EXPERIENCE OF PRIMARY AMOEBIC MENINGOENCEPHALITIS IN ICU PNS SHIFA KARACHI.
Infection of human specially affecting central nervous system by free living amoebas is infrequent but often life threatening occurrence in both normal that is immuno-competent and immuno-compromised individuals1. Free living amoeba includes many genera with high distribution in natural and artificial environment such as air water dust and soil23. Among them members of only genera Naegleria fowleri Acanthamoeba and Balamuthia mandrillaris have been in association with human diseases formerly known as leptomyxid amoeba4. The disease become evident in two different clinical fashion. One is the more acute form which is almost universally fatal and occur in previously healthy individuals5. This form is known as Primary Amoebic Meningoencephalitis (PAM) caused by Naegleria fowleri6. It was first described in 1965 by Fowler and Carter in Australia5. The other is a more chronic form is known as Granulomatous amoebic meningoencephalitis (GAM) caused by Acanthamoeba and Balamuthia mandrillaris13.
Naegleria fowleri is a thermophilic amoeba that grows well in tropical climates7. Naegleria species has been isolated from the thermal discharge of power plants hot springs sewage and even from nasal passages of healthy person7. The trophozoites active stage of Naegleria fowleri infects the brain through the olfactory bulb by penetrating nasal epithelium. The incubation period is 5-15 days. The trophozoites of N. fowleri are difficult to distinguish morphologically from macrophages. Cultured amoeba produce flagellates in distilled water at 370C within 15-30 minutes.
All six patients were male. Their ages were ranged from twenty to fifty five years. All were residents of Karachi but lived in different districts. They didn't have recent history of travelling both domestic and international. They had rapidly deteriorating course of illness: presented with a short history of 2-3 days illness with common symptoms comprising of fever vomiting and headache followed by altered consciousness in form of confusion agitation and then coma. Four of them had seizures too. Patients went on ventilator within 48 hours of altered mental status. This is noteworthy that all the patients were referred from both primary and secondary care units after 3 days of their illness.
Clinical examination of five patient revealed confusion disorientation and irritability with fever tachycardia and initially stable blood pressure and respiration. One of the patient presented with deep coma hypotension and low oxygen saturation. There were no pallor icteric cyanosis clubbing pedal edema lymphadenopathy or raised JVP. Skin and ENT examinations were normal.
Central nervous system examination showed signs of meningeal irritation with no sign of focal neurologic deficit. Examination of fundus showed bilateral papilledema in two of the patients. The examination of other systems revealed no abnormality. The diagnosis of acute pyogenic meningitis was made. In all patients investigations were carried out at PNS Shifa laboratory. Peripheral blood film showed normocytic normochromic anaemia in three patients raised total leukocyte count (TLC) predominantly neutrophils in five patients and low platelet count was in one patient. Typhidot IgM was positive in one patient ICT malaria and Dengue IgM was negative. Finding of urine analysis LFTS's RFT's ultrasound abdomen and x-ray chest were normal initially. In terminal stages all six patients showed signs of sepsis then septic shock and multi-organ dysfunction syndrome with deranged LFT's RFT's and coagulopathy. Repeated blood cultures were negative. Computed tomography (CT) scan showed generalised edema with increased vascularity in post contrast study (suggestive of meningitis). CT scan of one patient showed subarachnoid hemorrhage and one of them showed obstructive hydrocephalus. Magnetic resonance imaging (MRI) studies were done in two of the patients only and showed basal meningeal enhancement. Lumber puncture was done. With exception of one patient cerebrospinal fluid (CSF) analysis showed decreased glucose increased protein increased cell count predominantly neutrophils and presence of red blood cells. Wet mount film of CSF showed Naegleria fowleri amoeba.
Culture and immunological studies were not done due to non availability of these facilities. Gram's stain and bacterial culture were negative. Culture for Naegleria fowleri was not carried out. Preliminary diagnosis of PAM was made.
Patients were treated with Amphotericin B (1.5 mg/kg/day) and oral Rifampicin (20 mg/kg/day). Amphotericin B was given intravenously to all patients plus intrathecal in one patient too. The appropriate antibiotics combinations were used including Ceftriaxone and Vancomycin Azithromycin and Metronidazole. Medicines to reduce brain edema and inflammation were given along with other supportive measures like nutrition through nasogastric tube and round the clock nursing care in intensive care unit. All the patients died within 3-7 days of hospital admission resulting in 100% mortality. None of them underwent postmortem examination due to non willingness of their next of kin.
About 400 cases of PAM have been reported in the world mostly in USA and Europe. These infections are nearly uniformly fatal with only four survivors of PAM reported4. Till to date only one case series has been published in this region in 2009 consisting of thirteen patients suffering from PAM with 100% mortality2. That's exactly what we have seen in these patients in our set up that is 100% mortality. Documented route of infection include recreational water activities and ritual ablution. In previous few studies in different parts of the world domestic tap water untreated ground water and overland pipes showed Naegleria fowleri9. The presence of Naegleria fowleri amoeba in Karachi's municipal water supply may have several explanations.
Karachi lacks an indigenous source of water and water obtained from two suburban freshwater lakes is not adequately filtered or chlorinated. Moreover frequent leaks in water and sewage pipes can cause seepage of sewage in water supply which may be a potential reservoir.
PAM is a fulminant infection that typically leads to death in first or second week from onset of symptoms. The clinical course of Naegleria fowleri neurological infection has a sudden onset and a fulminant course due to diffuse hemorrhagic necrotizing meningoencephalitis6. Routine laboratory investigations are not helpful in distinguishing it from other causes of meningoencephalitis4. The CSF analysis shows raised proteins normal or decreased glucose pleocytosis with high count of white as well as red blood cells. Naegleria fowleri can be identified as wet mount examination of the CSF by its morphology and motility8. Diagnosis depends on clinical features positive history of contact with lake water and negative culture of bacteria viruses and fungi CSF detection of free living amoebas observation of amoeba in rhinopharyngeal cavity wash and testing with monoclonal antibodies2. Special culture media and microbiological expertise are required for culturing of amoeba.
Serological tests performed are indirect immunofluorescence (IFA) dot immunobinding asssay (DIBA) enzyme linked immuno transfer blot technique (EITB)7. Neuro- imaging findings are non specific brain edema favoring Naegleria fowleri suggestive of meningitis and punctate enhancing lesions due to Acanthamoeba. Although confirmation of the presence of amoeba in CSF is essential for an accurate diagnosis lumber puncture should not be done in the presence of acute brain swelling due to risk of herniation.
There is no gold standard treatment regimen for PAM1. Management strategy of PAM needs to be reviewed further. According to the literature preview a study has indicated that Amphotericin B (at a dose of 1-1.5 mg/kg/day) and Azithromycin (in dose of 7.5 mg/kg/days) have a synergistic action against Naegleria fowleri1347. Combination of Amphotericin B intravenously or intrathecally along with Fluconazole has promising results89. Rifampicin and Sulphadiazine along with anti edema measures have been tried with limited success56. Here an issue raised about the emergence of Amphotericin B resistant Naegleria fowleri8. CONCLUSION
PAM caused by Naegleria fowleri is a medical emergency. Rapid progression of the disease and limited awareness make this disease a diagnostic challenge. Successful outcome depends on early diagnosis and aggressive treatment. This is also an alarming situation for the government and municipal bodies. There should be a proper system of water purification and proper supply without mixing of sewerage water.
1. Kaushal V Chhina DK Ram S Singh G Kashal RK Kumar R. Primary amoebic meningoencephalitis due to Naegleria fowleri. JAPI 2008; 56: 459 - 462.
2. Shakoor S Beg MA Mahmood SF Bandea R Sriram R Noman F et al. Primary amoebic meningoencephalitis caused by Naegleria fowleri Karachi Pakistan. Emerg Inf Dis 2011; 17(2): 258 - 261.
3. Movahedi Z Shokrollahi MR Aghaali M Heydari. Primary amoebic meningoencephalitis in an Iranian Infant. Medicine. 2012; 1: 1 - 4.
4. Tungikar SI Kulkarni AG Deshpande AD Gosavi VS. Primary amoebic meningoencephalitis. JAPI 2006; 54: 327 - 329.
5. Sugita Y Fujii T Hayashi I Aoki T Yokoyama T Morimatsu M et al. Primary amoebic meningoencephalitis due to Naegleria fowleri: An autopsy case in Japan. Pathology International 1999; 49: 468 - 470.
6. Khanna V Khanna R Hebbar S Shashidhar S Mundkar S Munim F et al. Primary amoebic meningoencephalitis in an Infant due to Naegleria fowleri. Neurol Med 2011; 1.
7. Cabanes PA Wallet F Pringuez E Pernin P. Assesing the risk of primary amoebic meningoencephalitis from swimming in the presence of environmental Naegleria fowleri. AEM. 2001; 67(7): 2927 - 2931.
8. Craun GF Calderon RL Craun MF. Outbreak associated with recreational water in the United States. Int J Environ Health Res 2005; 15: 243-262.
9. Rai R Singh DK Srivastava AK Bhargava A. Primary amoebic meningoencephalitis. Indian Paediatrics 2008; 45: 1004-1005.