• Clinical Case: • 2 yr. old boy from South Bronx was admitted to the hospital with fever, rash and difficulty in walking.
• 10 days before he was treated for a rash and fever which was presumed to be pharyngitis.
• A presumptive diagnosis of Rocky Mountain Spotted fever was made & treated with chloramphenicol.
• Within 24 hrs. the patient became afebrile and soon the other symptoms were resolved.
RICKETTSIACEAE
• Classification: 3 genera
Rickettsia spp Orientia tsutsugamushi Ehrlichia spp
evolved from common ancestor
Bartonella (Rochalimaea) quintana - trench fever
& Coxiella burnetii – Q fever – are no longer considered to the members of the family.
The name rickettsia has been given in honour of Howard Ricketts who first identified the organism, its vector, and route of transmission of Rocky Mountain Spotted Fever.
General characteristics
They are very short, pleomorphic bacilli, non-motile, non-capsulted. They are Gram negative, though they do not take the stain well. They are obligate intracellular parasites. Multiplication is by binary fission within the host cell.
• Giemsa [bluish purple] • Gimenez and Machiavello [deep red]
Cultural characters: Do not grow on cell-free media. They can be cultivated in the yolk sacs of embryonated eggs. Can be cultivated on cell cultures –HeLa, HEp2, Detroit 6 etc.
Laboratory animal like mice is used for primary isolation
Antigenic Structure It possess 3 types of antigens Group specific soluble antigens Species specific antigen Alkali stable polysaccharide antigen
Alkali stable polysaccharide:
Found in many rickettsiae and is shared by certain strains of Proteus vulgaris. Weil-Felix test is based on cross reaction of the rickettsial antigen with the O antigen polysaccharide found in Proteus vulgaris OX-19, OX-2 and OX-K. The test measures the antiricketssial Ab in patient’s serum It is no longer used in United States.
Pathogenesis Organisms are maintained in nature and in arthropods – ticks, lice, fleas & mites. Mode of Transmission: To humans is by bite of vectors or through faeces of infected arthropod vector.
On entry to human body Organism multiplies locally & enters the blood stream Invades the vascular endothelial cells.
Leading to proliferation of cells, and perivascular infiltration
Resulting in thrombosis of vessels
Rupture and necrosis
Rickettsial infection of endothelial cells.
Typical lesion caused is a vasculitis.
Damage to vessels of skin results in rash, edema & hemorrhage is due to increased capillary permeability.
Rickettsiae produce endotoxin. Role of endotoxin in human disease remains unclear.
Rickettsia
species
Typhus group:
Natural cycle
Disease
Epidemic typhus Recrudescent typhus
Vectors
Hosts
Geographic distribution Worldwide Worldwide Worldwide USA USA
Rickettsia prowazekii R. mooseri R. felis
Human body lice None Fleas Fleas Fleas
Humans Humans Rodents Opossums Opossums
Murine typhus (Endemic typhus) Murine typhus like
Spotted Fever group:
R. rickettsii R. conorii R. sibirica R. japonica R. australis R. akari
Rocky Mountain spotted fever Boutonneuse fever North Asia tick typhus Japanese spotted fever Rickettsialpox
Ticks Ticks Ticks Ticks Mites
Small mammals, dogs, rabbits, birds Rodents, dogs Rodents Rodents, dogs Rodents House mice, rats
North & South America Africa, Southern Europe, India Eurasia, Asia Japan Australia Worldwide
Queensland tick typhus Ticks
12 tick-borne rickettsioses
R. conorii Astrakhan R. helvetica R. sibirica R. mongolotimonae
« R. heilongjiangii »
R. mongolotimonae R. conorii Israël R. helvetica R. conorii R. conorii Israël R. japonica
R. slovaca
R. conorii
R. rickettsii R. conorii R. australis Indian tick typhus Rickettsia
R. africae
R. honei
Q- Ticks are vectors for the transmission of each of the following diseases EXCEPT: A) Rocky Mountain Spotted Fever B) Epidemic Typhus C) Japanese spotted fever D) Boutonneuse fever
Spotted fever group:
Disease of this group includes –
Rocky mountain spotted fever (RMSF)
R. rickettsii
Other tick borne diseases
R. siberica, R. conori, R. australis
Rickettsial pox
R. akari
Rocky mountain spotted fever (RMSF):
Causative organism: R. rickettsii
Vectors: Dermacentor variabilis (dog tick)
Reservoirs: Dogs & rodents Transmission: is via tick bite The organism is passed by the transovarian route from tick to tick.
Humans are accidental hosts.
Incubation Period: 3-14 days
• Mainly seen in children during spring & early summer – ticks are active. • Symptoms: Sudden onset of fever, severe headache, mayalgia. • In 2-6 days, a typical rash is seen. It begins with macules and progress to petechiae. • The rash appears on the hand and feet & spreads inwards to the trunk. • It can be fatal if untreated.
Early Rash
Early (macular) rash on sole of foot.
Late Stage Petechial Rash
Other tick borne diseases: Causative organisms: R. siberica, R. conori, R. australis Vectors: Ixodid ticks Disease resemble RMSF Milder form A black spot having a necrotic centre (eschar) is present at the site of tick bite. Humans accidentally enter the natural cycle.
tick-bite eschar
3 weeks after removing the tick
Tick bite fever, Rickettsia conori. Notice the inoculation chancre
Skin rash during infection with Rickettsia conori.
Rickettsial Pox: Causative organism: R. akari
Vector: Liponyssoides sanguineus (Mites)
It’s a benign febrile disease
Carried by mouse to man by mite
Produces a vesicular rash
Mildest form, self limiting
Non fatal, resembles chicken pox
• Rash during rickettsial pox infection
Typhus fever Group:
Consists of – Epidemic typhus (Classical typhus)
R.prowazekii
Recrudescent infection (Brill–Zinsser)
R.prowazekii
Endemic typhus (murine typhus) R. mooseri (R.typhi)
Epidemic typhus:
Causative organism: R.prowazekii
Vector: Pediculus humanus corporis (human body louse) Pediculus humanus capitis
Transmission: Autoinoculation by the person while scratching the bite of infected body louse –produce abrasion- which is portal of entry for the organisms. Incubation Period: 6-15 days
• It is associated with wars & poverty. • It is found in Africa & South America but not in United States. • Symptoms: Chills, fever, headache, pain, stupor and delerium.
• Signs of severe meningoencephalitis, begin with rash.
• If untreated - death occurs due to peripheral vascular collapse or due to bacterial pneumonia.
Macular rash appears 4 – 7 days after the onset of illness. -first on the trunk and then to limbs. -The rash becomes petechial and spreads over the entire body except face, palms and soles.
Epidemic Typhus: Petechial Rash
Some develop a milder reactivity of latent infection after many years.
This is Recrudescent typhus / Brill-Zinsser Disease
Signs and symptoms: like epidemic typhus but are less severe. In United States it is seen in older people who had epidemic typhus during World War II.
Q- Each of the following statements concerning epidemic typhus is correct EXCEPT: A) The disease is characterized by a rash B) The Weil – Felix test can aid in diagnosis of the disease.
C) The disease is caused by a rickettsia
D) The causative organism is transmitted from rodents to human by a tick
Endemic typhus (Murine typhus): Causative organism: R. mooseri (R.typhi) Vector: Xenopsylla cheopis (rat flea) Reservoir: Rats Mode of infection: flea bite, or through contaminated food with infected flea feces & rat urine. Incubation Period: 1-2 weeks
• Rickettsia typhi hosts
• Symptoms: Gradual onset of fever with severe headache, chills, generalized pains
• A macular rash appears by about 5 days, first appearing on the trunk.
Scrub Typhus :
Causative organism: Orientia tsutsugamushi
Geographic appearance: Far east, especially Myanmar (Burma), India, Sri Lanka, New Guiena, Japan & Taiwan.
Vector & Reservoir: Chigger (Larval stage of mites)
The true reservoir is in mites that infest rodents. Mites transmit the infection transovarially. Man gets infected by bite of mite.
Clinical findings: • The disease resembles epidemic typhus clinically.
• Eschar – the punched – out ulcer with a blackened scab which indicates the location of mite bite is characteristic feature.
• Generalized lymphadenopathy & lymphocytosis are common. • Cardiac & cerebral involvement may be severe.
Laboratory diagnosis: Isolation of organism- is hazardous Serological test – Indirect immunofluorescence ELISA Weil – Felix test: is of historic interest.
• R. rickettsii in skin section of a pink macule taken on about the fourth day of R.M.S.F. • Preparation by Immune Fluorescense
• Rickettsia rickettsii - Rocky Mountain Spotted Fever Immunofluoresence reveals intracellular bacteria
TREATMENT: Tetracycline, Chloramphenicol. PREVENTION: Wearing protective clothing Using insect repellant Delousing with insecticide Use of rat-proofing buildings and using rat poisons. Clearing jungle vegetation in which rats and mites live.
Vaccination: A typhus vaccine containing formalin- killed R. prowazekii organisms is effective and useful in the military during the war time but available to civilians in United States.
There is no vaccine against Rocky mountain spotted fever.
• Reference:
– MIMS: chapter 21 – Levinson: chapter 26 – Jawetz: chapter 27