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Background: A major impediment to the treatment of TB is a diagnostic process that requires multiple visits. Descriptions of patient costs associated with diagnosis use different protocols and are not comparable. Methods: We aimed to describe the direct costs incurred by adults attending TB diagnostic centres in four countries and factors associated with expenditure for diagnosis. Surveys of 2225 adults attending smear-microscopy centres in Nigeria, Nepal, Ethiopia and Yemen. Adults >18 years with cough >2 weeks were enrolled prospectively. Direct costs were quantified using structured questionnaires. Patients with costs >75th quartile were considered to have high expenditure (cases) and compared with patients with costs <75th quartile to identify factors associated with high expenditure. Results: The most significant expenses were due to clinic fees and transport. Most participants attended the centres with companions. High expenditure was associated with attending with company, residing in rural areas/other towns and illiteracy. Conclusions: The costs incurred by patients are substantial and share common patterns across countries. Removing user fees, transparent charging policies and reimbursing clinic expenses would reduce the poverty-inducing effects of direct diagnostic costs. In locations with limited resources, support could be prioritised for those most at risk of high expenditure; those who are illiterate, attend the service with company and rural residents. [ABSTRACT FROM AUTHOR]

Background: Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance.Methods: To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods.Results: The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites.Conclusions: Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance mutations to improve the design of tuberculosis control measures, such as diagnostics, and inform patient management. [ABSTRACT FROM AUTHOR]

Background: The ChinaÂ's 1-3-7 strategy was initiated and extensively adopted in different types of counties (geographic regions) for reporting of malaria cases within 1 day, their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Assessing the level of compliance to the 1-3-7 strategy at the county level is a first step towards determining whether the surveillance and response strategy is happening according to plan. This study assessed if the time-bound targets of the 1-3-7 strategy were being sustained over time. Such information would be useful to improve implementation of the 1-3-7 strategy in China. Methods: This cross-sectional study involved country-wide programmatic data for the period January 1st 2013 to June 30th 2014. Data variables were extracted from the national malaria information system and included socio-demographic information, type of county, date of diagnosis, date of reporting, date of case investigation, case classification (indigenous, or imported, or unknown), focus investigation, date of reactive case detection (RACD), and date of indoor residual spraying (IRS). Summary statistics and proportions were used and comparisons between groups were assessed using the chi-square test. Level of significance was set at a P-value ≤ 0.05. Results: Of a total of 5,688 malaria cases from 731 counties, there were 55 (1%) indigenous cases (only in Type 1 and Type 2 counties) and 5,633 (99%) imported cases from all types of counties. There was no delay in reporting malaria cases by type of county. In terms of case investigation, 97.5% cases were investigated within 3 days with the proportion of delays (1.5%) in type 2 counties, being significantly lower than type 1 counties (4.1%). Regarding active foci, 96.4% were treated by RACD and/or IRS. Conclusions: The performance of 1-3-7 strategy was encouraging but identified some challenges that if addressed can further improve implementation. [ABSTRACT FROM AUTHOR]

A literature review for operational research on malaria control and elimination was conducted using the term 'malaria' and the definition of operational research (OR). A total of 15 886 articles related to malaria were searched between January 2008 and June 2013. Of these, 582 (3.7%) met the definition of operational research. These OR projects had been carried out in 83 different countries. Most OR studies (77%) were implemented in Africa south of the Sahara. Only 5 (1%) of the OR studies were implemented in countries in the pre-elimination or elimination phase. The vast majority of OR projects (92%) were led by international or local research institutions, while projects led by National Malaria Control Programmes (NMCP) accounted for 7.8%. With regards to the topic under investigation, the largest percentage of papers was related to vector control (25%), followed by epidemiology/transmission (16.5%) and treatment (16.3%). Only 19 (3.8%) of the OR projects were related to malaria surveillance. Strengthening the capacity of NMCPs to conduct operational research and publish its findings, and improving linkages between NMCPs and research institutes may aid progress towards malaria elimination and eventual eradication world-wide. [ABSTRACT FROM AUTHOR]

Background: Evidence for scrapie transmission from VRQ/VRQ ewes to lambs via milk was first reported in 2008 but in that study there were concerns that lateral transmission may have contributed to the high transmission rate observed since five control lambs housed with the milk recipients also became infected. This report provides further information obtained from two follow-up studies, one where milk recipients were housed separately after milk consumption to confirm the validity of the high scrapie transmission rate via milk and the second to assess any difference in infectivity from colostrum and subsequent milk. Protein misfolding cyclic amplification (PMCA) was also used to detect prion protein in milk samples as a comparison with the infectivity data and extended to milk samples from ewes without a VRQ allele. Results: Seven pairs of lambs fed colostrum and milk individually from seven scrapie-affected sheep (pre-clinical or clinical) presented with disease-associated prion protein, PrPd, in rectal lymphoid tissue at 4-5 months of age. Five further pairs of lambs fed either colostrum or subsequent milk from five pre-clinical scrapie-affected sheep equally presented with PrPd in lymphoid tissue by 9 months of age. Nine sheep were lost due to intercurrent diseases but all remaining milk or colostrum recipients, including those in the original study with the lateral transmission controls, developed clinical signs of scrapie from 19 months of age and scrapie was confirmed by brain examination. Unexposed control sheep totalling 19 across all three studies showed no evidence of infection. Scrapie PrP was amplified repeatedly by PMCA in all tested milk samples from scrapie-affected VRQ/VRQ sheep, and in one scrapie-affected ARQ/ARQ sheep. By contrast, milk samples from five VRQ/VRQ and 11 ARQ/ARQ scrapie-free sheep did not have detectable scrapie PrP on repeated tests. Conclusions: Feeding of milk from scrapie-affected sheep results in a high transmission rate in VRQ/VRQ sheep and both colostrum and milk transmit scrapie. Detection of scrapie prion protein in individual milk samples from scrapie-affected ewes confirms PMCA as a valuable in vitro test. [ABSTRACT FROM AUTHOR]

A precise understanding of the genomic and epigenomic features of chronic lymphocytic leukemia (CLL) may benefit the study of the disease's staging and treatment. While recent reports have shed some light on these aspects, several challenges need to be addressed before translating this research into clinical practice. Thus, even the best candidate driver genes display low mutational rates compared to other tumors. This means that a large percentage of cases do not display clear tumor-driving point mutations, or show candidate driving point mutations with no obvious biochemical relationship to the more frequently mutated genes. This genomic landscape probably reflects either an unknown underlying biochemical mechanism playing a key role in CLL or multiple biochemical pathways independently driving the development of this tumor. The elucidation of either scenario will have important consequences on the clinical management of CLL. Herein, we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterize the underlying biochemical events that drive this disease. [ABSTRACT FROM AUTHOR]

The article discusses the Global Technical Strategy for Malaria 2016-2030 which is adopted by the 68th World Health Assembly in May 2015 which aims to control and eliminate the human suffering caused by malaria. It outlines the three main pillars of Global Technical Strategy which is considered as a reliable way to build research capacity in public health programmes.

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

Background: The China's 1-3-7 strategy was initiated and extensively adopted in different types of counties (geographic regions) for reporting of malaria cases within 1 day, their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Assessing the level of compliance to the 1-3-7 strategy at the county level is a first step towards determining whether the surveillance and response strategy is happening according to plan. This study assessed if the time-bound targets of the 1-3-7 strategy were being sustained over time. Such information would be useful to improve implementation of the 1-3-7 strategy in China., Methods: This cross-sectional study involved country-wide programmatic data for the period January 1st 2013 to June 30th 2014. Data variables were extracted from the national malaria information system and included socio-demographic information, type of county, date of diagnosis, date of reporting, date of case investigation, case classification (indigenous, or imported, or unknown), focus investigation, date of reactive case detection (RACD), and date of indoor residual spraying (IRS). Summary statistics and proportions were used and comparisons between groups were assessed using the chi-square test. Level of significance was set at a P-value ≤ 0.05., Results: Of a total of 5,688 malaria cases from 731 counties, there were 55 (1 %) indigenous cases (only in Type 1 and Type 2 counties) and 5,633 (99 %) imported cases from all types of counties. There was no delay in reporting malaria cases by type of county. In terms of case investigation, 97.5 % cases were investigated within 3 days with the proportion of delays (1.5 %) in type 2 counties, being significantly lower than type 1 counties (4.1 %). Regarding active foci, 96.4 % were treated by RACD and/or IRS., Conclusions: The performance of 1-3-7 strategy was encouraging but identified some challenges that if addressed can further improve implementation.

A literature review for operational research on malaria control and elimination was conducted using the term 'malaria' and the definition of operational research (OR). A total of 15 886 articles related to malaria were searched between January 2008 and June 2013. Of these, 582 (3.7%) met the definition of operational research. These OR projects had been carried out in 83 different countries. Most OR studies (77%) were implemented in Africa south of the Sahara. Only 5 (1%) of the OR studies were implemented in countries in the pre-elimination or elimination phase. The vast majority of OR projects (92%) were led by international or local research institutions, while projects led by National Malaria Control Programmes (NMCP) accounted for 7.8%. With regards to the topic under investigation, the largest percentage of papers was related to vector control (25%), followed by epidemiology/transmission (16.5%) and treatment (16.3%). Only 19 (3.8%) of the OR projects were related to malaria surveillance. Strengthening the capacity of NMCPs to conduct operational research and publish its findings, and improving linkages between NMCPs and research institutes may aid progress towards malaria elimination and eventual eradication world-wide.

Background: Protein misfolding cyclic amplification (PMCA) is a method that facilitates the detection of prions from many sources of transmissible spongiform encephalopathy (TSE). Sheep scrapie represents a unique diversity of prion disease agents in a range of susceptible PRNP genotypes. In this study PMCA was assessed on a range of Great Britain (GB) sheep scrapie isolates to determine the applicability to veterinary diagnosis of ovine TSE., Results: PrPSc amplification by protein misfolding cyclic amplification (PMCA) was assessed as a diagnostic tool for field cases of scrapie. The technique was initially applied to thirty-seven isolates of scrapie from diverse geographical locations around GB, and involved sheep of various breeds and PRNP genotypes. All samples were amplified in either VRQ and/or ARQ PrPC substrate. For PrPSc from sheep with at least one VRQ allele, all samples amplified efficiently in VRQ PrPC but only PrPSc from ARH/VRQ sheep amplified in both substrates. PrPSc from ARQ/ARQ sheep displayed two amplification patterns, one that amplified in both substrates and one that only amplified in ARQ PrPC. These amplification patterns were consistent for a further 14/15 flock/farm mates of these sheep. Furthermore experimental scrapie strains SSBP1, Dawson, CH1641 and MRI were analysed. SSBP1 and Dawson (from VRQ/VRQ sheep) amplified in VRQ but not ARQ substrate. MRI scrapie (from ARQ/ARQ sheep) nor CH1641 did not amplify in ARQ or VRQ substrate; these strains required an enhanced PMCA method incorporating polyadenylic acid (poly(A)) to achieve amplification., Conclusions: PrPsc from 52 classical scrapie GB field isolates amplified in VRQ or ARQ or both substrates and supports the use of PMCA as a rapid assay for the detection of a wide range of ovine classical scrapie infections involving multiple PRNP genotypes and scrapie strains.