Lymphoreticular and Hematopoetic Infections
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General Goal: To know the causes of this disease, the most common modes of transmission, and the major manifestations of this disease.

Specific Educational Objectives: The student should be able to:

1. identify the causes of this disease.

2. recite the common means of transmission and identify the major disease manifestations..

3. tell what groups of people and occupations are more likely to get this disease and how to avoid getting infected with this pathogen.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, and M.A. Pfaller, 6th Edition. pp. 374-375.

References: Morbidity Mortality Weekly Report, February 13, 1998/47(05);89-91 last accessed 3/19/10;

Fatal Rat-Bite Fever --- Florida and Washington, 2003, Morbidity Mortality Weekly Report, January 7, 2005 / 53(51 & 52);1198-1202 last accessed 3/19/10;

Rat-bite fever (RBF) is an acute febrile illness that is usually accompanied by a skin rash. Here are some reports of cases of RBF; case 1case 2, and case 3. RBF refers to two similar diseases caused by different gram-negative facultative anaerobes: streptobacillary RBF caused by infection with Streptobacillus moniliformis and spirillary RBF (also called Sodoku) by Spirillum minus.


Streptobacillus moniliformis, (gram negative rod= string of bead appearance)

Spirillum minus ( alternatively named Spirillum minor; gram negative spiral shaped organism)

RBF is rare in the U.S. The most common cause of RBF in the U.S. is due to S. moniliformis.

Most cases in the United States are caused by S. moniliformis acquired through rat bites or scratches. However, RBF can occur in humans following handling of an infected rat, ingestion of food or water contaminated with infected rat excreta or following exposure to rat urine when handling rat cage materials . Nasopharyngeal carriage rates in healthy laboratory rats range from 10% to 100%; carriage rates in wild rats range from 50% to 100%. It has been estimated that 10% of rat bites result in some form of RBF.

Cases of RBF also have been associated with the bites of mice, squirrels, and gerbils and exposure to animals that prey on these rodents (e.g., cats and dogs)

Sporadic cases have been reported in children without histories of direct rodent contact but who lived in rat-infested dwellings.

S. moniliformis can be transmitted by contamination of food and water with rat feces and/or urine. One rat produces 20-50 droppings per day and excretes 14 ml of urine per day. Outbreaks of RBF in Haverhill, Mass. in 1926 and an epidemic in England in 1983 were associated with ingestion of raw milk contaminated by rat feces and/or urine. The disease is called Haverhill fever when S. moniliformis is transmitted by drinking rat-excrement contaminated milk or water. S. minus is not transmitted by the ingestion of contaminated food or water.

Rat bite

Minimal local inflammation, prompt healing, little lymphadenitis.

Bacteremia may occur with disseminated lesions appearing 1-3 days after the bite and later becoming pyogenic (pus formation).


Streptobacillary RBF caused by infection with S. moniliformis

Incubation period can range from 1 to 22 days, but onset usually occurs 2-10 days after the bite of a rat. The clinical syndrome is characterized by flu-like symptoms including irregularly relapsing fever (101-104oF) accompanied by chills, vomiting and headaches, and asymmetric polyarthritis generally affecting the large joints followed within 2 to 4 days by a maculopapular rash on the extremities, palms and soles.The rash is usually on the extensor surfaces of the extremities. The WBC count of those suffering from streptobacillary RBF ranges between 6,000 and 30,000. Reagin tests (syphilis serology) are false-positive in 25% of the cases

The wound from the bite heals spontaneously. Headache, nausea, vomiting, myalgia, minimal regional lymphadenopathy, anemia, endocarditis, myocarditis, meningitis, pneumonia, and focal abscesses have been reported. Although most cases resolve spontaneously within 3 weeks, 13% of untreated cases are fatal.

Bacterial endocarditis, myocarditis, pericarditis and abscesses in the brain or other tissues are rare but serious complications.

It is often confused with Rocky Mountain Spotted fever, infection with coxsackie B virus and meningoccemia. RBF due to S. moniliformis can usually be differentiated from spirillary RBF (Sodoku) clinically.

Spirillary RBF or Sodoku caused by infection with Spirillum minus.

Occurs worldwide, but is most common in Asia. This form of RBF is characterized by a longer incubation period (4 to 28 days but usually longer than 10 days). The initial wound may persist with edema and ulceration or may heal only to  reappear at the onset of symptoms. Sodoku is characterized by a recurrent fever (101-104oF). Cycles of fever lasting from 2 to 4 days recur generally for 4 to 8 weeks but may continue for months. These febrile cycles rarely last longer than one year. A roseolar-urticarial rash sometimes develops. It is generally less prominent than the rash produced by S. moniliformis. Arthritis is rare.

Regional lymphadenitis and lymphangitis with malaise, headaches, and enlargement of the lymph nodes adjacent to the wound are also common. The WBC count ranges between 5,000 and 30,000.

Sodoku may easily be confused with diseases characterized by relapsing fever such as malaria, meningoccemia or Borrelia recurrentis infection especially if there is no history of rodent bite. reagin tests (syphilis serology) are false-positive in half the cases. Complications may include endocarditis, myocarditis, hepatitis, splenomegaly, and meningitis. If left untreated mortality results in 6% to 10% of the cases.

Haverhill fever
Clinically similar to streptobacillary RBF but is usually accompanied by more severe gastrointestinal symptoms (nausea, abdominal pain, and/or vomiting) and pharyngitis.


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. minor 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.


Penicillin is the drug of choice. Doxycycline or tetracycline may be given for penicillin-allergic patients. Recommended treatment by the Center for Disease Control is intravenous penicillin for 5-7 days followed by oral penicillin for 7 days. Other antibiotics such as erythromycin, chloramphenicol, clindamycin and cephalosporins have been used with success however the effectiveness of these agents has not been assessed rigorously.

Prompt cleaning of wounds with antiseptic solution, and reducing the risk of rat bites. The effect of chemoprophylaxis following rodent bites or scratches on RBF is unknown. No vaccines are available for these diseases.

Improve conditions to minimize rodent contact with humans is the best preventative measure for RBF. Animal handlers, laboratory workers, sanitation and sewer workers must take special precautions against exposure. Wild rodents, dead or alive, should not be touched and pets must not be allowed to ingest rodents.

Those living in the inner cities where overcrowding and poor sanitation cause rodent problems are at risk for RBF. Half of all cases reported are children under 12 living in these conditions.

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Revised 11/20/14
©2014 Neal R. Chamberlain, Ph.D., All rights reserved.