Combined Rapid (TUBEX) Test for Typhoid-Paratyphoid A Fever Based on Strong Anti-O12 Response: Design and Critical Assessment of Sensitivity

Rapid diagnostics can be accurate but, often, those based on antibody detection for infectious diseases are unwittingly underrated for various reasons. Herein, we described the development of a combined rapid test for two clinically-indistinguishable bacterial diseases, typhoid and paratyphoid A fever, the latter fast emerging as a global threat. By using monoclonal antibodies (mAbs) to bacterial antigens of known chemical structures as probes, we were able to dissect the antibody response in patients at the level of monosaccharides. Thus, a mAb specific for a common lipopolysaccharide antigen (O12) found in both the causative organisms was employed to semi-quantify the amounts of anti-O12 antibodies present in both types of patients in an epitope-inhibition particle-based (TUBEX) immunoassay. This colorimetric assay detected not only anti-O12 antibodies that were abundantly produced, but also, by steric hindrance, antibodies to an adjoining epitope (O9 or O2 in the typhoid or paratyphoid bacillus, respectively). Sensitivity and, particularly, reaction intensities, were significantly better than those obtained using an anti-O9 or anti-O2 mAb-probe in the examination of paired sera from 22 culture-confirmed typhoid patients (sensitivity, 81.8% vs 75.0%) or single sera from 36 culture-confirmed paratyphoid patients (52.8% vs 28.6), respectively. Importantly, sensitivity was better (97.1% for typhoid, 75.0% for paratyphoid) if allowance was made for the absence of relevant antibodies in certain specimens as determined by an independent, objective assay (ELISA) — such specimens might have been storage-denatured (especially the older paratyphoid samples) or procured from non-responders. Benchmarking against ELISA, which revealed high concordance between the two tests, was useful and more appropriate than comparing with culture methods as traditionally done, since antibody tests and culture target slightly different stages of these diseases. Paired sera analysis was insightful, revealing 64% of typhoid patients who had no change in antibody titer over 4–16 days, and 14% with no IgM-IgG class-switching

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress

Prevention and assessment of infectious diseases among children and adult migrants arriving to the European Union/European Economic Association: a protocol for a suite of systematic reviews for public health and health systems.

INTRODUCTION: The European Centre for Disease Prevention and Control is developing evidence-based guidance for voluntary screening, treatment and vaccine prevention of infectious diseases for newly arriving migrants to the European Union/European Economic Area. The objective of this systematic review protocol is to guide the identification, appraisal and synthesis of the best available evidence on prevention and assessment of the following priority infectious diseases: tuberculosis, HIV, hepatitis B, hepatitis C, measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis (polio), Haemophilus influenza disease, strongyloidiasis and schistosomiasis. METHODS AND ANALYSIS: The search strategy will identify evidence from existing systematic reviews and then update the effectiveness and cost-effectiveness evidence using prospective trials, economic evaluations and/or recently published systematic reviews. Interdisciplinary teams have designed logic models to help define study inclusion and exclusion criteria, guiding the search strategy and identifying relevant outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: There are no ethical or safety issues. We anticipate disseminating the findings through open-access publications, conference abstracts and presentations. We plan to publish technical syntheses as GRADEpro evidence summaries and the systematic reviews as part of a special edition open-access publication on refugee health. We are following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols reporting guideline. This protocol is registered in PROSPERO: CRD42016045798

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Determining the HPV vaccine schedule for a HIV-infected population in sub Saharan Africa, a commentary

Background: Epidemiological studies have established human papillomavirus (HPV) infection as the central cause of invasive cervical cancer (ICC) and its precursor lesions. HIV is associated with a higher prevalence and persistence of a broader range of high-risk HPV genotypes, which in turn results in a higher risk of cervical disease. Recent WHO HPV vaccination schedule recommendations, along with the roll out of HAART at an earlier CD4 count within the female HIV-infected population, may have programmatic implications for sub Saharan Africa. This communication identifies research areas, which will need to be addressed for determining a HPV vaccine schedule for this population in sub Saharan Africa. A review of WHO latest recommendations and the evidence concerning one-dose HPV vaccine schedules was undertaken. Conclusion: For females >= 15 years at the time of first dose and immunocompromised and/or HIV-infected, a 3-dose schedule (0, 1-2, 6 months) is recommended for all three vaccines. There is some evidence that there is similar protection against HPV 16 and 18 infection from a single vaccination than from two or three doses, however there is no cross protection conferred to other genotypes. There is a need for periodic prevalence studies to determine the vaccination coverage of bivalent, quadrivalent and nonavalent vaccine targeted oncogenic HPV genotypes in women with CIN 3 or ICC at national level. In light of the increasing number of sub Saharan HIV-infected girls initiating HAART at a CD4 count above 350 mm(3), there are a number of clinical, virological and public health research gaps to address before a tailored vaccine schedule can be established for this population

PYY is a negative regulator of bone mass and strength

Objective Bone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal, anorexigenic hormone, peptide YY (PYY). Selective deletion of the PYY receptor Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY in mice has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. As PYY analogs are under development for treatment of obesity, we aimed to clarify the relationship between PYY and bone mass. Methods The skeletal phenotype of Pyy knockout (KO) mice was investigated during growth (postnatal day P14) and adulthood (P70 and P186) using X-ray microradiography, micro-CT, back-scattered electron scanning electron microscopy (BSE-SEM), histomorphometry and biomechanical testing. Results Bones from juvenile and Pyy KO mice were longer (P < 0.001), with decreased bone mineral content (P < 0.001). Whereas, bones from adult Pyy KO mice had increased bone mineral content (P < 0.05) with increased mineralisation of both cortical (P < 0.001) and trabecular (P < 0.001) compartments. Long bones from adult Pyy KO mice were stronger (maximum load P < 0.001), with increased stiffness (P < 0.01) and toughness (P < 0.05) compared to wild-type (WT) control mice despite increased cortical vascularity and porosity (P < 0.001). The increased bone mass and strength in Pyy KO mice resulted from increases in trabecular (P < 0.01) and cortical bone formation (P < 0.05). Conclusions These findings demonstrate that PYY acts as a negative regulator of osteoblastic bone formation, implicating increased PYY levels in the pathogenesis of bone loss during anorexia or following bariatric surgery

Health sector reforms and human resources for health in Uganda and Bangladesh: mechanisms of effect

BACKGROUND: Despite the expanding literature on how reforms may affect health workers and which reactions they may provoke, little research has been conducted on the mechanisms of effect through which health sector reforms either promote or discourage health worker performance. This paper seeks to trace these mechanisms and examines the contextual framework of reform objectives in Uganda and Bangladesh, and health workers' responses to the changes in their working environments by taking a 'realistic evaluation' approach. METHODS: The study findings were generated by triangulating both qualitative and quantitative methods of data collection and analysis among policy technocrats, health managers and groups of health providers. Quantitative surveys were conducted with over 700 individual health workers in both Bangladesh and Uganda and supplemented with qualitative data obtained from focus group discussions and key interviews with professional cadres, health managers and key institutions involved in the design, implementation and evaluation of the reforms of interest. RESULTS: The reforms in both countries affected the workforce through various mechanisms. In Bangladesh, the effects of the unification efforts resulted in a power struggle and general mistrust between the two former workforce tracts, family planning and health. However positive effects of the reforms were felt regarding the changes in payment schemes. Ugandan findings show how the workforce responded to a strong and rapidly implemented system of decentralisation where the power of new local authorities was influenced by resource constraints and nepotism in recruitment. On the other hand, closer ties to local authorities provided the opportunity to gain insight into the operational constraints originating from higher levels that health staff were dealing with. CONCLUSION: Findings from the study suggest that a) reform planners should use the proposed dynamic responses model to help design reform objectives that encourage positive responses among health workers b) the role of context has been underestimated and it is necessary to address broader systemic problems before initiating reform processes, c) reform programs need to incorporate active implementation research systems to learn the contextual dynamics and responses as well as have inbuilt program capacity for corrective measures d) health workers are key stakeholders in any reform process and should participate at all stages and e) some effects of reforms on the health workforce operate indirectly through levels of satisfaction voiced by communities utilising the services