Until the beginning of the 19th century, no clear clinical differentiation could be made between typhus and typhoid–two of the major pestilence. Brill-Zinsser disease: Recrudescence of epidemic typhus years after the initial attack. The agent that causes epidemic typhus (Rickettsia prowazekii) remains. Brill-Zinsser disease occurs as a late recrudescence of epidemic typhus. The clinical effect of a newly developed azalide, called azithromycin, against Rickettsia.
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Nicholson, Joseph Singleton, Catherine M. Recrudescent Rickettsia prowazekii infection, also known as Brill-Zinsser disease, can manifest decades after untreated primary infection but is rare in contemporary settings.
We report the first known case of Brill-Zinsser disease in a patient originally infected with a zoonotic strain of R. Brill-Zinsser disease is a form of recrudescent epidemic typhus that occurs years or decades after primary typhus infection [ 1—4 ]. However, in dixease United States, improved sanitation and hygiene measures have largely eliminated diseawe human body louse vector and epidemic typhus as public health zinssser . In addition, the availability of tetracycline-class antibiotics to effectively treat rickettsial infections has reduced the severity and duration of infections [ 14 ].
Although the classic louseborne cycle of Rickettsia prowazekii is not common in the United States, R.
Brill-Zinsser disease |
There have been at least 47 cases documented in humans since Centers for Disease Control and Prevention, unpublished data [ 56 ]. Most of these cases had reported contact prior to illness onset with the southern flying squirrel, Glaucomys volans, which serves as a zoonotic reservoir for a sylvatic cycle of infection [ 56 ]. In this report, we describe the first known reported case of Brill-Zinsser disease following a primary infection with sylvatic epidemic typhus acquired from flying squirrels.
The patient had been treated for a subacute rib fracture in March and underwent a myringotomy procedure in April but had been otherwise healthy. Infection with the tick-borne pathogens Ehrlichia chaffeensis or Anaplasma phagocytophilum was considered in the differential diagnosis on the basis of clinical presentation and the patient’s rural Massachusetts residence, although the patient denied recent exposure to ticks. The patient was given empirical treatment with oral doxycycline at mg twice daily.
The patient had previously received a diagnosis of R. Approximately 13 days after zinssser activity, the patient developed headache, rash, chills, fatigue, and arthralgias.
Sylvatic typhus was not initially considered, and the patient was prescribed ciprofloxacin at mg twice daily for 10 days; recovery occurred over a span of 21 days. Although the patient denied recent contact with flying squirrels, he reported that his symptoms felt similar to those experienced during his previous typhus infection. After consultation with the Centers for Disease Control and Prevention, serum samples were submitted for serological assessment.
In addition, archived serum that had been collected from the patient in after his initial R. Typhus-group serological analysis was conducted using indirect immunofluorescence assays against R.
The assay format, buffers, and other reagents were used in accordance with methods previously described . The patient demonstrated a rapid increase in serum IgG antibody titers to R. A low increase in IgM antibody titers was noted, with a maximum titer of 1: Results of nested polymerase chain reaction PCR assay for typhus-group rickettsiae in the patient’s acute serum sample collected on 9 July were negative.
Results of tests for IgG antibodies to E. The patient’s prior R. The patient’s fever resolved by day 5 of doxycycline therapy, and complete resolution of clinical signs was achieved by day In this report, we describe the first case of Brill-Zinsser disease following sylvatic R.
The patient’s typhus infection was confirmed by a significant increase in R. The development of Brill-Zinsser disease in this patient during is supported by increasing IgG antibody titers to R.
The patient denied recent exposure to possible reservoirs or vectors of R. The low-level antibody titers to R. Although results of PCR of the patient’s acute serum sample were negative, this finding is not wholly unexpected.
The patient had started doxycycline therapy 3 days prior to the date of serum collection, which decreases the sensitivity of the assay.
Furthermore, an acute whole blood sample was not available, and this may have served as a better tool for assessment.
Past studies have described patients with Brill-Zinsser disease as those with a fever of unknown origin who had a history of living in an area where typhus is endemic and who presented with a headache and rash [ 23 ]. In more contemporary case reports Table 3patients with Brill-Zinsser disease have displayed a variety of signs and symptoms, and rash has been absent in at least 1 other published case report [ 9—12 ].
This patient experienced an illness compatible with either acute or recrudescent typhus infection, albeit perhaps more mild than some other cases reported in the literature.
Past studies have suggested that only a fraction of patients with traditional louseborne typhus go on to experience recrudescent typhus . Brill-Zinsser disease ddisease be linked to waning immunity, stress, or other factors that facilitate recrudescence, although the precise mechanism is unknown and may vary among individuals.
In a mouse model for Brill-Zinsser disease, transient rickettsemia can be reactivated through diseasr administration of immunosuppressive doses of dexamethasone . This patient had been treated for a rib injury and underwent myringotomy in the 6 months prior to receiving a diagnosis of Brill-Zinsser disease, and it is possible that these stressful events may have influenced reactivation.
The lack of previous reports of Brill-Zinsser disease following sylvatic R. An additional reason why Brill-Zinsser disease may be infrequently identified following sylvatic typhus infection is treatment of properly diagnosed infections with the drug of choice, tetracyclines, during acute illness.
Doxycycline is considered the drug of choice for treatment of all rickettsial infections, including R. Other antibiotics are generally considered less effective for treatment of rickettsial infection and have been associated with an increased risk of fatal outcome . Chloramphenicol and fluoroquinolones have been shown to have some variable degree of efficacy in treatment of infections ziinsser another typhus group rickettsiae, R.
In a mouse model of recrudescent typhus, animals treated with doxycycline during primary infection produce significantly reduced levels of rickettsemia after administration disexse dexamethasone, suggesting that appropriately timed treatment with this antibiotic may reduce the risk of later Brill-Zinsser disease .
At the time of this patient’s clinical presentation insylvatic typhus was not initially suspected as the cause of illness, and treatment with a tetracycline group antibiotic was not incorporated as part of the therapeutic regimen. The patient’s primary infection was thus essentially untreated, and this may have in uenced the patient’s later development of Brill-Zinsser disease.
Although no fatal cases have been reported to date in association with sylvatic typhus, severe cases requiring hospitalization and intensive care have occurred, and it is presumed that these infections carry diswase potential for fatal outcome if not recognized and promptly treated.
Physicians should maintain a high clinical suspicion for bril, in patients presenting with febrile illness and other signs suggestive brilo rickettsial infection that also report possible exposure to flying squirrels, whether direct eg, contact or indirect eg, living or working in a building with an infestation.
Suspected cases should be treated empirically with doxycycline, and appropriate diagnostic tests for rickettsial infections should be requested. In addition to PCR or culture of whole blood or rash-site skin biopsy sample, paired acute and convalescent serum samples should be tested for presence of antibodies to R.
Finally, physicians should consider Brill-Zinsser disease in patients presenting with new-onset fever if a prior diagnosis of typhus has been made and should consider empirical treatment with doxycycline pending the outcome of appropriate diagnostic tests. Oxford University Press is a department of the University of Oxford.
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Close mobile search navigation Article navigation. Abstract Recrudescent Rickettsia prowazekii infection, also known as Brill-Zinsser disease, can manifest decades after untreated primary infection zimsser is rare in contemporary settings. View large Download slide.
Ecologic studies on the interepidemic survival of louse-borne epidemic typhus fever. Treatment of epidemic typhus: Cluster of sylvatic epidemic typhus cases associated with flying squirrels, — An indirect immunofluorescence assay using a cell culture-derived antigen for the detection of antibodies to the agent of human granulocytic ehrlichiosis.
Serological response of patients diseasr from primary and recrudescent typhus: Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model. Analysis of risk hrill for fatal Rocky Mountain spotted fever: Comparison of the effectiveness of five different diaease regimens on infection with Rickettsia typhi: Add comment Close comment form modal.
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