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Table of Contents
LETTERS TO THE EDITOR
Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 1188-1189
 

HSV-2 meningitis in a young woman presenting with acute tonsillitis


1 Scientist B, Hepatitis Group, ICMR-National Institute of Virology, Pune, Maharashtra, India
2 Department of Medicine, Dr. D. Y. Patil Medical College Hospital and Research Centre, DPU Vidyapeeth, Pune, Maharashtra, India
3 Scientist-F and Group Leader, Encephalitis Group, ICMR-National Institute of Virology, Pune, Maharashtra, India

Date of Submission11-May-2022
Date of Decision13-Jul-2022
Date of Acceptance22-Jul-2022
Date of Web Publication04-Nov-2022

Correspondence Address:
Vijay P Bondre
Scientist-F, ICMR-National Institute of Virology, 130/1, Sus Road, Pashan, Pune - 411 021, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.aian_425_22

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How to cite this article:
Tomar S, Thomson BG, Kanitkar SA, Bondre VP. HSV-2 meningitis in a young woman presenting with acute tonsillitis. Ann Indian Acad Neurol 2022;25:1188-9

How to cite this URL:
Tomar S, Thomson BG, Kanitkar SA, Bondre VP. HSV-2 meningitis in a young woman presenting with acute tonsillitis. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Jan 29];25:1188-9. Available from: https://www.annalsofian.org/text.asp?2022/25/6/1188/360461




Sir,

Herpes simplex virus type 2 (HSV-2) is a common cause of viral meningitis, and the leading etiological agent of recurrent Mollaret's meningitis. HSV-2 is the second most common cause of adult viral meningitis in developed countries,[1] occurring even in the absence of clinical genital herpes.[2] In contrast, there are very few case reports of HSV-2 meningitis from India[3] and this kind of evidence has rarely been documented. We report a case of a young, immunocompetent woman presenting to the hospital with Acute Tonsillitis and later developing meningitis due to HSV-2 during the course of the hospital stay.

A 22-year-old woman presented in October 2018 with chief complaints of throat pain, odynophagia with low-grade fever for 3 days. A month back, she was diagnosed with Hypothyroidism and was on 50 mcg levothyroxine hormone, once a day. She had no other significant medical history or symptoms suggestive of genital ulcerations. The patient was afebrile at the time of examination, with normal blood pressure (110/70 mm Hg), and systemic examination was normal. On local throat examination, the tonsillar fossa showed bilateral enlarged tonsils with congestion extending to the posterior pharyngeal wall. A diagnosis of Severe Acute Tonsillitis was made, and treatment with intravenous Ceftriaxone 1 gm twice a day and gargles of povidone-iodine, started.

On Day 2 of admission, the patient complained of severe throbbing headache, which was acute in onset, gradually progressive, and not relieved by analgesics. She also developed meningeal signs, that is, nuchal rigidity with fever (102°F), chills, and photophobia. She had seven to eight episodes of bilious, non-projectile vomiting, containing food particles, immediately after her meals. There was no altered sensorium or any other features suggesting an encephalitic picture. Examination of the fundus showed no evidence of papilledema.

Investigations of blood/urine routine culture and sensitivity and throat swab for H1N1 infection, were negative. A magnetic resonance imaging (MRI) brain [Figure 1], was performed and showed no abnormality. Lumbar puncture was undertaken and her cerebrospinal fluid (CSF) sample was sent for routine microscopy, culture and sensitivity, adenosine deaminase, and Tuberculosis-polymerase chain reaction (PCR). She was started on Injection Acylovir 800 mg three times a day. Her serology reports were negative for dengue NS1, typhoid fever, and rapid malaria test.
Figure 1: MRI findings of 22 year old female on day 2 of admission, showing no abnormality

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CSF examination revealed that the CSF was transparent, colorless with no clots, cobwebs or coagulum, and revealed increased cell count (900 cells/μl), predominantly lymphocytes. The protein content of CSF was 46 mg/dl and the glucose level was 67 mg/dl with a corresponding blood glucose of 100 mg/dl. The MRI was repeated on Day 5 and it showed no abnormality.

Her serum T3, T4, and TSH tests were normal. Other tests including routine biochemistry, renal, and liver function tests were done on days 1, 4, and 7 and were in the normal range. Her hematology reports revealed hemoglobin of 11 g/dl with a WBC count of 8,000 WBCs per microliter and platelet count of 190,000 per microliter and peripheral smear was normal. Blood and urine culture reports showed no growth. Cartridge Based Nucleic Acid Amplification Test (CBNAAT) was negative for M. tuberculosis. Ultrasonography Abdomen and Pelvis was normal.

The CSF and sera samples of the patient were referred to ICMR-National Institute of Virology Pune for virological investigations, where these were tested to be negative for IgM antibodies against Japanese encephalitis virus (JEV), Chandipura virus (CHPV), Dengue virus, and Chikungunya virus. The CSF specimens were investigated by PCR to detect herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) infections.[4] A 282-bp DNA fragment specific to HSV-2 was amplified from the DNA extracted from the CSF and was confirmed by sequencing as described earlier.[5] The HSV-2 partial sequence of 282 base pairs amplified from the Envelope glycoprotein D (US6) gene (GenBank accession number: MW691140) showed 100% sequence identity with genomic sequences generated from clinical isolates of Human alpha herpesvirus 2. Virus isolation[5] was also attempted in Baby Hamster Kidney-21(BHK-21) cells but did not yield positive results.

HSV-2 is transmitted through genital contact, causing persistent infection, which may cause frequent, symptomatic, and self-limited genital ulcers, but in most cases, the infection is subclinical.[6] CNS infections caused due to HSV-2 are less frequently diagnosed than HSV-1 infections, and meningitis caused could be due to primary infection or reactivation of latent infection. In previous studies, a prior history of genital herpes has been reported in up to 40% of HSV-2 meningitis cases and concurrent outbreaks in 86%, but more recent data have shown genital outbreaks at the time of meningitis in less than 10% of the cases.[7]

HSV-2 is rarely isolated by the culture of the virus, thus, PCR is the standard means for identifying cases through the detection of HSV-2 DNA in the cerebrospinal fluid.[8]

In 1944, French neurologist Pierre Mollaret first described recurrent benign lymphocytic meningitis, also called “Mollaret's meningitis” and “recurrent aseptic meningitis,” recurring in 20% to 50% of the cases.[7],[9] This is a rare disease and around 59 cases have been reported in the English literature,[7] reflecting the tip of the iceberg, as the majority of cases would have remained undiagnosed due to a lack of clinical suspicion.

Our patient presented to the hospital with chief complaints of acute tonsillitis with low-grade fever and odynophagia and developed meningeal signs on Day 2 of admission. This case report highlights the impact of promptly conducting simple and easily available tests like CSF cytology, which could indicate toward the etiology of the infection, helping in the early initiation of treatment. In our case, an increased CSF cell count (900 cells/μl) with a lymphocytic picture was seen, pointing toward a viral etiology, and the patient was empirically started on intravenous Acylovir. She showed improvement and was completely fit during her discharge. She did not report any recurrent symptoms and continues to be well, without experiencing any long-term neurological sequelae, which have been documented in a few previous studies.[7] This could be attributed to several factors, one being that the patient was immunocompetent. Importantly, the patient received empirical antiviral treatment on the first suspicion of underlying viral etiology, although a purely meningeal clinical picture was observed and confirmatory laboratory test results were awaited, reflecting how early intervention could change the clinical course of the patient. Anecdotally, late antiviral treatment implementation has been associated with mortality in some cases.[10]

To the best of our knowledge, HSV-2 meningitis has rarely been reported in India[3] but it should be considered a differential diagnosis in an adult patient presenting with meningeal signs and symptoms, even in the absence of genital lesions. Undertaking a spinal tap proactively to collect CSF for cell cytology analysis on suspicion of a CNS infection can help in providing clues to the etiology of the infection. As HSV-2 is a treatable cause of viral meningitis, a prompt diagnosis and early treatment initiation can help in achieving quick recovery in the patient, additionally preventing long-term neurological sequelae.

Acknowledgements

Authors are thankful to the Director, ICMR-NIV, Pune, for supporting the investigations; Ms. Shubhangi Mahamuni and Ms. Daya Pavitrakar for their technical support. Financial support (project ENC1501) by ICMR, New Delhi, India is greatly appreciated.

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.



 
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Logan S, MacMahon E.Viral meningitis. BMJ 2008;336:36-40.  Back to cited text no. 2
    
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Gupta A, Jogi V, Goyal MK, Modi M, Khurana D. Chronic meningitis in systemic lupus erythematosus: An unusual etiology. Ann Indian Acad Neurol. 2014 Oct;17(4):426-8. doi: 10.4103/0972-2327.144019. PMID: 25506165; PMCID: PMC4251017.  Back to cited text no. 3
    
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Read SJ, Kurtz JB. Laboratory diagnosis of common viral infections of the central nerv-ous system by using a single multiplex PCR screening assay. J Clin Microbiol 1999;37:1352-5.  Back to cited text no. 4
    
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Bondre VP, Sankararaman V, Andhare V, Tupekar M, Sapkal GN. Genetic characterization of human herpesvirus type 1: Full-length genome sequence of strain obtained from an encephalitis case from India. Indian J Med Res 2016;144:750-60.  Back to cited text no. 5
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Johnston C, Corey L. Current Concepts for Genital Herpes Simplex Virus Infection: Di-agnostics and Pathogenesis of Genital Tract Shedding. Clin Microbiol Rev 2016;29:149-61. doi: 10.1128/CMR.00043-15. PMID: 26561565; PMCID: PMC4771215.  Back to cited text no. 6
    
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Miller S, Mateen FJ, Aksamit AJ Jr. Herpes simplex virus 2 meningitis: a retrospective cohort study. J Neurovirol 2013;19:166-71. doi: 10.1007/s13365-013-0158-x. Epub 2013 Mar 15. PMID: 23494382.  Back to cited text no. 7
    
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Shalabi M,Whitley RJ. Recurrent benign lymphocytic meningitis. Clin Infect Dis 2006;43:1194-7.  Back to cited text no. 8
    
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Gadhiya KP, Nookala V. A Rare Case of Mollaret's Meningitis Complicated by Chronic Intractable Migraine and Papilledema: Case Report and Review of Literature. Cureus. 2020.  Back to cited text no. 9
    
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Najioullah F, Bosshard S, Thouvenot D, Boibieux A, Menager B, Biron F, et al. Diagnosis and surveillance of herpes simplex virus infection of the central nervous system. J Med Virol 2000;61:68-73.  Back to cited text no. 10
    


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