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Typhus Fever: Etiology, pathogenesis and laboratory diagnosis

This blog post is the outline of my lecture class in bachelor level (MBBS).  It will be useful for the students for quick review of the most important facts regarding Typhus fever and other related disease of Rickettsiaceae family.

Important characteristics of Rickettsiaceae  family

  1. Obligate intracellular parasite
  2. Multiply in the cytoplasm of host cells by binary fissions
  3. Most rickettsiae survive only for short times outside a host (reservoir/vector.
  4. Transmission by hematogenous route by blood sucking arthropod vectors: Lice, fleas, ticks and mites.
  5. Gram staining reaction: Stain poorly with gram stain, cell wall resembles with that of gram negative rods
  6. Alternative staining: Giemsa stain, acridine orange etc.
  7. Morphology: Very short rods (coccobacilli) barely visible in light microscope
  8. Rickettsiae grow readily in yolk sacs of embryonated eggs, but isolation is only done in reference laboratories because of bio-safety issues.

Rickettsiaceae family includes five genera

    1. Rickettsia
    2. Orientia
    3. Ehrlichia
    4. Anaplasma
    5. Neorickettsia

—  Spectrum of Rickettsial diseases

Rickettsia encompasses following three groups of bacteria:

    1. The spotted fever group: Rickettsia akari , R.rickettsii
    2. The typhus group: R. prowazekii, R. typhi
    3. The scrub/Chigger-borne typhus group: Orientia tsustsugamushi

Epidemiology and Pathogenesis

Pathogenesis

  1. Arthropod vectors deposit the organism in the blood stream
  2. Endothelial cells in the blood stream engulf these organisms (induced by the organism itself) and carried to the cell cytoplasm within a vacuole.
  3. Organism escape from the vacuole or phagosome.
  4. Multiplication of the organisms- which causes cell injury and cell deaths manifested as vascular lesions which disseminated through out the body
  5. Skin, Heart, Brain, Lungs and Muscles are primarily affected
  6. Organisms transmits inside the body via cell to cell spread, lymphatic drainage, hematogenous route and can also be latent (e.g. R. prowazekii)
  7. Formation of disseminated endothelial lesions
  8. Activation of clotting systems
    • disseminated intravascular coagulopathy (DIC)
  9. Death usually by cardiac failure

Epidemic typhus  (Louse borne typhus)

Brill Zinsser disease (Recrudescent typhus)

Recurrent form of epidemic typhus, signs and symptoms similar to those of epidemic typhus but are

Murine typhus

Scrub Typhus

  1. Was a prominent problem during World War II and Vietnam war
  2. Causative agent Rickettsia tsutsugamushi
  3. Vector: Chigger mite.
  4. After 10- 12 days of incubation, scrub typhus  begins abruptly with fever, chills and headache.
  5. Many patients develop sloughing lesions at the bite sites and later a generalized spotty rash.
  6. Fatality rate up to 50%, rare with prompt antibiotic treatment
  7. No vaccine available.
  8. Prevention by controlling mite populations

Laboratory diagnosis of Typhus fever

Sample: Blood drawn soon after onset of illness.

Culture: Limited usefulness; technically difficult and also hazardous

Culture: In Guinea pigs, mice or embryonated eggs.  Culture facility not available in Nepal.

Staining

Direct immunofluoresecent antibody test: used to detect rickettsiae in ticks and section of tissues. Most useful to detect R. rickettsii in skin biopsy specimens to aid in the diagnosis of Rocky Mountain Spotted Fever.

Serological tests: Laboratory diagnosis of rickettsial diseases is based on serologic analysis.

—  Commonly employed tests are:

  1. Indirect immunofluorescence assay (IFA):
  2. Widely used
  3. used to detect IgG and IgM
  4. Enzyme Immunoassay e.g. ELISA

Other tests are

Weil-Felix test

Other tests: 

Polymerase Chain Reactions (PCR): Has been used to diagnose Rocky Mountain Spotted Fever, Scrub typhus, murine typhus and Q Fever.

Sensitivity of PCR to detect Rocky Mountain Spotted Fever is about 70% comparable to that of Skin Biopsy with immunocytology.

After reading this blog, test your knowledge with these questions: Top Ten most important Multiple Choice Questions (MCQs) about rickettsial disease.