Infeciologia

#Does #Highly Active Antiretroviral Therapy Contribute to #Syphilis Incidence by #Impairing Immunity to #Treponema Pallidum?

Postado em

Michael L Rekart; Wilfred Ndifon; Robert C Brunham; Jonathan Dushoff; Sang Woo Park; Sanjana Rawat; Caroline E Cameron

Abstract

Background and hypothesis Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic.

Methods We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects.

Conclusions and implications Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum. This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum.

Introduction

STDs, HIV-1 and Men Who Have Sex With Men. In British Columbia (BC), Canada, from 2005 to 2014, infectious syphilis case reports (primary, secondary and early latent) rose 90.6% (288–549), chlamydia 39.9% (9540–13 348) and gonorrhoea 63.8% (1100–1802), corresponding to rate changes per 100 000 population of +72.4%, +33.9% and +47.6%, respectively.[1] Female syphilis cases decreased while male cases jumped from 202 to 524, accounting for 95% of all 2014 cases. Men who have sex with men (MSM) accounted for 60.4% (122) of cases in 2005, rising to 88.9% (466) in 2014. There was a fourfold increase in MSM syphilis from 2010 to 2014 (115–466 cases), including 112 reinfections (24%) in 2014. The HIV-1 coinfection rate in MSM during this period was 50%–75%. From 2005 to 2014, the male infectious syphilis rate increased 235% (9.7–22.8) compared with a much smaller increase for chlamydia (56.9%; 141.7–222.4) and gonorrhoea (42.1%; 39.7–56.4) in men.

Comparatively larger increases in syphilis cases were also observed in the USA from 2005 to 2014. Primary and secondary syphilis cases rose 128.1% (8724–19 999), chlamydia 47.7% (976 445–1 441 789) and gonorrhoea 3.1% (339 593–350 062), corresponding to rate changes of +117.2%, +38.5% and −3.4%, respectively.[2] Males contributed an increasing proportion of syphilis cases, accounting for 91% in 2014. From 2007 to 2014, among the 27 US states that collected sex partner data for ≥70% of males, MSM cases increased steadily to 82.9%. In Los Angeles County between January and May, 2010, 76% of 537 early syphilis cases were MSM and ≥58% of these were HIV-1 positive.[3] HIV-1 infection in US MSM has also been statistically associated with repeat syphilis infection.[4]

In the UK from 1998 to 2013, new syphilis cases in MSM rose from 23 (26.0% of all cases) to 2546 (71.3% of all cases). From 2009 to 2013 in England, the odds of being diagnosed with syphilis increased from 2.71 (95% CI 2.41 to 3.05, p<0.001) to 4.05 (95% CI 3.70 to 4.45, p<0.001) in HIV-1 positive relative to HIV-1 negative/undiagnosed MSM.[5]

Results

Highly Active Antiretroviral Therapy and Syphilis

First-line highly active antiretroviral therapy (HAART) regimens may comprise (1) two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), commonly tenofovir (TDF) and emtricitabine (FTC) or lamivudine (3TC), plus a non-nucleoside reverse transcriptase inhibitor (NNRTI), commonly efavirenz, (2) two NRTIs and an integrase strand-transfer inhibitor (InSTI) or (3) two NRTIs and a boosted protease inhibitor (PI). PIs, InSTIs and fusion/entry inhibitors are used as second-line and third-line alternative agents. In BC, 86.1% of patients take two NRTIs with a boosted PI (34%), NNRTI (30%), InSTI (19%) or fusion/entry inhibitor (1%).[6] Common NRTIs include TDF (64%), FTC (59%) and 3TC (40%). An additional 11% (741 patients) take InSTIs in other HAART combinations. In total, 30% (2056) take InSTIs. HAART usage has grown steadily including a 288% increase in InSTI usage from 2010 to 2015 (530–2056 patients).

Because HAART stimulates and supports immune system recovery from HIV-1-related immunosuppression, one might expect HAART to be associated with declining infection rates for most pathogenic organisms. However, several studies support the hypothesis that HAART may be associated with syphilis acquisition. Receiving HAART (adjusted HR=1.81 (95% CI 1.25 to 2.62, p<0.002)), older age and MSM status were independent risk factors for syphilis seroconversion by multivariate logistic regression analysis in 1010 people who were infected with HIV in Northeast China from 2009 to 2013.[7] Using Poisson regression analysis, Park and coauthors[8] found that the period-specific incidence rate of early syphilis in 539 patients receiving HAART in Korea significantly increased in proportion to the years after starting HAART (p<0.001). These two studies were conducted in stable cohorts but they did not control for specific sexual risk behaviours.

Additional studies have reported a significant proportion of new syphilis cases in persons receiving HAART, including 32.7% of all 1089 new syphilis cases in France from 2000 to 2003 and 71% of the 502 cases who knew their HIV-1 positive status.[9] Among 104 early syphilis and 36 late or indeterminate latent syphilis cases in a Malaga study from 2004 to 2011, 65 of 85 (76.4%) with prior known HIV-1 infection were taking HAART.[10] A retrospective, descriptive study at the University of Alabama found 40 incident syphilis cases from 2004 to 2007 in 1544 patients who were HIV-1 positive.[11] Two-thirds were receiving HAART when syphilis was diagnosed including all five patients with primary syphilis. The proportion of the entire cohort on HAART was not reported. Among 3448 patients followed in a Parisian Hospital Infectious Disease Service from January 2000 to December 2002, 48 of 71 (67.6%) patients with a new diagnosis of syphilis were taking HAART.[12] For BC, over 8000 males have tested HIV-1 positive, and HAART usage in MSM is more than 80%.[1,6] However, the percentage taking HAART when syphilis was diagnosed is unknown.

Behavioural Change

One explanation for high rates of syphilis in MSM is increased risky sex, often in the context of optimistic risk perception. Similarly, any association between syphilis and HAART might be a surrogate marker for risky sex in individuals treated with HAART rather than an effect of HAART itself. Seroadaptive behaviours to prevent HIV-1 transmission, such as serosorting (ie, selective unprotected sex with partners of the same HIV status), have also been implicated in increasing STD incidence including syphilis.[13] What then is the evidence for HIV-1 treatment optimism and behavioural change in MSM and persons on HAART?

Several studies support treatment optimism including a 2013 literature review, which concluded that quantitative studies were ‘largely in support’ of an association between optimistic beliefs and HIV-1 transmission risk.[14] However, other studies have shown no change or decreased risky behaviour and/or no lessening of risk perception, as discussed later in this section.

Many HIV-1-infected MSM believe they have a responsibility to protect their sex partners,[15] and many eliminate or reduce HIV-1 transmission behaviours after HIV-1 diagnosis. A 2005 US meta-analysis concluded that high-risk sexual behaviour with partners who were HIV-1 negative was significantly reduced (68%, 95% CI 59% to 76%, p<0.001) after HIV-1 diagnosis.[16] Persson used the Swiss Consensus Statement that people on effective HIV-1 treatment cannot transmit HIV-1 as a surrogate for HIV-1 treatment optimism in interviews of HIV-1 discordant couples. Participants were highly sceptical of the Statement’s prevention message and not one described it as having any direct relevance to their sexual decision making.[17]

Much of the HIV-1 treatment optimism literature focuses on behavioural change in persons on HAART and subsequent to HAART initiation. In 512 patients receiving HAART in Bangkok, unprotected sex risk was found in only 27 patients (5%) and multivariate analysis showed no association with beliefs about HIV-1 transmission while taking HAART.[18] A 2009 meta-analysis of unprotected anal intercourse (UAI) among HIV-1 diagnosed US MSM found no association with HAART[15] and a cross-sectional study of 420 London men who were HIV-1 positive showed that men on HAART had fewer sexual partners and less UAI.[19] Among 456 HIV-1 positive US MSM, Remien et al[20] found no increased sexual risk behaviour and substantial ongoing perception of HIV-1 transmission risk while on HAART. Using data from a prospective behavioural study nested in a randomised controlled trial of early HAART (Temprano), Jean et al[21] found significant decreases over 24 months in sexual activity (OR 0.72, 95% CI 0.57 to 0.92), multiple partnerships (OR 0.57, 95% CI 0.41 to 0.79), unprotected sex (OR 0.59, 95% CI 0.47 to 0.75) and risky sex (OR 0.58, 95% CI 0.45 to 0.76).

We could find only one study that found a link between increasing syphilis incidence and seroadaptive behaviours such as serosorting in individuals treated with HAART with unsuppressed viral load, but this would not explain rising syphilis incidence out-of-proportion to other STDs.[13]

Some studies have implicated core groups in this syphilis outbreak,[22] while other studies have shown little or no significant increase in risky sex, number of contacts or concurrency among core group members. In a retrospective study of syphilis among MSM in San Francisco, number of sex partners, illicit substance use, partner meeting venues and commercial sex were not associated with repeat syphilis infection.[4] In the Alabama, Bangkok and Temprano cohorts referenced earlier, similar core group characteristics were not associated with incident syphilis, unprotected sex risk or multiple partnerships, respectively.[11,18,21] Finally, a mathematical model of behaviour in a core group predicted a transient spike in unprotected sex that was counteracted by other pathways on longer timescales, leading to lower rates of unprotected sex on the whole.[23]

Modelling studies conducted herein to test our hypothesis are in support of both behavioural change and HAART treatment being able to increase syphilis prevalence, with the combined effect being more than additive (Figure 1). Specifically, we developed a mathematical model of HIV-1 and Treponema pallidum coinfection in a population with two risk groups and assortative mixing between groups. Susceptible individuals acquire infection from a partner who is infected with a fixed probability per sexual encounter. In the case of HIV-1, the infection probability is lower if the partner who is HIV-1 positive is on HAART versus untreated, but it is higher if the partner who is either HIV-1 negative or HIV-1 positive is already infected with T. pallidum versus uninfected. Individuals who are infected receive treatment at a constant rate dependent on the pathogen. Individuals lose their treated status at a disease-dependent rate. Individuals infected with HIV-1 have a disease-imposed mortality rate that is lower for individuals on HAART.

Figure 1.

A susceptible-infective-treated model of HIV-1 and Treponema pallidum epidemiology predicts that both highly active antiretroviral therapy (HAART) and behavioural change substantially boost syphilis prevalence above baseline. The model used two risk groups and assortative mixing between groups. Using baseline parameters from the literature,24 we varied parameters quantifying HAART effects and partnership formation rates on susceptibility to and transmission of T. pallidum. We introduced HAART at 20 years and plotted syphilis prevalence without (left panel) and with (right panel) a threefold effect of HAART on susceptibility to T. pallidum, under different assumptions about the effect of HAART on partnership formation rates (for details and code, see https://github.com/dushoff/Syphilis_and_ARVs). Compared with the baseline of no effect (left panel, black line), the combined effect of increased susceptibility and behavioural change (right panel, coloured lines) is larger than the sum of the effects of behavioural change alone (left panel, coloured lines) and increased susceptibility alone (right panel, black line).

We numerically simulated the model using baseline parameters taken from the literature.[24] We initialised each simulation with a small number of individuals who are infected and introduced HAART 20 years later. We explored effects on syphilis prevalence of HAART-induced changes in behaviour versus immunology. For behavioural change, we assumed that individuals on HAART adopt more risky sexual behaviours by increasing their partnership formation rates, which increases their ability to transmit T. pallidum. For immunological change, we assumed that individuals on HAART have a higher susceptibility to T. pallidum than individuals who are untreated. The simulation results show that either behavioural (Figure 1, left panel, blue and red lines) or immunological (Figure 1, right panel, black line) change alone can produce syphilis outbreaks with peak prevalence that is substantially higher than baseline. Strikingly, the peak prevalence of the syphilis outbreak produced by both behavioural and immunological changes (Figure 1, right panel, blue and red lines) is larger than the sum of the peaks of outbreaks produced independently by either type of change (Figure 1, left panel, blue and red lines; right panel, black line). Therefore, the immunological effects of HAART and HAART-induced behavioural change can in principle act synergistically to increase syphilis prevalence by amounts comparable with that observed in the ongoing outbreak.

Discussion

Biological Plausibility

Protection against the extracellular pathogen T. pallidum, the causative agent of syphilis, is dependent upon T cell expansion and the generation of an early Th1-stimulating, interferon γ (IFN γ)-producing host proinflammatory response that potentiates the primary clearance mechanism of T. pallidum, macrophage-mediated opsonophagocytosis.[25] The latter process is dependent on unperturbed mitochondrial function to ensure peak metabolic activity within macrophages,[26] opsonic antibody production and IFN γ-mediated macrophage activation.[27] Opsonic antibody quality is reduced in individuals infected with HIV-1[28] and certain HAART agents significantly suppress mitochondrial function,[26] the proinflammatory response[29] and macrophage activation,[30] leading to reduced treponemal clearance via opsonophagocytosis. InSTIs have been shown to suppress the proinflammatory response in cohort studies[29] and opsonophagocytosis is reduced in vitro following treatment of macrophages with NRTIs, consistent with mitochondrial damage.[26]

Further, the well-documented depletion of CD4+ memory T cells in individuals infected with HIV-1[30] would enhance their susceptibility to syphilis reinfection. NRTIs, especially TDF, have been shown to inhibit telomerase activity leading to accelerated shortening of telomerase length in peripheral blood mononuclear cells (PBMCs),[31] which may lead to the accumulation of replicative senescent cells[32] with limited ability to protect against pathogens such as T. pallidum. Reciprocally, upregulation of monocyte expression of CCR5 receptors by treponemal lipoproteins enhances the susceptibility of monocytes to HIV-1 infection,[33] further weakening the innate and adaptive immune responses to T. pallidum.

Collectively, these observations provide viable explanations for (1) an enhanced susceptibility of individuals infected with HIV-1, especially those on HAART, to syphilis infection and reinfection and (2) higher syphilis incidence among individuals treated with HAART compared with chlamydia and gonorrhoea, infections caused by pathogens that are less reliant on opsonophagocytosis for clearance.

Potential Approach for Hypothesis Testing

HAART decreases the proinflammatory response in patients infected with HIV-1,[29] but this may result from an HAART-induced reduction of lymphocytes’ ability to upregulate inflammatory markers, in line with our hypothesis, or from the disappearance of a major cause of inflammation (ie, a fall in HIV-1 viral load). These different effects can be teased apart using experiments in macaques, which have been used as models for human infection with T. pallidum[34] and develop AIDS-like disease following simian immunodeficiency virus (SIV) infection. T. pallidum challenge after specific HAART administration with or without prior SIV infection can provide insight into how HAART affects the proinflammatory response and syphilis susceptibility in the absence or presence of retrovirus.

Prospective cohort studies can compare opsonophagocytic activity of macrophages and susceptibility to syphilis among healthy individuals who are HIV-1 negative receiving preventative pre-exposure prophylaxis (PrEP), healthy controls, untreated patients with HIV-1 and patients with HIV-1 receiving the same HAART as healthy individuals. To determine the effect of HAART on CD4+ memory T cells, one can measure the number of CD4+ memory T cells by flow cytometry in PBMCs of persons on and off HAART with particular attention to TDF.

A retrospective case–control and/or a prospective cohort study comparing the prevalence and epidemiological features of infectious syphilis cases among patients who are HIV-1 positive and treated with HAART, patients who are HIV-1 positive and untreated and patients who are HIV-1 negative, including the usage of specific HAART agents, would be enlightening. Syphilis databases without HAART information could be linked to treatment databases to delineate overlapping factors including HAART usage.

Conclusion

Clinicians and researchers typically view HAART suppression of the proinflammatory response positively because it decreases HIV-1-associated pathological sequelae. However, this immune dampening may have detrimental effects including enhanced susceptibility to infection with T. pallidum and the occurrence of unusual clinical manifestations such as ocular syphilis. The possibility also exists that HAART-mediated immune dampening may predispose an individual to other conditions that are non-infectious in origin and depend upon a particular immune response for control, including certain types of cancer. In this regard, it is of interest to note that HAART treatment has been suggested to be associated with a higher risk of anal cancer and, potentially, other non-AIDS-defining cancers.[35] Overall, these findings suggest a possible link between HAART and an increased risk for selected diseases of infectious and non-infectious origin, a potential unforeseen consequence that warrants further study. If borne out, it will be imperative that the highly exciting and efficacious global implementation of PrEP be carried out with awareness towards the potential need for enhanced patient management.

Anúncios

#Microbiota de donantes sanos para mejorar el #sistema inmunitario de pacientes con #infección por el VIH

Postado em

Investigadores del Hospital Universitario Ramón y Cajal de Madrid, pertenecientes al Grupo de Estudio del Sida (Gesida) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), han puesto en marcha un estudio pionero para analizar por vez primera la seguridad y eficacia de una innovadora terapia para mejorar el sistema inmunitario de los pacientes con VIH a partir de la microbiota intestinal de donantes sanos.

La transferencia de estas bacterias intestinales, en pequeñas dosis y de manera repetida, busca prevenir y ralentizar la aparición de comorbilidades asociadas a la infección así como, en términos generales, mejorar el estado de salud del paciente.

En las primeras semanas de la infección, el VIH infecta y destruye la mayor parte de los linfocitos CD4 del intestino, en donde residen el 80% del total de estas células del cuerpo. Tras el inicio del tratamiento antirretroviral, se ha observado que, respecto a lo que sucede en la sangre, en la mucosa intestinal la recuperación inmunológica es más tardía e incompleta.

La alteración de la composición y el funcionamiento de las bacterias intestinales -fundamentales para la efectividad del sistema inmunitario- se relacionan asimismo con la persistencia de déficits inmunológicos e inflamación.

El exceso de inflamación favorece un envejecimiento acelerado en la población portadora del virus, hecho que se debe en gran medida, a un trasvase de productos bacterianos desde el intestino a la sangre. Este proceso duplica asimismo el riesgo de padecer enfermedades asociadas al envejecimiento, tales como patologías cardiovasculares, cánceres o enfermedad renal avanzada.

Estudios previos han demostrado que la composición y actividad de las bacterias intestinales alteradas en las personas con VIH puede favorecer o dificultar la recuperación inmunológica, la inflamación y, posiblemente, la aparición de complicaciones médicas.

En el caso de conseguir que este proyecto pionero muestre su efectividad, los beneficios potenciales que obtendrían los pacientes al normalizar la flora intestinal están relacionados con los fenómenos en los que las bacterias intestinales parecen estar más involucradas.

Ya que si permite una mayor recuperación inmunológica, una mejor respuesta a las vacunas y una reducción de los niveles de inflamación, permitiría una menor aparición de complicaciones médicas.

“La transferencia de microbiota en dosis y bajas y repetidas no se ha analizado hasta la fecha en otros estudios. De demostrar su eficacia, esta novedosa estrategia terapéutica no sólo beneficiaría a las personas con VIH. También podría explorarse en otras enfermedades en los que la microbiota intestinal parece jugar un papel fundamental como, por ejemplo, enfermedad inflamatoria intestinal, colon irritable, obesidad, diabetes, enfermedades autoinmunes, etc.”, ha explicado Sergio Serrano, de la Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal y coordinador de este estudio.

Para llevar a cabo este estudio, sus promotores han llevado a cabo a través de la plataforma Precipita, una iniciativa de micromecenazgo para sufragar parte de este proyecto de investigación con la que ya han conseguido algo más de 11.700 euros.

#Respiratory Health Status Is Impaired in UK #HIV-Positive Adults With #Virologically Suppressed HIV Infection

Postado em

J Brown; JA McGowan; H Chouial; S Capocci; C Smith; D Ivens; M Johnson; L Sathia; R Shah; FC Lampe; A Rodger; M Lipman

Abstract and Introduction

Abstract

Objectives We sought to evaluate whether people living with HIV (PLWH) using effective antiretroviral therapy (ART) have worse respiratory health status than similar HIV-negative individuals.

Methods We recruited 197 HIV-positive and 93 HIV-negative adults from HIV and sexual health clinics. They completed a questionnaire regarding risk factors for respiratory illness. Respiratory health status was assessed using the St George’s Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) breathlessness scale. Subjects underwent spirometry without bronchodilation.

Results PLWH had worse respiratory health status: the median SGRQ Total score was 12 [interquartile range (IQR) 6–25] in HIV-positive subjects vs. 6 (IQR 2–14) in HIV-negative subjects (P < 0.001); breathlessness was common in the HIV-positive group, where 47% compared with 24% had an MRC breathlessness score ≥ 2 (P = 0.001). Eighteen (11%) HIV-positive and seven (9%) HIV-negative participants had airflow obstruction. In multivariable analyses (adjusted for age, gender, smoking, body mass index and depression), HIV infection remained associated with higher SGRQ and MRC scores, with an adjusted fold-change in SGRQ Total score of 1.54 [95% confidence interval (CI) 1.14–2.09; P = 0.005] and adjusted odds ratio of having an MRC score of ≥ 2 of 2.45 (95% CI 1.15–5.20; P = 0.02). Similar findings were obtained when analyses were repeated including only HIV-positive participants with a viral load < 40 HIV-1 RNA copies/mL.

Conclusions Despite effective ART, impaired respiratory health appears more common in HIV-positive adults, and has a significant impact on health-related quality of life.

Introduction

Antiretroviral therapy (ART) has transformed HIV infection into a manageable chronic condition.[1] Despite this, people living with HIV (PLWH) continue to have higher rates of comorbidities such as cardiovascular[2] and renal disease,[3] as well as some malignancies.[4] There is also evidence that, despite ART, PLWH may have a higher prevalence of chronic respiratory illness.[5] For instance, in the large US Veterans Aging Cohort Study, after adjustment for smoking status and other characteristics, chronic obstructive pulmonary disease (COPD) was 50–60% more common in PLWH than in HIV-negative participants.[6] The development of persistent, noncommunicable respiratory disease such as COPD in HIV-positive individuals may impact significantly on their quality of life.[7]

There are, however, limitations to the currently available data concerning chronic respiratory disease in HIV-positive people on ART. In particular, most reported studies have included significant proportions of participants without virological suppression. Also, results may be influenced by residual confounding factors such as tobacco smoking and recreational drug use. Furthermore, most studies assessing respiratory health in HIV-positive populations have focused on objective measurements of lung function (such as spirometry) rather than the subjective impact of respiratory impairment on health-related quality of life.[5,8] This is an important issue, as respiratory symptoms can correlate poorly with objectively measured lung function,[9] yet may have a significant effect on quality of life. There is a need, therefore, to better understand the degree to which PLWH with access to effective ART have worse respiratory health than HIV-negative individuals (with similar risk factors), and the impact of this on their quality of life.[10]

The use of validated patient-reported outcome measures allows the systematic evaluation of the impact of pathologies on health-related quality of life, and enables direct comparisons to be made between different groups and populations. These instruments can attempt to quantify general health status (such as the EuroQoL 5D 5L (EQ5D)) or may be disease or organ specific [e.g. the St George’s Respiratory Questionnaire (SGRQ)]. In this study, we used these measures to provide an assessment of overall respiratory health (rather than an assessment specific to one condition such as COPD) – which we refer to as “respiratory health status”.

We sought to evaluate whether respiratory health status was impaired in a contemporary (on ART) HIV-infected population and to test the hypothesis that HIV-positive adults have worse respiratory health than HIV-negative people with similar risk factors; to assess whether impaired respiratory health correlated with spirometric impairment in this population, and to explore the effect of potential confounding factors such as smoking, recreational drug use, and physical and mental comorbidities. In addition, for those with HIV infection, we describe the relationship between HIV-related factors such as blood CD4 count, HIV load and duration of HIV infection and respiratory health status.

Methods

Study Population

We conducted a cross-sectional observational study in the HIV ambulatory care service and sexual health clinics (at Royal Free and Barnet Hospital sites) of the Royal Free London NHS Trust, London, UK from February to July 2015. Consecutive clinic patients were invited to take part in the study when they attended routine care appointments. Subjects provided written informed consent. London sexual health clinics were chosen as the site for recruitment of HIV-negative participants as this population was anticipated to have similar lifestyle characteristics, including smoking behaviours, to the HIV clinic population. As service users in the sexual health clinics were significantly younger than those attending clinics for HIV care, recruitment in sexual health clinics was restricted to those over the age of 35 years to achieve a sample that approximated the age of the HIV-positive participants. There were no exclusion criteria for the HIV-positive group. Ethical approval was granted by the London – Camden and Islington Research Ethics Committee (14/LO/1646).

Procedures

Participants completed a questionnaire including items on risk factors for respiratory illness, smoking and recreational drug use and health-related quality of life (using the EQ5D).[11–13] As depression might affect the experience and expression of respiratory symptoms (and therefore act as an important confounding factor), symptoms of depression were evaluated using the Patient Health Questionnaire – 9 (PHQ-9) (a scale providing scores of 0–27, where scores of ≥ 10 suggest the presence of moderate or severe depressive symptoms[14]). Respiratory health status was measured using (a) the SGRQ and (b) the Medical Research Council dyspnoea (breathlessness) scale, a scale with scores from 1 to 5 recording the severity of breathlessness on exertion.[15,16]

The SGRQ is a patient-reported outcome measure which quantifies respiratory health using a 50-item self-completed questionnaire.[15] Responses are translated onto a scale from 0 to 100 in which higher scores indicate worse respiratory health status, with domains assessing symptoms, activities and impacts as well as a total score. Although initially developed for use in asthma and COPD, it is not disease-specific and has been widely used in other respiratory conditions.

Subjects underwent spirometry without bronchodilation (Carevision Micro I spirometer, Beckton Dickinson, New Jersey, USA) and had their height and weight measured. Normal values for spirometry were calculated using the Global Lung Function Initiative equations;[17] airflow obstruction was defined as an Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FVC) of < 0.7. For current and past blood test results, data were obtained from hospital databases with participant consent. Self-reported HIV status was noted and not independently confirmed in the sexual health clinic population.

Statistical Analysis

Data were recorded and analysed in excel (Microsoft) and spss version 22 (IBM, New York, USA). Univariable comparisons between HIV-positive and -negative participants were undertaken using χ[2] and Fisher’s exact tests for categorical variables and unpaired t-tests or Mann–Whitney U-tests for continuous variables, as appropriate. To adjust for participant characteristics and to assess the independent associations of factors with respiratory measures, multivariable regression analyses were performed. SGRQ Total scores were log-transformed to normalize their distribution for these analyses. Multivariable linear regression analyses were used to assess factors independently associated with log-transformed SGRQ Total scores and estimates were then back-transformed to derive adjusted fold-changes in SGRQ score for covariates of interest. Multivariable logistic regression models were used to assess factors independently associated with having an MRC dyspnoea score of ≥ 2. For the multivariable analyses, a core set of variables of importance were selected a priori (age, tobacco smoking, gender and HIV status) and, following univariable analysis, additional variables found to be significantly associated at the 5% level with respiratory health status were added to the multivariable model.

Results

Study Participants

Of 402 individuals invited to participate, 290 (72%) agreed: 197 HIV positive and 93 HIV negative. Recruitment of HIV-negative individuals was lower as fewer eligible individuals attended these clinics over the study period – however, the response rate was similar, being 75% among HIV-positive individuals and 73% among HIV-negative individuals. Demographics and details of comorbid conditions are listed in Table 1 and Table 2.

The median blood CD4 count of HIV-positive participants was 627 cells/μL [interquartile range (IQR) 456–838 cells/μL]; 171 (94%) of PLWH reported using ART, with a median duration of treatment of 7 years. Eighty-nine per cent of all PLWH and 93% of those using ART had an undetectable plasma HIV load (< 40 HIV-1 RNA copies/mL) at their last clinic visit. The median nadir CD4 count of this cohort was 250 cells/μL (IQR 122–365 cells/μL). No significant differences were found in gender, educational attainment or being non-UK born between HIV-positive and -negative participants, but PLWH were more often ethnically white (72% vs. 60%, respectively; P = 0.001). HIV-negative participants had a lower median age than those recruited from the HIV ambulatory care clinic (43 vs. 50 years, respectively; P = 0.05) and were more likely to be heterosexual (71% vs. 32%, respectively; P < 0.01).

The HIV-positive and -negative groups had similar reported prevalences of a range of physical comorbidities (asthma, COPD, diabetes, heart disease and stroke). However, symptoms of depression were more common in the HIV-positive group: 39 (20%) of the HIV-positive group and 13 (14%) of the HIV-negative group had PHQ-9 scores of ≥ 10, indicating moderate/severe depression (P = 0.64).

Smoking and Recreational Drug use

Sixty (30%) HIV-positive and 31 (33%) HIV-negative participants were current smokers; 54 (28%) and 22 (25%), respectively, were ex-smokers (Table 3). In smokers, PLWH reported more intensive smoking than HIV-negative individuals, with a median of 15 (IQR 8–20) vs. 10 (5–13) cigarettes per day for current smokers, respectively (P < 0.001).

Past recreational drug use was more often reported in those with HIV infection, with 60% indicating drug use ever compared with 48% of HIV-negative participants (P = 0.05). No significant differences were found in the proportion of participants indicating any recreational drug use in the past 3 months.

Spirometry, Respiratory Symptoms and Health-related Quality of Life

Spirometry was within normal limits in most people: 18 (11%) HIV-positive and seven (9%) HIV-negative participants had evidence of airflow obstruction (FEV1/FVC < 0.7) (P = 0.55).

The MRC dyspnoea and SGRQ scores suggested a higher prevalence of breathlessness and respiratory health status impairment in PLWH (Table 4). SGRQ scores were higher in the HIV-positive group for all domains, with median SGRQ Total scores of 12 in the PLWH and 6 in HIV-negative participants (P < 0.01). Breathlessness was more common in the HIV-positive group, with 47% having an MRC dyspnoea score ≥ 2 (on a scale of 1–5), suggesting at least moderate breathlessness, compared with 25% of the HIV-negative participants (P = 0.001); 13% of HIV-positive vs. 1% of HIV-negative participants had MRC dyspnoea scores of ≥ 3 (P = 0.001).

There was no significant difference in general health-related quality of life scores between the HIV-positive and HIV-negative groups, with median EQ5D (UK) index values of 0.88 and 0.85 (P = 0.06) and median Visual Analogue Scale scores of 78 and 72, respectively (P = 0.46).

Factors Associated With Respiratory Health Status Impairment in Univariable Analyses

In addition to HIV status, we explored other possible contributors to impaired respiratory health in the whole study sample (Table S1). Higher SGRQ scores were associated with impaired lung function, with a median total SGRQ score of 28.5 (IQR 7.2–41.9) in people with an FEV1 < 80% predicted compared with 9.1 (IQR 4.4–17.4) in those with an FEV1 in the normal range (P < 0.01). Symptoms of depression were associated with impaired self-reported respiratory health status: median SGRQ Total scores were 26.5 in the 52 participants with PHQ-9 scores of ≥ 10, and 7.7 in the 238 participants with PHQ-9 scores < 10.

Combining HIV-positive and HIV-negative groups, no significant associations were found between gender, ethnicity, smoking status or recreational drug use and impaired respiratory health status in univariable analyses. An association between body mass index (BMI) and SGRQ Total score was seen (with higher scores in those with BMI < 20 or > 25), which approached statistical significance (P = 0.07).

Associations Between HIV-related Parameters and Respiratory Health

In analyses restricted to HIV-positive participants, neither current nor nadir CD4 count was significantly associated with higher SGRQ Total score (although trends were seen for higher scores being related to lower current or nadir blood CD4 counts). No significant difference in median SGRQ Total score was identified in those with and without an HIV load < 40 copies/mL (Table 5). After adjustment for age in a log-scale linear regression model, there was a trend towards higher SGRQ Total scores in people with a longstanding HIV diagnosis. A significant association was present between higher SGRQ Total score and longer interval from HIV diagnosis to starting ART.

Multivariable Analysis of Factors Associated With Respiratory Health Status Including all Participants

To allow adjustment for potential confounding factors, we constructed multivariable (log scale) linear regression models including all participants, with log SGRQ as the dependent variable. In addition to those factors chosen a priori (smoking status, age and gender), PHQ-9 scores and BMI were also included as they reached statistical significance at the 5% level in univariable analysis.

After adjustment for these other factors, HIV infection remained independently associated with an increased SGRQ Total score, with a 54% higher SGRQ Total score compared with HIV-negative individuals [adjusted fold-change 1.54; 95% confidence interval (CI) 1.14–2.09; P = 0.005] (Table 6). Depression (PHQ-9 score ≥ 10) was also independently associated with a higher SGRQ Total score (adjusted fold-change 1.90; 95% CI 1.42–2.53; P < 0.001).

We found similar factors to be independently associated with an MRC dyspnoea score ≥ 2 in a multivariable logistic regression model (Table S2). Here, the adjusted odds ratio (aOR) for an MRC dyspnoea score of ≥ 2 was 2.84 (95% CI 1.35–6.00; P = 0.006) in HIV-positive compared with HIV-negative participants. Independent associations were found with female gender (aOR 4.69; 95% CI 1.85–11.45; P = 0.001) and depression (aOR 6.30; 95% CI 2.75–14.46; P < 0.001).

Comparing HIV-positive Participants With an Undetectable HIV Viral Load With HIV-negative Participants

As other studies have suggested that untreated HIV infection is associated with chronic respiratory impairment,[18,19] a greater prevalence of respiratory symptoms within the PLWH population as a whole might result from increased symptoms only among HIV-positive individuals not yet taking ART, or on ART without virological suppression. We therefore undertook a subgroup analysis comparing HIV-negative participants with HIV-positive participants whose HIV viral load was measured as being undetectable (< 40 copies/mL) within 6 months of the study visit. Participants who declined consent to access clinical records were excluded from this analysis, leaving 157 HIV-positive participants with documented virological suppression, compared with the 93 HIV-negative participants. Those with virological suppression had similar demographic characteristics to the PLWH study population as a whole (Table S3) and had a median CD4 count of 684 (IQR 473–839) cells/μL. The differences in respiratory health scores between HIV-positive (HIV suppressed) and HIV-negative groups were similar to those present in the complete data set: median SGRQ Total scores were 12 (IQR 6–25) and 6 (IQR 2–14), respectively (P < 0.001); and seventy (47.3%) of the HIV-positive group had MRC dyspnoea scores of ≥ 2 compared with 20 (24.7%) of the HIV-negative group (P = 0.001). In a log-scale linear regression model (including the same predictive factors as the whole-group analysis), HIV status remained independently associated with a higher SGRQ Total score, with a similar effect size to that in the whole group (fold-change in SGRQ 1.53; 1.13–2.06; P = 0.007).

Sensitivity Analysis

To further explore the possible effect of the difference in age distribution between the HIV-positive and HIV-negative groups, we undertook a sensitivity analysis where we examined only those aged ≤ 52 years (the 75th centile of the HIV-negative participants). Using this restricted analysis (including 127 HIV-positive and 69 HIV-negative participants), the age distributions were similar, with a median age of 42 years in both groups. The previously demonstrated differences remained, with median SGRQ Total scores of 11.2 (IQR 6–20) in the PLWH and 6.2 (IQR 3–15) in the HIV-negative group (P = 0.01). MRC dyspnoea scores were also higher, with 55 (46%) of the HIV-positive and 16 (27%) of the HIV-negative participants having a MRC dyspnoea score ≥ 2 (P = 0.01).

Discussion

We compared HIV-positive individuals to an HIV-negative group with similar exposures to risk factors such as tobacco smoking. Our results suggest that HIV infection remains associated with impaired respiratory health despite virological suppression on ART. Although some differences were present in the age and ethnicity compositions of our two groups, these could not explain the differences in respiratory health status seen after adjustment in multivariable analyses.

Breathlessness was common in HIV-positive participants, with 47% of PLWH reporting this to be present and of at least moderate severity, compared with 25% of the HIV-negative participants. Using the SGRQ respiratory health questionnaire (which assesses not only respiratory symptoms but also the impacts on activity and quality of life), we found a 6-point difference in the median total score between HIV-positive and HIV-negative groups (a minimum clinically important difference in SGRQ being around 4 points[20]), suggesting that there is a meaningful impairment of the respiratory health of PLWH. This difference was present despite the prevalence of airflow obstruction in our HIV-positive subjects (11%) being lower than that reported in other HIV-positive populations (for instance 23% in Italy and 27% in the USA[8,21]). Of note, there was also no difference in the prevalence of airflow obstruction in our study between the HIV-positive and HIV-negative groups.

To our knowledge, no other study has used patient-reported outcomes to compare respiratory health status in HIV-positive and HIV-negative populations. Two previous reports used the SGRQ to evaluate respiratory health in HIV-positive adults: Hirani et al. evaluated 98 consecutive HIV-positive individuals (84% male) attending HIV care services in Philadelphia, USA, and found a mean SGRQ Total score of 7;[22] in contrast, Leung et al. reported a mean SGRQ Total score of 32 in 199 HIV-positive men attending care services in Vancouver, Canada.[9] Our data therefore provide the first estimate of the difference in respiratory health (as experienced by individuals) between HIV-positive adults with optimized access to ART and HIV-negative adults.

What might be contributing to these findings? Impairment of lung function not measured by spirometry may be present, which could result from a higher frequency of respiratory infection prior to effective ART and lead to long-term lung damage:[23] this could also result from the direct effect of HIV in the lung.[24] Other possibilities include cardiovascular disease or other nonrespiratory comorbidities which can lead to respiratory symptoms. Depression was strongly associated with impaired respiratory health in our population and this may contribute to the burden of physical symptoms (although it should be noted that the difference in respiratory health status persisted after adjustment for depression in our population). Persistent HIV-associated immune dysregulation despite ART may also contribute – an effect documented in the development of atherosclerosis.[25] This hypothesis is supported by Attia et al.’s finding that levels of circulating CD14 are associated with radiographic emphysema in HIV-positive individuals.[26] Prospective studies are needed to determine the relative importance of these possible causes.

The strengths of our study include the presence of an HIV-negative control group with similar exposures to tobacco smoking and recreational drugs and the use of well-validated measures of respiratory health status. Our high response rate (72%) suggests that participants were representative of the wider clinic population, who in turn are similar to the UK HIV-infected population as a whole.[27]

Limitations include recruitment at a single study site and the cross-sectional nature of the data collected, meaning that temporality cannot be established. As people were not randomly selected to participate, recruitment bias is possible. Spirometry was our only objective measure of lung function, whereas several studies have suggested that impairment of gas transfer is more common than airflow obstruction in PLWH.[28,29] The differences in age and ethnicity between groups could have influenced our results; however, our findings persisted after adjustment in multivariable analyses; and our sensitivity analysis is reassuring in that the difference in age distribution between HIV-positive and HIV-negative participants appeared to have little impact on the results. Finally, we relied on self-reported HIV status in the HIV-negative participants, so we cannot exclude the possibility that HIV-positive or undiagnosed individuals were included in this group. However, we believe that this is unlikely to be a major issue as the prevalence of undiagnosed HIV infection in our sexual health clinics is low (data not shown). If this did occur, it would have acted to weaken the association between HIV infection and respiratory health status impairment.

Interventions that can preserve the respiratory health of people with chronic HIV infection are needed. The earlier use of ART may reduce non-AIDS-related comorbidities, including respiratory illness – although, notwithstanding a median duration of follow-up of only 2.8 years, this was not associated with differences in lung function decline in the recent Strategic Timing of Antiretroviral Treatment (START) trial.[30] However, the impaired respiratory health of PLWH despite effective virological suppression found in our study suggests that more than ART alone is required to maintain the health of this population. Reducing the effect of known risk factors such as tobacco is important, as many HIV-positive populations have high rates of smoking.[31,32] Thus, the provision of appropriate smoking cessation services should be a priority. However, why HIV infection is associated with apparent worse respiratory health even in never-smokers remains uncertain and requires further investigation.

#Adult Tonsillitis: Causes, Symptoms & Treatments

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Adult Tonsillitis: Causes, Symptoms & Treatments

By Medical-Online | October 6, 2017

The tonsils are situated at the back of the throat, one on each side and two in total. They are made of glandular (lymphatic) tissues, and look like two small pads. Their main role is to protect your mouth from bacteria by creating white blood cells and antibodies that attack germs entering your mouth.

Tonsillitis occurs when bacteria or viruses infect the tonsils, causing them to become inflamed. This condition can affect anyone: although tonsillitis is more common in children, tonsillitis among adults is not uncommon.

Resultado de imagem para tonsillitis

What Causes Adult Tonsillitis?

Tonsillitis is caused by either a viral or bacterial infection. The condition can be caught by breathing into infected viral or bacterial droplets, which can be expelled from an infected person via a sneeze or a caught. It is also possible for other methods of contact to spread the infection.

There have also been cases of tonsillitis which have had fungal or parasitic causes. The most common causes are the viruses Epstein-Barr, and adenovirus. If tonsillitis is caused by Group A streptococcal bacteria, then it is often referred to as “strep throat.”

What Are the Symptoms of Tonsillitis in Adults?

There are many symptoms that are caused by tonsillitis which can also be attributed to other conditions.If you experience any of the symptoms below, ensure to speak with your health care professional.

1. Tonsil-Related Symptoms

Tonsillitis causes the tonsils to become inflamed, which leads to many physical changes that can be noted as symptoms of the condition. The tonsils may be swollen, and it is often the case that the lymph nodes also become inflamed and firm. If the tonsils have white spots on them, your tonsillitis may be caused by a bacterial infection.

2. Throat-Related Symptoms

The most common symptom of tonsillitis experienced by many is a sore throat, which can also include difficulty and pain when swallowing. It is also possible for sever tonsillitis to develop into a mild case of laryngitis, which can lead to a scratchy throat or potentially the inability to speak.

3. Flu-Like Symptoms

Due to the nature of the condition, and the bacterial or viral cause of tonsillitis, it is common for those infected to experience flu-like symptoms. These can include fevers, headaches, ear aches or body aches.

How to Treat Tonsillitis in Adults

The treatment for tonsillitis varies, from doing nothing at one end of the spectrum, to surgical removal of the tonsils at the other. It is possible for tonsillitis to go away on its own when caused by a virus, but other treatments may also be required. Below are the treatments currently used for adults suffering with tonsillitis.

1. Home Remedies

Home remedies, or home care strategies, are the only method of treatment used when tonsillitis is caused by a viral infection. These treatments are to ease the symptoms and to speed up the recovery. Some at home strategies that have helped those experiencing symptoms are

Rest – Ensure to get plenty of rest and avoid any strenuous physical activity. Also make sure you get plenty of sleep.
Hydrate – Ensure to remain hydrated and drink lots of water.
Diet – Avoid spicy, acidic, and hard, rough foods during the recovery. Drink clear fluids and broths. Ices can also help to ease a sore throat.
Gargle Saltwater – If you can, gargle water mixed with salt to ease a sore throat. Mix about one teaspoon of salt into a glass of warm water, gargle and spit out. Ensure you do not swallow it.
Control Air Humidity – If the air around you is dry, then this can worsen the symptoms. Use a cool-air humidifier to humidify the dry air.
Avoid Irritating Substances – Avoid irritants such as cleaning chemicals and smoke.
Medication – Medication that can be bought over the counter, such as ibuprofen, can be used to ease the discomfort of tonsillitis.
You can also watch the video below to try some natural home remedies to ease the symptoms of tonsillitis.

2. Drugs

If the cause of tonsillitis in adults is discovered to be bacterial, then your health care professional will prescribe a course of antibiotics to eliminate the bacterial infection for you. The most common treatment is penicillin taken orally. It is very important to take the medication as directed by your doctor. This means, continuing the treatment even if the symptoms dissipate.Failure to do so can cause the bacterial infection to come back again. It is also important not to take more than suggested at one time, as this could also lead to further complications.

3. Surgery
If other treatment methods have been deemed to be ineffective, then surgery is the final solution. Surgery will be suggested for those with chronic or bacterial tonsillitis that do not respond to antibacterial treatment. Surgery will also be suggested to those who have frequently occurring tonsillitis. If the symptoms of a patient’s tonsillitis make their life unmanageable, then surgery will be suggested immediately. This includes if a patient is having trouble breathing or eating. The surgery, also known as a tonsillectomy, usually takes around an hour and generally requires no overnight stay at the hospital. The recovery time varies from five to ten days.

#Experts Alarmed by Yellow Fever Cases in Asia

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Experts Alarmed by Yellow Fever Cases in Asia

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Janis C. Kelly  October 03, 2017     Eleven cases of yellow fever (YF) brought to China in 2016 were quickly contained but set off fear that the disease might gain a foothold in Asia, where 1.8 billion unvaccinated people could be at risk.The introduction, by workers returning to China from Angola, highlight the dire straits epidemiologists face in trying to contain a disease with limited vaccine supplies. Shortages of YF vaccine developed because of outbreaks and the need for mass vaccinations in Angola and Brazil. By July 24, 2017, stocks of the only YF vaccine approved in the United States had been depleted, and supplies are not expected to become available for routine civilian use again until mid-2018.Daniel R. Lucey, MD, MPH, and Halsie Donaldson, MS, both from the Division of Infectious Diseases, Georgetown University Medical, Washington, DC, write that the new risk for YF in Asia means that “the global vaccine stockpile must contain more than the projected 1.38 billion doses needed to eliminate existing YF epidemics by 2026.” They published their findings online September 25 in Annals of Internal Medicine. The authors also explain that the 80-year-old, egg-based method currently used to manufacture YF vaccine cannot be scaled up quickly enough to stop urban epidemics.”Thus, new YF vaccines based on cell culture and DNA technologies should be developed now, rather than in the mid to long term cited in the [World Health Organization’s] Global Strategy to Eliminate Yellow fever Epidemics,” the authors write.Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine, professor of Pediatrics and Molecular & Virology and Microbiology, and head of Pediatric Tropical Medicine at Baylor College of Medicine, Houston, Texas, agreed that new methods for producing YF vaccine are urgently needed, even without the potential for YF outbreaks in Asia.”With regard to Asia, it remains somewhat of a mystery as to why YF has not spread there, as has Japanese encephalitis. Some have speculated that circulating dengue and [Japanese encephalitis] strains may provide some cross-protective herd immunity, but we really don’t know the answer,” Dr Hotez told Medscape Medical News. “But there are 3 million Chinese working in Africa now, through their belts-and-road initiative, and there is a theoretical threat to Asia. Moreover, we can be sufficiently concerned about YF in the western hemisphere and Africa alone to raise the issue of YF vaccine shortage.”Dr Hotez said that Dr Lucy and Donaldson are right to be concerned about the potential for YF outbreaks in both Africa and the Americas, as well as the possibility of YF vaccine shortages. “In the western hemisphere, we have seen during the last few years the rise of dengue, Zika, chikungunya, and other arboviruses transmitted by Aedes aegypti, so the threat of YF is very real. This is due to shifts in poverty and climate change. The risk to other areas, including the United States, has been further heightened by increased population density in urban areas, making transmission more likely, and by the widespread presence of mosquitoes able to transmit the virus,” he said.However, Dr Hotez also echoed the comment by Seth Berkley, MD, chief executive from Global Alliance for Vaccines and Immunization, that emergency vaccine stockpiles should be the last line of defense against YF, after better mosquito control, routine YF immunization, and preemptive vaccination campaigns. According to Dr Berkley, emergency YF vaccine stockpiles are essential, but “if we have to call upon them, we have in some way already failed. They should be our last line of defense.”
Dr Berkley notes that the current global emergency stockpile of YF vaccine is about 6 million doses, a supply that could be quickly exhausted if Rio (population 12 million) and one other major city had YF outbreaks.Meanwhile, shortages in the United States are already limiting the availability of YF travel vaccinations, which are required for travelers to enter some countries.Dr Hotez told Medscape Medical News that part of the problem is the demand for YF vaccine has not been high until recently. “There is not always a high market incentive for vaccine manufacturers to make vaccines for pandemic threats, which is why the new organization [Coalition for Epidemic Preparedness Innovations] has been established,” he said.In the United States, YF vaccination is not routinely recommended except for patients traveling to an endemic area. Containing a potential outbreak is likely to be complicated by the fact that few US physicians have ever seen a case of YF, which causes a self-limited fever in 85% of patients but black vomit; bleeding from nose, mouth, and eyes; jaundice; and renal damage in the other 15%, half of whom die from the infection.

The authors and Dr Hotez have disclosed no relevant financial relationships.Ann Intern Med. Published online September 26, 2017.

Medscape Medical News © 2017

#Statins may reduce risk for #Staphylococcus aureus bacteraemia

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The association was most pronounced among patients with chronic kidney disease and diabetes.
Statin users have a 27 per cent lower risk of contracting community-acquired Staphylococcus aureus bacteremia (CA-SAB) according to a new  study  published in Mayo Clinic Proceedings.
For the study, researchers from Denmark and Spain analysed records of close to 30,000 people using Danish medical registries over a 12-year period. Statin users were categorised as current users (new or long-term use), former users, and nonusers.
They found the risk for CA-SAB decreased gradually with increasing statin dosage, and the association was most pronounced among patients with chronic kidney disease and diabetes. Adjusted odds ratios (OR) were 0.96 for new users, 0.71 for long-term users, and 1.12 for former users compared with nonusers. Compared with nonusers, adjusted OR was 0.84 for current users receiving less than 20mg/d, 0.71 for 20-39 mg/d, and 0.63 for 40mg/d or more.
“Our results indicate that statins may have an important place in the prevention of bloodstream infection caused by S. aureus, which would hold important clinical and public health implications. Nevertheless, our observations warrant confirmation in other settings and the biological mechanisms by which statin treatment may protect against this type of infection should be explored further,” said lead investigator Jesper Smit.

#Smokers With #HIV Face Higher Risk From #Lung Cancer Than From #AIDS

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By Lisa Rapaport

(Reuters Health) – Smokers living with HIV who consistently take antiretroviral medications may be far more likely to die of lung cancer than of AIDS, a U.S. study suggests.

Roughly 60,000 of the 644,200 adults age 20 to 64 currently in treatment for HIV in the U.S. will die of lung cancer by age 80 if current smoking habits don’t change, researchers estimate.

“Today, the number one killer of people with HIV on treatment in the U.S. is not the virus, it’s smoking,” said lead study author Dr. Krishna Reddy of Massachusetts General Hospital and Harvard Medical School in Boston.

“The widespread use of antiviral medicines today is enabling people with HIV to live longer, but they are now dying from cancer at rates often higher than those among the general population,” Reddy said by email. “Lung cancer is chief among these cancers.”

More than 40% of people living with HIV in the U.S. smoke cigarettes, more than double the prevalence in the general population, researchers note in JAMA Internal Medicine, online September 18.

For the study, researchers estimated the odds of dying from lung cancer based on whether people starting HIV care at age 40 were current smokers, and if so, whether or not they quit.

Overall, they found, people with HIV who continued to smoke were 6 to 13 times more likely to die from lung cancer than from traditional AIDS-related causes.

Among men who smoked and continued to do so, researchers estimated that 29% of the heavy smokers would die of lung cancer by age 80, as would 23% of moderate smokers and 19% of light smokers.

For women who smoked and continued to do so, researchers estimated that 29% of heavy smokers would die of lung cancer by age 80, as would 21% of moderate smokers and 17% of light smokers.

Men and women with HIV who quit smoking would see their risk of dying from lung cancer go down dramatically, however.

The study wasn’t a controlled experiment designed to prove how smoking influences mortality in people living with HIV, the authors note.

People with HIV may have worse survival odds with lung cancer because they’re diagnosed when tumors are more advanced or because their immune systems are less able to tolerate cancer treatments, said Dr. Ronald Mitsuyasu of the David Geffen School of Medicine at the University of California, Los Angeles.

“This may also be due in part or primarily to higher tobacco use, and should strongly support quitting,” Mitsuyasu, who wasn’t involved in the study, said by email.

With effective treatment, people living with HIV have a similar life expectancy to people not infected with the virus, said Dr. Anthony Olszanski of Fox Chase Cancer Center in Philadelphia.

“HIV-infected people have taken charge of their fate by being compliant with their antiretroviral medication,” Olszanski, who wasn’t involved in the study, said by email.

“It is important for them now to take charge of their other health-related risks,” Olszanski added. “Quitting smoking is likely to drastically decrease their risk of developing lung cancer as well as other smoking-related illnesses.”

SOURCE: http://bit.ly/2fvfM4A

JAMA Intern Med 2017.