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Green, Jennifer S. MD*; Singh, Jasjit MD; Cheung, Michele MD; Adler-Shohet, Felice C. MD; Ashouri, Negar MD

The Pediatric Infectious Disease Journal: February 2011 - Volume 30 - Issue 2 - p 163-165
doi: 10.1097/INF.0b013e3181f4cc25
Brief Reports

Murine typhus is typically a mild febrile illness caused by Rickettsia typhi, generally confined to Texas and Southern California. Clinicians should consider early treatment with doxycycline when presented with a child having protracted fever, rash, and headache. We present 5 pediatric cases and a literature review highlighting the changing epidemiology and diagnostic difficulty of typhus.

From the Divisions of *Academic Affairs and †Infectious Disease, Children's Hospital of Orange County, Orange, CA; ‡Department of Public Health, County of Orange Health Care Agency, Orange, CA.

Accepted for publication July 27, 2010.

Address for correspondence: Jennifer Green, MD, Children's Hospital of Orange County, 455 S. Main St., Orange, CA 92686. E-mail:

Murine, or endemic typhus, is a febrile illness caused by Rickettsia typhi, an obligate intracellular Gram-negative organism. Fever may be accompanied by severe headache and myalgias. A discrete maculopapular rash typically appears on days 5 to 7 of illness. Since symptoms have considerable overlap with a variety of illnesses, particularly viral syndromes, the diagnosis is often not considered. We present 5 pediatric cases of confirmed murine typhus in Orange County, California, which highlight the need to consider the diagnosis of endemic typhus in the child with prolonged fever and rash. These children received extensive and costly evaluations before the diagnosis of typhus was considered. The changing epidemiology and review of the literature are presented to aid the clinician in considering this infection in the diagnosis of the child with fever of unknown origin.

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Clinical and laboratory features of the 5 cases are presented in Tables 1 and 2. Each of these patients eventually was hospitalized for evaluation of fever. All of our cases presented after at least 1 week of fever following multiple evaluations and treatments for potential alternative diagnoses. Of the 5 patients, 4 had rashes. Headache, abdominal pain, myalgias, and emesis were prominent symptoms. All had elevated C-reactive protein, mild hepatitis, and mild hyponatremia. Cases 1 and 2 presented with the more classic picture of prolonged fever, rash, and headache in a teenaged child. Both responded rapidly to empiric doxycycline therapy, becoming afebrile within 24 hours. Case 3 had milder illness typically seen in the younger child. Case 4 demonstrates the diagnostic difficulty of considering the diagnosis when rash is not present. This child was admitted to the pediatric intensive care unit because of severe thrombocytopenia and concern for possible hemolytic-uremic syndrome. Case 5 highlights the clinical overlap between murine typhus and Kawasaki disease as this patient met full criteria for Kawasaki disease, including an isolated cervical lymphadenopathy, and received intravenous immunoglobulin and aspirin before the diagnosis of murine typhus was performed. All patients had diagnosis of murine typhus confirmed by indirect fluorescent antibody testing (IFA), with acute titers sent to commercial laboratories (Specialty Laboratories in Valencia, CA for cases 1, 3, and 4 and Focus Diagnostics in Cypress, CA for cases 2 and 5) and convalescent titers to the Orange County Health Department.





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Endemic typhus, first described in 1926, is a zoonotic disease with a rat reservoir and a flea vector, most commonly Xenopsylla cheopis. Humans are incidental hosts. Historically, it has been considered an urban disease because of over-crowding and poor sanitation.1 Currently less than 100 cases are reported annually in the United States.2 However, the exact prevalence of murine typhus is difficult to determine because of under reporting and under-diagnosis.3 Aside from a 2002 outbreak in Hawaii, cases are mostly limited to Texas and Southern California.1 In 2009 in California, there were 25 reported cases of typhus, 6 of which were in Orange County.4 There is evidence that typhus exists in other states, as demonstrated by Marshall's data of seropositive children in Oklahoma, Kentucky, and Kansas.3

As early as 1970, researchers noticed a trend in typhus cases in suburban locations rather than the typical urban setting. Adams et al5 documented an increase in R. typhi seropositive animals, specifically opossums, in the Los Angeles suburbs. Opossums carry a different species of flea, Ctenocephalides felis or “cat flea,” which is ubiquitous and infects peridomestic animals such as opossums, skunks, and free ranging cats and dogs.5 It has been shown that C. felis can transmit R. typhi to humans.6 Since suburban dwellers are more likely to have contact with peridomestic animals, murine typhus is now being maintained in the suburban areas of Southern California and Texas. There is also increasing evidence that many of the clinically diagnosed cases of murine typhus may, in fact, be caused by Rickettsia felis, a recently discovered pathogen.7

Symptoms of endemic typhus may be mild, particularly in younger children, and seldom last for more than 2 weeks, leading to under diagnosis. However, visceral involvement, such as aseptic meningitis, or endocarditis, can occur. During a recent outbreak in Austin, Texas of 53 patients, only 8 of whom were children, 70% were hospitalized, with 30% in the intensive care unit.8 Untreated severe disease can be fatal in 4% of cases.1

Our cases exhibited features consistent with those previously described in the literature. The most common symptoms in a case series of 30 pediatric patients were fever, rash, and headache, and the most common laboratory abnormalities were elevated erythrocyte sedimentation rate, elevated transaminase values, hyponatremia, and leukopenia with a left shift.9 Our patients had similar findings and, additionally, abdominal pain was common. Unfortunately, patients without these common symptoms may not be recognized such as was case 4 who lacked a rash. Lymphadenopathy, especially isolated lymphadenopathy, is not a common finding,9 thus adding to the complexity of case 5. The difficulty comes in confirming the clinical suspicion of typhus, as these symptoms and laboratory values are nonspecific and frequently lead to extensive infectious workup and treatments before to serologic confirmation. Because typhus serologies are performed only in certain specialty laboratories, results are often delayed making empiric administration of doxycycline imperative if the diagnosis is suspected to prevent severe or life-threatening disease.10 Doxycycline is considered a safe and superior therapy in children less than 8 years old, regardless of risk of teeth staining.11

IFA and enzyme immunoassays have largely replaced the Weil Felix agglutination test and peak at about 4 weeks after infection. A 4-fold titer increase between acute and convalescent serum specimens is diagnostic. IFA, the standard diagnostic test, identifies antibodies to the Rickettsial heat-labile protein antigens and lipopolysaccharide antigens.10 Enzyme immunoassay uses antigen-coated wells to identify different types of Rickettsial infections. The different Rickettsial species are so closely related that there is significant cross-reactivity, especially between R. typhi and R. felis, which are 98.5% homologous.12 A polymerase chain reaction test that amplifies the spotted fever group genetic segment or the typhus group segment during the acute phase of infection is not currently commercially available.1

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Clinical manifestations of endemic typhus can mimic other protracted febrile illnesses such as viral infections and noninfectious processes such as Kawasaki disease. Clinicians should consider the diagnosis even in patients without rash, who have consistent clinical and laboratory features, particularly those residing in endemic areas like southern California, southern Texas, and Hawaii. Empiric doxycycline while awaiting confirmatory serologic results can lead to rapid improvement and avoid life-threatening complications.

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1. Civen R, Ngo V. Murine typhus: an unrecognized suburban vectorborne disease. Clin Infect Dis. 2008;46:913.
2. Boostrom A, Beier MS, Macaluso JA, et al. Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas. Emerg Infect Dis. 2002;8:549–554.
3. Marshal G. Rickettsia typhi seroprevalence among children in the southeast United States. Pediatr Infect Dis J. 2000;19:1103–1104.
4. Horton MB. Monthly Summary Reports of Selected California Reportable Diseases, December 2009. California Department of Public Health. 26 Jan 2010. Available at: Accessed July 11, 2010.
5. Adams WH, Emmons RW, Brooks JE. The changing ecology of murine (endemic) typhus in Southern California. Am J Trop Med Hyg. 1970;19:311–318.
6. Sorvillo FJ, Gondo B, Emmons R, et al. A suburban focus of endemic typhus in Los Angeles County: association with seropositive domestic cats and opossums. Am J Trop Med Hyg. 1993;48:269–273.
7. Azad AF, Radulovic S, Higgins JA, et al. Flea-borne rickettsioses: ecologic considerations. Emerg Infect Dis. 1997;3:319–327.
8. Adjemian J, Parks S, McElroy K, et al. Murine typhus in Austin, Texas, USA, 2008. Emerg Infect Dis. 2010;16:412–417.
9. Fergie JE, Purcell K, Wanat D. Murine typhus in South Texas children. Pediatr Infect Dis J. 2000;19:535–538.
10. LaScola B, Raoult D. Laboratory diagnosis of Rickettsioses: current approaches to diagnosis of old and new Rickettsial diseases. J Clin Microbiol. 1997;35:2715–2727.
11. Endemic typhus (Murine typhus). In: Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:710–711.
12. Schriefer ME, Sacci JB, Dumler S, et al. Identification of a novel rickettsial infection in a patient diagnosed with murine typhus. J Clin Microbiol. 1994;32:949–954.

murine typhus; endemic typhus; Rickettsia typhi; pediatric

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