Date Published: June 14, 2013
Publisher: Public Library of Science
Author(s): Stalin Viswanathan, Vivekanandan Muthu, Nayyar Iqbal, Bhavith Remalayam, Tarun George, Friedemann Paul. http://doi.org/10.1371/journal.pone.0066595
Scrub typhus is prevalent in India although definite statistics are not available. There has been only one study on scrub typhus meningitis 20 years ago. Most reports of meningitis/meningoencephalitis in scrub typhus are case reports
A retrospective study done in Pondicherry to extract cases of scrub typhus admitted to hospital between February 2011 and January 2012. Diagnosis was by a combination of any one of the following in a patient with an acute febrile illness- a positive scrub IgM ELISA, Weil-Felix test, and an eschar. Lumbar puncture was performed in patients with headache, nuchal rigidity, altered sensorium or cranial nerve deficits.
Sixty five cases of scrub typhus were found, and 17 (17/65) had meningitis. There were 33 males and 32 females. Thirteen had an eschar. Median cerebrospinal fluid (CSF) cell count, lymphocyte percentage, CSF protein, CSF glucose/blood glucose, CSF ADA were 54 cells/µL, 98%, 88 mg/dL, 0.622 and 3.5 U/mL respectively. Computed tomography was normal in patients with altered sensorium and cranial nerve deficits. Patients with meningitis had lesser respiratory symptoms and signs and higher urea levels. All patients had received doxycycline except one who additionally received chloramphenicol.
Meningitis in scrub typhus is mild with quick and complete recovery. Clinical features and CSF findings can mimic tuberculous meningitis, except for ADA levels. In the Indian context where both scrub typhus and tuberculosis are endemic, ADA and scrub IgM may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis.
Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, and is characterized by an eschar, lymphadenopathy, multisystem involvement and a rapid response to doxycycline. Scrub typhus is seen in all terrains of the tsutsugamushi triangle, a geographical region of south and east Asia and the southwest Pacific and is related mostly to agricultural activities . Although it was known in China in the 3rd century A.D, scrub typhus (tsutsugamushi fever) was described by Hakuju Hashimoto in 1810 in people living on the banks of the Shinano river  and later by Baelz and Kawakami in 1879  as Japanese “flood fever” . Tsutsugamushi describes a Japanese term for tsutsuga “illness” and mushi “insect/creature”. Taiwan is the centre of the tsutsugamushi triangle and the first case reported in that country was in 1915 . The first and second cases in Korea were reported in 1951 and 1986 respectively  and it now has the highest reported incidence in the world . About one million new cases are identified annually . The first reported cases in India were in 1934, in Himachal Pradesh . We do not have definite statistics in India due to lack of awareness, unavailability and high cost of diagnostic kits and the fact that it is not a reportable illness.
The Pondicherry Institute of Medical Sciences is a 550- bedded teaching hospital serving the coastal town of Pondicherry and surrounding districts of Tamil Nadu with a population of nearly seven million. We did a retrospective analysis of all adult cases (≥16 years) of scrub typhus that were admitted in the hospital between February 2011 and January 2012. Computerized records of the Medical Records Department were searched using the terms, “scrub typhus”, “typhus”, “scrub typhus meningitis” and “rickettsial meningitis”. Confirmed cases of scrub typhus were selected based on a positive scrub IgM ELISA (Scrub Typhus Detect™ IgM ELISA, InBios India, detecting IgM antibodies to Orientia tsutsugamushi derived recombinant antigens), a positive Weil-Felix test (WFT), the presence of an eschar or a combination of the three in a patient with an acute febrile illness. Probable cases of scrub typhus without any of the above three were excluded from the study even if recovery following doxycycline was noted. Sixty nine adult cases were found- 65 of scrub typhus, three of Indian tick typhus and one of endemic typhus with none of the four having meningitis. There were no pediatric cases found during the study period. Sixty five cases were included in the study and divided into two groups based on the presence or absence of meningitis. The remaining four patients without scrub typhus (but positive titers of WFT OX:2, OX:19) were excluded from the study.
Seventeen (26%) patients had clinical and laboratory evidence of meningitis and male: female ratio for this group was 10∶7(Table 2). The meningitis group also had a significantly higher percentage of patients with low grade fever and a lower percentage with respiratory symptoms. On examination the temperature, pulse and respiratory rates and incidence of crackles were significantly lower in patients with meningitis. Arthralgia, fatigue, edema, lymphadenopathy, pleural effusions, crackles and rhonchi were seen only in the control group but were not statistically significant. Mean duration of hospital stay was lower in patients without meningitis. Elevated urea, elevated total WBC counts in blood and a normal chest X-ray (CXR) were significantly associated with the presence of scrub meningitis (Table 3). A higher percentage of patients in the control group had elevated ESR, AST (×3times), bilirubin, GGT and WFT positivity (>1∶80) but without statistical significance. A positive WFT (≥1∶20) was seen in 33 patients (10/15 patients with meningitis) but only 7(7/15) patients had WFT titers >1∶80.
In India, scrub typhus has been reported in at least 16 states (Jammu & Kashmir, Himachal Pradesh, Rajasthan, Haryana, Maharashtra, Karnataka, Andhra Pradesh, Kerala, Tamil Nadu, Pondicherry, West Bengal, Sikkim, Uttaranchal, Assam, Arunachal Pradesh, and Nagaland) ,,. Although most studies from Tamil Nadu are from one institute , documentation has been done in at least 15 districts ,.
Scrub typhus meningitis is a milder complication compared to respiratory or gastrointestinal problems even if it is associated with altered sensorium or cranial nerve deficits and generally resolves completely with doxycycline therapy. Due to the presence of lymphocytic pleocytosis with increased CSF protein, TBM is a close differential diagnosis. This may result in rifampicin based ATT masking the diagnosis of scrub typhus and sometimes results in patients continuing long term therapy for TBM. Since India is endemic for both TB and scrub typhus, awareness of simple-to-treat scrub typhus with access to specific tests like scrub IgM and CSF ADA may go a long way in avoiding unwarranted treatment in patients.