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 ~  Abstract
 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~  References
 ~  Article Figures

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  Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 33  |  Issue : 4  |  Page : 590-593
 

Fatal meningitis by Cryptococcus laurentii in a post-partum woman: A manifestation of immune reconstitution inflammatory syndrome


Department of Laboratory Medicine, QRG Central Hospital and Research Centre, Faridabad, Haryana, India

Date of Submission01-Nov-2014
Date of Acceptance02-Apr-2015
Date of Web Publication16-Oct-2015

Correspondence Address:
N Mittal
Department of Laboratory Medicine, QRG Central Hospital and Research Centre, Faridabad, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.167337

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 ~ Abstract 

Cryptococcal meningitis in immunocompetent post-partum women has been rarely reported. Immune restoration during post-partum period leads to unmasking of many opportunistic infections that may have been acquired during pregnancy but manifest itself in the post-partum period due to immune reconstitution inflammatory syndrome. This case highlights the importance of considering opportunistic pathogens in immunocompetent patients who may be undergoing immune restoration. We report here a fatal case of post-partum immunocompetent women who presented with clinical features of meningitis. Prognosis of the cryptococcal meningitis not only depends on the immune status of the patient but also on how early the disease is diagnosed in the course of illness.


Keywords: Cryptococcus laurentii, immune reconstitution syndrome, meningitis, post-partum


How to cite this article:
Mittal N, Vatsa S, Minz A. Fatal meningitis by Cryptococcus laurentii in a post-partum woman: A manifestation of immune reconstitution inflammatory syndrome. Indian J Med Microbiol 2015;33:590-3

How to cite this URL:
Mittal N, Vatsa S, Minz A. Fatal meningitis by Cryptococcus laurentii in a post-partum woman: A manifestation of immune reconstitution inflammatory syndrome. Indian J Med Microbiol [serial online] 2015 [cited 2019 Sep 16];33:590-3. Available from: http://www.ijmm.org/text.asp?2015/33/4/590/167337



 ~ Introduction Top


Cryptococcus gained importance as a major opportunistic infection with the advent of AIDS epidemic.[1] Recently, it was found to be the most common type of infection in the immune reconstitution inflammatory syndrome (IRIS) in solid organ transplant recipients too.[2] Similar to solid organ transplantation and HIV infection, the post-partum period is also associated with rapid immune changes and is thus conducive to the appearance of immune reconstitution syndrome.

Immune status of a pregnant woman reverts back to its pre-pregnancy status after 3–6 weeks.[3] Though this immune restoration is beneficial but opportunistic infections acquired during pregnancy may get unmasked or worsened during this period of immune reconstitution. Such abrupt return of the inflammatory responses also leads to excessive tissue damage and pose challenges for the management of these infections.

Here we report a fatal case of meningitis in a post-partum immunocompetent female patient, with Cryptococcus laurentii as the causative agent possibly a manifestation of IRIS.


 ~ Case Report Top


A 30-year-old post-partum female patient was transferred to our hospital from another hospital with the chief complaints of headache, altered sensorium, and drowsiness since 15 days with intermittent episodes of vomiting. On examination, the patient was not following any verbal commands. Pupils were bilaterally normal and reacting to light. Neck rigidity was present. Plantar reflexes were decreased in both the limbs. Vitals signs were normal with respiratory rate 20/min, blood pressure (BP) 130/90 mmHg. On cardio-vascular system examination S1,S2 were regular with heart rate 110/min. Glasgow coma scale was E3M2V1. There was no history of seizures, chronic cough, drug abuse, ear discharge or earache. No history of tuberculosis, diabetes or malignancy or any such chronic illness.

Patient had a past history of hospitalisation in labour at 38 weeks of pregnancy 2 months back. An emergency caesarean-section was performed because of foetal distress and a healthy new-born appropriate for gestational age was delivered. Patient remained well for 21 days after caesarean section and subsequently became symptomatic. Patient was admitted to a hospital where she was put on some antibiotics but no definitive diagnosis was made, she remained there for 15 days and when the patient condition did not improve she was shifted to our hospital.

After admission in our hospital patient was put on intravenous (IV) antibiotics (ceftriaxone 2 g IV BP q12 h, meropenem 2 g IV q8 h, and vancomycin 1 g IV BP q12 h) along with the anti-tuberculosis therapy and supportive treatment. Blood and cerebrospinal fluid (CSF) samples were taken before administering antibiotics. Blood sample was sent for liver function test, kidney function test, serology for HIV, syphilis, hepatitis, and complete blood count. CSF sample was sent for Gram stain, Ziehl–Neelsen stain, India ink preparation, pyogenic culture, rapid acid-fast Bacilli (AFB) culture, and fungal culture. Laboratory investigations revealed that all the parameters for liver function tests, kidney function tests, and serum electrolytes were within normal limits. Serology for hepatitis, syphilis, and HIV were negative. However, acute HIV could not be ruled out since the patient was not tested for HIV viral Load.

Non-contrast computed tomography scan of the head was done on the next day after admission to hospital. Significant findings included few small hypodensities in bilateral capsulo-ganglionic regions [Figure 1]. There were no signs of increased intracranial tension and magnetic resonance imaging brain scan was advised.
Figure 1: Computed tomography scan showing few discrete hypodense lesions in bilateral basal ganglia region

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Magnetic resonance imaging of brain with contrast revealed multiple punctate round and oval T2/fluid attenuated inversion recovery hyperintense lesions in bilateral basal ganglia, thalami [Figure 2], periventricular areas, supraventricular white matter [Figure 3], and brain stem. IV contrast did not reveal any significant contrast enhancement. Rest of the areas were normal.
Figure 2: Magnetic resonance imaging scan showing multiple punctate round and oval T2 hyperintense lesions in bilateral basal ganglia region

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Figure 3: Magnetic resonance imaging scan showing punctate round and oval hyperintense lesions in periventricular and subcortical white matter

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Lumbar puncture was performed and revealed an increased opening pressure. CSF analysis revealed total leucocyte count 80 cells/mm 3 with 85% polymorphs and 25% lymphocytes, reduced glucose level and elevated protein level.

Gram stain revealed Gram positive spherical yeast cells with elongated budding yeast cells surrounded by orange halos. On Ziehl–Neelsen stain no AFB were found. India ink preparation revealed spherical yeast cells with thickened cell walls, large capsules, and elongated budding yeast cells.

Cerebrospinal fluid culture was done on Sabouraud's dextrose agar and blood agar. On Sabouraud's dextrose agar after an incubation period of 48 h cream-coloured colonies grew which became deeper orange-yellow with age having a smooth mucoid texture. On blood agar, a similar type of colonies grew after 72 h. Subsequent identification was done with both conventional methods (germ tube, urea hydrolysis, fermentation, and assimilation test) and automated system (Vitek 2 Compact System, bioMeriux, France). Germ tube test was negative and urea was hydrolysed by the isolate. The isolate was negative for nitrate utilisation test and gave positive assimilation tests with lactose, melibiose, glucose, galactose, maltose, sucrose, and inositol. Thus, the isolate was characterised as C. laurentii. Vitek 2 system also confirmed the identity of the isolate as C. laurentii. Blood cultures did not show the growth of any organism.

Patient was put on amphotericin B intravenously (1 mg/kg/day IV) soon after encapsulated yeast cells were reported on India ink preparation of CSF sample. Flucytosine could not be started simultaneously due to non-availability of the drug, but it was planned to add this drug as soon as possible. Though patient was put on amphotericin B as soon as the provisional diagnosis of cryptococcal meningitis was made, but the patient's condition deteriorated continuously as she had presented in the hospital very late that is after 15 days of onset of symptoms and finally she died of septic shock after 2 days of initiating therapy. Therefore despite all the measures, our patient could not survive.


 ~ Discussion Top


Cryptococcal meningitis in post-partum immunocompetent women is a rare entity. Thus, immune status of the patient in such type of cases might be misleading as they may appear immunocompetent but they might be under the process of immune restoration and present with infections related to immune reconstitution inflammatory syndrome.

During pregnancy, there is a shift of immune system to proinflammatory responses to prevent rejection of the foetus.[4] This shift towards Th2 response is also known to favour the establishment of cryptococcal infection.[5] Resolution of immunosuppression during post-partum period results in reversal of Th2 to Th1 response, which can be associated with inflammatory responses that mimic worsening of disease or its expression or relapse. It has already been established that in HIV-infected individuals and transplant recipients this Th1 response is responsible for characteristic inflammatory lesions found in cryptococcal-IRIS syndrome.[6]

A review by Costa et al. describes some case reports of cryptococcal infections being acquired in first, second, and third trimester of pregnancy and in the post-partum period.[7] Case reports are there which suggest quiescent cryptococcal infection during pregnancy as either there was mother to child transmission, which worsened acutely in post-partum period or there was unmasking of cryptococcal-IRIS during pregnancy, which was precipitated by starting HIV antiretroviral therapy with post-partum paradoxical deterioration.[8],[9] Apart from meningitis other form of cryptococcosis such as osteomyelitis and pneumonia have also been described getting worsened or unmasked during pregnancy.[10],[11]

To conclude, the patient in our case succumbed to her illness due to delay in diagnosis because of lack of clinical suspicion. Therefore, this case report provides an insight to suspect opportunistic infections in cases which may appear immunocompetent but may be under the process of immune restoration. Although Cryptococcus is usually not considered as the causative agent of meningitis in post-partum patients, now it should be regarded as a possible entity in the cases, which do not show improvement on prolonged antibiotic therapy.

 
 ~ References Top

1.
Levitz SM. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis 1991;13:1163-9.  Back to cited text no. 1
    
2.
Sun HY, Singh N. Opportunistic infection-associated immune reconstitution syndrome in transplant recipients. Clin Infect Dis 2011;53:168-76.  Back to cited text no. 2
    
3.
Elenkov IJ, Wilder RL, Bakalov VK, Link AA, Dimitrov MA, Fisher S, et al. IL-12, TNF-alpha, and hormonal changes during late pregnancy and early postpartum: Implications for autoimmune disease activity during these times. J Clin Endocrinol Metab 2001;86:4933-8.  Back to cited text no. 3
    
4.
Clark DA, Croitoru K. TH1/TH2,3 imbalance due to cytokine-producing NK, gammadelta T and NK-gammadelta T cells in murine pregnancy decidua in success or failure of pregnancy. Am J Reprod Immunol 2001;45:257-65.  Back to cited text no. 4
    
5.
Decken K, Köhler G, Palmer-Lehmann K, Wunderlin A, Mattner F, Magram J, et al. Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans. Infect Immun 1998;66:4994-5000.  Back to cited text no. 5
    
6.
Singh N, Lortholary O, Alexander BD, Gupta KL, John GT, Pursell K, et al. Allograft loss in renal transplant recipients with Cryptococcus neoformans associated immune reconstitution syndrome. Transplantation 2005;80:1131-3.  Back to cited text no. 6
    
7.
Costa ML, Souza JP, Oliveira Neto AF, Pinto E Silva JL. Cryptococcal meningitis in HIV negative pregnant women: Case report and review of literature. Rev Inst Med Trop Sao Paulo 2009;51:289-94.  Back to cited text no. 7
    
8.
Sirinavin S, Intusoma U, Tuntirungsee S. Mother-to-child transmission of Cryptococcus neoformans. Pediatr Infect Dis J 2004;23:278-9.  Back to cited text no. 8
    
9.
Kiggundu R, Rhein J, Meya DB, Boulware DR, Bahr NC. Unmasking cryptococcal meningitis immune reconstitution Inflammatory syndrome in pregnancy induced by HIV antiretroviral Therapy with postpartum paradoxical exacerbation. Med Mycol Case Rep 2014;5:16-9.  Back to cited text no. 9
    
10.
Annapureddy SR, Masterson SW, David HG, Greig JR. Post partum osteomyelitis due to Cryptococcus neoformans. Scand J Infect Dis 2007;39:354-6.  Back to cited text no. 10
    
11.
LaGatta MA, Jordan C, Khan W, Toomey J. Isolated pulmonary cryptococcosis in pregnancy. Obstet Gynecol 1998;92:682-4.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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