A multi-system infection is caused by an agent that can…
1) disseminate (spread) to infect multiple tissues
2) Replicate and/or persist in those tissues
3) Cause disease in multiple tissues
What is the difference between bacteria that MUST cause multisystem infection vs. those that are opportunists
The opportunists are bugs that are artificially introduced into places they don’t normally go
Several Genera of opportunists - commensal flora
Normally cause problems primarily in immunocompromised patients
Professional multisystem pathogens
All can cause disseminated infections in immunocompotent hosts
Blood and tissue donors are screened for which types of multisystem pathogen?
Professionals
Important mechanisms used by professionally multisystem bacteria
Immune evasion - Antigenic variation - Serum resistance - Cloaking Invasiveness - cell invasion - tissue invasion
Antigenic Variation in Lyme disease Borrelia
Recombination of VIs locus (surface protein)
Serum resistance in Borrelia
Complement inactivation - binding to factor H
Cloaking in Borrelia
Binding of fibronectin and other plasma proteins
Opportunists route of entry:
Disruptions to physical barriers constituting first line of host defenses
SYSTEMIC disruptions to host defenses maybe be due to chemotherapy, irradiation, immunosuppressive therapy
Professional pathogens route of entry
Overcoming physical barriers and dissemination are essential to biology of organism
The most prevalent multisystem bacterial infections in the US
Vector borne:
NON-vector borne:
Vector Borne: Anaplasmosis; Ehrlichiosis; Rocky Mountain Spotted Fever; Lyme Disease
NON-vector borne: Syphilis
Key information for Vector-Borne Infections
Biological transmission: specific life stage in vector; transmission through oral or fecal routes
Vector Competence: The ability of a vector to transmit pathogen
Transstadial transmission:
When a pathogen is transmitted or maintained in the different life stages of the same individual vector
Transovarial transmission
WHen a pathogen is transmitted from one vector generation to the next
Key information for Vector-Borne Infections
LOCATION
SEASON
Mosquito-Borne Diseases in US
NONE are bacterial
Tick Borne Diseases in Wisconsin
Lyme Disease
Human granulocytic anaplasmosis
New: Ehrlichia muris like species Ehrlichiosis
Larvae Ticks are usually __ _____ and have __ legs
Nymphs and adults have ___ legs and are ______ ______
not infected; 6; 8; potentially infected
Pathogens are acquired by ticks from _____ ______ during first bloodmeal as larvae
reservoir animals
____ to _____ _____ is peak season for nymphs to transmit infections
Spring; Early Summer
____ is secondary peak of infection from adults
Fall
Why are the shapes of the incidence curves for RMSF and ehrlichiosis somewhat different from those of Lyme disease and anaplasmosis?
Geographic distribution of vector ticks
What does Enzootic mean?
Endemic in animals (A. phagocytophilum)
Anaplasmosis
Structure:
Locaton/Secretion:
Invasion:
Structure: TINY gram negative coccobacillus
Locaton/Secretion: Obligate intracellular, replicates in vacuoles, no LPS, has type IV secretion
Invasion: Invades neutrophils, inhibits apoptosis
Enzootic cycle of E. Chaffenisis (Reservoir Host)
Deer
Ehrlichiosis:
Agents:
Structure:
Invasion/Secretions:
E. Chaffeensis - transmitted by Amblyomma americanum
Emerging: E. muris-like
Structure: Tiny gram negative coccobacilli
Invasion/Secretions: Obligate intracellular, invade monocytes and neutrophils; replicates in vacuoles - Type IV secretion
Anaplasmosis and Ehrlichiosis CLINICAL
Incubation is 1-2 weeks Most Common Signs/Symptoms: - Fever/Chills - Headache - Anoresia - Leukopenia - Increased liver aminotransferases
Anaplasmosis and Ehrlichiosis Diagnosis
Morulate in neutrophils or monocytes, seen in blood smear
May be difficult to find in smear
PCR can be used to identify organism based on temperature
Serology at 30 days is marker of infection
Anaplasmosis and Ehrlichiosis Therapy
Oral doxycycline (also for lyme disease) If under 8 or pregnant: doxycycline 3 days past defervescence Rifampin is alternative
Enzootic cycle of Rickettsia Rickettsii
Eggs are infected Hatch into infected larvae Small rodents = bloodmeal Infected nymph Infected adult tick Human = incidental host
Rocky Mountain Spotted Fever Agent:
Rickettsia rickettsii
Rickettsia Rickettsii
Structure:
Invasion:
Secretion:
Structure: Tiny gram negative coccobacilli - DOES HAVE LPS AND PEPTIDOGLYCAN
Invasion: Obligate intracellular, replicates in cytoplasm, may also invade nucleus - bacterium escapes phagosome by forming actin tail
Secretion: Type IV secretion
Rocky Mountain Spotted Fever Rickettsiosis: CLINICAL
Incubation time: 1 week
Fever, malaise, sever headache, myalgia, anorexia…
Rash 3-5 days after onset of illness: starts on ankles, wrist, forehead; small red macules progress to maculopapules then to petechiae
Thrombocytopenia, pro-coagulant coagulopathy
Rocky Mountain Spotted Fever Diagnosis
CDC: There is no test available at this time that can provide a conclusive result in time to make important decisions about treatment
Rocky Mountain Spotted Fever: Therapy
Oral Doxycycline
Chloramphenicol if patient has allergy to tetracyclines or if patient is pregnant and disease is mild
Lyme Disease: Epidemiology
Most common vector-borne infection in Northern Hemisphere
Lyme disease Enzootic Cycle
Humans - Inadvertent host
Larvae/Nymph host: small rodents
Adult tick host: Deer
Lyme Disease
Agent:
Structure:
Invasion:
Agent: Borrelia burgdoferi
Structure: Gram negative spirochete, extracellular, no LPS, toxins, special secretion systems
Invasion: Requires >36 hours of tick bite for transmission; antigenic variation, complement evasion
Lyme Disease: Clinical Early localized: Early, disseminated: Late: Size of Lesion:
Early localized: Days - 2 weeks
Early, disseminated: Days - months
Late: Months - Years
Size of Lesion: > 5cm
Lyme Disease:
Early Disseminated:
Late:
Early Disseminated: Fever, malaise, secondary EM, AV nodal block, arthralgia, facial palsy
Late: Arthritis, encephalopathy
Lyme Disease: Diagnosis
Current recommendations:
- Clear EM lesion - Sufficient to start therapy
IF no clear EM lesion at presentation (> 3 weeks)
- Antibody titer (IgM vs IgG - strain to strain variability)
- ELISA, then immunoblot
Lyme Disease Serology
Not necessary if there is a clinical diagnosis of EM rash without evidence of systemic infection
IgM typically becomes positive in 2-3 weeks
IgG typically becomes + in 3-6 weeks, continues expanding
Both IgM and IgG may remain positive for years after treatment
Lyme Disease: Therapy
Preferred: oral doxycycline for early, or with no CNS involvement
amoxicillin for patients who are pregnant or under 8
CNS involvement - IV ceftriaxone
Vector Borne Infections - Take home points
Geography and Season are Key
Symptoms may vary with individual patients
Symptoms are often non specific
Few specific virulence factors identified
Difficult to grow in culture (not useful for diagnosis)
Diagnoses rely on taking a thorough history of the patient
Syphilis - Causative agent
Treponema Pallidum
Enzootic cycle of Treponema Pallidum
THERE IS NONE
Syphilis
Agents:
Treponema pallidum pallidum - world wide STD
Treponema palidum endemicum: regions of Africa, not STD
Lots of oral treponemes
Syphilis clinical:
Primary - lesion called a “shanker” - painless - highly infectious
Secondary - Several highly infectious lesions
Tertiary (30%) (Gumma, Cardiovascular syphilis, neurosyphilis)
Syphilis: Secondary
6 weeks - 6 months after primary; lasts 4-12 weeks
Difuse, non-itchy rash all over
Condyloma latum - wart-like infectious lesion
Syphilis: Latent
Patient is asymptomatic
Can last years to decades
Syphilis: Tertiary
Tabes dorsalis; loss of sensory and motor neuron function leading to intense pain, personality changes, dementia, ataxia, deterioration of optic nerves leading to blindness
Gummas (granuloma like lesions)
Aortic aneurism
DAMAGE IS DUE TO HOST RESPONSE
Syphilis: Congenital
Transmitted from mother to child during pregnancy or birth
Some symptoms/signs in child:
- Failure to thrive, fever, no bridge to nose
- rash of mouth genitals and anus
Syphilis: Diagnostics
Non-specific, screening serology: - Rapid Plasma Reagin (RPR) Venereal disease Research Laboratory - Anti-cardiolipin test Specific, confirmatory serology (fluorescent antibody absorbed test)
Syphilis: Therapy
Preferred: Long Acting Penicillin for primary and secondary; IV for tertiary
Alternatives: Ceftriaxone, Erythromycin, Doxycycline
Bacteria that cause multisystem infections TAKE HOME POINTS
Cause disseminated infection and disease involving multiple organ systems including CNS in intact, immunocompetent individuals
Are available to avoid the host immune response to cause relapses or persistent infection
Should be treated with antibiotics with high tissue penetrance
Diagnostics do not rely on culture