Scrub typhus meningoencephalitis

Nayyar Iqbal; Sudhagar Mookkappan; Aneesh Basheer

REVIEW ARTICLE

Year : 2015 | Volume : 1 | Issue : 1 | Page : 3-5

Scrub typhus meningoencephalitis

Nayyar Iqbal, Sudhagar Mookkappan, Aneesh Basheer
Department of General Medicine, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry, India

Date of Submission	27-Jul-2015
Date of Acceptance	27-Aug-2015
Date of Web Publication	9-Nov-2015

Correspondence Address:
Nayyar Iqbal
Department of General Medicine, Pondicherry Institute of Medical Sciences, Kalapet, Puducherry - 605 014
India

Source of Support: None, Conflict of Interest: None

Check

Abstract

Scrub typhus is one of the most common undifferentiated fevers in South India. Scrub meningoencephalitis commonly presents with a severe headache and altered sensorium, along with fever. Sometimes, it is associated with seizures and focal neurological deficit. The cerebrospinal fluid analysis shows lymphocytic predominance with elevated protein and normal glucose. Tubercular meningitis is a common differential diagnosis. Prompt treatment with doxycycline is associated with favorable outcome.

Keywords: Encephalitis, meningitis, scrub typhus

How to cite this article:
Iqbal N, Mookkappan S, Basheer A. Scrub typhus meningoencephalitis. J Curr Res Sci Med 2015;1:3-5

How to cite this URL:
Iqbal N, Mookkappan S, Basheer A. Scrub typhus meningoencephalitis. J Curr Res Sci Med [serial online] 2015 [cited 2021 Jul 30];1:3-5. Available from: https://www.jcrsmed.org/text.asp?2015/1/1/3/168917

Introduction

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi. It is transmitted by larval mites of Leptotrombidium deliense group. It is one of the most common rickettsial fevers in South India including Pondicherry.^[1] The word typhus in Greek means fever with altered sensorium and the scrub is used for the vegetation that harbors the vector.^[2] Outbreaks of scrub occur during the rainy season and cooler months of the year. In South India, around 50% of undifferentiated fever is attributed to scrub typhus.

The clinical manifestation begins after an incubation period of 6–21 days. Fever, headache, arthralgia, cough, and diarrhea are a common initial manifestation. The pathogonomic features are the presence of eschar and lymphadenopathy.^[3],[4] Various complications have been reported in cases of scrub typhus-such as acute respiratory distress syndrome, meningitis, meningoencephalitis, cerebral infarction, Guillain–Barre syndrome, transverse myelitis, coma, acute hepatitis, acute renal failure, gastrointestinal bleeding, disseminated intravascular coagulation, shock, and myocarditis.^[5]

Pathogenesis

Orientia tsutsugamushi is an intracellular parasite. It is transmitted by larva of trombiculid mites called chiggers. Man gets infected while traversing the mite infested area, that is, mainly the area with scrub vegetation. Chiggers tend to feed under the skin folds such as the groin, axilla, and under the breast, but it can feed anywhere on the body. The salivary gland of chiggers harbors the bacteria, which get injected into the host while feeding on them. The eschar is formed at the site of the bite on the skin [Figure 1]. The infection spreads through hematogenous as well as lymphatic route.^[6] The organism has a predilection for the endothelium of small blood vessels for its multiplication. This leads to the inflammation of the blood vessels causing focal or diffuse vasculitis and perivasculitis involving central nervous system, lung, heart, and kidney.^[7] The organism causes the infiltration of mononuclear cells in meninges, hemorrhages in the brain, and formation clusters of microglial cells (typhus nodules).^[8]

Figure 1: Eschar at pubic region adopted from Sudhagar Mookkappan, et al. Australas Med J. 2014;7(3):164-167

Click here to view

Clinical Features

Scrub typhus is common cause of acute febrile illness in South India. The common clinical manifestation is fever with headache and myalgia. Clinical feature of scrub meningoencephalitis is similar to viral or tubercular meningitis (TBM). The common clinical presentation is headache and altered mental status preceded with fever. Few of the patients may also present with generalized seizures. Neck rigidity is not a common clinical sign in scrub meningoencephalitis. Although, Eswaradass and Eswaradass have reported neck rigidity in all of his cases.^[9] Mean duration of fever prior to the presentation is around 8 days. Patients can present as early as 3 days of fever and as late as 2 weeks.^[10],[11] Male and female are equally affected by this illness. Eschar, which is the pathogonomic feature of scrub typhus, was infrequently seen in a various study of scrub meningoencephalitis [Table 1]. Lymphadenitis is very rare clinical sign associated with this illness. Study by Sharma et al. reported lymphadenitis in 3% of the cases.^[11] Cerebral ischemic infarction was rare complication of scrub meningoencephalitis noted in the studies.^{[10],[11],[13]}

Table 1: Clinical features of scrub meningoencephalitis in different studies from 1997 to 2015

Click here to view

Cerebrospinal fluid (CSF) analysis is always lymphocytic predominant with elevated protein and normal glucose. CSF adenosine deaminase (ADA) is always normal [Table 2]. CSF polymerase chain reaction (PCR) is a confirmative test to diagnose scrub meningoencephalitis.^[8],[12] The cost and availability of nested PCR make it difficult in the community setting. Serum scrub IgM ELISA is now readily available; hence, the confirmation of scrub typhus in the setting of a clinical feature of meningoencephalitis can be done by this method.

Table 2: Comparison of CSF analysis in different studies

Click here to view

Differential Diagnosis

The differential diagnosis of scrub meningoencephalitis is viral or tubercular meningoencephalitis. In a country like India, tubercular meningoencephalitis is important differential diagnosis followed by cerebral malaria. CSF analysis plays a key role in differentiating these illnesses. Thwaites et al. has proposed diagnostic criteria for TBM. According to this patient with an acute febrile illness with duration of fever for <6 or 7 days, normal blood leukocyte count and <75% of neutrophils in CSF is suggestive of TBM.^[16] CSF ADA >10 increases the probability of TBM.^[17] In scrub meningitis, the patient may have leukocytosis in blood with thrombocytopenia along with deranged liver function test and CSF ADA is invariably <7.^[5] Second, patient with scrub typhus shows prompt improvement with doxycycline. Other close differential diagnosis in our setting is cerebral malaria, especially if the patient has a travel history to malaria endemic zone. CSF analysis is normal but may show mild pleocytosis and increase in protein level.^[18] Peripheral smear and malarial antigen with typical history may be a key to the diagnosis of cerebral malaria.

Treatment

Doxycycline 100 mg twice daily for 7–14 days is the treatment of choice.^[2] There has been report of doxycycline-resistant from South-East Asian countries.^[19],[20] In pregnant woman, azithromycin is the drug of choice. In case of poor response to doxycycline, chloramphenicol, or rifampicin may be used. Rifampicin should be used in combination, either with azithromycin or doxycycline to prevent the development of resistance. The use of rifampicin in a country like India where tuberculosis is very common is not routinely recommended.^[13]

Outcome

Treatment with doxycycline generally has a favorable outcome, although deaths have been reported in few studies.^{[10],[13],[15]} Deaths were associated with late presentations and multiorgan dysfunctions. A focal neurological deficit like 6^th nerve palsy, bilateral cortical blindness, and ischemic stroke has also been reported.^[5]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Iqbal N, Titus S, Basheer A, George S, George S, Mookkappan S, et al. Polyarthritis and massive small bowel bleed: An unusual combination in scrub typhus. Australas Med J 2015;8:89-95.
2.	Ramasubramanian V, Senthur NP. Scrub typhus. In: Muruganathan A, editor. The Association of Physicians of India – Medicine Update. 1^st ed. Mumbai: Jaypee Brothers; 2013. p. 19-22.
3.	Iqbal N, Viswanathan S, Remalayam B, Muthu V, George T. Pancreatitis and MODS due to scrub typhus and dengue co-infection. Trop Med Health 2012;40:19-21.
4.	Vivekanandan M, Mani A, Priya YS, Singh AP, Jayakumar S, Purty S.Outbreak of scrub typhus in Pondicherry. J Assoc Physicians India 2010;58:24-8.
5.	Viswanathan S, Muthu V, Iqbal N, Remalayam B, George T. Scrub typhus meningitis in South India – A retrospective study. PLoS One 2013;8:e66595.
6.	Mahajan SK. Scrub typhus. J Assoc Physicians India 2005;53:954-8.
7.	Rajapakse S, Rodrigo C, Fernando D. Scrub typhus: Pathophysiology, clinical manifestations and prognosis. Asian Pac J Trop Med 2012;5:261-4.
8.	Pai H, Sohn S, Seong Y, Kee S, Chang WH, Choe KW. Central nervous system involvement in patients with scrub typhus. Clin Infect Dis 1997;24:436-40.
9.	Eswaradass P, Eswaradass C. Clinical, laboratory findings and complications of scrub typhus-meningoencephalitis: Case series. Neurology 2015;84:S311.
10.	Kar A, Dhanaraj M, Dedeepiya D, Harikrishna K. Acute encephalitis syndrome following scrub typhus infection. Indian J Crit Care Med 2014;18:453-5. [PUBMED]
11.	Sharma SR, Masaraf H, Lynrah KG, Lyngdoh M. Tsutsugamushi disease (scrub typhus) meningoencephalitis in North Eastern India: A prospective study. Ann Med Health Sci Res 2015;5:163-7. [PUBMED]
12.	Kim DM, Yun NR, Yang TY, Lee JH, Yang JT, Shim SK, et al. Usefulness of nested PCR for the diagnosis of scrub typhus in clinical practice: A prospective study. Am J Trop Med Hyg 2006;75:542-5.
13.	Varghese GM, Mathew A, Kumar S, Abraham OC, Trowbridge P, Mathai E. Differential diagnosis of scrub typhus meningitis from bacterial meningitis using clinical and laboratory features. Neurol India 2013;61:17-20. [PUBMED]
14.	Boorugu H, Chrispal A, Gopinath KG, Chandy S, Prakash JJ, Abraham AM, et al. Central nervous system involvement in scrub typhus. Trop Doct 2014;44:36-7.
15.	Abhilash KP, Gunasekaran K, Mitra S, Patole S, Sathyendra S, Jasmine S, et al. Scrub typhus meningitis: An under-recognized cause of aseptic meningitis in India. Neurol India 2015;63:209-14. [PUBMED]
16.	Thwaites GE, Chau TT, Stepniewska K, Phu NH, Chuong LV, Sinh DX, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet 2002;360:1287-92.
17.	Gupta BK, Bharat A, Debapriya B, Baruah H. Adenosine deaminase levels in CSF of tuberculous meningitis patients. J Clin Med Res 2010;2:220-4.
18.	Misra UK, Kalita J, Prabhakar S, Chakravarty A, Kochar D, Nair PP. Cerebral malaria and bacterial meningitis. Ann Indian Acad Neurol 2011;14 Suppl 1:S35-9.
19.	Lee S, Chung E, Kim E, Sea J. A case of doxycycline-resistant tsutsugamushi meningoencephalitis. Neurol Asia 2014;19:205-6.
20.	Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D, Strickman D. Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: A randomised trial. Lancet 2000;356:1057-61.