**2.3. Clinical features**

in 1879 by Baclz and Kawakami as Japanese 'flood fever'. It is widespread in the so-called 'tsutsugamushi triangle' which extends from Pakistan, India, Nepal in the West, to South Eastern Siberia, Japan, China and Korea in the North, to Indonesia, the Philippines, Northern Australia and the Pacific islands in the South. Taiwan is the centre of the tsutsugamushi triangle, and Korea has the highest reported incidence in the world [2]. About one million new cases

62 Meningoencephalitis - Disease Which Requires Optimal Approach in Emergency Manner

In India, the disease had occurred among troops during World War II in the state of Assam and West Bengal. Although the disease is endemic in India, epidemics have also been reported.

Epidemiological reports confirm strong existence of scrub in hilly/rain prone areas. Outbreaks reveal an autumn-winter type and a summer type of pattern. In comparison with the summer

Increasing prevalence of scrub typhus reported from some Asian countries may be related to

Scrub typhus is caused by an obligate intracellular gram-negative bacterium called *Orientia tsutsugamushi*. Ogata in 1931 isolated the organism and named it *Rickettsia* tsutsugamushi. Now it has been renamed as *O. tsutsugamushi*. The organism lacks a cell wall. There are six important serotypes of *O. tsutsugamushi*—Gilliam, Karp, Kato, Shimokoshi, Kawasaki and Kuroki. A new strain has been isolated from a case of scrub typhus in Australia which was

The mite has four stages: egg, larva, nymph and adult. The larval forms (chiggers) transmit the disease to humans and other vertebrates. The larvae feed on rodents particularly wild rats of subgenus Rattus, The infection in humans is acquired during outdoor recreational and agricultural activities, by the bite of the larval stage of mites. The areas are usually secondary scrub growth which grows after clearance of primary forest hence the term scrub typhus. Humans are therefore accidental hosts for the pathogen. Vertical transovarial transmission occurs in mites. One case of transplacental spread has been reported in a pregnant woman,

Following the bite, the pathogen multiplies at the site of inoculation and produces both systemic and local manifestation. Infection spreads through both haematogenous and lymphatic routes. The severity of the illness depends on both host-related and pathogen-related factors. Pathogenrelated factors may be related to the different strains of *O. tsutsugamushi*. Host-related factors as seen in humans with G6PD deficiency who has a worse prognosis also play a role. Target cells for multiplication are the endothelial cells of the various systems. The immune response induced by the pathogen is a combination of humoral and cell-mediated immunity. There occurs a rise of cytokines during an acute infection. There also occurs a rise in macrophage colony stimulating factor, interferon gamma and granulocyte colony stimulating factor. Therefore, the macrophage and T-lymphocyte response may be the main factor in immunity against the infection. However, the parasite has also evolved to evade the immune response of the host. The pathogen can down-regulate the expression of glycoprotein 96, in infected macrophages and endothelial

quite different from the classic strains and has been named as Litchfield.

who delivered a preterm baby with scrub typhus IgM positivity.

are identified annually.

urbanization of rural areas.

**2.2. Pathophysiology**

type, the autumn-winter type is less severe.

The incubation period of *O. tsutsugamushi* in humans is around 10–12 days (can vary between 6 and 21 days). The clinical manifestations vary from a mild febrile illness to a severe potentially disease. The systemic features of the infection include fever, gastrointestinal disturbance, malaise, cough, myalgia and headache. A maculopapular rash starting from the trunk and spreading to the limbs is seen towards the end of the first week of the fever. Diffuse lymphadenopathy is commonly observed.

A necrotic 'eschar' at the bite site is almost diagnostic of scrub typhus (**Figure 1**).

The eschar resembles skin burn of cigarette butt. Eschar is found in 7–80% patients of scrub typhus [3]. In the authors study, eschar was detected in 28.81% of the patients of scrub typhus and 30.77% patients of meningoencephalitis due to scrub typhus [6]. The wide range of detection may be due to the difficulty in detecting eschars in dark-skinned individuals, difference in the eschar inducing capacity of the different strains of *O. tsutsugamushi*. The groin, axilla, waist and other exposed parts of the body are common sites of eschar detection. In the authors

**Figure 1.** Eschar at bite site.

study, eschar was mostly found in the inguinal region. Different pattern of eschar distribution found in males and females due to the differences in skin folds, clothing and pressure points created by garments. The eschar not only has immense diagnostic relevance but is also important prognostically. Absence of an eschar is a risk factor for mortality [2].

Neurological involvement is often a prominent clinical manifestation of scrub typhus. However, they are still an unclear entity. Meningitis or meningoencephalitis can occur in upto one-fifth of affected patients. In the authors study, meningoencephalitis was found in 13.2% of scrub typhus patients [6]. The various neurological manifestations of scrub typhus [5] are as given in (**Table 1**).

Meningitis has features of headache, vomiting, fever, neck stiffness, along with cerebrospinal fluid (CSF) pleocytosis. Altered sensorium and fever with CSF pleocytosis are features of encephalitis. Altered sensorium with fever but normal CSF is found in encephalopathy.

Neurological manifestations in scrub typhus does not occur in isolation but are accompanied by systemic features like jaundice, breathlessness, cough, renal impairment and in some cases, with multi-organ dysfunction. In the authors study [6] neurological manifestations were associated with lymphadenopathy (46.15%), jaundice (53.85%), pulmonary oedema (23.08%), oliguria (15.38%), hepatomegaly (38.46%) and splenomegaly (7.69%). Multi-organ dysfunction was found in 15.38% patients of scrub typhus with neurological manifestation.

The most common symptom of scrub typhus is fever. The fever is usually mild and accompanied by myalgia. In the authors study the mean duration of fever was 5.61 days, prior to meningoencephalitis presentation.

Headache is a common symptom in scrub typhus (46–77%). A severe holocranial headache almost invariably occurs and thereby helps in identifying suspected cases. Headache occurs


**Table 1.** Neurological involvement in scrub typhus.

not only in patients of meningitis or meningoencephalitis but in other scrub typhus patients also. However, in those cases, the headache is less severe.

In scrub typhus meningitis, the severe headache is associated with neck stiffness and fever. Other signs of meningeal irritation like Kernig's sign may also be present. These meningeal signs are detected in upto 45% patients. In the author's study, meningeal signs were present in 76.92% patients [6].

Altered sensorium is present in scrub typhus patient with encephalitis and meningoencephalitis. In the author's study, altered sensorium was found in all patients; however, other studies have reported a lower incidence.

Seizure occurs in scrub typhus with neurological involvement in 22–50% cases, though uncommon myoclonic seizure was found in one patient in the author's series.

Cranial nerve deficits are seen in 25% patients. Most commonly sixth nerve involvement is seen, which maybe unilateral or bilateral. Facial palsy may occur in isolation or in association with Guillain Barre syndrome [2]. Cochlear nerve involvement occurs in about 19% patients and cause sensorineural hearing loss, otalgia and tinnitus. This may be due to direct invasion by the pathogen or due to a secondary immune-mediated effect.

Other uncommon neurological manifestations of scrub typhus mentioned are infarction, cerebellitis, haemorrhages, subdural hematoma and Guillain Barre syndrome [2].
