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Background and Aim: This retrospective study examined the prevalence of co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the frequency of chronic hepatitis in HIV-infected patients with respect to both the different risk groups and the serological results., Patients and Methods: All Zurich participants of the Swiss HIV Cohort Study were evaluated who had available results of hepatitis B and C serology and ALT., Results: Of the total 279 patients, 52% belonged to the intravenous drug user, 34% to the homosexual, and 11% to the heterosexual risk category. Serologically, previously acquired infection with HBV alone could be demonstrated in 92 (33%), HCV alone in 9 (3%), and both HBV and HCV in 130 (47%) patients. Only 3% of patients with sexually acquired HIV infection had anti-HCV antibodies, whereas co-infection with HBV and HCV was present in 87% of intravenous drug users. Among the 222 patients with previous HBV contact, 25 (11%) had positive HBsAg and 91 (41%) had "anti-HBc alone", both assumed to represent active HBV infection. 66 (24%) of 279 patients had chronic hepatitis with ALT elevation lasting > or = 6 months. Chronic hepatitis was present in 46% of those with active HBV and HCV co-infection, in 36% of those with HCV infection alone and in 18% of those with active HBV infection alone (P < 0.001). Of the 66 cases of chronic hepatitis, 58 were associated with HCV infection, and only 2 cases had no serological signs of active HBV or HCV infection., Conclusion: In patients with sexually acquired HIV infection, HBV had frequently been co-transmitted. In contrast, almost all of those infected by means of intravenous drug use had a co-infection with both HBV and HCV. The latter seems to play the strongest role in the development of chronic hepatitis with persistent ALT elevation. A chronic ALT elevation was almost always associated with serologically active HBV or HCV infection.

History and Clinical Findings: A 39-year-old HIV positive patient developed myalgia, headache and cough 4 weeks after a tick bite. His temperature was 37.4 degrees C and a circular pale erythema was noted over the left lower leg., Investigations: C-reactive protein was raised to 120 mg/l, white blood cell count was 5860/microliter, CD4-lymphocyte count 250/microliter. The chest radiogram showed pneumonitic infiltration in the left lower lobe. There were IgM antibodies against Borrelia burgdorferi., Treatment and Course: Left lower lobe pneumonia and chronic erythema migrans were diagnosed and he was given oral azithromycin (500 mg on the first day and 250 mg for 4 days). The pneumonia cleared up, but 2 weeks later he developed symptoms of meningitis (496 cells per microliter, 87% lymphocytes, positive Borrelia burgdorferi antibody titer), which quickly and lastingly responded to ceftriaxon (2 g daily by brief infusion for 14 days)., Conclusion: This immune-compromised HIV-infected patient developed disseminated borreliosis with CNS involvement 2 weeks after the occurrence of chronic erythema migrans. The initial treatment of the latter with azithromycin was unable to prevent the meningitis. It is unlikely that there was a causal connection between the borreliosis and the pneumonia.

History and Findings: A 76-year-old man went to an ENT outpatient clinic because of stabbing pain in the left throat and difficult swallowing. He was found to have tonsillitis on the left and cervical lymphadenitis. The symptoms regressed on treatment with amoxycillin and clavulanic acid, but the cervical lymphadenitis persisted. Fine-needle biopsy of the cervical swelling was not diagnostic. Computed tomography of the neck showed an encapsulated liquid space-occupying lesion with infiltration of surrounding soft tissues., Treatment and Course: The cervical lymph-node mass was excised and histologically found to contain epithelioid granulomas with a few giant cells and scattered centrally caseous necroses. Tuberculostatic treatment was started; drainage fluid from the wound grew acid-fast bacilli, identified by gene probe as Mycobacterium gordonae., Conclusions: Mycobacterium gordonae is ubiquitous in the environment and is being identified ever more frequently in microbiological laboratories, usually as contaminant. It rarely causes infections of soft tissues and the lungs or systemically.

History and Findings: A 35-year-old HIV-infected man with a CD4 cell count of 100/microliter who had returned from a holiday in Spain presented with fever, chronic diarrhoea, cough, oral ulcers, subcutaneous nodules of about 1 cm in diameter and crusted skin ulcers of about 2 cm in diameter at his right arm, both wrists and buttocks., Investigations: Microscopic examination and culture of smears of a skin ulcer revealed acid-fast bacteria. Mycobacterial cultures of blood, sputum, urine and stool remained sterile., Treatment and Course: Before the microorganisms were identified culturally, atypical mycobacteriosis was assumed and treatment with rifampicin, ethambutol, isoniazid and clarithromycin was started. Mycobacterium haemophilum was identified by using molecular biological techniques. Within 3 weeks the patient became afebrile and the skin ulcers healed completely. After a 7-week course, the treatment had to be stopped, and one month later painful subcutaneous nodules developed again at his arms and legs. A relapse of Mycobacterium haemophilum infection was confirmed by culture of a fine needle aspirate of a nodule. The same treatment was restarted and the nodules disappeared., Conclusions: Mycobacterium haemophilum, first identified in 1978, is an emerging pathogen in immunocompromised patients. Clinical manifestations usually are skin ulcers, subcutaneous nodules and subcutaneous abscesses, and less frequently, systemic infection. Treatment options of this life threatening disease have yet to be defined but therapeutic response to tuberculostatic combination therapy has been observed. Since Mycobacterium haemophilum is a fastidious organism, special laboratory methods are required for cultivation as well as for identification.

Objective: To determine retrospectively the clinical features and course of HIV-associated intestinal Cryptosporidium infection and its response to paromomycin., Patients and Methods: Case notes of all patients treated for cryptosporidiosis over a two-year period at an HIV out-patient clinic were analysed (26 men, four women; median CD4-lymphocyte count: 20/microliter). Median follow-up time was 6(1-22) months., Results: 15 patients had persistent diarrhoea, two remained asymptomatic, seven had a remission and in five the disease took a fulminant course with severe diarrhoea ending in death within 4 months. 15 of the patients died during the period of observation, eight of them of cryptosporidiosis-associated cachexia. Mean survival time was about one year. Eight patients had multiple intestinal infections at the time the diagnosis was made and seven developed them later, which correlated with the poorer survival chances. Four patients had proven and 13 probably cryptosporidiosis-associated involvement of the biliary tract, but this did not affect the survival chances. 21 of 28 patients with diarrhoea were treated with paromomycin. In 13 of them there was for a time complete or partial response to treatment, but no response in eight. Those who responded well or partially to paromomycin had a significantly better survival chance than those without response. There was no correlation between the severity of immunosuppression and the severity of the cryptosporidiosis-associated diarrhoea, the response to paromomycin and the worse survival chance in the presence of multiple intestinal infections., Conclusions: The reasons for the different courses taken by HIV-associated cryptosporidiosis and the different therapeutic responses remain unclear. There is no known causal treatment, but 60% of patients improved temporarily on paromomycin.

Case notes of 722 HIV-infected patients who had died between March 1986 and August 1993 were analysed to evaluate the prevention and characteristic features of sinusitis associated with HIV infection. In 73 patients (10%) sinusitis had been diagnosed at least once on the basis of radiological or clear-cut clinical criteria. In addition, 15 patients with sinusitis were identified among those attending an HIV out-patient clinic. There were altogether 126 episodes of sinusitis in 88 patients (62 men, 26 women; mean age 33 [19-69] years). In 62 patients the CD4 lymphocyte count was under 100/microliters. The most commonly affected site was the maxillary sinuses. Patients with mirror formation had a significantly longer duration of illness than those without (P = 0.021). In 58 patients the symptoms of fever, headache and rhinitis were predominantly caused by the sinusitis, in 49 only partially so, and in 19 sinusitis was a chance diagnosis. In 10 of 49 attacks of sinusitis the concurrent disease (e.g. cerebral toxoplasmosis, malignant non-Hodgkin lymphoma) had not been recognized by the referring doctor. There were 1-5 recurrences over an observation period of 11.8 (0-72) months in 23 patients.-These findings show that sinusitis frequently occurs in HIV-infected patients, takes a protracted course and is difficult to distinguish from concomitant diseases by its clinical presentation. If symptoms persist, possible concurrent respiratory infection or CNS involvement must be looked for. Sinus needle aspiration is of decisive importance to ascertain the causative organism.

To assess the sensitivity and negative predictive value of sputum examination for Pneumocystis carinii in HIV-positive patients, follow-ups were performed in HIV-infected patients who had been investigated for the presence of Pneumocystis carinii (376 examinations of sputum and 71 bronchoalveolar lavages). Pneumocystis carinii pneumonia was diagnosed 65 times in 64 patients (57 male and 7 female, median age 35 [23-67]years). In 52% of the cases (n = 34) the pathogen was identified in the sputum, in 48% (n = 31) by means of the bronchoalveolar lavage. Of 342 negative findings in sputum examination, five were definitely false negative since the subsequent lavage yielded pneumocysts. In nine further cases Pneumocystis carinii pneumonia could not be excluded because of the course of the disease. In patients from whom sputum samples were available the sensitivity of pathogen identification was at least 70.8% and the negative predictive value at least 95.9%. Since preceding prophylaxis did not render identification in the sputum more difficult, examination of spontaneous or provoked sputum is indicated as a first hand measure in all patients infected with HIV in whom Pneumocystis carinii pneumonia is suspected.

Within one year a 46-year-old HIV-positive man developed Pneumocystis carinii pneumonia, candida oesophagitis and recurrent mucocutaneous herpes simplex infections. He finally developed a constant fever without any infection-localizing features. There was pancytopenia, increased activities of the transaminases, lactate dehydrogenase, amylase and lipase, as well as diffuse ST-segment changes in the ECG and discrete pulmonary infiltrates. The anti-toxoplasmosis titre was 8 IU/ml. Despite extensive diagnostic tests no firm diagnosis could be established. The pulmonary infiltrate and the fever regressed under antibiotic treatment with co-trimoxazole. Two months later his general condition deteriorated again with some disorientation and subfebrile temperature, epididymitis and renewed rise in abnormal laboratory values. For the first time computed tomography showed some punctate contrast-medium concentrations in the subcortical area and the medulla. The patient died on the same day. Histological material obtained at the time of autopsy revealed pseudocysts with Toxoplasma gondii and necrotizing inflammation in the brain, myocardium and lungs, as well as the entire gastrointestinal and urogenital tracts. In addition, cytomegalovirus infection of the lung and adrenals was demonstrated. Anti-toxoplasmosis IgG titre, determined postmortem, again registered a marked rise to 251 IU/ml. This suggests that there was reactivation of the toxoplasmosis as part of the immunosuppression process.

The pattern of change over time of CD4-lymphocyte counts was investigated prospectively in 420 patients infected with HIV-1 (106 women, 314 men; mean age 34.9 [21-70] years) to assess its value in prognosticating progression to AIDS. Only those CD4-lymphocyte values were taken into account which had been measured in the asymptomatic stage of the HIV infection and before introduction of antiviral treatment. An average of 4.5 (range 3-10) measurements per person were available. Mean observation time was 2.4 years, the mean annual CD4-lymphocyte decrease was 48 cells/microliters. 121 patients (28.8%) had a fall in CD4-lymphocyte count which in the regression analysis significantly differed from zero. In this group there occurred 19 progressions to AIDS (15.7%), in contrast to only 20 (6.6%) in the 299 patients with a nonsignificant CD4 fall (P < 0.01). Multivariate analysis with the Cox regression indicated that the annual reduction in the CD4 count and the initial CD4 count were the only values of prognostic significance regarding progression to AIDS. There was no evidence that percentage and absolute CD4-lymphocyte counts had a different predictive value. When the initial CD4 count was high (> 900 cells/microliters), there was on average a steeper reduction in CD4-lymphocyte counts than when it was lower. This findings argues against a linear CD4 fall during the total period of observation. The annual CD4 fall, described with linear regression, is a prognostic criterion on its own for early recognition of those patients at a high risk of progression to AIDS while still in the asymptomatic stage of HIV infection.

30 patients infected with HIV (20 men, 10 women; mean age 34 [26-54] years), suspected of having Pneumocystis carinii (Pc) pneumonia, had undergone bronchoalveolar lavage which proved negative for Pc. They were then kept under observation for 5 months. No transbronchial biopsy was performed. 27 patients were in stage IV of the HIV infection, and 14 had been on pentamidine prophylaxis. The most frequent diagnosis with the bronchial lavage was bacterial infection (19 patients), next most frequent was mycobacterial infection (6, atypical in 5). A neoplasia (Kaposi sarcoma; non-Hodgkin lymphoma) was found in two, with pulmonary involvement. The diagnosis remained unclear in only three patients who were treated as for Pc pneumonia. The remaining 27 patients did not receive any treatment against Pc. Nonetheless, there were no cases of Pc pneumonia in the 5 months of observation so that bronchoalveolar lavage has a negative predictive value of 90% (27 of 30), high enough to make additional bronchial biopsy unnecessary.

A 41-year old man of Brazilian origin, suffering from AIDS for one year, fell ill with pyrexia of over 39 degrees C, dyspnoea, chest pain and deterioration in his general condition. At the same time he noted a discrete skin eruption, mainly on the upper limbs. Diarrhoea began later. A chest radiograph revealed bilateral infiltrates. The blood showed leucocytosis (11,000/microliters) with pronounced increase of eosinophil granulocytes (47.5%). Alkaline phosphatase was raised to 170 U/l. Suspicion of strongyloidiasis was confirmed by the discovery of numerous Strongyloides stercoralis larvae in the faeces. A few days after starting treatment with mebendazole, 400 mg daily, he felt better and the diarrhoea stopped. However, as the lung infiltrates remained unchanged and hilar lymph node enlargement now appeared, the dose of mebendazole was raised to 2500 mg daily. The abnormal findings then cleared up: Strongyloides stercoralis larvae ceased to be demonstrable and the patient gained 10 kg in weight.

A 29-year-old man who had been abroad for several years (mainly Mexico) fell ill with fever (up to 39.8 degrees C), night sweats, weight loss of 10 kg in 6 months (height 181 cm, weight 50.5 kg) and abdominal pain. Computed tomography of the abdomen revealed many enlarged abdominal lymph nodes. Serological tests were positive for HIV antibodies. Fine-needle biopsy of one of the enlarged lymph nodes revealed numerous macrophages with round inclusions, typical for Histoplasma capsulatum. Disseminated histoplasmosis was confirmed by direct antigen demonstration in serum and urine. The patient's serious clinical condition clearly improved and lymph node enlargement regressed after starting specific i.v. treatment with amphotericin B (initially 20 mg/dl, then 50 mg/dl). Although complete cure of the histoplasmosis in connection with the HIV infection is not to be expected, the patient has remained without symptoms for four months on 50 mg weekly of amphotericin B i.v., later changed to imidazole derivatives (400 mg ketoconazole or 200 mg itraconazole, respectively.

A man who, only in 1979 and on a few occasions, had homosexual contacts, transmitted AIDS virus HTLV-III in 1980 and 1981 to two previously healthy women who did not belong to any AIDS risk group. One of them now has an early form of AIDS, while the other died of AIDS in its full form and her child, born in 1983, has fairly far progressed early symptoms of AIDS. Serum antibodies against HTLV-III were demonstrated in all four subjects.

Mycobacterial infections were confirmed in 629 HIV-infected persons (1.4%). Five patients had a generalized infection with Mycobacterium avium complex (MAC), four an extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (M. tbc). In general, the tuberculosis was the first severe opportunistic infection, while infections with MAC were more frequent in patients with already manifest AIDS. Common to all patients were a septic temperature and definite shift to the left of neutrophil granulocytes. Four of five patients with MAC also had diarrhoea, and three of four with tuberculosis additionally had peripheral lymphomas. The chest x-ray films were normal in six of the nine patients. The diagnosis was made in six patients primarily by the microscopic demonstration of acid-fast bacteria in lymph node tissue or stool, in three patients by culture from blood or liver tissue. Microscopic stool examination was helpful: in three of five patients with MAC and one of two with M. tbc in the stool culture, acid-fast bacteria had already been demonstrated. In an individual case MAC infections could not be distinguished either clinically or morphologically from infections with M. tbc, but only by culture.

Since 1983 the morbidity and mortality rates as well as results of haematological, immunological and (later) HIV serological tests were recorded prospectively for 497 HIV-positive patients during 1837 clinic visits at least twice within at most six months for a median period of observation of 18 months (range 6-64 months). The rate of progression to a higher stage was calculated according to the method of Kaplan-Meier. The rate for asymptomatic patients was 16% after one and 33% after two years; for patients with persisting generalized lymphadenopathy it was 13% and 21%, respectively, for those with AIDS-related complex 28% and 47%, respectively, and for those with AIDS 33% and 82%, respectively. As for results of laboratory tests, patients with progressive disease had significantly lower titres of anti-HIV nuclear antibodies, as well as a higher incidence of HIV-p24 antigen. Haemoglobin levels, platelet and lymphocyte counts and number of CD-4-positive lymphocytes were significantly lower, Neopterin and beta 2-microglobulins higher (P less than 0.01).

Ceftazidime, a new cephalosporin, is characterized by very good in-vitro action against P. aeruginosa. Nonetheless, clinical and (or) microbiological failure occurred in four patients with severe P. aeruginosa infections being treated with ceftazidime. Main cause infections being treated with ceftazidime. Main cause of the discrepancy between in-vitro and in-vivo results during treatment of three patients was a rapid drop in bacterial sensitivity. Superinfection with resistant microorganisms was excluded by the identity of the isolated bacteria in the different epidemiological markers before and during treatment. This rise in resistance was also demonstrated in-vitro by culturing clinically isolated material in ceftazidime-containing media: a 16-fold decrease in sensitivity was demonstrated within three subcultures. Increased beta-lactamase activity of the resistant strains makes it likely that enzymatic inactivation was part of the resistance mechanism. Good inducibility of beta-lactamases and absent resistance transfer argue for chromosomal localisation of the resistance. Because of the development of resistance, severe infections caused by P. aeruginosa should not be treated by ceftazidime alone. In order early to discover the development of resistance, microbiological samples should be taken periodically and examined for their sensitivity.

The effectiveness of antibiotic prophylaxis against endocarditis was assessed by testing the bactericidal and bacteriostatic action in serum of 12 healthy volunteers who had taken the recommended antibiotics according to laid down guidelines. Blood was obtained from these subjects every two hours for 12 hours after oral intake of amoxicillin (3 g as a single dose), clindamycin (600 mg a single dose) or erythromycin (1.5 g plus another 0.5 g after six hours), the serum being tested against three Strep. viridans strains. Two of the three strains were "tolerant", i.e. in relation to the minimal inhibition concentration (MIC) their growth was inhibited, but--in relation to the minimal bactericidal concentration (MBC)--they were not killed. A bacteriostatic effect by amoxicillin and clindamycin was demonstrated by a micromethod against all three strains during the 12-hour period. But erythromycin did not achieve bacteriostasis in all serum samples. A bactericidal effect was demonstrated only in those samples that contained amoxicillin, and then only against the non-tolerant of the three strains. These results support the view that amoxicillin and clindamycin are effective in the prophylaxis against Strep. viridans bacteraemia because of their constant bacteriostatic effect, as measured in serum.

A pneumothorax occurred in a 29-year-old HIV-positive woman with rapidly progressive dyspnoea at rest and left-thoracic pain, dry cough and fever. Sputum test revealed Pneumocystis carinii pneumonia. Treatment was started with 20 mg/kg trimethoprim and 100 mg/kg sulfamethoxazole, but was poorly tolerated and changed for pentamidine, 4 mg/kg i.v. from the fifth day onwards. A chest drain was inserted, but pleurodesis became necessary after two further lung collapses. After three weeks secondary prophylaxis of the Pn. carinii pneumonia was started with pentamidine inhalations (60 mg every two weeks). The patient gradually improved under this regimen. Pneumothorax is a rare complication of Pn. carinii pneumonia, but should be considered in patients with rapid respiratory deterioration. In addition, Pn. carinii pneumonia should be considered in HIV-positive patients with pneumothorax.

Four methods were used to assess gentamicin concentrations in 37 sera of patients treated with gentamicin. It was shown that the bioassay (agar diffusion) and the enzyme immunoassay correlated well, and the latex agglutination inhibition test badly, with the radioenzyme assay which was used as the reference method. Among presently available methods only the bioassay can be performed with relatively little equipment.