Conflicting advice.
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Biomedical subjects
Publications and source records attributed to D Shanson.
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Azole-resistant HIV-related candidosis is increasingly recognized. We evaluated two new in-vitro susceptibility tests (the NCCLS proposed MIC method and Odds' assessment of relative growth in single anti-fungal concentration) as predictors of the clinical outcome of 66 HIV-positive patients with oral candidosis, of whom 22 were azole naive, 27 had always previously responded to azole therapy and 17 had persistent candidosis unresponsive to 7 days of standard azole therapy. None of the last group responded to increased daily doses of fluconazole or itraconazole capsules, though nine responded to itraconazole cyclodextrin solution 200 mg bd for 7 days. Our findings suggest that agreement between the Odds' test and the MIC method was excellent (96-98%) and that both could discriminate between isolates of azole-unresponsive patients and those of azole-responsive patients. For fluconazole susceptibility an MIC > or = 8 mg/L detected fluconazole-unresponsive patients with a sensitivity of 94% and specificity of 100%; Odds' method achieved 100% sensitivity and 100% specificity using all cut-offs between 77 and 88% relative growth in medium containing fluconazole (10(-5) M; 3 mg/L). For itraconazole and ketoconazole agreement between MIC and Odds' method was again excellent (98% and 96%, respectively) but five azole-unresponsive patients appeared to have ketoconazole-susceptible organisms as defined by both tests, and similarly 11 appeared to have itraconazole-susceptible organisms by both tests despite failing to respond to the capsule formulation of the drug. Of these 11, eight responded to itraconazole solution; this finding implies that itraconazole capsule failure might represent poor drug absorption rather than fungal resistance.
The sensitivity of 12 commonly used anti-HIV-1/HIV-2 enzyme immunoassays was evaluated. The assays, each of which utilises at least one synthetic HIV antigen, were tested against a panel of 1092 specimens previously designated anti-HIV positive. In a total of 13 104 tests there were eight false negative results attributable to assay insensitivity: three were on two serum samples collected close to seroconverison and five on another serum specimen. These eight false negative results arose in seven different assays. Five other false results were attributable to technical error. This false negativity rate indicates that all of the assays performed adequately and leads to an estimate of one false negative result in a thousand tests in routine diagnostic practice. Because of the antigenic heterogeneity of HIV strains, similar evaluations would be required in several regions before this satisfactory level of sensitivity in anti-HIV assays incorporating synthetic antigens could be said to be universal.
Ten episodes of musculoskeletal sepsis have been seen in nine patients with HIV infection. Seven patients had AIDS, circulating CD4-positive lymphocyte counts being less than 0.1 x 10(9)/l in six. Septic arthritis recurred in seven patients, osteomyelitis in three and pyomyositis and bursitis each occurred in one patient. Staphylococcus aureus was isolated from four patients, atypical micro-organisms being found in three. Presentation of musculoskeletal infection in this patient group may be atypical but rapid diagnosis is important as early antimicrobial therapy is often successful.
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Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.
Thirty of 81 consecutive HIV antibody positive patients referred with non-cryptosporidial diarrhoea had no potential infectious cause; most had AIDS related complex rather than the full blown syndrome. Opportunistic infections with cytomegalovirus (CMV), mycobacterium avium-intracellulare (MAI), and herpes simplex virus (HSV), which allowed a diagnosis of AIDS to be made, were found in 19 patients and were the presenting features of AIDS in five. Other potential pathogenic species included entamoeba, giardia, campylobacter, and salmonella (without septicaemia). Cytomegalovirus infection was often accompanied by abdominal pain. Severe weight loss (greater than 10 kg) at presentation was found in patients with CMV infection and MAI. Bloody diarrhoea was confined to the group with HSV procitis. Malignant causes of diarrhoea were rare. Two patients developed a squamous carcinoma of the anorectal margin and one a non-Hodgkin's lymphoma. In only two of 12 patients who had Kaposi's sarcoma was this considered as a cause of diarrhoea. Rigid sigmoidoscopy showed macroscopic abnormalities in over a third (32) of the 81 patients with non-cryptosporidial diarrhoea. Most commonly this was severe inflammation (17) or discrete ulceration (four) [three of whom had CMV colitis]. Kaposi's sarcoma was identified in 11 patients. Non-specific inflammation was seen histologically in 40 of the 60 patients with no sigmoidoscopic inflammatory changes. Barium enema only revealed an abnormality in a minority of the patients and a colonoscopy only revealed information additional to rigid sigmoidoscopy in two patients--one with CMV ulcers in the transverse colon and the other with evidence of Kaposi's sarcoma not seen in the rectum. Ten patients had a rectal biopsy examined by electron microscopy as no infective cause of diarrhoea was uncovered. In four of these microtubular structures which are commonly seen in viral infections were found and two had prelymphomatous changes and in one of these frank lymphoma has developed. We recommend multiple stool analysis, sigmoidoscopy and rectal biopsy as the initial investigations in these patients reserving tests of malabsorption, colonoscopy, and barium enema for the small number of more difficult cases.
The efficacy and toxicity of oral azidothymidine has been studied in 145 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The median survival time of AIDS patients on azidothymidine was 4.5 times higher when compared to a historical AIDS group who had not received the drug. This result must be interpreted with caution because of changes in treatment of HIV infection and growing awareness of AIDS which may have led to earlier diagnosis in the group treated with azidothymidine. The mortality was significantly higher in those patients who received transfusions and was particularly high in those who were transfused before azidothymidine. There was a significant difference in the occurrence of opportunistic infections in the patients who received transfusions compared with those who did not. AIDS patients treated immediately after an episode of Pneumocystis carinii pneumonia survived significantly longer than those in whom treatment was delayed for three months or more, and longer than those who were treated with azidothymidine because of another opportunistic infection or Kaposi's sarcoma. The T4 cell median counts increased in patients treated with azidothymidine reaching a peak at the end of the fourth month of treatment in the ARC group and at the end of the first month in the AIDS group with a subsequent fall in both groups. Sixty per cent of patients were p24 viral antigen positive at the start of treatment and 19 per cent of these patients had a fall of more than 50 per cent in antigen level while 32 per cent became antigen negative following treatment with azidothymidine. The mortality in the patients where the antigen disappeared or in whom there was a major fall of more than 50 per cent in antigen level was significantly less than in those where there was no change in antigen level. Twenty-nine patients were treated with azidothymidine because of skin Kaposi's sarcoma and in 17 tumour regressed or was stable. Thirty-two per cent of patients treated with azidothymidine became anaemic. Neutropenia occurred in 3 per cent of patients. Platelets increased initially after treatment but subsequently fell to thrombocytopenic levels in eight patients. Nine of 12 patients with thrombocytopenia before azidothymidine was commenced responded with an increased platelet count.
In a prospective study of 150 health care workers in the United Kingdom who had been accidentally exposed to the human immunodeficiency virus no evidence of transmission was found. Larger studies in the United States and anecdotal accounts in publications from other countries confirm that the risk of occupational infection is very low. Health care workers must adopt safe procedures at all times, however, to avoid exposure to infection.
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