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India has the highest burden of Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) worldwide. Innovative technology is the need of the hour to identify these cases that remain either undiagnosed or inadequately diagnosed due to the unavailability of appropriate tools at primary healthcare settings. We developed and evaluated 3 kits, namely ‘TB Detect’ (containing BioFM-Filter device), ‘TB Concentration and Transport’ (containing Trans-Filter device) and ‘TB DNA Extraction’ kits. These kits enable bio-safe equipment-free concentration of sputum on filters and improved fluorescence microscopy at primary healthcare centres, ambient temperature transport of dried inactivated sputum filters to central laboratories and molecular detection of drug resistance by PCR and DNA sequencing (Mol-DST). In a 2-site evaluation (n = 1190 sputum specimens) on presumptive TB patients, BioFM-Filter smear exhibited a significant increase in positivity of 7% and 4% over ZN smear and LED-FM smear (p<0.05), respectively and an increment in smear grade status (1+ or 2+ to 3+) of 16% over ZN smear and 20% over LED-FM smear. The sensitivity of Mol-DST in presumptive MDR-TB and XDR-TB cases (n = 148) was 90% for Rifampicin (95% confidence interval [CI], 78–96%), 84% for Isoniazid (95% CI, 72–92%), 83% for Fluoroquinolones (95% CI, 66–93%) and 75% for Aminoglycosides (95% CI, 35–97%), using phenotypic DST as the reference standard. Test specificity was 88–93% and concordance was ~89–92% (κ value 0.8–0.9). The patient-friendly kits described here address several of the existing challenges and are designed to provide ‘Universal Access’ to rapid TB diagnosis, including drug-resistant disease. Their utility was demonstrated by application to sputum at 2 sites in India. Our findings pave the way for larger studies in different point-of-care settings, including high-density urban areas and remote geographical locations. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) incidence in South Africa is among the highest globally. Initial loss to follow-up (ILFU), defined as not starting on TB treatment within 28 days of testing positive, is undermining control efforts. We assessed the feasibility, acceptability, and potential of a mHealth application to reduce ILFU. Methods: An mHealth application was developed to capture patients TB investigation data, provide results and monitor treatment initiation. This was implemented in two primary health clinics (PHC) in inner-city Johannesburg. Feasibility was assessed by comparing documentation of personal details, specimen results for same individuals during implementation period (paper register and Mhealth application). Effectiveness was assessed by comparing proportion of patients with results within 48 hours, and proportion started on treatment within 28 days of testing TB positive during pre- implementation (paper register) and implementation (mHealth application) periods. In-depth interviews with patients and providers were conducted to assess acceptability of application. Results: Pre-implementation, 457 patients were recorded in paper registers [195 (42.7%) male, median age 34 years (interquartile range IQR (28–40), 45 (10.5%) sputum Xpert positive]. During implementation, 319 patients were recorded in paper register and the mHealth application [131 (41.1%) male, median age 32 years (IQR 27–38), 33 (10.3%) sputum Xpert positive]. The proportion with complete personal details: [mHealth 95.0% versus paper register 94.0%, (p = 0.54)] and proportion with documented results: [mHealth 97.4% versus paper register 97.8%, (p = 0.79)] were not different in the two methods. The proportion of results available within 48 hours: [mHealth 96.8% versus paper register 68.6%), (p <0.001)], and the proportion on treatment within 28 days [mHealth 28/33 (84.8%) versus paper register 30/44 (68.2%), (p = 0.08)] increased during implementation but was not statistically significant. In-depth interviews showed that providers easily integrated the mHealth application into routine TB investigation and patients positively received the delivery of results via text message. Time from sputum collection to TB treatment initiation decreased from 4 days (pre-implementation) to 3 days but was not statistically significant. Conclusions: We demonstrated that implementation of the mHealth application was feasible, acceptable to health care providers and patients, and has potential to reduce the time to TB treatment initiation and ILFU in PHC settings. [ABSTRACT FROM AUTHOR]

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa—a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years—a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a bacterial infection that is well-known in the palaeopathological record because it can affect the skeleton and consequently leaves readily identifiable macroscopic alterations. Palaeopathological case studies provide invaluable information about the spatio-temporal distribution of TB in the past. This is true for those archaeological periods and geographical regions from when and where no or very few TB cases have been published until now–as in the Sarmatian period (1st–5th centuries CE) in the Barbaricum of the Carpathian Basin. The aim of our paper is to discuss five newly discovered TB cases (HK199, HK201, HK225, HK253, and HK309) from the Sarmatian-period archaeological site of Hódmezővásárhely–Kenyere-ér, Bereczki-tanya (Csongrád-Csanád county, Hungary). Detailed macromorphological evaluation of the skeletons focused on the detection of bony changes likely associated with different forms of TB. In all five cases, the presence of endocranial alterations (especially TB-specific granular impressions) suggests that these individuals suffered from TB meningitis. Furthermore, the skeletal lesions observed in the spine and both hip joints of HK225 indicate that this juvenile also had multifocal osteoarticular TB. Thanks to the discovery of HK199, HK201, HK225, HK253, and HK309, the number of TB cases known from the Sarmatian-period Carpathian Basin doubled, implying that the disease was likely more frequent in the Barbaricum than previously thought. Without the application of granular impressions, the diagnosis of TB could not have been established in these five cases. Thus, the identification of TB in these individuals highlights the importance of diagnostics development, especially the refinement of diagnostic criteria. Based on the above, the systematic macromorphological (re-)evaluation of osteoarchaeological series from the Sarmatian-period Carpathian Basin would be advantageous to provide a more accurate picture of how TB may have impacted the ancestral human communities of the Barbaricum. [ABSTRACT FROM AUTHOR]

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]

Introduction: The field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB. Methods: Pubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts. Results & Discussion: From 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4), key determinants of diagnostic delay (n = 5), operational context (n = 5), and the pre-diagnostic infectious period (n = 1). The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7), and alternative nucleic acid amplification tests (NAATs) (n = 4). Most (n = 16) of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER). Conclusion: Although models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical models. Further models are needed that address a wider array of diagnostic and epidemiological settings, that explore the inherent uncertainty of models and that include additional epidemiological data on transmission implications of false-negative diagnosis and the pre-diagnostic period. [ABSTRACT FROM AUTHOR]

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4–6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5–95.3) sensitivity and 100% (95% CI: 94.4–100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2–93.6) for culture performed on site and 72.2% (95% CI: 54.8–85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7–100) and 100% (95% CI: 94.5–100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited. [ABSTRACT FROM AUTHOR]

An exciting trend in clinical diagnostics is the development of easy-to-use, minimally invasive assays for screening and prevention of disease at the point of care. Proximity Extension Assay (PEA), an homogeneous, dual-recognition immunoassay, has proven to be sensitive, specific and convenient for detection or quantitation of one or multiple analytes in human plasma. In this paper, the PEA principle was applied to the detection of procalcitonin (PCT), a widely used biomarker for the identification of bacterial infection. A simple, short PEA protocol, with an assay time suitable for point-of-care diagnostics, is presented here as a proof of concept. Pairs of oligonucleotides and monoclonal antibodies were selected to generate tools specifically adapted to the development of an efficient PEA for PCT detection. The assay time was reduced by more than 13-fold compared to published versions of PEA, without significantly affecting assay performance. It was also demonstrated that T4 DNA polymerase could advantageously be replaced by other polymerases having strong 3'>5' exonuclease activity. The sensitivity of this improved assay was determined to be about 0.1 ng/mL of PCT in plasma specimen. The potential use of such an assay in an integrated system for the low-plex detection of biomarkers in human specimen at the point of care was discussed. [ABSTRACT FROM AUTHOR]

Introduction: Research on simplified antibiotic regimens for outpatient treatment of 'Possible Serious Bacterial Infection' (PSBI) and the subsequent World Health Organization (WHO) guidelines provide an opportunity to increase treatment coverage. This multi-country implementation research initiative aimed to learn how to implement the WHO guideline in diverse contexts. These experiences have been individually published; this overview paper provides a summary of results and lessons learned across sites. Methods summary: A common mixed qualitative and quantitative methods protocol for implementation research was used in eleven sites in the Democratic Republic of Congo (Equateur province), Ethiopia (Tigray and Oromia regions), India (Haryana, Himachal Pradesh, Maharashtra, and Uttar Pradesh states), Malawi (Central Region), Nigeria (Kaduna and Oyo states), and Pakistan (Sindh province). Key steps in implementation research were: i) policy dialogue with the national government and key stakeholders, ii) the establishment of a 'Technical Support Unit' with the research team and district level managers, and iii) development of an implementation strategy and its refinement using an iterative process of implementation, programme learning and evaluation. Results summary: All sites successfully developed and evaluated an implementation strategy to increase coverage of PSBI treatment. During the study period, a total of 6677 young infants from the study catchment area were identified and treated at health facilities in the study area as inpatients or outpatients among 88179 live births identified. The estimated coverage of PSBI treatment was 75.7% (95% CI 74.8% to 78.6%), assuming a 10% incidence of PSBI among all live births. The treatment coverage was variable, ranging from 53.3% in Lucknow, India to 97.3% in Ibadan, Nigeria. The coverage of inpatient treatment ranged from 1.9% in Zaria, Nigeria, to 33.9% in Tigray, Ethiopia. The outpatient treatment coverage ranged from 30.6% in Pune, India, to 93.6% in Zaria, Nigeria. Overall, the case fatality rate (CFR) was 14.6% (95% CI 11.5% to 18.2%) for 0-59-day old infants with critical illness, 1.9% (95% CI 1.5% to 2.4%) for 0-59-day old infants with clinical severe infection and 0.1% for fast breathing in 7–59 days old. Among infants treated as outpatients, CFR was 13.7% (95% CI 8.7% to 20.2%) for 0-59-day old infants with critical illness, 0.9% (95% CI 0.6% to 1.2%) for 0-59-day old infants with clinical severe infection, and 0.1% for infants 7–59 days old with fast breathing. Conclusion: Important lessons on how to conduct each step of implementation research, and the challenges and facilitators for implementation of PSBI management guideline in routine health systems are summarised and discussed. These lessons will be used to introduce and scale-up implementation in relevant Low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: In August 2011, the German Protection against Infection Act was amended, mandating the reporting of healthcare associated infection (HAI) outbreak notifications by all healthcare workers in Germany via local public health authorities and federal states to the Robert Koch Institute (RKI). Objective: To describe the reported HAI-outbreaks and the surveillance system’s structure and capabilities. Methods: Information on each outbreak was collected using standard paper forms and notified to RKI. Notifications were screened daily and regularly analysed. Results: Between November 2011 and November 2012, 1,326 paper forms notified 578 HAI-outbreaks, between 7 and 116 outbreaks per month. The main causative agent was norovirus (n = 414/578; 72%). Among the 108 outbreaks caused by bacteria, the most frequent pathogens were Clostridium difficile (25%) Klebsiella spp. (19%) and Staphylococcus spp. (19%). Multidrug-resistant bacteria were responsible for 54/108 (50%) bacterial outbreaks. Hospitals were affected most frequently (485/578; 84%). Hospital outbreaks due to bacteria were mostly reported from intensive care units (ICUs) (45%), followed by internal medicine wards (16%). Conclusion: The mandatory HAI-outbreak surveillance system describes common outbreaks. Pathogens with a particular high potential to cause large or severe outbreaks may be identified, enabling us to further focus research and preventive measures. Increasing the sensitivity and reliability of the data collection further will facilitate identification of outbreaks able to increase in size and severity, and guide specific control measures to interrupt their propagation. [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]

Objective: Cultural changes faced by immigrants and ethnic minorities after moving to a host country may have a detrimental or beneficial influence on their oral health and oral health-related behaviors. Therefore, this paper reviews the literature to see the impact of acculturation on immigrants and ethnic minorities’ oral health outcomes. Methods: We searched seven electronic databases up to January 2018. All cross-sectional and longitudinal quantitative studies that examined associations between acculturation and oral health status and/or oral health behaviors among ethnic minority and immigrant population[s] were included. Study selection, data extraction, and risk of bias assessment were completed in duplicate. The Newcastle-Ottawa checklist was used to appraise the methodological quality of the quantitative studies. A meta-analytic approach was not feasible. Results: A total of 42 quantitative studies were identified. The studies showed a positive association between acculturation and oral health status/behaviors. The most frequently used acculturation indicators were language spoken by immigrant and ethnic minorities and length of stay at the host country. High-acculturated immigrant and ethnic minority groups demonstrated better oral health outcomes, oral health behaviors, dental care utilization, and dental knowledge. Conclusions: According to existing evidence, a positive effect of acculturation on oral health status and behaviors was found. Practical implications: Dental practitioners should be culturally competent to provide the appropriate services and treatments to immigrant and ethnic minorities. Policymakers should also be sensitive to cultural diversities and properly address the unique needs of each group in order to maintain oral health equity. [ABSTRACT FROM AUTHOR]

Objective: Clinical code sets are vital to research using routinely-collected electronic healthcare data. Existing code set engineering methods pose significant limitations when considering reproducible research. To improve the transparency and reusability of research, these code sets must abide by FAIR principles; this is not currently happening. We propose ‘term sets’, an equivalent alternative to code sets that are findable, accessible, interoperable and reusable. Materials and methods: We describe a new code set representation, consisting of natural language inclusion and exclusion terms (term sets), and explain its relationship to code sets. We formally prove that any code set has a corresponding term set. We demonstrate utility by searching for recently published code sets, representing them as term sets, and reporting on the number of inclusion and exclusion terms compared with the size of the code set. Results: Thirty-one code sets from 20 papers covering diverse disease domains were converted into term sets. The term sets were on average 74% the size of their equivalent original code set. Four term sets were larger due to deficiencies in the original code sets. Discussion: Term sets can concisely represent any code set. This may reduce barriers for examining and reusing code sets, which may accelerate research using healthcare databases. We have developed open-source software that supports researchers using term sets. Conclusion: Term sets are independent of clinical code terminologies and therefore: enable reproducible research; are resistant to terminology changes; and are less error-prone as they are shorter than the equivalent code set. [ABSTRACT FROM AUTHOR]

Indiscriminate use of antibiotics to treat infections that are of viral origin contributes to unnecessary use which potentially may induce resistance in commensal bacteria. To counteract this a number of host gene transcriptional studies have been conducted to identify genes that are differently expressed during bacterial and viral infections in humans, and thus could be used as a tool to base decisions on the use of antibiotics. In this paper, we aimed to evaluate the potential of a selection of genes that have been considered biomarkers in humans, to differentially diagnose bacterial from viral infections in the pig. First porcine PBMC were induced with six toll-like receptor (TLR) agonists (FliC, LPS, ODN 2216, Pam3CSK4, poly I:C, R848) to mimic host gene expression induced by bacterial or viral pathogens, or exposed to heat-killed Actinobacillus pleuropneumoniae or a split influenza virus. Genes that were differentially expressed between bacterial and viral inducers were further evaluated on clinical material comprising eleven healthy pigs, and six pigs infected with A. pleuropneumoniae. This comprised three virally upregulated genes (IFI44L, MxA, RSAD2) and four bacterially upregulated genes (IL-1β, IL-8, FAM89A, S100PBP). All six infected pigs could be differentially diagnosed to healthy pigs using a host gene transcription assay based on the geometric average of the bacterially induced genes IL-8 and S100PBP over that of the virally induced gene MxA. [ABSTRACT FROM AUTHOR]

Background: Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis. Methods: Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy. Results: From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39–5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23–0.69 per 100 person-years]) with significant heterogeneity observed between the studies. Conclusions: Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis. [ABSTRACT FROM AUTHOR]

Animal diseases are global issues affecting the productivity and financial profitability of affected farms. Johne’s disease is distributed on farms worldwide and is an endemic contagious bacterial infection in ruminants caused by Mycobacterium avium subspecies paratuberculosis. In cattle, the clinical disease manifests itself as chronic enteritis resulting in reduced production, weight loss, and eventually death. Johne’s disease is prevalent in the UK, including Scotland. Direct costs and losses associated with Johne’s disease have been estimated in previous research, confirming an important economic impact of the disease in UK herds. Despite this, the distributional impact of Johne’s disease among milk consumers and producers in Scotland has not been estimated. In this paper, we evaluate the change in society’s economic welfare, namely to dairy producers (i.e. infected and uninfected herds) and milk consumers in Scotland induced by the introduction of Johne’s disease in the national Scottish dairy herd. At the national-level, we conclude that the economic burden falls mainly on producers of infected herds and, to a lesser extent, milk consumers, while producers of uninfected herds benefit from the presence of Johne’s. An infected producer’s loss per cow is approximately two times larger in magnitude than that of an uninfected producer’s gain. Such economic welfare estimates are an important comparison of the relative costs of national herd prevalence and the wider economic welfare implications for both producers and consumers. This is particularly important from a policy, public good, cost sharing, and human health perspective. The economic welfare framework presented in this paper can be applied to other diseases to examine the relative burden of society’s economic welfare of alternative livestock disease scenarios. In addition, the sensitivity analysis evaluates uncertainty in economic welfare given limited data and uncertainty in the national herd prevalence, and other input parameters, associated with Johne’s disease in Scotland. Therefore, until the prevalence of Johne’s is better understood, the full economic cost to Scottish dairy herds remains uncertain but in the meantime the sensitivity analysis evaluates the robustness of economic welfare to such uncertainties. [ABSTRACT FROM AUTHOR]

This paper aims to reschedule online metro trains in delay scenarios. A graph representation and a mixed integer programming model are proposed to formulate the optimization problem. The solution approach is a two-stage optimization method. In the first stage, based on a proposed train state graph and system analysis, the primary and flow-on delays are specifically analyzed and identified with a critical path algorithm. For the second stage a hybrid genetic algorithm is designed to optimize the schedule, with the delay identification results as input. Then, based on the infrastructure data of Beijing Subway Line 4 of China, case studies are presented to demonstrate the effectiveness and efficiency of the solution approach. The results show that the algorithm can quickly and accurately identify primary delays among different types of delays. The economic cost of energy consumption and total delay is considerably reduced (by more than 10% in each case). The computation time of the Hybrid-GA is low enough for rescheduling online. Sensitivity analyses further demonstrate that the proposed approach can be used as a decision-making support tool for operators. [ABSTRACT FROM AUTHOR]

Objective: To carry out a systematic review with meta-analysis of prevalence of caries in Latin America and Caribbean children considering studies performed in this new century. Methods: Two reviewers searched PubMed, Embase, LILACS and governmental databases through May 2016 to identify papers published in English, Portuguese or Spanish. Studies in those countries performed with 5–6 or 11–13 year-old children and that presented separate prevalence figures from primary and permanent teeth were selected. We performed a descriptive analysis of studies and meta-analysis to calculate the overall prevalence and 95% confidence intervals (95% CI) in both primary and permanent teeth. We also analyzed the trends of prevalence of caries through the years and influence of other variables on caries prevalence using multilevel analysis. Results: Seventy-five studies were included from the 1,306 articles initially retrieved. The meta-analysis of caries prevalence grouped for Latin American and the Caribbean countries were highly different from Brazil and other investigated countries for primary teeth (5–6 years-old—Brazil: 0.52, other countries:0.70) and permanent teeth (11–12 years-old—Brazil: 0.56, other countries: 0.63). For studies conducted only in Brazil the prevalence was significant lower for primary but not for permanent teeth. In Brazil, a downward trend of caries prevalence was observed in 11-13-year-old children. Conclusion: Despite the decline of caries prevalence in permanent teeth, mainly in Brazil, the disease still affects more than half of the children population in Latin American and Caribbean countries in the 21st Century. [ABSTRACT FROM AUTHOR]

Pertussis is a contagious respiratory disease which mainly affects young children and can be fatal if left untreated. The World Health Organization estimates 16 million pertussis cases annually worldwide resulting in over 200,000 deaths. It is prevalent mainly in developing countries where it is difficult to diagnose due to the lack of healthcare facilities and medical professionals. Hence, a low-cost, quick and easily accessible solution is needed to provide pertussis diagnosis in such areas to contain an outbreak. In this paper we present an algorithm for automated diagnosis of pertussis using audio signals by analyzing cough and whoop sounds. The algorithm consists of three main blocks to perform automatic cough detection, cough classification and whooping sound detection. Each of these extract relevant features from the audio signal and subsequently classify them using a logistic regression model. The output from these blocks is collated to provide a pertussis likelihood diagnosis. The performance of the proposed algorithm is evaluated using audio recordings from 38 patients. The algorithm is able to diagnose all pertussis successfully from all audio recordings without any false diagnosis. It can also automatically detect individual cough sounds with 92% accuracy and PPV of 97%. The low complexity of the proposed algorithm coupled with its high accuracy demonstrates that it can be readily deployed using smartphones and can be extremely useful for quick identification or early screening of pertussis and for infection outbreaks control. [ABSTRACT FROM AUTHOR]

The survey described in this research paper aimed to investigate the economic and health impacts of birds on dairies. Birds are common pests on dairies, consuming and contaminating feed intended for cattle. As a result, dairy operators experience increased feed costs and increased pathogen and disease risk. We surveyed dairy operators attending the 2017 Washington Dairy Conference to examine the impact of birds on dairies in Washington State. Dairy operators reported feed losses valued at $55 per cow resulting in annual losses totaling $5.5 million in the Western region of the state and $9.2 million in the Eastern region of the state. Shooting was the most commonly used bird management method and European starlings (Sternus vulgaris) were the most frequently implicated species statewide. Bird abundance greater than 10,000 birds per day was associated with larger herd size and with self-reported presence of Johne’s disease and Salmonella. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review was conducted to gain insight into the efficacy of transmission of infectious agents to colony sentinels by soiled bedding transfer based on publications studying this subject in mice and rats. This information is essential to establish recommendations for the design of health monitoring programs which use sentinels to determine the microbiological status of laboratory animal colonies. Results: Fifteen original articles retrieved from PubMed, Embase, and CAB abstracts met the inclusion criteria. The design of the studies varied substantially per infectious agent with regard to dose of soiled bedding, exposure time, and sentinel strains used. Conclusion: With our conservative criteria for effectiveness, soiled bedding transfer appeared to be effective for MHV, MPV, TMEV, Helicobacter spp., and fur mite infections and ineffective for Sendai virus. For other infectious agents, such as MNV, EDIM, MVM, SDAV, Clostridium piliforme, and pinworms, too few data were available to be able to draw robust conclusions on the efficacy of soiled bedding transfer. Recommendation: The identified evidence only pertains to a portion of the infectious organisms included in the FELASA 2014 guidelines. As many animal facilities design their health monitoring program according to these recommendations, additional studies are warranted to draw comprehensive conclusions on the effective transmission of the infectious agents listed in these guidelines by soiled bedding transfer. [ABSTRACT FROM AUTHOR]

The zebrafish Danio rerio has become a popular model host to explore disease pathology caused by infectious agents. A main advantage is its transparency at an early age, which enables live imaging of infection dynamics. While multispecies infections are common in patients, the zebrafish model is rarely used to study them, although the model would be ideal for investigating pathogen-pathogen and pathogen-host interactions. This may be due to the absence of an established multispecies infection protocol for a defined organ and the lack of suitable image analysis pipelines for automated image processing. To address these issues, we developed a protocol for establishing and tracking single and multispecies bacterial infections in the inner ear structure (otic vesicle) of the zebrafish by imaging. Subsequently, we generated an image analysis pipeline that involved deep learning for the automated segmentation of the otic vesicle, and scripts for quantifying pathogen frequencies through fluorescence intensity measures. We used Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, three of the difficult-to-treat ESKAPE pathogens, to show that our infection protocol and image analysis pipeline work both for single pathogens and pairwise pathogen combinations. Thus, our protocols provide a comprehensive toolbox for studying single and multispecies infections in real-time in zebrafish. [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]

Background: Developing countries still struggle with late detection and mortality from pertussis. A review of clinical case definitions is necessary for early disease detection. This paper aimed to study possible clinical characteristics for earlier pertussis detection in a sporadic setting. Methods: We conducted a retrospective review of medical and laboratory records in a general paediatric ward of a district hospital in a developing country. Inclusion criteria were all children hospitalised with nasopharyngeal swab taken for Bordetella pertussis. We compared sensitivity and specificity of World Health Organization diagnostic criteria with other clinical characteristics. Polymerase chain reaction Bordetella pertussis was the gold standard used. Results: Out of 207 eligible admissions, the study retrieved 128 complete records. Approximately half of the children were less than 3 months old. The World Health Organization diagnostic criteria had a low sensitivity (15%), but high specificity (92%). In comparison, combinations that included paroxysmal cough, ill contact and facial congestion had higher sensitivity. Increasing cough duration improved specificity while compromising sensitivity. Conclusion: Several clinical characteristics such as paroxysmal cough, facial congestion and a history of ill contact have potential for early clinical detection. Conventional emphasis on cough duration may hamper early detection. [ABSTRACT FROM AUTHOR]

Biofilm-related infections of bones pose a significant therapeutic issue. In this article we present in vitro results of the efficacy of gentamicin released from a collagen sponge carrier against Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae biofilms preformed on hydroxyapatite surface. The results indicate that high local concentrations of gentamicin released from a sponge eradicate the biofilm formed not only by gentamicin-sensitive strains but, to some extent, also by those that display a resistance pattern in routine diagnostics. The data presented in this paper is of high clinical translational value and may find application in the treatment of bone infections. [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]

Background: The proportion of women attending four or more antenatal care (ANC) visits is widely used for monitoring, but provides limited information on quality of care. Effective coverage metrics, assessing if ANC interventions are completely delivered, can identify critical gaps in healthcare service delivery. We aimed to measure coverage of at least one screening and effective coverage of ANC interventions in the public health system in the West Bank, Palestine, and to explore associations between infrastructure-related and maternal sociodemographic variables and effective coverage. Methods: We used data from paper-based clinical records of 1369 pregnant women attending ANC in 17 primary healthcare clinics. Infrastructure-related variables were derived from a 2014 national inventory assessment of clinics. Sample size calculations were made to detect effective coverage ranging 40–60% with a 2–3% margin of error, clinics were selected by probability sampling. We calculated inverse probability weighted percentages of: effective coverage of appropriate number and timing of screenings of ANC interventions; and coverage of at least one screening. Results: Coverage of one screening and effective coverage of ANC interventions were notably different for screening for: hypertension (98% vs. 10%); fetal growth abnormalities (66% vs. 6%); anemia (93% vs. 14%); gestational diabetes (93% vs. 34%), and antenatal ultrasound (74% vs. 24%). Clinics with a laboratory and ultrasound generally performed better in terms of effective coverage, and maternal sociodemographic factors had no associations with effective coverage estimates. Only 13% of the women attended ANC visits according to the recommended national schedule, driving effective coverage down. Conclusion: Indicators for ANC monitoring and their definitions can have important consequences for quantifying health system performance and identifying issues with care provision. To achieve more effective coverage in public primary care clinics in the West Bank, efforts should be made to improve care provision according to prescribed guidelines. [ABSTRACT FROM AUTHOR]

In Mycobacterium tuberculosis (Mtb) the detection of single nucleotide polymorphisms (SNPs) is of high importance both for diagnostics, since drug resistance is primarily caused by the acquisition of SNPs in multiple drug targets, and for epidemiological studies in which strain typing is performed by SNP identification. To provide the necessary coverage of clinically relevant resistance profiles and strain types, nucleic acid-based measurement techniques must be able to detect a large number of potential SNPs. Since the Mtb problem is pressing in many resource-poor countries, requiring low-cost point-of-care biosensors, this is a non-trivial technological challenge. This paper presents a proof-of-concept in which we chose simple DNA-DNA hybridization as a sensing principle since this can be transferred to existing low-cost hardware platforms, and we pushed the multiplex boundaries of it. With a custom designed probe set and a physicochemical-driven data analysis it was possible to simultaneously detect the presence of SNPs associated with first- and second-line drug resistance and Mtb strain typing. We have demonstrated its use for the identification of drug resistance and strain type from a panel of phylogenetically diverse clinical strains. Furthermore, reliable detection of the presence of a minority population (<5%) of drug-resistant Mtb was possible. [ABSTRACT FROM AUTHOR]

Background: Leprosy remains a disease of concern in many countries including Nepal. To achieve the target of elimination, the WHO strategy promotes comprehensive education of patients, healthcare workers (HCWs), and the public on leprosy-related issues. However most educational programs are based on the concerns of HCWs and not on patients’ needs. The objective of this paper is to explore the educational needs of leprosy affected patients in Nepal and compare them to the needs perceived by HCWs. Methodology/principal findings: Semi directive interviews were conducted with patients and HCWs. The data was analyzed using the basic interpretative qualitative framework. The study was conducted in two leprosy referral centers, one university hospital and one primary health care center: Lalgadh Leprosy Hospital and Services Centre, Anandaban Hospital and its satellite clinic in Patan, B. P. Koirala Institute of Health Sciences in Dharan, and the Itahari primary health care centre. The results show that there remains a lack of knowledge regarding the disease (origins, manifestations, prevention and treatment) contributing to late care seeking behavior and high levels of stigma, with an important psychological and financial stress for patients. All of the HCWs displayed a good understanding of patients’ difficulties and needs and acknowledged the key role of patient education. However, they expressed several challenges in managing patients due to lack of time, human resources and training in patient education. Conclusions/significance: Further efforts need to be made to increase patients’ general knowledge of the disease in order to motivate them to seek healthcare earlier and change their perception of the disease to reduce stigma. HCWs need proper training in patient education and counseling for them to acquire the necessary skills required to address the different educational needs of their patients. The use of lay and peer counselors would be an option to address the workload and lack of time expressed by HCWs. [ABSTRACT FROM AUTHOR]

The strategy of the “Belt and Road” initiative aims not only to promote the cooperation and the development of economic trade, but also to boost the integration and development in multiple fields—especially in the field of health. This paper explores the health levels of member-states in the Belt and Road initiative from the perspective of regional differences and spatial patterns. Data from the 68 member-states in the Belt and Road initiative were selected from the statistical data on disease and socioeconomics in all countries from the 2015 publication by the World Bank and the World Health Organization. Health indicators that can reflect health levels of member states were selected. Moran’s I and Getis-Ord Gi* were used to analyze the spatial clustering and hot/cold spots of the health status. After that a novel spatial statistical method “geographical detector” was used to analysis the spatial stratified heterogeneity of the selected health indicators. The result showed that the health level of the member states fluctuated around the world average and varied greatly within the member states. The health status of the member states showed spatial clustering, and the q-statistics of the geographical detector confirmed that the health status demonstrated statistically significant spatial heterogeneity for different continent the member states reside. In general, member states in Europe and Oceania demonstrated higher health status, while those in South Asia, Southeast Asia, Africa and part of Middle East have lower health status. In particular, special attention should be paid to control communicable diseases in African member states. Different regions and member states face different kinds of health threats in various degrees. Member states should strengthen health cooperation between themselves and work closely with other countries to make the “belt and road” a healthy road. [ABSTRACT FROM AUTHOR]

Introduction: The Indian Tuberculosis (TB) Programme currently faces the dual challenges of tackling increasing numbers of drug resistant (DR) TB cases and regulating practices of a pluralistic private sector catering to TB patients. A study of health seeking behaviour of DR-TB patients in such a situation, offers an opportunity to understand the problems patients face while interacting with health systems. Methodology: Forty-six DR-TB patients drawn from 15 high TB burden wards in Mumbai were interviewed using an open ended interview tool. Interviews were audio recorded and transcribed. Pathway schematics developed from analysis of patient records, were linked to transcripts. Open coding was used to analyse these units and themes were derived after collating the codes. Results and discussion: The paper presents themes interwoven with narratives in the discussions. These include awareness-action gap among patients, role of neighbourhood providers, responsiveness of health systems, the not-such a ‘merry go round’ that patients go/are made to go on while seeking care, costs of diagnostics and treatment, and how DR-TB is viewed as the ‘big TB’. Conclusion: The recommendations are based on a preventative ethos which is sustainable, compared to interventions with top-down approaches, which get piloted, but fail to sustain impact when scaled up. [ABSTRACT FROM AUTHOR]

Salmonella Typhi and Salmonella Paratyphi A are the leading causative agents of enteric fever which cause morbidity and mortality worldwide. Currently, there is no combination vaccine which could protect infection from both the strains. In this paper, we are focusing on the development of a novel bivalent typhoidal Outer Membrane Vesicles (OMVs) based immunogen against enteric fever. We have isolated Salmonella Typhi and Paratyphi A OMVs and also characterized OMVs associated antigens. Then we immunized adult mice with three doses of our newly formulated bivalent immunogen orally (25 μg/200 μl). After three doses of oral immunization, we found our immunogen could significantly induce humoral response. We have also found serum IgG against LPS, Vi-polysaccharide etc. OMV immunization induces CD4, CD8 and CD19 population in immunized mice spleen. It also induces Th1 and Th17-cell mediated immunity. We also found bivalent OMVs immunization can prevent more than lethal dose of heterologous Salmonella strains mediated systemic infection in adult mice model. We determined that, the protective immune responses depend on the humoral and cell-mediated immune response. Furthermore, we have evaluated the mode of protective immune response carried out by anti-OMVs antibody by significantly inhibiting bacterial motility and mucin penetration ability. Taken together, these findings suggest that our bivalent immunogen could be used as a novel candidate vaccine against enteric fever. [ABSTRACT FROM AUTHOR]

Bacterial polysaccharides have numerous clinical or industrial uses. Recombinant plants could offer the possibility of producing bacterial polysaccharides on a large scale and free of contaminating bacterial toxins and antigens. We investigated the feasibility of this proposal by cloning and expressing the gene for the type 3 synthase (cps3S) of Streptococcus pneumoniae in Nicotinia tabacum, using the pCambia2301 vector and Agrobacterium tumefaciens-mediated gene transfer. In planta the recombinant synthase polymerised plant-derived UDP-glucose and UDP-glucuronic acid to form type 3 polysaccharide. Expression of the cps3S gene was detected by RT-PCR and production of the pneumococcal polysaccharide was detected in tobacco leaf extracts by double immunodiffusion, Western blotting and high-voltage paper electrophoresis. Because it is used a component of anti-pneumococcal vaccines, the immunogenicity of the plant-derived type 3 polysaccharide was tested. Mice immunised with extracts from recombinant plants were protected from challenge with a lethal dose of pneumococci in a model of pneumonia and the immunised mice had significantly elevated levels of serum anti-pneumococcal polysaccharide antibodies. This study provides the proof of the principle that bacterial polysaccharide can be successfully synthesised in plants and that these recombinant polysaccharides could be used as vaccines to protect against life-threatening infections. [ABSTRACT FROM AUTHOR]

Background: Homebased index case HIV testing (HHTC) has shown higher uptake and good yield than traditional HIV testing methods. World Health Organization has called for increased operational research to evaluate HIV care processes particularly linkage to care. In this paper, we present project results of the time taken to link newly identified PLHIV to care after HHTC in the Manicaland and Midlands provinces of Zimbabwe. Methods: We retrospectively reviewed community-facility referral data from the Zimbabwe HIV Care and Treatment project for newly diagnosed PLHIV for the period March–September 2016. A referral slip was given to a client after receiving a positive HIV results and was presented and filed upon reaching a health facility. In July 2016, the project started working with trained expert clients to assist with linkage to care. Data was entered in a spreadsheet and then imported for descriptive statistical analysis with EpiInfoTM Version 7.2.0.1. Odd ratios were used to identify factors associated with linkage to care within seven days. Results: Out of 1004 newly identified PLHIV between March and September 2016, 650 (64.7%) were linked to care. The median time taken to be linked to care was four days (Interquartile range 19 days). Overall, 63.1% (410) of PLHIV were linked to care within seven days of diagnosis and 85% within 30 days. PLHIV were more likely to be linked to care within seven days of diagnosis between July and September 2016 (OR = 4.1; p< 0.001), a period when ZHCT started working with expert clients to support linkage to care. Conclusion: HHTC resulted in almost 63% of newly diagnosed PLHIV being linked into care within seven days, and 85% within 30 days. Linkage to care within seven days was significantly associated with the period of engaging expert clients in the project. We recommend community based HIV testing programs to work with expert clients to ensure timely linkages of new PLHIV. [ABSTRACT FROM AUTHOR]

Background: Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. Methods: A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. Results: Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. Conclusion: Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) represents the ninth leading cause of death worldwide. In 2016 are estimated 1.3 million TB deaths among HIV negative people and an additional 374,000 deaths among HIV positive people. In 2016 are estimated 1.4 million new cases of TB in people living with HIV (PLHIV), 74% of whom were living in Africa. In light of these data, the reduction of mortality caused by TB in PLHIV is strongly required specially in low-income countries as Mozambique. According to international guidelines, the initial TB screening in HIV+ patients should be done with the four symptoms screening (4SS: fever, current cough, night sweats and weight loss). The diagnostic test more used in resource-limited countries is smear microscopy (SMEAR). World Health Organization (WHO) recommended Lateral Flow urine LipoArabinoMannan assay (LF-LAM) in immunocompromised patients; in 2010 WHO endorsed the use of Xpert Mycobacterium Tuberculosis/Rifampicin (MTB/RIF) test for rapid TB diagnosis but the assay is not used as screening test in all HIV+ patients irrespectively of symptoms due to cost and logistical barriers. The paper aims to evaluate the cost-effectiveness of three screening protocols: standard (4SS and SMEAR in positive patients to 4SS); MTB/RIF; LF-LAM / MTB/RIF. Methods: We developed a model to assess the cost-effectiveness of the MTB/RIF protocol versus the common standard and LF-LAM / MTB/RIF protocol. The model considered a sample of 1,000 HIV+ antiretroviral treatment naïve patients in Mozambique. We evaluated disability-adjusted life year (DALY) averted for each protocol, cost per DALY, and incremental cost-effectiveness ratio (ICER), over 1-year, assuming a national healthcare system perspective. The model considered the delayed diagnosis as the time elapsed between a false negative test and the diagnosis and treatment of TB. Additional health system organization delay is defined as the time interval between positive test and treatment initiation caused by a delay in the delivery of results due organization of services. We conducted a sensitivity analysis on more relevant variables. Results: The MTB/RIF protocol was cost-effective as compared to the standard protocol with an ICER of $56.54 per DALY saved. In a cohort of 1,000 patients MTB/RIF and LF-LAM / MTB/RIF protocol generated 1,281 and 1,254 DALY’s saved respectively, with a difference of 174 and 147 DALY respect to the standard protocol. The total cost of MTB/RIF protocol was lower ($92,263) than the standard ($147,226) and the LF-LAM / MTB/RIF ($113,196). Therefore, the cost per DALY saved including new infections due to delayed diagnosis with the standard protocol was $79.06, about 5 fold higher than MTB/RIF and LF-LAM / MTB/RIF protocols. The cost of additional TB infections due to delays in diagnosis plus health system delay seemed the more relevant costs. The low sensibility and sensitivity of the standard protocol led to a high number of false negatives, thus delayed TB diagnoses and treatment lead to the development of newly transmitted TB infections. Conclusions: Our study shows that the MTB/RIF adoption could lead to an increasing of TB case-finding and a reduction in costs compared with standard and LF-LAM / MTB/RIF protocols. [ABSTRACT FROM AUTHOR]

Clinical and subclinical mastitis affects 30% of cows and is regarded as the most significant economic burden on the dairy farm reducing milk yield and quality and increasing culling rate. A proprietary Acoustic Pulse Therapy (APT) device was developed specifically for treating dairy cows. The APT device was designed to produce deep penetrating acoustic pulses that are distributed over a large treated area at a therapeutic level. This paper presents findings from a clinical assessment of this technology for the treatment of dairy cows with subclinical and clinical mastitis. In subclinical mastitis, a group of 116 cows from 3 herds were identified with subclinical intramammary infection and enrolled in the study; 78 cows were assigned to the treatment group and 38 cows to the control group. Significant differences (P<0.001) were found where 70.5% of the cows in the treatment group returned to normal milk production, compared with only 18.4% of the control group. Daily milk yields of the treated cows increased significantly (P<0.05) and the percentage of cows with log somatic cell count under 5.6 cells/mL was significantly higher (P<0.001). Milk of the infected quarters appeared normal with lactose greater than 4.8%, but this difference was not significant. Of the treated cows with identified bacteria, 52.6% of the quarters were cured, while in the control group only 25.0% (P<0.001). Specifically, all cows identified with Escherichia coli in the treatment group were cured, with 66.6% cured with no intervention in the control. Spontaneous cure of glands infected with coagulase negative staphylococci (CNS) and Streptococci was low while treatment successfully increased the cure of CNS from 13.3% to 53.8% and that of Streptococci from 18.2% to 36.4%. Of the 4 cows identified with Staphylococcus aureus, 3 were cured. The clinical mastitis study group included 29 infected cows that were submitted either to a gold standard antibiotic treatment subgroup of 16 cows (n = 16) or to an APT treatment subgroup of 13 cows (n = 13). A cure of 18.7% was shown for the antibiotic treatment, of which logSCC returned to <5.6 cell/mL and 56.2% were culled. A cure of 76.9% was shown for the APT treatment with only one cow culled (7.7%). [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade. Methods: The Web of Science database was searched for publications from January 2007 to December 2016 with “tuberculosis” in the title. References were analysed using the R bibliometrix package. A year-stratified 5% random subset was drawn to extract funding sources and identify research areas. Findings: The annual growth rate of publications was 7.3%, and was highest (13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was the most productive country, with 18.4% of references, followed by India (9.7%), China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis, the most common research area was ‘fundamental research’ (33.8%). Frequently acknowledged funders were US and EU-based, with China and India emerging as top funders. Collaborations appeared more frequently between high-income countries and low/medium income countries (LMICs), with fewer collaborations among LMICs. Conclusion: The past decade has seen a continued increase in TB publications. While USA continues to dominate research output and funding, BRICS countries have emerged as major research producers and funders. Collaborations among BRICS would enhance future TB research productivity. [ABSTRACT FROM AUTHOR]

Epidemiological studies use saliva on a regular basis as a non-invasive and easy-to-take sample, which is assumed to be a microbial representative of the oral cavity ecosystem. However, comparative studies between different kinds of saliva samples normally used in microbial studies are scarce. The aim of the current study was to compare oral microbiota composition between two different saliva samples collected simultaneously: non-stimulated saliva with paper points and stimulated saliva collected after chewing paraffin gum. DNA was extracted from saliva samples of ten individuals, then analyzed by 16S rRNA pyrosequencing to describe bacterial diversity. The results demonstrate significant differences between the microbiota of these two kinds of saliva. Stimulated saliva was found to contain an estimated number of species over three times higher than unstimulated saliva. In addition, bacterial composition at the class and genus level was radically different between both types of samples. When compared to other oral niches, both types of saliva showed some similarity to tongue and buccal mucosa, but they do not correlate at all with the bacterial composition described in supra- or sub-gingival dental plaque, questioning their use in etiological and epidemiological studies of oral diseases of microbial origin. [ABSTRACT FROM AUTHOR]

Background: Migrant labourers living in the slums of urban and industrial patches across India make up a key sub-population so far controlling Tuberculosis (TB) in the country is concerned. This is because many TB patients from these communities- remain under reached by the Revised National Tuberculosis Control Programme (RNTCP) of India. This marginalized community usually seeks early-stage healthcare from “friendly neighbourhood” non-formal health providers (NFHPs). Because, RNTCP has limited capacity to involve the NFHPs, an implementation research project was conceived, whereby an external partner would engage with the NFHPs to enable them to identify early TB symptomatics from this key sub-population who would be then tested using Xpert MTB/RIF technology. Diagnosed TB cases among them would be referred promptly to RNTCP for treatment. This paper aimed to describe the project and its impact. Methods: Adopting a quasi-experimental before-after design, four RNTCP units from two major urban-industrial areas of Odisha were selected for intervention, which spanned five quarters and covered 151,400 people, of which 30% were slum-dwelling migrants. Two similar units comprised the control population. The hypothesis was, reaching the under reached in the intervention area through NFHPs would increase TB notification from these traditionally under-notifying units. RNTCP notification data during intervention was compared with pre-intervention era, adjusted for contemporaneous changes in control population Results: The project detected 488 Xpert+ TB cases, of whom 466 were administered RNTCP treatment. This translated into notification of additional 198 new bacteriologically positive cases to RNTCP, a 30% notification surge, after adjustment for 2% decline in control. This meant an average quarterly increase in notification of 41.20(20.08, 62.31; p<0.001) cases. The increase was immediate, evident from the rise in level in the time series analysis by 50.42(10.28, 90.55; p = 0.02) cases. Conclusion: Engagement with NFHPs contributed to an increase in TB notification to RNTCP from key under reached, slum-dwelling migrant populations. [ABSTRACT FROM AUTHOR]

Introduction: Health Care Workers (HCWs) are among the highest risk groups for contracting tuberculosis (TB), which is ranked the third most common occupational health disease in South Africa. Little is known about the true extent of the burden of TB among South African HCWs and current surveillance approaches are inadequate. The study aimed to determine the feasibility of using postal and web-based surveys accessed through registries of registered professionals to estimate the prevalence of TB among HCWs in South Africa. Materials and methods: We conducted a cross sectional survey on a sample of professional nurses and doctors (general practitioners) registered on the Medpages database platform; a subscription based registry for practising health care professionals. The survey included professionals who were actively involved in the clinical management of patients, either in public or private health care facilities. The paper based survey, including pre-paid return envelopes, was distributed via the post office and web-based surveys were distributed via e-mail through a hyperlink. Descriptive statistics were used to summarize the data and the Chi-square test to determine associations between categorical variables. Active TB was defined as any history of TB Results: Out of a total of 3,400 health care professionals contacted, 596 (18%) responses were received: 401 (67%) web-based and 195 (33%) postal. A significantly higher percentage of complete forms were from postal compared to web-based (97% [189/195] versus 87% [348/401], p<0.001). Younger (<60 years) professionals were more likely to use the web-based compared to postal (87% [236/270] versus 71% [134/189], p<0.001). Overall, the prevalence of active TB infection was 8.7%, (95%CI: 6.3%–11.7%) and there was no difference observed between doctors and nurses (10.8% [18/167] versus 7.5% [22/292], p = 0.236). Conclusion: This novel approach demonstrated the feasibility of using an existing registry of professionals to conduct surveys to estimate the prevalence of TB. Our findings showed a high TB prevalence; however the estimate might have been biased by the low response rate. Further research to optimise our approach could lead to a viable option in improving surveillance among health care professionals. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the efficacy of the combination of CPP-ACP and fluorides compared with fluorides monotherapy on patients with early caries lesions. The Medline, Embase and Cochrane databases up to August 2017 were scanned, with no restrictions. Studies satisfied the guideline of randomised controlled trials (RCTs), the patients with early caries lesions and data considering the efficacy of fluorides and CPP-ACP versus fluorides alone were selected. There was no language restriction during the literature search process, however, only papers in English or Chinese were included during the selection process. Outcome variables include laser fluorescence, quantitative light-induced fluorescence, lesion area and visual inspection scores. Mean differences were calculated during the data extraction process. Ten studies including 559 patients were selected in the meta-analysis. Fluorides combined with CPP-ACP achieved the same efficacy for early caries lesions on smooth surfaces compared with fluorides monotherapy (mean difference: -13.90, 95% confidence interval: [-39.25, 11.46], P = 0.28), and the combination treatment showed significantly better efficacy than fluorides monotherapy for occlusal early caries lesions (mean difference: -21.02, 95% confidence interval: [-27.94, -14.10], P<0.01). However, further well-designed studies are still needed. [ABSTRACT FROM AUTHOR]

In light of the increasing refusal of some parents to vaccinate children, public health strategies have focused on increasing knowledge and awareness based on a “knowledge-deficit” approach. However, decisions about vaccination are based on more than mere knowledge of risks, costs, and benefits. Individual decision making about vaccinating involves many other factors including those related to emotion, culture, religion, and socio-political context. In this paper, we use a nationally representative internet survey in the U.S. to investigate socio-political characteristics to assess attitudes about vaccination. In particular, we consider how political ideology and trust affect opinions about vaccinations for flu, pertussis, and measles. Our findings demonstrate that ideology has a direct effect on vaccine attitudes. In particular, conservative respondents are less likely to express pro-vaccination beliefs than other individuals. Furthermore, ideology also has an indirect effect on immunization propensity. The ideology variable predicts an indicator capturing trust in government medical experts, which in turn helps to explain individual-level variation with regards to attitudes about vaccine choice. [ABSTRACT FROM AUTHOR]

We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella′s lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella′s LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine. [ABSTRACT FROM AUTHOR]

Background: Smoking has been associated with a higher risk of contracting pneumonia, but contradictory results have shown that smoking may or may not decrease the risk of dying in pneumonia. The aim of this study is to investigate how smoking is associated with contracting any infection and pneumonia and death. Method and findings: Participants were drawn from the population-based Cohort of Swedish Men and the Swedish Mammography Cohort, which are representative of the Swedish population. Participants have answered detailed lifestyle questionnaires and have been followed in national registers, such as the Patient Register, Cause of Death register and Swedish Intensive Care Registry. The risks of contracting infection and pneumonia or dying in infection and pneumonia were assessed using Cox regression. Of 62,902 cohort participants, 25,297 contracted an infection of which 4,505 died; and 10,471 contracted pneumonia of which 2,851 died. Compared to never smokers, former smokers at baseline had hazard ratio (HR) 1.08 (95% confidence interval (CI) 1.05–1.12) of contracting and HR 1.19 (95% CI 1.11–1.28) of dying in infection and HR 1.17 (95% CI 1.12–1.23) of contracting and HR 1.16 (95% CI 1.06–1.27) of dying in pneumonia during follow-up. Compared to never smokers, current smokers at baseline had HR 1.17 (95% CI 1.13–1.21) of contracting infection and HR 1.64 (95% CI 1.52–1.77) dying in infection; HR 1.42 (95% CI 1.35–1.49) of contracting pneumonia and HR 1.70 (95% CI 1.55–1.87) of dying in pneumonia during follow-up. The risk of contracting and dying in infection and pneumonia increased in a dose-response manner with number of pack years smoked and decreased with years since smoking cessation. Conclusion: Smoking is associated with contracting and dying in any infection and pneumonia and the risk increases with pack years smoked, highlighting the importance of both primary prevention and smoking cessation. [ABSTRACT FROM AUTHOR]

Bacterial blight is a serious disease of carrot production worldwide. Under favorable conditions, the causal organism Xanthomonas hortorum pv. carotae causes serious loss especially in seed production because of its seed-borne character. Unlike fungal diseases, the treatment of bacterial diseases is limited and methods such as hot water or sodium hypochlorite (bleach) treatment are mainly used by seed companies. Here, we compared the efficacy of hot water treatment, sodium hypochlorite treatment and treatment with three phenolic compounds–carvacrol, thymol and eugenol, to eliminate Xanthomonas growth in vitro and subsequently in vivo on seeds of Xhc low, medium and highly infested carrot seed lots. The complete elimination of Xhc from germinated plants was obtained only for Xhc low infested seed lot with 1% sodium hypochlorite and carvacrol solutions in concentrations of 0.0196%– 0.313%. The significant reduction of Xhc presence in germinated plants of Xhc medium infested seed lot was achieved with 1% sodium hypochlorite treatment and hot water treatment. However, hot water treatment resulted in a significant reduction of seed germination percentage as well. Considering the elimination of Xhc infection from germinated plants and the effect on seed germination and plant vigor, 0.0196% carvacrol solution was suggested as an alternative to 1% sodium hypochlorite treatment regarding additional costs related to the liquidation of used treated water and to hot water treatment that has been proved to be insufficient to obtain disease-free plants. [ABSTRACT FROM AUTHOR]

Background: Even though cholera has existed for centuries and many parts of the country have sporadic, endemic and epidemic cholera, it is still an under-recognized health problem in India. A Cholera Expert Group in the country was established to gather evidence and to prepare a road map for control of cholera in India. This paper identifies cholera burden hotspots and factors associated with an increased risk of the disease. Methodology/Principle findings: We acquired district level data on cholera case reports of 2010–2015 from the Integrated Disease Surveillance Program. Socioeconomic characteristics and coverage of water and sanitation was obtained from the 2011 census. Spatial analysis was performed to identify cholera hotspots, and a zero-inflated Poisson regression was employed to identify the factors associated with cholera and predicted case count in the district. 27,615 cholera cases were reported during the 6-year period. Twenty-four of 36 states of India reported cholera during these years, and 13 states were classified as endemic. Of 641 districts, 78 districts in 15 states were identified as “hotspots” based on the reported cases. On the other hand, 111 districts in nine states were identified as “hotspots” from model-based predicted number of cases. The risk for cholera in a district was negatively associated with the coverage of literate persons, households using treated water source and owning mobile telephone, and positively associated with the coverage of poor sanitation and drainage conditions and urbanization level in the district. Conclusions/Significance: The study reaffirms that cholera continues to occur throughout a large part of India and identifies the burden hotspots and risk factors. Policymakers may use the findings of the article to develop a roadmap for prevention and control of cholera in India. [ABSTRACT FROM AUTHOR]

Objectives: Influence of meteorological variables on the transmission of bacillary dysentery (BD) is under investigated topic and effective forecasting models as public health tool are lacking. This paper aimed to quantify the relationship between meteorological variables and BD cases in Beijing and to establish an effective forecasting model. Methods: A time series analysis was conducted in the Beijing area based upon monthly data on weather variables (i.e. temperature, rainfall, relative humidity, vapor pressure, and wind speed) and on the number of BD cases during the period 1970–2012. Autoregressive integrated moving average models with explanatory variables (ARIMAX) were built based on the data from 1970 to 2004. Prediction of monthly BD cases from 2005 to 2012 was made using the established models. The prediction accuracy was evaluated by the mean square error (MSE). Results: Firstly, temperature with 2-month and 7-month lags and rainfall with 12-month lag were found positively correlated with the number of BD cases in Beijing. Secondly, ARIMAX model with covariates of temperature with 7-month lag (β = 0.021, 95% confidence interval(CI): 0.004–0.038) and rainfall with 12-month lag (β = 0.023, 95% CI: 0.009–0.037) displayed the highest prediction accuracy. Conclusions: The ARIMAX model developed in this study showed an accurate goodness of fit and precise prediction accuracy in the short term, which would be beneficial for government departments to take early public health measures to prevent and control possible BD popularity. [ABSTRACT FROM AUTHOR]