Ehrlichia chaffeensis

IlDNI Volume 11, Number 3, March 1992 Associate Editors

Editor

Charles W. Stratton, MD

Charles E. Cherubin, MD

Richard F. Jacobs, MD

Department of Pathology Vandegoilt University Medical Center Nashville, Tennessee

Veterans Administration Medical Center Wilkes-Barre, Pennsylvania

Arkansas C~tiidren's Hospital Little Rock, A~kansas

Roger G. Finch, FRCP, MRC Path

John T. Sinnott IV, MD

Nottinghana City Hospital Nottingham, United Kingdom

University of South Florida Tampa, Florida

H. Bradford Hawley, MD

Philippe Van der Auwera, MD,PhD

Wright State School of Medicine Dayton, Ohio

lnstitut Jules Bordet Brussels, Belgium

Ehrlichia chaffeensis

i.iolll CI|I.'

G o r d o n E. Schutz, MD Ehrlichia clulffeensis Gordon E. Sehutz

Questions about Listeria monocytogenes Susceptibility Testing Charles E. Cherubin CASE REPORT Erythema Nodosum Leprosum CharlesW. Stratton COMMENTS ON CURRENT PUBLICATIONS

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Assistant Professor of Pediatrics, Undversityof Arkansasfor Medical Sciences, Arkansas Children's Hospital, Division of lnfectious Diseases, Little Rock, Arkansas

Ehrlichiosis is a tick-borne, intraleukocytic rickettsial disease recently named Ehrlichia chaffeensis. Members of the family Ehrlichia have been known to cause disease in animals such as dogs, horses, cattle, sheep, wild dee~, and bison since 1935. Human disease first attributed to Ehrlichia was described in 1954 in a Japanese man with an illness characterized by fever, headache, malaise, conjunctival infection, pharyngitis, and enlarged cervical, axillary, and inguinal lymph nodes. This organism was later name Ehrlichia sennetsu and this illness, termed Sennetsu fever, is limited to Japan and possibly to other areas in Southeast Asia. Human ehrlichiosis in the United States was first reported in 1986 in a 51-year-old white male with an illness characterized by fever, hypotension, confusion, acute renal failure, hepatoceilular injury, hemorrhage, and pancytopenia.

Epidemiology Since 1986, ehrlichiosis has been re-

ported in 19 states, with the highest rates occurring in Oklahoma, Arkansas, Missouri, Virginia, and Tennessee. The patients have ranged in age from 2 to 82 years with almost half of the reported cases being over 50 years of age. Three-quarters of the patients are male and they are almost exclusively white (non-Hispanic). The majority of illness occurs in those months with high tick activity (May to July). Approximately 75% of patients are from rural areas and have a history of tick bite. Ticks are the only known vector for the Ehrlichia species but the tick vector for Ehrlichia chaffeensis is yet unidentified.

Clinical Manifestations The incubation period for human infection has been estimated to average 12 to 14 days (range I to 3 weeks). Like other rickettsial diseases, ehrlichiosis presents as an acute febrile illness (range: 38-41°C) with other as0278-2316 IDINDN 11(3) 17-24, 1992

18 Infectious Diseases Newsleuer 11(3) March 1992 Table 1. Common Signs and Symptoms of Ehrlichia chaffeensis Fever Headache Chills or rigor Malaise Nausea Myalgia Anorexia Vomiting Rash

sociated complaints ffable 1). Although reports of rashes are an uncommon feature in adults, they have been described to occur in as many as 80% of children. These rashes have variable characteristics, but are usually described as maeulopapular or petechial and may include the palms and soles, similar to Rocky Mountain spotted fever (RMSF). When present, however, they do not progress to involve the entire body like RMSF. Hematologic abnormalities are present in the majority of patients with Ehrlichia infections and tend to be consistent in both adult and pediatric cases. Leukopenia, often with lymphopenia, and thrombocytopenia are detected usually within the first week of illness. In contrast, anemia tends to occur later in the course of the illness. Common laboratory features are outlined in Table 2. 2. Abnormal Laboratory Findings with Ehrlichiosis Table

Leukopenia (with lymphopenia) Thmmbocytopenia

Diagnosis The differential diagnosis for infections caused by Ehrlichia chaffeensis encompasses most tick-borne febrile illnesses. Ehrlichiosis presents in a similar fashion to RMSF but usually lacks a rash. Patients with ehrlichiosis also tend to have a profound pancytopenia. Other disorders that should be considered include tularemia, babesiosis, Colorado tick fever, and Lyme disease. The diagnosis of infection by Ehrlichia chaffeensis relies on indirect immunofluorescence. The diagnostic criteria are a fourfold rise or fall in titer and a peak titer of better than 1:80. The specificity of the test is less than perfect and approximately onethird of patients may have significant titers for other rickettsial diseases, such as Coxiella burnetti, Rickettsia rickettsii, and Rickettsia typhi. No explanation is apparent for this at present. Now that the etiologic agent has been confirmed, there can be development of new confirmatory laboratory methods. Treatment As with other rickettsial diseases, tetracycline is the antimicrobial agent of choice for ehrlichiosis. For those patients older than 9 years of age, tetracycline (25-50 mg/kg/day in four daily doses) or doxycycline (100 mg twice daily) for 10-14 days is currently recommended. In patients who are of a younger age, chloramphenicol (50-75 mg/kg/day in four daily doses) may be used.

Anemia Elevated hepatic aminotransferases Elevated serum bilimbin Elevated serum urea nitrogen Elevated serum cteatinine

Prevention

A proper wardrobe is essential in preventing tick transmitted diseases. Clothing that covers exposed areas

such as arms and legs can aid the adventurer in excluding unwanted companions. Permethrin can be used on clothing to prevent tick attachment and insect repellants that employ N,Ndiethyl-m-toluamide (DEET) can be used for further protection. Concentrations of greater than 35% DEET have not been proven to be more effective and have a greater risk for side effects especially in small children. Close and regular inspection of all body parts is essential while in areas highly populated with ticks. Adult ticks are usually on the body for 1 to 2 h prior to attachment and the duration of attachment may be directly related to disease transmission. When ticks are discovered they should be removed. The recommended method for tick removal is to grasp the tick as close to the skin as possible with tweezers or protected fingers and then pull the tick straight out with steady, even pressure. Care should be taken to avoid twisting or jerking the tick as mouthparts may break off and be left in the skin. After the tick is removed, the area should be disinfected. More traditional methods of tick removal, including the use of fingernail polish, isopropyl alcohol, hot matches, crushing, or puncturing the tick, may only induce salivation or regurgitation into the wound, thus spreading infected secretions. The empiric use of antimicrobial agents after a tick bite to prevent the acquisition of tick-borne diseases has not been demonstrated to be effective. Bibliography Centers for Disease Control: Rocky Mountain spotted fever and human ehrlichiosis~United States, 1989. MMWR 39:281-284, 1990. Costello CM, Steere AC, Pinkerton RE, et ah A prospective study of tick bites in

. . . . . use ot ~.~/aion NOTB: No r~P °usibility is ammmcdby Ihe publisher f°r any injmy and/°r damap t° I ~ m ~ s °r ~ us a m ~ °f ~ l~fi~' ~h$~ °r ~ ' °r ~ m ~ y is justified, of ~ ~ , pmdu~, ~aio~ or i ~ ~ n t ~ ~ ~ e m~efi~ h~e~. No s u ~ t ~ t~t or ~ e should ~ ~ out ~ l ~ s , ~ the ~ ' s j u d ~ e u t , i~ risk B ~ e of ~ i d ~ ¢ m ~ ~ m ~ ~ , we ~ m m m d ~ m ~ e ~ t v ~ n of ~ m m ~ d ~ g dmagm should ~ m~e. D ~ s i o ~ , v i e s , ~ d r ~ d ~ i o n s ~ m ~ ~ , c~ of ~ ~d ~g ~ ~e ~e r ~ m i ~ of ~ ~ n . ~c~ D ~ N ~ f f ~ (~SN ~ - 2 3 1 6 ) ~ ~ mm~ ~ ~e ~x~ vo~e ~ ~ ~ E ~ S¢~ce ~ b l ~ g Co., hc., 655 Avenue of ~ e A m ~ , N ~ York, N ~ York 1~10. ~ ~ USA ~ Hmov~, PA 17331. S ~ ~ c e ~ y ~ ~sti~fions, $ 1 ~ . ~ ; i n d i v i ~ , $92.~. For ~stage outside ~ e U.S., add ~ . ~ (C~ada and Mexico r~u~e no ~ • t i ~ ~ m ~ ) . S ~ n d - d ~ ~ s ~ g e ~ d at N ~ Y ~ , ~Y, ~ d at ~ i t i o n ~ m~l~g o ~ c ~ . P m t m m ~ S~d a d ~ s c h ~ g ~ to lnfe~io~ Disuses Newslen~, El~vi~ Sci~ce ~ b l ~ h ~ g ~ . , hc., 655 Avenue of ~ e ~ , N ~ York, N ~ York 1~10.

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Infectious Diseases Newsletter 11(3) March 1992 an endemic area for Lyme disease. J Infect Dis 159:136-139, 1989. Edwards MS, Jones JE, Leass DL, et at: Childhood infection caused by Ehrlichia canis or a closely related organism. Pediatr Infect Dis 7:651-654, 1988. Eng TR, Harkess JR, Fishbein DB, et at: Epidemiologie, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988. JAMA 264:22512258, 1990. Fishbein DB, Kemp A, Dawson JE, et al: Human ehrlichiosis: Prospective active

surveillance in febrile hospitalized patients. J Infect Dis 160:803-809, 1989. Gentile DA, Kennedy BC: Wilderness medicine for children. Pediatrics 88:967-981, 1991. Harkess JR, Ewing SA, Brumit T, et al: Ehrlichiosis in children. Pediatrics 87:199-203, 1991. Maeda K, Markowitz N, Hawley RC,et at: Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med 316:853-856, 1987. McDade JE: Ehrlichiosis-A disease of ani-

mals and humans. J Infect Dis 161:609617, 1990. Needham GR: Evaluation of five popular methods for tick removal. Pediatrics 75:997-1002, 1985. Walker DH, Fishbein DB: Epidemiology of rickettsial diseases. Eur J Epidemiol 7:237-245, 1991. Address correspondence to Gordon E. Schutz, MD, Assistant Professor of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Division of Infectious Discases, Little Rock, AK 72202.

Questions about Listeria monocytogenes Susceptibility Testing Charles E. Cherubin, MD Veterans Administration Medical Center, Wilkes-Barre, Pennsylvania

Listeriosis is now thought to be an infection obtained by ingestion of food contaminated by l_z'steria monocytogenes. Immunocompetent hosts are able to deal with such ingested microorganisms whereas the immunosuppressed are not. Thus, cases are seen most often in neonates, pregnant women, and immunocompromised hosts, such as transplant patients. Interestingly, the incidence of listeriosis in the United States appears to be increasing, with food-related outbreaks being reported more frequently. In addition, this pathogen becomes more problematic because of a recent report of transferable plasmid-mediated resistance. Clearly, susceptibility testing will become increasingly important in the clinical setting and as a means of identifying new agents that might be clinically effective. The ability of susceptibility testing of Listeria to provide clinically relevant data, however, raises some important questions. Considerable clinical experience with bacterial meningitis has shown that bactericidal activity in the cerebral spinal fluid is necessary for a good therapeutic response. However, the minimal bactericidal concentrations (MBCs) for penicillin or ampicillin against Listeria monocytogenes are generally well above 10 kg/ml despite extremely low minimal inhibitory con-

centrations (MICs) of <1 kg/ml (Table 1). I.z'steria meningitis, which can be cured clinically using either penicillin or ampicillin, would then at first glance appear to be an exception to this rule. Other bacteriastatic antibiotics with low MICs and high MBCs (Table 1), such as tetracycline and chloramphenicol, however, have been found to be ineffective for the therapy of Listeria meningitis. What, then, can be used as a clinically relevant in vitro test to distinguish these antibiotics as well as others? Moreover, where do the newer cephalospofins fit? These agents have been shown to be clinically effective for many types of bacterial meningitis. Are these newer cephalospodns similar to penicillin or ampicillin, or similar to tetracycline or chloracyphenicol? MIC-MBCs (Table 1) suggest the latter as the following case will illustrate (case courtesy of Dr. Walid Khayr): Case 1

A 69-year-old male insulin-dependent diabetic was admitted to the hospital with/he diagnosis of bacterial meningitis and started on ceftriaxone as therapy. Approximately 48 h later, the CSF culture was reported as growing group B beta-hemolytic streptococcus (not completely inappropriate because Listeria can have bipolar staining, and ©1992 Elsevier Science Publishing Co., Inc.

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produce small zones of beta-hemolysis in blood agar and can have a positive spot CMAP test, as do group B streptococci). The patient did not improve on ceftriaxone and indeed his state had worsened; he was thus begun on high dose penicillin in addition to the ceftriaxone. At 72 h, the laboratory reported that the organism, in fact, was Listeria monocytogenes. Therapy was changed to ampicillin and ceftriaxone for 3 weeks, which resuited in a complete bacteriologic cure, although the patient's course was complicated by an internal hydrocephalis necessitating implantation of a CSF shunt. Disregarding the appropriateness of initial or subsequent antibiotic therapy, the needed points are made by this case. Cephalosporins are increasingly used as initial empiric therapy for meningitis. These are ineffective in the therapy of Listeria sepsis or meningitis. It should be noted that there often is a period of delay and/or confusion in making the diagnosis of a Listeria infection. Finally, it should be emphasized that penicillin or ampicillin alone are effective therapy, and their activity is not improved by concomitant cephalospodn administration. Because of the lack of clinically useful data provided by the results of