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 Table of Contents 
ORIGINAL ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 6  |  Page : 2008-2011  

Cryptococcal meningitis: An under-reported disease from the hills of Uttarakhand: A hospital-based cross-sectional study


1 Department of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Emergency Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Submission11-Mar-2019
Date of Decision12-Mar-2019
Date of Acceptance01-Apr-2019
Date of Web Publication26-Jun-2019

Correspondence Address:
Dr. Mohit Bhatia
Department of Microbiology, All India Institute of Medical Sciences, Virbhadra Marg, Rishikesh, Uttarakhand - 249 203
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_216_19

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  Abstract 


Background: Cryptococcal meningitis is a fatal opportunistic neuroinfection and an AIDS defining illness. It can also occur in non-HIV patients who are immunodefecient due to chronic glucocorticoid use, organ transplantation, malignancy and sarcodiosis. Materials and Methods: A cross-sectional study was conducted in a tertiary care hospital from July to December 2018. CSF samples of 364 patients were received by Microbiology laboratory during this period for the purpose of aerobic bacterial, fungal and TB culture, respectively. All samples were subjected to examination by direct wet mount, Gram stain and India ink preparation. Ziehl Neelsen staining, solid culture for Mycobacterium tuberculosis on Lowenstein Jensen medium and Gene Xpert was also performed on all CSF samples. These samples were further subjected to fungal culture on Sabouraud's dextrose agar. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) was used for identifying all bacterial (except M. tuberculosis) and fungal isolates. Results: Out of 364 CSF samples received, 288 were sterile after 48 hours of aerobic incubation. Bacterial isolates, M. tuberculosis and Cryptococcus spp. were obtained in culture from 51, 21 and 4 samples, respectively. The prevalence of cryptococcal meningitis in our study was 1.09% (4/364). Cryptococcus neoformans var grubii was the most common isolate (2/4; 50%) followed by Cryptococcus neoformans var neoformans (1/4; 25%) and Cryptococcus neoformans var gattii (1/4; 25%), respectively. Conclusion: Cryptococcal meningitis is a rapidly fatal condition which requires a high index of suspicion and calls for a collective effort from family physicians and diagnosticians alike. This disease is under-reported from Uttarakhand and therefore calls for further research from this region.

Keywords: Amphotericin B, cryptococcal meningitis, MALDI-TOF


How to cite this article:
Mohanty A, Bhatia M, Kabi A, Chatterjee K, Kaistha N, Omar BJ, Gupta PK, Gupta P. Cryptococcal meningitis: An under-reported disease from the hills of Uttarakhand: A hospital-based cross-sectional study. J Family Med Prim Care 2019;8:2008-11

How to cite this URL:
Mohanty A, Bhatia M, Kabi A, Chatterjee K, Kaistha N, Omar BJ, Gupta PK, Gupta P. Cryptococcal meningitis: An under-reported disease from the hills of Uttarakhand: A hospital-based cross-sectional study. J Family Med Prim Care [serial online] 2019 [cited 2019 Jul 19];8:2008-11. Available from: http://www.jfmpc.com/text.asp?2019/8/6/2008/261376




  Introduction Top


Cryptococcosis is an acute, subacute or chronic fungal infection caused by encapsulated heterobasidiomycetous yeast like fungus Cryptococcus neoformans. Till date five serotypes have been described. Serotypes A, D and AD hybrids are globally responsible for 98% of all cryptococcal infections in AIDS patients, whereas serotypes B and C predominantly affect immunocompetent individuals, but also have been recently reported in AIDS patients.[1],[2]

Cryptococcal meningitis is a fatal opportunistic neuroinfection and an AIDS defining illness seen in up to 69% of HIV-positive patients.[3] It can also occur in non-HIV patients who are immunodefecient due to chronic glucocorticoid use, organ transplantation, malignancy and sarcodiosis.[4] It is a rapidly fatal infection which requires early diagnosis and prompt treatment.

With the advent of antiretroviral therapy, the incidence of cryptococcosis has shown a steady decline in developed countries [5] when compared with developing where access to anti-retroviral therapy and other necessary healthcare resources are a major limitation.

The incidence of cryptococcal meningitis in India has risen dramatically over the past 20 years.[3] However, there is paucity of literature on cryptococcosis from the state of Uttarakhand. This study was undertaken to evaluate the prevalence and clinical presentation of cryptococcal meningitis in patients who presented to a tertiary care teaching hospital.


  Materials and Methods Top


A cross-sectional study was conducted in a tertiary care hospital located in Rishikesh, Uttarakhand with a study period of 6 months starting from July to December 2018. CSF samples of 364 patients were received by Microbiology laboratory during this period for the purpose of aerobic bacterial, fungal and TB culture, respectively. All samples were subjected to examination by direct wet mount, Gram stain and India ink preparation. Ziehl Neelsen staining, solid culture for Mycobacterium tuberculosis on Lowenstein Jensen medium and Gene Xpert was also performed on all CSF samples. These samples were further subjected to fungal culture on Sabouraud's dextrose agar. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) (Bruker Biotyper Microflex, MA, USA) was used for identifying all bacterial (except M. tuberculosis) and fungal isolates.


  Results Top


Out of 364 CSF samples received, 288 were sterile after 48 hours of aerobic incubation. Bacterial isolates, M. tuberculosis and Cryptococcus spp. were obtained in culture from 51, 21 and 4 samples, respectively. The bacterial profile of 51 CSF samples has been depicted in [Table 1].
Table 1: Microbiological profile of CSF samples

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The prevalence of cryptococcal meningitis in our study was 1.09% (4/364). Cryptococcus neoformans var grubii was the most common isolate (2/4; 50%) followed by Cryptococcus neoformans var neoformans (1/4; 25%) and Cryptococcus neoformans var gattii (1/4; 25%), respectively. Out of four laboratory-confirmed cryptococcal meningitis patients, 3 (75%) were HIV positive. Clinical and laboratory profile of these patients has been shown in [Table 2]. Gram stain, India ink and culture findings of these patients have been depicted in [Figure 1], [Figure 2], [Figure 3], respectively.
Table 2: Clinical and laboratory profile of cryptococcal meningitis patients

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Figure 1: Gram stain showing budding yeast cells

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Figure 2: India ink showing capsulated round yeast cells

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Figure 3: SDA tube showing mucoid, creamy pasty colonies of Cryptococcus spp.

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  Discussion Top


The genus Cryptococcus contains at least 39 species, but only few are able to cause disease in human beings. Most human infections are caused by C. neoformans. The portal of entry is via inhalation of airborne particles, with bird droppings and associated soil being major environmental source following which it frequently pitches itself in the meninges, lungs, bones, adrenals, kidneys, liver and spleen.

The clinical presentation of this disease is variable and therefore difficult to differentiate from other multisystem aliments such as tuberculosis, other tropical infections and malignancies. The most common presenting complaint in our study was headache (100%) which is in concordance with other studies from India.[6],[7] Fever (50%), altered sensorium (25%) and seizure history (25%) were next in line, similar to a study by Abhilash et al. (75%, 40% and 18%, respectively).[6]

Current identification methods for yeasts rely heavily on physical characteristics and biochemical properties of the isolate. Rapid tests such as India ink are often used to quickly and presumptively identify the Cryptococcus spp. But even experienced observers can confuse the halo around cells (suggestive of capsule) with artifacts produced by reactions between leukocytes and carbon particle in the India ink stain. For these limitations, rapid tests must be confirmed by additional methods. We used MALDI-TOF-MS to identify all our clinical isolates which is known to have very high sensitivity and specificity. It also allows rapid identification of microbes, which in turn guides the clinicians in early initiation of appropriate therapy, thereby reducing overall time and cost of care. All the four isolates generated confidence scores of more than 2.0 which is considered to be secure species level identification.[8]

There has been a substantial increase in reporting of cryptococcosis in both immunosuppressed and immunocompetent individuals in recent years, which reflects an enhanced clinical awareness and improved diagnostic capability.

To the best of our knowledge, there is only one case report on cryptococcal meningitis from the state of Uttarakhand by Patil et al.[9] Ours is the first cross-sectional study on prevalence and clinical profile of cryptococcal meningitis from the state of Uttarakhand. Cumulative records of cryptococcal meningitis from India and rest of the world have been depicted in [Table 3] and [Table 4], respectively.
Table 3: Cumulative records of cryptococcal meningitis from different parts of India

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Table 4: Cumulative records of cryptococcal meningitis from different parts of world

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  Conclusion Top


Cryptococcal meningitis is a rapidly fatal condition which requires a high index of suspicion and calls for a collective effort from family physicians and diagnosticians alike. This disease is under-reported from Uttarakhand and therefore calls for further research from this region.[23]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lanchaster DJ, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective therapy. Clin Infect Dis 2001;33:690-9.  Back to cited text no. 1
    
2.
Litvintesva AP, Thakur R, Reller LB, Mitchell TG. Prevalence of clinical isolates of Cryptococcus gattii serotype C among patients with AIDS in Sub-Saharan Africa. J infect Dis 2005;192:888-92.  Back to cited text no. 2
    
3.
Bicanic T, Harrison TS. Cryptococcal meningitis. Br Med Bull 2005;72:99-118.  Back to cited text no. 3
    
4.
Mirza SA, Phelan M, Rimland D, Graviss E, Hamil R, Brandt ME, et al. The changing epidemiology of cryptococcosis: An update from population-based active surveillance in 2 large metropolitan areas, 1992-2000. Clin Infect Dis 2003;36:789-94.  Back to cited text no. 4
    
5.
Pandit L, Agrawal A, Shenoy S, Kamath G. Cryptococcal meningitis and pulmonary cryptococossis in a non-HIV infected patient. Eur J Gen Med 2006;3:80-2.  Back to cited text no. 5
    
6.
Abhilash KP, Mitra S, Arul JJ, Raj PM, Balaji V, Kannangai R, et al. Changing paradigm of cryptococcal meningitis: An eight year experience from a tertiary hospital in South India. Indian J Med Microbiol 2016;33:25-9.  Back to cited text no. 6
    
7.
Prasad KN, Agarwal J, Nag VL, Verma AK, Dixit AK, Ayyagari A. Cryptococcal infection in patients with clinically diagnosed meningitis in a tertiary care center. Neurol India 2003;51:364-6.  Back to cited text no. 7
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8.
Buchan BW, Ledeboer NA. Advances in identification of clinical yeast isolates by use of matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 2013;51:1359-66.  Back to cited text no. 8
    
9.
Patil R, Sangwan J, Juyal D, Lathwal S. Meningitis due to Cryptococcal gattii in an immunocompetent patient. J Clin Diag Res 2013;10:2274-5.  Back to cited text no. 9
    
10.
Dash M, Padhi S, Sahu R, Turuk J, Pattanaik S, Misra P. Prevalence of cryptococcal meningitis among people living with human immunodeficiency virus/acquired immunodeficiency syndrome in a tertiary care hospital, Southern Odisha, India. J Nat Sci Biol Med 2014;5:324-8.  Back to cited text no. 10
    
11.
Lungran P, Devi AV, Singh WS, Damroulien S, Mate H, Golmei A. Cryptococcosis: Its prevalence and clinical presentation among HIV positive and negative patients in Rims, Manipur. IOSR J Dent Med Sci 2014;7:38-41.  Back to cited text no. 11
    
12.
Kumar S, Wanchu A, Chakrabarti A, Sharma A, Bambery P, Singh S. Cryptococcal meningitis in HIV infected: Experience from a North Indian tertiary center. Neurol India 2008;56:444-9.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Thakur R, Sarma S, Kushwaha S. Prevalence of HIV-associated cryptococcal meningitis and utility of microbiological determinants for its diagnosis in a tertiary care center. Indian J Pathol Microbiol 2008;51:212-4.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Lakshmi V, Sudha T, Teja VD, Umabala P. Prevalence of central nervous system cryptococcosis in Human Immunodeficiency Virus reactive hospitalized patients. Indian J Microbiol 2007;25:146-9.  Back to cited text no. 14
    
15.
Naik KR, Saroja AO, Doshi DK. Hospital-based retrospective study of cryptococcal meningitis in a large cohort from India. Ann Indian Acad Neurol 2017;20:225-8.  Back to cited text no. 15
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16.
Patel AK, Patel KK, Ranjan R, Shah S, Patel JK. Management of cryptococcal meningitis in HIV-infected patients: Experience from western India. Indian J Sex Transm Dis AIDS 2010;31:22-6.  Back to cited text no. 16
    
17.
Baradkar V, Mathur M, De A, Kumar S, Rathi M. Prevalence and clinical presentation of Cryptococcal meningitis among HIV seropositive patients. Indian J Sex Transm Dis AIDS 2009;30:19-22.  Back to cited text no. 17
    
18.
Kadam D, Chandanwale A, Bharadwaj R, Nevrekar N, Joshi S, Patil S, et al. High prevalence of cryptococcal antigenaemia amongst asymptomatic advanced HIV patients in Pune, India. Indian J Med Microbiol 2017;35:105-8  Back to cited text no. 18
    
19.
Tseng HK, Liu CP, Ho MW, Lu PL, Lo HJ, Lin YH, et al.; Taiwan Infectious Diseases Study Network for Cryptococcosis. Microbiological, epidemiological, and clinical characteristics and outcomes of patients with cryptococcosis in Taiwan, 1997-2010. PLoS One 2013;8:e61921.  Back to cited text no. 19
    
20.
Chau TT, Mai NH, Phu NH, Nghia HD, Chuong LV, Sinh DX, et al. A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam-high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease. BMC Infect Dis 2010;10:199.  Back to cited text no. 20
    
21.
Nunes JO, Tsujisaki RA, Nunes MO, Lima GM, Miranda AM, Pontes ERJC, et al. Cryptococcal meningitis epidemiology: 17 years of experience in a state of the Brazilian Pantanal. Rev Soc Bras Med Trop 2018;51:485-92.  Back to cited text no. 21
    
22.
Frola C, Guelfand L, Blugerman G, Szyld E, Kaufman S, Cahn P, et al. Prevalence of cryptococcal infection among advanced HIV patients in Argentina using lateral flow immunoassay. PLoS One 2017;12:e0178721.  Back to cited text no. 22
    
23.
Kharel G, Karn R, Rajbhandari R, Ojha R, Agarwal JP. Spectrum of cryptococcus meningoencephalitis in tertiary hospital in Nepal. J Inst Med 2018;40:27-32.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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