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 ~  Abstract
 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~ Conclusion
 ~  References
 ~  Article Tables

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  Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 33  |  Issue : 1  |  Page : 154-158
 

Eosinophilic meningitis: A case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum


1 Department of Pediatrics, Bai Jerbai Wadia Hospital for Children, and Pediatric Infectious Diseases Consultant, Nanavati Hospital, Mumbai, India
2 Consultant Pediatrician, Ankur Hospital, Virar, Maharashtra, India
3 Department of Pediatrics, Bai Jerbai Wadia Hospital for Children, Mumbai, India

Date of Submission01-Nov-2013
Date of Acceptance23-May-2014
Date of Web Publication5-Jan-2015

Correspondence Address:
I Shah
Department of Pediatrics, Bai Jerbai Wadia Hospital for Children, and Pediatric Infectious Diseases Consultant, Nanavati Hospital, Mumbai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.148430

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 ~ Abstract 

Eosinophilic meningitis is defined as the presence of >10 eosinophils/μL in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. Eosinophilic meningitis has been reported in two case series and two case reports in India till date and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents.


Keywords: Angiostrongylus cantonensis, Children, eosinophilic meningitis, Gnathostoma spinigerum


How to cite this article:
Shah I, Barot S, Madvariya M. Eosinophilic meningitis: A case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum. Indian J Med Microbiol 2015;33:154-8

How to cite this URL:
Shah I, Barot S, Madvariya M. Eosinophilic meningitis: A case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum. Indian J Med Microbiol [serial online] 2015 [cited 2019 Dec 7];33:154-8. Available from: http://www.ijmm.org/text.asp?2015/33/1/154/148430



 ~ Introduction Top


Eosinophilic meningitis is defined as the presence of >10 eosinophils/μL in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. [1] Because eosinophils are not normally found in the CSF, their presence is suggestive of various etiologies that can be divided into infectious and noninfectious categories which include parasites such as Angiostrongylus cantonensis and Gnathostoma spinigerum, fungal infections of the brain, drugs such as intraventricular antimicrobials and myeloproliferative diseases such as hypereosinophilic syndrome, Hodgkin's disease, leukaemia and lymphoma. [2],[3] Rare causes could be due to other parasites, bacterial and viral meningitis and other drugs. [2] Absolute peripheral eosinophilia more than 1,500 cells/cu.mm. suggests parasitic infestation. [4] Commonest causes of eosinophilic meningitis are angiostrongyliasis (rat lung worm) and gnathostomiasis worldwide. [5] In India, eosinophilic meningitis has been reported in 2 case series [6],[7] and 2 case reports [8],[9] and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia, both residents of western suburbs of Mumbai and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents.


 ~ Case Report Top


Case 1

A 14-month-old female child presented with fever, decreased appetite and lethargy for 5 days. There were no convulsions, vomiting, photophobia or headache. Also, there was no history of contact with a patient having tuberculosis (TB). There was no history of recent vaccination, head trauma or ear discharge or exposure to animals but there was history of rats in the house. There was no history of ingestion of pork, beef or sea food by the child. The parents did not give history of pica (to rule out ingestion of rat faeces) or recent travel. On examination, her vital signs were normal, and there were no signs of raised intracranial pressure. No skin rash was identified. She had pallor, hepatosplenomegaly and was drowsy but arousable with no focal neurologic deficits. Cranial nerves were unaffected, and tone and reflexes were found to be normal. Meningeal signs (Neck rigidity, Kernig's and Brudzinski's signs) were absent. Investigations showed a peripheral blood total leucocyte count of 10,300/μL with 10% eosinophils (absolute eosinophil count 1030 cells/μL). A night time peripheral smear did not reveal any microfilariae. Stool and urine analysis did not reveal any parasites or cysts. An initial CSF analysis revealed 290 leucocytes/μL with 48% eosinophils with a protein level of 25 mg/dl and a sugar level of 50 mg/dl. Cultures of blood and CSF did not grow any organism. Chest roentgenogram, Mantoux test, human immunodeficiency virus (HIV) Elisa, Toxoplasma IgM and IgG were negative. She was started on empiric antibiotic therapy with injectable Ceftriaxone. On day 3 of hospitalisation, she developed a squint of the right eye. Fundi examination was normal. Magnetic resonance imaging (MRI) of brain revealed a non-enhancing lesion in the right frontoparietal parenchyma, likely representing meningoencephalitis. In view of the eosinophilic meningoencephalitis non-responsive to antibacterial therapy, a parasitic cause was strongly suspected and she was subsequently started on injectable dexamethasone and albendazole (15 mg/kg/day). Within 5 days, the absolute eosinophil count decreased and CSF eosinophilia also improved. She showed clinical recovery in terms of disappearance of pyrexia and central nervous system (CNS) symptoms. Her serial haemograms and CSF anaylsis are depicted in [Table 1]. She was treated with albendazole for 2 weeks and steroids for 3 weeks. Ceftriaxone was stopped after 7 days of therapy.
Table 1: Serial haemogram and cerebrospinal fluid analyses of both patients


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Case 2

A 2-year-old male child presented with history of fever lasting for 2 days a week prior to presentation followed by loss of appetite and lethargy for 6 days and projectile vomiting since 2 days. Similar to the child in case 1, this child also was too young to give any history of headache or photophobia. There was a history of contact with cats and dogs as well as presence of lizards in the house. A specific history of ingestion of milk contaminated by cats was elicited. There was no history of pica. Also, there was no history of recent travel, ingestion of pork, beef or sea food or recent vaccination. Examination findings revealed that the child had normal vital signs with no signs of raised intracranial pressure. No evidence of lymphadenopathy or hepatosplenomegaly was seen. There was no other focus of infection evident on other systemic examination. Neurologic examination revealed the child to be lethargic but responsive. He had neck rigidity but no focal neurologic deficits. Cranial nerves and motor system examination were normal. Investigations revealed a peripheral blood total leucocyte count of 21,400/μL with 24% eosinophils. Erythrocyte sedimentation rate (ESR) was normal. CSF analysis revealed 350 leucocytes with 40% eosinophils and a protein level of 74 gm/dl with a sugar level of 39 mg/dl. MRI brain was normal. Investigations were ordered to delineate the etiology. Chest roentgenogram, Mantoux test, HIV Elisa, Toxoplasma IgM and IgG were all within normal limits. Similar to the child in case 1, he was initially treated empirically with injectable Ceftriaxone, to which he showed no clinical response. Subsequently, albendazole at a dose of 15 mg/kg/day for 3 weeks and steroids (2 weeks) were added. Repeat CSF analyses done after 12 days of therapy showed 215 leucocytes with 16% eosinophils and after 19 days of therapy showed 380 cells with 21% eosinophils. Thus, CSF eosinophilia had not completely responded to the antihelminthic therapy. Also his peripheral eosinophilia persisted. Suspecting the cause to be other than angiostrongyliasis, and entertaining possibility of gnathostomiasis in view of contact with cats, he was treated with additional ivermectin (150 mcg/kg/day) for 5 days, after which the peripheral eosinophilia decreased to 14%. He subsequently showed complete recovery in terms of clinical picture and eosinophilia. His serial haemograms and CSF analyses are depicted in [Table 1].


 ~ Discussion Top


Both our patients were residents of western suburbs of Mumbai and had variable exposure to rats and cats. Both had a similar presentation and as parasites are the most common causes of eosinophilic meningitis and as both our patients had significant peripheral eosinophilia, we strongly suspected parasitic infection as the cause of eosinophilic meningitis in both our patients. They also responded to antihelminthic agents which strongly supported a parasitic cause of the eosinophilic meningitis. More importantly, both were previously healthy children carrying no risk factor or pointer towards a non parasitic cause of eosinophilic meningitis. (Immunodeficiency, exposure to drugs, contact with or evidence of tuberculosis) We were unable to obtain a serologic or microbiologic diagnosis for the proposed parasites due to the non-availability of various serological tests for the same in our country.

Here, we review the two most common parasitic causes of eosinophilic meningitis and the basis for proposing these parasites as the etiologic agents in the above two cases.

Angiostrongyliasis is the most common cause of eosinophilic meningitis worldwide. [5] The definitive hosts of the nematode are rats and humans get infected by ingesting the infected intermediate hosts or any of the paratenic hosts, including prawns, crabs and frogs, or by eating raw vegetables containing material from the intermediate or paratenic hosts (e.g. shells and secretions). [5] Though rats are not directly involved in transmitting infective forms to humans, their presence in close contact with the patient in case 1 gives us a clue that the life cycle of the said parasite might have involved the patients.

For case 1, though a history of ingesting an intermediate or paratenic host was not elicited, humans also get infected by consuming vegetables infected by excreta of these hosts. This is the presumed mode of transmission of Angiostrongylus in case 1.

In the case series reported from South India, the acquisition of infection was from eating raw flesh of monitor lizards, which is considered an aphrodisiac. [6],[7] In our second patient, though there was a history of lizards in the house, infection acquired through lizards seems less likely as it is acquired through consumption of raw flesh or blood of lizard.

Clinical manifestations of angiostrongyliasis usually occur 1 week to 1 month after exposure and include fever, headache and painful paresthesias [10] , cranial nerve palsies, most commonly of nerves 7 and 8 and visual disturbances secondary to a direct larval invasion of the ocular structures. [11] Spontaneous resolution of symptoms can occur in 1-2 weeks although the headaches and paresthesiae canpersist for weeks to months. These are predominantly reported in affected adults. As both our patients were of paediatric age group, they had fever and lethargy as the chief clinical manifestations. The signs and symptoms of meningitis in young children are related to the non-specific findings associated with a systemic infection (fever, anorexia and poor feeding, headache) and to manifestations of meningeal irritation. As we noticed in case 1, in many children with meningitis, particularly in those younger than 12-18 months, signs of meningeal irritation are not consistently present. Also the first child did develop a squint but no other cranial nerve palsies were seen in both our patients.

Diagnosis of angiostrongyliasis is based largely on the history of possible exposure, clinical presentation and CSF eosinophilia. [12] CSF findings indicative of angiostrongyliasis include an increased protein level, a normal glucose level and an elevated absolute leukocyte count with eosinophilia ranging from 10% to 90%. [12] Angiostrongyliasis usually does not produce focal lesions on neuroimaging. [13] Similar findings were noted in our patients though the first patient had focal lesions on MRI.

Although angiostrongyliasis is often a self-limited disease, treatment options consist of steroidtherapy, antihelminthic therapy or a combination of these strategies. [5] As the disease manifestations are mostly due to the host inflammatory reaction, steroids are being used as part of the therapy, though various studies show the role of steroids in eosinophilic meningitis to be controversial. [5] As albendazole is the drug of choice for treating angiostrongyliasis [12] , both our patients received steroids and albendazole for minimum period of 2 weeks whereas the second child needed albendazole for almost a month and also a short course of ivermectin for a suspected gnathostomiasis.

The other common cause of eosinophilic meningitis is gnathostomiasis. [5] The definitive hosts of Gnathostoma species are dogs and cats [14] that ingest the third-stage larvae, which then mature in the stomach of the host and eggs are passed in the faeces. The larvae that hatch can develop into the second stage when they are ingested by crustaceans of the genus Cyclops. These crustaceans are then eaten by a range of paratenic hosts, including fish, frogs, pigs, snakes, fowl and eels. [15] The helminth matures into the third phase when it migrates to hostmuscle tissue and encysts. [15] Humans become infected when they ingest raw or undercooked paratenic hosts. [14],[15] Less common modes of infection are ingestion of water containing infected copepods and penetration of advanced larvae through the skin of food handlers. [16] Infection with Gnathostoma species is typically categorized into cutaneous, visceral and CNSforms. [17] The dermatological manifestations of Gnathostoma infection include panniculitis, creeping eruptions and pseudofurunculosis with a predilection to the trunk. [14] Similar to Angiostrongylus infection, Gnathostoma infection can directly invade the eye and cause pain, uveitis, increased intraocularpressure and blindness. [14] In the CNS, Gnathostoma infection is often more severe than Angiostrongylus infection. [13] CNS gnathostomiasis usually presents with radicular pain and paresthesias of the trunk and extremities and, less frequently, with paresis or paralysis which probably results from direct migration of the worm along cranial or peripheral nerves into the spinal cord. [14] It can also result in meningeal inflammation, myelitis or encephalitis, cranial nerve palsies and subarachnoid haemorrhages. [14] The pointers to the diagnosis are presence of peripheral and CSF eosinophilia and a history of contact with host animals. CSF analysis usually shows pleocytosis with eosinophilia, normal glucose levels and normal or elevated protein levels. [14] Head computed tomography (CT) may reveal nodular lesions, areas of haemorrhage with tracks, and even hydrocephalus. [14] Treatment of gnathostomiasis differs on the basis of the location of infection. For cutaneous disease, albendazole and ivermectin therapy is recommended. [18] Treatment of neurological gnathstomiasis is primarily supportive, because the role of steroids and antihelminthics in CNS gnathostomiasis has not been clearly defined. [14] Since our second patient continued to have eosinophilia in spite of steroids and albendazole, ivermectin was added to which he showed response. This is the primary indicator of a probable diagnosis of gnathostomiasis in our patient in case 2. The proposed mechanism of transmission in our case is through ingestion of contaminated water. Though there was a history of exposure to cat secretions in case 2, which could point to the possibility of toxoplasmosis as the cause of the peripheral eosinophilia, the argument is that toxoplasma is unlikely to cause eosinophilic meningitis in an immunocompetent child. [16]

The definitive diagnosis of both angiostrongyliasis and gnathostomiasis requires identification of the organism in host tissues. However, organism isolation in CNS is difficult and lacks sensitivity. [19] Serological tests can be used. The specificity and sensitivity of these assays vary greatly and are limited by cross-reactivity with other parasitic infections. [20] These tests are not available in India; hence we could not confirm the etiology of these cases. But pointers to the etiological agent being Angiostrongylus in the first case were the history of exposure to rats and the prompt response to therapy with steroids and albendazole. In the second case, non response to the same therapy and response to ivermectin led to a suspicion of gnathostomiasis. Apart from these two most common causes, several other parasitic as well as non parasitic causes of eosinophilic meningitis have been reported. We effectively ruled out malignancies, drugs and viral and bacterial meningitis as the causes based on history, non-response to antibacterial therapy and response to antihelminthic therapy. Other parasitic causes which could be plausible in these scenarios included Schistosomiasis, Cysticercosis, Toxocariasis, Paragonimiasis, Hydatidosis and Strongyloidiasis. Schistosoma was unlikely to be the cause as there was no history of exposure to pond water or pruritic skin lesions (swimmer's itch) in both our patients. Also, schistosoma infection predominantly involves nerve roots and eosinophilic CSF pleocytosis is rare. [16]

Cysticercus could be one of the proposed etiologies but there was no history of consumption of uncooked pork in both our children. Also, neurocysticercois is neither a febrile disease nor a typical meningitis syndrome. [16] It presents as cystic lesions on neuroimaging, which was not seen in both our patients. Another parasite, Toxocara, is rare cause of CNS infection and meningitis. Baylisascarisis was also unlikely as human disease is rare and always entails sequelae or death, while both our patients improved without any sequelae. Paragonimiasis would have led to pulmonary involvement, which was not present in our cases. Also, there was no history of consumption of crustaceans. In hydatidosis, CNS cysts do not typically elicit a strong inflammatory reaction, even when they are in the subarachnoid space. Eosinophilic meningitis may occur as a complication of surgical resection, but this is rare. Both our patients had neither cystic lesions nor any history of neurosurgery performed. In Strongyloides infection, eosinophilic meningitis does not occur. Interestingly, from India, only one case report [8] could prove the microbiologic diagnosis of Angiostrongylus, as the worm was retrieved from the eye in this case. In the case series [6],[7] and another case report [9] from India, all the afflicted males had history of ingestion of monitor lizards as an aphrodisiac. Even though the serologic diagnosis could not be made in all these cases, the specific history of exposure to flesh of monitor lizard pointed to the diagnosis of angiostrongyliasis. However, Parameswaran et al.,[6] reported two female adult patients with eosinophilic meningitis and no history of lizard consumption, but were presumed to have angiostrongyliasis on the basis of response to antihelminths.


 ~ Conclusion Top


meningitis, though rare in children, may be seen due to a host of conditions, most commonly parasitic infections of the CNS. History of exposure to the intermediate hosts should lead to a strong suspicion of these infestations. In such cases, early therapy with antihelminths and steroids is beneficial.

 
 ~ References Top

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2.
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Chan YC, Ho KH, Chuah YS, Lau CC, Thomas A, Tambyah PA. Eosinophilic meningitis secondary to allergic Aspergillus sinusitis. J Allergy Clin Immunol 2004;114:194-5.  Back to cited text no. 3
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Sawanyawisuth K, Sawanyawisuth K, Senthong V, Limpawattana P, Intapan PM, Tiamkao S, et al. Peripheral eosinophilia as an indicator of meningitic angiostrongyliasis in exposed individuals. Mem Inst Oswaldo Cruz 2010;105:942-4.  Back to cited text no. 4
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Ramirez-Avila L, Slome S, Schuster F, Gavali S, Schantz P, Sejvar J, et al. Eosinophilic Meningitis due to Angiostrongylusand Gnathostoma Species. Clin Infect Dis 2009;48:322-7.  Back to cited text no. 5
    
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Parameswaran K. Case series of eosinophilic meningoencephalitis from South India. Ann Indian Acad Neurol 2006;9:217-22.  Back to cited text no. 6
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Baheti N, Sreedharan M, Krishnamoorthy T, Nair M, Radhakrishnan K. Eosinophilic meningitis and an ocular worm in a patient from Kerala, South India. J Neurol Neurosurg Psychiatry 2008;79:271.  Back to cited text no. 8
    
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Pai S, Madi D, Achappa B, Mahalingam S, Kendambadi R. An interesting case of eosinophilic meningitis. J Clin Diagn Res 2013;7:734-5.  Back to cited text no. 9
    
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Slom TJ, Cortese MM, Gerber SI, Jones RC, Holtz TH, Lopez AS. An outbreak of eosinophilic meningitis caused by Angiostrongylus cantonensis in travelers returning from the Caribbean. N Engl J Med 2002;346:668-75.  Back to cited text no. 10
    
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Jindrak K. Angiostrongyliasis cantonensis (eosinophilic meningitis, Alicata'sdisease). In: Hornabrook RW, editor. Topics on Tropical Neurology. Vol. 12. Philadelphia: FA Davis; 1975. p. 133-64.  Back to cited text no. 11
    
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Fernando RL, Fernando SS, Leong AS. Tropical Infectious Diseases: Epidemiology, Investigation, Diagnosis and Management. Vol. 1. Ed. 1. San Francisco: Greenwich; 2001. p. 384.  Back to cited text no. 12
    
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Lo Re V, Gluckman SJ. Eosinophilic meningitis. Am J Med 2003;114:217-23.  Back to cited text no. 13
    
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Rusnak JM, Lucey DR. Clinical gnathostomiasis: Case report and review of the English-language literature. Clin Infect Dis 1993;16:33-50.  Back to cited text no. 14
    
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Kuberski T, Wallace GD. Clinical manifestations of eosinophilic meningitis due to Angiostrongylus cantonensis. Neurology 1979;29:1566-70.  Back to cited text no. 19
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Chye S, Chang J, Yen C. Immunodiagnosis of human eosinophilic meningitis using an antigen of Angiostronyglus cantonensis L5 with molecular weight 204 kD. Acta Tropica 2000;75:9-17.  Back to cited text no. 20
    



 
 
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