Christer Lidman

Longer survival after HIV infection for injecting drug users than for homosexual men: implications for immunology.

Background: Comparisons of progression in HIV‐1 infection between injecting drug users (IDU) and homosexual men have been inconclusive due to short follow‐up periods, often with less well‐defined starting points and endpoints. In addition, comparisons of survival after infection have been to some extent obscured by higher non‐AIDS mortality in IDU. Methods: In a retrospective cohort study, homo‐/bisexual men and IDU were followed, with dates of seroconversion defined within ± 1 year by a previously negative HIV antibody test. Endpoints were CD4 cell count below 200 × 106/l, AIDS, and death from AIDS. Results: Sixty‐three homo‐/bisexual men and 125 IDU fulfilled the entry criteria, with no significant differences in age at or date for seroconversion. Mean follow‐up times were 6.7 and 7.0 years, respectively. The homo‐/bisexual group had a significantly accelerated progression rate to all three endpoints: time to CD4 cell count below 200 × 106/l (P= 0.002), to AIDS (P = 0.0003), and to death from AIDS (P < 0.0001). Adjusting for age and sex only made marginal alterations. Ten years after infection, 54% of homosexual men had developed an AIDS‐defining condition and 51% had died from AIDS, whereas the corresponding percentages in the IDU group were 26 and 15%, respectively. There was, however, no difference in overall mortality due to an almost constant, non HIV‐related, yearly mortality of some 4% in IDU. Conclusions: In our cohort there was a highly significant difference in disease progression and death from AIDS between homo‐/bisexual men and IDU. This difference was proposed to be due to the transmission route determining the initial immune response and suggested that this route may have played a more important role than virus variability on the subsequent prognosis.

Swedish guidelines on the management of community-acquired pneumonia in immunocompetent adults-Swedish Society of Infectious Diseases 2012

Abstract This document presents the 2012 evidence based guidelines of the Swedish Society of Infectious Diseases for the in- hospital management of adult immunocompetent patients with community-acquired pneumonia (CAP). The prognostic score ‘CRB-65’ is recommended for the initial assessment of all CAP patients, and should be regarded as an aid for decision-making concerning the level of care required, microbiological investigation, and antibiotic treatment. Due to the favourable antibiotic resistance situation in Sweden, an initial narrow-spectrum antibiotic treatment primarily directed at Streptococcus pneumoniae is recommended in most situations. The recommended treatment for patients with severe CAP (CRB-65 score 2) is penicillin G in most situations. In critically ill patients (CRB-65 score 3–4), combination therapy with cefotaxime/macrolide or penicillin G/fluoroquinolone is recommended. A thorough microbiological investigation should be undertaken in all patients, including blood cultures, respiratory tract sampling, and urine antigens, with the addition of extensive sampling for more uncommon respiratory pathogens in the case of severe disease. Recommended measures for the prevention of CAP include vaccination for influenza and pneumococci, as well as smoking cessation.

Limited Value of Routine Microbiological Diagnostics in Patients Hospitalized for Community-acquired Pneumonia

Current guidelines recommend microbiological diagnostic procedures as a part of the management of patients hospitalized for community-acquired pneumonia (CAP), but the value of such efforts has been questioned. Patients hospitalized for CAP were studied retrospectively, focusing on the use of aetiological diagnostic methods and their clinical impact. Adult patients, without known human immunodeficiency virus infection, admitted to hospital for CAP during 12 months, were evaluated with regard to the importance of aetiological diagnosis for tailoring antibiotic therapy, antibiotic-associated diarrhoea, Clostridium difficile disease, length of hospital stay and mortality. Of the 605 studied patients, 482 (80%) were subjected to Mycoplasma pneumoniae and/or respiratory virus serology and/or cultures of blood and/or sputum. They had a better prognosis than patients not subjected to microbiological diagnostics (mortality within 3 months was 9% vs 24%, p = 0.001), apparently reflecting differences in general health (e.g. less dementia diagnosis) but not the outcome of diagnostics. A presumptive aetiology was obtained only in 132 of the 482 patients, Streptococcus pneumoniae and M. pneumoniae being the most common agents (in 49 and 36 patients, respectively). Establishing an aetiological diagnosis had no impact on the number of in-hospital changes of therapy, on the proportion of new regimens having a narrower antimicrobial spectrum than the initial one or on the outcome. Therapy was changed to a drug directed specifically against the identified pathogen in only 16 out of these 132 patients and again without any overall improvement in the outcome variables. In a setting with a low frequency of antibiotic-resistant respiratory tract pathogens current routine microbiological diagnostics were found to be of limited value for the clinical management of patients hospitalized for CAP. Improved diagnostics in CAP are urgently needed, as establishing an aetiological diagnosis carries a potential for optimizing the antibiotic therapy.

Hepatitis C infection among injection drug users in Stockholm Sweden: Prevalence and gender

Hepatitis C virus (HCV) infection is widespread among injection drug users. Young women seem to be at higher risk of acquiring HCV. To optimize future intervention and prevention measures, we studied the epidemiology of human immunodeficiency virus (HIV), hepatitis B (HBV), and HCV infection among men and women. Inclusion criteria for this cross-sectional multicentre study were: history of ever injecting drugs, age > 18 y, and no previous HIV diagnosis. In 310 participants, plasma/serum samples were analysed for HBV, HIV and HCV (anti-HCV, HCV-RNA, and HCV genotype). HCV antibodies were noted in 268 (86.5%) participants, of whom 207 (77.0%) also had detectable HCV-RNA. Genotypes 1 and 3 dominated, at 35.9% and 33.0%, respectively. Women acquired HCV (but not HBV) to a significantly higher degree (RR 2.97, 95% confidence interval 1.11–7.93) during the first y of injecting drugs. They also recovered spontaneously from HCV infection more frequently (RR 2.49, 95% CI 1.28–4.53). The HCV prevalence of about 50% within 2 y after initiation of injection drug use underlines the need for early intervention efforts. Possible causes for higher HCV prevalence and the implications of favourable spontaneous recovery rates among women should be considered when designing intervention and prevention measures.

No Evidence of Nosocomial Pneumocystis carinii Infection via Health Care Personnel

Clusters of Pneumocystis carinii pneumonia (PCP) in immunocompromised settings suggest person-to-person transmission. We examined whether personnel in a ward for HIV-infected patients were carriers of P. carinii. None of 29 sputum samples from 19 personnel caring for HIV-infected patients had detectable amounts of P. carinii DNA, as determined by the two PCR methods used. Two of 26 personnel were found, by an immunofluorescence assay, to have serum antibodies for P. carinii. The results do not support the hypothesis that personnel represent major vectors or transient reservoirs for spreading P. carinii infection to immunocompromised hosts.

Knowledge of status and assessment of personal health consequences with hepatitis C are not enough to change risk behaviour among injecting drug users in Stockholm County, Sweden.

This was a multicentre study with risk perception as the theoretical framework, investigating if risk behaviours change when injecting drug users (IDUs) are aware of their hepatitis C virus (HCV) status and had assessed the health consequences with HCV infection. Two hundred and thirteen participants aged 15–40 y were analysed. Sharing of needles and of other injecting equipment were common both among participants who reported HCV-positive status (74%, 95% confidence interval (CI) 65.3–80.1%) and among those who reported HCV status unknown (68%, 95% CI 56.0–78.4%). Participants associating very severe health consequences with HCV infection and those who did not know of any health consequences with HCV infection shared needles at almost the same rate (78%, 95% CI 62.5–87.7 vs 69%, 95% CI 8.0–78.9, respectively). Sharing of other injecting equipment was most common among participants with verified HCV-positive status (adjusted risk ratio 5.64, 95% CI 2.64–12.07). Knowledge of HCV status and assessment of health consequences with HCV infection were not enough to change injecting risk behaviours. Sharing of other injecting equipment was a more important risk factor than sharing needles for participants with verified HCV-positive status. It is suggested that professionals engage IDUs in risk analysis and open a dialogue about assessment in order to identify, quantify and characterize risks.

Pneumocystis carinii Pneumonia in Stockholm, Sweden: Treatment, Outcome, One-Year-Follow-up and Pyrimethamine Prophylaxis

In 33 consecutive AIDS patients with a first episode of Pneumocystis carinii pneumonia (PCP) we evaluated treatment, outcome, recurrence rate and pyrimethamine as chemoprophylaxis in a 1-year follow-up. Only 2 patients had a CD4 lymphocyte cell count greater than 0.2 X 10(9)/l. Trimethoprim-sulfamethoxazole (TMP-SMX) was initially given to 32 patients but in 20 of these patients severe adverse reactions caused us to discontinue treatment. Of these 20 patients 11 were started on i.v./i.m. pentamidine but in 6 adverse reactions forced us to withdraw pentamidine. Patients were retrospectively divided with regard to duration of therapy into 2 groups. We could not find any difference between patients in Group 1 treated for less than or equal to 14 days and patients in Group 2 treated for greater than 14 days when comparing outcome, number of recurrences and mean time until recurrence. In 16/21 patients given only TMP-SMX initially in a high dose (means = 16 mg trimethoprim/kg/day), dose reduction was performed to means = 10.5 mg trimethoprim/kg/day after a mean time of 6.9 days. The case-fatality rate for these patients was 10% (2/21) and the overall case-fatality rate was 15% (5/33). We chose pyrimethamine (50-175 mg/week) as secondary prophylaxis for PCP. At 1-year follow-up another 16 patients had died (21/32) and 9/27 (33%) discharged patients had had one recurrence each of PCP. All recurrences occurred among patients treated with only TMP-SMX for the acute episode of PCP. Of these 27 discharged patients 23 had been given pyrimethamine and 8 (36%) of these had experienced a recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4+ Cells and CD4 + Percent as Risk Markers for Pneumocystis carinii Pneumonia (PCP): Implications for Primary PCP Prophylaxis

The incidence of Pneumocystis carinii pneumonia (PCP) during 2 years in HIV-infected patients with less than or equal to 100 x 10(6)/l CD4+ cells, less than or equal to 200 x 10(6)/l CD4+ cells and less than 20% CD4+ cells of total T lymphocytes were compared. The relative PCP risk in 57 patients with less than or equal to 100 CD4+ cells was more than twice higher than in 120 patients with less than or equal to 200 CD4+ cells. The latter had almost twice higher relative PCP risk than 271 patients with less than or equal to 20% CD4+ cells. Only 3/56 patients who acquired PCP had greater than 200 CD4+ cells and 15/56 patients had greater than 100 CD4+ cells. Centers for Disease Control (CDC) recommends primary PCP prophylaxis in HIV-infected patients when the number of CD4+ cells is less than 200 x 10(6)/l or when the CD4+ is less than 20. On the basis of the presented data we suggest that primary prophylaxis is considered only when CD4+ cells fall below 200 x 10(6)/l.

Aerosolized pentamidine as primary prophylaxis for Pneumocystis carinii pneumonia: efficacy, mortality and morbidity.

Objective:Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with HIV infection has been recommended by the Centers for Disease Control and Prevention. We evaluated alternatives to routine primary PCP prophylaxis with aerosolized pentamidine.Methods:A total of 121 HIV-infected patients with CD4+ cell counts ≤ 200 × 106/l or an AIDS diagnosis were enrolled in a controlled study of aerosolized pentamidine as primary PCP prophylaxis. Patients were randomly assigned to treatment (n = 61) with aerosolized pentamidine once every month or to no treatment (n = 60). Patients were evaluated for PCP, mortality, morbidity and progression of HIV disease. Morbidity was estimated from the number of days patients were unable to work due to illness, number of days hospitalized and AIDS events.Results:Baseline characteristics were similar in the treatment and control groups and mean CD4+ cell counts were 116 and 107 × 106/l, respectively. Eight incidents of PCP and 19 deaths were observed in the treatment group during a median follow-up of 16.4 months (range, 2.3–32.4 months). Nineteen incidents of PCP and 13 deaths, of which one was related to an acute episode of PCP, were noted in the control group. Median follow-up of controls was 18.5 months (range, 3.1–32.9 months). Patients in the treatment group were unable to work 19% of the observation time and were hospitalized for 4.3% of that time. Corresponding figures were 20 and 3.0%, respectively, in the control group.Conclusions:Aerosolized pentamidine had significant prophylactic efficacy, but we could not detect any major effect on mortality and morbidity. The overall mortality and morbidity were not markedly influenced by PCP. Clinical check-ups and treatment of acute PCP could be a justifiable alternative to drug prophylaxis with aerosolized pentamidine in selected patients.

Fiberoptic bronchoscopy and sputum examination for diagnosis of pulmonary disease in AIDS patients in Stockholm.

For diagnosing pulmonary disease on 82 occasions in 68 patients (64 males) aged 39 (23-73) years infected with HIV-1 we used flexible fiberoptic bronchoscopy (FFB) with bronchoalveolar lavage (BAL) or washing with or without transbronchial lung biopsy (TBB) and brushing. A clinical diagnosis of lower respiratory tract disease was obtained in 68/82 episodes (83%). An etiological diagnosis was reached by FFB in 59/82 episodes (72%). Pneumocystis carinii (PC), the dominating pathogen causing pneumonia in 54/82 episodes (66%), was detected by FFB in 51/54 (94%). In spite of being isolated in bronchoscopy material in 36/82 episodes (44%) cytomegalovirus (CMV) seemed to be the cause of pneumonia only in 2/36 (5%) episodes. Except PC and CMV, only bacteria (including mycobacteria) were found as infectious etiological agents. Kaposis sarcoma and pulmonary edema were diagnosed in one patient each. For detection of PC in 37 episodes we compared staining of BAL fluid with indirect immunofluorescence (IF) using monoclonal antibodies (MoAB) with staining of BAL material by silver methenamine (Grocott). Staining with IF MoAB alone of BAL fluid only seemed to be even more sensitive than silver methenamine staining of BAL, TBB and brushing material. When using IF MoAB staining of BAL fluid, TBB and brushing added nothing to the result, except in the patient with Kaposis sarcoma, diagnosed by TBB. Sputum investigation using IF MoAB for detection was increasingly adopted during the study time. It was very useful (sensitivity approximately 74%) and reduced the number of required FFBs.