Background. As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)–infected children survive ...into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure. Methods. We included 59 HIV-infected AYAs from the Netherlands who had entered into pediatric care and transitioned from pediatric to adult healthcare. We used HIV RNA load and cART data from the Dutch Stichting HIV Monitoring database (1996–2014), and collected social and treatment data from patients' medical records from all Dutch pediatric HIV treatment centers and 14 Dutch adult treatment centers involved. We evaluated risk factors for virological failure (VF) in a logistic regression model adjusted for repeated measurements. Results. HIV VF occurred frequently during the study period (14%–36%). During the transition period (from 18 to 19 years of age) there was a significant increase in VF compared with the reference group of children aged 12–13 years (odds ratio, 4.26 95% confidence interval, 1.12–16.28; P = .03). Characteristics significantly associated with VF were low educational attainment and lack of autonomy regarding medication adherence at transition. Conclusions. HIV-infected AYAs are vulnerable to VF, especially during the transition period. Identification of HIV-infected adolescents at high risk for VF might help to improve treatment success in this group.
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BFBNIB, NUK, PNG, UL, UM, UPUK
HIV-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been ...comprehensively assessed.
Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection.
122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (interquartile range 0.6-2.7). HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count <200 cells/mm3, and recent CD4 cell count <500 cells/mm3.
Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM.
Objectives – Studies demonstrating reduced quality of life and psychological well‐being in multiple sclerosis (MS) have typically investigated patients within more advanced stages of disease. The aim ...of the present paper was to evaluate the emotional burden and quality of life of recently diagnosed MS patients and their partners.
Methods – Data on health‐related quality of life (SF‐36), anxiety and depression (Hospital Anxiety and Depression Scale) and disease‐related distress (Impact of Event Scale) were obtained in 101 patients and their partners (n = 78).
Results – On average 8 months after diagnosis (range 0–24 months), 34% of the patients and 40% of the partners had clinically high levels of anxiety, and 36% of the patients and 24% of the partners had levels of severe distress. Scores of anxiety, depression and distress were higher in patients with more functional limitations (Expanded Disability Status Scale = 3.0). Quality of life was significantly poorer in patients compared with controls, particularly among those with higher disability.
Conclusions – Both patients and their partners demonstrated high levels of anxiety and distress in the early period after the diagnosis. These findings indicate careful attention by health care professionals to identify those who may benefit from further psychological support.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
To determine which antecedent infections are specifically associated with the Guillain-Barré syndrome (GBS).
Infections with many agents have been reported preceding GBS. Some infections are related ...to specific clinical and immunologic subgroups in GBS. Most agents were reported in case reports and uncontrolled small series of GBS patients only, and their relation to GBS and its subgroups remains unclear.
A serologic study for 16 infectious agents in 154 GBS patients and 154 sex- and age-matched controls with other neurologic diseases. Acute phase, pretreatment samples were used from clinically well-defined GBS patients. The seasonal distribution of serum sampling in the GBS and control group was the same.
Multivariate analysis showed that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus (13%), and Epstein-Barr virus (10%) were significantly more frequent than in controls. Mycoplasma pneumoniae infections occurred more often in GBS patients (5%) than in controls in univariate analysis. Infections with Haemophilus influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster virus (1%) were also demonstrated in GBS patients, but not more frequently than in controls. C. jejuni infections were associated with antibodies to the gangliosides GM1 and GD1b and with a severe pure motor form of GBS. Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor sensory deficits. Other infections were not related to specific antiganglioside antibodies and neurologic patterns.
Recent infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae are specifically related to GBS. The variety of infections may contribute to the clinical and immunologic heterogeneity of GBS.
Background: Certain stem cell transplantation procedures might slow down inflammatory pathology in multiple sclerosis (MS). Aims: To halt disease progression in aggressive MS by a bone marrow ...transplantation (BMT) protocol aimed at maximum T cell suppression. Methods: Autologous BMT was performed in 14 patients with rapid secondary progressive MS (median EDSS score at baseline, 6; median disease duration, five years). To accomplish rigorous T cell ablation, a strong conditioning protocol was chosen—cyclophosphamide, total body irradiation, and antithymocyte globulin. To minimise the possibility of reinfusing mature T cells in the graft, bone marrow, not peripheral blood, was used as the CD34+ stem cell source. Results: Median follow up was 36 months (range, 7–36). Post-transplant haemopoietic recovery was successful in all patients. Early toxicity included Epstein-Barr virus related post-transplantation lymphoproliferative disorder. Longterm effects were development of antithyroid antibodies (three) and myelodysplastic syndrome (one). One patient died of progressive disease five years after transplantation. Treatment failure, defined by EDSS increase sustained for six months or more, was seen in nine patients and stabilisation or improvement in five. Other clinical parameters generally showed the same outcome. No gadolinium enhanced lesions were seen on post-treatment magnetic resonance imaging, in either cerebral or spinal cord scans. However, cerebrospinal fluid oligoclonal bands remained positive in most cases. Conclusions: This strong immunosuppressive regimen did not prevent clinical progression in patients with aggressive secondary MS. The lack of efficacy, together with some serious side effects, does not favour the use of similar rigorous T cell depleting protocols in the future.
In this investigation we study the impact of Guillain–Barré syndrome (GBS) on psychological distress, depressive symptoms, and health status of patients during the first year after GBS. At 3, 6, and ...12 months, patients were given the General Health Questionnaire, the Sickness Impact Profile, and the Center for Epidemiologic Studies Depression Scale. Eighty‐five patients participated. Psychological distress and depressive symptoms were present but improved between 3 and 6 months. At 12 months the psychosocial health status was still impaired. Patients who perceived their physical residua to be moderately to seriously disruptive and patients with muscle ache and cramps had worse scores on all scales. It can be concluded that most of the improvement occurred in the first 6 months. Psychosocial health status, however, was still impaired at 1 year, but depressive symptoms played no role. Treatment of muscle ache and cramps, and the disruptive effect of physical residua should be seriously considered. Muscle Nerve, 2010
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The group of patients with Guillain‐Barré syndrome (GBS) is very heterogenous with regard to antecedent infections, immunological parameters, clinical manifestations, and response to treatment. In ...this study, the presumed pathogenic factors anti‐GM1 antibodies and Campylobacter jejuni infections were related to the clinical characteristics. Serum from 154 patients with GBS, 63 patients with other neurological diseases (OND), and 50 normal controls (NC) were tested for the presence of antibodies against GM1 and C. jejuni. Anti‐GM1 antibodies were detected in 31 (20%) GBS patients, 5 (8%) OND patients, and in none of the NC. Evidence for a recent C. jejuni infection was found in 49 (32%) GBS patients and less often in OND patients (11%) or NC (8%). In GBS patients, the presence of anti‐GM1 antibodies was significantly associated with C. jejuni infections. The subgroup of GBS patients with anti‐GM1 antibodies suffered more often from a rapidly progressive and more severe neuropathy with predominantly distal distribution of weakness, without deficits of cranial nerves or sensory distrubances. The subgroup with C. jejuni infection also more often had a severe pure motor variant of GBS. Recovery of the patients with anti‐GM1 antibodies and C. jejuni infection was not as good after plasma exchange compared with intravenous immunoglobulins.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the Miller Fisher syndrome (MFS) variant of the Guillain‐Barré syndrome, weakness is restricted to extraocular muscles and occasionally other craniobulbar muscles. Most MFS patients have serum ...antibodies against ganglioside type GQ1b of which the pathophysiological relevance is unclear. We examined the in vitro effects of MFS sera, MFS IgG, and a human monoclonal anti‐GQ1b IgM antibody on mouse neuromuscular junctions (NMJs). It was found that anti‐GQ1b antibodies bind at NMJs where they induce massive quantal release of acetylcholine from nerve terminals and eventually block neuromuscular transmission. This effect closely resembled the effect of the paralytic neurotoxin α‐latrotoxin at the mouse NMJs, implying possible involvement of α‐latrotoxin receptors or associated downstream pathways. By using complement‐deficient sera, the effect of anti‐GQ1b antibodies on NMJs was shown to be entirely dependent on activation of complement components. However, neither classical pathway activation nor the formation of membrane attack complex was required, indicating the effects could be due to involvement of the alternative pathway and intermediate complement cascade products. Our findings strongly suggest that anti‐GQ1b antibodies in conjunction with activated complement components are the principal pathophysiological mediators of motor symptoms in MFS and that the NMJ is an important site of their action. Ann Neurol 1999;45:189–199
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background.
Since 2000, incidence of sexually acquired hepatitis C virus (HCV)-infection has increased among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). To date, few ...case-control and cohort studies evaluating HCV transmission risk factors were conducted in this population, and most of these studies were initially designed to study HIV-related risk behavior and characteristics.
Methods.
From 2009 onwards, HIV-infected MSM with acute HCV infection and controls (HIV-monoinfected MSM) were prospectively included in the MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study at 5 large HIV outpatient clinics in the Netherlands. Written questionnaires were administered, covering sociodemographics, bloodborne risk factors for HCV infection, sexual behavior, and drug use. Clinical data were acquired through linkage with databases from the Dutch HIV Monitoring Foundation. For this study, determinants of HCV acquisition collected at the inclusion visit were analyzed using logistic regression.
Results.
Two hundred thirteen HIV-infected MSM (82 MSM with acute HCV infection and 131 MSM without) were included with a median age of 45.7 years (interquartile range IQR, 41.0–52.2). Receptive unprotected anal intercourse (adjusted odds ratio aOR, 5.01; 95% confidence interval CI, 1.63–15.4), sharing sex toys (aOR, 3.62; 95% CI, 1.04–12.5), unprotected fisting (aOR, 2.57; 95% CI, 1.02–6.44), injecting drugs (aOR, 15.62; 95% CI, 1.27–192.6), sharing straws when snorting drugs (aOR, 3.40; 95% CI, 1.39–8.32), lower CD4 cell count (aOR, 1.75 per cubic root; 95% CI, 1.19–2.58), and recent diagnosis of ulcerative sexually transmitted infection (aOR, 4.82; 95% CI, 1.60–14.53) had significant effects on HCV acquisition.
Conclusions.
In this study, both sexual behavior and biological factors appear to independently increase the risk of HCV acquisition among HIV-infected MSM.
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