Umaporn Chantbuddhiwet , MD QSNICH

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Umaporn Chantbuddhiwet , MD
QSNICH
RICKETTSIOSES
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Bacteriology

• Definition of Rickettsiaceae family
• Small gram-negative bacteria, associated
• (or not) with arthropods and necessitating
• (or not) eukaryotic cells from growth
• 16 S r RNA sequence-based phylogeny

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Rickettsiales

• Intracellular alpha proteobacteria
• associated with eukaryotic hosts
• (arthropods or helminths)
• Obligate intracellular pleomorphic coccobacilli
• Multiply by binary fission
• zoonosis (except for R. prowazekii )
• Transovarian transmission

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Rickettsiae are traditionally divided into 3
groups

• Spotted fever group
• Typhus group
• Epidemic typhus R. prowazekii
• Murine typhus R. typhi
• Scrub typhus group
• Orientia tsutsugamushi

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Pathophysiology

• Rickettsia species escape rapidly from the
  phagosome to multiply within the cytoplasm
• Spotted fever rickettsiae motile in the
  cytoplasm through actin polymerization invade
  neighboring cells
• R.probazekii destruction of the host cell
• Target cell

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spotted fever group
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Spotted fever group

• Most tick - borne rickettsiosis
• R. akari (Ricketsialpox) mite
• R. felis flea
• Disease named by geographic distribution
• Rocky Mountain spotted fever
• Queensland tick typhus
• North asian tick typhus.
• Human are incidental host
• Natural host are small mammal
• wild rodents, mouse, dog

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• Prototype Rocky mountain spotted fever (RMSF)
• severe clinical manifestation
• Case fatality rate of 23
• R. rickettsii
• Fever, myalgia, headache and rash
• Meningitis, meningoencephalitis
• Renal failure
• pulmonary involvement
• Few reports in Thailand

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Reported RMSF cases per 1,000,000 populations/yr
in US (1981-1991)
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First cases of spotted fever group rickettsiosis
in Thailand

• Presented with fever, headache, lymphadenopathy
  and petechial maculopapular rash.
• Diagnosis by indirect fluorescent antibody test,
  indirect immunoperoxidase test and ELISA for
  spotted fever group.
• All response well to single dose of doxycycline.

Am J Trop Med Hyg 1994 Jun50(6)682-6
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typhus group
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Typhus group

• Epidemic typhus
• R. prowazekii
• Human - natural host
• Louse - vector and natural reservior
• Brill-Zinsser disease (recurrence years after 1st
  attack)
• Murine typhus
• R. typhi
• Natural host Rodents
• Flea - vector and natural reservior
• No eschar, less severe than epidemic typhus

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scrub typhus
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Scrub typhus

• First report in Thailand in 1952.
• Most common rickettsial infection in Thailand.
• One of the most common cause of FUO in Thailand
• Zoonotic

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Etiology

• Orientia tsusugamushi (formerly Rickettsia)
• Obligate intracellular bacteria grow in the
  cytoplasm of infected cells
• Transmission
• Human incidental host
• Chigger vector and reservoir
• Wild rodents natural host

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Chigger

• Larval stage of trombiculid mite
• Fed only once on human or rodents
• Stay within several meters of where they hatch
• 90 - 100 of their offspring from infected mite
  are capable for transmitting the organism

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Pathogenesis

• inoculation of pathogen when infected chigger
  feeds
• local multiplication
  at bite site
• Eschar and regional
  lymphadenopathy
  Rickettsemia
• infect target cell ( vascular
  endothelium )

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Clinical manifestation

• Incubation period 6-18 days
• Abrupt fever, severe headache, myalgia
• Tender regional lymphadenopathy, splenomegaly
• Eschar (60 in primary infection)
• small painless papule in day 9-18
• blackened scab seen at axillary, inguinal,
  genital area and bitten site (Thai 30-60)

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• Maculopapular rash on trunk and spread to
  extremities on day 5 (Thai 7-36)
• Slow pulse despite of high fever
• ocular pain, conjunctivitis, non productive
  cough, tinnitus
• Self limited in 2 weeks (without antibiotic)

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• Complication
• Aseptic meningitis, meningoencephalitis
• Myocarditis -gt heart failure
• Pneumonia -gt ARDS
• DIC
• Laboratory finding
• Routine studies are no diagnostic value
• Leukopenia may occur early then lymphocytosis in
  the later
• Albuminuria is common

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Laboratory diagnosis

• Direct detection
• Isolation
• Serologic tests
• Molecular techniques

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Direct detection

• Cluster of fluorescence with O.tsutsugamushi
  showed in the cytoplasm of leukocyte

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Isolation

• Embryonated chicken egg yolk sacs
• Laboratory animals guinea pigs, mouse
• Cell cultures monocyte, L929 mouse fibroblast
  cell
• Shell vial assay Vero, L929 cells

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Serologic test

• Detection of Antibody
• Weil-Felix (OX-K, OX-2, OX-19)
• Indirect immunofluorescent assay (IFA)
• Indirect immunoperoxidase assay (IIP)
• Enzyme-linked immunosorbent assay (ELISA)
• Dot-bloted ELISA
• Latex agglutination

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Molecular technique

• Clinical samples
• Skin biopsy specimen
• Paraffin-embedded tissues
• CSF
• Peripheral blood mononuclear cells (PBMC)

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Treatment

• Doxycycline, tetracycline and chloramphenicol are
  effective Px
• Fever dissipates in less than 24 hr. in most
  patients
• Relapse may occur, esp. when Rx. begun before
  d4-d5 of illness

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Treatment

• In children recommended
• doxycycline 2.2 mg/kg/dose x 2 dose
  
• then 2.2 mg/kg/day divided bid
• In severe cases/can not eat
• chloramphenicol 50-100 mg/kg/day IV
• -----gt oral form doxycycline
• Rx.duration until fever subside 2-4 d or at least
  5 d. for prevent relapse

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Acknowledgement

• Pediatrics Department,
• Faculty of Tropical Medicine
• Special thanks to
• Dr. Varee Wongchotigul