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This is the first report from Ethiopia of a case of cryptococcal meningitis in a patient with AIDS. A 20-year-old woman was admitted to Tikur Anbessa Hospital in January 1990 with complaints of generalized pruritic skin lesions of six months, and headache, fever, and poor appetite of three months duration. The headache and low-grade intermittent fever were accompanied by nausea, vomiting, anorexia, and progressive weight loss, without diarrhea. She had had multiple sex partners. Upon admission, after being bedridden for two weeks, she appeared acutely ill and restless. Her temperature was 39.5 degrees Celsius, and she had oral thrush. There was no lymphadenopathy. Widespread, irregular erythematous and whitish macular patches (3 x 5 to 8 x 10 sq. cm in size) with peripheral scaling and tiny vesicles were found on the skin, pubic and perineal regions. She had neck stiffness, but was conscious and well-oriented. Hemoglobin (Hb) was 10.5 g%; the white cell count (WBC) was 3400/cu. mm; the erythrocyte sedimentation rate (ESR) was 92 mm/hr; the platelet count was 175,000/mm; and blood films were negative for hemoparasites. Urinalysis showed 3+ albumin and many pus cells and red cells/HPF. Urine culture was negative, and the VDRL test was nonreactive. Lumbar puncture, which was performed upon arrival, showed clear cerebrospinal fluid (CSF), with normal protein and glucose levels and no cells. CSF culture showed yeast cells, and an India ink preparation was positive for Cryptococcus neoformans. Blood taken for bacterial culture grew yeast cells. Renal and liver function tests, and chest x-rays were normal. A potassium hydroxide (KOH) preparation from a skin snip showed rounded yeast cells. ELISA and Western blot tests were both positive. The patient was given supportive treatment and amphotericin B (0.6 mg/kg daily). Although the fever decreased, the patient's general condition did not improve. She complained of headache, photophobia, nausea, and vomiting. Lumbar puncture was repeated eight days after the start of treatment; CSF culture and India ink preparations were negative. Urea nitrogen (BUN) repeated two weeks later was normal. Four weeks after admission, the patient suddenly vomited massive amounts of fresh blood and died before transfusion could be given. A discussion follows regarding the clinical manifestations, diagnosis, and treatment of this disease, particularly in AIDS patients, with a review of the literature.
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PMID:Cryptococcal meningitis in a young Ethiopian woman with AIDS. 139 20

2 AIDS patients are described who had cryptococcal meningitis accompanied by increased intracranial pressure (ICP) and visual complications, a finding thought to be relatively rare in AIDS. Of the 2-6% of AIDS patients who develop cryptococcal meningitis, many have disseminated and recurrent infections. The 1st case was a 45-year old Ugandan woman who presented with stiff neck, and right VIth cranial nerve palsy. She was treated with amphotericin B and flucytosine with some improvement, but on the 9th day she awoke with headache, drowsiness, and total blindness, although no papilledema. Her CSF pressure was 40 cm H20. She recovered after a month of intravenous chemotherapy and acetazolamide, but remained blind. Her sudden blindness was thought to be due to bilateral optic nerve infarction. The 2nd case was a 32-year old male homosexual, admitted with headache, vomiting, confusion, and drowsiness. He had stiff neck, and a CSF of 40 cm containing Cryptococcus neoformans. He was given amphotericin B, flucytosine, and has CSF drained every other day. On day 21 papilledema was seen in the right eye, and acetazolamide was started to lower CSF pressure. This patient recovered without loss of vision. 3 published series of cryptococcus meningitis in AIDS patients remarked about the low incidence of raised ICP, while 1 reported 9 of 27 with neurological and ophthalmic complications. The visual complications and increased ICP in these patients was thought to be due to inflammatory arachnoiditis or direct cryptococcal infiltration.
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PMID:Raised intracranial pressure and visual complications in AIDS patients with cryptococcal meningitis. 156 10

Twenty-six patients with cryptococcal meningitis were seen in Auckland between 1969 and 1989. The incidence of cryptococcal meningitis in Auckland residents was 0.12 cases/100,000/year. Ten (38%) of the patients were Maori or Pacific Island Polynesians. Nineteen (73%) had a predisposing cause, including immunosuppressive therapy in nine and the acquired immunodeficiency syndrome (AIDS) in seven. The most common presenting syndrome was a subacute or chronic meningitis. Other clinical syndromes included a slowly progressive ataxia, polyradiculopathy, and headache with vomiting. In two patients, the symptoms of meningitis were overshadowed by those of systemic cryptococcal infection. Delay in making the diagnosis was common. The most sensitive method for diagnosing cryptococcal meningitis was the cerebrospinal fluid cryptococcal antigen test. Antifungal therapy cured 17 of the 25 (68%) treated patients overall, 15 of the 19 (79%) without AIDS and six of the seven with no underlying disease.
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PMID:Cryptococcal meningitis in Auckland 1969-89. 202 Apr 43

Cryptococcal meningitis is the most frequent fungal infection of the central nervous system, known readily to complicate with immuno-compromised patients. There are only a few cases of primary infection in healthy non-immuno-compromised patients. Amphotericin-B (AMPH-B) and 5-Fluorocytosine (5-FC) are effective agents against Cryptococcal meningitis, although, their toxicity and drug resistance are limiting factors. However, in recent years Miconazole has been widely used against fungal infections and it's effectiveness has been reported. This is a 68 y.o. male who was admitted to Toyohashi Municipal Hospital on March 15, 1987 because of headache, vomiting, diplopia and gait disturbance. Continuous lumbar drainage was performed since lumbar puncture revealed surprisingly high cerebrospinal fluid (CSF) pressure and presence of many Cryptococcus neoformans, i.v. AMPH-B and p.o. 5-FC was also administrated. A 7 day course of i.v. AMPH-B and p.o. 5-FC showed no improvement with side effects of macrohematuria and anorexia. Then Miconazole was administrated i.v. and intrathecal (i.t.). The clinical signs and CSF laboratory data improved after a 90 day course of Miconazole therapy and the patient was discharged on August 24. But the patient was readmitted from March 10 to April 30, 1988, because of a slight increase of C. neoformans in CSF (17/mm3) and improved by i.v. and i.t. Miconazole. The total Miconazole dosage was 90.6 g (i.t.: 505 mg) at the first admission and 36 g (i.t.: 50 mg) at the second admission, but no side effect was seen. The reduction of elevated CSF pressure with continuous CSF drainage was also important for the treatment of such cases with increased intracranial pressure.
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PMID:[A case of cryptococcal meningitis successfully treated with miconazole and CSF drainage]. 261 99

A multicenter prospective randomized trial of four versus six weeks of amphotericin B, 0.3 mg/kg per day, plus flucytosine, 150 mg/kg per day, was performed with 194 patients with cryptococcal meningitis. One or more toxic drug reactions developed in 103 patients: azotemia (51), renal tubular acidosis (two), leukopenia (30), thrombocytopenia (22), diarrhea (26), nausea/vomiting (10), and hepatitis (13). The four- and six-week regimens were complicated by toxicity in 44 percent and 43 percent of cases, respectively. Toxicity appeared during the first two weeks of therapy in 56 percent and during the first four weeks in 87 percent. Azotemia did not occur more frequently in renal transplant recipients or diabetic patients. Cytopenias did not appear more often in patients with hematologic malignancies or those receiving immunosuppressive therapies. Toxic reactions that contributed to death developed in five patients (two with azotemia, one with pancytopenia, one with hepatitis, one with ileus). Amphotericin B-induced azotemia was not a significant risk factor for the subsequent development of bone marrow, gastrointestinal, or hepatic toxicity attributable to flucytosine. Flucytosine toxicity was associated with peak serum flucytosine levels of 100 micrograms/ml or more during two or more weeks of therapy (p = 0.005). Peak 5-fluorouracil levels were not predictive of toxicity. An initial dose of flucytosine is recommended based on the creatinine clearance: 150 mg/kg per day at a creatinine clearance above 50 ml/minute, 75 mg/kg per day at a creatinine clearance of 26 to 50 ml/minute, and 37 mg/kg per day at a creatinine clearance of 13 to 25 ml/minute. The serum creatinine level should be monitored twice weekly and the creatinine clearance weekly during therapy in order to anticipate changes in serum flucytosine concentration. In addition, it is recommended that the serum flucytosine level be determined two hours after an oral dose once a week, and that the dose be adjusted to maintain a level of 50 to 100 micrograms/ml.
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PMID:Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis. 330 26

A case of cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome (AIDS) is described, as well as the epidemiology, pathogenesis, clinical manifestations, diagnosis, and therapeutic management of the disease. In July 1987 a 38-year-old white man was admitted to the hospital because of confusion, disorientation, and headache. His medical history was notable for a positive human immunodeficiency virus test. Culture of the cerebrospinal fluid was positive for Cryptococcus neoformans. The patient was started on amphotericin B 16 mg/day (0.3 mg/kg/day) intravenously and flucytosine 2 g every six hours (150 mg/kg/day) orally. Despite premedication with diphenhydramine and acetaminophen, he experienced rigors that were treated with hydrocortisone and meperidine. Three weeks later he was discharged on flucytosine 2 g orally every six hours and amphotericin B 50 mg intravenously every other day. One week later the patient developed fever and chills; blood cultures were positive for methicillin-sensitive Staphylococcus aureus, and his peripheral leucocyte count was 1.8 X 10(3)/cu mm. Flucytosine was discontinued, and he was treated with intravenous nafcillin while remaining on amphotericin B. In October the patient complained of nausea, vomiting, weakness, and agitation. A CSF latex agglutination titer for cryptococcal antigen was 1:32. He was treated with amphotericin B 50 mg daily until symptoms resolved and then continued on amphotericin B 50 mg twice weekly. Cryptococcosis is the most common life-threatening fungal infection among AIDS patients. In contrast to immunocompetent hosts, this population invariably develops disseminated disease, with 85% having meningeal involvement. The most effective therapy for cryptococcal meningitis in patients with AIDS has not been established.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Management of cryptococcal meningitis in patients with AIDS. 341 73

Cryptococcal meningitis is a life-threatening disease. Headache, vomiting, cranial nerve symptoms and mental changes are the most common symptoms, but as many as 15% may have no symptoms referable to the CNS. For chemotherapy four drugs are available: namely amphotericin B, 5-fluorocytosine, miconazole and ketoconazole. Most cases have been treated by combination of amphotericin B and 5-fluorocytosine. The intrathecal administration of amphotericin B should be considered for patients who fail to respond to the usual intravenous therapy. The case is reported of a patient who died due to hydrocephalus, and the CSF-levels of the administered drugs are presented. Some pitfalls of therapy are discussed.
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PMID:[Cryptococcal meningitis]. 396 Feb 20

An 18-year-old female was given prednisolone and azathioprine for treatment of systemic lups erythematosus. She was admitted to Fukuoka University Hospital because of headache and vomiting. Examinations revealed she was suffering from cryptococcal meningitis. Fluconazole (FLCZ) 400 mg a day was administrated for therapy. Her general condition improved and the serum level of cryptococcal antigen decreased one month after therapy. This therapy resulted in abatement of subjected symptoms and sterilization of the cerebral spinal fluid. This case suggested that therapy with FLCZ alone is useful for patients with cryptococcal meningitis, therefore the standard therapy with amphotericin B (AMPH) or the combination.
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PMID:[A case report: cryptococcal meningitis and fluconazole therapy]. 782 10

Headache is a common complaint. In most patients, it is usually a problem of migrainous or tension-type headache. It is crucial that a physician is able to differentiate sinister causes of headache from the more benign ones. Six cases are presented to illustrate the fact that there are clues in the history to suggest a sinister cause of headache even though there are minimal or no neurological deficits on physical examination. At some point of time, these cases were examined by a senior physician but they were diagnosed as migrainous or tension-type headaches. The first case is a 41-year-old labourer with cryptococcal meningitis. He presented with severe headaches at a relatively late age. A 20-year-old female complained of the worst headache she ever had and this was due to a subarachnoid haemorrhage. The third case was a young woman with a large parietal meningioma. Her headaches had recently assumed a different character. The fourth case involved an investment manager who developed headaches with transient diplopia and projectile vomiting and investigations revealed an ependymoma. A shipyard worker complained of a constant headache which disturbed his sleep. Two weeks after medical consultation, the character of his headache changed and he developed diplopia in all directions of gaze. He succumbed to pituitary apoplexy. The final case is a 28-year-old woman who had a complicated migraine. CT scan of the brain showed a large arterio-venous malformation.
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PMID:Warning symptoms of sinister headache. 799 8

Eleven cases of cryptococcal meningitis were diagnosed and biotyped from September 1991 to August 1992 in Papua New Guinea (PNG). Seven isolates were Cryptococcus neoformans var. gattii from paediatric and adult patients, one with diabetes mellitus and 4 were C. neoformans var. neoformans from adults, of whom 2 had human immunodeficiency virus type 1 (HIV-1) infection, and one each had tuberculosis and Plasmodium vivax malaria. Significant clinical findings were headache, fever, meningism, vomiting, photophobia, papilloedema and cranial nerve lesions. Five patients (45.5%) died; 3 of these were adults with var. gattii and 2 were men with both var. neoformans and HIV-1 infections. This prospective tropical study documents the emergence of C. neoformans var. neoformans in patients with HIV-1 infection in a country where previously var. gattii had predominated in the immunocompetent. There has been no earlier report of cryptococcosis in an HIV-1 seropositive patient in PNG. Despite presumed exposure to both varieties of C. neoformans, var. gattii infections had been most frequent. As HIV-1 spreads, the proportion of hosts infected with var. neoformans may rise. The course of meningitis caused by the 2 varieties of C. neoformans may differ, with mortality in the tropics remaining particularly high. In PNG the environmental source of C. neoformans remains elusive.
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PMID:Meningitis caused by Cryptococcus neoformans var. gattii and var. neoformans in Papua New Guinea. 873 Mar 14


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