Rickettsial diseases: Pathogenesis, Typhus fever group, Spotted fever group




Rickettsial diseases: Pathogenesis, Typhus fever group, Spotted fever group
Rickettsial diseases: Pathogenesis, Typhus fever group, Spotted fever group

Rickettsia

 Classification:

  • Order: Rickettsiales
  • Tribe: Rickettsiae
  • Family: Rickettsiaceae
  • Genera: Rickettsia, Orientia, Ehrlichia

Introduction:

  • Rickettsiae are obligate, intracellular, small Gram-negative bacilli.
  • It multiplies within the cytoplasm of eukaryotic cells.
  • Size: 0.3×1-2 µm.
  • Genome: 1-1.5 million base pairs
  • Rickettsiae are primary pathogens of arthropods like:
    • Lice
    • Fleas
    • Ticks
    • Mites
  • Transmitted to humans by these arthropod vectors.
  • Rickettsiae were originally thought to be a virus because:
    • Have small size
    • Stain poorly with Gram stain
    • Grows only in the cytoplasm of eukaryotic cells
    • Obligate intracellular parasites
  • Rickettsiae are bacteria because:
    • Have Gram-negative cell wall
    • Contain both DNA and RNA
    • Contain enzymes for Kreb cycle
    • Contain ribosomes for protein synthesis
    • Susceptible to antibiotics

Morphology of Rickettsiae:

  • They are small Gram-negative coccobacilli.
  • Size: 0.3-0.6 to 0.8-2 µm.
  • Non-motile
  • Non-capsulated
  • Stains poorly with Gram stain
  • Stains well with these stains:
  • Deep red with Machiavello and Gimenez stain
  • Bluish purple with Giemsa and Castaneda stain

Culture characteristics of Rickettsiae:

  • Rickettsiae do not grow in cell-free media.
  • Most Rickettsia grows in the cytoplasm inside the cell.
  • Rickettsia causing spotted fever grows in the nucleus of the cell.
  • Cell lines:
    • HeLa, Hep2, Detriot-6, mouse fibroblasts, and other continuous cell lines.
  • Chick embryo:
    • Grows in the yolk sac of 5-6 days old chick embryo.

Human Infections Caused by Rickettsia:

Bacteria Diseases
Rickettsia prowazekii Epidemic or louse-borne typhus; relapsing louse-borne typhus or Brill-Zinsser disease
Rickettsia typhi Endemic or flea-borne murine typhus
Rickettsia rickettsiae Rocky Mountain spotted fever
Rickettsia akari Rickettsial pox
Rickettsia conori Boutonneuse fever

Antigenic Structure of Rickettsia:

  1. Group-specific antigen:
  • It is the soluble antigen.
  • It is present on the surface of the organisms.
  • From the repeated washings and centrifugation, it can be extracted.
  1. Species- or strain-specific antigen:
  • It is present in the cell wall of the bacteria.
  1. Alkali-stable polysaccharide antigen:
  • It is a surface antigen.
  • It is present in some species of Rickettsia and some strains of Proteus (Proteus OX19, OX2 and OXK).
  • This sharing of antigen form the basis of the Weil-Felix test.

Pathogenesis of Rickettsia:

  • Rickettsia has the capacity of multiplication inside the cell.
  • The important virulent factor is adhesion.
  • Adhesins are the outer membrane protein that facilitates the entry of the organism into the host cells.
  • When they enter the cell, multiplication occurs and accumulates in large numbers.
  • It then lyses the host cells.
  • Rickettsia can cause rickettsemia when it multiplies after reaching the circulation.
  • In the endothelial cells of small arterial capillary and venous vessels, Rickettsia is localized.
  • Then the endothelial cellular hyperplasia occurs at those sites.
  • It results in multiorgan vasculitis.
  • It may lead to the thrombosis and development of small nodules.
  • Gangrene may result in the extremities, ear lobes, nose, and genitalia. It is due to the thrombosis of supplying blood vessels.
  • Vasculitis may lead to:
    • Increased vascular permeability with consequent edema
    • Loss of blood volume
    • Hypoalbuminemia
    • Reduced osmotic pressure
    • Hypotension

Typhus Fever Group:

  • Epidemic or louse-borne typhus caused by Rickettsia prowazekii
  • Relapsing louse-borne typhus or Brill-Zinsser disease caused by prowazekii.
  • Endemic or flea-borne murine typhus caused by Rickettsia typhi.

1. Epidemic or Louse-borne Typhus:

  • It is caused by Rickettsia prowazekii.
  • It is transmitted by the human body louse Pediculus humanus corporis causing the acute febrile illness.
  • It is named after the scientist Von Prowazek. He died of typhus fever while studying this disease.
  • prowazekii is an invasive bacterium.
  • It leads to vasculitis by multiplying in the endothelial cells of blood vessels.
  • The average incubation period is 8 days whereas it may vary low as 2-3 days.
  • Characteristics of epidemic typhus:
    • High fever
    • Severe headache
    • Chills
  • On the 4th or 5th day, the petechial or macular rash appears
  • The rashes first start to appear on the trunk.
  • Without affecting the face, palms, and sole it then spreads to the extremities.
  • In nearly, 40 % of patients rashes are seen.
  • The patient may become stuporous and delirious if they are left untreated.
  • In the disease process, the cloudy state of consciousness appears. The name typhus is derived from it. The meaning of tyhus is cloud or smoke.
  • Complications:
    • Myocarditis
    • Central nervous system (CNS) dysfunction
    • Mortality rate is as high as 60% in old or immunocompromised persons.

2. Relapsing or Recrudescent Typhus:

  • Example of a recrudescent case of typhus fever is Brill-Zinsser disease.
  • This condition was seen in the patients who were cured of the disease or the patients who were treated with antibiotics.
  • Even after the antibiotic treatment, the recurrence of typhus fever has re-emerged after many months, years and decades.
  • It is because of the persistence of prowazekii in the body tissues which re-emerges later.
  • Primary reservoir of epidemic typhus: Human
  • If a person is suffering from typhus fever from brill-Zinsser disease, and when lice feed on it, it will be infected with prowazekii.
  • Vector of epidemic typhus: Body louse ( humanus corporis )
  • Pubic louse does not transmit it.
  • Occasionally transmission may occur by head louse (humanus capitis )
  • In the alimentary tract of louse prowazekii, lives and multiplies.
  • Within the 3-5 days of infection, the bacteria gets excreted in feces.
  • After the infection, lice die.
  • During the blood meal when the rickettsia-harboring louse bites the human, infection is transmitted.
  • During the feeding, lice defecate.
  • The contaminated louse feces gets inoculated into the minute lesion of the bite wound when the host scratches on it.
  • From there the bacteria reach the circulation, multiplies and cause rickettsemia.
  • Infection may also be transmitted rarely through the conjunctiva or inhalation of aerosols of dry louse feces.

3. Endemic or Flea-borne Murine Typhus:

  • It is caused by typhi.
  • It has a short duration and the disease is milder than epidemic typhus.
  • Incubation period: 7 to 14 days.
  • Symptoms:
    • Fever
    • Headache
    • Malaise
    • Myalgia
  • In about 50% of infected patients, rash develops on the 3rd to 5th day of infection.
  • Rash appears on the chest and abdomen.
  • It may spread to palms and soles.
  • May last up to 3 weeks in the untreated course.
  • Reservoirs: Rat ( Rattus rattus ), mice, and cat
  • Humans are the accidental hosts.
  • Vectors for transmission of disease: Rat flea (Xenopsylla cheopis ) or cat flea (Ctenocephalides felis).
  • It is transmitted from rats to rat by the rat flea.
  • It is transmitted to humans accidentally by the feces of infected fleas.
  • When the fleas feed on the mice, cat, or natural host, it becomes infected.
  • It then transmits the disease to humans by biting.
  • At the site of the bite, inoculation occurs.
  • Disease transmission also may occur by:
    • Cat flea felis
    • Inoculation or inhalation of aerosolized infectious specimens
    • Ingestion
    • Contaminated food with infected rat urine or flea feces

Spotted Fever Group:

  1. Rocky Mountain spotted fever caused by Rickettsia rickettsiae.
  2. Rickettsialpox caused by R. akari
  • Boutonneuse fever caused by R. conori
  • Kenyatick-bite fever,
  • African tick typhus
  • The Mediterranean spotted fever
  • Indian tick typhus
  • Marseilles fever

1. Rocky Mountain Spotted Fever:

  • Incubation period: 7 days
  • Symptoms:
    • Fever
    • Severe headache
    • Chills
    • Myalgia
    • Development of rash three or more days
    • At first, a rash develops on the wrist, ankles, palms, and soles.
    • It then spreads to the trunk.
    • In the early stage, the rash is maculopapular but in the later stage, it becomes petechial and hemorrhagic.
  • Complications:
    • Respiratory failure
    • Encephalitis
    • Renal failure
    • Patient may die within 5 days of onset of symptoms.
  • Ticks are the host, reservoir, and vector of rickettsiae.
  • Vectors:
    • Woodtick (Dermacentor andersoni )
    • American dog tick (Dermacentor variabilis)
    • Lone star tick (Amblyomma Americana ).
    • When the tick bites the human, it gets transmitted by saliva.

2. Rickettsial Pox:

  • It is caused by akari.
  • It is a milder form of infection.
  • Natural reservoir: Common home mouse ( Mus musculus )
  • By the bite of mouse mite (Liponyssoides sanguineus ), R. akari Iis transmitted from mouse to mouse.
  • Incubation period: 7 days
  • Papule develops at the site of the bite which progresses to ulcer and leads to eschar formation.
  • In 3-10 days fever, headache, malaise, and myalgia develop.
  • After the emergence of fever, a popular vesicular rash appears un 3-4 days.
  • Recovery starts after the illness of 10-14 days.
  • Without treatment complete healing of rash takes 2-3 weeks.

What are the conditions/ characteristics that differentiate Rickettsial pox from other rickettsial infections?

  • Presence of eschar at the site of the bite
  • Presence of vesicular pustular eruption