Rat bite fever

Morphology, pathogenesis and transmission of Rat-bite fever

1. Prepared by
Dr.S.Shobana
Associate Professor
Department of Genetic Engineering
SRM Institute of Science and Technology
Morphology, pathogenesis and
transmission of Rat bite fever

2. Rat fever is an infectious disease caused by two
bacteria
StreptobacillaryRBF is caused by Streptobacillus
moniliformisin North America
SpirillaryRBF is caused by Spirillum minus and it
is more common in Asia
Both organisms are normal oral flora in rodents.

3. Streptobacilli moniliformis
It is a highly pleomorphic, filamentous, gram-
negative, nonmotile, and non-acid-fast rod.
• It appears straight but may be fusiform and may
develop characteristic lateral bulbar swellings.
•It is typically arranged in chains and loosely tangled
clumps and varies in its dimensions, from 0.1 to 0.5
um by 2.0 to 5.0 um, up to 10 to 15 um, with long,
curved segments
• Exists in two variant types, the normally occurring
bacillary form and the inducible or spontaneously
occurring, cell wall-deficient L form, growing with a
“fried-egg” colony morphology
• L form is considered nonpathogenic and
spontaneous conversion between the two forms in
vitro has been reported.
• Considered to be responsible for clinical relapses
and resistance to therapy.

4. Spirillum minus
Another etiologic agent of rat bite fever,
discovered during the 19th century
• initially named Spirochetamorsusmurislater
was renamed Spirillum minus in 1924.
•It is a short, thick, gram negative, tightly coiled
spiral rod
• Size is 0.2 to 0.5 um and has two to six helical
turns
• Spirillum minus cannot be cultured on
synthetic media
• Diagnosis relies on direct visualization of
characteristic spirochetes with Giemsa stain,
Wright stain, or dark-field microscopy

5. Transmission:
S.moniliformisandS.minusarepartofthenormalrespiratoryfloraofrodents.
•Eitherorganismmaybetransmittedtohumansthroughbitesorscratches.
•Infectioncanalsoresultfromhandlinganinfectedrodent(evenwithnoreportedbiteorscratch),oringestionof
foodordrinkcontaminatedwiththesebacteria(Haverhillfever).
•RatsareconsideredthenaturalreservoirofRBF
•Pathogenhasalsobeenfoundinotherrodentspeciessuchas,miceandgerbils.
•Person-to-persontransmissionhasnotbeenreported.

6. Pathogenesis:
•Pathologicalstudiesshowsdegenerative
changesinthekidneysandliver.
•Such as erythrophagocytosis,
hepatosplenomegaly,interstitialpneumonia,
lymphnodesinushyperplasia,endocarditis,
andmyocarditisalongwithdegenerative
changesinthekidneysandliver.
•Biopsyofskinlesionsseeninratbitefeverhas
demonstratedleukocytoclasticvasculitis
•Experimentalinfectioninmiceresultsina
progressivepolyarthritis,beginningwith
fibrinopurulentexudatewithinthejointspace
•Onday4oftheinfectionperiarticularabscess
andnecrosisonday7periostitisdevelops
•Degreeofpolyarthritisdependsonthesizeof
theinoculum
•Pathogencanpersistwithinjointspacesat3
monthsofinfectionmayoccurdespitethe
clearanceoforganismsfromblood,liver,and
spleen.

7. Diagnosis:
S. moniliformis infection can be diagnosed by blood culture.
However the organism grows slowly and has strict growth requirements, making it difficult for most laboratories to culture.
No serologic test is available for S. moniliformis; the previous slide agglutination test is no longer available because of
performance limitations.
A number of laboratories are using real time-PCR on patient samples to diagnose patients with RBF due to S. moniliformis.
S. minus infection is diagnosed by dark-field preparations of blood smears or tissue or from exudates from lesions or
adjacent lymph nodes where it exhibits darting motility.
Giemsa and Wright stains are most often used for staining.
If this is unsuccessful, then blood from inoculated mice is examined using dark-field microscopy (rarely done).
No specific serological test is available.

8. Signs & symptoms:
• S. moniliformis-associated rat bite fever is a systemic illness characterized by fever, rigors, and migratory
polyarthralgias.
• After exposure, the incubation period ranges from 3 days to over 3 weeks but typically is less than 7 days.
• Many patients report symptoms suggestive of an upper respiratory tract infection during this time.
• If a bite has occurred, it typically heals quickly, with minimal residual inflammation and no significant regional
lymphadenopathy.
• At disease onset, fevers begin abruptly and may range from 38.0°C to 41°C.
• Rigors associated with fevers are prominent.
• Fever may resolve in 3 to 5 days but can relapse
• Other symptoms in the initial phase of illness include headache, nausea, vomiting, sore throat, and severe
myalgias.

9. Prevention:
Laboratory rodents, or breeding colonies for
rodent pets, can be cleared of infection by
establishing cesarean derived, barrier
maintained SPF stocks.
These animals are monitored regularly for S.
moniliformis infections.
Such colonies have been established for
laboratory rats, mice and guinea pigs.
Although research animals usually come from
SPF colonies, rodents sold as pets may be
conventionally bred.
Pets and SPF animals should be protected from
contact with animals that may carry S.
moniliformis or Sp. minus, such as wild rats.
To reduce the incidence of cervical abscesses in
guinea pigs, abrasive materials should not be
used in feed or litter.

10. Treatment:
•Adults with rat bite fever should receive 400,000 to 600,000 IU/day (240 to 360 mg) of
intravenous penicillin G for 7 days,
•Children should receive 20,000 to 50,000 IU/kg of body weight/day of intravenous penicillin G
for 5 to 7 days,
•This followed by 7 days of oral penicillin V, 25 to 50 mg/kg/day divided four times per day 27 -30
•For penicillin-allergic patients, both streptomycin and tetracycline appear to be effective
•Cephalosporins have also been used successfully and may be considered if cross-allergenicity
with penicillin is felt to be unlikely.
•Other antimicrobials may be considered, based on the in vitro susceptibility data
•The appropriate treatment length for children is 6-week regimens
•Generally considered effective for other causes of bacterial endocarditis.
•Use of streptomycin appears to enhance activity against the cell wall-deficient L forms of S.moniliformis