotted fever?

Answer 35

Obligate intracellular, replicates in cytoplasm, may also invade nucleus.

DOES have LPS and PG, type IV secretion system.

Cell invasion and absence of PAMP and TLR recognition.

Question 36

What is the onset of rocky mountain spotted fever? What are some symptoms?

Answer 36

“scary sudden”

Fever, malaise, severe headache, myalgia, anorexiam abd. pain, nausea.

Rash 3-5 days after onset of illness that starts on ankles, wrists and forehead.

Question 37

What are clinical signs of rocky mountain spoted fever? What is the treatment?

Answer 37

Thrombocytopenia, pro-coagulant coagulopathy, leukopenia, elevated aminotransferases, hyponatremia.

Oral doxycycline.

No test available to get a conclusive result about this disease.

Question 38

What is congenital syphilis?

What are characteristics? What is the treatment?

Answer 38

Transmitted mother to child during pregnancy or birth.

Failure to thrive, fever, no bridge to nose (saddle nose), rash of the mouth, genitals, or anus.

Notched teeth (hutchinson’s teach). Deafness, blindness, clouding or cornea, bone pain.

Treatment same as for adults.

Question 39

A 37 yo man limps into your office in Rhode Island in december complaining of pain in one knee which is swollen. He also has numbness and tingling in his hands and feet. He has a history of mild non-specific illness early in june with lingering malaise and headaches. He lives in a rural area near Connecticut border. What would you test him for?

Answer 39

Lyme disease, babesiosis, and human granulocytic anaplasmosis.