VET MICRO 526 USM

ZOONOSES, EIDS AND ONE HELATH – DR. FRENIEMER P. DACAYA CVM

2nd SEMESTER / 2023-2024

RAT BITE FEVER

OVERVIEW but how often this happens and how long the
• Rat bite fever is a rare bacterial disease that organisms might be carried is still unclear.
spreads through infected rats or rodents
usually from a bite, scratch, contact with
animal secretions or ingestion of secretion
from an infected animal.
• Symptoms vary according to what type of
bacteria causes rat-bite fever. But they
generally include headache, skin rash and
fever. They may also include joint and muscle
pain or swollen lymph nodes.

CAUSATIVE AGENT
• Streptobacillus moniliformis
• Spirillum minus EPIDEMIOLOGY
• US and Europe: Usually Streptobacillus
1. S. moniliformis moniliformis
o Gram-negative pleomorphic • Asia: Spirillum minus
bacterium showing filaments in • The typical victim of rat bite fever is a child
chains with numerous bulbous younger than five years old living in poverty.
swellings. Pet store workers and laboratory technicians
2. Sp. minus working with rats are also at risk. The risk of
o Spiral-shaped Gram-negative infection after a rat bite is about 10%.
bacterium, actively motile via 2-6 • The disease is rare, with only several cases
spirals and bipolar bundles of documented each year. As an example,
flagella. between 2000 and 2012, only 17 cases were
identified in California. However, its actual
INFCETION IN ANIMALS incidence is unknown because RBF is not a
• The primary host (rats) both the black rat nationally notifiable disease, and many cases
(Rattus rattus) and the Norwegian rat go undiagnosed since these bacteria are
(Rattus norvegicus), kept as pets and used difficult to identify.
in animal research. • Human infections with Spirillum minus have
• The bacteria live in the upper respiratory tract been reported mainly from Asia, but occasional
of rats and other rodents. Studies have shown cases of rat bite fever have been attributed to
that many domestic rats and over half of wild this organism in North America, Europe and
rats carry S. moniliformis. Africa.
• Other rodents that can carry the bacteria are:
o Mice, guinea pigs, gerbils, and According to a study about rat bite fever
squirrels. published in the national library of medicine,
o Infrequently, dogs, cats, ferrets, Although rat-bite fever is uncommon, it is
weasels, cattle, pigs, koalas, non increasingly seen as a result of changing
human primates, and turkeys, but patterns of urban living and pet-keeping
this is not well documented. practices. If unrecognized, this infection can
have debilitating sequelae and can be life-
Animals that eat rodents, including cats, dogs, threatening.
ferrets, weasels and pigs might be infected or
colonized with the organism as they have been TRANSMISSION
implicated in few human cases. According to • Bites or scratch
the center for food security and public health, • Touching a surface contaminated with
oral colonization might be possible in infected rat or animal secretions like spit,
carnivores that have bitten or eaten rodents

5 DVM A EBBOY, FLORENTINO, FULGAR, GUARINO, HIERRO, SUCAYAN

 VET MICRO 526 USM
ZOONOSES, EIDS AND ONE HELATH – DR. FRENIEMER P. DACAYA CVM
2nd SEMESTER / 2023-2024

RAT BITE FEVER

pee, or poop and then touching an open • Adults ages 65 and older, women who are
wound or your mouth, nose, or eyes. pregnant, or those with weakened immune
• Ingesting food or drinks that contain the systems who have difficulty fighting off
bacteria, usually from infected animal infections.
secretions.
• There are reports of clinical cases after other Historically, over 50% of reported cases
forms of contact, including handling a rat, being occurred in children living in poverty. However,
exposed to its urine, kissing it, and sharing the disease is expanding its horizon and now
food. also includes pet store workers and laboratory
technicians as rats have become popular pets
Since rats are considered to be the reservoir and research subjects). Any person who
hosts for S. moniliformis, and they usually comes into contact with the bacteria that cause
carry this organism asymptomatically as a part RBF is at risk for becoming sick with the
of the normal nasopharyngeal flora. disease. Remember, without early diagnosis
and appropriate treatment, RBF can cause
• Person-to-person transmission of zoonotic severe disease and death.
Streptobacillus or Sp. minus has not been
reported. CLINICAL SIGNS
• Streptobacillary rat-bite fever • S. moniliformis
o Sometimes people become infected o Abrupt onset of high fever
when they drink unpasteurized milk that o Headache
contains the bacteria. The infection that o Chills
results from consuming the bacteria is o Vomiting
called Haverhill fever. o Rash
• Spirillary rat-bite fever (sodoku) o Polyarthritis
o People usually get the infection when
they are bitten by a rat or occasionally S. moniliformis RBF (clinical symptoms
a mouse. Consuming Spirillum bacteria include an abrupt onset of high fever, followed
does not cause the infection. by headache, chills, vomiting and rash) The
petechial rash develops over the extremities in
Consuming Spirillum bacteria does not cause particular the palms and soles but sometimes
the infection. I would like to emphasize pala it is present all over the body. Haverhill fever
under the transmission na as of now person to (believed to develop after the consumption of
person transmission has not been reported in water, milk, or food contaminated by rat
RBF. excreta) ( Clinical symptoms include fever,
chills, pharyngitis, and pronounced vomiting
WHO IS AT RISK? which may be followed by skin rashes and
• Those who have pet rats or other rodents in polyarthralgia. Migratory polyarthralgia or
their home. septic arthritis, usually affecting the large
• People who have been bitten or scratched by joints asymmetrically, develops in many
a rat or other rodent. patients within 1 week and, if untreated, may
• Those who work with rats or other rodents, persist for several days or months. Symmetric
such as at animal research laboratories or pet polyarthritis develops in about 50-70% of
stores. patients Bacterial endocarditis, septic arthritis,
• People who live or spend time in areas with and abscesses in the brain or other tissues are
rodent infestations. rare but serious. Some patients have infected
pericardial effusion and infected amniotic fluid.
• Children who have contact with rodents.
(Symptoms usually appear 3-10 days after
• Children 5 years old or younger are at higher
exposure)
risk for infection with RBF because their
immune systems may still be developing.

5 DVM A EBBOY, FLORENTINO, FULGAR, GUARINO, HIERRO, SUCAYAN

 VET MICRO 526 USM
ZOONOSES, EIDS AND ONE HELATH – DR. FRENIEMER P. DACAYA CVM
2nd SEMESTER / 2023-2024

RAT BITE FEVER

observed compared to S. moniliformis RBF)

Diarrhea, vomiting, and CNS symptoms may
occur.

DIAGNOSTICS
• S. moniliformis
o Clinical evaluation
o Culture (of the streptobacillary form)
and sometimes rising antibody titers
o S. moniliformis can be grown in
culture. It is fastidious and required
media enriched with 10-20% blood,
serum or ascitic fluid for growth.
Bacterial growth shows a typical “puff-
ball” or “bread crumb-like”
appearance. They can develop into L-
forms which have a “fried egg”
appearance.

In a study published by national library of

medicine entitled “rat bite fever septic arthritis:
illustrative case and literature review” it is
being said that the culture of the elbow aspirate
demonstrated growth of a pleomorphic gram-
• Sp. minus negative bacillus at 72 h in cooked meat broth
o Recurrent fever in CO2 at 35°C. Typical “cotton ball” colonies
o Lesion at the site of the bite were observed. The organism grew optimally in
o Swollen lymph nodes 5% CO2 on horse blood agar, but not on
o Arthritis MacConkey, nutrient or chocolate agar. The
o Diarrhea colonies were grey, non-haemolytic and 1–2
o Vomiting mm in diameter at 72 h. Gram stain
demonstrated a pleomorphic, filamentous,
Sp. minus RBF usually manifest at a later stage gram-negative rod with bizarre forms and
than RBF by S. moniliformis since it has an intracellular swellings. The isolate was
incubation period of 2-3 weeks ( with a identified as Streptobacillus moniliformis
maximum of 4 months). Recurrent fever (fever using phenotypic methods, and the
that goes away and comes back) in untreated identification was confirmed by 16S rRNA gene
patients, 2- to 4-day cycles of fever usually sequencing. -- It was difficult to establish
recur for 4 to 8 weeks, but febrile episodes which media best promoted growth, but
rarely recur for > 1 year. The clinical course is enriched media seemed important and
similar to streptobacillary RBF however, there consistent with the finding that blood agar is
is a presence of an indurated, painful and often the most common media used to recover non-
ulcerated lesions at the site of the bite. The blood isolates - In a study published by
skin lesion may appear as the fever develops. Kämmerer et al nung July 2021, blood culture
(although the rash is less common compared tests might not be a sufficiently reliable
to the streptobacillary form, some patients diagnostic procedure, and authors have
develop a distinctive rash consisting of large observed, in particular, culture failure rates of
violaceous or reddish macules. The regional up to 33 % . As a result, complementary assays
lymph nodes are often swollen and tender. such as multiplex PCR diagnostic assays may
Arthritis and myalgia occur infrequently. be required for a more rapid and definitive
(assymetrical polyarthritis is less frequently diagnosis

5 DVM A EBBOY, FLORENTINO, FULGAR, GUARINO, HIERRO, SUCAYAN

 VET MICRO 526 USM
ZOONOSES, EIDS AND ONE HELATH – DR. FRENIEMER P. DACAYA CVM
2nd SEMESTER / 2023-2024

RAT BITE FEVER

o ELISA • Joints
o Indirect immunofluorescence o Streptobacillary RBF
Immunoblotting (western blotting), ▪ Migratory polyarthralgia is
and PCR tests frequent and septic arthritis of
• Sp. Minus large joints occurs in some
o Direct visualization of Spirillum from patients.
blood smears or tissue from lesions or o Spirillary RBF J
lymph nodes. ▪ Joint manifestations are rare.
o Giemsa stain or darkfield examination • Skin
of blood from inoculated mice. o Streptobacillary RBF
o Direct visualization is required because ▪ Maculopapular, petechial, or
S. minus cannot be cultured on purpuric and hemorrhagic
synthetic media. vesicles that may develop on
the peripheral extremities.
Spirllum minus cannot be cultured in artificial o Spirillary RBF
media. So spirillary RBF is usually diagnosed ▪ Red-brown macules with
by identifying consistent with Sp. minus in occasional urticaria.
blood, exudates or tissues including lymph
node aspirates, the bite wound or DIFFERENTIAL DIAGNOSIS
erythematous plaques by Giemsa stain or dark- • Several bacterial and viral infections like:
field microscopy. Because Sp. minus cannot o Lyme disease, leptospirosis,
be cultured, no serological or molecular (PCR) brucellosis, Rocky Mountain spotted
tests are available for diagnosis. fever, S. pyogenes and S. pyogenes-
associated infection, diseases,
disseminated S. aureus gonorrhea,
meningococcemia, viral
exanthemas, and secondary
syphilis.
o The spirallary RBF may easily be
confused with malaria or Borrelia
recurrentis infection because both are
characterized by relapsing fever.

TREATMENT
• The IV antibiotic is usually one of the
following:
Eto yung photos ng blood agar and yung o Penicillin G 200,000 units every 4
cooked meat booth in carbon dioxide at 35 hours
degrees Celsius. o Ceftriaxone 1 g once a day
• After 6 or 7 days, patients who have
HOW TO DIFFERENTIATE? clinically improved can be switched to one
• Bite site of the following oral antibiotics to complete
o Streptobacillary RBF the 14-day course:
▪ The bite site if present, typically o Amoxicillin 500 mg 3 times a day
heals quickly, without significant o Ampicillin 500 mg 4 times a day
regional lymphadenopathy. o Penicillin V 500 mg 4 times a day
o Spirillary RBF • Both types of rat-bite fever are treated with
▪ Fever persists, becomes antibiotics such as penicillin and ceftriaxone
indurated, and may ulcerate, given by vein and then switched to an antibiotic
with associated regional such as ampicillin, amoxicillin, or penicillin
lymphadenopathy.

5 DVM A EBBOY, FLORENTINO, FULGAR, GUARINO, HIERRO, SUCAYAN

 VET MICRO 526 USM
ZOONOSES, EIDS AND ONE HELATH – DR. FRENIEMER P. DACAYA CVM
2nd SEMESTER / 2023-2024

RAT BITE FEVER

taken by mouth. Doxycycline is given to people PREVENTION AND CONTROL

who are allergic to penicillin. • Avoid exposure to rats Proper handling
• If Streptobacillus moniliformis causes techniques.
endocarditis, high doses of penicillin plus • Food and water storage should be designed to
another antibiotic are used. prevent contamination by rodents.
• RBF can present similarly to other febrile rash • Pasteurisation of milk and sterilization of
illnesses, such as Rocky Mountain Spotted drinking water.
Fever (RMSF). If RBF and RMSF are both in • Proper handling techniques.
differential diagnosis, doxycycline should be • Hand to mouth contact should be avoided
considered as first-line treatment given the when handling a rodent .
need for rapid treatment and limited • Bite wounds or scratches should be cleaned
diagnostics for both diseases. This promptly and thoroughly.
consideration applies to pediatric patients

Treatment of streptobacillary rat-bite fever and

spirillary rat-bite fever is a 14-day course of
antibiotics that usually begins with an IV
antibiotic for 6 to 7 days before switching to an
oral antibiotic. According to some papers, one
way of optimizing antibiotic use daw is to
switch from IV to oral therapy with the
following advantages: Ginapababa ani ang
cost and then gina reduced pud and workload.
According to Medscape, switching from IV to
oral therapy as soon as patients are clinically
stable can reduce the length of hospitalization
and cover associated costs, While intravenous
medication may be more bioavailable and have
greater effects, some oral drugs produce
serum levels comparable to those of the
parenteral form.

Oral antibiotics can be used for patients with

mild disease for the entire course of therapy.
Doxycycline 100 mg orally every 12 hours for
14 days is used for patients allergic to
penicillin. Patients with S. moniliformis
endocarditis require high-dose penicillin G
plus either streptomycin or gentamicin for 4
weeks.

According to CDC, the RBF can present

similarly to other febrile rash illnesses, such as
Rocky Mountain Spotted Fever (RMSF). If RBF
and RMSF are both in differential diagnosis,
doxycycline should be considered as first-line
treatment given the need for rapid treatment
and limited diagnostics for both diseases. This
consideration applies to pediatric patients.

5 DVM A EBBOY, FLORENTINO, FULGAR, GUARINO, HIERRO, SUCAYAN