Central nervous system infection due to Acanthamoeba: A case series.

Sir,

Infection of humans with free-living amoebas is often a life-threatening occurrence in immunocompromised and rarely in immunocompetent hosts.[1] Central nervous system (CNS) infection by free-living amoeba has been reported worldwide with only 2–3% survival rate.[2] Granulomatous amoebic encephalitis (GAE) which is an insidious, chronic, and mostly fatal disease is caused by species of Acanthamoeba and Balamuthia mandrillaris.[3]

The dilemma in accurate diagnosis and specific treatment delays early management of these cases often leading to fatalities or chronicity with recurrences.

Here, we report a series of cases highlighting the presentation of Acanthamoeba encephalitis in immunocompetent children with varied clinical manifestations, leading to diagnostic dilemmas, and the possible therapeutic interventions.

A previously healthy, 4-year-old boy, a resident of Uttar Pradesh presented with a history of a generalized headache for 1 month, intermittent high-grade fever associated with vomiting for 1 week. This was accompanied by 7–8 episodes of generalized tonic-clonic seizures lasting for 3–5 min for 1 day. The child had a history of geophagia and would often play in the garden with compost soil. There was no history of swimming or contact with tuberculosis. The patient was Human immunodeficiency virus (HIV) seronegative. On admission to our hospital, the child was restless and febrile and was in a tonic posture. CNS examination showed marked neck stiffness; brudzinski's and kernig's sign were positive with no focal neurological deficit. Cerebrospinal fluid (CSF) examination revealed: Proteins 16 mg%, sugar 40 mg% with 20 cells/mm3 (predominantly lymphocytes). The wet mount of CSF showed the presence of organisms morphologically resembling trophozoites of Acanthamoeba species. Giemsa stained smear confirmed the presence of amoeba. CSF microscopy and cultures were negative for bacteria and fungi. CSF was inoculated onto nonnutrient agar plates covered with a lawn of Escherichia coli and incubated at 37°C. After 24 h of incubation, many cysts consistent with Acanthamoeba species were observed [Figure 1]. A diagnosis of amoebic meningoencephalitis was made. Computed tomography (CT) scan report showed mild hydrocephalus. Blood and stool culture for bacteria and fungi were also negative. The patient was treated with mannitol, dexamethasone, and phenytoin. Amphotericin-B, rifampicin, and trimethoprim-sulfamethoxazole were subsequently initiated and continued for 21 days in appropriate doses. Nursing care, nutrition was maintained, and antipyretics were given four hourly. Treatment was continued, and thereafter patient's condition improved and discharged from the hospital. The patient came back again after 1.5 months with similar complaints. With the help of clinical picture, CSF cytology, CSF wet mount examination a diagnosis of Acanthamoeba meningoenencephalitis was made. The patient was treated with Mannitol, Phenytoin, and a combination of Amphotericin-B, Rifampicin, and Trimethoprim-sulfamethoxazole in appropriate doses, the response to treatment was not favorable and patient succumbed to his illness.

Figure 1

Wet mount picture of Acanthamoeba cyst from culture isolation ×40

During a 1½ year period, we witnessed 6 more cases of amoebic encephalitis diagnosed on direct microscopy and subsequently isolated on culture [Table 1]. However, in one case Acanthamoeba could not be isolated in culture and, in this case, diagnosis was confirmed on the basis of direct microscopy findings. Blood cultures and CSF culture for bacteria and fungi were negative in all cases. No acid fast bacilli were seen on Ziehl Neelsen staining of CSF smears, and peripheral blood smear examination revealed the absence of malarial parasites.

Table 1

Demographic profile, clinical picture, investigations conducted, treatment administered, and response to treatment

Acanthamoeba is free-living amoebae widely distributed in the environment. The routes of entry include a break in the skin or by inhalation of windblown cyst leading to amoebae invasion of the CNS through hematogenous spread. The involvement of the CNS can result in fatal consequences within days or weeks. Occasional survivors of disease have also been reported.[14] In our series of cases, all were in the pediatric age group and had a rural background with close proximity to soil. These patients might have acquired the infection through inhalation of cyst. In three of our cases, presentation was acute, and rest of the cases had a sub-acute or chronic presentation. The acute presentation could be due to the accompanying risk factors [Table 1] as reported previously in a recent case.[5] The clinical picture of GAE may resemble viral, bacterial or tuberculosis meningitis. Three of our cases were empirically started on anti-tubercular (TB) therapy suspecting of TB meningitis as it being a common diagnosis in developing countries. The majority of GAE cases due to Acanthamoeba are limited to individuals with a weakened immune system; particularly at risk are individuals with fungal and mycobacterial infections, patients on immunosuppressive therapy, HIV seropositive patients, etc.[6] According to some recent reports, Acanthamoeba infection was also seen in immunocompetent persons.[124] All our cases were HIV seronegative, one patient was undergoing immunosuppressive therapy for malignancy, and another patient had TB meningitis with communicating hydrocephalus as a risk factor. Rests of the patients were immunocompetent with no accompanying illness.

The symptoms of GAE are similar to other CNS pathogens which makes GAE diagnosis problematic. The CT or magnetic resonance imaging scan may prove inconclusive. The CSF findings, although not confirmatory of GAE, are of value in diagnosing the CNS involvement. Pleocytosis with lymphocytic predominance is an important feature as observed in all of our cases.[7] The confirmatory evidence comes from direct microscopic observation of amoebae in the CSF and amoeba culture.[8] Acanthamoeba can also be grown axenically, and for rapid diagnosis molecular methods have been developed.[79]

Delayed diagnosis and limited efficacy of anti-amoebic agents to cross the blood-brain barrier often lead to failure in treatment. Current therapeutic agents have been tried in various combinations, but none of the regimes have been proved to be particularly effective, especially in immunocompromised patients.

In our series of cases, two children presenting with amoebic encephalitis with accompanying risk factors and one case presenting with recurrence of amoebic encephalitis succumbed to their illness. Rest of the cases responded clinically with a combination of amphotericin-B, trimethoprim-sulfamethoxazole, and rifampicin. This regime has been found to be effective in the treatment of a similar case reported earlier.[10] A long-term sequel could not be monitored as they were lost to follow-up after discharge from the hospital.

The current series of cases highlights the importance of including GAE in the differential diagnosis of patients with chronic as well as acute and sub-acute CNS syndrome with no apparent cause. A high index of suspicion should be maintained even in immunocompetent persons without any history of swimming. It will help in more aggressive diagnosis, understanding of associated risk factors and early therapeutic interventions.

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Conflicts of interest

There are no conflicts of interest.