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Rickettsia

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Pascale Gruber

Posted on 7 May 2006

Introduction

Small, gram –negative, aerobic, coccobacilli, obligate intracellular parasites
Do not stain well with Gram stain but stain red with Giemsa or Gimenez stain

Taxonomic classification:

  • Order: Rickettsiales
  • Family: Rickettsiaceae
  • Tribe: Rickettsieae
  • Genus: Rickettsia
 
Genus includes 3 distinct groups:
  • Spotted fever group:
    • Rocky Mountain Spotted fever (RMSF)
    • Oriental spotted fever
    • Rickettsial pox
    • Boutonneuse fever
  • Typhus group:
    • Louse-bourne (epidemic) typhus
    • Brill-Zinsser disease
    • Murine (endemic or flea-bourne) typhus
  • Other Rickettsial diseases
    • Scrub typhus (Tsutsugamushi disease)
    • Q fever
    • Ehrlichia organisms and Bartonella (Trench fever)

World wide geographical distribution:

Disease Geographical distribution
Rocky mountain spotted fever USA
Rickettsialpox
Russia, South Africa, Korea
Boutonneuse fever Mediterranean
Louse-borne typhus Europe, Asia, Africa
Brill-Zinsser disease
Europe, Asia, Africa
Murine (endemic or flea-borne) typhus
Worldwide esp. over-populated areas
Scrub typhus Japan, Pakistan, Solomon Islands
Q fever Australia Canada
  • In Hong Kong past 10 years (1995-2004): 67 cases of spotted fever group, 58 cases scrub typhus, 51 cases murine typhus. Fatality: 2 spotted fever group, 0 scrub, 1 murine typhus. No cases of epidemic louse bourne typhus in HK past few decades. Scrub and murine typhus reportable disease but spotted fever group not reportable. Most local cases secondary to outdoor activity eg walking, camping, jogging. 30% murine typhus due to rat infestation. More commonly seen in adults

    Data from Department of Health, HKSAR

Rickettsial disease:

  • Vary in clinical severity according to virulence, host factors
  • Worse if elderly, male, alcohol excess, underlying disease and G6PD deficiency
  • Most virulent R. rickettsii & R. prowazekii
  • Infections begin with introduction of organism to skin eg tick bite, cutaneous abrasions contaminated by louse/flea faeces
  • Humans only accidental host in most infections

Pathogenesis

  • Enter dermal cells->proliferate locally->Eschar->spread to regional lymph nodes-> body
  • Attacks endothelial cells
  • Adherence of host cell outer membrane protein. Outer membrane Omp A implicated and antibodies to Omp A have shown to block adherence
  • Once attached, they are phagocytosed
  • Mechanism of intracellular movement and destruction differ amongst spotted fever group (SFG) and typhus
  • In typhus group the organism multiplies until the cell is packed with organisms and then bursts but in SFG there are relatively fewer organisms which do not lyse the cell but escape by stimulating host cell actin tails that allow the organism to propel through the cytoplasm. They emerge from the cells causing membrane damage and influx of water.
  • Injury to the endothelial cells cause the clinical symptoms and signs of rash, interstitial pneumonia, encephalitis, interstitial nephritis, GI involvement, pancreatitis, and liver dysfunction

Diagnosis of rickettsial disease

  • Difficult, relies on combination of clinical, epidemiological and lab. findings
  • History of louse or flea infestation or tick bite helpful
  • Localised to certain geographical areas
  • Diagnosis to consider in PUO
  • Differential diagnosis include dengue, leptospirosis, measles, malaria, rubella
  • Mainstay from lab diagnosis is serology both acute and convalescent samples
  • The indirect immunofluorescence assay (IFA) is the standard serological test.  It has high sensitivity and specificity. Positive cases detected by a four fold ­ in titres. Limitation in inability to diagnose early infections due to delay in antibody response and cross reactivity between typhus and SFG.
  • Weil-Felix (WF) test is  insensitive & non specific
    • WF detects antibody against antigens from proteus strains: P. Vulgaris OX2, P. Vulgaris OX19 and P. Mirabilis OXK.
    • Rise in OX2 antibody level is common in SFG
    • OX19 more specific for typhus and RMSF
    • OXK for scrub typhus
       
  • Other serological test targets specific antigens
  • Culture of agent: time consuming, difficult  & not routinely performed
  • Recent advance s- acute infection diagnosis possible by PCR

Non-specific laboratory features

  • Mild leukopenia, anaemia & thrombocytopenia
  • Hyponatraemia
  • Hypoalbuminaemia
  • Hepatic and renal abnormalities
  • R. Rickettsii
  • 1st recognised 1896 Snake River Valley Idaho called black measles
  • Misnomer-occurs all over the USA
  • Severe disease, most frequently reported Rickettsial disease in USA
  • 90% between months of April to Sept
  • Onset after tick bite by 1 week (40% people unaware of tick bite)
  • Reservoir dogs and rodents
  • Clinical symtpoms: fever, headache, muscle pain
  • Rash 3-5 days after onset of symptoms: ankles, wrists which start as pink macules, then become maculopapular and finally petechial
  • Non-specific symptoms also common eg nausea, vomiting, diarrhoea, abdo pain, cough
  • Long term complications rare but include partial paralysis, gangrene, hearing loss
  • Mortality 3-5%(was 30% before the advent of tetracycline/chloramphenicol)
  • Lab diagnosis:
  • -serological assay IFA to detect IgG or IgM antibodies
  • -Immunostaining
  • Rx: doxycycline 100mg Q12H 5-10/7
  • Failure to respond after 24-72 hours then diagnosis must be questioned
  • Prevention is key and exposure should be limited

Other spotted fevers

Boutonneuse fever (Mediterranean spotted fever)

  • -Tick borne rickettsiosis caused by R conorri
  • -Endemic in Mediterranean area
  • -Risk factor: Contact with dogs
  • -Incubation period 6-10 days.
  • -Eschar at tick bite site, followed by high fever, headache, malaise, flu-like symptoms
  • -Generalized maculopapular rash involving palms & soles with sparing of face
  • -Usually recovers in 10 days
  • -In 5-6% of patients, major neurological and even multiple organ involvement
  • -Risk factors for severe form include advanced age, immunocompromised state, chronic alcoholism, G6PD deficiency and delay of treatment

Oriental spotted fever/Japanese spotted fever

  • -Caused by R japonica
  • -First reported in Japan 1984
  • -Vector tick
  • -Inoculation eschar occurs in 90% of patients
  • -Rash begins as macular eruption and then becomes petechial after 3-4 days, peak at 10 days and disappears after 2 weeks.
  • -No regional lymphadenopathy
  • -Other clinical feature include headache, fever. Eschar seen in 90% of cases and tends to be very shallow
  • -Severe cases of encephalitis, DIC, multiple organ failure and ARDS have been reported

Rickettsialpox

  • Caused by R akari
  • Found New York City, Korea, Ukraine and Slovenia
  • Maintained  in mite –mouse cycle with humans accidental host
  • -Painless papule appear at mite feeding site. After 2-7 days becomes an eschar. Other features: fever, chills, headache, myalgia, rash.
  • -Rash initially is maculopapular and changes to vesicular form. When dried out, replaced by crust
  • -Clinically resembles chickenpox
  • -Recover even if left untreated
  • -No fatalities reported.

Typhus group

Epidemic louse borne typhus

  • Also known as Jail fever, hospital fever, famine fever
  • R. prowazekii
  • Human body louse is vector
  • Widespread during epidemics, Europe 17-19th century, World war 1 contributed to 3 million deaths in Russia and even more in Poland and Romania, Irish Potato famine
  • Usually occurs in cold climate with poor hygiene
  • Disease transmitted to an infected human who scratches the bite and rubs louse faeces into the wound and inhalation of aerosol containing dried faeces
  • R. Prowazekii can remain viable and virulent in the dried faeces for many days
  • Incubation period 1-2 weeks
  • Symptoms can be severe including: high fever, myalgia, cough, chills, headache, photophobia, delirum, stupor, hypotension and rash after 5 days
  • No eschar at inoculation site
  • Can be fatal in 10 – 30% of patients depending of nutritional status and co-morbid conditions

Brill-Zinsser disease (relapsing louse borne typhus)

  • recurs years after initial attack
  • when host defence falter, viable organisms retained in body are activated
  • Reactivation seen when the host defence is low, tends to be a mild infection

Murine (endemic or flea borne) typhus

  • R Typhi
  • Vector fleas
  • Reservoir cats and rats
  • Widely distributed in tropical and subtropical area
  • Fever, headache, chills, myalgia, 50% rash (often poorly visible)
  • One attack provides life long immunity
  • Most cases are mild, but fatality rate can be as high as 3%

Scrub typhus

  • Mite borne disease cause by R. tsutsugamushi, which typically bite human on lower extremities or genital area
  • Common in rural south & southeastern Asia and Pacific area
  • Incubation 6-12 days followed by fever, chills, headache, lymphadenopathy
  • 50% have inoculation eschar
  • Rash 5-8th day extending to arms and legs
  • Pneumonitis, delirium, stupor,
  • More severe manifestations include renal failure, septicaemia, encephalopathy, myocarditis
  • Untreated mortality 0-30% according to area, strain of infectious agent and previous exposure
  • Rx doxycycline or chloramphenicol

Q fever

  • Coxiella Burnetti
  • Recently classified in gamma group of proteobacteria (not Rickettsia)
  • Found in sheep, cattle, goats esp. placental tissue but also milk, urine and faeces
  • Acquired by inhalation of aerosolised organisms unlike other human rickettsial organisms
  • Farmers and abattoir workers are at risk
  • Incubation period: 2 to 6 weeks with 3 main presentations in acute Q fever
  • Self-limiting disease with fever and myalgia
  • Pneumonia progressing to ARDS
  • Hepatitis, pericarditis, myocarditis, meningoencephalitis, thyroiditis, ancreatitis, Guillain-Barre syndrome
  • Chronic Q fever: Chronic endocarditis, osteomyelitis, hepatitis, glomerulonephritis
  • Acute Q fever is usually self-limiting. Mortality for chronic > 60%
  • Lab diagnosis: IFA, ELISA, complement fixation
  • Treatment: tetracycline, chloramphenicol

Summary

  • Can be difficult to diagnose
  • Consider in differential diagnosis of PUO
  • High index of suspicion in endemic areas esp. history of mite, tick or louse bite
  • Lab diagnosis involve serologic assays (IFA, Weil-Felix test) and PCR
  • Treatment tetracycline or chloramphenicol
  • Diagnosis reconsider if no response 24-72 hrs
  • Key is prevention-long sleeves, insect repellent, control of reservoirs including dogs and rodents

Further reading

  1. Rickettsioses as paradigms of new or emerging infectious diseases. Clinical Microbiology Reviews 1997
  2. Tick-Borne Rickettsioses around the World: Emerging Diseases Challenging Old Concepts. Clinical Microbiology Reviews 2005
  3. Laboratory diagnosis of Rickettsioses. Journal of Clinical Microbiology 1997
  4. Rickettsioses and the International Traveler. CLinical Infectious diseases 2004
  5. The threat of rickettsial diseases to military medicine and international public health. Clinical Infectious Diseases 2002
  6. Q Fever : emedicine 2004

© Pascale Gruber May 2006


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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