Variation in morphotype, karyotype and DNA type of fluconazole resistant Candida albicans from an AIDS patient.

Azole-resistant oropharyngeal and oesophageal candidiasis is a recent phenomenon observed in patients with AIDS usually previously treated with fluconazole. Some variation has been observed in antifungal susceptibility testing among separate colonies of Candida albicans from the same patient. This raises the question of whether there are multiple clones present or simply phenotypic variation in expression of azole resistance. To address this question we took 18 isolates grown from multiple swabs taken before and after experimental azole therapy from a single HIV-positive individual with fluconazole-resistant oral candidiasis and compared morphotype, karyotype, PCR-based DNA typing and azole susceptibility. Ten of the isolates were from a single 2-day period. Amongst these 10 there were seven morphotypes, five karyotypes and four polymerase chain reaction (PCR) types. Three further morphotypes, one karyotype and two PCR types were found amongst the eight isolates obtained during the subsequent 4 months. Limited variation in susceptibility to two azoles--fluconazole and D0870--was also seen. This work emphasizes both the large genotype and phenotypic variability of C. albicans isolates in the mouth of AIDS patients with fluconazole resistance, and the difficulties in interpretation of present typing methods.

Azole resistance in Candida.

Resistance of Candida to azoles is an increasing problem. Susceptibility testing of Candida against fluconazole and ketoconazole is now feasible and desirable. Good correlation of resistance in vitro with clinical failure of fluconazole therapy has now been shown in mucosal candidiasis. The relationship, if any, between resistance and clinical failure in the context of invasive candidiasis is not clear at present and additional correlative work needs to be done. Monitoring of resistance trends in Candida is clearly important now.

Karyotyping of fluconazole-resistant yeasts with phenotype reported as Candida krusei or Candida inconspicua.

The yeasts Candida krusei and Candida inconspicua have similar phenotypes, which may make discrimination of these organisms difficult. In this study we determined the karyotypes of 51 isolates of these two yeast species by contour-clamped homogeneous electric field electrophoresis. We found that the 43 isolates that had the C. krusei phenotype had three karyotype-specific characteristics. These isolates produced either two or three bands between 2,000 and 3,000 kb and no band between 1,300 and 2,000 kb, and there was either a single bright band at 1,300 or 1,200 kb or two separate bands at 1,300, 1,200, or 1,100 kb. Using this technique, we were able to distinguish 27 different C. krusei types on the basis of band variations. The seven isolates identified as C. inconspicua on the basis of phenotype differed in that they produced at least one band between 1,300 and 2,000 kb. These isolates produced six to nine bands, in contrast to C. krusei strains, which produced three to six bands. The MIC of fluconazole for all of the isolates was at least 12.5 mg/liter, as determined by a broth dilution method.

Recurrent transient neurological deficits in advanced HIV infection.

OBJECTIVES: To report the occurrence of a syndrome of recurrent neurological deficits in advanced HIV disease and to discuss its management and prognosis. DESIGN: Retrospective case study. SETTING: A regional treatment centre for HIV-infected individuals in northwest England. MAIN OUTCOME MEASURES: Transient neurological deficit was defined as a focal neurological deficit of rapid onset which resolved completely within 24 h. Frequency, character and duration of episodes were recorded. Prior illnesses, CD4 count, changes in drug therapy and brain imaging investigations were also documented. RESULTS: Seven cases with recurrent transient neurological deficits were identified among 748 patients over a 10-year period. Six had a CD4 cell count < 50 x 10(6)/l. The episodes lasted between 1 and 12 h and resolved completely without lasting sequelae. Dysphasia and hemiparesis were the most common presentations. Recurrent episodes for each patient tended to follow a similar pattern. None had computed tomographic evidence of cerebral infarction or clinical evidence of completed stroke. Prognosis was varied and not evidently altered by the episodes of neurological deficit. Three patients may have benefited from treatment with migraine prophylactics. CONCLUSION: A syndrome of recurrent transient neurological deficits may occur in advanced HIV disease. We believe that in some cases this may be due to local cerebral vasospasm, comparable to a classic migraine aura.

Fluconazole-resistant candidosis in an HIV cohort.

OBJECTIVES: To report the occurrence of HIV-related mucosal candidosis that fails to respond to fluconazole, to establish the correlation between in vitro susceptibility testing and clinical failure, and to assess the efficacy of alternative treatments. DESIGN: Chart review of all patients with fluconazole failure and all patients with CD4 counts < 50 x 10(6)/l continuing to respond to fluconazole, and prospective in vitro susceptibility testing of Candida. SETTING: A regional treatment centre for HIV-infected individuals in north-west England. PATIENTS: A cohort of 155 HIV-positive individuals with CD4 counts < 300 x 10(6)/l cells. MAIN OUTCOME MEASURES: Clinical fluconazole failure was defined as symptomatic oropharyngeal or oesophageal candidosis despite fluconazole > or = 100 mg per day for 10 days. In vitro susceptibility to fluconazole was determined for Candida isolates. Cumulative 12-month fluconazole dose and time from first fluconazole therapy and prophylaxis were recorded. RESULTS: Nine (5.8%) patients meeting the definition of fluconazole failure were identified. In vitro susceptibility to fluconazole of temporally related oropharyngeal isolates was reduced in all cases. Intravenous amphotericin B was the only effective treatment for these patients when symptoms were severe suggesting azole cross-resistance. One patient, who had received alternative treatments for 9 months, reverted from in vitro and clinical fluconazole sensitivity but relapsed within 6 weeks of resuming fluconazole. The median fluconazole dose over the preceding 12 months for the eight adult cases was 386 mg weekly. The median dose for the same period was 79 mg weekly in 28 patients with CD4 counts < 50 x 10(6)/l but without fluconazole failure (difference, 307; 95% confidence interval, 199-514; P < 0.0001). CONCLUSION: A substantial problem of clinical fluconazole failure has developed among HIV-positive patients who have recurrent problematic mucosal candidosis.

Leishmaniasis of the tongue treated with liposomal amphotericin B.

A 66-year-old man, immunosuppressed because of a lymphoma and with severe ischaemic heart disease and proteinuria, presented with a swelling on the tongue due to leishmaniasis. His travel history suggested that he had acquired the infection in the Mediterranean area some years earlier. He was treated with liposomal amphotericin B for 21 days and made a good recovery despite a temporary deterioration in renal function. Oral lesions are a rare manifestation of Old World leishmaniasis. Liposomal amphotericin B is a novel treatment that may be well tolerated when there is concern about the toxicity of more established drugs.

Detection of Brucella melitensis and Brucella abortus by DNA amplification.

Suitable reaction conditions and oligonucleotide primers were sought for the detection of Brucella melitensis and Brucella abortus by the polymerase chain reaction. Primers were chosen from within the coding sequence of a gene encoding a 31 kDa B. abortus antigen. The test was shown to be sensitive, and specificity was demonstrated using DNA derived from a panel of Gram-negative pathogens. There was no detectable difference between B. melitensis and B. abortus in the sensitivity of the reaction or in the size of the amplification product. The technique should be applicable in the diagnosis of brucellosis.

Blastomycosis in Africa: clinical features, diagnosis, and treatment.

Four cases of blastomycosis seen in two acute care hospitals in Harare, Zimbabwe, are described. All patients had symptoms of at least 2 months' duration before presentation, and all had radiographic evidence of pulmonary consolidation. Three patients had confirmed bone involvement, and two had chronic discharging sinuses. The features of blastomycosis in Africa are reviewed, and problems of diagnosis and treatment are discussed. It is concluded that blastomycosis in Africa may often be misdiagnosed as tuberculosis or pyogenic infection in the absence of adequate facilities for mycologic investigation.

Case report: renal lymphoma in a patient with Waldenstrom's macroglobulinaemia.

A case of lymphoma confined solely to the kidneys in a patient with Waldenstrom's macroglobulinaemia is described. Primary lymphomatous involvement of the kidney is very rare in this condition. Ultrasound showed enlarged kidneys partially encased by tumour masses. The radiological features are described and the literature reviewed.

Nocardiosis: a neglected chronic lung disease in Africa?

Nocardia organisms were cultured from the sputum of 11 patients at the central hospitals in Harare, Zimbabwe, over a 12 month period. Pulmonary nocardiosis was diagnosed in one further patient on the basis of direct microscopy. Among the nine patients available for follow up, pulmonary nocardiosis was considered to be the major clinical problem in six. The patients usually presented with a chronic pulmonary infection with fever and cough without evidence of dissemination of underlying systemic disease. The chest radiograph showed consolidation in any part of the lung, and this was seen to extend slowly over several months. Prolonged diagnostic delay was a frequent problem. Haemoptysis, alcohol abuse, and empirical treatment for tuberculosis commonly featured in the history. Treatment with sulphonamides was generally successful in those patients who complied. Nocardiosis is a treatable lung disease that may be more common in developing countries than is currently recognised.

Serological diagnosis of neurocysticercosis: evaluation of ELISA tests using cyst fluid and other components of Taenia solium cysticerci as antigens.

An ELISA system was developed to assist with the diagnosis of neurocysticercosis. Antigens were prepared from the fluid, the protoscolex and the cyst wall of cysticerci dissected from infected pigs. The fluid antigen was tested both fresh and after freeze-drying and one year's storage. Sera from patients with proven neurocysticercosis were most reactive using the fluid and least reactive using the cyst wall antigens. Freeze-drying and prolonged storage of fluid antigen did not reduce its reactivity and repeated testing of sera with this antigen gave optical density values within 15% of the original value. Using this ELISA system positive results were obtained from all patients with active neurocysticercosis. Sera from patients with calcified cysts were usually non-reactive or marginally reactive to the fluid antigen.