CASE REPORT

Naegleria : A Rare Survival

R. Jain, S. Prabhakar, M. Modi, R. Bhatia, R. Sehgal*

Department of Neurology and Parasitology* Postgraduate Institute of Medical Education and Research Chandigarh - 160 012, India

Summary

Acute amebic caused by free-living amebae fowleri is extremely rare and uniformly fatal with only seven survivals reported till date. An interesting case of naegleria meningitis diagnosed by wet mount cytology of cerebrospinal fluid (CSF) and treated with amphoterecin B, and ornidazole with complete recovery is presented. In cases of suspected pyogenic meningitis, if CSF staining, antigen detection or culture is negative for bacteria, a wet mount cytology of CSF for naegleria is suggested. Early treatment with amphoterecin B and rifampicin may improve survival.

Key words : Naegleria fowleri, Amebic meningoencephalitis

Neurol India, 2002; 50 : 470-472

Introduction meningitis or CNS malignancy.2 About 300 cases of PAM have been reported internationally, mostly from The free living amebae Naegleria fowleri, US, Australia and Europe. These infections are nearly Acanthemeba species and Bala muthiamandrillaris uniformly fatal with only seven survivors of PAM cause extremely rare and sporadic central nervous reported in western literature.3-9 From India, only one system (CNS) infections termed as primary amebic survivor of naegleria meningitis has been reported meningoencephalitis (PAM) which were first earlier, the present case being the second one. described in 1965 by Fowler and Carter in Australia.1 Typically, N.fowleri produces an acute amebic Case Report meningoencephalitis (AAM) which is clinically indistinguishable from acute bacterial meningitis, A 26 year old female presented with history of fever, where as acanthemeba cause subacute to chronic headache, vomiting and altered sensorium of 10 days infection as granulomatous amebic encephalitis duration. Fever was mild to moderate without any (GAE) which may mimic a brain abscess, chronic associated chills or rigors. Headaches were bifrontal, occipital, nonthrobbing, more in the morning and Correspondence to : Dr. S. Prabhakar, Professor and Head, associated with recurrent episodes of projectile Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012, India. vomiting. Associated neck pain was present. There E-mail : [email protected] was no evidence of any cranial nerve involvement,

Neurology India, 50, December 2002 470 Naegleria Meningitis

Fig. 1a. b and c : T2WI and contrast MRI showing multiple contrast enhancing ring lesions in brainstem, cerebellum, temporal and parietal lobes. focal deficit, altered sensorium or seizures. Patient for acute naegleria meningitis was started. Rifampicin neither swam nor had taken any recent bath in pond, was continued in a dose of 450 mg orally per day. pool or lake. All relevant history for tuberculosis was was started in a dose of 1mg/kg/day negative. A plain and contrast CT done on 3rd day of with a strict monitoring of renal functions and serum onset of illness, revealed multiple contrast enhancing electrolytes. Ornidazole was also added in doses of lesions. Following CT, CSF was also examined in a 500 mg every 8 hour. Steroids were gradually tapered private hospital, which revealed 950 cells/mm3 over two weeks. After a week’s therapy, there was (P3,L97) with 410 mg/dl protein and 52 mg/dl of improvement in clinical signs and symptoms. Repeat sugar and with negative cysticercal serology. Based CSF after two weeks of treatment was absolutely on CSF, CT and clinical status, she was started on four normal with no evidence of naegleria trophozoites. drug anti-tubercular therapy (ATT), dexamethasone Treatment was continued for three weeks and later and mannitol. The patient was referred to patient was discharged. On follow up, three months Postgraduate Institute of Medical Education and later patient was totally asymptomatic. Research after a week with no improvement in clinical status. Discussion

On examination, there was marked neck stiffness and Primary amebic meningoencephalitis is divided into Kernig’s sign was positive. Fundus examination acute amebic meningoencephalitis (AAM) and revealed a congested disc with reduced venous granulomatous amebic encephalitis (GAE). AAM is pulsations. Investigations revealed a TLC of principally caused by N.fowleri in a patient with 19,100/mm3 (P88,L10,M1,E1). Repeat CSF analysis excellent health with prior intimate contact with fresh revealed 360 cells/mm3 (P20 L80), ADA of 11 units water, especially in summer months. The portal of with PCR for tuberculosis, cryptococcal antigen, entry is via the olfactory mucosa and neuroepithelium. cysticeral serology, malignant cell cytology, AFB Incubation period is 3-8 days with acute and rapidly culture, gram stain being all negative. To our surprise, fatal course. Patient usually dies within 7-10 days of the cytology of wet mount CSF revealed plenty of onset of symptoms. Clinical picture resembles acute motile trophozoites of naegleria. The finding was bacterial meningitis.2,10,11 Diagnostic test involves confirmed with a repeat CSF that revealed plenty of CSF study with direct visualization of naegleria under actively motile trophozoites consistent with the light microscope which are actively motile and can be morphology of naegleria. Amebic culture was stained with Heidenhain’s iron hematoxylin and negative. CSF PCR for tuberculosis and gram stain Wheatley’s trichrome stain.2. There is pleocytosis were negative on second examination also. Chest X- with neutrophilic dominance and a high protein with ray, collagen vascular profile, ultrasound abdomen low sugar. Indirect hemagglutination, ELISA, indirect were normal and nasal smear for naegleria was /direct immunofluorescence are other methods used negative. MRI brain (plain and contrast) revealed for diagnosis. However, serology is not useful in multiple small enhancing disc lesions with meningeal diagnosis during the acute stage, as antibodies to enhancement (Fig. 1 and 2). Based on the clinical naegleria species have also been detected in normal profile and CSF cytology, an aggressive management person.12,13 MRI is usually suggestive of cerebral

471 Neurology India, 50, December 2002 Jain et al edema with meningeal enhancement.14 The drug of Reference choice is amphotericin-B (intra thecal and intra venous). Rifampicin, tetracyclin may be added for 1. Fowler M, Carter RF : Acute pyogenic meningitis probably better results. Although amoebicidal drugs as due to acanthameba Sp.: a preliminary report. BMJ 1965; metronidazole and ornidazole have no activity against 2 :740-742. free living ameba, we still used it in view of the 2. Niu MT, Duma RJ : Amebic infection of the nervous system. atypical presentation of the index case and their good Handbook of Clinical Neurology 8 : 309-337. 3. Anderson K, Jamieson A : Primary amebic efficacy against cerebral amebiasis. All the survivors meningoencephalitis. Lancet. 1972; 1 : 90-2-3. reported till date were treated with amphotericin B. In 4. Apley J, Clarke SKR, Roome APCH et al. : Primary amebic contrast, GAE is caused principally by acanthameba meningoencephalitis in Britian. BMJ 1970; 1 : 596-599. species especially in immunosuppressive hosts. The 5. Seidel JS, Harmatz P, Visvesvera GS : Successful course is subacute to chronic but is terminally fatal. treatment of PAM. N Engl J Med 1982; 306 : 346-348. Usually the trophozoites are not seen in CSF smear 6. Brown RL : Successful treatment of PAM. Arch Intern Med and cytology usually reveals a lymphocytic 1991; 151 : 1201-1202. pleocytosis. MRI reveals multifocal contrast 7. Loschiava F, Ventura-Spagnolo T, Sessa E et al : Acute enhancing lesions with predilection for diencephalon, PAM from naegleria fowleri. Report of a clinical case with a favourable outcome. Acta Neurol (Napoli) 1993; 15 : 333- thalamus, brain stem and posterior fossa 340. structures.2,14,15 Naegleria infection has also been 8. Poungverin N, Jarya P : The fifth nonlethal case of PAM. reported from other sources such as tap water and J Med Assoc Thia 1991; 74 : 112-115. air.16,17 Sub- clinical infection due to naegleria may 9. Wang A, Kay R, Poon WS : Successful treatment of amebic occur in a healthy individual when these amebae meningoencephalitis in a Chinese living in Hong Kong. Clin colonise the nose and throat.18 Neurol Neurosurg 1993; 95 : 249-252. 10. Singh SN, Patwari AK, Dutta R et al : Naegleria meningitis. Indian Pediatrcs 1993; 35 : 1012-1015. The index case presumably acquired infection from 11. Marciano-Cabral F, Petri Jr WA : Free living amebae. In : air and had a subacute course similar to the other Principles and practice of infectious diseases. Vol. 2. survival of naegleria meningitis reported from India.10 Mandel. GL, Bannet JE. (eds.). Churchill living stone, New MRI and CT pictures in this case were more York.. 1994; 2408-2414. suggestive of GAE instead of AAM. Although CSF 12. Reilly MF, Marchiano F et al : Agglutination of N. Fowleri had shown plenty of actively motile trophozoites and N. Gruberi by antibodies in human serum. J Clin Microbiol 1983; 17 : 576-581. suggestive of naegleria infection, but the presence of 13. John DT : PAM and the biology of N. Fowleri. Ann Rev lymphocytic pleocytosis is unusual. In view of the fact Microbiol 1982; 36 : 101-123. that the present case had features of both naegleria 14. Kidney D.D, Kim SH : CNS Infections with free living meningitis as well as a subacute to chronic Amebas: Neuroimaging findings AJR 1998; 171 : 8-9-12. granulomatous disease caused by acanthameba, two 15. Sell JJ, Rupp FW, Orrison WW : GAE caused by possibilities emerge. Either the patient was having a acanthameba. Neuroradiology 1997; 39 : 434-436. mixed infection, which seems less likely or a lesser 16. Warhurst DC, Mann PG : PAM in Both Spa, England. In : virulent strain of naegleria was responsible for the Proceeding of the 2nd Intrernational Conference on Biology same. and pathogenicity of small free-living Amebae. Florida Gainesville, University of Florida. 1980; 55. 17. Lawande RV, Abraham SN, John I : Recovery of soil In conclusion, although PAM is rare and has poor amebas from nasal passage of children during dusty prognosis, it should be considered in any patient of Hasmattan period in Zaria. i1979; 71 : 201-203. pyogenic meningitis without evidence of bacteria by 18. John DT : PAM and the biology of Naegleria fowleri. Ann staining, antigen detection and culture. CSF cytology Rev Microbiol 1982; 36 : 101-123. of wet mount becomes mandatory in such cases as early treatment with amphotericin may improve survival. Accepted for publication : 19th September, 2001.

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