Measures of health and disease in Africa: are current methods giving us useful information about trends in cardiovascular diseases?

An enormous burst of interest in the public health burden from chronic disease in Africa has emerged as a consequence of efforts to estimate global population health. Detailed estimates are now published for Africa as a whole and each country on the continent. These data have formed the basis for warnings about sharp increases in cardiovascular disease (CVD) in the coming decades. In this essay we briefly examine the trajectory of social development on the continent and its consequences for the epidemiology of CVD and potential control strategies. Since full vital registration has only been implemented in segments of South Africa and the island nations of Seychelles and Mauritius - formally part of WHO-AFRO - mortality data are extremely limited. Numerous sample surveys have been conducted but they often lack standardization or objective measures of health status. Trend data are even less informative. However, using the best quality data available, age-standardized trends in CVD are downward, and in the case of stroke, sharply so. While acknowledging that the extremely limited available data cannot be used as the basis for inference to the continent, we raise the concern that general estimates based on imputation to fill in the missing mortality tables may be even more misleading. No immediate remedies to this problem can be identified, however bilateral collaborative efforts to strength local educational institutions and governmental agencies rank as the highest priority for near term development.

Respiratory effects of an exposure to grain dust among grain workers in the Vaud region (Switzerland)

Introduction: Bioaerosols such as grain dust, via biologically active agents, elicit local inflammation and direct immunological reactions within the human respiratory system. Workplace-dependent exposure to grain dust (GD) may thus induce asthma, chronic bronchitis, and hypersensitivity pneumonitis. The aim of this study is to assess the clinical impact of occupational exposure to GD and to determine quantitative biological markers of bioaerosol exposure in grain workers. Methods: This longitudinal study has been conducted from summer 2012, to summer 2013, comprising 6 groups of 30 active workers with different GD exposure patterns (4 groups of grain workers, 2 control groups). After obtaining informed consent, two evaluations at high- and low-exposing seasons take place, during which an occupational history and a detailed medical history are questionnaire-assessed, lung function is evaluated by spirometry, airway inflammation is measured by exhaled nitric oxide (eNO), and specific blood IgG and IgE are titrated. The preliminary results presented hereafter are those of two of the four exposed groups, namely harvesters and mill workers, compared to the control groups, at first assessment (n=100). Results: Mean age is 38.4 [years]; 98% are male. Exposed groups differ from controls (p<0.05) in daily contact with animals (57% vs. 40%) and active smoking (39% vs. 11%). Grain workers have more respiratory (50%), nasal (57%), ocular (45%), dermatologic (36%) and systemic (20%) occupational symptoms than controls (6.4%, 19%, 16%, 6.4%, 1.6% respectively, p<0.05). Lower mean peak-expiratory-flow (PEF) values (96.1 ± 18.9 vs. 108.2 ± 17.4 [% of predicted], p<0.05) and eNO values (13.9 ± 9.6 vs. 20.5 ± 14.7 [ppm], p<0.05) are observed in the exposed groups. Conclusion: Preliminary results show a higher prevalence of clinical symptoms and a lower mean PEF value in the exposed groups. Detailed supplementary analyses are pending.

The global regulator GacA of Pseudomonas fluorescens CHA0 is required for the suppression of root diseases in dicotyledons but not in Gramineae

Pseudomonas fluorescens strain CHA0 suppresses various plant diseases caused by soil-borne fungi. The pseudomonad produces the antimicrobial metabolites 2,4-diacetylphloroglucinol (Phl), pyoluteorin (Plt) and hydrogen cyanide, which are important for disease suppression, as well as the siderophores pyoverdine (Pvd), salicylic acid (Sal) and pyochelin (Pch). In the current work, a derivative of CHA0 with a mutation in the global regulator gene gacA (GacA−), which is unable to produce Phl, Plt and HCN, failed to protect the dicotyledonous plants cress and cucumber against damping-off caused by Pythium ultimum. In contrast, the GacA− mutant could still protect the Gramineae wheat and maize against damping-off mediated by the same strain of P. ultimum, and wheat against take-all caused by Gaeumannomyces graminis. However, the GacA− mutant overproduced Pch and Pvd. To gain more insight into disease protection afforded by the GacA− mutant, a GacA− Pvd− double mutant (strain CHA496) was constructed by gene replacement. Strain CHA496 overproduced Pch and Sal compared with CHA0 and protected wheat against P. ultimum and G. graminis, whereas cress and cucumber were not protected. Addition of FeCl3 repressed Pch and Sal production by strain CHA496 in vitro and impaired the protection of wheat in soil microcosms. In conclusion, a functional gacA gene was necessary for the protection of dicotyledons against root diseases, but not for that of Gramineae. Results indicated also that Pch and/or Sal were involved in the ability of the GacA− Pvd− mutant of CHA0 to suppress root diseases in Gramineae.

Do different measures of early life socioeconomic circumstances predict adult mortality? Evidence from the British Whitehall II and French GAZEL studies

BACKGROUND: Father's occupational position, education and height have all been used to examine the effects of adverse early life socioeconomic circumstances on health, but it remains unknown whether they predict mortality equally well. METHODS: We used pooled data on 18,393 men and 7060 women from the Whitehall II and GAZEL cohorts to examine associations between early life socioeconomic circumstances and all-cause and cause-specific mortality. RESULTS: During the 20-y follow-up period, 1487 participants died. Education had a monotonic association with all mortality outcomes; the age, sex and cohort-adjusted HR for the lowest versus the highest educational group was 1.45 (95% CI 1.24 to 1.69) for all-cause mortality. There was evidence of a U-shaped association between height and all-cause, cancer and cardiovascular mortality robust to adjustment for the other indicators (HR 1.41, 95% CI 1.03 to 1.93 for those shorter than average and HR 1.36, 95% CI 0.98 to 1.88 for those taller than average for cardiovascular mortality). Greater all-cause and cancer mortality was observed in participants whose father's occupational position was manual rather than non-manual (HR 1.11, 95% CI 1.00 to 1.23 for all-cause mortality), but the risks were attenuated after adjusting for education and height. CONCLUSIONS: The association between early life socioeconomic circumstances and mortality depends on the socioeconomic indicator used and the cause of death examined. Height is not a straightforward measure of early life socioeconomic circumstances as taller people do not have a health advantage for all mortality outcomes.

Pharmacogenomics of HIV Therapy: Summary of a Workshop Sponsored by the National Institute of Allergy and Infectious Diseases

Approximately 1 million people in the United States and over 30 million worldwide are living with human immunodeficiency virus type 1 (HIV-1). While mortality from untreated infection approaches 100%, survival improves markedly with use of contemporary antiretroviral therapies (ART). In the United States, 25 drugs are approved for treating HIV-1, and increasing numbers are available in resource-limited countries. Safe and effective ART is a cornerstone in the global struggle against the acquired immunodeficiency syndrome. Variable responses to ART are due at least in part to human genetic variants that affect drug metabolism, drug disposition, and off-site drug targets. Defining effects of human genetic variants on HIV treatment toxicity, efficacy, and pharmacokinetics has far-reaching implications. In 2010, the National Institute of Allergy and Infectious Diseases sponsored a workshop entitled, Pharmacogenomics A Path Towards Personalized HIV Care. This article summarizes workshop objectives, presentations, discussions, and recommendations derived from this meeting.

Facteurs influençant le retour au travail après transplantation chez 61 patients rénaux ou hépatiques

Le taux de retour au travail après greffe est généralement bas. Or, on sait que le retour au travail après greffe améliore la qualité de vie des transplantés. Le but de notre étude était donc de comprendre les raisons possibles à ce faible taux en montrant les facteurs professionnels, individuels ou médicaux pouvant l'influencer. Parmi les 61 greffés rénaux ou hépatiques suivis au centre de transplantation d'organe (CTO) du CHUV, 39% ont repris le travail après greffe. Trois facteurs étaient significatifs de retour au travail après greffe, à savoir «travail avant greffe», «diplôme» et «âge < 45 ans». Ainsi, il est utile pour la pratique médicale de connaître les facteurs potentiels influençant le retour au travail car cela permet d'évaluer, au stade prégreffe, les chances de retour au travail et si besoin de proposer des mesures spécifiques le favorisant.

Changes in leisure time and occupational physical activity over 8 years: The Cornellà health Interview Survey Follow-Up Study

Aim: To describe changes in leisure time and occupational physical activity status in an urban Mediterranean population-based cohort, and to evaluate sociodemographic, health-related and lifestyle correlates of such changes. Methods: Data for this study come from the Cornellè Health Interview Survey Follow-Up Study, a prospective cohort study of a representative sample (n¿=¿2500) of the population. Participants in the analysis reported here include 1246 subjects (567 men and 679 women) who had complete data on physical activity at the 1994 baseline survey and at the 2002 follow-up. We fitted Breslow-Cox regression models to assess the association between correlates of interest and changes in physical activity. Results: Regarding leisure time physical activity, 61.6% of cohort members with ¿sedentary¿ habits in 1994 changed their status to ¿light/moderate¿ physical activity in 2002, and 70% who had ¿light/moderate¿ habits in 1994 did not change their activity level. Regarding occupational physical activity, 74.4% of cohort members who were ¿active¿ did not change their level of activity, and 64.3% of participants with ¿sedentary¿ habits in 1994 changed to ¿active¿ occupational physical activity. No clear correlates of change in physical activity were identified in multivariate analyses. Conclusion: While changes in physical activity are evident in this population-based cohort, no clear determinants of such changes were recognised. Further longitudinal studies including other potential individual and contextual determinants are needed to better understand determinants of changes in physical activity at the population level.

Limited heterogeneity of autoantigens and T cells in autoimmune diseases?

For many induced and spontaneous autoimmune diseases, a predominant role for T cells in the organ-specific destruction process has been shown. In one of the induced models of autoimmunity, experimental allergic encephalomyelitis (EAE), a very small heterogeneity of T-cell receptor (TcR) molecules is expressed by the pathogenic T cells in both rats and mice. Contrary to induced autoimmune diseases, little is known about the autoantigens recognized by these autoimmune T cells and the heterogeneity of their TcR in spontaneous autoimmune diseases. The aim of this work was to establish a system which allows characterization of relevant autoantigens in spontaneous insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. A completely different approach was taken to characterize the gene products of the minor lymphocyte stimulatory (Mls) loci. These gene products are responsible for the clonal elimination or the clonal stimulation of T cells expressing particular TcR V beta genes and therefore could be implicated in induction of autoimmune diseases by oligoclonal T-cell populations. The finding that Mls antigens are encoded by retroviral sequences leads to the hypothesis that viruses could be the inducing agents of autoimmune diseases.

Drug adherence in chronic kidney diseases and dialysis.

Poor long-term adherence and persistence to drug therapy is universally recognized as one of the major clinical issues in the management of chronic diseases, and patients with renal diseases are also concerned by this important phenomenon. Chronic kidney disease (CKD) patients belong to the group of subjects with one of the highest burdens of daily pill intake with up to >20 pills per day depending on the severity of their disease. The purpose of the present review is to discuss the difficulties encountered by nephrologists in diagnosing and managing poor adherence and persistence in CKD patients including in patients receiving maintenance dialysis. Our review will also attempt to provide some clues and new perspectives on how drug adherence could actually be addressed and possibly improved. Working on drug adherence may look like a long and tedious path, but physicians and healthcare providers should always be aware that drug adherence is in general much lower than what they may think and that there are many ways to improve and support drug adherence and persistence so that renal patients obtain the full benefits of their treatments.

Divergent effect of cobalt and beryllium salts on the fate of peripheral blood monocytes and T lymphocytes.

Occupational exposure to metals such as cobalt and beryllium represents a risk factor for respiratory health and can cause immune-mediated diseases. However, the way they act may be different. We show here that the two metals have a divergent effect on peripheral T lymphocytes and monocytes: BeSO(4) induces cell death in monocytes but not in T lymphocytes, which instead respond by producing Interferon gamma (IFN-γ); conversely, CoCl(2) induces apoptosis in T lymphocytes but not in monocytes. Interestingly, both metals induce p53 overexpression but with a dramatic different outcome. This is because the effect of p53 in CoCl(2)-treated monocytes is counteracted by the antiapoptotic activity of cytoplasmic p21(Cip1/WAF1), the activation of nuclear factor κB, and the inflammasome danger signaling pathway leading to the production of proinflammatory cytokines. However, CoCl(2)-treated monocytes do not fully differentiate into macrophage or dendritic cells, as inferred by the lack of expression of CD16 and CD83, respectively. Furthermore, the expression of HLA-class II molecules, as well as the capability of capturing and presenting the antigens, decreased with time. In conclusion, cobalt keeps monocytes in a partially activated, proinflammatory state that can contribute to some of the pathologies associated with the exposure to this metal.

Mandatory infectious diseases consultation for MRSA bacteremia is associated with reduced mortality.

OBJECTIVES: Although infectious disease (ID) consultation has been associated with lower mortality in Staphylococcus aureus bloodstream infections, it is still not mandatory in many centers. This study aimed at assessing the impact of ID consultation on diagnostic and therapeutic management of methicillin-resistant S. aureus (MRSA) bacteremia. METHODS: Retrospective cohort study of all patients with MRSA bacteremia from 2001 to 2010. ID consultations were obtained on request between 2001 and 2006 and became mandatory since 2007. RESULTS: 156 episodes of MRSA bacteremia were included, mostly from central venous catheter (32%) and skin and soft tissue (19%) infections. ID consultation coverage was 58% between 2001 and 2006 and 91% between 2007 and 2010. ID consultation was associated with more echocardiography (59% vs. 26%, p < 0.01), vancomycin trough level measurements (99% vs. 77%, p < 0.01), follow-up blood cultures (71% vs. 50%, p = 0.05), deep-seated infections (43% vs. 16%, p < 0.01), more frequent infection source control (83% vs. 57%, p = 0.03), a longer duration of MRSA-active therapy (median and IQR: 17 days, 13-30, vs. 12, 3-14, p < 0.01) and a 20% reduction in 7-day, 30-day and in-hospital mortality. CONCLUSIONS: ID consultation was associated with a better management of patients with MRSA bacteremia and a reduced mortality.

Neutrophils in infectious diseases

Host defense to intracellular pathogens depends upon both innate and adaptive cell-mediated immune responses. Polymorphonuclear neutrophil leukocytes which belong to the innate immune system are the first cells that are recruited massively within hours of microbial infection. Neutrophils are the main players in the killing of microorganisms and recently new methods of killing including nets formation have been described. Neutrophils mediate tissue damage at infected sites. By promoting tissue injury neutrophils contribute to the initiation of inflammation, which is now recognized as an essential step in launching immunity. The importance of neutrophils as decision shaper in the development of an immune response is only emerging as they have long been considered by immunologists as short lived, non-dividing cells, of poor interest. Now, neutrophils are emerging as key components of the inflammatory response, and are shown to have immunoregulatory roles in microbial infections. In addition, neutrophils were also reported to contribute to the recruitment and activation of antigen presenting cells. Thus early interactions between neutrophils and surrounding cells may influence the development/resolution of both inflammatory lesion and pathogen-specific immune response. The impact of neutrophils on cells present at the site of infection are only beginning to be studied and deserves more attention.In this e-book the reader will find updated information about the role of neutrophils in the pathogenesis of 1) bacterial diseases including sepsis, mycobacteria and Chlamydia infections, and of 2) parasitic diseases including leishmaniasis and toxoplasmosis. The role of neutrophils in the protection against microorganisms has largely been underestimated and, until recently, their role was mostly thought to limited to a "kill and die" response. New neutrophil mode of killing, such as their release of extracellular traps to kill extracellular bacterial pathogens, together with several microbial strategies designed to escape NETs are presented in Chapter 1. We will emphasize standard and advanced light microscopy techniques that allowed major advances in the understanding of neutrophil biology, through the visualization of the interaction of selected pathogens with neutrophils in living animals (Chapter 2).The aim of this e-book is to provide an overview of the recent advances made in the field of neutrophil biology. It will provide a basis for understanding future development that will occur in this area, and provide the reader with a short overview of some of the exciting new directions in which neutrophil research is moving.