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PubMed2002

[A clinical study of 26 cases of cryptococcal meningitis].

OBJECTIVE: To study the diagnosis and therapy of cryptococcal meningitis. METHODS: Retrospective review of the clinical features, treatment and outcome of 26 patients with cryptococcal meningitis from October 1981 to September 2001 at Peking Union Medical College Hospital. RESULTS: The age of the patients ranged from 5 to 62 years (mean: 35.6 years), 12 were male and 14 were female. There were 16 patients with underlying diseases, 9 had systemic lupus erythematosus (SLE), 4 had human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS) and 3 had other diseases. 12 patients had contact with pigeons. The nonspecific clinical and laboratory findings in these patients led to misdiagnosis: as lupus encephalopathy in 6 cases and tuberculous meningitis in 5 cases. 23 of the 26 cases were positive of cryptococcus on cerebrospinal fluid (CSF) smear. 13 cases were positive on CSF culture, but latex coagulate test performed in 20 cases were all positive, 15 patients had high intracranial pressure (> 300 mm H(2)O), 9 patients with dilated ventricle received brain ventricular draining. Only 2 cases used fluconazole monotherapy. One patient only used amphotericin B. The rest of the patients were given amphotericin B in combination with flucytosine (12 patients) or fluconazole (5 cases), or flucytosine combined with fluconazole (6 cases). The mean dose of amphotericin B was 2.6 g, the highest dose of amphotericin B and liposomal amphotericin B was 10.05 g and 20 g, respectively. The outcome of the 26 cases showed that 17 were cured, 4 improved, 3 patients were died and 2 patients gave up any further treatment. From Oct. 1981 to Sep. 1996 we found only 9 cases, but in recent 5 years we found 17 cases. CONCLUSIONS: The incidence of cryptococcal meningitis was increasing in the recent 5 years. The conditions associated with this disease include extensive broad spectrum antibiotics, immunosuppressive drugs or ligh-dose corticosteroids and increasing cases of HIV/AIDS. The early diagnosis and treatment of cryptococcal meningitis may reduce death rate. We still recommended amphotericin B plus flucytosine as the standard therapy for cryptococcal meningitis. Ventricular drainage and amphotericin B intraventricularly via an implanted tube into dilated ventricle could improve the clinical condition of serious cryptococcal meningitis and decrease the dosage of systemic use of amphotericin B, therefore, reduce the side-effects of the drugs.

Acquired Immunodeficiency Syndrome↗

PubMed2003

Cryptococcal meningitis in pediatric systemic lupus erythematosus.

Cryptococcal meningitis is an uncommon but often fatal complication of systemic lupus erythematosus (SLE). We report on a 13-year-old girl with SLE using high-dose prednisolone for several months, presented to us with low grade fever, intermittent vomiting and headache. Physical examination, including papilloedema and meningeal irritation, was unremarkable. Serum and cerebrospinal fluid (CSF) cryptococcal antigen titer was 1: 128 by latex agglutination method. CSF culture yielded Cryptococcus neoformans. We used amphotericin B deoxycholate (a cumulative dose of 1.95 gm) and fluconazole (200 mg day-1) for 6 weeks. Clinical response was good. Then, we continued fluconazole 200 mg per qd as suppressive therapy for thirty-four months. There were no neurological sequelae or relapse after 20-month follow-up. Timely diagnosis and effective antifungal therapy could improve the prognosis of cryptococcal meningitis in SLE patients.

Adolescent↗

PubMed2001

Clinical manifestations of AIDS with cryptococcal meningitis.

OBJECTIVE: To increase the awareness of AIDS with cryptococcal meningitis. METHODS: Eighteen cases of confirmed AIDS with cryptococcal meningitis in the Bata Regional Hospital, Equatorial Guinea from January 1997 to November 1999 were analyzed. RESULTS: The clinical manifestations of the 18 cases were: insidious onset, fever, severe headache, generalized pain, nausea and vomiting, weight loss and dehydration, and enlarged cervical lymph nodes. Boa's and Cullen's signs were positive. The positive rates of cerebrospinal fluid (CSF) India ink stain and the polysaccharide capsule antigen (ELISA) were 77.8% and 99.4%, respectively. The positive rate of CSF culture of cryptococcus was 100%. The mortality rate was 83.3%. CONCLUSION: Cryptococcal meningitis is the most common opportunistic infection and one of the major causes of deaths in AIDS patients. The misdiagnosis and mortality rates were very high and could be explained by a lack of awareness for the occurrence of AIDS with cryptococcal meningitis, late presentation, serious illness and severe complications, and delayed and inadequate therapy.

AIDS-Related Opportunistic Infections↗

PubMed1982

Ketoconazole therapy of murine cryptococcal meningitis.

Currently, even optimal therapy of cryptococcal meningitis is associated with appreciable mortality, drug toxicity, and prolonged hospitalization. Ketoconazole, a new oral imidazole, has therefore been evaluated in a murine model of cryptococcosis. Cryptococcal meningitis was induced in BALB/c mice by intracranial injection of Cryptococcus neoformans. The mice developed infection characterized by diffuse meningitis and extracerebral dissemination. Oral ketoconazole therapy prolonged survival of infected mice, but most mice ultimately succumbed to infection. Ketoconazole dramatically reduced the cryptococcal counts in the liver, but had minimal effect on counts in the brain. Paralleling these results were high concentrations of ketoconazole found in lung, spleen, and heart muscle and lower concentrations (2 to 5 micrograms/ml) found in the brain. The detection of biologically active drug in the brain, and the prolongation of survival afforded by ketoconazole, suggest a potential role for this agent in the theory of cryptococcal meningitis.

Animals↗

PubMed2005

Raised intracranial pressure complicating cryptococcal meningitis: immune reconstitution inflammatory syndrome or recurrent cryptococcal disease?

We report the case of a patient with advanced HIV disease and cryptococcal meningitis, who after an initially good clinical and mycological response to systemic anti-fungal treatment developed symptomatic raised intracranial pressure 10 days after initiation of highly active anti-retroviral therapy. We describe the subsequent clinical management and the features that suggest that this persistently raised ICP was more likely due to an immune reconstitution syndrome (IRIS) following HAART rather than relapse of cryptococcal disease or failure of anti-fungal therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Cryptococcal meningitis with malaria. A case report.

Cryptococcal meningitis is an uncommon infection globally, including Nigeria. This systemic fungal infection often is associated with immunodeficiency. The most common causes of meningitis in Nigeria in the 2-3 year age group are the malaria parasites and bacteria. The concomitant infections of Cryptococcal neoformans and Plasmodium falciparum are uncommon. We present here the report of a case of fatal cryptococcal meningitis with malaria infection in a 2 year old child from Nigeria (one of the malaria endemic regions of the world). This case emphasizes the importance of doing a combination of fungal and bacterial cultures as well as looking for malarial parasites in the determination of etiological agents of meningitis in any hospital in Africa. We suggest that cerebrospinal fluid from meningitis cases must be cultured using Sabouraud dextrose agar and any growth on the agar must be examined using Indian ink.

Autopsy↗

PubMed2004

Intrathecal production and secretion of vascular endothelial growth factor during Cryptococcal Meningitis.

BACKGROUND: Patients with cryptococcal meningitis (CM) show elevated intracranial pressure (ICP) and blood-brain barrier (BBB) disruption in most cases. Elevated ICP is an important contributor to mortality. Vascular endothelial growth factor (VEGF) might be the mediator of BBB disruption during CM. METHODS: We measured VEGF levels in serum, plasma, and cerebrospinal fluid (CSF) of 95 patients and 63 control subjects, and we analyzed the required trigger and cellular source of VEGF secretion in vitro. RESULTS: Cryptococcus neoformans and its capsular antigens dose-dependently induced VEGF secretion by polymorphonuclear neutrophils, monocytes, and peripheral blood mononuclear cells (PBMCs). VEGF production by PBMCs induced by antigens strongly exceeded production by monocytes (P<.001). The addition of major histocompatibility complex class II antibody inhibited this production of VEGF (P=.005). Confirming the in vitro data, patients with CM showed significantly elevated VEGF levels in CSF (P<.001), plasma (P=.028), and serum (P<.001), compared with healthy control subjects. Calculated VEGF indices demonstrated that VEGF was produced intrathecally. CONCLUSIONS: Our findings suggest that VEGF plays a role in the pathophysiology of CM. We propose that CD4(+) T lymphocytes--stimulated by monocytes acting as antigen-presenting cells--are the cells that produce VEGF in response to cryptococcal antigens.

Adult↗

PubMed1992

Raised intracranial pressure and visual complications in AIDS patients with cryptococcal meningitis.

The clinical course of cryptococcal meningitis in AIDS shows some important differences from the features of the illness in non-AIDS patients. Complications such as raised intracranial pressure and visual impairment that are recognised in non-AIDS patients may be less frequent in those with AIDS. Persistent intracranial hypertension should be managed actively to prevent visual impairment. In AIDS patients, in whom ventriculo-peritoneal shunts carry additional risks, acetazolamide can be used successfully to lower the CSF pressure and prevent visual loss.

Acquired Immunodeficiency Syndrome↗

PubMed1996

The management of cryptococcal meningitis in Papua New Guinea.

Cryptococcal meningitis is a difficult disease to treat and requires biochemical and haematological monitoring to detect the common adverse effects of treatment. Combination therapy with amphotericin B and flucytosine for at least 6 weeks is the best treatment so far evaluated. The role of azole drugs should become clearer as the results of large multicentre studies become available in the future. High case fatality and morbidity rates despite standard treatment suggest that other ancillary treatments such as corticosteroids and other treatments directed at lowering raised intracranial pressure may also be required in some patients.

Amphotericin B↗

PubMed1995

Cryptococcal pneumonia in AIDS: is cryptococcal meningitis preceded by clinically recognizable pneumonia?

Identification of cryptococcal infection while it is still in its pulmonary phase might improve the prognosis for patients with AIDS who contract cryptococcosis. Since cryptococcal pneumonia is infrequently diagnosed in the AIDS patient, especially compared with the frequency of diagnosis of cryptococcal meningitis, this retrospective study was designed to investigate the frequency of pulmonary complaints in the months before diagnosis of cryptococcal meningitis. The medical records of 18 patients diagnosed with cryptococcal meningitis were analyzed. Of 18 patients, 14 (78%) had respiratory symptoms during the 4-month period before meningitis appeared, as compared with nine of 18 (50%) at the time of diagnosis and four of 16 (25%) in the 4 months following diagnosis. Seven of the 14 cases of pulmonary disease prediagnosis were of unknown etiology; three were eventually diagnosed as cryptococcal infections during evaluation of the meningitis. The remaining eight infections were attributed to bacteria, respiratory viruses, or Pneumocystis carinii, although three of these cultures also contained yeast, presumed to be Candida species, which were not further examined. Our data suggest the importance of singling out AIDS patients who may have pulmonary cryptococcosis. Cryptocococcsis should be included in the differential diagnosis of pulmonary infection in HIV-positive patients with CD4+ lymphocyte counts < 200/mm3, and full identification of yeasts recovered from sputum or bronchoalveolar lavage fluid cultures should be done. A larger study should be undertaken to better define the incidence of clinically recognizable pulmonary cryptococcosis in AIDS patients.

AIDS-Related Opportunistic Infections↗

PubMed1981

Asymptomatic cryptococcal meningitis.

Two cases of asymptomatic cryptococcal meningitis are described. The disease was diagnosed only after Cryptococcus neoformans was cultured from lung tissue and urine. These cases represent 2 of 11 meningitis cases seen in a 10-yr period at this hospital. Of 11 cases of extraneural cryptococcosis, 6 had lumbar punctures and these 2 had positive culture results. Asymptomatic cryptococcal meningitis is not rare. Our experience suggested that lumbar punctures should be performed routinely in patients with cultures yielding Cryptococcus neoformans from extraneural sites.

Cryptococcosis↗

PubMed1992

Cryptococcal meningitis in patients with AIDS.

In the U.S., cryptococcal meningitis is the most common form of fungal meningitis and a major cause of morbidity and mortality among immuno-suppressed patients. In the AIDS patient, cryptococcal meningitis often presents with fever and headache and is best treated with intravenous amphotericin B and oral flucytosine, or fluconazole. However, toxic effects may result from the therapy. This disease frequently relapses necessitating life-long treatment to prevent reactivation. Essential management principles focusing upon health education are presented to promote comprehensive nursing care for patients testing positive for the human immunodeficiency virus who also have cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗

PubMed1999

Risk factors for cryptococcal meningitis in HIV-infected patients.

To identify the risk factors for cryptococcal meningitis in patients with HIV disease we conducted a nested case-control study of 37 incident cases of cryptococcal meningitis and 74 controls, identified from a cohort of more than 2000 HIV-infected patients. Conditional logistic regression was used to study demographic and AIDS-related variables in addition to fluconazole and steroid use. No difference in demographic variables, HIV risk factors, or stage of AIDS was detected between cases and controls. Exposure to fluconazole for more than 90 days reduced the risk of cryptococcal meningitis by 82% (OR=0.18; 95% CI=0.04-0.85; p=0.03). We did not find a difference in steroid use between cases and controls for either the length or amount of steroid exposure (p=0.41). No difference in survival during follow-up in the clinic was observed by the log-rank test (p=0.74). Among the cases, a cryptococcal antigen was positive in more than 97% of the CSF or blood samples. CSF and blood cultures were positive in 81 and 44% of the samples, respectively. We conclude that demographic factors did not affect the risk of cryptococcal meningitis in an inner city United States population. While fluconazole use has a protective effect, steroid use was not associated with an increased risk of cryptococcal meningitis in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

PubMed2002

Cryptococcal meningitis in a neonate.

A case of cryptococcal meningitis in a neonate born to an HIV-negative women is described. The cryptococcal infection was proved using standard microbiological and antigen detection techniques. Although cryptococcal meningitis has previously been described in both immunocompromised and immunocompetent children, the present case represents youngest case of cryptococcosis reported to date.

Anti-Bacterial Agents↗

PubMed1997

Cryptococcal meningitis in African children.

Three cases of cryptococcal meningitis in Malawian children aged 6 weeks, 3 years and 9 years are described. Only 23 cases of cryptococcal meningitis in children have been described previously, but in children from Europe and the USA. These are therefore the first cases of cryptococcosis to be described in African children.

Child↗

PubMed1996

Cryptococcal meningitis in AIDS--need for early diagnosis.

Cryptococcal meningitis is the most common opportunistic fungal infection in patients with Acquired Immunodeficiency Syndrome (AIDS) contributing to the increased morbidity and mortality. This important infection in AIDS seems to be under diagnosed in India. We discuss the clinical features, laboratory diagnosis and therapy of seven cases of cryptococcal meningitis detected in our hospital. Diagnosis was established in all cases by identification of the fungus in cerebrospinal fluid (CSF) by India Ink preparation and positive fungal culture in CSF and/or Blood. Six patients were treated with Amphotericin B and Flucytosine. Two were cured and have not relapsed on suppressive therapy. Two died during treatment. Two were lost to follow up. All the three patients who died had positive fungal culture in blood and CSF. Presence of Cryptococcemia in Cryptococcal meningitis is an indicator of poor prognosis. A high index of clinical suspicion and routine mycological surveillance essential to identify this infection.

AIDS-Related Opportunistic Infections↗

PubMed1998

Management of elevated intracranial pressure in patients with Cryptococcal meningitis.

BACKGROUND: The most important predictor of early mortality in patients with HIV-associated cryptococcal meningitis is mental status at presentation; patients who present with altered mental status have up to 25% mortality. Historically, cerebrospinal fluid (CSF) diversion in HIV-negative patients with cryptococcal meningitis and signs of elevated intracranial pressure (ICP) has improved survival. In an effort to affect survival and morbidity rates in patients with HIV-associated cryptococcal meningitis, we have initiated aggressive management of elevated ICP in patients with focal neurologic deficits, mental obtundation, or both. METHODS: We identified 10 patients with HIV-associated cryptococcal meningitis who presented with symptoms consistent with elevated ICP, including headache, mental obtundation, papilledema, and cranial nerve palsies. Elevated opening pressure was defined as > 20 cm CSF during lumbar puncture. In patients with elevated opening pressures who had focal neurologic deficits or mental status changes refractory to serial lumbar puncture, management consisted of immediate placement of lumbar drains for continuous drainage of CSF to maintain normal ICP (10 cm CSF). Patients with persistent elevations of spinal neuraxis pressure following lumbar drainage underwent placement of lumbar peritoneal shunts. RESULTS: All patients returned to their baseline level of consciousness following normalization of ICP. Two patients were weaned from lumbar drainage. Eight patients eventually required placement of lumbar peritoneal shunts for persistently elevated ICP despite successful antifungal therapy. Follow-up ranged from 1 to 15 months. One shunt infection occurred, one lumbar peritoneal shunt was converted to a ventriculoperitoneal shunt, and one shunt was removed. CONCLUSIONS: Elevated ICP in patients with HIV-associated cryptococcal meningitis is a significant source of morbidity and mortality. The use of lumbar drainage and selective placement of lumbar peritoneal shunts in the management of elevated ICP in patients with HIV-associated cryptococcal meningitis can ameliorate the sequelae of elevated ICP.

Adult↗

PubMed1990

Evaluation of latex cryptococcal agglutination test in cryptococcal meningitis.

There is a growing demand for laboratory diagnosis of cryptococcal meningitis, which is partly due to the increasing incidence of AIDS in Thailand. Presently, latex cryptococcal agglutination test (LCAT) is the most sensitive and specific test for laboratory cryptococcal meningitis. However, the test is very expensive and not readily available. LCAT must be developed locally to meet the need in Thailand. Rabbit antibody to C. neoformans was raised and used to sensitize latex particles used in LCAT. The developed LCAT was compared with a reference LCAT. The locally made LCAT was almost identical to the reference LCAT in sensitivity and specificity. It was extensively compared with the culture and India ink examination, in 73 cerebrospinal fluid specimens from cryptococcal meningitis and 155 specimens from other diseases. LCAT was found specific and more sensitive than fungal culture and India ink examination. LCAT is now extensively used in Thailand and recommended by Thai experts for use in all general hospitals. It is a simple, sensitive, specific, rapid and inexpensive tool for both diagnosis, prognosis and follow-up of cryptococcal meningitis.

Animals↗