Cryptococcal meningitis should rather be classified as meningocephalitis, since histology images reveal the involvement of brain parenchyma, in addition to the subarachnoid space [1]. Most cases of cryptococcosis (80% in high income countries, and 95% in low and middle income countries) occur in patients infected with human immunodeficiency virus (HIV) [2]. Cryptococcosis can be the first indication of AIDS in some patients [3]. HIV patients are most susceptible when they are immunocompromised enough for the CD4 cell count to be below 100 cells per microliter. With the introduction of combination antiretroviral therapy, cryptococcosis cases are on the decline after culminating in the early nineties; at least in the high income countries [2] [4].

The organism is inhaled and enters the lung first, but patients often do not show symptoms of infection in the lung [4]. Most patients appear to have subacute or chronic meningitis; however, cryptococcus can also cause acute meningitis. Patients report fever, headache, malaise, nausea, vomiting, altered mental state, and stiff neck [3]. Increased intracranial pressure is often a problem in cryptococcal meningitis; it may result in seizures [2], hydrocephalus, and cranial nerve neuropathy [5]. Some of the patients with altered sensorium also develop loss of vision. Rarely, patients may develop hemiparesis due to cerebral infarction [6]. About a third of the patients with cryptococcal meningitis have the disease disseminated to other sites such as the kidneys, or skin [4].

Immunocompetent patients have papilloedema, hydrocephalus, and focal lesions more often than immunocompromised ones [4] [7].

• Fever

  CASE REPORT A 65-year-old HIV-negative patient with a previous splenectomy, presented with a three-day history of fever, vomiting, and headache. His symptoms progressed to generalized body aches, persistent fever, and neck stiffness. [ncbi.nlm.nih.gov]

• Fatigue

  We present the case of a 52-year-old woman admitted with headaches, vomiting and fatigue for 3 weeks. She was diagnosed with cryptococcal meningitis and treated with antifungal therapy. [ncbi.nlm.nih.gov]

  In the lungs, symptoms can be similar to PCP and include coughing and shortness of breath, fever and fatigue. [i-base.info]

  Symptoms include headache, nausea, fever, fatigue, irritability, sensitivity to light, stiff neck, change in mental state, and hallucinations. [news-medical.net]

  The first symptoms of this infection are usually fever, fatigue, nausea, vomiting and headache. Cryptococcal meningitis may cause a person to become confused and have memory loss. [aidsinfo.nih.gov]

  Dependent on the infectious syndrome, symptoms include fever, fatigue, chest pain, dry cough, swelling of abdomen, headache, blurred vision and confusion. [disabled-world.com]

• Malaise

  Symptoms include fever, malaise, and headache. Cryptococcal meningitis most often affects people with weakened immune systems, including people with HIV. In people with HIV, cryptococcal meningitis is an AIDS-defining condition. [aidsinfo.nih.gov]

  Patients report fever, headache, malaise, nausea, vomiting, altered mental state, and stiff neck. Increased intracranial pressure is often a problem in cryptococcal meningitis; it may result in seizures, hydrocephalus, and cranial nerve neuropathy. [symptoma.com]

  Patients with cryptococcal pneumonia often experience cough, chest pains, low-grade fever, malaise, and shortness of breath. [verywell.com]

  Other symptoms experienced by 14 (7%) patients included abdominal pain, coma, diarrhea, vomiting, deafness, dizziness, malaise and nausea. [acmicrob.com]

• Splenectomy

  CASE REPORT A 65-year-old HIV-negative patient with a previous splenectomy, presented with a three-day history of fever, vomiting, and headache. His symptoms progressed to generalized body aches, persistent fever, and neck stiffness. [ncbi.nlm.nih.gov]

  Predisposing factors among HIV negative individuals include glucocorticosteroid therapy, solid-organ transplantation, chronic organ failure (renal or hepatic) syndromes, rheumatologic disorders, chronic lung disease, hematologic or other malignancies, splenectomy [omicsonline.org]

• Vomiting

  An 8-year-old previously healthy female presented with a 3 weeks history of headache, neck stiffness, deafness, fever and vomiting and was diagnosed with cryptococcal meningitis. [ncbi.nlm.nih.gov]

• Nausea

  CONCLUSION: Cryptococcal meningitis should be considered during pregnancy in cases of unexplained headache, altered vision, altered mental status, nausea and fever. [ncbi.nlm.nih.gov]

  Amphotericin B has many side effects including kidney damage, high fever, low blood pressure, decreased numbers of red or white blood cells, nausea, vomiting and chills. [aidsinfo.nih.gov]

• Diplopia

  Loss of vision, diplopia and ocular motility deficit have been reported previously ( 5 – 7 ). [spandidos-publications.com]

  Headache, high fever, nuchal pain and stiffness, photophobia, confusion, nausea, vomiting and diplopia are the common presenting symptoms of cryptococcal meningitis (CM). [sajhivmed.org.za]

• Headache

  A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. [ncbi.nlm.nih.gov]

• Confusion

  The author reports a male patient who presented to our emergency department with headache for 3 days and confusion for a day. The reported patient was on two immunosuppressive drugs, namely prednisone and azathiorprine for his ulcerative colitis. [ncbi.nlm.nih.gov]

  The first signs of meningitis include fever, fatigue, a stiff neck, headache, nausea and vomiting, confusion, blurred vision or sensitivity to bright light. The symptoms may come on slowly. [aidsinfonet.org]

  However, symptoms can escalate quickly to include a severe headache, confusion, a stiff neck, vomiting and a high fever. What are meningitis care options? If any of the symptoms mentioned above appear, seek immediate medical attention. [nicklauschildrens.org]

  Confusion and disorientation. Sensitivity to light. Cryptococcal meningitis can lead to stroke and coma. In the lungs, symptoms can be similar to PCP and include coughing and shortness of breath, fever and fatigue. [i-base.info]

• Seizure

  A 27 year old African lady was admitted with generalized tonic clonic seizures lasting 5 to 10 min. [ncbi.nlm.nih.gov]

  Majority of HIV-uninfected patients (84.6%) presented with seizures whereas only 14.7% of HIV-infected patients had seizures at presentation. [ijmm.org]

  Increased intracranial pressure is often a problem in cryptococcal meningitis; it may result in seizures, hydrocephalus, and cranial nerve neuropathy. Some of the patients with altered sensorium also develop loss of vision. [symptoma.com]

  Case report A 48-year-old lady presented with altered sensorium after an episode of generalized tonic-clonic seizures. There was no preceding headache, vomiting, fever or previous seizures. [tropicalgastro.com]

  Cryptococcal meningitis is a serious fungal infection of the covering the brain and spinal cord with a death rate of 60-70 per cent and which can also cause brain damage, hearing loss and seizures. [mrc.ac.uk]

• Altered Mental Status

  CONCLUSION: Cryptococcal meningitis should be considered during pregnancy in cases of unexplained headache, altered vision, altered mental status, nausea and fever. [ncbi.nlm.nih.gov]

  On examination, she was in altered mental status (Glasgow coma scale (GCS) 9/15) (E2M4V3). Oral candidiasis was noticed. Neck rigidity was absent. On per abdominal examination, liver span was 10 cm. [tropicalgastro.com]

• Neck Stiffness

  Clinical presentation typically includes fever, headache, photophobia, neck stiffness, and/or altered mental status. Unusual presentations may delay diagnosis. [ncbi.nlm.nih.gov]

  Headache was the most common symptom followed by neck stiffness and fever. [acmicrob.com]

Cryptococcal meningitis needs to be differentiated from meningitis caused by other organisms, for example tuberculous meningitis [4] and viral meningitis [1].

The identification of positive fungal culture in the cerebrospinal fluid is regarded the best practice [4]. The cerebrospinal fluid is often characterized by elevated opening pressure because of raised intracranial pressure, and usually displays lymphocytic pleocytosis, and high protein and low glucose concentrations. The organism can be identified after India ink staining in the light microscope. This test is regarded as positive if the number of colony forming units is higher than 1000 to 10,000 per ml; AIDS patients usually have much higher concentrations of the organism. Both cellular and subcellular components of the fluid can be sources of false-positive counts; these can be reduced by performing the test on the pellet of a centrifuged sample [4]. The culture helps in identifying the infecting species, and in determining the organism’s resistance to antifungal agents [2].

The organism can also be identified using antigen testing. Cryptococcal antigen assays are performed using the latex agglutination test or by lateral flow immunoassay, both of which are sensitive and specific [8]. The lateral flow immunoassay is a simple, quick, low cost test [9] that can be carried out on urine samples, an important consideration for situations when cerebrospinal fluid cannot be collected [2] [8]. It can be used in a point-of care setting, and since it detects the antigen before the appearance of clinical signs, it facilitates early diagnosis [10].

Computed tomographic scan (CT) or magnetic resonance imaging (MRI) is used to check for detection of complications in the brain, such as mass lesions (cryptococcomas) or hydrocephalus [2].

• Hyponatremia

  Hyponatremia is one of the most common electrolyte imbalances in HIV patients. The differential diagnosis may include hypovolemic hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and adrenal insufficiency. [ncbi.nlm.nih.gov]

• Cryptococcus Antigen

  Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. [ncbi.nlm.nih.gov]

Initial treatment adhered to international guidelines; however, the patient could not tolerate an effective double-antifungal therapy during the first 2 months of treatment. [ncbi.nlm.nih.gov]

Dr Joseph Jarvis, AMBITION-cm project coordinator If effective, the new treatment would provide for the first time a safe and shortened treatment for cryptococcal meningitis in low-resource settings. [edctp.org]

Initial clinical and biochemical markers and prognosis were collected and compared between the two groups. [ncbi.nlm.nih.gov]

Links: clinical features predisposing factors for fungal infection of the CNS differential diagnosis investigations treatment prognosis cryptococcosis [gpnotebook.co.uk]

Ophthalmologists should be aware that cryptococcosis can mimic more benign etiologies including IIH and neuroretinitis. Additionally, C. gattii, an emerging organism, can infect immunocompetent patients. [ncbi.nlm.nih.gov]

Case Discussion Etiologies of leptomeningeal enhancement include: infection (viral, bacterial, or fungal), sarcoid, or neoplastic (lymphoma or carcinomatous). [radiopaedia.org]

[…] disorder) C0085436 31197 ENG S PF Y FN MEDCIN cryptococcal meningitis (diagnosis) C0085436 14232007 ENG S PF Y FN US Edition of SNOMED CT Cryptococcal meningitis (disorder) C0348991 MTHU020119 ENG S PF Y PT ICPC2-ICD10 Thesaurus cryptococcosis; cerebral (etiology [decs.bvsalud.org]

Author information 1 Infectious Disease Institute, Makerere University, Kampala, Uganda. 2 Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA. 3 Division of Epidemiology and [ncbi.nlm.nih.gov]

Epidemiology of Cryptococcus and cryptococcosis in China. Fungal Genet Biol 2015;78:7-15. DOI PubMed 46. Hodge G, Cohen SH, Thompson GR 3rd. [nnjournal.net]

View Article : Google Scholar : PubMed/NCBI 2 Sloan DJ and Parris V: Cryptococcal meningitis: Epidemiology and therapeutic options. Clin Epidemiol. 6:169–182. 2014. [spandidos-publications.com]

Hepatitis C and systemic cryptococcal co-infections have been reported previously. [10 - 13 ] Both organisms share certain pathophysiological characteristics like long incubation period, both down regulate organism specific immunity to persist in human [tropicalgastro.com]

[…] neurologic sequelae among survivors indicates that therapy for CM is far from being satisfactory. 5 – 7 New nonconventional MR imaging techniques such as DWI have been proposed as tools to improve diagnostic accuracy and achieve a better understanding of the pathophysiology [ajnr.org]

CONCLUSION: CRAG screening for PLWH with low CD4 represents excellent value for money with the potential to prevent cryptococcal morbidity and mortality in Uganda. [ncbi.nlm.nih.gov]

How is it prevented? Because Cryptococcus neoformans can be found in many parts of the environment, it is very difficult to prevent coming into contact with it. [poz.com]

Professor Harrison leads a research programme on the prevention and treatment of cryptococcal meningitis in collaboration with colleagues from London and Liverpool and across sites in Sub-Saharan Africa. [lstmed.ac.uk]

CAN MENINGITIS BE PREVENTED? Taking fluconazole when your CD4 count is below 50 can help prevent cryptococcal meningitis. But there are several reasons why most health care providers don’t use it: Most fungal infections are easy to treat. [aidsinfonet.org]

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