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Table of Contents
CASE REPORT
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 177-179

Cryptococcal meningitis in an immunocompetent young adult: A rare occurrence


Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Submission01-Feb-2019
Date of Decision18-Apr-2019
Date of Acceptance25-Feb-2020
Date of Web Publication27-Oct-2020

Correspondence Address:
Naval Chandra
Additional Professor, 4th Floor, Department of General Medicine, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500 082, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_19_19

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  Abstract 


Meningitis, when caused by fungi such as Cryptococcus, is usually seen in immunocompromised hosts. However, immunocompetent patients are rarely susceptible to cryptococcal meningitis (CM). We report the case of a 22-year-old immunocompetent male who presented with fever, headache for which he received treatment initially as viral/bacterial meningitis; but as there was no response further diagnostic work-up confirmed the diagnosis of CM. We report this case in view of the rarity of cryptococcal infection in immunocompetent hosts and also to increase the awareness among physicians to consider fungal infections in one of the differentials early in the hospital course while managing patients with meningitis even if they are immunocompetent. This helps in early targeted therapy and thus reduces the morbidity and mortality associated with this deadly disease.

Keywords: Cryptococcal meningitis, diagnosis, immunocompetent


How to cite this article:
Vanka PK, Kumar K R, Chandra N, Swaroopa D, Ganji S, Eegi VS. Cryptococcal meningitis in an immunocompetent young adult: A rare occurrence. J Clin Sci Res 2020;9:177-9

How to cite this URL:
Vanka PK, Kumar K R, Chandra N, Swaroopa D, Ganji S, Eegi VS. Cryptococcal meningitis in an immunocompetent young adult: A rare occurrence. J Clin Sci Res [serial online] 2020 [cited 2020 Nov 27];9:177-9. Available from: https://www.jcsr.co.in/text.asp?2020/9/3/177/298954




  Introduction Top


Cryptococcal meningitis (CM) is usually seen in immunocompromised hosts. Both Cryptococcus neoformans and Cryptococcus gattii species can cause infection. C. neoformans var. neoformans is the species predominantly associated with infection in immunocompromised patients, whereas C. neoformans var. gattii infection has been reported in immunocompetent patients.[1] The annual incidence is 0.4–1.3/100,000 in healthy population (no central nervous system [CNS]), but it increases up to 2–7 cases/100,000 in HIV patients.[2] Here, we report a case of CM in an immunocompetent young male patient.


  Case Report Top


A 22-year-old male patient, a resident of Bidar, doing scrap business by profession, with no known comorbidities previously, visited our hospital with complaints of high-grade fever with chills and rigors for 3 days and severe headache for 3 days which was holocranial but more in the retro-orbital region. The patient also complained of recurrent nonbilious, nonprojectile vomiting and generalized muscle pains. There was no history of blurring of vision or diplopia. There was no history of seizures and altered sensorium. Twenty-five days before this presentation, he had moderate grade intermittent fever associated with generalized muscle pains and mild holocranial headache for 7 days. He had taken treatment at a private hospital where he was treated as enteric fever in view of positive Widal test (paratyphi AH 1:320 and BH 1:320) and was discharged in a stable condition after 9 days. He was asymptomatic for 6 days before he developed presenting symptoms.

On examination, he was conscious but irritable. There was no history of pallor, icterus, cyanosis, clubbing, and lymphadenopathy. The patient was febrile (101o F) with a pulse rate of 102 bpm, blood pressure of 110/70 mmHg, and respiratory rate of 18 breaths/min. Jugular venous pressure was normal. CNS examination showed no cranial nerve palsies and no motor or sensory disturbances, terminal neck stiffness was present, but Kernig's sign was negative. Fundus examination showed mild papilledema. Cardiovascular, respiratory, and gastrointestinal system examination revealed no abnormalities. A provisional diagnosis of enteric fever and to rule out meningitis was considered.

On laboratory testing, complete blood picture showed hemoglobin of 12 g/dL, total leucocyte count 11,000/mm3, platelets 4.5 lakhs/mm3. Renal function and liver function tests were normal. Serum electrolytes showed a reduced sodium (129 mEq/L). Serological testing was negative for human immunodeficiency virus (HIV) infection. Chest radiograph was normal. Magnetic resonance imaging brain (plain and contrast) showed diffuse leptomeningeal enhancement with few nodular enhancing areas in the right frontal lobe favoring meningitis [Figure 1]. It also showed lacunar infarcts in the pons and left globus pallidus. Widal test was negative.
Figure 1: Contrast-enhanced magnetic resonance imaging of the brain showing leptomeningeal enhancement

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The patient was started on antibiotics after collecting blood culture and cerebrospinal fluid (CSF) samples. CSF opening pressure was 13 cm of H2O. CSF glucose was 36 mg/dL, protein was 65 mg/dL, and chloride was 113 mg/dL. CSF rcell count revealed red blood cells 5/mm3 and leukocytes were 56/mm3 with 100% lymphocytes. Gram staining, acid-fast bacilli (AFB) staining, and GeneXpert testing of CSF were all negative. Both CSF and blood cultures were sterile. A diagnosis of viral or partially treated bacterial meningitis was considered, and he was treated with antibiotics and antiviral agents. The fever spikes decreased but headache persisted. Repeat fundus examination showed bi-lateral Grade 2 papilloedema. Neurology evaluation reiterated these findings and the patient was and advised to continue the same medication as fever subsided. However, in view of persistent severe headache, nausea, and papilloedema on examination despite treatment with antibiotics and antivirals, we suspected possibility of fungal infection such as Cryptococcus and we did guarded lumbar puncture in view of raised intracranial pressure, and CSF was sent for cryptococcal antigen (CrAg) latex agglutination (LA) test (using Remel™ Cryptococcus Antigen Test Kit, Thermo Scientific, Remel, Lenexa, KS, USA) which was positive (titers of 1:32). However, CSF India ink stain showed no cryptococci, and fungal cultures were sterile. Hence, we repeated CrAg as the patient is immunocompetent, and it was again positive (titers of 1:32) on both lateral flow assay (IMMY kit, Immuno-Mycologics, Norman, USA) and LA. Serum CrAg by LA was also positive (1:32). The patient was started on amphotericin B (AmB, 1 mg/kg/day) and flucytosine (100 mg/kg/day), and the patient had a marked decrease in the severity of headache within 4 days of antifungal therapy. Papilloedema decreased significantly. Both drugs were given totally for 2 weeks and later switched over to oral fluconazole 400 mg/day to continue for 10 weeks. The patient was stable during follow-up.


  Discussion Top


The most common manifestation of cryptococcal infection in an immunocompromised patient is the CNS involvement; conversely, it is a very uncommon manifestation in nonimmunocompromised patients. Intact T-cell immunity helps to protect colonized population from CNS involvement. This could be the reason why CM is rare in non-HIV and nontransplant patients.[2] Until the advent of HIV/AIDS, more than 85% of patients diagnosed with CM had some associated deficiency of cell-mediated immunity, and this number is likely raised today.[3] Other immunocompromised conditions include chronic alcoholism, malignancy, or transplantation, sarcoidosis, Hodgkin's lymphoma, collagen vascular disease, splenectomy, chronic organ failure, and systemic immunosuppressive therapy.[1] Our patient had none of them. Cryptococcal infection is acquired from the environment. The tropical climate found in the Indian subcontinent represents a suitable milieu for C. neoformans.[4]C. neoformans and C. gattii inhabit different ecologic niches. C. neoformans is frequently found in soils contaminated with avian excreta, whereas C. gattii instead inhabits a variety of arboreal species, including several types of eucalyptus trees but not found in bird feces.[1] Our patient had no history of exposure to birds. The patient is doing scrap business and may have been exposed to dust mixed with bird droppings, according to his knowledge. Cryptococci are encapsulated yeast. They vary in size ranging from 5 to 25 μ with a characteristic thick polysaccharide capsule having antiphagocytic property. When capsular antigen initiates immune dysfunction when released into the tissues.[5] The cryptococcal polysaccharide capsular antigen is measured as the diagnostic marker of infection.[3] Characteristic findings of CSF include low glucose and high proteins. Elevated CSF opening pressure occurs in more than 50% of patients. The diagnosis of CM is determined if the patient met any one of the following: CSF-positive culture, positive India ink, and positive cryptococcal antigen.[6] Our patient was diagnosed by demonstrating cryptococcal antigen by LA method in both CSF and blood samples. CM patients with intact immune systems usually present with the typical features of meningitis such as fever, stiff neck, and headache, whereas in patients with AIDS, CM symptoms may be subtle and include fever and lethargy.[5] Our case has a typical presentation. His immune system was intact, and his first symptom was fever with severe headache and vomiting. For cryptococcal meningoencephalitis without a concomitant immunosuppressive condition, the recommended regimen is AmB (0.5–1 mg/kg) plus flucytosine (100 mg/kg) daily for 6–10 weeks. Alternatively, patients can be treated with AmB (0.5–1 mg/kg) plus flucytosine (100 mg/kg) daily for 2 weeks and then with fluconazole (400 mg/day) for at least 10 weeks.[1] Patients with immunosuppression are treated with the same initial regimens except that consolidation therapy with fluconazole is given for a prolonged period to prevent relapse.[1] Cryptococcosis is often curable in individuals with no apparent immunologic dysfunction with antifungal therapy.[1] To conclude, CM is rare in immunocompetent patients. Lack of awareness among treating clinicians and low index of suspicion makes the diagnosis often delayed or missed, resulting in poor prognosis with severe consequences.

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.

Acknowledgments

The authors would like to thank the Department of Microbiology and Department of Radiodiagnosis, NIMS, Hyderabad.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Casadevall A. Cryptococcosis. In: Jameson LJ, Kasper DL, Longo DL, Fauci AS, Hauser SL, Braunwald E, et al., editors. Harrison's Principles of Internal Medicine. 20th ed. New York: McGraw-Hill; 2018. p. 1526-9.  Back to cited text no. 1
    
2.
Lopez-Rivera F, Cintron-Colon H, Rivera X, Monroig H, Diaz J, Lozada F. Central nervous system cryptococcosis in non-immunosuppressed patient. J Med Cases 2017;8:274-6.  Back to cited text no. 2
    
3.
Jones GA, Nathwani D. Cryptococcal meningitis. Br J Hosp Med 1995;54:439-45.  Back to cited text no. 3
    
4.
Swati G, Gopalakrishnan R, Sureshkumar D, Senthur Nambi P, Ramasubramanian V. A case series of cryptococcal infections in immune competent hosts. J Contemp Clin Pract 2017;3:64-9.  Back to cited text no. 4
    
5.
Vandemark MV, Lovasik DA, Neatherlin JS, Omert T. Infectious and autoimmune processes. In: Bader MK, Littlejohns LR, editors. AANN's Core Curriculum for Neuroscience Nursing. 4th ed. St. Louis, MO: Saunders; 2004. p. 619-80.  Back to cited text no. 5
    
6.
Abassi M, Boulware DR, Rhein J. Cryptococcal meningitis: Diagnosis and management update. Curr Trop Med Rep 2015;2:90-9.  Back to cited text no. 6
    


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