BACTERIAL INFECTIONS CAUSED BY: SPIROCHETES

ENDEMIC TREPONEMATOSES

Chronic nonvenereal spirochetal infections spread by body contact.

Epidemiology

Endemic syphilis is found mainly in arid countries of the eastern Mediterranean region and West Africa (Sahel); transmission results from mouth-to-mouth contact or sharing of eating and drinking utensils. Yaws is found in humid equatorial countries, and transmission is favored by scanty clothing, poor hygiene, and skin trauma. Pinta occurs among the Indians of Mexico, Central America, and South America and is not very contagious; transmission is not well understood.

The causative agents, Treponema pallidum subspecies endemicum (endemic syphilis [nonvenereal syphilis, bejel]), T. pallidum subspecies pertenue (yaws [frambesia]), and T. carateum (pinta), are morphologically and serologically indistinguishable from T. pallidum subspecies pallidum (syphilis).

Symptoms and Signs

Endemic syphilis begins in childhood as a mucous patch, usually on the buccal mucosa, followed by papulosquamous and erosive papular lesions of the trunk and extremities. Periostitis of the leg bones is common. Gummatous lesions of the nose and soft palate develop in later stages.

Yaws begins as a granulomatous or macular lesion at the inoculation site, usually on the legs, after an incubation period of several weeks. The lesion heals but is followed by a generalized eruption of soft granulomas on the face, extremities, and buttocks, often at mucocutaneous junctions. These granulomas heal slowly and may relapse. Keratotic lesions may develop on the soles, causing painful ulcerations (crab yaws). Destructive lesions may develop later, including periostitis (particularly of the tibia), proliferative exostoses of the nasal portion of the maxillary bone (goundou), juxta-articular nodules, gummatous skin lesions, and, ultimately, mutilating facial ulcers, particularly around the nose (gangosa).

Pinta produces lesions confined to the dermis. They begin at the inoculation site as small papules and progress to erythematous plaques in several months. Erythematous, squamous patches develop later, mainly on the extremities, face, and neck. After several months, symmetric slate-blue patches develop, usually on the face and extremities and over bony prominences; later they become depigmented, resembling vitiligo. Hyperkeratosis may occur on the soles and palms. Destructive lesions leave a scar.

Diagnosis, Prophylaxis and Treatment

Diagnosis is made by the typical appearance of lesions in persons from endemic areas. The Venereal Disease Research Laboratory and fluorescent treponemal antibody absorption tests are positive but do not distinguish these diseases from venereal syphilis. Early lesions are often darkfield-positive for spirochetes and are indistinguishable from T. pallidum subspecies pallidum. The International Task Force for Disease Eradication has judged that elimination of transmission of these diseases, not eradication, is a feasible goal.

Public health control includes active case finding and the treatment with benzathine penicillin of exposed family and childhood contacts. For each disease, one IM injection of 1.2 million U of benzathine penicillin G produces healing, with rapid disappearance of the spirochetes. Children < 45 kg (< 100 lb) should receive 600,000 U.

RELAPSING FEVER (Tick, Recurrent, or Famine Fever)

An acute disease caused by several species of Borrelia spirochetes, transmitted by lice or ticks, and characterized by recurrent febrile episodes lasting 3 to 5 days, separated by intervals of apparent recovery.

Epidemiology and Pathogenesis

Relapsing fever is the term applied to recurrent fevers, clinically similar but etiologically distinct. The insect vector may be the soft ticks of the genus Ornithodoros or the body louse, depending on geographic location. The louse-borne relapsing fevers are endemic only in parts of Africa and South America; the tick-borne, in the Americas, Africa, Asia, and Europe. In the USA, the disease is generally confined to the western states, where occurrence is highest between May and September.

Borrelia are delicate, threadlike organisms 8 to 30 µ long, with pointed ends and 4 to 10 large, irregular coils. They appear in the blood during a febrile period and can be found in internal organs, especially the spleen and brain.

The louse is infected by feeding on a patient during the febrile stage. The spirochetes are not transmitted directly to man; when the louse is crushed, they are released and enter abraded skin or bites. Ticks acquire the spirochetes from rodents acting as reservoirs; humans are infected when spirochetes in the tick's saliva or coxal fluid (excreta) enter the skin as the tick bites. Congenital borreliosis has also been reported.

Symptoms, Signs and Complications

The incubation period ranges from 3 to 11 days (median, 6 days). Sudden chills mark the onset, followed by high fever, tachycardia, severe headache, vomiting, muscle and joint pain, and often delirium. An erythematous macular or purpuric rash may appear early over the trunk and extremities; conjunctival, subcutaneous, or submucous hemorrhages may be present. Mild polymorphonuclear leukocytosis may occur. Late in the course of the fever, jaundice, hepatomegaly, splenomegaly, myocarditis, and cardiac failure may occur, especially in louse-borne disease. Fever remains high for 3 to 5 days, then clears abruptly, indicating a turning point in the disease. The duration of illness ranges from 1 to 54 days (median, 18 days).

The patient is usually asymptomatic for several days to a week or more. Relapse, related to the cyclic development of the parasites, occurs with a sudden return of fever and, often, arthralgia and all the former symptoms and signs. Jaundice is more common during relapse. The illness clears as before, but 2 to 10 similar febrile episodes may follow at intervals of 1 to 2 wk. The episodes become progressively less severe, and recovery eventually occurs as the patient develops immunity.

Complications include abortion, ophthalmitis, exacerbation of asthma, and erythema multiforme. Iritis or iridocyclitis and CNS involvement can occur.

Diagnosis and Prognosis

Diagnosis is suggested by the recurrent fever and confirmed by the appearance of spirochetes in the blood during a febrile episode. The spirochetes may be seen on darkfield examination or Wright's- or Giemsa-stained thick and thin blood smears. (Acridine orange stain for examining blood or tissue is more sensitive than Wright's or Giemsa stain for peripheral blood smears.) Because the tick feeds transiently and painlessly at night, most patients do not give a history of tick bite, but may report an overnight exposure to caves or rustic dwellings. In tick-borne infection, intraperitoneal injection of the patient's blood into a mouse or rat produces large numbers of spirochetes in the animal's tail blood within 3 to 5 days. The differential diagnosis includes Lyme arthritis, malaria, dengue, yellow fever, leptospirosis, typhus, influenza, and the enteric fevers.

The mortality rate is generally 0 to 5% but may be considerably higher in very young, pregnant, old, malnourished, or debilitated persons or during epidemics of louse-borne fever.

Prophylaxis and Treatment

Tick-borne infections are difficult to prevent because tick-control measures are imperfect, although tick repellents containing diethyltoluamide (deet) for the skin and permethrin for clothing may be helpful (see Rocky Mountain Spotted Fever). Body lice are uncommon and louse-borne relapsing fever is rare in the USA.

In tick-borne fever, tetracycline or erythromycin 500 mg po q 6 h is given for 5 to 10 days; a single 500-mg oral dose of either drug cures louse-borne fever. Doxycycline 100 mg po bid for 5 to 10 days is also effective. Erythromycin estolate 40 mg/kg/day po in 2 to 3 divided doses is given to children < 8 yr. When vomiting or severe disease precludes oral administration, tetracycline 500 mg in 100 or 500 mL of saline may be given IV once or twice daily (for children > 8 yr, 25 to 50 mg/kg/day in 4 divided doses).

Therapy should be started early during fever or during the afebrile stage, but should be avoided near the end of the episode because of the danger of Jarisch-Herxheimer reaction (see Syphilis), which is occasionally fatal in louse-borne infection. Personnel and equipment should be available in case the reaction occurs. The severity of the Jarisch-Herxheimer reaction may be lessened in tick-borne relapsing fever by giving acetaminophen 650 mg po 2 h before and 2 h after the first dose of tetracycline or erythromycin.

Dehydration and electrolyte imbalance should be corrected with parenteral fluids. Codeine 30 to 60 mg po q 4 to 6 h may be used to relieve severe headache. Nausea and vomiting should be treated with dimenhydrinate 50 to 100 mg po (or 50 mg IM) q 4 h or with prochlorperazine 5 to 10 mg po or IM 1 to 4 times/day. If heart failure occurs, specific therapy is indicated.

LEPTOSPIROSIS (Infectious [Spirochetal] Jaundice)

An inclusive term for all infections due to an organism of the genus Leptospira, regardless of serotype.

Epidemiology

Leptospirosis, a zoonosis occurring in many domestic and wild animal hosts, varies from inapparent illness to fatal disease. A carrier state exists in which animals shed leptospires in their urine for months. Human infections are acquired by direct contact with an infected animal's urine or tissue or indirectly by contact with contaminated water or soil. Abraded skin and exposed mucous membranes (conjunctival, nasal, oral) are the usual portals of entry in humans. Infection occurs at any age; >= 75% of cases occur in males. Leptospirosis can be an occupational disease (eg, of farmers or sewer and abattoir workers), but most patients in the USA are exposed incidentally during recreational activities (eg, swimming in contaminated water). Dogs and rats are other common probable sources. The 40 to 100 cases reported annually in the USA occur mainly in late summer and early fall. Because distinctive clinical features are lacking, probably many more cases are not diagnosed and reported.

Symptoms and Signs

The incubation period ranges from 2 to 20 (usually 7 to 13) days. The disease is characteristically biphasic. The septicemic phase is abrupt in onset, with headache, severe muscular aches, chills, and fever. Conjunctival suffusion is characteristic, usually appearing on the 3rd or 4th day. Splenomegaly and hepatomegaly are uncommon. This phase lasts 4 to 9 days, with recurrent chills and fever that often spikes to > 39° C (102° F). Defervescence follows; then, on the 6th to 12th day of illness, the second or immune phase occurs, correlating with appearance of antibodies in the serum. Fever and earlier symptoms recur, and signs of meningitis may develop. CSF examination after the 7th day discloses pleocytosis in at least 50% of patients. Iridocyclitis, optic neuritis, and peripheral neuropathy occur infrequently. If acquired during pregnancy, leptospirosis, even during the convalescent period, may cause abortion.

Weil's syndrome (icteric leptospirosis) is a severe form of leptospirosis with jaundice and usually azotemia, hemorrhages, anemia, disturbances in consciousness, and continued fever. Onset is similar to that of less severe forms; the signs of hepatocellular and renal dysfunction appear from the 3rd to 6th day. Renal abnormalities include proteinuria, pyuria, hematuria, and azotemia. Hemorrhagic manifestations are due to capillary injury. Thrombocytopenia may occur. Hepatic damage is minimal, and complete healing occurs.

Aseptic meningitis may occur with any serotype. The CSF cell count is between 10 and 1000/µL (usually < 500/µL), with predominantly mononuclear cells. CSF glucose is normal; protein is < 100 mg/dL. In most patients with aseptic meningitis, no manifestations of significant liver and kidney disease are present.

Canicola fever is one of many geographic strains of leptospires but is in no way clinically or epidemiologically distinct from other leptospires.

Laboratory Findings

The WBC count is normal or slightly elevated in most cases but may reach 50,000/µL in severely ill, icteric patients. Leukocytosis > 15,000/µL suggests liver involvement; the presence of > 70% neutrophils helps differentiate leptospirosis from viral illnesses. In jaundiced patients, intravascular hemolysis may cause marked anemia. Serum bilirubin levels, usually < 20 mg/dL (342 µmol/L), may reach 40 mg/dL (684 µmol/L) in severe infection; BUN is usually < 100 mg/dL 36 mmol urea/L). These findings indicate liver and renal involvement.

Diagnosis and Prognosis

The diagnosis is confirmed by demonstration of the organism or by positive serologic tests. Blood should be drawn early in the illness for culture and to obtain a serum sample from the acute stage for serologic studies. Leptospires may be isolated from blood, urine, or CSF during the first phase of illness by inoculation onto Fletcher's; Ellinghausen, McCullough, Johnson, Harris (EMJH); or polysorbate (Tween 80) albumin medium. After the 1st wk, leptospires may be found in the urine by culture or darkfield examination. A radiometric method using the BACTEC 460 system allows detection of leptospires in human blood after only 2 to 5 days of incubation. A serum sample from the convalescent stage should be obtained during the 3rd or 4th wk of illness for serologic tests, including slide and microscopic agglutination studies, an indirect fluorescent antibody test, and highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) and dot-ELISA techniques.

Differential diagnosis includes meningitis or meningoencephalitis, influenza, hepatitis, acute cholecystitis, and renal failure. With the enteroviruses, which commonly cause aseptic meningitis, there is usually no history of biphasic illness. Such a history suggests leptospirosis or cytomegalovirus infections. Leptospirosis should be considered in any patient with FUO that occurs in an epidemiologic setting conducive to exposure to leptospires.

Mortality is nil in anicteric patients. With jaundice, the mortality rate is 5 to 10%; in patients > 60 yr, the rate is higher.

Prophylaxis and Treatment

Doxycycline 200 mg po given once weekly during the period of exposure prevents disease. Patient isolation is not required, but urine must be disposed of carefully. For acute infections, antibiotic therapy is effective even when begun relatively late in the disease. In severe illness, penicillin G 6 to 12 million U/day IV or ampicillin 500 to 1000 mg q 6 h IV is recommended. In less severe cases, doxycycline 100 mg bid, ampicillin 500 to 750 mg q 6 h, or amoxicillin 500 mg q 6 h po may be given for 5 to 7 days. Supportive care, including fluid and electrolyte therapy, is also important in severe cases.

LYME DISEASE (Lyme Borreliosis)

A tick-transmitted, spirochetal, inflammatory disorder causing a rash (erythema [chronicum] migrans) that may be followed weeks to months later by neurologic, cardiac, or joint abnormalities.

Epidemiology and Pathology

Lyme disease was recognized in 1975 because of close clustering of cases in Lyme, Connecticut. It has since been reported in 49 states, but > 90% of cases occur from Massachusetts to Maryland, in Wisconsin and Minnesota, and in California and Oregon. For several years, Lyme disease has been the most commonly reported tick-borne illness in the USA. Lyme disease occurs also in Europe, across the former Soviet Union, and in China and Japan. Onset is usually in the summer and early fall. Most patients are children and young adults living in heavily wooded areas.

Lyme disease is caused by a spirochete, Borrelia burgdorferi, transmitted primarily by minute ticks of the Ixodes ricinus complex. In the USA, the white-footed mouse is the primary animal reservoir for B. burgdorferi and the preferred host for nymphal and larval forms of I. scapularis (dammini), the deer tick. Deer are the preferred host for the adult ticks in the USA; sheep in Europe. Other mammals (eg, dogs) can be incidental hosts and can develop Lyme disease.

Deer ticks in the nymphal stage, which attack humans, are very small and are difficult to see. Once attached to the skin, they continue to engorge on blood for days. Transmission of B. burgdorferi does not usually occur until the infected tick has been in place for at least 36 to 48 h; thus, screening for ticks after potential exposure and removing them can help prevent infection.

B. burgdorferi enters the skin at the site of the tick bite. It may spread in lymph, producing regional adenopathy, or disseminate in blood to organs or other skin sites. The relative paucity of organisms in the involved tissue suggests that most manifestations of infection are due to host immune response rather than to the destructive properties of the organism.

Symptoms and Signs

Erythema migrans, the hallmark and best clinical indicator of Lyme disease, develops in at least 75% of patients, beginning as a red macule or papule, usually on the proximal portion of an extremity or on the trunk (especially the thigh, buttock, or axilla), between 3 and 32 days after a tick bite. The area expands, often with central clearing, to a diameter of up to 50 cm. Soon after onset, nearly 1/2 of untreated U.S. patients develop multiple, usually smaller, lesions without indurated centers. Cultures of biopsies of these secondary lesions have been positive, indicating dissemination of infection. Erythema migrans generally lasts for a few weeks; evanescent lesions may appear during resolution, and resolved skin lesions may reappear faintly, sometimes before recurrent attacks of arthritis. Mucosal lesions do not occur.

A musculoskeletal flu-like syndrome - malaise, fatigue, chills, fever, headache, stiff neck, myalgias, and arthralgias - commonly accompanies erythema migrans (or precedes it by a few days). Frank arthritis is rare at this stage. Less common are backache, nausea and vomiting, sore throat, lymphadenopathy, and splenomegaly. Symptoms are characteristically intermittent and changing, but malaise and fatigue may linger for weeks. Some patients develop symptoms of fibromyalgia.

Neurologic abnormalities develop in about 15% of patients within weeks to months of erythema migrans (generally before arthritis occurs), commonly last for months, and usually resolve completely. Most common are lymphocytic meningitis (CSF pleocytosis of about 100 cells/µL) or meningoencephalitis, cranial neuritis (especially Bell's-like palsy, which may be bilateral), and sensory or motor radiculoneuropathies; they may occur alone or in combination.

Myocardial abnormalities occur in about 8% of patients within weeks of erythema migrans. They include fluctuating degrees of atrioventricular block (1st-degree, Wenckebach, or 3rd-degree) and, rarely, myopericarditis with reduced ejection fractions and cardiomegaly.

Arthritis develops in about 60% of patients within weeks to months (occasionally up to 2 yr) of disease onset (as indicated by erythema migrans). Intermittent swelling and pain in a few large joints, especially the knee, typically recur for several years. Affected knees commonly are much more swollen than painful, often hot, rarely red. Baker's cysts may form and rupture. Malaise, fatigue, and low-grade fever may precede or accompany attacks of arthritis. About 10% of patients develop chronic (unremittent for >= 6 mo) knee involvement. Other late findings (occurring years after onset) associated with Lyme disease include an antibiotic-sensitive skin lesion--acrodermatitis chronica atrophicans--and chronic CNS abnormalities.

Laboratory and X-ray Findings

Diagnosis of early Lyme disease in a patient with typical erythema migrans in an endemic area does not require laboratory confirmation. Also, despite an ELISA sensitivity of 89% and specificity of 72%, if the clinical suspicion is low (pretest probability of disease < 20%), a positive test is more likely to be false-positive than true-positive. Thus, testing is best reserved for patients in whom suspicion is high. On skin biopsy, erythema migrans resembles an insect bite--epidermal and dermal involvement at the center (which is often indurated), dermal in the periphery. All layers of the dermis are heavily infiltrated with mononuclear cells around blood vessels and skin appendages. At the center, the papillary dermis is edematous, and the epidermis has a thickened keratin layer and intra- and extracellular edema.

Recovery of B. burgdorferi from most tissues and body fluids by culture is difficult and requires weeks. Testing for spirochetal DNA with polymerase chain reaction, although not yet generally available, may be useful diagnostically, especially with fluid from joints of untreated patients. Titers of specific antispirochetal antibodies--first IgM, then IgG--are determined preferably by ELISA or by indirect immunofluorescence but are less useful before the patient has made antibodies; confirmation of positive titers by Western blot is needed. Elevated titers in CSF relative to serum may be helpful when neurologic disease is suspected.

Cryoprecipitates and circulating immune complexes often occur early, and the ESR may be elevated. The Hct and WBC and differential counts usually are normal. Rheumatoid and antinuclear factors rarely are present, and infection does not cause false-positive VDRL results. Serum complement components are either normal or elevated during active disease. The urinalysis and serum creatinine levels usually are normal; AST and LDH levels may be slightly elevated when erythema migrans is present.

High C1q-binding activity occurs in sera of most patients with erythema migrans and tends to persist in patients who develop neurologic or cardiac abnormalities. By the time arthritis appears, immune complexes are usually no longer evident in sera but are found in synovial fluid.

Patients who develop chronic arthritis have an increased frequency of the B-cell alloantigen HLA-DR4 but not of HLA-B27 (as occurs commonly in patients with spondyloarthropathies).

Synovial fluid findings vary but typically show a WBC count of about 25,000/µL (range, 500 to 110,000/µL), mostly granulocytes; about 5 g/dL of protein; and C3 and C4 levels usually > 1/3 higher than those of serum.

Synovial membrane from affected joints may be indistinguishable from that of RA patients. Nonspecific findings include villous hypertrophy, vascular congestion, and colonization with lymphocytes and plasma cells that may resemble early lymphoid follicles and, as in RA, are presumably capable of producing antibody locally. In addition, there may be an obliterative endarteritis and, rarely, demonstrable spirochetes. Pannus formation and erosion of cartilage and bone rarely may occur.

X-ray findings usually are limited to soft tissue swelling, but a few patients have had erosion of cartilage and bone.

Differential Diagnosis

In children, Lyme disease must be distinguished from juvenile RA; in adults, from Reiter's syndrome and atypical RA. Important negative findings include absence (usually) of morning stiffness, subcutaneous nodules, iridocyclitis, mucosal lesions, rheumatoid factor, and antinuclear antibodies. Lyme disease presenting with a musculoskeletal flu-like syndrome in summer may resemble ehrlichiosis, an emerging infection transmitted by the same tick; the lack of leukopenia, thrombocytopenia, elevated transaminases, and inclusion bodies in neutrophils helps distinguish Lyme disease. Acute rheumatic fever is considered in the occasional patient with migratory polyarthralgias and either an increased PR interval or chorea (as a manifestation of meningoencephalitis). However, patients with Lyme disease rarely have heart murmurs or evidence of a preceding streptococcal infection. The lack of axial involvement distinguishes it from spondyloarthropathies with peripheral joint involvement. Lyme disease may mimic idiopathic Bell's palsy as well as other causes of lymphocytic meningitis, peripheral neuropathies, and chronic fatigue and other CNS syndromes.

Treatment

Most features of Lyme disease respond to antibiotics, but the time to complete resolution may extend well beyond the period of treatment, and treatment of early disease is the most successful. Optimal therapy for many conditions, including arthritis and CNS involvement, is still evolving; however, the regimens specified are curative in most patients.

Children < 8 yr receive amoxicillin 250 mg tid or 30 to 50 mg/kg/day po in 3 divided doses (maximum 2 to 3 g/day) for 10 to 21 days. In children > 8 yr, doxycycline 4 mg/kg/day po (maximum, 200 mg/day divided bid) is an alternative choice. For children allergic to penicillin, cefuroxime axetil 30 mg/kg/day divided bid (maximum 1 to 2 g/day) or erythromycin 250 mg qid or 30 to 50 mg/kg/day po in 3 to 4 divided doses (maximum 2 g/day) for 10 to 21 days is almost as effective. For early or late neurologic disease, children are given IV (IM is painful) ceftriaxone 75 to 100 mg/kg/day (maximum 2 g) or IV penicillin G 300,000 U/kg/day in 6 divided doses (maximum, 20 million U/day) for 14 to 21 days.

Pregnant women receive amoxicillin 500 mg tid for 21 days if the disease is early and localized. Any manifestation of disseminated disease requires the administration of penicillin G 20 million U/day IV for 14 to 28 days. No treatment is necessary for pregnant women who are seropositive but asymptomatic.

For symptomatic relief, aspirin (90 mg/kg/day in children) or other NSAIDs may be used. Complete heart block may require a temporary pacemaker. For tense knee joints due to effusions, aspiration of fluid and the use of crutches are indicated. Patients with arthritis of the knee that persists despite antibiotic therapy may respond to arthroscopic synovectomy.

A vaccine based on recombinant outer-surface protein specific to B. burgdorferi was available but was removed from the U.S. market in 2002.

RAT-BITE FEVER

Rat-bite fever is transmitted to humans in up to 10% of rat bites. However, there may be no history of rat bite in microbiologically proven cases. Both the streptobacillary and spirillary forms affect mainly crowded urban dwellers and biomedical laboratory personnel. The streptobacillary form is more common.

Streptobacillary Rat-Bite Fever

Rat-bite fever caused by the pleomorphic gram-negative bacillus Streptobacillus moniliformis.

S. moniliformis is present in the oropharynx of healthy rats. Epidemics have been associated with ingestion of unpasteurized S. moniliformis-contaminated milk (Haverhill fever), but infection is usually a consequence of a bite by a wild rat or mouse; weasels and other rodents have also been implicated.

The primary wound usually heals promptly, but after an incubation period of 1 to 22 (usually < 10) days, a viral-like syndrome develops abruptly, causing chills, fever, vomiting, headache, and back and joint pains. A morbilliform, petechial rash appears in about 3 days on the hands and feet of most patients. Polyarthralgia or arthritis, usually affecting the large joints asymmetrically, develops in many patients within a week and may persist for several days or months if untreated. Bacterial endocarditis and abscesses in the brain or other tissues are rare but serious. Some patients have infected pericardial effusion and infected amniotic fluid.

Diagnosis is confirmed by culturing the organism from blood or joint fluid. Measurable agglutinins develop during the 2nd or 3rd wk and are diagnostically important if the titer increases. The WBC count ranges between 6,000 and 30,000/µL. Although the streptobacillary form usually can be differentiated clinically from the spirillary form, it can be confused with Rocky Mountain spotted fever, infection with coxsackievirus B, and meningococcemia.

Treatment is procaine penicillin G 1.2 million U/day IM or penicillin V 2 g/day po for 7 to 10 days. Erythromycin 2 g/day po may be used for patients allergic to penicillin.

Spirillary Rat-Bite Fever (Sodoku)

Rat-bite fever caused by Spirillum minus.

S. minus infection is acquired through a rat or, occasionally, a mouse bite. The wound usually heals promptly, but inflammation recurs at the site after an incubation period of 4 to 28 (usually > 10) days, accompanied by a relapsing fever and regional lymphadenitis. A roseolar-urticarial rash sometimes develops but is less prominent than the streptobacillary rash. Systemic symptoms commonly accompany the fever, but arthritis is rare.

Diagnosis is made by demonstration of the spirillum in blood smears or tissue from the lesions or lymph nodes, or by Giemsa stain or darkfield examination of blood from inoculated mice. The WBC count ranges between 5,000 and 30,000/µL. The Venereal Disease Research Laboratory test results are false-positive in half the patients. The disease may easily be confused with malaria, meningococcemia, or Borrelia recurrentis infection, all of which are characterized by relapsing fever. In untreated patients, 2- to 4-day cycles of fever usually recur for 4 to 8 wk, but febrile episodes rarely recur for > 1 yr.

Treatment is procaine penicillin G 1.2 million U/day IM or penicillin V 500 mg po qid. Tetracycline 500 mg po qid may be used for patients allergic to penicillin. Duration of treatment should be 14 days; if endocarditis exists, a longer course is required and should begin with parenteral treatment.

Source: Merck