By Joseph E. Safdieh, MD

Assistant Professor of Neurology, Weill Cornell Medical College

Dr. Safdieh reports no financial relationships relevant to this field of study.

Synopsis: Scrub typhus infections involve the nervous system in a majority of cases and should be suspected in patients who live in, or are returning from, endemic regions with a compatible clinical syndrome.

Source: Misra UK, et al. Neurological manifestations of scrub typhus. J Neurol Neurosurg Psychiatry 2015;86:761-776.

Rickettsial diseases are bacterial infections transmitted to humans through bites from infected ticks, lice, fleas, or mites. Rickettsial diseases manifest in three forms, including typhus, spotted fever, and scrub fever. The most common rickettsial disease in the United States is Rocky Mountain spotted fever, caused by Rickettsia rickettsii. Other rickettsial diseases occur with more frequency in other parts of the world and can cause neurologic manifestations including meningoencephalitis. Scrub typhus is caused by Orientia tsutsugamushi and is endemic in northern Japan, northeastern Russia, parts of Australia, Pakistan, and India. Scrub typhus has varied clinical manifestations from a nonspecific febrile illness to severe multi-organ failure, with scattered reports of neurologic involvement as well. The diagnosis is often delayed, leading to poor outcomes including death. Scrub typhus responds well to antibiotic therapy, so it is important to make the proper diagnosis.

In this paper, the authors present a cross-sectional study evaluating the medical and neurologic manifestations of scrub typhus at a tertiary care teaching hospital in North India. Over the course of 2 years, 37 patients were identified. There was no gender predilection. Median age of the patients was 37 years. The median course of illness was 2 weeks. All patients had fever and myalgias. The vast majority of patients had headache, respiratory symptoms, and altered sensorium (> 80%). Typical eschar skin lesion was present in only half of the patients, as was nuchal rigidity. Eight patients (22%) had seizures as part of their disease course. Other clues to the diagnosis included lymphadenopathy (65%), vomiting (73%), hepatomegaly (35%), and focal weakness (38%). Almost all patients were anemic, half demonstrated thrombocytopenia, and half demonstrated leukocytosis. Elevated ALT was present in 89% of the patients.

Twenty-eight of the 31 patients with altered sensorium underwent lumbar puncture. In those patients, the mean cerebrospinal fluid (CSF) white blood cell count was 112 with a predominantly lymphocytic pleocytosis as well as elevated protein. Patients with altered sensorium but normal CSF were classified as experiencing an encephalopathy syndrome as opposed to a meningoencephalitis syndrome. Many of the patients with meningoencephalitis presentation experienced at least 10 days of progressive symptoms, suggesting a subacute meningitis. MRI scan was performed in most patients, and was normal in all but one patient who demonstrated meningeal enhancement. No patients had parenchymal lesions. EEG demonstrated slowing in 25% of encephalitic patients but none demonstrated epileptiform activity.

All patients were treated with oral doxycycline and ultimately all patients recovered, although patients with a higher degree of disability on admission were more likely to recover slowly. Most patients improved rapidly within 48 hours of doxycycline therapy.


This is an important study for a number of reasons. For neurologists who practice in countries where scrub typhus is endemic, this paper provides significant data as to the typical presentation, signs, diagnostic testing, and prognosis of patients. For other neurologists, this paper educates us about this important Rickettsial illness, especially the rapid globalization of the world’s population. While it is unlikely that a neurologist in the United States would see this illness, it should be considered in the differential diagnosis of febrile encephalopathy or meningoencephalitis in patients who have travelled to endemic regions. This is especially important, as this disease is rapidly and easily treatable with oral doxycycline but can be fatal without treatment. It is important for U.S. neurologists to stay informed about the various infections that can affect the central nervous system, regardless of the endemic territories. Today, infectious diseases are all global.