Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254/Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.info:eu-repo/semantics/publishedVersio

Barriers to health care services for migrants living with HIV in Spain

BACKGROUND: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. METHODS: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. RESULTS: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2–7.2]) and women (OR: 10.5 [95%CI: 3.1–34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9–5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2–3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3–30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3–25.1]) were more likely to report barriers. CONCLUSION: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints

Characteristics and clinical relevance lost T-Cell homeostasis and T-cell dysregulation in HIV-1 infected patients receiving antiretroviral therapy

In the early years of the HIV epidemic, HIV infection was considered a terminal disease characterized by the onset of opportunistic infections and malignancies known as AIDS-defining illnesses (ADIs). The earliest surrogate laboratory marker for this syndrome was a decline in the CD4:CD8 ratio. Upon the identification of HIV as the causative agent of the disease, studies of viral dynamics led to a better understanding of HIV pathogenesis. Results from these studies led to the establishment of the CD4+ T-cell count and HIV viral load as the preferred biomarkers for the monitoring and management of HIV related clinical outcomes. Over the last 2 decades, the advent of effective antiretroviral therapy (ART) has transformed this disease from an acute and lethal condition to a manageable chronic infection. Although ADIs are no longer a major threat to successfully treated HIV patients, an emerging set of non-AIDS illnesses (NADIs) have been identified. These comorbidities, which are usually found in aging individuals, are postulated to result from persistent immune dysfunction that is generally associated with chronic inflammation and immunological aging; a process often referred to as inflammaging. This new clinical picture has prompted research on the long-term residual immune changes stemming from prior chronic HIV infection in the context of successful antiretroviral therapy. The work presented in this thesis provides a foundation for the rational monitoring of treated HIV patients, using a composite measurement of clinically available immune markers. Whereas other studies have historically stressed the depletion of CD4+ T-cell counts as the hallmark of HIV-mediated immunologic dysfunction; the findings described herein indicate that the immuno-pathogenic impact of HIV infection is multifaceted and only partially reversible with long-term suppressive treatment. This thesis also provides a basis for further understanding the role of inflammaging in the context of successfully treated HIV infection. Our findings may prove relevant to the development of new HIV treatment strategies in the era of effective ART.Au commencement de l'épidémie du VIH, l'infection par le VIH était perçue comme une maladie mortelle caractérisée par l'émergence d'infections et de tumeurs opportunistes liées au SIDA; la phase terminale de la maladie. La dérégulation du rapport CD4:CD8, fût l'un des premiers marqueurs associés à l'immuno-pathologie causée par le VIH. Les analyses de recherche sur les dynamiques de réplication virale ont contribué aux connaissances accrues de la pathogénèse du VIH. Suite aux résultats de ces analyses, le taux de cellules T CD4 et la charge virale du VIH sont devenus les marqueurs de choix pour le suivi et le traitement des conditions cliniques liées à l'infection par le VIH. Au cours des 20 dernières années, l'avènement de la trithérapie a révolutionné la vie des personnes infectées par le VIH en transformant l'infection par le VIH en une maladie chronique. Cependant, bien que les maladies liées au SIDA ne représentent plus un problème majeur pour les individus traités pour le VIH, certaines de maladies non-liées au SIDA sont désormais une cause majeure de mortalité chez les individus infectés par le virus. Ces maladies sont généralement observées chez les personnes âgées, et semblent être associées à des dérèglements immunitaires qui caractérisent un état d'inflammation chronique et de sénescence immunitaire appelé «inflammaging». Cette nouvelle présentation clinique de l'infection par le VIH a influencée de nouvelles recherches sur les conséquences de la chronicité de la maladie sur le système immunitaire. La présente thèse propose le choix rationnel d'un groupe de marqueurs immunologiques qui permettraient une évaluation intégrale du système immunitaire des patients traités pour le VIH. Bien que la baisse du taux de cellules T CD4 soit généralement considérée comme le principal dérèglement immunitaire chez les patients infectés par le VIH, les résultats présentés dans cette thèse indiquent que l'infection par le VIH affecte d'autres paramètres immunitaires, qui ne sont pas complètements rétablis malgré un traitement efficace. Cette thèse contribue également à une meilleure compréhension de la sénescence immunitaire dans un contexte d'infection par le VIH sous contrôle thérapeutique. Nos résultats pourraient être utiles pour le développement de nouvelles stratégies de traitement du VIH à l'ère des traitements antirétroviraux efficaces

International Journal of Economics, Commerce and Management EFFECT OF STAFF TRAINING ON LEVEL OF COMPLIANCE TO PUBLIC PROCUREMENT SYSTEM IN PARASTATALS IN KENYA

Abstract Public procurement is increasingly recognized as a central instrument t

Comprehensive evaluation of the immune risk phenotype in successfully treated HIV-infected individuals.

Despite successful treatment and CD4+ T-cell recovery, HIV-infected individuals often experience a profound immune dysregulation characterized by a persistently low CD4:CD8 T-cell ratio. This residual immune dysregulation is reminiscent of the Immune Risk Phenotype (IRP) previously associated with morbidity and mortality in the uninfected elderly (>85 years). The IRP consists of laboratory markers that include: a low CD4:CD8 T-cell ratio, an expansion of CD8+CD28- T-cells and cytomegalovirus (CMV) seropositivity. Despite the significant overlap in immunological phenotypes between normal aging and HIV infection, the IRP has never been evaluated in HIV-infected individuals. In this pilot study we characterized immune changes associated with the IRP in a sample of successfully treated HIV-infected subjects.18 virologically suppressed HIV-infected subjects were categorized into 2 groups based on their IRP status; HIV+IRP+, (n = 8) and HIV+IRP-, (n = 10) and compared to 15 age-matched HIV uninfected IRP negative controls. All individuals were assessed for functional and phenotypic immune characteristics including: pro-inflammatory cytokine production, antigen-specific proliferation capacity, replicative senescence, T-cell differentiation and lymphocyte telomere length.Compared to HIV-infected subjects without an IRP, HIV+IRP+ subjects exhibited a higher frequency of TNF-α-producing CD8+ T-cells (p = 0.05) and a reduced proportion of CD8+ naïve T-cells (p = 0.007). The IRP status was also associated with a marked up-regulation of the replicative senescence markers CD57 and KLGR1, on the surface of CD8+T-cells (p = 0.004). Finally, HIV+IRP+ individuals had a significantly shorter mean lymphocyte telomere length than their non-IRP counterparts (p = 0.03).Our findings suggest that, despite similar levels of treatment-mediated viral suppression, the phenotypic and functional immune characteristics of HIV+IRP+ individuals are distinct from those observed in non-IRP individuals. The IRP appears to identify a subset of treated HIV-infected individuals with a higher degree of immune senescence

Relationship between the IRP and lymphocyte telomere length.

<p>Average telomere length (aTL) was measured in kilobases (kb) per diploid genome. Lymphocyte aTL comparisons were made between uninfected controls (blue), HIV+IRP- (purple) and HIV+IRP+ (red). Statistical significance was determined using the Mann–Whitney U test. *p<0.05, **p<0.01, ***p <0.001.</p

Participants’ characteristics.

<p>Participants’ characteristics.</p

Relationship between the Immune Risk Phenotype (IRP) and Staphylococcus Enterotoxin B induced pro-inflammatory cytokine secretion.

<p>Percentages of IL-2, IFN-γ or TNF-α producing T-cells in response to Staphylococcus Enterotoxin B (SEB) stimulation within the CD4+ (A) and CD8+ (B) T-cell compartments. Comparisons were made between uninfected controls (blue), HIV+IRP+ (purple) and HIV+IRP+ (red) subjects. Statistical significance was determined using the Mann–Whitney U test. *p<0.05, **p<0.01, ***p <0.001.</p

Delay in cART initiation results in persistent immune dysregulation and poor recovery of T-cell phenotype despite a decade of successful HIV suppression.

Successful combination antiretroviral therapy (cART) increases levels of CD4+ T-cells, however this increase may not accurately reflect long-term immune recovery since T-cell dysregulation and loss of T-cell homeostasis often persist. We therefore assessed the impact of a decade of effective cART on immune regulation, T-cell homeostasis, and overall T-cell phenotype.We conducted a retrospective study of 288 HIV+ cART-naïve patients initiating therapy. We identified 86 individuals who received cART for at least a decade, of which 44 consistently maintained undetectable plasma HIV-RNA levels throughout therapy. At baseline, participants were classified into three groups according to pre-treatment CD4+ T-cell counts: Group I (CD4<200 cells/mm3); Group II (CD4: 200-350 cells/mm3); Group III (CD4>350 cells/mm3). Outcomes of interest were: (1) CD4+ T-cell count restoration (CD4>532 cells/mm3); (2) normalization of CD4:CD8 T-cell ratio (1.2-3.3); (3) maintenance of CD3+ T-cell homeostasis (CD3: 65%-85% of peripheral lymphocytes); (4) normalization of the complete T-cell phenotype (TCP).Despite a decade of sustained successful cART, complete T-cell phenotype normalization only occurred in 16% of patients, most of whom had initiated therapy at high CD4+ T-cell counts (>350 cells/mm3). The TCP parameter that was the least restored among patients was the CD4:CD8 T-cell ratio.Failure to normalize the complete T-cell phenotype was most apparent in patients who initiated cART with a CD4+ T-cell count <200 cells/mm3. The impact of this impaired T-cell phenotype on life-long immune function and potential comorbidities remains to be elucidated