Toward an open-access global database for mapping, control, and surveillance of neglected tropical diseases

Background

After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs). Disease risk estimates are a key feature to target control interventions, and serve as a benchmark for monitoring and evaluation. What is currently missing is a georeferenced global database for NTDs providing open-access to the available survey data that is constantly updated and can be utilized by researchers and disease control managers to support other relevant stakeholders. We describe the steps taken toward the development of such a database that can be employed for spatial disease risk modeling and control of NTDs.

Methodology

With an emphasis on schistosomiasis in Africa, we systematically searched the literature (peer-reviewed journals and ‘grey literature’), contacted Ministries of Health and research institutions in schistosomiasis-endemic countries for location-specific prevalence data and survey details (e.g., study population, year of survey and diagnostic techniques). The data were extracted, georeferenced, and stored in a MySQL database with a web interface allowing free database access and data management.

Principal Findings

At the beginning of 2011, our database contained more than 12,000 georeferenced schistosomiasis survey locations from 35 African countries available under http://www.gntd.org. Currently, the database is expanded to a global repository, including a host of other NTDs, e.g. soil-transmitted helminthiasis and leishmaniasis.

Conclusions

An open-access, spatially explicit NTD database offers unique opportunities for disease risk modeling, targeting control interventions, disease monitoring, and surveillance. Moreover, it allows for detailed geostatistical analyses of disease distribution in space and time. With an initial focus on schistosomiasis in Africa, we demonstrate the proof-of-concept that the establishment and running of a global NTD database is feasible and should be expanded without delay.     

Repurposing human PDE4 inhibitors for neglected tropical diseases: Design,synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors

A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub-micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation.     

Electrochemical evaluation of (Ti, Nb) ON-coated dental alloys for quality assurance

The chemically stable (Ti, Nb) ON hard coating is suitable for passivating the 18 dental alloys investigated. The exchange current densities are less than jg = 1 microA/cm2. The corrosion current densities are included in this, and are therefore generally lower. The electrochemical investigations provide no hints as to local corrosion for (Ti, Nb) ON-coated dental alloys, which could be a hazard for patients or for dental work, owing to galvanic corrosion or pitting on long-term use. Irrespective of the coated dental alloy, the coatings have pores, through which the electrolyte is in contact with the substrate material. The resulting local elements have high source resistances, so that with a relative pore-area not exceeding 2% only low galvanic current densities occur.     

Nudge strategies for behavior-based prevention and control of neglected tropical diseases: A scoping review and ethical assessment

BackgroundNudging, a strategy that uses subtle stimuli to direct people’s behavior, has recently been included as an effective and low-cost behavior change strategy in low- and middle- income countries (LMIC), targeting behavior-based prevention and control of neglected tropical diseases (NTDs). The present scoping review aims to provide a timely overview of how nudge interventions have been applied within this field. In addition, the review proposes a framework for the ethical consideration of nudges for NTD prevention and control, or more broadly global health promotion.MethodsA comprehensive search was performed in several databases: MEDLINE, PsycINFO, and Embase (Ovid), Web of Science Core Collection, CINAHL, ERIC and Econ.Lit (EBSCO), as well as registered trials and reviews in CENTRAL and PROSPERO to identify ongoing or unpublished studies. Additionally, studies were included through a handpicked search on websites of governmental nudge units and global health or development organizations.ResultsThis scoping review identified 33 relevant studies, with only two studies targeting NTDs in particular, resulting in a total of 67 nudge strategies. Most nudges targeted handwashing behavior and were focused on general health practices rather than targeting a specific disease. The most common nudge strategies were those targeting decision assistance, such as facilitating commitment and reminder actions. The majority of nudges were of moderate to high ethical standards, with the highest standards being those that had the most immediate and significant health benefits, and those implemented by agents in a trust relationship with the target audience.ConclusionThree key recommendations should inform research investigating nudge strategies in global health promotion in general. Firstly, future efforts should investigate the different opportunities that nudges present for targeting NTDs in particular, rather than relying solely on integrated health promotion approaches. Secondly, to apply robust study designs including rigorous process and impact evaluation which allow for a better understanding of ‘what works’ and ‘how it works’. Finally, to consider the ethical implications of implementing nudge strategies, specifically in LMIC.     

A class of latent Markov models for capture-recapture data allowing for time, heterogeneity, and behavior effects

We propose an extension of the latent class model for the analysis of capture-recapture data which allows us to take into account the effect of a capture on the behavior of a subject with respect to future captures. The approach is based on the assumption that the variable indexing the latent class of a subject follows a Markov chain with transition probabilities depending on the previous capture history. Several constraints are allowed on these transition probabilities and on the parameters of the conditional distribution of the capture configuration given the latent process. We also allow for the presence of discrete explanatory variables, which may affect the parameters of the latent process. To estimate the resulting models, we rely on the conditional maximum likelihood approach and for this aim we outline an EM algorithm. We also give some simple rules for point and interval estimation of the population size. The approach is illustrated by applying it to two data sets concerning small mammal populations.     

Assemblage diversity,cell density and within-slide variability: Implications for quality assurance/quality control and uncertainty assessment in diatom-based monitoring

This study was undertaken to evaluate the variability associated with the microscope analysis step in the application of the Eastern Canadian Diatom Index (IDEC: Indice Diatomées de l’Est du Canada), with the general objective of developing a suitable quality assurance/quality control (QA/QC) program for this biological index. For this purpose, we estimated within-slide variability (replicability) and inter-analysts variability (reproducibility), as a function of diatom assemblage diversity and slide cell density. Overall, our results show that variability associated with diatom assemblage characterization is low, which ensures that IDEC scores reflect environmental changes rather than variability at the microscope analysis step. The main recommendations ensuing from this study are (for the IDEC in particular but also for diatom-based monitoring in general):

• (1)An error term of ±2 IDEC units corresponding to the within-slide variability (replicability) should accompany all reported IDEC scores.
• (2)A deviation of ±3 points from the audit's IDEC scores should be considered as an acceptable difference. Considering the above-mentioned estimated error term of ±2 associated with all IDEC scores, an overall deviation of 7 would still be satisfactory.
• (3)Samples showing low diversity (Hill's N2 ≤5) should automatically be submitted for QA/QC.
• (4)A Bray–Curtis (analyst vs audit) similarity of ≥60% should also be included as a QA/QC criterion, and should increase to ≥70% for poorly diversified assemblages (Hill's N2 ≤5).
• (5)A diatom valve density of ≤15 per field of view should be targeted in order to reduce variability at the enumeration step.

The results of this study illustrate how a relatively simple and straightforward approach to QA/QC can greatly strengthen the reliability of ecological inferences from an index based on a group of organisms with a high taxonomical diversity. It also highlights the importance of regular communication between analysts in order to maintain a high degree of concordance within taxonomical identification.     

A quantitative indicator framework for stand level evaluation and monitoring of environmentally sustainable forest management

An indicator framework was designed as an operational science-based tool for the evaluation of the environmental aspects of sustainable forest management at stand level in Flanders (Belgium). The framework aims to assess the effects of forest management on forest composition, structure and functioning. It consists of seven principles and 19 criteria, to which 157 potential indicators, selected from literature, were assigned; 40 of these were considered as suitable by an expert panel, based on 10 operational selection criteria. All indicators were quantitative variables measurable in the field.After elaboration of a measurement protocol, the indicator framework was validated in 115 forest stands, distributed over the three main forest types of Flanders. The new indicator framework exhibited greater sensitivity to forest management practices and demonstrated better discriminating power than the method that is currently used by the Flemish forest administration to estimate the naturalness and environmental quality of a forest stand. Following a detailed cost calculation of each indicator and based on the sensitivity of each indicator to forest management practices, the indicator framework was further reduced to a final set of 29 indicators. This framework can also be applied in other regions, provided that local threshold values are defined to convert indicator values to indicator scores.The selection procedure and the possible contribution of this set to the forest management in Flanders are discussed.     

Variations in the water quality of a small urban tropical catchment: implications for load estimation and water quality monitoring

This paper presents findings on the quality of runoff draining a small urban tropical catchment in Singapore. Variations in runoff quality were studied by continuous, regular and storm event water sampling over a period of eleven months for suspended sediment, nutrient and inorganic variables. Storm events and anthropogenic activities exerted the most influence on runoff quality. Concentration-discharge rating relationships were derived to assess the rating curve method for calculating load of the variables monitored. The poor rating relationships obtained indicated that the method was not suitable for load estimation in this catchment. Instead, an interpolation method was used to calculate sediment loads. The preliminary results highlighted the importance of conducting small-scale, relatively short-term studies to identify and assess specific water quality problems facing each catchment. Such a sampling strategy might be more useful than either routine or continuous sampling in the context of planning more detailed monitoring strategies and management options suitable for disturbed catchments.     

Assessment of the required performance and the development of corresponding program decision rules for neglected tropical diseases diagnostic tests: Monitoring and evaluation of soil-transmitted helminthiasis control programs as a case study

Recently, the World Health Organization established the Diagnostic Technical Advisory Group to identify and prioritize diagnostic needs for neglected tropical diseases, and to ultimately describe the minimal and ideal characteristics for new diagnostic tests (the so-called target product profiles (TPPs)). We developed two generic frameworks: one to explore and determine the required sensitivity (probability to correctly detect diseased persons) and specificity (probability to correctly detect persons free of disease), and another one to determine the corresponding samples sizes and the decision rules based on a multi-category lot quality assurance sampling (MC-LQAS) approach that accounts for imperfect tests. We applied both frameworks for monitoring and evaluation of soil-transmitted helminthiasis control programs. Our study indicates that specificity rather than sensitivity will become more important when the program approaches the endgame of elimination and that the requirements for both parameters are inversely correlated, resulting in multiple combinations of sensitivity and specificity that allow for reliable decision making. The MC-LQAS framework highlighted that improving diagnostic performance results in a smaller sample size for the same level of program decision making. In other words, the additional costs per diagnostic tests with improved diagnostic performance may be compensated by lower operational costs in the field. Based on our results we proposed the required minimal and ideal diagnostic sensitivity and specificity for diagnostic tests applied in monitoring and evaluating of soil-transmitted helminthiasis control programs.