Beta 2-microglobulin levels in drug users: the influence of risk behaviour.

beta 2-microglobulin (beta 2M) levels were measured in 217 Edinburgh drug users to assess their usefulness as a marker for HIV-related disease. Eighty HIV-seronegative drug injectors had significantly higher levels than 100 HIV-seronegative blood-donor controls. Amongst 137 asymptomatic HIV-seropositive drug users, those who were defined as continued drug users had significantly higher beta 2M levels and percentages of CD3+ T lymphocytes with DR Class II expression than non-injecting drug users. beta 2M levels correlated with the percentage of activated DR+ CD3+ T lymphocytes. These findings indicate that changes in beta 2M levels may reflect differences in drug-injecting behaviour and are not influenced solely by HIV status or progression. These changes in beta 2M probably represent differing degrees of immunostimulation resulting from the antigenic challenges afforded by continued or frequent drug injection. It is important to establish normal ranges for beta 2M from HIV-seronegative controls who are matched with respect to risk group and behaviour. All these factors should be taken into account if beta 2M is to be used as a marker of HIV progression.

Disseminated disease due to Mycobacterium avium complex in AIDS.

We retrospectively analysed 46 cases of disseminated infection with Mycobacterium avium complex (MAC) within a cohort of 702 HIV-infected patients in Edinburgh. Clinical features were compared with case-matched controls (AIDS cases without disseminated MAC), and survival and progression times were controlled for confounding variables that influence survival. Disseminated MAC was diagnosed antemortem in 18% of AIDS patients, and was the AIDS-defining diagnosis in 6% of all AIDS cases. Concomitant colonization of respiratory and gastrointestinal tracts was common (61% and 48%, respectively). In 58% of cases, CD4+ counts were < 10 cells/mm3 (median 6 cells/mm3). Weight loss, anaemia, leucopenia, and elevated liver transaminases and alkaline phosphatase were significantly more common among cases than controls. Therapy was given in 74%, and not tolerated in 32%. Following AIDS diagnosis, disseminated MAC incidence was 14% at one year, 25% at 2 years and 36% at 3 years. Median survival after disseminated MAC diagnosis was 6 months, with shorter survival in untreated cases. However, overall survival from AIDS diagnosis was not significantly different between patients who did or did not develop disseminated MAC. Disseminated MAC contributes significantly to AIDS morbidity, and its incidence increases with prolonged AIDS survival. Although survival following diagnosis is short, the development of disseminated MAC in AIDS probably does not affect overall survival. In cohorts with a low incidence, an alternative to prophylaxis might be surveillance and early diagnosis.

The impact of chronic hepatitis C virus infection on HIV disease and progression in intravenous drug users.

OBJECTIVE: It is unclear whether co-infection with hepatitis C virus (HCV) can influence HIV related morbidity or mortality, either by accelerating HIV-related disease progression, or by contributing to end stage liver disease. The aim of this study was to examine the effect of HCV infection on the severity and progression of HIV disease in a cohort of Edinburgh intravenous drug users (IDUs). METHODS: In 240 (47%) out of 508 patients in the Edinburgh IDU cohort both HIV seroconversion dates and anti-HCV serology were available. Demographic variables and HIV-related progression between anti-HCV positive and anti-HCV negative groups were compared. Parameters assessed included clinical endpoints (time of development of significant symptoms attributable to HIV (CDC stage IV), time of development of AIDS, and time of death) and immunological endpoints (time of CD4+ counts dropping below 200/mm3, 100/mm3 and 50/mm3). RESULTS: Two hundred and two out of 240 patients (84%) had positive anti-HCV serology. There was no significant difference in the frequency of clinical and immunological endpoints between the anti-HCV positive and negative groups. Progression analysis from HIV seroconversion to HIV related clinical endpoints indicated that anti-HCV serology was not a significant factor influencing the rate of HIV progression (relative risks (RR) for anti-HCV positive group: seroconversion to CDC IV, 1.01; seroconversion to AIDS, 1.05; seroconversion to death, 0.90). Likewise, HCV serostatus did not significantly affect progression to immunological endpoints (RR for anti-HCV positive group: seroconversion to CD4+ < 200/mm3, 1.04; seroconversion to CD4+ < 100/mm3, 1.13; seroconversion to CD4+ < 50/mm3, 0.97. Overall mortality from end stage liver failure was 4% in HCV-seropositive patients without AIDS. This suggests that HCV has had a clinically (though not statistically) significant impact on overall survival in this cohort. CONCLUSIONS: This study demonstrates that HCV co-infection does not influence the rate of progression to either clinical or immunological endpoints in our population of HIV-infected drug users. Further data are required to assess the effect of HIV on thge progression of HCV-related liver disease.

Citrobacter freundii bacteraemia presenting as typhoid fever.

Citrobacter infections usually arise opportunistically in immunocompromised persons. We report the case of a young man in whom Citrobacter freundii caused a primary invasive illness similar to typhoid fever.

AIDS in Edinburgh drug users: observations on the epidemic and implications for its future management.

We are now witnessing the anticipated explosion of cases of AIDS resulting from the epidemic of HIV infection among Edinburgh drug users in the first half of the last decade. We expect the number of new cases of AIDS to continue to increase, although the rate at which they do so may be mitigated by intervention which slows the rate of progression to AIDS. There is evidence that current management of patients may postpone a diagnosis of AIDS until later in the natural history of HIV infection when immunity is very low as manifested by CD4+ lymphocyte counts. Health care planners need to provide resources for an increasing number of HIV-infected persons who have not yet fulfilled the definition of AIDS but who nevertheless require extensive resources both in the community and in hospital.

Seven years experience of acute hepatitis B in a regional department of infectious diseases and tropical medicine.

A total of 280 cases of acute hepatitis B arising between 1979 and 1985 were retrospectively reviewed. Following an increase in the number of cases in 1983 and 1984, the incidence declined sharply in 1985. The main risk for infection was intravenous drug misuse (51.1%). Only one patient died from fulminant hepatitis. After leaving hospital, 110 patients were kept under surveillance. None suffered from chronic liver disease and none became a carrier of hepatitis B virus.

The spectrum of chest infections in HIV positive patients in Edinburgh.

In a retrospective analysis of all known HIV-positive patients admitted to the City Hospital before November 1989, 208 patients accounted for 612 admissions, 72% being injection drug users (IDUs). One hundred and eighty admissions (29%) were for chest-related disorders, and this was the commonest reason for admission. Unlike other U.K. centres where more than 50% chest problems are due to Pneumocystis carinii pneumonia (PCP), only 27% of our chest admissions were for PCP. Fifty-four percent of chest admissions were for bacterial chest infections (BCIs), the commonest organism isolated being Haemophilus influenzae. Despite the fact that most (50/97) of these admissions were in patients with 'asymptomatic' HIV disease (CDC classification 2 and 3), 50% had radiological pneumonia, 43% were hypoxic, 28% were hypercapnic and the average duration of hospitalisation was 10 days. BCIs were more common in HIV-positive IDUs when compared with HIV-negative IDUs, other HIV-positive patients and the general age-matched population. Medical provision for IDU-related HIV disease should take into account the high rate of BCIs and of hospital admissions in patients who do not yet have CDC stage 4 disease.

Use of zidovudine for drug misusers infected with human immunodeficiency virus.

The use of zidovudine in drug misusers, especially current drug misusers, has not been extensively studied. Since periods of abstinence may be interspersed with drug misuse, it is necessary to establish the safety of zidovudine in injection drug misuse-related human immunodeficiency virus (HIV) infection under a variety of conditions. HIV serology became available in October 1985 and we have now examined medically 289 HIV seropositive patients, 85% of whom acquired their infection via injection drug misuse. Since March 1987 we have treated 40 individuals with zidovudine, 25 of whom were former or current injection drug misusers and one who was a heterosexual contact of a drug misuser. Eighteen patients were taking various types of opiates. Six of this latter group injected either occasionally or regularly whilst taking zidovudine. There were no adverse clinical events associated with zidovudine treatment and continued opiate drug misuse whether by mouth or by injection. Although defaults from clinic visits were a problem, these defaults were not associated with any particular form of drug misuse. Compliance with zidovudine therapy as judged by change in the mean corpuscular volume was no different for the various risk groups. In our experience it is possible to treat safely current and former drug misusers with zidovudine.

Potential risks of ultraviolet radiation in HIV infection.

The hazards of ultraviolet radiation (UVR) include immunosuppression, activation of human immunodeficiency virus (HIV) type 1 expression, and photocarcinogenesis particularly in immunosuppressed individuals. Fifty-eight male homosexuals positive for HIV antibody and 61 controls not at risk for HIV infection answered a questionnaire on their attitudes and exposure to natural and artificial sources of UVR. Controls were matched for sex but were not from an at-risk group for HIV infection. Mean ages were similar for both groups. HIV seropositives had greater recreational UVR exposure than controls: 12/58 versus 4/61 had regular use of a sunbed (P less than 0.05), and experienced 11.6 weeks versus 9.5 weeks of prolonged natural UVR exposure (P = 0.056) over a four-year period. One reason for this difference may be the misconception present in two-thirds of the HIV seropositive group that a suntan would improve their health and the outcome of their HIV infection. Those with HIV infection must be made aware that there is a potential for further immunosuppression and viral activation from UVR and they should be advised to avoid undue recreational exposure.

Clinical features, outcome and survival from cerebral toxoplasmosis in Edinburgh AIDS patients.

Nineteen cases of cerebral toxoplasmosis (CTOX) are reported from a group of Edinburgh AIDS patients. All patients were severely immunodeficient at the time of presentation with CD4 count < 50 cells/mm3. Thirteen patients had suffered a previous AIDS-defining illness. In Edinburgh, CTOX has developed in 48% of patients who are seropositive for toxoplasma and have a CD4 count < 50 cells/mm3. It is estimated that at least half of the toxoplasma seropositive patients will develop CTOX if they survive for 21 months after reaching a time in their illness when the CD4 count = 50 cells/mm3. The incidence of CTOX in toxoplasma-seronegative patients with a CD4 count < 50 cells/mm3 is 1.3%. All patients showed improvement on treatment and there was no correlation between clinical or radiological features and patient survival. Those patients unable to tolerate first choice anti-toxoplasma therapy had a significantly shorter survival than the remainder but there was no single therapeutic regimen which conferred a survival advantage. Eighteen patients had died at the time of study and the median survival following diagnosis of cerebral toxoplasmosis was 10 months (range 3-38 months). Postmortem examination of the brain was available in 8, 4 of whom had concomitant cerebral lymphoma. The survival from AIDS or CD4 count = 50 cells/mm3 did not differ significantly between those with treated CTOX and a control group who had no toxoplasma infection, suggesting that treatment is reasonably effective. CTOX is a disease associated with severe HIV-related immunodeficiency and, in those with a CD4 count < 50 cells/mm3, occurs more than 35 times as frequently in toxoplasma-seropositive than toxoplasma-seronegative patients. Treatment is effective but the outcome of treated disease cannot be predicted from presenting clinical or radiological features. Concomitant space-occupying cerebral pathology is evident in 50% of post-mortem examinations.

Cytomegalovirus retinitis and AIDS in Edinburgh.

The medical records, retinal drawings and fundus photographs of all patients with cytomegalovirus retinitis (CMVR) and AIDS in Edinburgh between 1986-1992 were reviewed to determine the efficacy of treatment in preserving vision. Ophthalmoscopic features of CMVR were observed in 32 eyes of 24 patients with AIDS, 19 males and 5 females. HIV transmission in this group was by homo/bisexual contact (16), injection drug use (7) and blood transfusion (1). Unilateral blurring was the commonest visual symptom although 9 (38%) patients had no visual symptoms. All patients presented with a corrected visual acuity of 6/12 or better in at least one eye. Following treatment with systemic ganciclovir or foscarnet 16 patients (66%) developed toxic side-effects of therapy and 13 (54%) experienced a recurrence of CMVR. Four (17%) patients developed a retinal detachment in one eye. The mean survival was 8.3 months after the diagnosis of CMVR. At final follow-up, between 2-26 months after the diagnosis of CMVR, 21 (87.5%) patients retained useful vision (6/18 or better) although 3 (12.5%) were effectively blind (less than 6/60). We conclude that with prompt diagnosis and treatment of CMVR vision can be preserved in the majority of cases.

Cytomegalovirus disease in AIDS: the Edinburgh experience.

Retrospective analysis of medical records of 557 HIV positive patients (including 113 with AIDS) revealed 17 patients with an antemortem clinical diagnosis of cytomegalovirus (CMV) disease. This group comprised 7 injection drug users (2 male and 5 female) and 10 homosexual men. Males were significantly older than females, and homosexual men were significantly older than drug users at the time of diagnosis of CMV. All 17 patients had evidence of retinitis, and 6 also had evidence of extraocular disease. CMV retinitis was the AIDS defining diagnosis in two patients, and the attack rate of CMV in all AIDS patients progressively increased with time, with a 3-year CMV-free survival of 57%. Fifteen patients with CMV disease had evidence of previous CMV infection (CMV IgG positive), with 7 also having a positive CMV IgM and 10 a positive viral culture. The mean CD4+ lymphocyte count at diagnosis of CMV was 17 cells/mm3, compared with 68 cells/mm3 at diagnosis of AIDS. Therapy was unsatisfactory, often being complicated by marrow suppression. Relapse occurred in 11 patients after initial improvement but despite this only 3 patients died with severe visual impairment. The mean survival after a diagnosis of CMV was 10.5 months. This study confirms that disease caused by CMV is usually a late manifestation of AIDS, and the increasing prevalence among patients with AIDS implies that, the longer the survival, the greater the risk of disease. Frequent fundoscopy in HIV positive patients is of paramount importance particularly in patients who have a CD4+ lymphocyte count of less than 100 cells/mm3.

Antimicrobial treatment of fish tank granuloma.

Three patients with fish tank granuloma of the hand and forearm are reported. Each patient was treated with antimicrobial regimes which have rarely or never been previously used in this condition. Two patients responded well to treatment, one who received ciprofloxacin plus clarithromycin and another who was given clarithromycin plus ethambutol. The third patient received six different antimicrobial regimes before responding to a combination of rifabutin and ciprofloxacin. Our experience suggests that there now exist a number of effective alternatives to antimicrobials which have been traditionally used in the treatment of cutaneous Mycobacterium marinum infection.

Malaria immunization--a Zimbabwean perspective.

PIP: A great deal of activity is being focused on the possibility of developing an effective vaccine for malaria. Drug resistance is the main problem. Of the new drugs under examination, only meflaquine, a quinine analogue, is at the stage of a clinical trial and even here it appears that resistance may be a problem. This review summarizes the current state of research on malaria immunization and adds some Zimbabwean perspectives. Natural immunity to malaria is directed against the blood stages of the parasites and is mediated by both humoral and cellular mechanisms. Resistance to malaria in both humans and animals can be transferred by passive immunization using immunoglobin infusions. Evidence indicates that the spleen has a central role in resistance to malaria. Malarial infection is known to be associated with immunosuppression. Of considerable practical importance is the observation that antibody responses to irradiated sporozoites in rodents were suppressed by acute Plasmodium berghei infection. Immunity is species specific, develops slowly and is short lived. There are 3 stages in the malaria life cycle at which immunization might be expected to be effective: the sporozoite, merozoite and gametocyte stages. 95% of malaria in Zimbabwe is caused by Plasmodium falciparum. A major requirement for effective immunization is an antigen preparation, which, while causing no harmful effects in itself will stimulate an immune response capable of inactivating the infective agent in question. A significant breakthrough has been achieved by Ruth Nussensweig and her colleagues using the techniques of molecular biology. There is a wide variation in the body's response to injected malarial antigens. Repeated injection with irradiated sporozoites (which are incapable of multiplying in the body) are able to induce shortlived immunity in man. Funding problems also exist in developing a useful vaccine; much of the research is funded by the WHO.^ieng

The impact of new national HIV testing guidelines at a district general hospital in an area of high HIV seroprevalence.

The latest UK national human immunodeficiency virus (HIV) testing guidelines, released in September 2008, state that HIV testing should be offered to all patients with indicator conditions and considered in all general medical admissions in high-prevalence areas. We audited testing rates at Blackpool Victoria Hospital, a high-prevalence area, one year before and one year after the publication of the new guidelines. In the year after publication the rate of HIV testing in patients with indicator diseases was as follows: hepatitis B 6%, hepatitis C 28%, tuberculosis 9% and lymphoma 14%. The overall rate of HIV testing in acute medical admissions was 0.5%. Our results demonstrate that traditional methods of guideline dissemination did not lead to implementation. We are now assessing alternative methods such as marking all positive laboratory results for indicator diseases with the phrase 'HIV testing should be considered' and implementing universal opt-out screening in our Clinical Decisions Unit.