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Co-diagnosis of HIV and tuberculosis presents a treatment dilemma. Starting both treatments at the same time can cause a flood of immune response called immune reconstitution inflammatory syndrome (IRIS) which can be lethal. But, how long to delay HIV treatment is less understood. In 2011, based on the conclusions of three separate studies, WHO recommended starting HIV treatment earlier for those with later HIV disease progression. This paper conducts a replication study of one of the three studies, by Havlir and colleagues. Using their publicly available data, we were able to replicate most of the results presented in the original paper. In our measurement and estimation analyses we use different estimation techniques to assess the robustness of the results. We find that adjusting for loss to follow-up does not affect the main results of the paper. However, an ANCOVA estimation and an instrumental variable model weaken the main result of the paper of better outcomes with early HIV treatment only for those who are sicker, reducing significance from the 5% to the 10% level. A change-point analysis also detects no changes in effect by timing of HIV treatment initiation or different thresholds of CD4 count for the primary outcome. This result suggests that the choice of start time for HIV treatment initiation should be based on other factors including potential drug interactions, overlapping side effects, a high pill burden and severity of illness rather than CD4 threshold and preset timeframes. While we caution against overgeneralizing, the result of this replication is aligned with more recent studies that show no evidence that early initiation of HIV treatment reduces mortality for any patients. [ABSTRACT FROM AUTHOR]

Background: Routine Data Quality Assessments (RDQAs) were developed to measure and improve facility-level electronic medical record (EMR) data quality. We assessed if RDQAs were associated with improvements in data quality in KenyaEMR, an HIV care and treatment EMR used at 341 facilities in Kenya. Methods: RDQAs assess data quality by comparing information recorded in paper records to KenyaEMR. RDQAs are conducted during a one-day site visit, where approximately 100 records are randomly selected and 24 data elements are reviewed to assess data completeness and concordance. Results are immediately provided to facility staff and action plans are developed for data quality improvement. For facilities that had received more than one RDQA (baseline and follow-up), we used generalized estimating equation models to determine if data completeness or concordance improved from the baseline to the follow-up RDQAs. Results: 27 facilities received two RDQAs and were included in the analysis, with 2369 and 2355 records reviewed from baseline and follow-up RDQAs, respectively. The frequency of missing data in KenyaEMR declined from the baseline (31% missing) to the follow-up (13% missing) RDQAs. After adjusting for facility characteristics, records from follow-up RDQAs had 0.43-times the risk (95% CI: 0.32–0.58) of having at least one missing value among nine required data elements compared to records from baseline RDQAs. Using a scale with one point awarded for each of 20 data elements with concordant values in paper records and KenyaEMR, we found that data concordance improved from baseline (11.9/20) to follow-up (13.6/20) RDQAs, with the mean concordance score increasing by 1.79 (95% CI: 0.25–3.33). Conclusions: This manuscript demonstrates that RDQAs can be implemented on a large scale and used to identify EMR data quality problems. RDQAs were associated with meaningful improvements in data quality and could be adapted for implementation in other settings. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. Methods: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. Results: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. Conclusions: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution. [ABSTRACT FROM AUTHOR]

TB is rated as one of the world’s deadliest diseases and South Africa ranks 9th out of the 22 countries with hardest hit of TB. Although many pieces of research have been carried out on this subject, this paper steps further by inculcating past knowledge into the model, using Bayesian approach with informative prior. Bayesian statistics approach is getting popular in data analyses. But, most applications of Bayesian inference technique are limited to situations of non-informative prior, where there is no solid external information about the distribution of the parameter of interest. The main aim of this study is to profile people living with TB in South Africa. In this paper, identical regression models are fitted for classical and Bayesian approach both with non-informative and informative prior, using South Africa General Household Survey (GHS) data for the year 2014. For the Bayesian model with informative prior, South Africa General Household Survey dataset for the year 2011 to 2013 are used to set up priors for the model 2014. [ABSTRACT FROM AUTHOR]

Background: CD4 cell counts is widely used as a biomarker for treatment progression when studying the efficacy of drugs to treat HIV-infected patients. In the past, it had been also used in determining eligibility to initiate antiretroviral therapy. The main aim of this was to model the evolution of CD4 counts over time and use this model for an early prediction of subject-specific time to cross a pre-specified CD4 threshold. Methods: Hospital based retrospective cohort study of HIV-infected patients was conducted from January 2009 to December 2014 at University of Gondar hospital, Northwest Ethiopia. Fractional polynomial random effect model is used to model the evolution of CD4 counts over time in response to treatment and to estimate the individual probability to be above a pre-selected CD4 threshold. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Results: A total of 1347 patients were included in the analysis presented in this paper. The cohort contributed a total of 236.58 per 100 person-years of follow-up. Later the data were divided into two periods: the first is the estimation period in which the parameters of the model are estimated and the second is the prediction period. Based on the parameters from the estimation period, model based prediction for the time to cross a threshold was estimated. The correlations between observed and predicted values of CD4 levels in the estimation period were 0.977 and 0.982 for Neverapine and Efavirenz containing regimens, respectively; while the correlation between the observed and predicted CD4 counts in the prediction period are 0.742 and 0.805 for NVP and EFV, respectively. Conclusions: The model enables us to estimate a subject-specific expected time to cross a CD4 threshold and to estimate a subject-specific probability to have CD4 count above a pre-specified threshold at each time point. By predicting long-term outcomes of CD4 count of the patients one can advise patient about the potential ART benefits that accrue in the long-term. [ABSTRACT FROM AUTHOR]

Background: HIV transmitted drug resistance (TDR) remains at moderate level in Latin America and the Caribbean (LAC). However, different epidemiologic scenarios could influence national and sub-regional TDR levels and trends. Methods and Findings: We performed a systematic review of currently available publications on TDR in antiretroviral treatment-naïve adults in LAC. Ninety-eight studies published between January 2000 and June 2015 were included according to critical appraisal criteria and classified by sub-region: Brazil (50), Mesoamerica (17), Southern Cone (16), Andean (8) and Caribbean (7). From these, 81 studies encompassing 11,441 individuals with data on DR mutation frequency were included in a meta-analysis. Overall TDR prevalence in LAC was 7.7% (95% CI: 7.2%-8.2%). An increasing trend was observed for overall TDR when comparing 2000–2005 (6.0%) and 2006–2015 (8.2%) (p<0.0001), which was associated with significant NNRTI TDR increase (p<0.0001). NRTI TDR decreased (4.5% vs. 2.3%, p<0.0001). NNRTI TDR increase was associated mainly with K101E, K103N and G190A. NRTI TDR decrease was associated mainly with M184V, K70R and T215Y. All sub-regions reached moderate overall TDR levels. The rapid increase in TDR to all antiretroviral classes in the Caribbean is notable, as well as the significant increase in NNRTI TDR reaching moderate levels in the Southern Cone. NRTI TDR was dominant in 2000–2005, mainly in the Caribbean, Mesoamerica and Brazil. This dominance was lost in 2006–2015 in all sub-regions, with the Southern Cone and the Caribbean switching to NNRTI dominance. PI TDR remained mostly constant with a significant increase only observed in the Caribbean. Conclusions: Given the high conceptual and methodological heterogeneity of HIV TDR studies, implementation of surveys with standardized methodology and national representativeness is warranted to generate reliable to inform public health policies. The observed increasing trend in NNRTI TDR supports the need to strengthen TDR surveillance and programme monitoring and evaluation in LAC. [ABSTRACT FROM AUTHOR]

Purpose: The 2014 outbreak of Ebola virus disease (EVD) in West Africa was the largest in history. Starting in September 2014, International Medical Corps (IMC) operated five Ebola treatment units (ETUs) in Sierra Leone and Liberia. This paper explores how future infectious disease outbreak facilities in resource-limited settings can be planned, organized, and managed by analyzing data collected on water, sanitation, and hygiene (WASH) and infection prevention control (IPC) protocols. Design/Methodology/Approach: We conducted a retrospective cohort study by analyzing WASH/IPC activity data routinely recorded on paper forms or white boards at ETUs during the outbreak and later merged into a database from two IMC-run ETUs in Sierra Leone between December 2014 and December 2015. Findings: The IMC WASH/IPC database contains data from over 369 days. Our results highlight parameters key to designing and maintaining an ETU. High concentration chlorine solution usage was highly correlated with both daily patient occupancy and high-risk zone staff entries; low concentration chlorine usage was less well explained by these measures. There is high demand for laundering and disinfecting of personal protective equipment (PPE) on a daily basis and approximately 1 (0–4) piece of PPE is damaged each day. Research limitations/Implications: Lack of standardization in the type and format of data collected at ETUs made constructing the WASH/IPC database difficult. However, the data presented here may help inform humanitarian response operations in future epidemics. [ABSTRACT FROM AUTHOR]

The analyses of large volumes of metagenomic data extracted from aggregate populations of microscopic organisms residing on and in the human body are advancing contemporary understandings of the integrated participation of microbes in human health and disease. Next generation sequencing technology facilitates said analyses in terms of diversity, community composition, and differential abundance by filtering and binning microbial 16S rRNA genes extracted from human tissues into operational taxonomic units. However, current statistical tools restrict study designs to investigations of limited numbers of host characteristics mediated by limited numbers of samples potentially yielding a loss of relevant information. This paper presents a Bayesian hierarchical negative binomial model as an efficient technique capable of compensating for multivariable sets including tens or hundreds of host characteristics as covariates further expanding analyses of human microbiome count data. Simulation studies reveal that the Bayesian hierarchical negative binomial model provides a desirable strategy by often outperforming three competing negative binomial model in terms of type I error while simultaneously maintaining consistent power. An application of the Bayesian hierarchical negative binomial model using subsets of the open data published by the American Gut Project demonstrates an ability to identify operational taxonomic units significantly differentiable among persons diagnosed by a medical professional with either inflammatory bowel disease or irritable bowel syndrome that are consistent with contemporary gastrointestinal literature. [ABSTRACT FROM AUTHOR]

The development of high-throughput sequencing technologies for 16S rRNA gene profiling provides higher quality compositional data for microbe communities. Inferring the direct interaction network under a specific condition and understanding how the network structure changes between two different environmental or genetic conditions are two important topics in biological studies. However, the compositional nature and high dimensionality of the data are challenging in the context of network and differential network recovery. To address this problem in the present paper, we proposed two new loss functions to incorporate the data transformations developed for compositional data analysis into D-trace loss for network and differential network estimation, respectively. The sparse matrix estimators are defined as the minimizer of the corresponding lasso penalized loss. Our method is characterized by its straightforward application based on the ADMM algorithm for numerical solution. Simulations show that the proposed method outperforms other state-of-the-art methods in network and differential network inference under different scenarios. Finally, as an illustration, our method is applied to a mouse skin microbiome data. [ABSTRACT FROM AUTHOR]

Image segmentation applied to medical image analysis is still a critical and important task. Although there exist several segmentation algorithms that have been widely studied in literature, these are subject to segmentation problems such as over- and under-segmentation as well as non-closed edges. In this paper, a simple method that combines well-known segmentation algorithms is presented. This method is applied to detect acid-fast bacilli (AFB) in bacilloscopies used to diagnose pulmonary tuberculosis (TB). This diagnosis can be performed through different tests, and the most used worldwide is smear microscopy because of its low cost and effectiveness. This diagnosis technique is based on the analysis and counting of the bacilli in the bacilloscopy observed under an optical microscope. The proposed method is used to segment the bacilli in digital images from bacilloscopies processed using Ziehl-Neelsen (ZN) staining. The proposed method is fast, has a low computational cost and good efficiency compared to other methods. The bacilli image segmentation is performed by image processing and analysis techniques, probability concepts and classifiers. In this work, a Bayesian classifier based on a Gaussian mixture model (GMM) is used. The segmentations' results are validated by using the Jaccard index, which indicates the efficiency of the classifier. [ABSTRACT FROM AUTHOR]

Leptospirosis is probably the most widespread zoonotic disease in the world especially in tropical countries. There has been an increase in individual studies, which assessed the frequency of leptospirosis in flood conditions. Some studies showed contact with floods was significantly associated with the occurrence of leptospirosis while other studies reported differently. The objective of this meta-analysis was to synthesize the evidence on the risk factors which are associated with human leptospirosis following flooding. We set up the inclusion criteria and searched for the original studies, addressing leptospirosis in human with related to flood in health-related electronic databases including PubMed, Embase, Ovid Medline, google scholar and Scopus sources. We used the terms ‘leptospirosis’, ‘flood’, ‘risk factor’ and terms from the categories were connected with “OR” within each category and by “AND” between categories. The initial search yielded 557 citations. After the title and abstract screening, 49 full-text papers were reviewed and a final of 18 observational studies met the pre-specified inclusion criteria. Overall, the pooled estimates of 14 studies showed that the contact with flooding was a significant factor for the occurrence of leptospirosis (pooled OR: 2.19, 95%CI: 1.48–3.24, I2:86%). On stratification, the strength of association was greater in the case-control studies (pooled OR: 4.01, 95%CI: 1.26–12.72, I2:82%) than other designs (pooled OR:1.77,95%CI:1.18–2.65, I2:87%). Three factors such as ‘being male’(pooled OR:2.06, 95%CI:1.29–2.83), the exposure to livestock animals (pooled OR: 1.95, 95%CI:1.26–2.64), the lacerated wound (pooled OR:4.35, 95%CI:3.07–5.64) were the risk factors significantly associated with the incidence of leptospirosis following flooding in the absence of within-study heterogeneity (I2: 0%). We acknowledge study limitations such as publication bias and type 2 statistical errors. We recommended flood control and other environmental modifications that are expected to reduce the risk of leptospiral infection, and a multi-sectoral effort to this aspect would have long-term benefits. [ABSTRACT FROM AUTHOR]

Objectives: Although systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice. Methods: We reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8–17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence. Results: 8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16–0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64–1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05–3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10–0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT. Conclusions: Overall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is endemic in people who inject drugs (PWID), with prevalence estimates above 60% for PWID in the United States. Previous modeling studies suggest that direct acting antiviral (DAA) treatment can lower overall prevalence in this population, but treatment is often delayed until the onset of advanced liver disease (fibrosis stage 3 or later) due to cost. Lower cost interventions featuring syringe access (SA) and medically assisted treatment (MAT) have shown mixed results in lowering HCV rates below current levels. However. little is known about the potential cumulative effects of combining DAA and MAT treatment. While simulation experiments can reveal likely long-term effects, most prior simulations have been performed on closed populations of model agents—a scenario quite different from the open, mobile populations known to most health agencies. This paper uses data from the Centers for Disease Control’s National HIV Behavioral Surveillance project, IDU round 3, collected in New York City in 2012 to parameterize simulations of open populations. To test the effect of combining DAA treatment with SA/MAT participation, multiple, scaled implementations of the two intervention strategies were simulated. Our results show that, in an open population, SA/MAT by itself has only small effects on HCV prevalence, while DAA treatment by itself can lower both HCV and HCV-related advanced liver disease prevalence. More importantly, the simulation experiments suggest that combinations of the two strategies can, when implemented together and at sufficient levels, dramatically reduce HCV incidence. We conclude that adopting SA/MAT implementations alongside DAA interventions can play a critical role in reducing the long-term consequences of ongoing HCV infection. [ABSTRACT FROM AUTHOR]

Maternal mortality remains very high in Mozambique, with estimates from 2015 showing a maternal mortality ratio of 489 deaths per 100,000 live births, even though the rates tend to decrease since 1990. Pregnancy related hemorrhage, gestational hypertension and diseases such as malaria and HIV/AIDS are amongst the leading causes of maternal death in Mozambique, and a significant number of these deaths occur within health facilities. Often, the analysis of data on maternal mortality involves the use of counts of maternal deaths as outcome variable. Previously we showed that a class of hierarchical zero-inflated models were very successful in dealing with overdispersion and clustered counts when analyzing data on maternal deaths and related risk factors within health facilities in Mozambique. This paper aims at providing additional insights over previous analyses and presents an extension of such models to account for spatial variation in a disease mapping framework of facility-based maternal mortality in Mozambique. [ABSTRACT FROM AUTHOR]

Clinical trials are necessary in order to develop treatments for diseases; however, they can often be costly, time consuming, and demanding to the patients. This paper summarizes several common methods used for optimal design that can be used to address these issues. In addition, we introduce a novel method for optimizing experiment designs applied to HIV 2-LTR clinical trials. Our method employs Bayesian techniques to optimize the experiment outcome by maximizing the Expected Kullback-Leibler Divergence (EKLD) between the a priori knowledge of system parameters before the experiment and the a posteriori knowledge of the system parameters after the experiment. We show that our method is robust and performs equally well if not better than traditional optimal experiment design techniques. [ABSTRACT FROM AUTHOR]

Rodent models are invaluable to understanding health and disease in many areas of biomedical research. Unfortunately, many models suffer from lack of phenotype reproducibility. Our laboratory has shown that differences in gut microbiota (GM) can modulate phenotypes of models of colon cancer and inflammatory bowel disease. We and others have also shown that a number of factors associated with rodent research, including vendor, cage system, and bedding can alter GM. The objective of this study was to expand these studies to examine the effect of additional bedding materials and methods of water decontamination on GM diversity and composition. To this end, Crl:CD1 (ICR) mice were housed on corn cob or compressed paper chip bedding and provided water that was decontaminated by four different methods: autoclaving with reverse osmosis, autoclaving with hydrochloric acid, autoclaving with sulfuric acid, and autoclaving alone. Feces was collected at day 0, and at day 28 (endpoint), fecal and cecal samples were collected. DNA was extracted from samples, amplified by PCR using conserved bacterial primer sets and subjected to next generation sequencing. Sequence data were analyzed using Qiime and groups were compared using principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA). Two factor PERMANOVA of cecal GM data revealed significant changes when comparing bedding and water decontamination methods, while no significant effects were noted in the fecal GM data. Subsequent PERMANOVA and PCoA of cecal data revealed that several combinations of bedding and water decontamination methods resulted in differing GM, highlighting the complexity by which environmental factors interact to modulate GM. [ABSTRACT FROM AUTHOR]

Predicting the population-level effects of an infectious disease intervention that incorporate multiple modes of intervention is complicated by the joint non-linear dynamics of both infection transmission and the intervention itself. In this paper, we consider the sensitivity of Dynamic Optimal Control Profiles (DOCPs) for the optimal joint investment in both a contagiousness and susceptibility-based control of HIV to bio-behavioral, economic, and programmatic assumptions. The DOCP is calculated using recently developed numerical algorithms that allow controls to be represented by a set of piecewise constant functions that maintain a constant yearly budget. Our transmission model assumes multiple stages of HIV infection corresponding to acute and chronic infection and both within- and between-individual behavioral heterogeneity. We parameterize a baseline scenario from a longitudinal study of sexual behavior in MSM and consider sensitivity of the DOCPs to deviations from that baseline scenario. In the baseline scenario, the primary determinant of the dominant control were programmatic factors, regardless of budget. In sensitivity analyses, the qualitative aspects of the optimal control policy were often robust to significant deviation in assumptions regarding transmission dynamics. In addition, we found several conditions in which long-term joint investment in both interventions was optimal. Our results suggest that modeling in the service of decision support for intervention design can improve population-level effects of a limited set of economic resources. We found that economic and programmatic factors were as important as the inherent transmission dynamics in determining population-level intervention effects. Given our finding that the DOCPs were robust to alternative biological and behavioral assumptions it may be possible to identify DOCPs even when the data are not sufficient to identify a transmission model. [ABSTRACT FROM AUTHOR]

The 2015-16 Zika epidemic spread quickly from north to south in Brazil. Two striking features were the much higher incidence in young adult women due to sexual transmission, and the serious congenital malformations and miscarriages associated to Zika infection in pregnant women. In this paper we use case reporting data along with live-birth records to reconstruct the full size of the epidemic through a Bayesian probabilistic graph model representing the Zika transmission probabilities of observation (case reporting) and of birth loss (through miscarriage or abortion). We find that the probability of observing (reporting) a Zika case is different between men and women and ranges between 10 to 13%. From these estimates we reconstruct the full size of the Zika epidemic in Rio de Janeiro in 2015-16. [ABSTRACT FROM AUTHOR]

This paper describes the web-based automated disease-related topic extraction system, called to DiTeX, which monitors important disease-related topics and provides associated information. National disease surveillance systems require a considerable amount of time to inform people of recent outbreaks of diseases. To solve this problem, many studies have used Internet-based sources such as news and Social Network Service (SNS). However, these sources contain many intentional elements that disturb extracting important topics. To address this challenge, we employ Natural Language Processing and an effective ranking algorithm, and develop DiTeX that provides important disease-related topics. This report describes the web front-end and back-end architecture, implementation, performance of the ranking algorithm, and captured topics of DiTeX. We describe processes for collecting Internet-based data and extracting disease-related topics based on search keywords. Our system then applies a ranking algorithm to evaluate the importance of disease-related topics extracted from these data. Finally, we conduct analysis based on real-world incidents to evaluate the performance and the effectiveness of DiTeX. To evaluate DiTeX, we analyze the ranking of well-known disease-related incidents for various ranking algorithms. The topic extraction rate of our ranking algorithm is superior to those of others. We demonstrate the validity of DiTeX by summarizing the disease-related topics of each day extracted by our system. To our knowledge, DiTeX is the world’s first automated web-based real-time service system that extracts and presents disease-related topics, trends and related data through web-based sources. DiTeX is now available on the web through . [ABSTRACT FROM AUTHOR]

Type IV secretion systems (T4SS) are multi-protein complexes in a number of bacterial pathogens that can translocate proteins and DNA to the host. Most T4SSs function in conjugation and translocate DNA; however, approximately 13% function to secrete proteins, delivering effector proteins into the cytosol of eukaryotic host cells. Upon entry, these effectors manipulate the host cell’s machinery for their own benefit, which can result in serious illness or death of the host. For this reason recognition of T4SS effectors has become an important subject. Much previous work has focused on verifying effectors experimentally, a costly endeavor in terms of money, time, and effort. Having good predictions for effectors will help to focus experimental validations and decrease testing costs. In recent years, several scoring and machine learning-based methods have been suggested for the purpose of predicting T4SS effector proteins. These methods have used different sets of features for prediction, and their predictions have been inconsistent. In this paper, an optimal set of features is presented for predicting T4SS effector proteins using a statistical approach. A thorough literature search was performed to find features that have been proposed. Feature values were calculated for datasets of known effectors and non-effectors for T4SS-containing pathogens for four genera with a sufficient number of known effectors, Legionella pneumophila, Coxiella burnetii, Brucella spp, and Bartonella spp. The features were ranked, and less important features were filtered out. Correlations between remaining features were removed, and dimensional reduction was accomplished using principal component analysis and factor analysis. Finally, the optimal features for each pathogen were chosen by building logistic regression models and evaluating each model. The results based on evaluation of our logistic regression models confirm the effectiveness of our four optimal sets of features, and based on these an optimal set of features is proposed for all T4SS effector proteins. [ABSTRACT FROM AUTHOR]

This paper proposes a novel approach that uses meteorological information to predict the incidence of influenza in Galicia (Spain). It extends the Generalized Least Squares (GLS) methods in the multivariate framework to functional regression models with dependent errors. These kinds of models are useful when the recent history of the incidence of influenza are readily unavailable (for instance, by delays on the communication with health informants) and the prediction must be constructed by correcting the temporal dependence of the residuals and using more accessible variables. A simulation study shows that the GLS estimators render better estimations of the parameters associated with the regression model than they do with the classical models. They obtain extremely good results from the predictive point of view and are competitive with the classical time series approach for the incidence of influenza. An iterative version of the GLS estimator (called iGLS) was also proposed that can help to model complicated dependence structures. For constructing the model, the distance correlation measure was employed to select relevant information to predict influenza rate mixing multivariate and functional variables. These kinds of models are extremely useful to health managers in allocating resources in advance to manage influenza epidemics. [ABSTRACT FROM AUTHOR]

When standard optimization methods fail to find a satisfactory solution for a parameter fitting problem, a tempting recourse is to adjust parameters manually. While tedious, this approach can be surprisingly powerful in terms of achieving optimal or near-optimal solutions. This paper outlines an optimization algorithm, Adaptive Stochastic Descent (ASD), that has been designed to replicate the essential aspects of manual parameter fitting in an automated way. Specifically, ASD uses simple principles to form probabilistic assumptions about (a) which parameters have the greatest effect on the objective function, and (b) optimal step sizes for each parameter. We show that for a certain class of optimization problems (namely, those with a moderate to large number of scalar parameter dimensions, especially if some dimensions are more important than others), ASD is capable of minimizing the objective function with far fewer function evaluations than classic optimization methods, such as the Nelder-Mead nonlinear simplex, Levenberg-Marquardt gradient descent, simulated annealing, and genetic algorithms. As a case study, we show that ASD outperforms standard algorithms when used to determine how resources should be allocated in order to minimize new HIV infections in Swaziland. [ABSTRACT FROM AUTHOR]

Norovirus is a major cause of viral gastroenteritis, with shellfish consumption being identified as one potential norovirus entry point into the human population. Minimising shellfish norovirus levels is therefore important for both the consumer’s protection and the shellfish industry’s reputation. One method used to reduce microbiological risks in shellfish is depuration; however, this process also presents additional costs to industry. Providing a mechanism to estimate norovirus levels during depuration would therefore be useful to stakeholders. This paper presents a mathematical model of the depuration process and its impact on norovirus levels found in shellfish. Two fundamental stages of norovirus depuration are considered: (i) the initial distribution of norovirus loads within a shellfish population and (ii) the way in which the initial norovirus loads evolve during depuration. Realistic assumptions are made about the dynamics of norovirus during depuration, and mathematical descriptions of both stages are derived and combined into a single model. Parameters to describe the depuration effect and norovirus load values are derived from existing norovirus data obtained from U.K. harvest sites. However, obtaining population estimates of norovirus variability is time-consuming and expensive; this model addresses the issue by assuming a ‘worst case scenario’ for variability of pathogens, which is independent of mean pathogen levels. The model is then used to predict minimum depuration times required to achieve norovirus levels which fall within possible risk management levels, as well as predictions of minimum depuration times for other water-borne pathogens found in shellfish. Times for Escherichia coli predicted by the model all fall within the minimum 42 hours required for class B harvest sites, whereas minimum depuration times for norovirus and FRNA+ bacteriophage are substantially longer. Thus this study provides relevant information and tools to assist norovirus risk managers with future control strategies. [ABSTRACT FROM AUTHOR]

Introduction: It is unclear whether the treatment of an HIV infection with highly active antiretroviral therapy (HAART) affects intensive care unit (ICU) outcomes. In this paper, we report the results of a systematic review and meta-analysis performed to summarize the effects of HAART on the prognosis of critically ill HIV positive patients. Materials and methods: A bibliographic search was performed in 3 databases (PubMed, Web of Science and Scopus) to identify articles that investigated the use of HAART during ICU admissions for short- and long-term mortality or survival. Eligible articles were selected in a staged process and were independently assessed by two investigators. The methodological quality of the selected articles was evaluated using the Methodological Index for Non-Randomized Studies (MINORS) tool. Results: Twelve articles met the systematic review inclusion criteria and examined short-term mortality. Six of them also examined long-term mortality (≥90 days) after ICU discharge. The short-term mortality meta-analysis showed a significant beneficial effect of initiating or maintaining HAART during the ICU stay (random effects odds ratio 0.53, p = 0.02). The data analysis of long-term outcomes also suggested a reduced mortality when HAART was used, but the effect of HAART on long-term mortality of HIV positive critically ill patients remains uncertain. Conclusions: This meta-analysis suggests improved survival rates for HIV positive patients who were treated with HAART during their ICU admission. [ABSTRACT FROM AUTHOR]

In this paper, we present and analyze an SEIR Zika epidemic model. Firstly, we investigate the model with constant controls. The steady states of the model is found to be locally and globally asymptotically stable. Thereafter, we incorporate time dependent controls into the model in order to investigate the optimal effects of bednets, treatments of infective and spray of insecticides on the disease spread. Furthermore, we used Pontryagin’s Maximum Principle to determine the necessary conditions for effective control of the disease. Also, the numerical results were presented. [ABSTRACT FROM AUTHOR]

Since the microbiome has a significant impact on human health and disease, microbe-disease associations can be utilized as a valuable resource for understanding disease pathogenesis and promoting disease diagnosis and prognosis. Accordingly, it is necessary for researchers to achieve a comprehensive and deep understanding of the associations between microbes and diseases. Nevertheless, to date, little work has been achieved in implementing novel human microbe-disease association prediction models. In this paper, we develop a novel computational model to predict potential microbe-disease associations by bi-random walk on the heterogeneous network (BiRWHMDA). The heterogeneous network was constructed by connecting the microbe similarity network and the disease similarity network via known microbe-disease associations. Microbe similarity and disease similarity were calculated by the Gaussian interaction profile kernel similarity measure; moreover, a logistic function was applied to regulate disease similarity. Additionally, leave-one-out cross validation and 5-fold cross validation were implemented to evaluate the predictive performance of our method; both cross validation methods performed well. The leave-one-out cross validation experiment results illustrate that our method outperforms other previously proposed methods. Furthermore, case studies on asthma and inflammatory bowel disease prove the favorable performance of our method. In conclusion, our method can be considered as an effective computational model for predicting novel microbe-disease associations. [ABSTRACT FROM AUTHOR]

This paper forecasts the 2016 canine Anaplasma spp. seroprevalence in the United States from eight climate, geographic and societal factors. The forecast’s construction and an assessment of its performance are described. The forecast is based on a spatial-temporal conditional autoregressive model fitted to over 11 million Anaplasma spp. seroprevalence test results for dogs conducted in the 48 contiguous United States during 2011–2015. The forecast uses county-level data on eight predictive factors, including annual temperature, precipitation, relative humidity, county elevation, forestation coverage, surface water coverage, population density and median household income. Non-static factors are extrapolated into the forthcoming year with various statistical methods. The fitted model and factor extrapolations are used to estimate next year’s regional prevalence. The correlation between the observed and model-estimated county-by-county Anaplasma spp. seroprevalence for the five-year period 2011–2015 is 0.902, demonstrating reasonable model accuracy. The weighted correlation (accounting for different sample sizes) between 2015 observed and forecasted county-by-county Anaplasma spp. seroprevalence is 0.987, exhibiting that the proposed approach can be used to accurately forecast Anaplasma spp. seroprevalence. The forecast presented herein can a priori alert veterinarians to areas expected to see Anaplasma spp. seroprevalence beyond the accepted endemic range. The proposed methods may prove useful for forecasting other diseases. [ABSTRACT FROM AUTHOR]

A previous report indicated that a formic acid chemical extraction method for the preparation of protein extracts for matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) identification, with filtration of extracts through 0.2 μm regenerated cellulose (RC) filters, would not reliably inactivate or exclude Bacillus anthracis Vollum cells or spores when tested under high stringency conditions. B. anthracis was recovered from 13/36 extracts (3/18 from vegetative cell extracts and 10/18 from bacterial spore extracts). In this paper we report the repetition of this study but with the substitution of the 0.2 μm, regenerated cellulose, filters with 0.1 μm polyvinylidene fluoride (PVDF) filters. Experiments were conducted under the same high stringency post-treatment viability test methods (100% of resulting protein content; 7 days Luria (L)-broth and a further 7 days L-agar plate incubation; or 7 days L-agar plate only incubation). B. anthracis was not recovered from any of 18 replicates generated from high concentrations of vegetative cells (107 to 108 cfu), but a single B. anthracis colony was recovered from one of 18 replicates generated from high concentrations of bacterial spores (108 cfu), using a post-treatment viability culture method of 7 days on L-agar plate only. We discuss our results in the context of other similar studies and also a requirement to develop standardised post-treatment viability test methods. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERVs) encode active retroviral proteins, which may be involved in the progression of cancer and other diseases. Matrix protein (MA), in group-specific antigen genes (gag) of retroviruses, is associated with the virus envelope glycoproteins in most mammalian retroviruses and may be involved in virus particle assembly, transport and budding. However, the amount of annotated MAs in ERVs is still at a low level so far. No computational method to predict the exact start and end coordinates of MAs in gags has been proposed yet. In this paper, a computational method to identify MAs in ERVs is proposed. A divide and conquer technique was designed and applied to the conventional prediction model to acquire better results when dealing with gene sequences with various lengths. Initiation sites and termination sites were predicted separately and then combined according to their intervals. Three different algorithms were applied and compared: weighted support vector machine (WSVM), weighted extreme learning machine (WELM) and random forest (RF). G − mean (geometric mean of sensitivity and specificity) values of initiation sites and termination sites under 5-fold cross validation generated by random forest models are 0.9869 and 0.9755 respectively, highest among the algorithms applied. Our prediction models combine RF & WSVM algorithms to achieve the best prediction results. 98.4% of all the collected ERV sequences with complete MAs (125 in total) could be predicted exactly correct by the models. 94,671 HERV sequences from 118 families were scanned by the model, 104 new putative MAs were predicted in human chromosomes. Distributions of the putative MAs and optimizations of model parameters were also analyzed. The usage of our predicting method was also expanded to other retroviruses and satisfying results were acquired. [ABSTRACT FROM AUTHOR]

This paper models the prevalence of antibodies to Borrelia burgdorferi in domestic dogs in the United States using climate, geographic, and societal factors. We then use this model to forecast the prevalence of antibodies to B. burgdorferi in dogs for 2016. The data available for this study consists of 11,937,925 B. burgdorferi serologic test results collected at the county level within the 48 contiguous United States from 2011-2015. Using the serologic data, a baseline B. burgdorferi antibody prevalence map was constructed through the use of spatial smoothing techniques after temporal aggregation; i.e., head-banging and Kriging. In addition, several covariates purported to be associated with B. burgdorferi prevalence were collected on the same spatio-temporal granularity, and include forestation, elevation, water coverage, temperature, relative humidity, precipitation, population density, and median household income. A Bayesian spatio-temporal conditional autoregressive (CAR) model was used to analyze these data, for the purposes of identifying significant risk factors and for constructing disease forecasts. The fidelity of the forecasting technique was assessed using historical data, and a Lyme disease forecast for dogs in 2016 was constructed. The correlation between the county level model and baseline B. burgdorferi antibody prevalence estimates from 2011 to 2015 is 0.894, illustrating that the Bayesian spatio-temporal CAR model provides a good fit to these data. The fidelity of the forecasting technique was assessed in the usual fashion; i.e., the 2011-2014 data was used to forecast the 2015 county level prevalence, with comparisons between observed and predicted being made. The weighted (to acknowledge sample size) correlation between 2015 county level observed prevalence and 2015 forecasted prevalence is 0.978. A forecast for the prevalence of B. burgdorferi antibodies in domestic dogs in 2016 is also provided. The forecast presented from this model can be used to alert veterinarians in areas likely to see above average B. burgdorferi antibody prevalence in dogs in the upcoming year. In addition, because dogs and humans can be exposed to ticks in similar habitats, these data may ultimately prove useful in predicting areas where human Lyme disease risk may emerge. [ABSTRACT FROM AUTHOR]

Whereas the number of people newly infected by HIV is continuing to decline globally, the epidemic continues to expand in many parts of the world. As the HIV/AIDS epidemic has matured in many countries, it is believed that the proportion of new infections occurring within couples has risen. Across countries, including Mozambique, a sizeable proportion of couples with HIV infection are discordant. A serodiscordant couple is a couple in which one partner has tested positive for HIV and the other has not. To describe the HIV serodiscordance among couples, a variety of association measures can be used. In this paper, we propose the serodiscordance measure as a new alternative measure. Focus is on the specification of flexible marginal and random effects models for multivariate correlated binary data together with a full-likelihood estimation method, to adequately and directly describe the measure of interest. Fitting joint models allows examining the effects of different risk factors and other covariates on the probability to be HIV positive for each member within a couple, and estimating common effects for both probabilities more efficiently, while accounting for the association between their infection status. Moreover, the interpretation of the proposed association parameter SDM is more direct and relevant and effects of covariates can be studied as well. Results show that the HIV prevalence for the province where a couple was located as well as the union number for the woman within a couple are factors associated with HIV serodiscordance. These findings are important for the Mozambican public health policy makers to design national prevention plans, which include policies to stimulate regular HIV testing for couples as well as adolescents and young adults, prior to getting married or living together as a couple. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis of latent tuberculosis infection (LTBI) is becoming increasingly concerning due to the increasing the HIV epidemic, which have increased the risk for reactivation to active tuberculosis (TB) infection. LTBI is diagnosed by tuberculin skin test (TST) and interferon-gamma release assays (IGRAs). Objectives: The aim of the present study was to conduct a meta-analysis of published papers on the agreement (kappa) between TST and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests for diagnosis of LTBI in HIV patient. Methods: Electronic databases including PubMed/Medline, Elsevier/Scopus and Embase/Ovid were reviewed up Jan. 2016. We performed a random effect model meta-analysis for estimation of pooled Kappa between the two methods of diagnosis. Meta regression was used for assessing potential heterogeneity and Egger’s test was used for assessing small study effect and publication bias. Results: The initial search strategy produced 6744 records. Of them, 23 cross-sectional studies met the inclusion criteria and 20 studies entered in meta-analysis. The pooled kappa was and prevalence-adjusted and bias-adjusted kappa (PABAK) were 0.37 (95% CI: 0.28, 0.46) and 0.59 (0.49, 0.69). The discordance of TST-/QFT-GIT+ was more than TST+/QFT-GIT-. Kappa estimate between two tests was linearly associated with age and prevalence index and inversely associated with bias index. Conclusion: Fair agreement between TST and QFT-GIT makes it difficult to know whether TST is as useful as the QFT-GIT in HIV-infected patients. The higher discordance of TST-/QFT-GIT+ in compared to TST+/QFT-GIT- can induce the higher sensitivity of QFT-GIT for diagnosis LTBI in HIV patients. Disagreement between two tests can be influenced by error in measurements and prevalence of HIV. [ABSTRACT FROM AUTHOR]

RNase H (RNH) is a pivotal domain in retrovirus to cleave the DNA-RNA hybrid for continuing retroviral replication. The crucial role indicates that RNH is a promising drug target for therapeutic intervention. However, annotated RNHs in UniProtKB database have still been insufficient for a good understanding of their statistical characteristics so far. In this work, a computational RNH model was proposed to annotate new putative RNHs (np-RNHs) in the retroviruses. It basically predicts RNH domains through recognizing their start and end sites separately with SVM method. The classification accuracy rates are 100%, 99.01% and 97.52% respectively corresponding to jack-knife, 10-fold cross-validation and 5-fold cross-validation test. Subsequently, this model discovered 14,033 np-RNHs after scanning sequences without RNH annotations. All these predicted np-RNHs and annotated RNHs were employed to analyze the length, hydrophobicity and evolutionary relationship of RNH domains. They are all related to retroviral genera, which validates the classification of retroviruses to a certain degree. In the end, a software tool was designed for the application of our prediction model. The software together with datasets involved in this paper can be available for free download at . [ABSTRACT FROM AUTHOR]

Biofilms are the preferred sessile and matrix-embedded life form of most microorganisms on surfaces. In the medical field, biofilms are a frequent cause of treatment failure because they protect the bacteria from antibiotics and immune cells. Antibiotics are selected according to the minimal inhibitory concentration (MIC) based on the planktonic form of bacteria. Determination of the minimal biofilm eradicating concentration (MBEC), which can be up to 1,000-fold greater than the MIC, is not currently conducted as routine diagnostic testing, primarily because of the methodical hurdles of available biofilm assessing protocols that are time- and cost-consuming. Comparative analysis of biofilms is also limited as most quantitative methods such as crystal violet staining are indirect and highly imprecise. In this paper, we present a novel algorithm for assessing biofilm resistance to antibiotics that overcomes several of the limitations of alternative methods. This algorithm aims for a computer-based analysis of confocal microscope 3D images of biofilms after live/dead stains providing various biofilm parameters such as numbers of viable and dead cells and their vertical distributions within the biofilm, or biofilm thickness. The performance of this algorithm was evaluated using computer-simulated 2D and 3D images of coccal and rodent cells varying different parameters such as cell density, shading or cell size. Finally, genuine biofilms that were untreated or treated with nitroxoline or colistin were analyzed and the results were compared with quantitative microbiological standard methods. This novel algorithm allows a direct, fast and reproducible analysis of biofilms after live/dead staining. It performed well in biofilms of moderate cell densities in a 2D set-up however the 3D analysis remains still imperfect and difficult to evaluate. Nevertheless, this is a first try to develop an easy but conclusive tool that eventually might be implemented into routine diagnostics to determine the MBEC and to improve outcomes of patients with biofilm-associated infections. [ABSTRACT FROM AUTHOR]

HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States. [ABSTRACT FROM AUTHOR]

Background: Much work has been done in recent years to determine the vector competence of Aedes albopictus (Skuse) for Zika virus (ZIKV). If competent, Ae. albopictus could become an important vector in the spread of ZIKV to areas which until now have been considered safe from the virus. Despite much speculation about Ae. albopictus’ competence for ZIKV, there have been, to date, no quantitative syntheses of Ae. albopictus’ competence, nor have the potentially confounding differences between studies been addressed. Methodology/ principle findings: This study represents a quantitative meta-analysis of the literature surrounding this topic by examining infection rates (IR) and transmission rates (TR) among sample populations of Ae. albopictus at 7 and 14 days post infection (dpi) across 15 journal articles comprising 23 studies. Our analyses examined potentially confounding variables in the studies contained therein, including: geographic origin of viral strain or mosquito population tested, whether sympatry of the tested viral strain and mosquito population was important, and freshness of blood meal. Our results suggest 1) Ae albopictus is a competent vector for ZIKV and 2) that origin of Ae. albopictus population and origin of viral strain had significant effects on the competence of Ae. albopictus to transmit ZIKV. Conclusions/ significance: These results indicate a need to further explore the effects of methodology on vector competence studies and to examine in more detail the geographic variation in the competence of Ae. albopictus for ZIKV as well as the underlying causes of said variation. The ability of Ae. albopictus to carry and transmit ZIKV also points to a need to create new vector control strategies in case of a ZIKV outbreak in an area where Ae. albopictus is prominent. Finally, this study represents a potential template for future meta-analyses in the field of vector competence, where this type of study has been under-utilized despite the abundance of relevant studies. [ABSTRACT FROM AUTHOR]

Background: We undertook a systematic review and meta-analysis to address the question “what is the impact of meningitis on IQ and development.” Methods: Search: conducted using standardized search terms across Medline, PsychInfo and EMBASE to 06/2014. Eligibility: human studies of any infectious aetiology of meningitis reporting IQ or infant developmental age or stage outcomes. Quality: Centre for Evidence Based Medicine, Oxford, quality tools. Analysis: random effects meta-analysis by organism. Results: 39 studies were included in the review, 34 providing data on IQ (2015 subjects) and 12 on developmental delay (382 subjects). Across all bacterial organisms, meningitis survivors had a mean IQ 5.50 (95% CI: -7.19, -3.80; I2 = 47%, p = 0.02) points lower than controls. IQ was significantly lower than controls for Neisseria meningitides (NM: 5 points) and Haemophilus influenzae b (Hib: 6 points) but not in viral meningitis, with only single studies included for Streptococcus pneumoniae (SP) and group B streptococcus (GBS). The pooled relative risk (RR) for low IQ (IQ<70) in survivors of bacterial meningitis compared with controls was 4.99 (95% CI: 3.17, 7.86) with no significant heterogeneity (I2 = 49%, p = 0.07). Developmental delay of approximately 0.5SD was reported in studies of bacterial meningitis but no delay in the only study of viral meningitis. Conclusions: We found moderate evidence that surviving bacterial meningitis has a deleterious impact on IQ and development but no evidence that viral meningitis had meaningful cognitive impacts. Survivors of bacterial meningitis should be routinely offered screening for cognitive deficits and developmental delay in addition to hearing loss. [ABSTRACT FROM AUTHOR]

Depression, one of the most common psychiatric disorders, is two- to three-times more prevalent in people living with HIV (PLHIV) than in the general population in many settings as shown in western countries but remains neglected in sub-Saharan Africa (SSA). We aimed to summarize the available evidence on the prevalence of depression and associated factors according to the scales used and the treatment status in PLHIV in SSA. The pooled prevalence estimates of depression ranged between 9% and 32% in PLHIV on antiretroviral treatment (ART) and in untreated or mixed (treated/untreated) ones, with a substantial variability according to the measurement scale used and also for a given scale. Low socio-economic conditions in PLHIV on ART, female sex and immunosuppression in mixed/untreated PLHIV were frequently reported as associated factors but with no consensus. As depression could have deleterious consequences on the PLHIV life, it is critical to encourage its screening and management, integrating these dimensions in HIV care throughout SSA. [ABSTRACT FROM AUTHOR]

The spread of KPC-type carbapenemases is mainly attributed to the global dissemination of Klebsiella pneumoniae (KP) strains belonging to the clonal group (CG) 258, including sequence type (ST) 258 and other related STs. Two distinct clades of CG258-KP have evolved, which differ mainly for the composition of their capsular polysaccharides, and recent studies indicate that clade 1 evolved from an ancestor of clade 2 by recombination of a genomic fragment carrying the capsular polysaccharide (cps) locus. In this paper, we investigated the ability of two ST258-KP strains, KKBO-1 and KK207-1, selected as representatives of ST258-KP clade 2 and clade 1, respectively, to activate an adaptive immune response using ex vivo-stimulation of PBMC from normal donors as an experimental model. Our data showed that KKBO-1 (clade 2) induces a Th17 response more efficiently than KK207-1 (clade 1): the percentage of CD4+IL17+ cells and the production of IL-17A were significantly higher in cultures with KKBO-1 compared to cultures with KK207-1. While no differences in the rate of bacterial internalization or in the bacteria-induced expression of CD86 and HLA-DR by monocytes and myeloid dendritic cells were revealed, we found that the two strains significantly differ in inducing the production of cytokines involved in the adaptive immune response, as IL-1β, IL-23 and TNF-α, by antigen-presenting cells, with KKBO-1 being a more efficient inducer than KK207-1. The immune responses elicited by KK207-1 were comparable to those elicited by CIP 52.145, a highly virulent K. pneumoniae reference strain known to escape immune-inflammatory responses. Altogether, present results suggest that CG258-KP of the two clades are capable of inducing a different response of adaptive immunity in the human host. [ABSTRACT FROM AUTHOR]

Hepatitis B virus-associated membranous nephropathy (HBV-MN) is the most common renal extra-hepatic manifestation in patients with chronic HBV infection. In September 2015, we searched the MEDLINE, EMBASE, and CENTRAL databases, and the reference lists of retrieved articles, to identify relevant studies. Descriptions of antiviral drugs used to treat HBV-MN were included in our review. Two authors independently screened all relevant articles, extracted data, and assessed the risk of bias. Nine hundred and fifty-four papers have been considered after electronic and manual searching, only five relevant studies were identified. Complete remission (OR = 26.87, 95% CI: 8.06 to 89.52), total remission (OR = 10.31, 95% CI: 3.59 to 29.63) of proteinuria and HBeAg clearance (OR = 20.91, 95% CI: 6.90 to 63.39) increased significantly after antiviral therapy. No significant differences were seen between interferon and nucleoside analog treatments. Our study found that antiviral therapy was an effective treatment in HBV-MN patients; interferon and nucleoside analogs were equally effective at causing proteinuria remission and HBeAg clearance. [ABSTRACT FROM AUTHOR]

Background: The role of human papilloma virus (HPV) in oral lichen planus (OLP) is controversial. Objectives: The primary aim of the current study is to calculate the pooled risk estimates of HPV infection in OLP when compared with healthy controls. Methods: Bibliographic searches were conducted in three electronic databases. Articles on the association between HPV and OLP were selected from case-control studies or cross-sectional studies, following predefined criteria. Pooled data were analyzed by calculating odds ratios (OR) and 95% confidence interval (CI). Results: Of the 233 publications identified, 22 case-control studies met the inclusion criteria. Collectively, 835 cases and 734 controls were available for analysis. The summary estimate showed that OLP patients have significantly higher HPV prevalence (OR: 6.83; 95% CI: 4.15–11.27) than healthy controls. In subgroup analyses, the association of HPV and OLP varied significantly by geographic populations. The ORs ranged from 2.43 to 132.04. The correlation of HPV and erosive-atrophic oral lichen planus (EA-OLP) (OR: 9.34) was comparable and well above that of HPV and non-EA-OLP (OR: 4.32). Among HPV genotypes, HPV 16 showed an extremely strong association with OLP (OR: 11.27), and HPV 18 showed a relatively strong one (OR: 6.54). Conclusion: In conclusion, a significant association was found between HPV and OLP. The strength of the association varied across geographic populations, clinical types of OLP, and HPV genotypes. The results suggest that HPV might play an important causal role in OLP and in its malignant to progression. [ABSTRACT FROM AUTHOR]

Introduction: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing electronic healthcare record (eHR) databases in Europe. Part of the data in such sources is missing due to incomplete follow-up hampering the accurate estimation of vaccination coverage. We compared different methods for coverage estimation from eHR databases; naïve period prevalence, complete case period prevalence, period prevalence adjusted for follow-up time, Kaplan-Meier (KM) analysis and (adjusted) inverse probability weighing (IPW). Methods: We created simulation scenarios with different proportions of completeness of follow-up. Both completeness independent and dependent from vaccination date and status were considered. The root mean squared error (RMSE) and relative difference between the estimated and true coverage were used to assess the performance of the different methods for each of the scenarios. We included data examples on the vaccination coverage of human papilloma virus and pertussis component containing vaccines from the Spanish BIFAP database. Results: Under completeness independent from vaccination date or status, several methods provided estimates with bias close to zero. However, when dependence between completeness of follow-up and vaccination date or status was present, all methods generated biased estimates. The IPW/CDF methods were generally the least biased. Preference for a specific method should be based on the type of censoring and type of dependence between completeness of follow-up and vaccination. Additional insights into these aspects, might be gained by applying several methods. [ABSTRACT FROM AUTHOR]

The Medical Monitoring Project (MMP) is an HIV surveillance system that provides national estimates of HIV-related behaviors and clinical outcomes. When first implemented, MMP excluded persons living with HIV not receiving HIV care. This analysis will describe new case-surveillance-based methods to identify and recruit persons living with HIV who are out of care and at elevated risk for mortality and ongoing HIV transmission. Stratified random samples of all persons living with HIV were selected from the National HIV Surveillance System in five public health jurisdictions from 2012–2014. Sampled persons were located and contacted through seven different data sources and five methods of contact to collect interviews and medical record abstractions. Data were weighted for non-response and case reporting delay. The modified sampling methodology yielded 1159 interviews (adjusted response rate, 44.5%) and matching medical record abstractions for 1087 (93.8%). Of persons with both interview and medical record data, 264 (24.3%) would not have been included using prior MMP methods. Significant predictors were identified for successful contact (e.g., retention in care, adjusted Odds Ratio [aOR] 5.02; 95% Confidence Interval [CI] 1.98–12.73), interview (e.g. moving out of jurisdiction, aOR 0.24; 95% CI: 0.12–0.46) and case reporting delay (e.g. rural residence, aOR 3.18; 95% CI: 2.09–4.85). Case-surveillance-based sampling resulted in a comparable response rate to existing MMP methods while providing information on an important new population. These methods have since been adopted by the nationally representative MMP surveillance system, offering a model for public health program, research and surveillance endeavors seeking inclusion of all persons living with HIV. [ABSTRACT FROM AUTHOR]

Background: Increased second-line antiretroviral therapy (ART) failure rate narrows future options for HIV/AIDS treatment. It has critical implications in resource-limited settings; including sub-Saharan Africa (SSA) where the burden of HIV-infection is immense. Hence, pooled estimate for second-line HIV treatment failure is relevant to suggest valid recommendations that optimize ART outcomes in SSA. Methods: We retrieved literature systematically from PUBMED/MEDLINE, EMBASE, CINAHL, Google Scholar, and AJOL. The retrieved studies were screened and assessed for eligibility. We also assessed the eligible studies for their methodological quality using the Joanna Briggs Institute’s appraisal checklist. The pooled estimates for second-line HIV treatment failure and its associated factors were determined using STATA, version 15.0 and MEDCALC, version 18.11.3, respectively. We assessed publication bias using Comprehensive Meta-analysis software, version 3. Detailed study protocol for this review/meta-analysis is registered and found on PROSPERO (ID: CRD42018118959). Results: A total of 33 studies with the overall 18,550 participants and 19,988.45 person-years (PYs) of follow-up were included in the review. The pooled second-line HIV treatment failure rate was 15.0 per 100 PYs (95% CI: 13.0–18.0). It was slightly higher at 12–18 months of follow-up (19.0/100 PYs; 95% CI: 15.0–22.0), in children (19.0/100 PYs; 95% CI: 14.0–23.0) and in southern SSA (18.0/100 PYs; 95% CI: 14.0–23.0). Baseline values (high viral load (OR: 5.67; 95% CI: 13.40–9.45); advanced clinical stage (OR: 3.27; 95% CI: 2.07–5.19); and low CD4 counts (OR: 2.80; 95% CI: 1.83–4.29)) and suboptimal adherence to therapy (OR: 1.92; 95% CI: 1.28–2.86) were the factors associated with increased failure rates. Conclusion: Second-line HIV treatment failure has become highly prevalent in SSA with alarming rates during the 12–18 month period of treatment start; in children; and southern SSA. Therefore, the second-line HIV treatment approach in SSA should critically consider excellent adherence to therapy, aggressive viral load suppression, and rapid immune recovery. [ABSTRACT FROM AUTHOR]

Background: Correlation with HPV viral load and worsening cervical lesions had been reported, but its potential for triage after primary HPV screening has not been adequately explored, especially when combined with HPV-16/18 genotyping. Objective: To evaluate combinations of human papillomavirus (HPV) viral load and genotyping for HPV-16/18 as secondary screening strategies. Methods: The Shenzhen Cervical Cancer Screening Trial Ⅱ (SHENCCAST Ⅱ) database was re-analyzed to explore new screening algorithms using the results of Hybrid Capture 2 (HC2), Mass Array Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass spectrometry System (MALDI-TOF-MS) and the ThinPrep cytologic test (TCT) obtained by endocervical sampling. Results: Compared with the recommended screening strategy of genotyping HPV-16/18 plus reflex to cytology, using viral load (10 RLU/CO as threshold) plus reflex to cytology resulted in less cytology but had a significantly higher sensitivity for cervical intraepithelial neoplasia 2+ (CIN2+)/CIN3+ without considerable changes in specificity and referral rates. Both of the strategy of using viral load ≥10 RLU/CO as cut-point for immediate colposcopy followed by triage genotyping HPV-16/18 for the other positive (≥1<10 RLU/CO) and the strategy of referring HPV-16/18 positives for immediate colposcopy followed by triage viral load (10 RLU/CO as threshold) for non-HPV-16/18 positives had comparable screening efficacy with algorithims that contain cytology. Conclusions: Primary HPV screening with triage of HPV-positive women by a combination of viral load and genotyping for HPV-16/18 provides good balance between sensitivity and specificity, the number of tests required, and referral rates. [ABSTRACT FROM AUTHOR]

Aim: To summarise and quantify the effect of tobacco smoking on the risk of developing community acquired pneumonia (CAP) in adults. Methods: We systematically searched MEDLINE, Embase, CINAHL, PsychINFO and Web of Science, from inception to October 2017, to identify case-control and cohort studies and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The review protocol was registered with the PROSPERO database (CRD42018093943). Study quality was assessed by the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) or hazard ratios (HRs) were estimated using a random-effects model. Results: Of 647 studies identified, 27 studies were included (n = 460,592 participants) in the systematic review. Most of the included studies were of moderate quality with a median score of six (IQR 6–7). Meta-analysis showed that current smokers (pooled OR 2.17, 95% CI 1.70–2.76, n = 13 studies; pooled HR 1.52, 95% CI 1.13–2.04, n = 7 studies) and ex-smokers (pooled OR 1.49, 95% CI 1.26–1.75, n = 8 studies; pooled HR 1.18, 95% CI 0.91–1.52, n = 6 studies) were more likely to develop CAP compared to never smokers. Although the association between passive smoking and risk of CAP in adults of all ages was not statistically significant (pooled OR 1.13, 95% CI 0.94–1.36, n = 5 studies), passive smoking in adults aged ≥65 years was associated with a 64% increased risk of CAP (pooled OR 1.64; 95% CI 1.17–2.30, n = 2 studies). Dose-response analyses of data from five studies revealed a significant trend; current smokers who smoked higher amount of tobacco had a higher risk of CAP. Conclusion: Tobacco smoke exposure is significantly associated with the development of CAP in current smokers and ex-smokers. Adults aged > 65 years who are passive smokers are also at higher risk of CAP. For current smokers, a significant dose-response relationship is evident. [ABSTRACT FROM AUTHOR]