Misdiagnosed murine typhus in a patient with multiple cerebral infarctions and hemorrhage: a case report
© Xu et al. 2015
Received: 13 December 2014
Accepted: 15 July 2015
Published: 30 July 2015
Rickettsias cause a wide spectrum of tick-, flea-, or mite-borne infections. Rickettsial infections have no classical manifestations and can often lead to encephalitis, which can be fatal if improperly diagnosed.
A 74-year-old male farmer was admitted to the hospital with fevers and a headache that had lasted for 10 days, followed by 4 days of unconsciousness, and his condition continued to deteriorate. Images showed multiple acute lesions in the brain stem, and bilateral cerebral and cerebellar hemispheres. He was finally diagnosed with endemic typhus and treated with antibiotics that resulted in improvement.
The present report describes a patient with a rickettsial infection and subsequent deterioration to coma because of an initial misdiagnosis. Because of the similarity to other infectious diseases, physicians should be more vigilant towards the history and radiologic results to ensure early detection and avoid complications which may prove to be fatal.
KeywordsEndemic or murine typhus Cerebral infarction Cerebral hemorrhage Multiple lesions
Rickettsial infections are caused by a wide spectrum of tick-, flea-, or mite-borne infections, the distribution of which is directly dependent on the arthropod vector or vectors . The most common symptoms of rickettsial infections include fevers, rashes, headaches, dizziness, myalgias, arthralgias, and anorexia, with the classic clinical triad being fevers, rash, and unremitting headache . Currently, there are no detailed data on the epidemiology of typhus, which is sometimes a localized outbreak [3, 4]. Previous Chinese epidemiologic data have shown that the prevalence of typhus fluctuates between 0.25 and 0.49 per 10,000 population . Endemic typhus caused by Rickettsia typhi is the most common type of rickettsial infection in China and is considered to be self-limiting [6, 7]. Herein we describe the misdiagnosis of a severe case of endemic typhus that presented with multiple, diffuse lesions in the cerebral white matter.
Results of laboratory tests
Reference Range for Adults
Admission (April 24)
The second day (April 25)
Discharge (May 16)
White cell count (per mm3)
Differential count (%)
Red cell count (per mm3)
Nucleated cell count (per mm3)
Liver function examination
Glutamic pyruvic transaminase (U/L)
Glutamic oxalo-acetic transaminase (U/L)
Phosphocreatine kinase (U/L)
Lactate dehydrogenase (U/L)
Burkitt’s lymphoma virus antibody (S/CO)
Herpes simplex virus type 1 antibody
Herpes simplex virus type II antibody
Serum IgG to rickettsial antibody
Timeline of events and symptoms
Clinical events and symptoms
Onset of disease
Date of emergency room visit
Color Doppler cardiac examination
Date of lumber puncture
Initiation of minocycline therapy
Baseline rickettsial antibody testing
Parasite antibody testing
Serial rickettsial antibody testing
Discussion and conclusions
In China, R. typhi is the leading cause for endemic murine typhus, which is primarily transmitted by the rat flea . Human murine typhus infection is characterized by high fevers, a skin rash, and a combination of a variety of symptoms, such as acute hepatitis, pneumonia, and meningitis. The patient described herein presented with fevers, headaches, dizziness, and coma. Because the patient did not have a rash, which is a typical sign of a rickettsial infection, the condition was initially misdiagnosed at the local hospital.
The unique clinical features of this patient included the following: 1) an elderly hypertensive male with a history of cigarette smoking and alcohol consumption; 2) a 2-week incubation period with a lack of any observable skin rashes and a rapidly deteriorating physical condition; and 3) imaging results that showed multiple cerebral infarctions in the white matter together with intra-cerebral and subarachnoid hemorrhage. On admission, we first ruled out infective endocarditis based on the negative echocardiographic findings. Second, considering the fevers, headaches, elevated C-reactive protein level, and multiple intracranial lesions, meningoencephalitis was thought to be a likely diagnosis. The presence of an eschar together with an insect bite history and positive serum rickettsia-specific antibody tests, led to the final diagnosis of murine typhus complicated by pneumonia, cerebral infarction, and intracranial and subarachnoid hemorrhage.
The correct diagnosis was delayed due to the absence of any skin rashes, although the absence of rashes has been described in 10 % of reported cases [8, 9]. The pathologic features of endemic typhus include systemic vasculitis, which can induce damage to multiple organs and the brain. Rickettsia typhi proliferates and spreads via the blood stream causing injury to endothelial and vascular smooth muscle cells, thus resulting in vasculitis. The infection can also involve cerebral arteries and lead to brain damage [10, 11]. Vascular injury is the pathophysiologic basis for meningoencephalitis and a skin rash. The probable mechanism leading to infarction may be caused by small artery spasm or occlusion, and hemorrhage caused by increased vascular permeability due to the infection.
The neuroimaging results correlated with the pathologic findings of cerebral vasculitis, infarctions, and arteriolar thrombonecrosis [12, 13]. Cranial CT scans of rickettsia-infected patients can be normal  or show cerebral infarction. MR imaging findings in typhus patients have been previously shown to include focal arterial infarctions, diffuse edema, meningeal enhancement, and the presence of prominent perivascular spaces [12, 15]. In our case, the cranial CT results at the local hospital showed no cerebral infarction or hemorrhage, and the follow-up MR imaging showed multiple white matter lesions, suggesting the presence of infarction, and intracranial and subarachnoid hemorrhage. Similar MR imaging results have been described in patients with cryptococcosis and Lyme disease, which are also characterized by cerebral vasculitis [16, 17]. A study showed that 67 % of patients with abnormal neuroimaging ultimately returned to normal neurologic status and 93 % showed normal imaging after antibiotic treatment . The patient regained consciousness after 2 weeks of antibiotic treatment and was able to walk unassisted after 1 month of therapy.
From the current case and literature review we concludes the following: 1) The medical history and disease evolution are key to the clinical diagnosis of murine typhus. This elderly male farmer presented with a rash that was initially overlooked. 2) Rickettsia typhi involving the endothelial and vascular smooth muscle cells resulting in vasculitis not only lead to brain injury, but also cause multisystem organ failure. The imaging studies showed multiple infarctions, edema, and hemorrhage, which are rare in this type of case.3) The proper therapeutic treatment for rickettsial infections is simple and effective with a good prognosis due to early diagnosis.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
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