Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected ...individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1, HIV-2 or dually HIV-1/HIV-2 infected individuals. In this study the gene encoding Interferon alpha-inducible protein 27 (IFI27) was found to be the most differentially expressed. Detailed expression analysis revealed significantly higher IFI27 expression in HIV infected individuals compared with seronegative individuals, irrespectively of HIV type. Moreover, IFI27 expression was higher in HIV-1 than in HIV-2 infected individuals. Multiple linear regression analysis, adjusting for age and sex, showed also that plasma viral load was the strongest predictor of IFI27 expression, followed by CD4% and HIV type. In line with this, IFI27 expression was found to be higher in HIV-2 viremic, compared with HIV-2 aviremic individuals. Still, HIV-2 aviremic individuals displayed elevated IFI27 expression compared with seronegative individuals. Furthermore, in HIV-2 infected individuals, IFI27 expression was also correlated with plasma markers previously linked to inflammation and disease progression in HIV infection. Taken together, our findings suggest that sustained elevation of type I interferon signaling, here reflected by elevated IFI27 expression in the chronic infection phase, is a key pathogenic feature of both HIV-1 and HIV-2.
Background: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) can cause endogenously derived infections and be a source of transmission to other people. Neither colonization time ...of asymptomatic MRSA colonization nor the effect of treatment aiming at MRSA eradication in children has been thoroughly investigated.
Methods: Two hundred ninety-three children <18 years in the mandatory follow-up program for MRSA-carriers in Malmö, Sweden were evaluated. Samples from the throat, nares, perineum and skin lesions from each child were screened for MRSA with a PCR-based broth enrichment method. PVL presence and spa-type were evaluated in a majority of cases. The sampling was repeated approximately every 6 month after initial detection. When three consecutive sets of negative samples during at least a 6-month period were obtained, the MRSA was considered permanently eradicated. MRSA eradication treatment given, on clinical grounds during follow-up, was noted.
Results: One year after detection 62% of the untreated children were still MRSA positive and after 2 years 28%. MRSA throat colonization and having MRSA positive household contacts significantly prolonged the observed colonization time. Topical MRSA eradication treatment was successful in 36% of cases and in 65% if systemic antibiotics were added. Presence of PVL correlated with shorter observed colonization time in the older age group and with increased eradication success among throat carriers.
Conclusion: MRSA throat colonization and having MRSA positive household contacts prolongs the time of MRSA colonization in children. Systemic antibiotics enhance the effect of MRSA eradication treatment.
An audit-based antimicrobial stewardship program profoundly reduced and altered antibtiotic use in a setting with low antimicrobial resistance with no negative effect on patient outcome
Background.
...Antimicrobial stewardship programs are increasingly implemented in hospital care. They aim to simultaneously optimize outcomes for individual patients with infections and reduce financial and health-associated costs of overuse of antibiotics. Few studies have examined the effects of antimicrobial stewardship programs in settings with low proportions of antimicrobial resistance, such as in Sweden.
Methods.
An antimicrobial stewardship program was introduced during 5 months of 2013 in a department of internal medicine in southern Sweden. The intervention consisted of audits twice weekly on all patients given antibiotic treatment. The intervention period was compared with a historical control consisting of patients treated with antibiotics in the same wards in 2012. Studied outcome variables included 28-day mortality and readmission, length of hospital stay, and use of antibiotics.
Results.
A reduction of 27% in total antibiotic use (2387 days of any antibiotic) was observed in the intervention period compared with the control period. The reduction was due to fewer patients started on antibiotics as well as to significantly shorter durations of antibiotic courses (P < .001). An earlier switch to oral therapy and a specific reduction in use of third-generation cephalosporins and fluoroquinolones was also evident. Mortality, total readmissions, and lengths of stay in hospital were unchanged compared with the control period, whereas readmissions due to a nonresolved infection were fewer during the intervention of 2013.
Conclusions.
This study demonstrates that an infectious disease specialist-guided antimicrobial stewardship program can profoundly reduce antibiotic use in a low-resistance setting with no negative effect on patient outcome.
Abstract Background and Aims The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have ...an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge. Method This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023). Results 97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection. Conclusion While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.
Plasmodium falciparum transmission has decreased significantly in Zambia in the last decade. The malaria transmission is influenced by environmental variables. Incorporation of environmental ...variables in models of malaria transmission likely improves model fit and predicts probable trends in malaria disease. This work is based on the hypothesis that remotely-sensed environmental factors, including nocturnal dew point, are associated with malaria transmission and sustain foci of transmission during the low transmission season in the Southern Province of Zambia.
Thirty-eight rural health centres in Southern Province, Zambia were divided into three zones based on transmission patterns. Correlations between weekly malaria cases and remotely-sensed nocturnal dew point, nocturnal land surface temperature as well as vegetation indices and rainfall were evaluated in time-series analyses from 2012 week 19 to 2013 week 36. Zonal as well as clinic-based, multivariate, autoregressive, integrated, moving average (ARIMAX) models implementing environmental variables were developed to model transmission in 2011 week 19 to 2012 week 18 and forecast transmission in 2013 week 37 to week 41.
During the dry, low transmission season significantly higher vegetation indices, nocturnal land surface temperature and nocturnal dew point were associated with the areas of higher transmission. Environmental variables improved ARIMAX models. Dew point and normalized differentiated vegetation index were significant predictors and improved all zonal transmission models. In the high-transmission zone, this was also seen for land surface temperature. Clinic models were improved by adding dew point and land surface temperature as well as normalized differentiated vegetation index. The mean average error of prediction for ARIMAX models ranged from 0.7 to 33.5%. Forecasts of malaria incidence were valid for three out of five rural health centres; however, with poor results at the zonal level.
In this study, the fit of ARIMAX models improves when environmental variables are included. There is a significant association of remotely-sensed nocturnal dew point with malaria transmission. Interestingly, dew point might be one of the factors sustaining malaria transmission in areas of general aridity during the dry season.
PurposeThe Swedish InfCareHIV cohort was established in 2003 to ensure equal and effective care of people living with HIV (PLHIV) and enable long-term follow-up. InfCareHIV functions equally as a ...decision support system as a quality registry, ensuring up-to-date data reported in real time.ParticipantsInfCareHIV includes data on >99% of all people with diagnosed HIV in Sweden and up to now 13 029 have been included in the cohort. InfCareHIV includes data on HIV-related biomarkers and antiretroviral therapies (ART) and also on demographics, patient-reported outcome measures and patient-reported experience measures.Findings to dateSweden was in 2015 the first country to reach the UNAIDS (United Nations Programme on HIV/AIDS)/WHO’s 90-90-90 goals. Late diagnosis of HIV infection was identified as a key problem in the Swedish HIV-epidemic, and low-level HIV viraemia while on ART associated with all-cause mortality. Increased HIV RNA load in the cerebrospinal fluid (CSF) despite suppression of the plasma viral load was found in 5% of PLHIV, a phenomenon referred to as ‘CSF viral escape’. Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. An increase of transmitted drug resistance was observed in the InfCareHIV cohort. Lower efficacy for protease inhibitors was not due to lower adherence to treatment. Incidence of type 2 diabetes and insulin resistance was high in the ageing HIV population. Despite ART, the risk of infection-related cancer as well as lung cancer was increased in PLHIV compared with HIV-negative. PLHIV were less likely successfully treated for cervical precancer and more likely to have human papillomavirus types not included in current HPV vaccines. Self-reported sexual satisfaction in PLHIV is improving and is higher in women than men.Future plansInfCareHIV provides a unique base to study and further improve long-term treatment outcomes, comorbidity management and health-related quality of life in people with HIV in Sweden.
We analyzed prevalence rates of syphilis (positive Treponema pallidum hemagglutinin antigen/T. pallidum particle antigen and venereal disease research laboratory test) among police officers in ...Guinea-Bissau from 1990 to 2010 and found a significant decline from 4.5% to 0.4% (P = 0.0065). Our results are in line with other recent reports from West Africa. More research is needed to identify the reasons for this decline.
Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only ...approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood.
We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution.
The median time to AIDS was 104 months (95% confidence interval CI, 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection.
Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).
HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we ...aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DR
), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1
, TIGIT
) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.
The impact of pre-antiretroviral treatment (ART) HIV-RNA on time to successful virological suppression and subsequent failure in HIV patients remains poorly investigated.
We used the Swedish ...InfCareHIV database and the Danish HIV Cohort Study to evaluate impact of pre-ART HIV-RNA on primary virological suppression (HIV-RNA < 50 copies/ml) and risk of secondary virological failure (two consecutive HIV-RNA > 200 copies/ml or one >1000 copies/ml). The study included 3366 Swedish and 2050 Danish ART naïve individuals who initiated ART in the period 2000-2018. We used Kaplan-Meier estimates and Cox regression analyses to estimate absolute risks and hazard ratios.
In both cohorts, more than 95% of patients with a pre-ART HIV-RNA <100 000 copies/ml obtained virological suppression within the first year after ART initiation contrasting 74% (Sweden) and 86% (Denmark) in those with HIV-RNA >1 000 000 copies/ml. Almost all patients obtained virological suppression after four years irrespective of pre-ART HIV-RNA. In contrast, we observed no substantial impact of pre-ART HIV-RNA on risk of virological failure once virological suppression was obtained.
High pre-ART HIV-RNA is strongly associated with increased time to successful virological suppression, but pre-ART HIV-RNA has no impact on risk of subsequent virological failure.
PDF
