Lecture organization Some Rickettsiae and spirochetes are zoonoses Which lecture covers them?

m? Rickettsieae and spirochetes or Zoonoses?

Which topics, which lectures

Rickettsiae & spirochetes Rocky Mountain Spotted Fever Rickettsial biology Rickettsioses Lyme Zoonoses Tick biology Other tickborne diseases

Why Rocky Mountain Spotted Fever?

Prototype rickettsiosis Main reason for deaths?

Etiology: Invertebrates
1. Rickettsia rickettsiae 2. Ticks (tolerate infection) Dermacentor andersonii, D. variabilis (hard) Transstadial, transovarial transmission

Etiology: Vertebrates
3. Reservoir Small rodents (squirrels) Tolerate infection 4. Humans Intruders into wildlife cycle Dead-end hosts

Etiology Microbe Vector Reservoir Host R. rickettsii Tick Rodents Intruder

Rocky Mountain Spotted Fever, 4 dots/case, US, 1999

Rocky Mountain Spotted Fever, Monthly Cases, US, 1999

125 100 75 50 25 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Rocky Mountain Spotted Fever, cases/100,000, by age, US, 1999

0.2

0.1

0 <1 1-4 5-14 15-24 25-39 40-64 > 64

Person
Outdoor activity Peak age 5-9 Mortality highest in elderly

Rocky Mountain Spotted Fever, cases/100,000 per year, US

0.6 0.4 0.2 0 1955

1965

1975

1985

1995

Development of illness Inoculation Rickettsemia Endothelial localization Vasculitis

Clinical recognition
Rash Fever Headache Other

Fever and headache Fever 102 to 105 degrees 2 to 3 weeks without treatment Headache: severe

Clinical recognition
Rash Fever Headache Other

Clinical recognition
Rash Fever Headache Other

Laboratory diagnosis
Skin biopsy: immunofluorescent stain Serology Weil-Felix archaic Immunofluorescent antibody No growth on routine culture

Prevention
Vector control impractical Vaccine unavailable So . . . caution outdoors Long clothing Skin inspection

Rocky Mountain Spotted Fever

Physician suspicion crucial R. rickettsii, ticks Not just Rockies Vasculitis Rash, fever, headache Doxycycline, look for ticks

Rickettsiae & spirochetes

Rocky Mountain Spotted Fever Rickettsial biology Other rickettsioses Spirochetes

Rickettsial biology: Bacteria . . . or viruses?

Antibacterials Most need host cells Cell membrane DNA and RNA Metabolism Fission

Lives free Antibiotic Rigid wall DNA and RNA Makes ATP Ribosomes

V 0 0 +/0 0 0

C 0 + +/+ 0 +

M + + 0 + + +

R +/+ + + + +

B + + + + + +

Order Rickettsiales Family Rickettsiaceae Tribe Rickettsiae Genus Rickettsia Genus Coxiella Genus Rochalimaea Family Bartonellaceae

Rickettsia Ehrlichia Bartonella Coxiella

Rickettsial groups
Spotted fever group Rocky Mountain Spotted Fever Other spotted fevers Rickettsialpox Typhus group Epidemic typhus, Brill-Zinsser Murine, scrub typhus

Rickettsial properties
Coccobacillary, < 1 micron Gram stain poorly, need Gimenez Have metabolic apparatus Use host ATP, NAD, CoA Extracellular survival poor, need vectors

Rickettsial biology
Bacteria, not viruses Clinical grouping Small, poor on Gram Have metabolic paths Perish outside cells

Rickettsiae & spirochetes

Rocky Mountain Spotted Fever Rickettsial biology Other rickettsioses Spirochetes

Other rickettsioses
Characteristics of a typical rickettsial disease Diseases other than Rocky Mountain Spotted Fever

Rickettsial epidemiology
Tick vectors (exceptions: typhus, rickettsialpox) Humans dead-end hostss (exception: epidemic typhus) Mid-spring/mid-summer peak Vector digestive tract

Typical rickettsial illness

Inoculation eschar (exception: Rocky Mountain Spotted Fever) Rickettsemia Endothelial growth Vasculitis 1-2 week incubation Rash, fever, headache

Rickettsial diagnosis
Must suspect clinically Immunoflorescent stained skin biopsy Weil-Felix pass Serology usually (but delay in getting results) Isolation hazardous Rule out others

Rickettsial control
Public health Reporting Vector/reservoir No vaccines

Rickettsial diseases other than Rocky Mountain Spotted Fever Other spotted fevers (in other parts of world) Rickettsialpox (urban, from mice and mites) Typhus group (epidemic typhus from lice)

Other rickettsioses Vector (often tick) Eschar, rickettsemia Vasculitis, serologic test Includes spotted fevers, rickettsialpox, typhus group

Rickettsiae & spirochetes

Rocky Mountain Spotted Fever Rickettsial biology Other rickettsioses Spirochetes

Vincents infection/Trench mouth Necrotizing ulcerative gingivitis Synergistic gum infection Occurs in poor oral hygiene, malnutrition, immunocompromise Penicillin, oral hygiene

Relapsing Fever Epidemic Endemic

B. recurrentis Lice Human-lice E. Africa, Andes Borrelia spp Ornithodoros tick Human intruder Worldwide: High, warm, humid

Relapsing fever pathogenesis Spirochetemia Sequestration Antigenic modification Widespread (liver, spleen, CNS, heart, GI, kidney)

Relapsing fever presentation

Abrupt fever, malaise, headache Arthralgia, cough, photophobia Conjunctival suffusion Petechiae Abdominal tenderness

Relapsing fever
Recovery in 3-6 days Relapse in 7-10 days Untreated, 40% die Blood smear positive 70% Tetracycline, chloramphenicol

Lyme disease, United States

Lyme disease by county, US, 1999

00
0

1-14

> 15 cases

Lyme disease, by county, 1996

North Central Northeast

5-9

10-29 >30

Lyme disease cases by month, US, 1999

3000 2000 1000 0
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

Erythema chronicum migrans

Early Da-wk ECM Da-mo Nerve Joint Heart

Late Mo-yr Joint Fatigue

Lyme diagnosis and treatment

Clinical, with special serology Treatment depends on stage Doxycycline, amoxicillin, cefuroxime IV penicillin or ceftriaxone (later)

Tick repellent DEET Skin, clothing CNS toxicity (directions) Permethrin: Clothing

Doxycycline vs. placebo after tick bite, N Engl J Med 2001 Doxy EM OK 1 234 239 Event 47 17 OK 109 136

Placebo 8

No one developed extracutaneous Lyme disease. Advice: Treat in high-risk areas.

Key points: Lyme disease Tickborne B. burgdorferi Local: Erythema migrans Dissem: Heart, nerve, joint Persist: Fatigue, joint Doxycycline, ceftriaxone

Frontiers of prevention Vaccine: Withdrawn Tick avoidance

Many spirochetes tickborne

Not tickborne Syphilis: Sex Leptospirosis: Animal urine; early conjunctival suffusion, later liver & kidneys Tickborne: Borrelia relapsing fever, change antigens & relapse

Spirochetal disease parallels

Lyme (& Syphilis) Initial rash: Erythema chron. mig. 2 stage: Nerves, heart, joints Late stage: Arthritis, fatigue Treatment: Penicillin, tetracycline

Rickettsia and spirochetes

Rocky Mountain Spotted Fever Headache, rash, fever Tickborne No growth on routine culture Doxycycline

Rickettsia and spirochetes Other rickettsia Poor extracellular survival Suspect clinically Typhus: humans, lice

Spirochetes Sequestration, antigenic change in relapsing fever Erythema chronicum migrans, tick in Lyme