Field Application of SD Bioline Malaria Ag Pf/Pan Rapid Diagnostic Test for Malaria in Greece

Greece, a malaria-free country since 1974, has experienced re-emergence of Plasmodium vivax autochthonous malaria cases in some agriculture areas over the last three years. In early 2012, an integrated control programme (MALWEST Project) was launched in order to prevent re-establishment of the disease. In the context of this project, the rapid diagnostic tests (RDT) of SD Bioline Malaria Ag Pf/Pan that detects hrp-2 and pan-LDH antigens were used. The aim of this study was to assess the field application of the RDT for the P. vivax diagnosis in comparison to light microscopy and polymerase chain reaction (PCR). A total of 955 samples were tested with all three diagnostic tools. Agreement of RDT against microscopy and PCR for the diagnosis of P. vivax was satisfactory (K value: 0.849 and 0.976, respectively). The sensitivity, specificity and positive predictive value of RDT against PCR was 95.6% (95% C.I.: 84.8-99.3), 100% (95% C.I.: 99.6-100.0) and 100% (95% CI: 91.7-100.0) respectively, while the sensitivity, specificity and positive predictive value of RDT against microscopic examination was 97.4% (95% C.I.: 86.1-99.6), 99.4% (95% C.I.: 98.6-99.8) and 86.1% (95% CI: 72.1-94.7), respectively. Our results indicate that RDT performed satisfactory in a non-endemic country and therefore is recommended for malaria diagnosis, especially in areas where health professionals lack experience on light microscopy.     

Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

Introduction

Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels.

Materials and Methods

Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men.

Results

The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)).

Conclusion

We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng/mL). Replication and gaining more accurate estimates of the effects of the 4 PSA-SNPs and additional variants associated with PSA levels and not prostate cancer could be obtained from subsequent GWAS from larger prospective studies.     

Prevention of Malaria Resurgence in Greece through the Association of Mass Drug Administration (MDA) to Immigrants from Malaria-Endemic Regions and Standard Control Measures

Greece was declared malaria-free in 1974 after a long antimalarial fight. In 2011–2012, an outbreak of P. vivax malaria was reported in Evrotas, an agricultural area in Southern Greece, where a large number of immigrants from endemic countries live and work. A total of 46 locally acquired and 38 imported malaria cases were detected. Despite a significant decrease of the number of malaria cases in 2012, a mass drug administration (MDA) program was considered as an additional measure to prevent reestablishment of the disease in the area. During 2013 and 2014, a combination of 3-day chloroquine and 14-day primaquine treatment was administered under direct observation to immigrants living in the epicenter of the 2011 outbreak in Evrotas. Adverse events were managed and recorded on a daily basis. The control measures implemented since 2011 continued during the period of 2013–2014 as a part of a national integrated malaria control program that included active case detection (ACD), vector control measures and community education. The MDA program was started prior to the transmission periods (from May to December). One thousand ninety four (1094) immigrants successfully completed the treatment, corresponding to 87.3% coverage of the target population. A total of 688 adverse events were recorded in 397 (36.2%, 95% C.I.: 33.4–39.1) persons, the vast majority minor, predominantly dizziness and headache for chloroquine (284 events) and abdominal pain (85 events) for primaquine. A single case of primaquine-induced hemolysis was recorded in a person whose initial G6PD test proved incorrect. No malaria cases were recorded in Evrotas, Laconia, in 2013 and 2014, though three locally acquired malaria cases were recorded in other regions of Greece in 2013. Preventive antimalarial MDA to a high-risk population in a low transmission setting appears to have synergized with the usual antimalarial activities to achieve malaria elimination. This study suggests that judicious use of MDA can be a useful addition to the antimalarial armamentarium in areas threatened with the reintroduction of the disease.     

Objectively Measured Daily Steps and Subsequent Long Term All-Cause Mortality: The Tasped Prospective Cohort Study

BackgroundSelf–reported physical activity has been inversely associated with mortality but the effect of objectively measured step activity on mortality has never been evaluated. The objective is to determine the prospective association of daily step activity on mortality among free-living adults.ConclusionsHigher daily step count was linearly associated with subsequent long term mortality among free living adults. These data are the first to quantify mortality reductions using an objective measure of physical activity in a free living population. They strongly underscore the importance of physical inactivity as a major public health problem.     

A Fast and Scalable Kymograph Alignment Algorithm for Nanochannel-Based Optical DNA Mappings

Optical mapping by direct visualization of individual DNA molecules, stretched in nanochannels with sequence-specific fluorescent labeling, represents a promising tool for disease diagnostics and genomics. An important challenge for this technique is thermal motion of the DNA as it undergoes imaging; this blurs fluorescent patterns along the DNA and results in information loss. Correcting for this effect (a process referred to as kymograph alignment) is a common preprocessing step in nanochannel-based optical mapping workflows, and we present here a highly efficient algorithm to accomplish this via pattern recognition. We compare our method with the one previous approach, and we find that our method is orders of magnitude faster while producing data of similar quality. We demonstrate proof of principle of our approach on experimental data consisting of melt mapped bacteriophage DNA.     

Creating Novel Activated Factor XI Inhibitors through Fragment Based Lead Generation and Structure Aided Drug Design

Activated factor XI (FXIa) inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1’-S2’ FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1’-S2’ binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC₅₀ of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1’-S2’ binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.     

A Systematic Review of the Role of Proprietary and Patent Medicine Vendors in Healthcare Provision in Nigeria

Background

Interventions to reduce the burden of disease and mortality in sub-Saharan Africa increasingly recognize the important role that drug retailers play in delivering basic healthcare services. In Nigeria, owner-operated drug retail outlets, known as patent and proprietary medicine vendors (PPMVs), are a main source of medicines for acute conditions, but their practices are not well understood. Greater understanding of the role of PPMVs and the quality of care they provide is needed in order to inform ongoing national health initiatives that aim to incorporate PPMVs as a delivery mechanism.

Objective and Methods

This paper reviews and synthesizes the existing published and grey literature on the characteristics, knowledge and practices of PPMVs in Nigeria. We searched published and grey literature using a number of electronic databases, supplemented with website searches of relevant international agencies. We included all studies providing outcome data on PPMVs in Nigeria, including non-experimental studies, and assessed the rigor of each study using the WHO-Johns Hopkins Rigor scale. We used narrative synthesis to evaluate the findings.

Results

We identified 50 articles for inclusion. These studies provided data on a wide range of PPMV outcomes: training; health knowledge; health practices, including drug stocking and dispensing, client interaction, and referral; compliance with regulatory guidelines; and the effects of interventions targeting PPMVs. In general, PPMVs have low health knowledge and poor health treatment practices. However, the literature focuses largely on services for adult malaria, and little is known about other health areas or services for children.

Conclusions

This review highlights several concerns with the quality of the private drug retail sector in Nigeria, as well as gaps in the existing evidence base. Future research should adopt a more holistic view of the services provided by PPMV shops, and evaluate intervention strategies that may improve the services provided in this sector.