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 Table of Contents  
Year : 2021  |  Volume : 41  |  Issue : 6  |  Page : 305-308

Pediatric scrub typhus complicated by meningitis

1 Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
2 Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei; epartment of Pediatrics, St Joseph Hospital, Kaohsiung City, Taiwan

Date of Submission16-Jul-2020
Date of Decision12-Aug-2020
Date of Acceptance25-Aug-2020
Date of Web Publication04-May-2021

Correspondence Address:
Dr. Wen-Tsung Lo
Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, 325 Cheng-Kung Road, Section 2, Neihu, Taipei 114, Taiwan; Department of Pediatrics, St Joseph Hospital, Kaohsiung
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmedsci.jmedsci_222_20

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Scrub typhus is caused by the intracellular pathogen Orientia tsutsugamushi, which is transmitted to humans by infected chigger mites. The disease causes a febrile illness accompanied by regional or generalized lymphadenopathy, hepatomegaly, splenomegaly, as well as nonspecific manifestations. Scrub typhus is an important cause of febrile disease in South and East Asia and in the Western Pacific, and can cause severe complications including meningoencephalitis and pneumonitis. Herein, we report a case of scrub typhus accompanied by meningitis, which was definitively diagnosed by serology assay, in a 4-year-old girl who presented with prolonged fever, skin rash, cough, general weakness, and poor appetite. Scrub typhus should be considered in the differential diagnosis when evaluating patients who present with nonspecific febrile illness or meningitis in areas that are endemic for O. tsutsugamushi.

Keywords: Pediatric, scrub typhus, Orientia tsutsugamushi, meningitis

How to cite this article:
Chou YL, Hsieh KH, Tien CH, Wang CC, Lo WT. Pediatric scrub typhus complicated by meningitis. J Med Sci 2021;41:305-8

How to cite this URL:
Chou YL, Hsieh KH, Tien CH, Wang CC, Lo WT. Pediatric scrub typhus complicated by meningitis. J Med Sci [serial online] 2021 [cited 2022 Dec 3];41:305-8. Available from: https://www.jmedscindmc.com/text.asp?2021/41/6/305/315476

  Introduction Top

Scrub typhus is a febrile, mite-borne infectious disease caused by Orientia tsutsugamushi.[1] O. tsutsugamushi is confined to the Asian Pacific rim, including Korea, China, Taiwan, Japan, Thailand, Malaysia, and in the tropical (northern) regions of Australia, and other regions like Pakistan and India. O. tsutsugamushi infects vascular endothelial cells and causes significant vascular leakage, which leads to significant vascular compromise and multiorgan dysfunction. The clinical manifestations may be insidious and nonspecific, including fever, chills, malaise, headache, lymphadenopathy, hepatomegaly, splenomegaly, skin rash, rhinorrhea, sore throat, dyspnea, abdominal pain, nausea or vomiting, diarrhea, poor appetite, dizziness, muscle ache, confused consciousness, and arthralgia.[1] This report presents a case of scrub typhus accompanied by meningitis in a young child.

  Case Report Top

A previously healthy 4-year-old girl was admitted to a hospital in Penghu because of an 11-day history of intermittent fever, cough with generalized weakness, and poor appetite. During treatment, the patient developed maculopapular skin rashes on the upper limbs and one episode of seizure. Due to persistent lethargy, she was then transferred to our hospital. On arrival, the patient presented with headache, photophobia, malaise, generalized weakness, nausea, and anorexia. Physical examination showed a body temperature of 38.1°C, a blood pressure of 88/46 mmHg, and a pulse rate of 120 beats/min. Lymphadenopathy on both sides of the neck and splenomegaly were noted. No hepatomegaly was found. Laboratory investigations showed a hemoglobin level of 9.7 g/dL, a peripheral white blood cell count of 20,240/mm[3] with 59.1% neutrophils, a platelet count of 201,000/mm[3], a blood urea level of 10 mg/dL, and a creatinine level of 0.3 mg/dL. Liver function tests revealed an albumin level of 2.3 g/dL, an aspartate aminotransferase level of 91 IU/L, and an alanine aminotransferase (ALT) level of 57 IU/L. C-reactive protein (CRP) was 5.45 mg/dL. Urinalysis showed normal results. Blood, urine, and sputum cultures showed no growth. Chest X-ray revealed increased interstitial infiltration in both lung fields, and abdominal ultrasonography demonstrated a prominent spleen (long axis was 11.8 cm).

On neurological examination, she was lethargic with poor oral response. Her sensory function was normal. Motor strengths of both upper and lower extremities were decreased (all about Grade 4). Peripheral deep tendon reflexes were normal and symmetrical. Because of neck stiffness, Brudzinski's sign and Kernig's sign were positive. Babinski's sign was absent. The patient was unable to take the tandem gait test due to weakness. Computed tomography scans of the brain on the 1st day of admission did not display abnormal densities or enhanced lesions. While collecting cerebrospinal fluid (CSF), opening pressure was normal. Analysis of CSF revealed a white blood cell count of 640/mm[3], a lymphocyte count of 377/mm[3], a glucose level of 73 mg/dL (blood glucose 109 mg/dL), and an elevated concentration of protein (224 mg/dL). Cultures of CSF were negative for viruses, bacteria, and acid-fast bacilli. Magnetic resonance imaging (MRI) of the brain on day 4 revealed an increased number of enhanced vessels along the cerebral sulci, cerebellar fissures, and the pontine surface. A combination of vancomycin (60 mg/kg/day in three divided doses), ceftriaxone (100 mg/kg/day once daily), and acyclovir (60 mg/kg/day in three divided doses) was started empirically, all given intravenously.

Because of poor response to therapy and that Penghu is endemic for scrub typhus, a serum sample was sent to the Taiwan Centers for Disease Control (CDC) for immunofluorescent antibody assays (IFA) of IgM and IgG antibody titers against O. tsutsugamushi, and the results were 1:160 and >1:640, respectively. Thus, azithromycin (10 mg/kg/day once daily) was administered on day 4. The consciousness of this girl recovered; her appetite improved. She was able to stand up and walk, and her headache and photophobia resolved on day 7. Her fever persisted, however, despite a 6-day regimen of azithromycin. One week after changing antibiotics to oral doxycycline (2.2 mg/kg/day), her fever finally resolved on day 17. She was discharged on the 24th hospital day.

  Discussion Top

Taiwan is endemic for scrub typhus, especially in the counties of Hualian, Taitung, Penghu, and Kinmen. The incidence of scrub typhus in Taiwan is 1.15 cases per year per 100,000 residents.[2] In Penghu, scrub typhus tends to occur among individuals aged 0–10 and 51–60 years, with the highest incidence occurring among those below 10 years of age.[3] The prevalent seasons are spring (April to June) and fall (October to December). Our patient is a resident of Penghu, and her illness occurred in October. She presented with nonspecific symptoms, and the doctors at her local clinic did not initially consider scrub typhus in the differential diagnosis. Silpapojakul et al.[4] showed that scrub typhus accounts for at least 6% of cases of acute fever of unknown origin among children in Thailand. Scrub typhus, therefore, should be considered in the differential diagnosis of patients with fever of unknown origin in endemic areas, especially in peak seasons. Kinmen, another county in Taiwan, is also highly endemic for scrub typhus, with nearly 100 confirmed cases reported annually since 2005. Most of the patients had mild disease and responded rapidly to treatment with minocycline. No severe complications have been reported.[5] The pathogenesis of scrub typhus is unknown. There is evidence that O. tsutsugamushi has special tropism for endothelial cells.[6] In autopsy cases, mononuclear cell infiltration of the leptomeninges and the presence of typhus nodules, which are clusters of microglia cells, and hemorrhages in the brain were found. These findings suggested immune-mediated inflammation, generalized vasculitis, and vascular leakage caused by O. tsutsugamushi infection.[1]

Our patient presented with symptoms of intermittent fever for >5 days, maculopapular skin rash, conjunctival injection, cervical lymphadenopathy, elevated CRP, ALT, and hypoalbuminemia. She was transferred to our hospital with a preliminary diagnosis of atypical Kawasaki disease. However, this diagnosis was ruled out after echocardiographic examination did not reveal evidence of pathological change of coronary arteries and because of the lack of oral mucosal change and indurations of extremities. According to the literature, the incidence of relative symptoms of scrub typhus was largely variable.[1],[7],[8] The incidence of conjunctival hyperemia ranges from 10% to 33%, while that of lymphadenopathy ranges from 12.5% to 93%. Furthermore, the incidence of fever ranges from 88% to 100%, that of skin rash ranges from 7% to 56%, the incidence of elevated CRP is 100%, the incidence of elevated ALT ranges from 60% to 91.3%, the incidence of leukocytosis ranges from 27% to 40%, and that of hypoalbuminemia ranges from 41% to 88.9%. The symptoms and laboratory findings mentioned above are also characteristic of Kawasaki disease. The pathogenesis of scrub typhus and Kawasaki disease was different, but the result of vasculitis either generalized or confined to small or medium arteries, respectively, could probably explain such similarities of clinical manifestations. Thrombocytopenia, seizure, and splenomegaly, which manifested in our patient, are relatively common symptoms in patients with scrub typhus but are rare in patients with Kawasaki disease. These less frequent but different manifestations indicate some etiological and pathological differences between the two diseases, and may be important topics for further investigation.

An eschar is a finding characteristic of scrub typhus; however, the mites that carry the causative pathogen are small (<5 mm) and the lesion is neither itchy nor painful.[1],[7],[8] It is seen in 50% of patients with primary infection and 30% of patients with recurrent infection.[1] Slight pleocytosis and mild protein elevation with normal blood glucose values in CSF are common findings in patients with scrub typhus.[5],[8] Marked pleocytosis (640/mm[3]) and elevated protein levels (224 mg/dL) in CSF in our patient may indicate meningitis. Studies have shown that MRI tends to disclose abnormal lesions in the gray matter of the spinal cord and brain.[1] In our patient, MRI of the brain revealed an increased number of visibly enhanced vessels along the cerebral sulci, cerebellar fissures, and the pontine surface, findings which are consistent with those reported previously.[1] When culture-negative meningitis is found in regions endemic for scrub typhus, serological tests for rickettsial infection are warranted.[1] In our patient, the diagnosis of scrub typhus was confirmed by IFA of IgM and IgG by CDC, Taiwan.

Scrub typhus is a fatal disease if no adequate therapy is administered. Doxycycline, chloramphenicol, and azithromycin are the antibiotics of choice, and the response is generally rapid. The mean response duration ranges from 1 to 3 days.[1],[7],[8] Despite clinical improvement of neurological manifestations in our patient under treatment with azithromycin for 6 days, fever persisted. The fever completely subsided on the 7th day of treatment with doxycycline. No sequela was found. Patients with scrub typhus who respond poorly to chloramphenicol and doxycycline have been reported in northern Thailand.[9] One randomized clinical trial has revealed that rifampin might be useful in treating these poorly responsive cases.[10] The delayed recovery in our patient, however, may be contributed to delayed diagnosis and treatment.

The incidence of scrub typhus complicated by meningoencephalitis or pneumonia ranges from 3% to 29.2% or 16.3% to 54%, respectively.[1],[7],[8] Both meningitis and bronchopneumonia occurred in our patient, which might indicate severe infection. Other rare complications include acute respiratory distress syndrome, disseminated intravascular coagulopathy, pericardial effusion, myocarditis, pleural effusion, subconjunctival hemorrhage, and infection-associated hemophagocytic syndrome.[1],[7],[8] Scrub typhus complicated by meningoencephalitis is less common in children. If a pediatric patient presents with meningoencephalitis or pneumonia combined with fever, lymphadenopathy, hepatomegaly, splenomegaly, and maculopapular rash, scrub typhus should be considered.

  Conclusion Top

Scrub typhus is a common infectious disease in Taiwan. The nonspecific symptoms and clinical findings of scrub typhus may preclude prompt diagnosis and treatment. Scrub typhus should be considered in the differential diagnosis when evaluating pediatric patients who present with nonspecific febrile illness and meningitis in areas that are endemic for O. tsutsugamushi. The study was reviewed and approved by the National Defense Medical Center Institutional Review Board (TSGHIRB No.:A202105046).

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Mahajan SK, Mahajan SK. Neuropsychiatric manifestations of scrub typhus. J Neurosci Rural Pract 2017;8:421-6.  Back to cited text no. 1
[PUBMED]  [Full text]  
Kuo CC, Huang JL, Ko CY, Lee PF, Wang HC. Spatial analysis of scrub typhus infection and its association with environmental and socioeconomic factors in Taiwan. Acta Trop 2011;120:52-8.  Back to cited text no. 2
Wang YC, Chen PC, Lee KF, Wu YC, Chiu CH. Scrub typhus cases in a teaching hospital in Penghu, Taiwan, 2006-2010. Vector Borne Zoonotic Dis 2013;13:154-9.  Back to cited text no. 3
Silpapojakul K, Ukkachoke C, Krisanapan S, Silpapojakul K. Rickettsial meningitis and encephalitis. Arch Intern Med 1991;151:1753-7.  Back to cited text no. 4
Su TH, Liu CJ, Chen DS, Kao JH. Milder clinical manifestation of scrub typhus in Kinmen, Taiwan. J Formos Med Assoc 2013;112:201-7.  Back to cited text no. 5
Moron CG, Popov VL, Feng HM, Wear D, Walker DH. Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus. Mod Pathol 2001;14:752-9.  Back to cited text no. 6
Jim WT, Chiu NC, Chan WT, Ho CS, Chang JH, Huang SY, et al. Clinical manifestations, laboratory findings and complications of pediatric scrub typhus in eastern Taiwan. Pediatr Neonatol 2009;50:96-101.  Back to cited text no. 7
Basu S, Saha A, Sarkar S, Sinha MK, Das MK, Datta R, et al. Clinical profile and therapeutic response of scrub typhus in children: A recent trend from eastern India. J Trop Pediatr 2019;65:139-46.  Back to cited text no. 8
Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, et al. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet 1996;348:86-9.  Back to cited text no. 9
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.  Back to cited text no. 10


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