Gershon A.A.,Columbia University |
Gershon M.D.,Columbia University |
Breuer J.,Center for Infectious Disease |
Levin M.J.,University of Colorado at Denver |
And 2 more authors.
Journal of Clinical Virology | Year: 2010
SUMMARY: The primary varicella zoster virus (VZV) infection results in chickenpox (varicella), which is transmitted via the airborne route. VZV is highly infectious, but in the USA the incidence of varicella has been reduced by 76-87% as a result of the varicella vaccine. The virus establishes latency in the dorsal root ganglia during varicella and, when reactivated, travels along the sensory nerve axons to cause shingles (herpes zoster [HZ]). There are over 1 million cases of HZ in the USA each year, with an estimated lifetime attack rate of 30%. The incidence of HZ, which causes significant morbidity, increases with age and reaches approximately 10 cases per 1,000 patient-years by age 80. Cell-mediated immunity (CMI) is known to decline with age as part of immunosenescence, and decreased CMI is associated with reactivation of VZV. This article provides an overview of our emerging understanding of the epidemiology and pathogenesis of varicella and HZ, in addition to exploring the current theories on latency and reactivation. Understanding the risk factors for developing HZ and the complications associated with infection, particularly in older people, is important for prompt diagnosis and management of HZ in primary care, and they are therefore also reviewed. © 2010 Elsevier B.V. All rights reserved.
Price C.L.,Imperial College London |
Hassi H.O.S.A.,Imperial College London |
English N.R.,Imperial College London |
Blakemore A.I.F.,Imperial College London |
And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010
Increased methylglyoxal (MG) concentrations and formation of advanced glycation end-products (AGEs) are major pathways of glycaemic damage in diabetes, leading to vascular and neuronal complications. Diabetes patients also suffer increased susceptibility to many common infections, the underlying causes of which remain elusive. We hypothesized that immune glycation damage may account for this increased susceptibility. We previously showed that the reaction mixture (RM) for MG glycation of peptide blocks up regulation of CD83 in myeloid cells and inhibits primary stimulation of T cells. Here, we continue to investigate immune glycation damage, assessing surface and intracellular cytokine protein expression by flow cytometry, T-cell proliferation using a carboxyfluorescein succinimidyl ester assay, and mRNA levels by RT-PCR. We show that the immunomodulatory component of this RM was MG itself, with MG alone causing equivalent block of CD83 and loss of primary stimulation. Block of CD83 expression could be reversed by MG scavenger N-acetyl cysteine. Further, MG within RM inhibited stimulated production of interleukin (IL)-10 protein from myeloid cells plus interferon (IFN)-γ and tumour necrosis factor (TNF)-α from T cells. Loss of IL-10 and IFN-γ was confirmed by RT-PCR analysis of mRNA, while TNF-α message was raised. Loss of TNF-α protein was also shown by ELISA of culture supernatants. In addition, MG reduced major histocompatibility complex (MHC) class I expression on the surface of myeloid cells and increased their propensity to apoptose. We conclude that MG is a potent suppressor of myeloid and T-cell immune function and may be a major player in diabetes-associated susceptibility to infection. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Halpin H.A.,University of California at Berkeley |
Milstein A.,Stanford University |
Shortell S.M.,University of California at Berkeley |
Vanneman M.,University of California at Berkeley |
Rosenberg J.,Center for Infectious Disease
Health Affairs | Year: 2011
One way to motivate hospitals to improve patient safety is to publicly report their rates of hospital-acquired infections, as California is starting to do this year. We conducted a baseline study of California's acute care hospitals just before mandatory reporting of hospital-acquired infection rates to the state began, in 2008. We found variability in many areas: For example, 70.1 percent of hospitals said that they were fully implementing evidence-based guidelines to fight infection by methicillin-resistant Staphylococcus aureus, but 22.8 percent of hospitals had not adopted any. Our analysis showed that rural hospitals, many of which lack resources to implement needed procedures, faced the greatest challenges in reporting and improving infection rates. Our findings should be of interest to Medicare policy makers who will implement the hospital-acquired infection performance measures in the Affordable Care Act, and to leaders in the thirty-eight states that have enacted legislation requiring reports of hospital-acquired infection rates. California's baseline data also present a unique opportunity to assess the impact of mandatory and public reporting laws. © 2011 by Project HOPE - The People-to-People Health Foundation, Inc.
An international team of scientists have developed a blood test, based on biomarkers in gene activity that can reliably predict whether a person with the Mycobacterium tuberculosis bacterium will develop active tuberculosis (TB). According to the World Health Organization, TB is the top infectious disease killer globally. In 2014, 9.6 million people became ill with TB and 1.5 million people died from the disease, which is spread from person to person through the air. About one-third of the world’s population has latent TB, which means they carry the bacteria but have not become ill and cannot transmit the disease. About 90 percent of people that carry the bacteria will not develop the illness, but 10 percent will develop symptoms. Up until now, there has been no way to predict wither a person infected by the bacteria will go on to develop active TB. For the study, published in online March 23 in The Lancet, researchers from the South African Tuberculosis Vaccine Initiative and the Center for Infectious Disease Research obtained blood samples from more than 10,000 subjects in Gambia and South Africa and analyzed gene activity. They collected blood samples from study participants every six months and monitored participants for two years. The findings identified a specific gene profile in immune cells in blood samples of people who eventually develop active TB, using whole blood RNA sequencing data from those who developed active TB compared to those who remained healthy. According to a statement the blood test can predict, with about 75 percent reliability, if active TB will develop. “Such a test could predict the occurrence of the disease more than a year before the disease develops,” lead investigator Willem Hanekom of the University of Cape Town said in a statement. “This long lead period will give doctors enough time to initiate treatment.” A parallel study is being led by Stefan H.E. Kaufmann of the Max Planck Institute for Infection biology to develop a pan-African biomarker test for TB by observing groups of subjects from several parts of Africa. The results will not be published until the end of the year, but findings so far suggest the same specific genes in immune cells are active, indicating an increased risk of developing active TB. “If we can predict early on that an individual will develop active tuberculosis, this will help greatly in containing the disease,” Kaufmann said in a statement. The blood test described in the recently published study will move to clinical trials to see if progression of the predicted active TB can be stopped with targeted treatment. Establish your company as a technology leader! For more than 50 years, the R&D 100 Awards have showcased new products of technological significance. You can join this exclusive community! Learn more.
Cornell M.,Center for Infectious Disease |
Johnson L.F.,Center for Infectious Disease |
Schomaker M.,Center for Infectious Disease |
Tanser F.,University of Cape Town |
And 11 more authors.
The Lancet HIV | Year: 2015
Background As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the eff ect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the eff ect of age on mortality of patients on ART in South Africa and whether this eff ect is mediated by baseline immunological status. Methods In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the fi rst time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDSSouthern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age. Findings Between Jan 1, 2004, and Dec 31, 2013, 84 078 eligible adults started ART. Of these, we followed up 83 566 patients for 174 640 patient-years. 8% (1817 of 23 258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44 909 patients still alive and in care were aged 50 years or older. Interpretation Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV. Funding National Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis.