Toxoplasma encephalitis – A presenting feature of HIV disease

Ala Ram; Pankaj Kumar Saini; Aakash Garg; Shakti Singh; Kavin Kumar; Sanjiv Maheshwari

doi:10.4103/cmrp.cmrp_105_21

Users Online: 120

CASE REPORT

Year : 2022 | Volume : 12 | Issue : 6 | Page : 283-286

Toxoplasma encephalitis – A presenting feature of HIV disease

Ala Ram, Pankaj Kumar Saini, Aakash Garg, Shakti Singh, Kavin Kumar, Sanjiv Maheshwari
Department of Medicine, Jawahar Lal Nehru Medical College, Ajmer, Rajasthan, India

Date of Submission	18-Oct-2021
Date of Decision	07-Aug-2022
Date of Acceptance	14-Nov-2022
Date of Web Publication	29-Dec-2022

Correspondence Address:
Dr. Ala Ram
Department of Medicine, Jawahar Lal Nehru Medical College, Ajmer, Rajasthan
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmrp.cmrp_105_21

Abstract

Central nervous system (CNS) toxoplasmosis is one of the leading causes of secondary CNS infection and seizures in human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) patients along with cryptococcosis and tuberculosis. Encephalitis can be a primary presentation in undiagnosed HIV patients. We are reporting a rare case of HIV/AIDS that presented to us with encephalitis and was later diagnosed as toxoplasma encephalitis. A 32-year-old male truck driver presented with altered behaviour for about 1 month and vomiting for 4 days. On clinical examination, papilloedema was present. Further investigations revealed serologically proven HIV with CD4 T lymphocyte count of 56 cells/microL. Brain imaging showed multiple ring-enhancing lesions in the bilateral cerebral hemispheres and right cerebellar hemisphere. Serum toxoplasma antibodies were found to be positive and a diagnosis of CNS toxoplasmosis encephalitis was made. Treatment with trimethoprim–sulphamethoxazole and highly active antiretroviral therapy was initiated following which there was a significant improvement in the patient's clinical condition. The patient is on regular follow-up now.

Keywords: Acquired immune deficiency syndrome, central nervous system, highly active antiretroviral therapy

How to cite this article:
Ram A, Saini PK, Garg A, Singh S, Kumar K, Maheshwari S. Toxoplasma encephalitis – A presenting feature of HIV disease. Curr Med Res Pract 2022;12:283-6

How to cite this URL:
Ram A, Saini PK, Garg A, Singh S, Kumar K, Maheshwari S. Toxoplasma encephalitis – A presenting feature of HIV disease. Curr Med Res Pract [serial online] 2022 [cited 2023 Apr 1];12:283-6. Available from: http://www.cmrpjournal.org/text.asp?2022/12/6/283/366166

Introduction

Toxoplasmosis has been one of the most common causes of secondary central nervous system (CNS) infection in patients with acquired immune deficiency syndrome. Toxoplasmosis is generally a late complication of human immunodeficiency virus (HIV) infection and usually occurs in patients with CD4 T lymphocyte cell counts <200 cells/ml³. Approximately 90% of patients with toxoplasma encephalitis have CD4 T lymphocytes count <200 cells/ml³ and 75% have CD4 T lymphocytes count <100 cells/ml³ at the time of clinical presentation.^[1] Cerebral toxoplasmosis is thought to represent a reactivation of latent tissue cysts. It is 10 times more common in patients with antibodies to the organism than in seronegative patients. The patients diagnosed with HIV infection should be screened for immunoglobulin G (IgG) antibodies to Toxoplasma gondii during the time of the initial workup. Those who are seronegative should be counselled to minimise the risk of primary infection including avoiding the consumption of undercooked meat and careful hand washing after contact with soil or changing the cat litter box. The most common clinical presentation of cerebral toxoplasmosis in patients with HIV infection is fever, headache, focal neurological deficit and seizures. Seizures can be present in 15%–40% of patients with cerebral toxoplasmosis. Cerebral toxoplasmosis is a common opportunistic infection in HIV patients but it has rarely been encountered before the diagnosis of HIV infection is established.^[2]

Case Report

A 32-year-male, non-vegetarian, alcoholic, cannabis smoker, and truck driver, presented to the emergency department with altered behaviour for around 1 month and vomiting 10–15 times a day for 4 days. There was no history of headache, fever, abnormal movements, recent vaccination and long-term medication use. There was also no past history of diabetes mellitus, hypertension or any other chronic illness. On admission, his pulse rate was 70 beats/min, blood pressure was 130/80 mm Hg, respiratory rate was 18/min, the temperature was 97° F and spO₂ was 98% on room air. On examination, he was found drowsy (Glasgow Coma Scale 12/15, E3V4M5) with irrelevant talks, without pallor, cyanosis, icterus, clubbing, significant lymphadenopathy or pedal oedema. Gross clinical neurological assessment including bilateral plantar reflex and signs of meningeal irritation were unremarkable except for bilateral fundi showing papilloedema. Examination of other systems was unremarkable.

Investigations

His cytology revealed mild leucopenia (TLC = 3000 cells/ml³) with slight lymphocytosis (L = 50%). Rest other cytological and biochemical parameters were normal. Arterial blood gases analysis, chest X-ray and ultrasound abdomen were also normal.

To know the cause of the altered sensorium, urgent non-contrast computed tomography (CT) of the head was performed which showed multiple hypodense lesions in the left frontal, left parietal, right parietal and left cerebellar region [Figure 1]a and [Figure 1]b.

Figure 1: (a) CT scan of brain showing multiple hypodense lesions in bilateral parietal regions. (b) CT scan of brain showing left cerebellar hypodense lesions. CT: Computed tomography

Click here to view

On strong clinical and radiological suspicion, an HIV test was performed after counselling the available attendants which were found to be positive and his CD4 cell count was 56 cells/ml³. His HBsAg and anti-hepatitis C virus antibody were negative.

Magnetic resonance imaging (MRI) brain showed multiple ill-defined focal lesions in bilateral cerebral hemispheres and right cerebellar hemisphere with peripheral contrast enhancement like eccentric target sign with mild-to-moderate vasogenic oedema likely infective pathology [Figure 2]a, [Figure 2]b, [Figure 2]c.

Figure 2: (a) MRI of brain, axial FLAIR sequence showing hyper-intense lesions involving left frontoparietal and right parietal region. (b) MRI Brain, sagittal contrast sequence showing ring enhancing lesions involving cortical and subcortical region of cerebrum. (c) MRI brain, coronal contrast sequence showing ring enhancing lesion in left parietal region (eccentric target sign) characteristic for CNS toxoplasmosis. MRI: Magnetic resonance imaging, FLAIR: Fluid-attenuated inversion recovery

Click here to view

With all the above investigations, the possibility of CNS toxoplasmosis was kept. To confirm the diagnosis and also to rule out other causes, the decision of cerebrospinal fluid (CSF) examination was taken with guarded lumbar puncture. CSF was clear on appearance with the pressure of 252 mmH₂O, cells count − 100 cells/ml³ with 80% lymphocytes, sugar – 47 mg/dl (blood sugar – 87 mg/dl), protein – 205 mg/dl, chloride − 111 mEq/L and adenosine deaminase – 3 U/L. Gram staining and AFB staining were negative and the aerobic culture was sterile. Indian ink and KOH mounted staining showed no fungal element. CSF cryptococcal antigen was absent and cartridge-based nucleic acid amplification test for Mycobacterium tuberculosis was found negative. With the background of HIV positivity, low CD4 counts and MRI findings, CNS toxoplasmosis was suspected, hence, serum toxoplasma antibodies were sent and found positive (IgG antibodies ≥400 IU/ml and immunoglobulin M [IgM] antibodies = 17.9 AU/ml).

On the basis of clinical history, clinical examination and investigations, the patient was diagnosed as 'CNS toxoplasmosis-toxoplasma encephalitis' with 'HIV infection' and treatment was planned with sulfadiazine/pyrimethamine and azithromycin. Other supportive, prophylactic antiepileptic and antiedema measures were also started. At the same time, the patient was registered in an antiretroviral therapy centre and after 5 weeks, highly active antiretroviral therapy (tenofovir 300 mg, lamivudine 300 mg and dolutegravir 50 mg once a day) was started. Prophylactic antifungal (fluconazole – 150 mg once a day) was also started due to low CD4 counts.

Outcome and follow-up

After starting treatment, the patient's clinical condition improved and on 10^th day, the patient was discharged on the above treatment. The patient is on regular follow-up thereafter.

Discussion

Toxoplasmosis is a protozoa infection which usually affects severe immune-deficient persons. It can be acquired by orally ingesting tissue cysts containing the latent bradyzoites, found in undercooked pork or lamb, or by ingesting oocytes that contain sporozoites specifically in cat litter. After ingestion, oocytes/cyst invades host tissue and differentiate into free tachyzoites; due to the host immune response tachyzoites convert into bradyzoites and persists indefinitely within the host with predilection of the brain, eye and muscle tissue.^[3] In an immune deficiency state (CD4 T lymphocytes counts <200 cells/ml³), reactivation of latent bradyzoites containing cysts usually manifests as necrotising abscess formation in basal ganglia, thalamus nuclei and grey-white matter junction. MRI findings of cerebral toxoplasmosis include multiple lesions in multiple locations; although in some cases, only a single lesion is seen. Pathologically, these lesions exhibit inflammation and central necrosis, as a result demonstrating ring enhancement on contrast MRI. There is usually evidence of surrounding oedema. Pathological findings depend upon the immune impairment-less inflammation and fibrosis seen in severely immune compromised patients.^[3] In addition to toxoplasmosis, the differential diagnosis of single or multiple enhancing mass lesions in HIV patients includes primary CNS lymphoma and less commonly, tubercular, fungal or bacterial abscess.^[4]

Distribution of lesions can help to differentiate between CNS toxoplasmosis from CNS lymphoma. CNS lymphoma lesion is mostly solitary, periventricular, subependymal in location, more locally infiltrative and shows butterfly pattern of spread and enhancement. In contrast, the toxoplasmosis lesion is located in the basal ganglia, thalamus and grey-white junction and shows an eccentric target sign (small enhancing nodule with wall of enhancing ring). It is highly specific for CNS toxoplasmosis but found in less than 30% of cases.^[5] However, there is substantial overlap between imaging and clinical findings in the above conditions, which usually requires a therapeutic trial of toxoplasmosis medications and observation for clinical improvement to confirm the diagnosis.^[6] Polymerase chain reaction amplification of CSF may also confirm toxoplasmosis or suggest an alternative diagnosis, such as progressive multifocal leucoencephalopathy (JC virus positive) or primary CNS lymphoma (Epstein–Barr virus-positive). Definitive diagnosis can be made by brain biopsy. This procedure can now be performed by a stereotactic CT-guided method that reduces the potential for complications. CT and MRI with contrast are currently the standard diagnostic imaging test for toxoplasmosis encephalitis.

In this case study, there are few learning points which can be useful for the early and proper diagnosis of toxoplasma encephalitis.

Toxoplasma encephalitis shows radiological evidence in advance stage of disease so serological (IgG and IgM) screening should be done in every HIV patient with low CD4 count. Seropositive Toxoplasmosis gondii patient should receive toxoplasmosis prophylaxis until CD4 T lymphocyte count reach >200 cells/ml³ for 6 months
Other CNS infections and malignancies should be differentiated from toxoplasma so early treatment can be started. Treatment with sulfadiazine and pyrimethamine is effective and clinical (not radiological) improvement can be seen within a week of starting therapy
Every patient with ring-enhancing space-occupying lesion in the brain should be suspected as CNS toxoplasmosis even without prior history of immunosuppression/HIV, as seen in this case, to accomplish early diagnosis and treatment.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Soleymani E, Babamahmoodi F, Davoodi L, Marofi A, Nooshirvanpour P. Toxoplasmic encephalitis in an AIDS patient with normal CD4 count: A case report. Iran J Parasitol 2018;13:317-22.
2.	Vijayvergia V, Bithu R, Singh SK, Maheshwari R. A case of cerebral toxoplasmosis as the initial presentation of HIV infection. Int J Curr Microbiol Appl Sci 2016;5:801-3.
3.	Weiss LM, Dubey JP. Toxoplasmosis: A history of clinical observations. Int J Parasitol 2009;39:895-901.
4.	Harrison WT, Hulette C. Cerebral toxoplasmosis: A case report with correlation of radiographic imaging, surgical pathology, and autopsy findings. Acad Forensic Pathol 2017;7:494-501.
5.	Abdel Razek AA, Watcharakorn A, Castillo M. Parasitic diseases of the central nervous system. Neuroimaging Clin N Am 2011;21:815-41, viii.
6.	Masamed R, Meleis A, Lee EW, Hathout GM. Cerebral toxoplasmosis: Case review and description of a new imaging sign. Clin Radiol 2009;64:560-3.