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Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 154-156

Dual infection of the brain, varicella zoster and tuberculosis in an immunocompetent adult: A rare scenario

Department of Neurology, St Stephen's Hospital, Delhi, India

Date of Submission12-Apr-2020
Date of Decision08-Jul-2020
Date of Acceptance19-Jul-2020
Date of Web Publication18-Aug-2020

Correspondence Address:
Dr. Gaurav Kumar Mittal
Department of Neurology, St Stephen's Hospital, Delhi - 110 054
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/INJMS.INJMS_24_20

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The spectrum of central nervous system diseases caused by mycobacterium tuberculosis (TB) and herpes virus is broad and overlapping, ranging from self-limiting meningitis to life-threatening encephalitis. In a country like India where TB is a common infection of the brain, antitubercular therapy finds itself as frontline empirical therapy in appropriate clinical scenarios. In this case report, we describe a challenging case of a middle-aged immunocompetent male whose cerebrospinal fluid came positive for herpes zoster which aided us in diagnosing viral meningoencephalitis. However, later on, when the patient deteriorated in spite of 21 days of antiviral therapy, repeat brain imaging revealed another pathology, which was TB. We wish to highlight the fact that both these pathogens can mimic each other in clinical presentation and investigations can be misleading. One should always keep them as early differentials in appropriate clinical scenarios so as not to squander crucial time in treatment.

Keywords: Antitubercular therapy, antiviral therapy, herpes zoster, meningoencephalitis, tuberculosis

How to cite this article:
Kaur H, Mittal GK, Mathew JJ, Sekhar S. Dual infection of the brain, varicella zoster and tuberculosis in an immunocompetent adult: A rare scenario. Indian J Med Spec 2020;11:154-6

How to cite this URL:
Kaur H, Mittal GK, Mathew JJ, Sekhar S. Dual infection of the brain, varicella zoster and tuberculosis in an immunocompetent adult: A rare scenario. Indian J Med Spec [serial online] 2020 [cited 2023 Jan 30];11:154-6. Available from: http://www.ijms.in/text.asp?2020/11/3/154/292389

  Introduction Top

Tuberculosis (TB) is a common infectious disorder affecting the brain, especially in the TB endemic countries, like India. Due to the increasing burden of immunocompromised patients, the incidence of viral encephalitis is alarmingly on the rise. It is very challenging to distinguish between the two in view of the overlapping clinical and laboratory features which are often misleading. Cerebrospinal fluid (CSF) profile of both these infectious disorders overlaps each other.[1]

We wish to illustrate a challenging case of a middle-aged immunocompetent male who presented with double infection of the brain with TB and herpes zoster.

  Case Report Top

A 45-year-old male with no prior comorbidities presented with complaints of nonproductive cough and headache for 2 weeks, fever lasting for 2 days (10 days back), and altered sensorium for 2 days. On initial examination, he was drowsy with Glasgow Coma Scale (GCS) of nine (spontaneous eye opening, no verbal response, and withdrawal to pain). He had neck stiffness, increased tone, brisk deep tendon reflexes, and extensor plantar reflex. There were no lymphadenopathy and hepatosplenomegaly. He had tachypnea (respiratory rate 40/min), tachycardia (pulse rate: 130/min), and blood pressure 150/90 mmHg. There was no rash. He was immediately intubated in the intensive care unit (ICU) in view of low GCS. Routine blood investigations revealed raised liver enzymes. Viral markers including human immunodeficiency virus were not detected. The chest radiograph was unremarkable. The patient was empirically started on modified antitubercular therapy (ATT) (levofloxacin, streptomycin, and ethambutol) along with antiviral (parenteral acyclovir) and intravenous (IV) antibiotics (ceftriaxone and vancomycin). Contrast-enhanced magnetic resonance imaging (CEMRI) of the brain showed hyperintensities in bilateral frontal, temporal regions in T2 and fluid-attenuated inversion recovery sequences with leptomeningeal enhancement [Figure 1]a and [Figure 1]b. CSF was xanthochromic and turbid with total cells of 600/mm3 (lymphocytic: 80% and neutrophils: 20%), protein of 1580 mg/dL, glucose of 53 mg/dL (corresponding blood glucose was 97 mg/dL), and adenosine deaminase of 14 U/L, and cartridge-based nucleic acid amplification test, autoimmune encephalitis panel, and stains were negative. CSF pan neurovirus panel revealed varicella-zoster infection by polymerase chain reaction (PCR) method. ATT was subsequently stopped. With an improvement in condition, the patient was extubated and shifted to intermediary care on 7th day of hospitalization. Hepatic function gradually improved. The patient received IV acyclovir for total 21 days with remarkable improvement. On 26th day of hospitalization, the patient developed decreased responsiveness and right upper limb focal seizure with secondary generalization. Repeat CEMRI of the brain on the 28th day of hospitalization revealed diffuse leptomeningeal enhancement in bilateral cerebral hemispheres and basal cisterns, along with enhancing exudates in basal cisterns [Figure 2]a and [Figure 2]b. Few discoid enhancing nodules were also noted in the bilateral temporoparietal lobes. Subtle areas of restricted diffusion were seen in the bilateral frontal lobe, splenium of the corpus callosum, and left occipital left centrum semiovale, along with grossly dilated ventricular system. Neurosurgery advised conservative management for hydrocephalus. In view of magnetic resonance imaging (MRI) findings, ATT along with steroid was immediately started and gradual improvement was noted. The patient's relatives refused for repeat lumbar puncture and CSF evaluation. He was extubated and shifted out of ICU. He was discharged for home care in a recovering but bedbound condition after 2 months of hospitalization. The patient was in a recovering condition at outpatient follow-up 2 weeks after discharge and is lost to follow-up.
Figure 1: Contrast-enhanced magnetic resonance imaging of the brain showing hyperintensities in the bilateral frontal and temporal regions in fluid-attenuated inversion recovery sequence (a) with leptomeningeal enhancement in T1 contrast sequence (b)

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Figure 2: Contrast-enhanced magnetic resonance imaging of the brain showing grossly dilated ventricles (a) with basal exudates in basal cistern (b)

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  Discussion Top

Reactivation of varicella-zoster virus (VZV) infection without rash, termed “zoster sine herpete,” has been described in several case reports and reviews in the literature.[2] Immunocompromised patients and the elderly are often seen to be affected by reactivation of VZV presenting with primary clinical features of dermatomal vesicular rashes and subsequent neurological sequelae, but it is a rare cause of meningitis among immunocompetent adults.[3] It is important to recognize the clinical presentation of VZV reactivation without rash because it represents active viral infection in the brain vessels and therefore requires prompt initiation of antiviral therapy with acyclovir. Varicella encephalitis is a dreaded complication of varicella infection. This entity is probably underdiagnosed, as most of us do not routinely suspect herpes zoster encephalitis in immunocompetent patients presenting with acute neurological deficits. The diagnosis of VZV meningoencephalitis can be made by the detection of VZV DNA in CSF or in lymphocytes or the presence of anti-VZV immunoglobulin G (IgG) antibody in CSF or of anti-VZV IgM antibody in CSF or serum.[4] In Hong et al.'s study from South Korea, about one-fifth of patients with VZV meningitis presented with very similar clinical features and CSF profiles as those with TB meningitis. Vesicular skin eruption occurred in only one-third of patients with VZV meningitis.[1]

In our case, the diagnosis of VZV encephalitis was considered, based on clinical features (fever, altered sensorium, and neck rigidity), MRI brain findings (showing bilateral frontal and temporal hyperintensities) and CSF showed PCR positivity for VZV. Injectable acyclovir was administered for 21 days (which was initiated empirically within hours of hospitalization), with remarkable improvement in the clinical condition of the patient (improved sensorium and afebrile state). On 5th day after the completion of acyclovir, the patient had seizure and became stuporous. Repeat CEMRI of the brain revealed multiple granulomatous lesions with hydrocephalous and basal exudates, suggestive of florid tubercular infection. After restarting ATT with steroids, he gradually improved. The exact timeline of occurrence of the infections is a point of debate. During the entire course of illness, we had clear cut evidence of dual infections of varicella-zoster encephalitis and tubercular meningitis. CSF was positive for VZV by PCR, which has very high sensitivity and specificity, leaving no doubt regarding VZV encephalitis. Later on, the appearance of granulomatous lesions, hydrocephalus, and basal exudates clearly suggested TB etiology. However, the initial CSF analysis revealed very high CSF protein, raised CSF adenosine deaminse (ADA) levels, and very high cell counts which are atypical for VZV encephalitis. This may be a pointer to suspect coinfection with another pathogen, thereby alerting us to search for relevant etiology. Which infection precipitated an immunocompromised state which leads to the latent disease becoming active cannot be confirmed. To the best of our knowledge, this is the first case with simultaneous viral and tubercular infection of the brain, timely detected, and treated with good outcome.

  Conclusion Top

Thus, we can infer from this case that clinical suspicion and appropriate investigations for VZV and TB meningitis are warranted, especially in a high-TB burden country where both can commonly occur with overlapping clinical features. As neurological sequelae of both these infections have high morbidity and mortality, clinicians should have a high index of suspicion and should be willing to initiate empirical antiviral therapy/ATT in appropriate clinical settings.

Take-home points are:

  • Dual infection of the brain (VZV and TB) should be considered in the setting of inappropriate response or worsening of clinical condition with initial treatment
  • Atypical CSF findings like very high CSF protein, cell counts, and ADA levels in the setting of proven VZV encephalitis should not stop one from searching for mimicking etiologies
  • One infection may lead to an immunocompromised state in an earlier immunocompetent individual, thereby leading to activation of other latent infection (s).

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's guardian has given consent for the patient's images and other clinical information to be reported in the journal. The patient's guardian understands that name and initials of the patient will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.


We wish to acknowledge the support of Dr. Sudhir Joseph, Director of St Stephen's Hospital, Delhi, India.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Hong SI, Kim T, Jung J, Park SY, Chong YP, Lee SO, et al. Tuberculous meningitis-mimicking varicella-zoster meningitis. Infect Chemother 2017;49:123-9.  Back to cited text no. 1
Ahmad NM, Boruchoff SE. Multiple cerebral infarcts due to varicella-zoster virus large-vessel vasculopathy in an immunocompetent adult without skin involvement. Clin Infect Dis 2003;37:e16-8.  Back to cited text no. 2
Gupta P, Ranjan R, Agrawal CS, Muralikrishnan K, Dave N, Rana DS. Meningitis with polymerase chain reaction for varicella zoster positivity in cerebrospinal flid of a young immunocompetent adult. J Neurosci Rural Pract 2016;7:591-3.  Back to cited text no. 3
[PUBMED]  [Full text]  
Suri V, Mendiratta L, Chatterjee S, Sardana R, Butta H. Unusual presentation of varicella zoster virus meningitis-Role of molecular rapid diagnostics in diagnosis and antimicrobial stewardship. Ann Indian Acad Neurol 2018;21:168-9.  Back to cited text no. 4
[PUBMED]  [Full text]  


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