Volume 16, Number 10—October 2010
Scrub Typhus Involving Central Nervous System, India, 2004–2006
Highlight and copy the desired format.
|EID||Mahajan SK, Rolain J, Kanga A, Raoult D. Scrub Typhus Involving Central Nervous System, India, 2004–2006. Emerg Infect Dis. 2010;16(10):1641-1643. https://dx.doi.org/10.3201/eid1610.100456|
|AMA||Mahajan SK, Rolain J, Kanga A, et al. Scrub Typhus Involving Central Nervous System, India, 2004–2006. Emerging Infectious Diseases. 2010;16(10):1641-1643. doi:10.3201/eid1610.100456.|
|APA||Mahajan, S. K., Rolain, J., Kanga, A., & Raoult, D. (2010). Scrub Typhus Involving Central Nervous System, India, 2004–2006. Emerging Infectious Diseases, 16(10), 1641-1643. https://dx.doi.org/10.3201/eid1610.100456.|
To the Editor: Scrub typhus, caused by Orientia tsutsugamushi, is one of the most common infectious diseases of rural southern Asia, southeastern Asia, and the western Pacific. The disease is transmitted to humans by the bite of larvae of trombiculid mites harboring the pathogen. The disease often appears as a nonspecific febrile illness. The clinical picture of scrub typhus is typically associated with fever, rash, myalgia, and diffuse lymphadenopathy (1). Immunofluorescence assay (IFA) is the test of choice for serodiagnosis of rickettsial diseases (2). Scrub typhus has been reported from northern, eastern, and southern India, and its presence has been documented in at least 11 Indian states (3–7).
Our study’s goal was to retrospectively analyze data of patients with scrub typhus involving the central nervous system. Scrub typhus was suspected on the basis of clinical signs such as febrile illness or fever with rash or eschar. The fever workup profile (Widal agglutination test, peripheral smear, blood, and urine culture) was noncontributory. Blood samples were obtained after patients gave informed consent. All patients with clinically suspected scrub typhus received antirickettsial drugs (doxycycline and/or azithromycin) empirically. IFA and PCR of blood samples were performed to confirm scrub typhus following standard protocol (3). DNA was extracted from the blood sample (buffy coat) by using QIAamp DNA Mini Kit (QIAGEN GmbH, Hilden, Germany) according to the manufacturer’s instructions. A standard PCR specific for the 56-kDa protein with forward and reverse primers (OtsuF: 5′-AATTGCTAGTGCAATGTCTG-3′ and OtsuR: 5′-GGCATTATAGTAGGCTGAG-3′) was performed (3). PCR products were purified by using the QIAquick PCR Purification Kit (QIAGEN) according to the manufacturer’s instructions. Sequencing reactions were done by using a DNA sequencing kit, dRhodamine Terminator Cycle Sequencing Ready Reaction Mix (Applied Biosystems, Foster City, CA, USA). Sequencing was performed on an ABI PRISM 310 DNA Sequencer (Applied Biosystems). The obtained sequences were identified by comparison with sequences available in GenBank by using the BLAST software (http://blast.ncbi.nlm.nih.gov) (3).
During 2004–2006, scrub typhus was confirmed in 27 patients; 4 had features of central nervous system involvement. All 4 had fever with altered sensorium and meningeal signs; 2 had seizures. No neurologic focal deficit was noted, but all showed cerebrospinal fluid abnormalities. One patient had an eschar, but none had a rash. Serum of 2 patients was subjected to IFA; both samples showed high titers (Table), and PCR for blood was positive for O. tsutsugamushi for all patients. Serum was not subjected to examination for leptospirosis. Patients were treated mainly on the basis of clinical grounds because results of serology were not available immediately. Some clinical features of scrub typhus and leptospirosis are similar, and dual infections have been reported (8); therefore, antimicrobial drugs active against both leptospirosis and scrub typhus were included in treatment regimens. One patient received doxycycline and azithromycin, and the remaining 3 received ceftriaxone in addition to doxycycline. Two patients improved, 1 died, and 1 left hospital against medical advice. The clinical and laboratory details, treatments, and outcomes of all patients are given in the Table.
O. tsutsugamushi is an obligate intracellular parasite of professional and nonprofessional phagocytes that invades the central nervous system as part of systemic infection and is found in endothelial cells of blood vessels and in circulating phagocytes. A severe headache occurs almost invariably and has been used as a key clinical criterion for identifying suspected cases. Severe features of central nervous system involvement, such as neck stiffness, neurologic weakness, seizures, delirium, and coma, have been reported. Meningismus or meningitis has been found in 5.7%–13.5% of patients (9). The greatest degree of central nervous system involvement in rickettsial diseases occurs in Rocky Mountain spotted fever and epidemic typhus, followed closely by scrub typhus. The meninges are more commonly involved by O. tsutsugamushi than by other rickettsial infections, and the overall histologic picture in the central nervous system is best described as a meningoencephalitis (9). An exhaustive study of 200 cases of scrub typhus showed central nervous system involvement in most patients. However, focal central nervous system damage was rare, and during the encephalitis stage, few objective neurologic signs were apparent, other than those suggesting more generalized cerebral involvement, such as confusion, tremor, and restlessness (10).
Now that it is established that O. tsutsugamushi does invade cerebrospinal fluid, scrub typhus should be considered a cause of mononuclear meningitis in areas in which it is endemic. In our study 1 patient died despite treatment with doxycycline and azithromycin, suggesting the possibility of resistance to these antimicrobial drugs as recently posited in a study conducted in southern India (6). Scrub typhus in these regions should be further investigated in prospective studies, and clinical isolates should be obtained to evaluate susceptibility to antimicrobial drugs.
- Raoult D. Scrub typhus. In: Mandell GL, Bennet JE, Dolin R, editors. Principles and practice of infectious diseases. 6th ed. Philadelphia: Churchill Livingstone; 2004. p. 2309–10.
- Blacksell SD, Bryant NJ, Paris DH, Doust AJ, Sakoda Y, Day NPJ. Scrub typhus serologic testing with indirect immunofluorescence method as a diagnostic gold standard: a lack of consensus leads to lot of confusion. Clin Infect Dis. 2007;44:391–401.
- Mahajan SK, Rolain JM, Kashyap R, Bakshi D, Sharma V, Prasher BS, Scrub typhus in Himalayas. Emerg Infect Dis. 2006;12:1590–2.
- Mahajan SK, Kashyap R, Kanga A, Sharma V, Prasher BS, Pal LS. Relevance of Weil-Felix test in diagnosis of scrub typhus in India. J Assoc Physicians India. 2006;54:619–21.
- Chaudhry D, Garg A, Singh I, Tandon C, Saini R. Rickettsial diseases in Haryana: not an uncommon entity. J Assoc Physicians India. 2009;57:334–7.
- Mathai E, Rolain JM, Verghese GM, Abraham OC, Mathai D, Mathai M, Outbreak of scrub typhus in southern India during the cooler months. Ann N Y Acad Sci. 2003;990:359–64.
- Prabagaravarthanan R, Harish BN, Parija SC. Typhus fever in Pondicherry. J Commun Dis. 2008;40:159–60.
- Lee CH, Liu JW. Coinfection with leptospirosis and scrub typhus in Taiwanese patients. Am J Trop Med Hyg. 2007;77:525–7.
- Drevets DA, Leenen PJM, Greenfield RA. Invasion of central nervous system by intracellular bacteria. Clin Microbiol Rev. 2004;17:323–47.
- Kim DE, Lee SH, Park KI, Chang KH, Roh KH. Scrub typhus encephalomyelitis with prominent neurological signs. Arch Neurol. 2000;57:1770–2.
- Table. Clinical features and laboratory investigations of patients who had scrub typhus with central nervous system involvement, India, 2004–2006
Please use the form below to submit correspondence to the authors or contact them at the following address:
Sanjay K. Mahajan, 25/3, US Club, Shimla, Himachal Pradesh, India 171001
Comment submitted successfully, thank you for your feedback.
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
- Page created: September 08, 2011
- Page last updated: September 08, 2011
- Page last reviewed: September 08, 2011
- Centers for Disease Control and Prevention,
National Center for Emerging and Zoonotic Infectious Diseases (NCEZID)
Office of the Director (OD)