An uncommon meningitis in an immunocompetent individual
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.173661
Source of Support: None, Conflict of Interest: None
Listeria meningitis is an unusual cause of community acquired bacterial meningitis. The usual predisposed population include the immunocompromised individuals, neonates, pregnant women and the elderly population. There are very few case reports of Listeria meningitis in an immunocompetent individual in the adult age group (15-50 years)., Our literature search did not yield any such report from India. We report a case of a previously healthy man suffering from community acquired bacterial meningitis which was subsequently proven to be due to Listeria.
A 46-year old man presented to the emergency department with a history of generalized tonic clonic seizures that had occurred an hour ago. There was no aura before the seizure. The tonic clonic movements lasted for 10 minutes and subsequently the patient was in a post-ictal phase of restlessness and confusion. The patient also had a history of headache, vomiting and fever during the preceding 5 days. The fever was intermittent, high grade, not associated with chills and rigors, was occurring daily and used to normalize with antipyretic medications. The headache was continuous, holocranial, throbbing and was associated with nausea and vomiting. The intensity of headache used to reduce with analgesics, but it would recur after some time. On examination, the patient was restless, disoriented to time, place and person, was moving all 4 limbs and had neck stiffness. On the 2nd day of admission, he developed erythematous maculopapular skin rashes all over his body.
His laboratory investigations revealed the following values: Hemoglobin 13.9 gm/dL, total leukocyte count 12,600/cumm, total bilirubin 1.2 mg/dL, serum glutamic oxaloacetic transaminase (SGOT) 95 U/L, serum glutamic pyruvic transaminase (SGPT) 55 U/L, kidney function tests normal, rapid malaria test negative, urine routine and microscopy normal and human immunodeficiency virus (HIV) serology nonreactive. Computed tomographic (CT) scan of the brain showed mild enhancement along the sulcal spaces in bilateral high fronto-parietal region and a mild ventricular dilatation [Figure 1]a. Cerebrospinal fluid (CSF) was turbid on gross appearance. It showed a protein of 720 mg/dL and a sugar of 49 mg/dL (the concurrent blood sugar was 251 mg/dL). The cytology of CSF showed a total cells count of 590/cumm of which polymorphs were 40% and lymphocytes were 60%. The Gram, Ziehl Neelsen and India ink staining were negative. Treatment with intravenous ceftriaxone 2 gms 12 hourly, vancomycin 500 mg 8 hourly and levetiracetam 500 mg 12 hourly was immediately instituted.
On day 3, the patient became drowsier with his Glasgow coma scale score being 8. He was intubated and put on mechanical ventilator. At this point, CT scan of the brain was repeated which showed an increase in hydrocephalus, and a diffuse irregular enhancement along the sulcal spaces and in basal cisterns [Figure 1]b. There was no parenchymal involvement. Neurosurgical opinion was taken and on day 4, a ventriculo-peritoneal (VP) shunt was placed. The same day, the CSF culture and sensitivity report was received which showed growth of Listeria monocytogenes nes [Figure 2]. Blood culture also showed the growth of Listeria monocytogenes. The Listeria colonies were small, white, smooth, translucent and moist with a coexisting subtle beta hemolysis. CSF polymerase chain reaction (PCR) tests for tuberculosis and herpes simplex virus were negative. His CD4 count was 359. After this CSF culture report, the patient was started on intravenous ampicillin, 4 gms 4 hourly.
On day 5, the patient became deeply unconscious, had extensor response to pain and right pupil became dilated and non-reactive to light. The CT scan of the brain at this point of time showed the VP shunt tube in the right lateral ventricle and dilatation of the left lateral, third and fourth ventricles [Figure 1]c. There was a hypodensity in the midbrain. The neurosurgical colleague, therefore, converted the malfunctioning VP shunt into an external ventricular drain that was draining the left lateral ventricle. CSF analysis from ventricle showed a hazy appearance, with a protein value of 1100 mg/dL, sugar value of 1.3 mg/dL (with the concurrent blood sugar being 100 mg/dL) and the total cell count being 710/cumm with 55% polymorphs and 55% lymphocytes. Despite all the instituted measures, the patient continued to deteriorate and died on the sixth day of admission.
Listeria monocytogenes is a gram positive, facultative anerobic, motile bacillus with the characteristic tumbling motility at 20-25°C. The Listeria organism is present in a large number of environmental samples. As per the Centers for Disease Control (CDC) estimates, about 3500 people in the United States are affected with serious Listeria infection every year. In the human population, 1-5% of people may be excreting Listeria in stools and this figure is as high as 29% in poultry workers. Very often, it is difficult to demonstrate the source of infection in a given case.
Listeria can tolerate a wide range of temperature (ranging from -7°C to body temperature) thus surviving refrigeration in the food items. It infects cell by inducing its own uptake and then spreads by cell-to-cell transmission. The intracellular location offers protection against humoral immunity. Listeria primarily enters through the intestines and then proliferates in the liver. In the event of uncontrolled proliferation in the hepatocytes in immunocompromised individuals, bacteremia develops and then organs like brain and uterus get secondarily involved. The different strains of Listeria have varying virulence and some strains just cause a febrile gastroenteritis and not an invasive disease. Seventeen serotypes of Listeria monocytogenes have been described and serotype 1a, 1b and 4b account for more than 90% of the clinical disease.
In a large series reporting on 46 adults with Listeria meningitis, all patients were either immunocompromised or over 50 years of age. Our patient was younger and did not have any risk factors. There are very few case reports describing the presence of Listeria meningitis in immunocompetent adults. Three adult cases of Listeria meningitis have been described from Vietnam of which 2 individuals were healthy prior to their developing meningitis. Another case of Listeria meningitis has been reported in a 24-year old healthy man from Kuwait. Two large series of meningitis from India did not report any case of Listeria meningitis., The reports of Listeria meningitis from India are summarized in [Table 1]. The risk factors identified in the Indian studies were extremes of age, HIV positive status, alcoholism and maternal vaginal Listeria infection.
Ampicillin is the preferred antibiotic agent for the treatment of Listeria meningitis. Alternatives include trimethoprim-sulfamethoxazole and aminoglycosides. The recommended duration of therapy is 2-3 weeks.
Apart from meningitis, the other central nervous system complications of Listeria infection include cerebritis, brain abscess, ventriculitis, rhombencephalitis and hydrocephalus. Our patient had developed hydrocephalus from the first day of admission, which showed progression on the scan done on day 3. Hydrocephalus has very rarely been reported in Listeria meningitis. Impairment of CSF absorption from the arachnoidal granulations due to the meningeal exudates, and blockade of CSF pathway due to inflammation, are the possible mechanisms for the development of hydrocephalus in Listeria meningitis. Successful response to CSF shunting along with concurrent administration of antimicrobial therapy has been reported in literature. For our patient too, a ventriculo-peritoneal shunt was placed, an external ventricular drainage was done from contralateral lateral ventricle and ampicillin was started, but the patient could not be saved. A very high rate of unfavourable outcome to the tune of 60% has been reported for Listeria meningitis, as has been our experience.
Listeria meningitis is a preventable and treatable cause of community acquired and sometimes widespread meningitis. The clinical features and CSF picture alone are not diagnostic and the definitive diagnosis requires culture positivity. An empirical regimen for bacterial meningitis consisting of the third generation cephalosporins and vancomycin are not effective against Listeria and therefore, a high index of suspicion is needed. Although it most commonly affects immunocompromised individuals and those at the extremes of age, even immunocompetent adults can present with Listeria meningitis. Advancements in the sequencing of Listeria genome and its analytical correlation with virulence of the organism, have helped in initiating a deeper understanding of its interaction with human tissue.
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[Figure 1], [Figure 2]