Angiostrongylus cantonensis Infection: A Cause of Fever of Unknown Origin in Pediatric Patients (original) (raw)

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Section of Infectious Diseases, Department of Pediatrics

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Baylor College of Medicine and Texas Children's Hospital

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Section of Infectious Diseases, Department of Pediatrics

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Baylor College of Medicine and Texas Children's Hospital

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Baylor College of Medicine

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Section of Allergy, Immunology and Rheumatology

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Section of Allergy, Immunology and Rheumatology

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Section of Allergy, Immunology and Rheumatology

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Section of Neurology and Developmental Neuroscience, Department of Pediatrics

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Baylor College of Medicine and Texas Children's Hospital

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Houston

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Section of Infectious Diseases, Department of Pediatrics

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Baylor College of Medicine and Texas Children's Hospital

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Baylor College of Medicine and Texas Children's Hospital

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Baylor College of Medicine and Texas Children's Hospital

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30 August 2016

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Catherine E. Foster, Erin G. Nicholson, Angela C. Chun, Maya Gharfeh, Sara Anvari, Filiz O. Seeborg, Michael A. Lopez, Judith R. Campbell, Lucila Marquez, Jeffrey R. Starke, Debra L. Palazzi, Angiostrongylus cantonensis Infection: A Cause of Fever of Unknown Origin in Pediatric Patients, Clinical Infectious Diseases, Volume 63, Issue 11, 1 December 2016, Pages 1475–1478, https://doi.org/10.1093/cid/ciw606
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Abstract

Fever of unknown origin (FUO) in children is frequently caused by infectious diseases. Angiostrongylus cantonensis, while a primary cause of eosinophilic meningitis, is rarely a cause of FUO. We present 2 pediatric cases of FUO caused by Angiostrongylus cantonensis acquired in Houston, Texas, outside its usual geographic distribution.

Fever of unknown origin (FUO) in children is a common reason for presentation to outpatient clinics and emergency centers, often leading to consultation with a pediatric infectious diseases specialist. There are varying definitions of FUO, but an acceptable definition in children is fever >38.3°C for at least 8 days' duration in a child in whom a history, physical examination, and initial laboratory studies have failed to reveal an etiology [1]. Parasitic causes of FUO are infrequent. We report 2 recent cases of Angiostrongylus cantonensis infection acquired in Houston, Texas, presenting as FUO in pediatric patients.

CASE 1

A previously healthy, former 34-week gestational age, 19-month-old girl presented with a 1- month history of daily fever to 39.4°C–40°C. She was evaluated on several occasions in the outpatient setting, was initially diagnosed with a viral illness, and completed a 10-day course of amoxicillin for acute otitis media. She was noted by her mother to be irritable, and was taken for further evaluation when she developed impaired balance and refusal to ambulate. She was fully vaccinated, lived in Houston, Texas, and had never traveled outside the city. She had no animal exposures or history of mollusk ingestion.

On admission, she was irritable and ataxic. Initial evaluation revealed a white blood cell (WBC) count of 22 400 cells/µL, with 45% neutrophils and 14% eosinophils. Cerebrospinal fluid (CSF) had 89 WBCs/μL (4% lymphocytes, 27% monocytes, and 67% eosinophils), 0 red blood cells (RBCs), glucose 22 mg/dL, and protein 95 mg/dL. Magnetic resonance imaging (MRI) demonstrated significant enhancement of the neuraxis (Figure 1).

Figure 1.

Contrast-enhanced magnetic resonance imaging (MRI) scans of the brain demonstrating patchy asymmetric linear and nodular enhancement in case 1 (A) and case 2 (B). Contrast-enhanced MRI scan of lumbar spine showing cauda equina enhancement in case 1 (C). Contrast-enhanced MRI scan of lumbar spine demonstrating multifocal nodular enhancement within the spinal cord in case 2 (D).

CSF bacterial and mycobacterial cultures were negative and cytology was normal. CSF polymerase chain reaction (PCR) tests for enterovirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were negative, and West Nile virus antibody was negative. Serology for human immunodeficiency virus, Bartonella henselae, Brucella, and Rickettsia was negative. A tuberculin skin test and blood T.SPOT were negative. Bone marrow biopsy to evaluate for malignancy was unremarkable. Ophthalmologic examination was normal. Over the next 12 days, she continued to have daily fever to 40.5°C with irritability and ataxia. Diagnostic testing for toxocariasis, strongyloidiasis, toxoplasmosis, A. cantonensis, and Bayliscariasis was pending. Treatment with methylprednisolone 2 mg/kg/day was initiated on hospital day 12, and fever and irritability improved. Upon completion of a 7-day course of corticosteroid, fever to 40.5°C returned and methylprednisolone was reinitiated with subsequent improvement. The CSF PCR for A. cantonensis performed at the Centers for Disease Control and Prevention (CDC) was positive. A 10-day course of albendazole 400 mg daily was prescribed and steroids were continued with a tapered course over 14 days. Two weeks after discharge, she had a normal neurological examination and was afebrile. Given the uncharacteristically prolonged febrile course, the patient underwent an immunologic evaluation, which was unrevealing.

CASE 2

A healthy 13-month-old boy presented with a 4-day history of fever, malaise, and emesis. Treatment with ceftriaxone was initiated when urinalysis showed numerous leukocytes, and urine culture grew >100 000 colony-forming units/mL of Proteus mirabilis. He was fully immunized, was born in Houston, had not traveled, and had no mollusk ingestion. He liked to chew on lettuce leaves. Complete blood count on admission was unremarkable.

On hospital day 4, he remained febrile and was noted to have a bulging fontanelle. Physical examination was significant for irritability and nuchal rigidity. CSF evaluation revealed 1055 WBCs/μL (25% lymphocytes, 13% monocytes, and 57% eosinophils), 0 RBCs, glucose 33 mg/dL, and protein 85 mg/dL. CSF bacterial culture was negative and cytology was normal. Brain MRI was normal, but MRI of the spine demonstrated meningeal enhancement along the distal cord with an intramedullary lesion at T7–T8. Pertinent negative laboratory testing included serology for trichinellosis, cysticercosis, and toxocariasis. Ophthalmologic examination was normal. The fever persisted for 15 days, and he received 16 days of ceftriaxone. CSF PCR for A. cantonensis was positive on hospital day 17, but treatment with corticosteroids or an antihelminthic agent was deferred as the patient was well. He was discharged but readmitted 3 days later with recurrence of fever and new onset of lethargy. Repeat CSF evaluation revealed 3006 WBCs/μL (19% lymphocytes, 5% monocytes, and 71% eosinophils), 2 RBCs/μL, glucose <20 mg/dL, and protein 196 mg/dL. MRI demonstrated interval development of nodular brain lesions and increased intramedullary spinal cord involvement (Figure 1). He was treated with prednisone 2 mg/kg/day for 2 weeks followed by a taper, and symptoms resolved. His neurologic examination was normal. A repeat CSF evaluation after 10 days of corticosteroid therapy revealed 194 WBCs/μL (91% lymphocytes, 5% monocytes, 4% eosinophils), 84 RBCs/μL, glucose 33 mg/dL, and protein 46 mg/dL.

DISCUSSION

Angiostrongylus cantonensis, a parasitic nematode also known as the rat lungworm, is the most common cause of eosinophilic meningitis worldwide [2–4]. The endemic regions of A. cantonensis include primarily Southeast Asia and the Pacific Basin [4]. Increasingly, cases have been observed outside of the endemic regions in areas such as Australia, Hawaii, and the Caribbean. The spread of A. cantonensis has occurred secondary to the dispersal of vector rats transported on shipping vessels and by the introduction of intermediate mollusk hosts. In the southeastern states along the Gulf of Mexico, A. cantonensis was identified in 2 nonindigenous snail species, Pomacea maculata and Achatina fulica, and the first reported case of human infection in this region was in New Orleans, Louisiana, secondary to ingestion of raw snails [5, 6]. Our patients are the first published cases of A. cantonensis infection acquired in Houston, Texas, indicating that the geographic distribution of this parasite has expanded, perhaps related to recurrent flooding in the Gulf Coast area.

Humans become infected by ingesting intermediate hosts (snails or slugs) or a paratenic host infected by third-stage larvae. Once ingested, the infective larvae invade the intestinal wall, enter the bloodstream, and migrate to neural tissue where they die, causing inflammation [7]. For most patients, angiostrongyliasis causes a self-limited eosinophilic meningitis without systemic symptoms or neurologic sequelae [4]. However, Epelboin et al found that young children had a significantly more guarded prognosis, with a 1-year mortality rate of 35.7% (5/14) and neurologic sequelae in 42.8% of survivors [8]. Both of our patients had CSF eosinophilia exceeding 50%, abnormal imaging, and hypoglycorrhachia, which are factors that have been associated with severe disease [8]. Additionally, our first patient had fever for 1 month prior to admission. These concerning findings suggest that close clinical follow-up is indicated, but whether monitoring should include neuroimaging and reevaluation of CSF parameters in addition to clinical neurologic examination is uncertain and not addressed in the limited literature about this infection in young children.

Our patients' clinical presentations and findings add to the literature that suggests angiostrongyliasis in young children manifests differently from that in adults [9–11]. Prolonged fever with more severe illness can occur, with an increased risk for neurologic sequelae and death in young children presenting with bulbar signs, flaccid paralysis, or coma [9, 10]. The degree of CSF pleocytosis has not been found to correlate with disease severity in children [9]. MRI findings have been described as areas of linear or nodular enhancement of the leptomeninges, most often in the brain [12]. Spinal cord involvement with enhancement of the nerve roots can also occur but is rare [12]. Both of our patients presented with meningoencephalomyelitis.

Our patients highlight the challenges associated with the diagnosis and management of A. cantonensis infection. The diagnosis was considered unlikely given the clinical presentation, absence of known mollusk ingestion, or travel from an endemic area. In addition, there were no common exposures that could be identified between the patients such as visiting local parks, recreational water areas, grocery stores, or mobile food trucks. Both patients presented within a 4-week period in the spring of 2016, during a time of severe flooding in Houston. Prior studies have noted increased incidence of angiostrongyliasis during rainy seasons [8], perhaps due to increased activity of intermediate hosts. Our second patient may have become infected by eating produce contaminated by snails or slugs infected with third-stage larvae. Infected juvenile snails may be only a few millimeters in size and translucent. Making the diagnosis of angiostrongyliasis is difficult because serologic tests are not commercially available and their sensitivity and specificity may be suboptimal. In addition, PCR testing on CSF and tissue is not widely available but can be obtained through the CDC.

The approach to treating angiostrongyliasis is not well defined. In countries with more experience in treating this infection, therapeutic regimens have included corticosteroids, antihelminthic agents, or a combination of both. However, use of antihelminthic agents has been controversial due to concern for worsening of neurologic symptoms in adults caused by inflammation secondary to dying parasites [11]. One of our patients was successfully treated with a combination of albendazole and corticosteroids and the other with corticosteroids alone.

We have described 2 pediatric cases of FUO caused by infection with locally acquired A. cantonensis. Successful diagnosis requires a high degree of suspicion and will become increasingly important with the spread of A. cantonensis outside its historical geographic boundaries. Further studies evaluating optimal treatment regimens are needed.

Note

Potential conflicts of interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Topic:

• fever of unknown origin
• angiostrongylus cantonensis
• child
• communicable diseases
• pediatrics
• infections
• eosinophilic meningitis

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