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Background: Global estimates for cholera annually approximate 4 million cases worldwide with 95,000 deaths. Recent outbreaks, including Haiti and Yemen, are reminders that cholera is still a global health concern. Cholera outbreaks can rapidly induce high death tolls by overwhelming the capacity of health facilities, especially in remote areas or areas of civil unrest. Recent studies demonstrated that stool specimens preserved on filter paper facilitate molecular analysis of Vibrio cholerae in resource limited settings. Specimens preserved in a rapid, low-cost, safe and sustainable manner for sequencing provides previously unavailable data about circulating cholera strains. This may ultimately provide new information to shape public policy response on cholera control and elimination. Methodology/Principal findings: Whole genome sequencing (WGS) recovered close to a complete sequence of the V. cholerae O1 genome with satisfactory genome coverage from stool specimens enriched in alkaline peptone water (APW) and V. cholerae culture isolates, both spotted on filter paper. The minimum concentration of V. cholerae DNA sufficient to produce quality genomic information was 0.02 ng/μL. The genomic data confirmed the presence or absence of genes of epidemiological interest, including cholera toxin and pilus loci. WGS identified a variety of diarrheal pathogens from APW-enriched specimen spotted filter paper, highlighting the potential for this technique to explore the gut microbiome, potentially identifying co-infections, which may impact the severity of disease. WGS demonstrated that these specimens fit within the current global cholera phylogenetic tree, identifying the strains as the 7th pandemic El Tor. Conclusions: WGS results allowed for mapping of short reads from APW-enriched specimen and culture isolate spotted filter papers this provided valuable molecular epidemiological sequence information on V. cholerae strains from remote, low-resource settings. These results identified the presence of co-infecting pathogens while providing rare insight into the specific V. cholerae strains causing outbreaks in cholera-endemic areas. [ABSTRACT FROM AUTHOR]

Background: Until recently, the Chagas disease vector, Triatoma infestans, was widespread in Arequipa, Perú, but as a result of a decades-long campaign in which over 70,000 houses were treated with insecticides, infestation prevalence is now greatly reduced. To monitor for T. infestans resurgence, the city is currently in a surveillance phase in which a sample of houses is selected for inspection each year. Despite extensive data from the control campaign that could be used to inform surveillance, the selection of houses to inspect is often carried out haphazardly or by convenience. Therefore, we asked, how can we enhance efforts toward preventing T. infestans resurgence by creating the opportunity for vector surveillance to be informed by data? Methodology/principal findings: To this end, we developed a mobile app that provides vector infestation risk maps generated with data from the control campaign run in a predictive model. The app is intended to enhance vector surveillance activities by giving inspectors the opportunity to incorporate the infestation risk information into their surveillance activities, but it does not dictate which houses to surveil. Therefore, a critical question becomes, will inspectors use the risk information? To answer this question, we ran a pilot study in which we compared surveillance using the app to the current practice (paper maps). We hypothesized that inspectors would use the risk information provided by the app, as measured by the frequency of higher risk houses visited, and qualitative analyses of inspector movement patterns in the field. We also compared the efficiency of both mediums to identify factors that might discourage risk information use. Over the course of ten days (five with each medium), 1,081 houses were visited using the paper maps, of which 366 (34%) were inspected, while 1,038 houses were visited using the app, with 401 (39%) inspected. Five out of eight inspectors (62.5%) visited more higher risk houses when using the app (Fisher’s exact test, p < 0.001). Among all inspectors, there was an upward shift in proportional visits to higher risk houses when using the app (Mantel-Haenszel test, common odds ratio (OR) = 2.42, 95% CI 2.00–2.92), and in a second analysis using generalized linear mixed models, app use increased the odds of visiting a higher risk house 2.73-fold (95% CI 2.24–3.32), suggesting that the risk information provided by the app was used by most inspectors. Qualitative analyses of inspector movement revealed indications of risk information use in seven out of eight (87.5%) inspectors. There was no difference between the app and paper maps in the number of houses visited (paired t-test, p = 0.67) or inspected (p = 0.17), suggesting that app use did not reduce surveillance efficiency. Conclusions/significance: Without staying vigilant to remaining and re-emerging vector foci following a vector control campaign, disease transmission eventually returns and progress achieved is reversed. Our results suggest that, when provided the opportunity, most inspectors will use risk information to direct their surveillance activities, at least over the short term. The study is an initial, but key, step toward evidence-based vector surveillance. [ABSTRACT FROM AUTHOR]

The predominant clonal evolution (PCE) model seeks to formulate a common population genetics framework for all micropathogens (namely, parasitic protozoa, fungi and yeasts, bacteria, and viruses). It relies on a definition of clonality that is only based on population structure features (namely, strongly restrained genetic recombination). Its clear-cut properties make it of strong interest for applied and basic research, since it permits the definition of stable, clearly delimited units of analysis below the species level: clonal genotypes and discrete genetic subdivisions (“near-clades”). These units of analysis can be used for clinical and epidemiological studies, vaccine and drug design, species description, and evolutionary studies on natural and experimental populations. In this review, the evolutionary and population genetics background of the model will be only briefly mentioned, while considerable emphasis will be given to its practical significance for the study and control of neglected tropical diseases. The goal of the paper is to make this practical usefulness accessible to a broad audience of readers, including scientists who are not evolution specialists, such as epidemiologists, field scientists, and clinicians. For extensive developments about the evolutionary background of the model, see our previous papers [–]. Citations of these former articles lead to the many references quoted in them, which cannot be listed again here. [ABSTRACT FROM AUTHOR]

Targeted environmental and ecosystem management remain crucial in control of dengue. However, providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge. An important piece of such information is the extent of the presence of potential dengue vector breeding sites, which consist primarily of open containers such as ceramic jars, buckets, old tires, and flowerpots. In this paper we present the design and implementation of a pipeline to detect outdoor open containers which constitute potential dengue vector breeding sites from geotagged images and to create highly detailed container density maps at unprecedented scale. We implement the approach using Google Street View images which have the advantage of broad coverage and of often being two to three years old which allows correlation analyses of container counts against historical data from manual surveys. Containers comprising eight of the most common breeding sites are detected in the images using convolutional neural network transfer learning. Over a test set of images the object recognition algorithm has an accuracy of 0.91 in terms of F-score. Container density counts are generated and displayed on a decision support dashboard. Analyses of the approach are carried out over three provinces in Thailand. The container counts obtained agree well with container counts from available manual surveys. Multi-variate linear regression relating densities of the eight container types to larval survey data shows good prediction of larval index values with an R-squared of 0.674. To delineate conditions under which the container density counts are indicative of larval counts, a number of factors affecting correlation with larval survey data are analyzed. We conclude that creation of container density maps from geotagged images is a promising approach to providing detailed risk maps at large scale. [ABSTRACT FROM AUTHOR]

Background: Rhodnius nasutus, a vector of the etiological agent Trypanosoma cruzi, is one of the epidemiologically most relevant triatomine species of the Brazilian Caatinga, where it often colonizes rural peridomestic structures such as chicken coops and occasionally invades houses. Historical colonization and determination of its genetic diversity and population structure may provide new information towards the improvement of vector control in the region. In this paper we present thoughtful analyses considering the phylogeography and demographic history of R. nasutus in the Caatinga. Methodology/Principal findings: A total of 157 R. nasutus specimens were collected from Copernicia prunifera palm trees in eight geographic localities within the Brazilian Caatinga biome, sequenced for 595-bp fragment of the mitochondrial cytochrome b gene (cyt b) and genotyped for eight microsatellite loci. Sixteen haplotypes were detected in the cyt b sequences, two of which were shared between different localities. Molecular diversity indices exhibited low diversity and a haplotype network revealed low divergence among R. nasutus sequences, with two central haplotypes shared by five of the eight populations analyzed. The demographic model that better represented R. nasutus population dynamics was the exponential growth model. Results of the microsatellite data analyses indicated that the entire population is comprised of four highly differentiated groups, with no obvious contemporary geographic barriers that could explain the population substructure detected. A complex pattern of migration was observed, in which a western Caatinga population seems to be the source of emigrants to the eastern populations. Conclusions/Significance: R. nasutus that inhabit C. prunifera palms do not comprise a species complex. The species went through a population expansion at 12–10 ka, during the Holocene, which coincides with end of the largest dry season in South America. It colonized the Caatinga in a process that occurred from west to east in the region. R. nasutus is presently facing an important ecological impact caused by the continuous deforestation of C. prunifera palms in northeast Brazil. We hypothesize that this ecological disturbance might contribute to an increase in the events of invasion and colonization of human habitations. [ABSTRACT FROM AUTHOR]

Introduction: This paper discusses the presence of Aedes aegypti pupae in different types of containers considering: volume, pH of the container, among other variables. Methods: A nonlinear method for selection was applied, based on Mutual Information, by placing in order of importance the most appropriate variables for identifying containers with and without Aedes aegypti pupae. Such variables were used for input into a Neural Network in layers for classification. Results: Among the experiments carried out, the best result obtained used the first eight variables selected by order of importance. The percentage of hits for containers which had no Aedes aegypti pupae was 73.3%, and 80.9% for those which did have Aedes aegypti pupae in the containers. This Neural Network method, a model with the capacity to emulate non-linear data, got better results in comparison with the discriminant power of the Logistic Regression model. Thus, the outcomes of using the Neural Networks method achieved better separability in classifying the containers with pupae and those with no pupae. Conclusion: This type of analysis will aid in the efforts to design an efficient program to control Aedes aegypti that can concentrate principally on containers which present the greatest productivity. [ABSTRACT FROM AUTHOR]

Background: The control and elimination of Plasmodium vivax will require a better understanding of its transmission dynamics, through the application of genotyping and population genetics analyses. This paper describes VivaxGEN (), a web-based platform that has been developed to support P. vivax short tandem repeat data sharing and comparative analyses. Results: The VivaxGEN platform provides a repository for raw data generated by capillary electrophoresis (FSA files), with fragment analysis and standardized allele calling tools. The query system of the platform enables users to filter, select and differentiate samples and alleles based on their specified criteria. Key population genetic analyses are supported including measures of population differentiation (FST), expected heterozygosity (HE), linkage disequilibrium (IAS), neighbor-joining analysis and Principal Coordinate Analysis. Datasets can also be formatted and exported for application in commonly used population genetic software including GENEPOP, Arlequin and STRUCTURE. To date, data from 10 countries, including 5 publicly available data sets have been shared with VivaxGEN. Conclusions: VivaxGEN is well placed to facilitate regional overviews of P. vivax transmission dynamics in different endemic settings and capable to be adapted for similar genetic studies of P. falciparum and other organisms. [ABSTRACT FROM AUTHOR]

Background: This paper presents a new agent-based model (ABM) for investigating T. b. rhodesiense human African trypanosomiasis (rHAT) disease dynamics, produced to aid a greater understanding of disease transmission, and essential for development of appropriate mitigation strategies. Methods: The ABM was developed to model rHAT incidence at a fine spatial scale along a 75 km transect in the Luangwa Valley, Zambia. The method offers a complementary approach to traditional compartmentalised modelling techniques, permitting incorporation of fine scale demographic data such as ethnicity, age and gender into the simulation. Results: Through identification of possible spatial, demographic and behavioural characteristics which may have differing implications for rHAT risk in the region, the ABM produced output that could not be readily generated by other techniques. On average there were 1.99 (S.E. 0.245) human infections and 1.83 (S.E. 0.183) cattle infections per 6 month period. The model output identified that the approximate incidence rate (per 1000 person-years) was lower amongst cattle owning households (0.079, S.E. 0.017), than those without cattle (0.134, S.E. 0.017). Immigrant tribes (e.g. Bemba I.R. = 0.353, S.E.0.155) and school-age children (e.g. 5–10 year old I.R. = 0.239, S.E. 0.041) were the most at-risk for acquiring infection. These findings have the potential to aid the targeting of future mitigation strategies. Conclusion: ABMs provide an alternative way of thinking about HAT and NTDs more generally, offering a solution to the investigation of local-scale questions, and which generate results that can be easily disseminated to those affected. The ABM can be used as a tool for scenario testing at an appropriate spatial scale to allow the design of logistically feasible mitigation strategies suggested by model output. This is of particular importance where resources are limited and management strategies are often pushed to the local scale. [ABSTRACT FROM AUTHOR]

In this paper we report a quantitative laser Biospeckle method using VDRL plates to monitor the activity of Trypanosoma cruzi and the calibration conditions including three image processing algorithms and three programs (ImageJ and two programs designed in this work). Benznidazole was used as a test drug. Variable volume (constant density) and variable density (constant volume) were used for the quantitative evaluation of parasite activity in calibrated wells of the VDRL plate. The desiccation process within the well was monitored as a function of volume and of the activity of the Biospeckle pattern of the parasites as well as the quantitative effect of the surface parasite quantity (proportion of the object’s plane). A statistical analysis was performed with ANOVA, Tukey post hoc and Descriptive Statistics using R and R Commander. Conditions of volume (100μl) and parasite density (2-4x104 parasites/well, in exponential growth phase), assay time (up to 204min), frame number (11 frames), algorithm and program (RCommander/SAGA) for image processing were selected to test the effect of variable concentrations of benznidazole (0.0195 to 20μg/mL / 0.075 to 76.8μM) at various times (1, 61, 128 and 204min) on the activity of the Biospeckle pattern. The flat wells of the VDRL plate were found to be suitable for the quantitative calibration of the activity of Trypanosoma cruzi using the appropriate algorithm and program. Under these conditions, benznidazole produces at 1min an instantaneous effect on the activity of the Biospeckle pattern of T. cruzi, which remains with a similar profile up to 1 hour. A second effect which is dependent on concentrations above 1.25μg/mL and is statistically different from the effect at lower concentrations causes a decrease in the activity of the Biospeckle pattern. This effect is better detected after 1 hour of drug action. This behavior may be explained by an instantaneous effect on a membrane protein of Trypanosoma cruzi that could mediate the translocation of benznidazole. At longer times the effect may possibly be explained by the required transformation of the pro-drug into the active drug. [ABSTRACT FROM AUTHOR]

Objective: In Peru, the past three decades have witnessed impressive growth in biomedical research catalyzed from a single research university and its investigators who secured international partnerships and funding. We conducted a bibliometric analysis of publications by Peruvian authors to understand the roots of this growth and the spread of research networks within the country. Methods: For 1997–2016, publications from Web of Science with at least one author affiliated with a Peruvian institution were examined by year, author affiliations, funding agencies, co-authorship linkages, and research topics. Results: From 1997–2016, the annual number of publications from Peru increased 9-fold from 75 to 672 totaling 6032. Of these, 56% of the articles had co-authors from the US, 13% from the UK, 12% from Brazil, and 10% from Spain. Universidad Peruana Cayetano Heredia (UPCH) was clearly the lead research institution noted on one-third of publications. Of the 20 most published authors, 15 were Peruvians, 14 trained at some point at UPCH, and 13 received advanced training abroad. Plotting co-authorships documented the growth of institutional collaborations, the robust links between investigators and some lineages of mentorship. Conclusions: This analysis suggests that international training of Peruvian physician-scientists who built and sustained longstanding international partnerships with funding accelerated quality research on diseases of local importance. The role of a single research university, UPCH, was critical to advance a culture of biomedical research. Increased funding from the Peruvian Government and its Council for Science, Technology and Innovation will be needed to sustain this growth in the future. Middle-income countries might consider the Peruvian experience where long-term research and training partnerships yielded impressive advances to address key health priorities of the country. [ABSTRACT FROM AUTHOR]

The article presents a case study of a first case of human infection with Plasmodium knowlesi in a 12-year-old Laotian boy who manifested-like symptoms and signs such as nausea, high fever and shivering. The Plasmodium knowlesi was identified by real-time polymerase chain reaction (PCR) and confirmed by DNA sequencing. The article discusses human infection with Plasmodium knowlesi, which is prevalent in monkeys in Southeast Asian countries.

The article focuses on the evolution of the Android-, web-based mobile application, called LINKS, and its key elements for greater efficiency in electronic data capture for global health programs. Information regarding the development of LINKS system and launch of the open source project Open Data Kit (ODK) is discussed. Among the benefits of LINKS include cost savings, data quality, and data collection and implementation of results.

Introduction: The prevalence of bacteremia caused by Gram negative non-fermentative (GNNF) bacteria has been increasing globally over the past decade. Many studies have investigated their epidemiology but focus on the common GNNF including Pseudomonas aeruginosa and Acinetobacter baumannii. Knowledge of the uncommon GNNF bacteremias is very limited. This study explores invasive bloodstream infection GNNF isolates that were initially unidentified after testing with standard microbiological techniques. All isolations were made during laboratory-based surveillance activities in two rural provinces of Thailand between 2006 and 2014. Methods: A subset of GNNF clinical isolates (204/947), not identified by standard manual biochemical methodologies were run on the BD Phoenix automated identification and susceptibility testing system. If an organism was not identified (12/204) DNA was extracted for whole genome sequencing (WGS) on a MiSeq platform and data analysis performed using 3 web-based platforms: Taxonomer, CGE KmerFinder and One Codex. Results: The BD Phoenix automated identification system recognized 92% (187/204) of the GNNF isolates, and because of their taxonomic complexity and high phenotypic similarity 37% (69/187) were only identified to the genus level. Five isolates grew too slowly for identification. Antimicrobial sensitivity (AST) data was not obtained for 93/187 (50%) identified isolates either because of their slow growth or their taxa were not in the AST database associated with the instrument. WGS identified the 12 remaining unknowns, four to genus level only. Conclusion: The GNNF bacteria are of increasing concern in the clinical setting, and our inability to identify these organisms and determine their AST profiles will impede treatment. Databases for automated identification systems and sequencing annotation need to be improved so that opportunistic organisms are better covered. [ABSTRACT FROM AUTHOR]

Background: Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis. This study pilots the use of smartphone microscopy and an artificial neural network-based object detection application named Kankanet to address those two needs. Methodology/Principal findings: A smartphone was equipped with a USB Video Class (UVC) microscope attachment and Kankanet, which was trained to recognize eggs of Ascaris lumbricoides, Trichuris trichiura, and hookworm using a dataset of 2,078 images. It was evaluated for interpretive accuracy based on 185 new images. Fecal samples were processed using Kato-Katz (KK), spontaneous sedimentation technique in tube (SSTT), and Merthiolate-Iodine-Formaldehyde (MIF) techniques. UVC imaging and ANN interpretation of these slides was compared to parasitologist interpretation of standard microscopy.Relative to a gold standard defined as any positive result from parasitologist reading of KK, SSTT, and MIF preparations through standard microscopy, parasitologists reading UVC imaging of SSTT achieved a comparable sensitivity (82.9%) and specificity (97.1%) in A. lumbricoides to standard KK interpretation (97.0% sensitivity, 96.0% specificity). The UVC could not accurately image T. trichiura or hookworm. Though Kankanet interpretation was not quite as sensitive as parasitologist interpretation, it still achieved high sensitivity for A. lumbricoides and hookworm (69.6% and 71.4%, respectively). Kankanet showed high sensitivity for T. trichiura in microscope images (100.0%), but low in UVC images (50.0%). Conclusions/Significance: The UVC achieved comparable sensitivity to standard microscopy with only A. lumbricoides. With further improvement of image resolution and magnification, UVC shows promise as a point-of-care imaging tool. In addition to smartphone microscopy, ANN-based object detection can be developed as a diagnostic aid. Though trained with a limited dataset, Kankanet accurately interprets both standard microscope and low-quality UVC images. Kankanet may achieve sensitivity comparable to parasitologists with continued expansion of the image database and improvement of machine learning technology. [ABSTRACT FROM AUTHOR]

Background: Vector control remains the primary method to prevent dengue infections. Environmental interventions represent sustainable and safe methods as there are limited risks of environmental contamination and toxicity. The objective of this study is to perform a systematic review and meta-analysis of the effectiveness of the following environmental methods for dengue vector control. Methodology/Principal findings: Following the PRISMA guidelines, a systematic literature search was conducted using the databases PubMed, EMBASE, LILACS, the Cochrane Library and Google Scholar. Quality assessment was done using the CONSORT 2010 checklist. For the meta-analysis the difference-in-differences (DID) and the difference-of-endlines (DOE) were calculated according to the Schmidt-Hunter method for the Breteau index (BI) and the pupae per person index (PPI). Nineteen studies were eligible for the systematic review, sixteen contributed data to the meta-analysis. The following methods were evaluated: (a) container covers with and without insecticides, (b) waste management and clean-up campaigns, and (c) elimination of breeding sites by rendering potential mosquito breeding sites unusable or by eliminating them. Study quality was highest for container covers with insecticides, followed by waste management without direct garbage collection and elimination of breeding places. Both, systematic review and meta-analysis, showed a weak effect of the interventions on larval populations, with no obvious differences between the results of each individual method. For the meta-analysis, both, container covers without insecticides (BI: DID -7.9, DOE -5) and waste management with direct garbage collection (BI: DID -8.83, DOE -6.2) achieved the strongest reductions for the BI, whereas for the PPI results were almost opposite, with container covers with insecticides (PPI: DID -0.83, DOE 0.09) and elimination of breeding places (PPI: DID -0.95, DOE -0.83) showing the strongest effects. Conclusions: Each of the investigated environmental methods showed some effectiveness in reducing larval and pupal densities of Aedes sp. mosquitoes. However, there is a need for more comparable high-quality studies at an adequate standard to strengthen this evidence. [ABSTRACT FROM AUTHOR]

Background: In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence. Before 2015 ST283 had only been reported from twenty humans in Hong Kong and two in France, and from one fish in Thailand. We hypothesised that ST283 was causing region-wide infection in Southeast Asia. Methodology/Principal findings: We performed a literature review, whole genome sequencing on 145 GBS isolates collected from six Southeast Asian countries, and phylogenetic analysis on 7,468 GBS sequences including 227 variants of ST283 from humans and animals. Although almost absent outside Asia, ST283 was found in all invasive Asian collections analysed, from 1995 to 2017. It accounted for 29/38 (76%) human isolates in Lao PDR, 102/139 (73%) in Thailand, 4/13 (31%) in Vietnam, and 167/739 (23%) in Singapore. ST283 and its variants were found in 62/62 (100%) tilapia from 14 outbreak sites in Malaysia and Vietnam, in seven fish species in Singapore markets, and a diseased frog in China. Conclusions: GBS ST283 is widespread in Southeast Asia, where it accounts for a large proportion of bacteraemic GBS, and causes disease and economic loss in aquaculture. If human ST283 is fishborne, as in the Singapore outbreak, then GBS sepsis in Thailand and Lao PDR is predominantly a foodborne disease. However, whether transmission is from aquaculture to humans, or vice versa, or involves an unidentified reservoir remains unknown. Creation of cross-border collaborations in human and animal health are needed to complete the epidemiological picture. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosis and treatment for visceral leishmaniasis (VL) is considered to be delayed amongst poor, rural women in highly endemic districts of Bihar and Jharkhand. The objective of this study was to assess and understand barriers to VL diagnosis and treatment for women in endemic districts with a high burden of VL. Methods: The study used a stratified and purposive sample of 33 female patients with VL, 11 health staff, 11 local (unqualified) health providers and 12 groups of community elders drawn from ten districts in Bihar and four in Jharkhand with high burdens of VL. The study was conducted within an exploratory and inductive framework, using semi-structured in-depth interviews and discussions. Results: Women accessing treatment more quickly tended to move faster from treating their symptoms on their own to seeking care from local providers. Perception among female patients of the illness being not serious (owing to initially non-specific and mild symptoms), lack of money, prioritisation of household chores over their need to seek care and the absence of a male guardian to accompany them in seeking care at facilities worked together to drive these choices. Most patients and their families did not suspect VL as the cause for their non-specific symptoms, but when VL was suspected, treatment shopping ended. Lack of prioritization of women’s health issues appears to be a pervasive underlying factor. Public health facilities were not an early treatment choice for the majority, but where it was, the diagnosis of VL was often not considered when presenting with under 2 weeks of symptoms, nor were appropriate follow-up plans instituted. Conclusion: The insidious presentation of VL and the low prioritisation of women’s health need to be jointly addressed through messages that emphasise the importance of early diagnosis and treatment of disease, which is low-cost in time and money when managed in public health facilities. Clear messages that project prioritising women’s care-seeking over household work as a smart choice and the need for rallying male support are needed. Additionally, efforts to reduce missed opportunities through early case suspicion and engaging private providers to better counsel women with suspected VL could close critical gaps in the continuum of care. [ABSTRACT FROM AUTHOR]

Author summary In this communication, a case of black grain eumycetoma produced by the fungus C. atrobrunneum is reported. The patient was initially misdiagnosed with M. mycetomatis eumycetoma based on the grains’ morphological and cytological features. However, further aerobic culture of the black grains generated a melanised fungus identified as C. atrobrunneum by conventional morphological methods and by internal transcribed spacer 2 (ITS2) ribosomal RNA gene sequencing. This is the first-ever report of C. atrobrunneum as a eumycetoma-causative organism of black grain eumycetoma. It is essential that the causative organism is identified to the species level, as this is important for proper patient management and to predict treatment outcome and prognosis. [ABSTRACT FROM AUTHOR]

Background: Crimean-Congo hemorrhagic fever (CCHF) is a serious disease with a high fatality rate reported in many countries. The first case of CCHF in Oman was detected in 1995 and serosurveys have suggested widespread infection of humans and livestock throughout the country. Methodology: Cases of CCHF reported to the Ministry of Health (MoH) of Oman between 1995 and 2017 were retrospectively reviewed. Diagnosis was confirmed by serology and/or molecular tests in Oman. Stored RNA from recent cases was studied by sequencing the complete open reading frame (ORF) of the viral S segment at Public Health England, enabling phylogenetic comparisons to be made with other S segments of strains obtained from the region. Findings: Of 88 cases of CCHF, 4 were sporadic in 1995 and 1996, then none were detected until 2011. From 2011–2017, incidence has steadily increased and 19 (23.8%) of 80 cases clustered around Eid Al Adha. The median (range) age was 33 (15–68) years and 79 (90%) were male. The major risk for infection was contact with animals and/or butchering in 73/88 (83%) and only one case was related to tick bites alone. Severe cases were over-represented: 64 (72.7%) had a platelet count < 50 x 109/L and 32 (36.4%) died. There was no intrafamilial spread or healthcare-associated infection. The viral S segments from 11 patients presenting in 2013 and 2014 were all grouped in Asia 1 (IV) lineage. Conclusions: CCHF is well-established throughout Oman, with a single strain of virus present for at least 20 years. Most patients are men involved in animal husbandry and butchery. The high mortality suggests that there is substantial under-diagnosis of milder cases. Preventive measures have been introduced to reduce risks of transmission to animal handlers and butchers and to maintain safety in healthcare settings. [ABSTRACT FROM AUTHOR]

Background: Neotricula aperta is the snail-intermediate host of the parasitic blood-fluke Schistosoma mekongi which causes Mekong schistosomiasis in Cambodia and the Lao PDR. Despite numerous phylogenetic studies only one DNA-sequence based population-genetic study of N. aperta had been published, and the origin, structure and persistence of N. aperta were poorly understood. Consequently, a phylogenetic and population genetic study was performed, with addition of new data to pre-existing DNA-sequences for N. aperta from remote and inaccessible habitats, including one new taxon from Laos and 505 bp of additional DNA-sequence for all sampled taxa,. Principal findings: Spatial Principal Component Analysis revealed the presence of significant spatial-genetic clustering. Genetic-distance-based clustering indicated four populations with near perfect match to a priori defined ecogeographical regions. Spring-dwelling taxa were found to form an ecological isolate relative to other N. aperta. The poor dispersal capabilities suggested by spatial-genetic analyses were confirmed by Bayesian inference of migration rates. Population divergence time estimation implied a mid-Miocene colonisation of the present range, with immediate and rapid radiation in each ecogeographical region. Estimated effective population sizes were large (120–310 thousand). Conclusions: The strong spatial-genetic structure confirmed the poor dispersal capabilities of N. aperta—suggesting human-mediated reintroduction of disease to controlled areas as the primary reason for control failure. The isolation of the spring-dwelling taxa and ecogeographical structure suggests adaptation of sub-populations to different habitats; the epidemiological significance of this needs investigation. The large effective population sizes indicate that the high population densities observed in surveyed habitats are also present in inaccessible areas; affording great potential for recrudescence driven by animal-reservoir transmission in remote streams. Mid-Miocene colonisation implies heterochronous evolution of these snails and associated schistosomes and suggests against coevolution of snail and parasite. Heterochronicity favours ecological factors as shapers of host-parasite specificity and greater potential for escape from schistosomiasis control through host-switching. [ABSTRACT FROM AUTHOR]

Mobile applications (apps) can bring health research and its potential downstream benefits closer to underserved populations. Drawing on experience developing an app for detecting and referring cases of cutaneous leishmaniasis in Colombia, called Guaral/app, we review key steps in creating such mobile health (mHealth) tools. These require consideration of the sociotechnical context using methods such as systems analysis and human-centered design (HCD), predicated on engagement and iteration with all stakeholders. We emphasize usability and technical concerns and describe the interdependency of technical and human considerations for mHealth systems in rural communities. [ABSTRACT FROM AUTHOR]

The gold-standard method for quantifying neutralizing antibody responses to many viruses, including dengue virus (DENV), is the plaque reduction neutralization test (PRNT, also called the immunofocus reduction neutralization test). The PRNT conducted on 96-well plates is high-throughput and requires a smaller volume of antiserum than on 6- or 24-well plates, but manual plaque counting is challenging and existing automated plaque counters are expensive or difficult to optimize. We have developed Viridot (Viridot package), a program for R with a user interface in shiny, that counts viral plaques of a variety of phenotypes, estimates neutralizing antibody titers, and performs other calculations of use to virologists. The Viridot plaque counter includes an automatic parameter identification mode (misses <10 plaques/well for 87% of diverse DENV strains [n = 1521]) and a mode that allows the user to fine-tune the parameters used for counting plaques. We compared standardized manual and Viridot plaque counting methods applied to the same wells by two analyses and found that Viridot plaque counts were as similar to the same analyst's manual count (Lin’s concordance correlation coefficient, ρc = 0.99 [95% confidence interval: 0.99–1.00]) as manual counts between analysts (ρc = 0.99 [95% CI: 0.98–0.99]). The average ratio of neutralizing antibody titers based on manual counted plaques to Viridot counted plaques was 1.05 (95% CI: 0.98–1.14), similar to the average ratio of antibody titers based on manual plaque counts by the two analysts (1.06 [95% CI: 0.84–1.34]). Across diverse DENV and ZIKV strains (n = 14), manual and Viridot plaque counts were mostly consistent (range of ρc = 0.74 to 1.00) and the average ratio of antibody titers based on manual and Viridot counted plaques was close to 1 (0.94 [0.86–1.02]). Thus, Viridot can be used for plaque counting and neutralizing antibody titer estimation of diverse DENV strains and potentially other viruses on 96-well plates as well as for formalization of plaque-counting rules for standardization across experiments and analysts. [ABSTRACT FROM AUTHOR]

Background: Malaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017. Methodology and principal findings: A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients’ clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia. Conclusion: The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients. [ABSTRACT FROM AUTHOR]

Introduction: Countries have traditionally been split into two major groups: developed or industrialized (“the North”) and developing or underdeveloped (“the South”). Several authors and organizations have challenged this classification to recognize countries that have reached an intermediate stage of social and economic development. As proposed by Morel and collaborators in 2005, the concept of Innovative Developing Countries (IDCs) defines a group of nations with impactful scientific programs. Here, IDCs are reexamined by a variety of metrics to highlight their role in health innovation through research and development (R&D) programs on neglected tropical diseases (NTDs) that also positively impact epidemic preparedness. Results: To address the global changes due to expanding globalization we updated the original indicator of the number of USPTO patents deposited by individual countries per GDP and per capita to the number of international patents applications, related to applicant residence and deposited under the Patent Cooperation Treaty (PCT) per GNI (or GDP) and per capita. A comparison of the originally described ranking of top innovative countries to those in the present study revealed new members that updated the list of IDCs and showed a prominent role now played by China. Analyzing scientific publications in international journals since the introduction of the IDC concept in 2005 we found that IDCs do prioritize Neglected Tropical Diseases (NTDs) as an area of research. Finally we investigated the role of IDCs in two major public health emergencies between 2012 and 2016, the outbreaks of Ebola in West Africa and Zika in South America. An analysis of the co-authorship country networks demonstrated an important role for IDC infrastructure and personnel in the prevention and control of these epidemics. Discussion and conclusions: Different techniques can be used to evaluate and measure innovative performance of countries. Country rankings published by traditional indexes, such as the Bloomberg Innovation Index (BII) and the Global Innovation Index (GII), only include high income economies among the top 20 performers. This is in sharp contrast to our approach, which identified 8-9 IDCs among the first 25 with China occupying the top position. Through an analysis of the pros and cons of the different methodologies, the IDC concept challenges more conventional approaches to address and estimate the innovative capacity of countries. [ABSTRACT FROM AUTHOR]

Background: Plague, caused by the bacterium Yersinia pestis, is a highly infectious, zoonotic disease. Hundreds of human plague cases are reported across the world annually. Qinghai Plateau is one of the most severely affected plague regions in China, with more than 240 fatal cases of Y. pestis in the last 60 years. Conventional epidemiologic analysis has effectively guided the prevention and control of local plague transmission; however, molecular genetic analysis is more effective for investigating population diversity and transmission. In this report, we employed different genetic markers to analyze the population structure of Y. pestis in Qinghai Plateau. Methodology/Principal finding: We employed a two-step hierarchical strategy to analyze the phylogeny of 102 Qinghai Plateau isolates of Y. pestis, collected between 1954 and 2011. First, we defined the genealogy of Y. pestis by constructed minimum spanning tree based on 25 key SNPs. Seven groups were identifi7ed, with group 1.IN2 being identified as the dominant population. Second, two methods, MLVA and CRISPR, were applied to examine the phylogenetic detail of group 1.IN2, which was further divided into three subgroups. Subgroups of 1.IN2 revealed a clear geographic cluster, possibly associated with interaction between bacteriophage and Y. pestis. More recently, Y. pestis populations appear to have shifted from the east toward the center and west of Qinghai Plateau. This shift could be related to destruction of the local niche of the original plague focus through human activities. Additionally, we found that the abundance and relative proportion of 1.IN2 subgroups varied by decade and might be responsible for the fluctuations of plague epidemics in Qinghai Plateau. Conclusion/Significance: Molecular genotyping methods provided us with detailed information on population diversity and the spatial-temporal distribution of dominant populations of Y. pestis, which will facilitate future surveillance, prevention, and control of plague in Qinghai Plateau. [ABSTRACT FROM AUTHOR]

Background: Singapore experiences endemic dengue, with 2013 being the largest outbreak year known to date, culminating in 22,170 cases. Given the limited resources available, and that vector control is the key approach for prevention in Singapore, it is important that public health professionals know where resources should be invested in. This study aims to stratify the spatial risk of dengue transmission in Singapore for effective deployment of resources. Methodology/principal findings: Random Forest was used to predict the risk rank of dengue transmission in 1km2 grids, with dengue, population, entomological and environmental data. The predicted risk ranks are categorized and mapped to four color-coded risk groups for easy operation application. The risk maps were evaluated with dengue case and cluster data. Risk maps produced by Random Forest have high accuracy. More than 80% of the observed risk ranks fell within the 80% prediction interval. The observed and predicted risk ranks were highly correlated (≥0.86, P <0.01). Furthermore, the predicted risk levels were in excellent agreement with case density, a weighted Kappa coefficient of more than 0.80 (P <0.01). Close to 90% of the dengue clusters occur in high risk areas, and the odds of cluster forming in high risk areas were higher than in low risk areas. Conclusions: This study demonstrates the potential of Random Forest and its strong predictive capability in stratifying the spatial risk of dengue transmission in Singapore. Dengue risk map produced using Random Forest has high accuracy, and is a good surveillance tool to guide vector control operations. [ABSTRACT FROM AUTHOR]

Background: Disease surveillance in rural regions of many countries is poor, such that prolonged delays (months) may intervene between appearance of disease and its recognition by public health authorities. For infectious disorders, delayed recognition and intervention enables uncontrolled disease spread. We tested the feasibility in northern Uganda of developing real-time, village-based health surveillance of an epidemic of Nodding syndrome (NS) using software-programmed smartphones operated by minimally trained lay mHealth reporters. Methodology and principal findings: We used a customized data collection platform (Magpi) that uses mobile phones and real-time cloud-based storage with global positioning system coordinates and time stamping. Pilot studies on sleep behavior of U.S. and Ugandan medical students identified and resolved Magpi-programmed cell phone issues. Thereafter, we deployed Magpi in combination with a lay-operator network of eight mHealth reporters to develop a real-time electronic map of child health, injury and illness relating to NS in rural northern Uganda. Surveillance data were collected for three consecutive months from 10 villages heavily affected by NS. Overall, a total of 240 NS-affected households and an average of 326 children with NS, representing 30 households and approximately 40 NS children per mHealth reporter, were monitored every week by the lay mHealth team. Data submitted for analysis in the USA and Uganda remotely pinpointed the household location and number of NS deaths, injuries, newly reported cases of head nodding (n = 22), and the presence or absence of anti-seizure medication. Conclusions and significance: This study demonstrates the feasibility of using lay mHealth workers to develop a real-time cartography of epidemic disease in remote rural villages that can facilitate and steer clinical, educational and research interventions in a timely manner. [ABSTRACT FROM AUTHOR]

Introduction: Schistosomiasis is a chronic parasitic trematode disease that affects over 240 million people worldwide. The Schistosoma lifecycle is complex, involving transmission via specific intermediate-host freshwater snails. Predictive mathematical models of Schistosoma transmission have often chosen to simplify or ignore the details of environmental human-snail interaction in their analyses. Schistosome transmission models now aim to provide better precision for policy planning of elimination of transmission. This heightens the importance of including the environmental complexity of vector-pathogen interaction in order to make more accurate projections. Methodology and principal findings: We propose a nonlinear snail force of infection (FOI) that takes into account an intermediate larval stage (miracidium) and snail biology. We focused, in particular, on the effects of snail force of infection (FOI) on the impact of mass drug administration (MDA) in human communities. The proposed (modified) model was compared to a conventional model in terms of their predictions. A longitudinal dataset generated in Kenya field studies was used for model calibration and validation. For each sample community, we calibrated modified and conventional model systems, then used them to model outcomes for a range of MDA regimens. In most cases, the modified model predicted more vigorous post-MDA rebound, with faster relapse to baseline levels of infection. The effect was pronounced in higher risk communities. When compared to observed data, only the modified system was able to successfully predict persistent rebound of Schistosoma infection. Conclusion and significance: The observed impact of varying location-specific snail inputs sheds light on the diverse MDA response patterns noted in operational research on schistosomiasis control, such as the recent SCORE project. Efficiency of human-to-snail transmission is likely to be much higher than predicted by standard models, which, in practice, will make local elimination by implementation of MDA alone highly unlikely, even over a multi-decade period. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) increases morbidity in Hepatitis B virus (HBV)-infected patients. In the mid-eighties, an outbreak of HDV fulminant hepatitis (FH) in the Central African Republic (CAR) killed 88% of patients hospitalized in Bangui. We evaluated infections with HBV and HDV among students and pregnant women, 25 years after the fulminant hepatitis (FH) outbreak to determine (i) the prevalence of HBV and HDV infection in this population, (ii) the clinical risk factors for HBV and/or HDV infections, and (iii) to characterize and compare the strains from the FH outbreak in the 1980s to the 2010 HBV–HDV strains. We performed a cross sectional study with historical comparison on FH-stored samples (n = 179) from 159 patients and dried blood-spots from volunteer students and pregnant women groups (n = 2172). We analyzed risk factors potentially associated with HBV and HDV. Previous HBV infection (presence of anti-HBc) occurred in 345/1290 students (26.7%) and 186/870 pregnant women (21.4%)(p = 0.005), including 110 students (8.8%) and 71 pregnant women (8.2%), who were also HBsAg-positive (p = 0.824). HDV infection occurred more frequently in pregnant women (n = 13; 18.8%) than students (n = 6; 5.4%) (p = 0.010). Infection in childhood was probably the main HBV risk factor. The risk factors for HDV infection were age (p = 0.040), transfusion (p = 0.039), and a tendency for tattooing (p = 0.055) and absence of condom use (p = 0.049). HBV-E and HDV-1 were highly prevalent during both the FH outbreak and the 2010 screening project. For historical samples, due to storage conditions and despite several attempts, we could only obtain partial HDV amplification representing 25% of the full-length genome. The HDV-1 mid-eighties FH-strains did not form a specific clade and were affiliated to two different HDV-1 African subgenotypes, one of which also includes the 2010 HDV-1 strains. In the Central African Republic, these findings indicate a high prevalence of previous and current HBV-E and HDV-1 infections both in the mid-eighties fulminant hepatitis outbreak and among asymptomatic young adults in 2010, and reinforce the need for universal HBV vaccination and the prevention of HDV transmission among HBsAg-positive patients through blood or sexual routes. [ABSTRACT FROM AUTHOR]

Plague, caused by Yersinia pestis, was classified as a reemerging infectious disease by the World Health Organization. The five human pneumonic plague cases in Yulong County in 2005 gave rise to the discovery of a Yulong plague focus in Yunnan province, China. Thereafter, continuous wild rodent plague (sylvatic plague) was identified as the main plague reservoir of this focus. In this study, the epizootics in Yulong focus were described, and three molecular typing methods, including the different region (DFR) analysis, clustered regularly interspaced short palindromic repeats (CRISPRs), and the multiple-locus variable number of tandem repeats (VNTR) analysis (MLVA) (14+12), were used for the molecular typing and source tracing of Y. pestis isolates in the Yulong plague focus. Simultaneously, several isolates from the vicinity of Yunnan were used as controls. The results showed that during the 10-year period from 2006 to 2016, an animal plague epidemic occurred in 6 of those years, and 5 villages underwent an animal plague epidemic within a 30-km2 area of the Yulong plague focus. Searching for dead mice was the most effective monitoring method in this plague focus. No positive sample has been found in 6937 captured live rodents thus far, suggesting that the virulence of strains in the Yulong plague focus is stronger and the survival time of mice is shorter after infection. Strains from Lijiang, Sichuan and Tibet were of the same complex based on a typing analysis of DFR and CRISPR. The genetic relationship of Y. pestis illustrated by MLVA “14+12” demonstrates that Tibet and Sichuan strains evolved from the strains 1.IN2 (Qinghai, 1970 and Tibet, 1976), and Lijiang strains are closer to Batang strains (Batang County in Sichuan province, 2011, Himalaya marmot plague foci) in terms of genetic or phylogenic relationships. In conclusion, we have a deeper understanding of this new plague focus throughout this study, which provides a basis for effective prevention and control. [ABSTRACT FROM AUTHOR]

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild. [ABSTRACT FROM AUTHOR]

Few data on dengue epidemiology are available for Lao PDR. Here, we provide information on the complexity of dengue epidemiology in the country, demonstrating dynamic circulation that varies over space and time, according to serotype. We recruited 1,912 consenting patients presenting with WHO dengue criteria at Mahosot Hospital, Vientiane (central Laos), between 2006 and 2010. Between 2008 and 2010, 1,413 patients with undifferentiated fever were also recruited at Luang Namtha (LNT) Provincial Hospital (northern Laos) and 555 at Salavan (SV) Provincial Hospital (southern Laos). We report significant variations in Dengue virus (DENV) circulation between the three sites. Peaks of DENV infection were observed in the rainy seasons, although 11% of confirmed cases in the provinces and 4.6% in the capital were detected during the dry and cool seasons (between December and February). Four DENV serotypes were detected among the 867 RT-PCR positive patients: 76.9% DENV-1, 9.6% DENV-2, 7.7% DENV-4 and 5.3% DENV-3. DENV-1 was the predominant serotype throughout the study except in LNT in 2008 and 2009 when it was DENV-2. Before July 2009, DENV-2 was not detected in SV and only rarely detected in Vientiane. DENV-3 and DENV-4 were commonly detected in Vientiane, before 2008 for DENV-4 and after 2009 for DENV-3. The phylogenetic analyses of DENV envelope sequences suggest concurrent multiple introductions of new strains as well as active DENV circulation throughout Laos and with neighboring countries. It is therefore of great importance to develop and strengthen a year-round nation-wide surveillance network in order to collect data that would allow anticipation of public health issues caused by the occurrence of large dengue outbreaks. [ABSTRACT FROM AUTHOR]

The article covers the implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test using the GeneXpert platform, in Liberia in response to the Ebola Virus Disease (EVD) outbreak in West Africa between 2014 and 2016. It discusses the effectiveness of coordination between surveillance and laboratory teams before noting the costs and methodology associated with the GeneXpert platform.

Internet-based surveillance methods for vector-borne diseases (VBDs) using “big data” sources such as Google, Twitter, and internet newswire scraping have recently been developed, yet reviews on such “digital disease detection” methods have focused on respiratory pathogens, particularly in high-income regions. Here, we present a narrative review of the literature that has examined the performance of internet-based biosurveillance for diseases caused by vector-borne viruses, parasites, and other pathogens, including Zika, dengue, other arthropod-borne viruses, malaria, leishmaniasis, and Lyme disease across a range of settings, including low- and middle-income countries. The fundamental features, advantages, and drawbacks of each internet big data source are presented for those with varying familiarity of “digital epidemiology.” We conclude with some of the challenges and future directions in using internet-based biosurveillance for the surveillance and control of VBD. [ABSTRACT FROM AUTHOR]

Human mobility, presence and passive transportation of Aedes aegypti mosquito, and environmental characteristics are a group of factors which contribute to the success of dengue spread and establishment. To understand this process, we assess data from dengue national and municipal basins regarding population and demographics, transportation network, human mobility, and Ae. aegypti monitoring for the Brazilian state of Acre since the first recorded dengue case in the year 2000 to the year 2015. During this period, several changes in Acre’s transport infrastructure and urbanization have been started. To reconstruct the process of dengue introduction in Acre, we propose an analytic framework based on concepts used in malaria literature, namely vulnerability and receptivity, to inform risk assessments in dengue-free regions as well as network theory concepts for disease invasion and propagation. We calculate the probability of dengue importation to Acre from other Brazilian states, the evolution of dengue spread between Acrean municipalities and dengue establishment in the state. Our findings suggest that the landscape changes associated with human mobility have created favorable conditions for the establishment of dengue virus transmission in Acre. The revitalization of its major roads, as well as the increased accessibility by air to and within the state, have increased dengue vulnerability. Unplanned urbanization and population growth, as observed in Acre during the period of study, contribute to ideal conditions for Ae. aegypti mosquito establishment, increase the difficulty in mosquito control and consequently its local receptivity. [ABSTRACT FROM AUTHOR]

Introduction: Giardiasis is an intestinal infection that affects more than two hundred million people annually worldwide; it is caused by the flagellated protozoan Giardia duodenalis. In tropical countries and in low or middle-income settings, like Brazil, its prevalence can be high. There is currently no systematic review on the presence of G. duodenalis in patients, animals or water sources in Brazil. Methods: This systematic review was performed according to recommendations established by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). As databases for our searches, we have used PubMed, Embase, Scopus and the Brazilian database SciELO using the keywords «Giardia*» and «Brazil». Results: This systematic review identified research studies related to G. duodenalis in water, giardiasis in animals, prevalence of giardiasis across Brazilian regions, genotyping of strains isolated in humans, and giardiasis in indigenous populations. We also propose a network of G. duodenalis transmission in Brazil based on genotypes analyses. Conclusion: This is the first time within the last twenty years that a review is being published on the occurrence of G. duodenalis in Brazil, addressing relevant issues such as prevalence, molecular epidemiology and analytical methods for parasite detection. Non-technical summary: Giardiasis is an intestinal disease that affect millions of people worldwide, including children. Its main route of transmission is by ingestion of food or water contaminated with the protozoan G. duodenalis. Transmission does not require an animal host, although transmission from animals to human (zoonotic transmission) has been confirmed as an important vector of human giardiasis. This study is a comprehensive description of the impact of giardiasis in Brazil based on studies published in the country from the past 20 years. We describe Giardia prevalence in humans (including indigenous populations), animals and water supplies. In addition, we create a transmission network model for the disease, based on genotype data previously identified in animal and human hosts as well as in environmental samples. The data compiled here will be useful for design of policies to prevent giardiasis transmission in Brazil. [ABSTRACT FROM AUTHOR]

Aedes albopictus is a highly invasive disease vector with an expanding worldwide distribution. Genetic assays using low to medium resolution markers have found little evidence of spatial genetic structure even at broad geographic scales, suggesting frequent passive movement along human transportation networks. Here we analysed genetic structure of Aedes albopictus collected from 12 sample sites in Guangzhou, China, using thousands of genome-wide single nucleotide polymorphisms (SNPs). We found evidence for passive gene flow, with distance from shipping terminals being the strongest predictor of genetic distance among mosquitoes. As further evidence of passive dispersal, we found multiple pairs of full-siblings distributed between two sample sites 3.7 km apart. After accounting for geographical variability, we also found evidence for isolation by distance, previously undetectable in Ae. albopictus. These findings demonstrate how large SNP datasets and spatially-explicit hypothesis testing can be used to decipher processes at finer geographic scales than formerly possible. Our approach can be used to help predict new invasion pathways of Ae. albopictus and to refine strategies for vector control that involve the transformation or suppression of mosquito populations. [ABSTRACT FROM AUTHOR]

Background: The Global Trachoma Mapping Project (GTMP) was implemented with the aim of completing the baseline map of trachoma globally. Over 2.6 million people were examined in 1,546 districts across 29 countries between December 2012 and January 2016. The aim of the analysis was to estimate the unit cost and to identify the key cost drivers of trachoma prevalence surveys conducted as part of GTMP. Methodology and principal findings: In-country and global support costs were obtained using GTMP financial records. In-country expenditure was analysed for 1,164 districts across 17 countries. The mean survey cost was $13,113 per district [median: $11,675; IQR = $8,365-$14,618], $17,566 per evaluation unit [median: $15,839; IQR = $10,773-$19,915], $692 per cluster [median: $625; IQR = $452-$847] and $6.0 per person screened [median: $4.9; IQR = $3.7-$7.9]. Survey unit costs varied substantially across settings, and were driven by parameters such as geographic location, demographic characteristics, seasonal effects, and local operational constraints. Analysis by activities showed that fieldwork constituted the largest share of in-country survey costs (74%), followed by training of survey teams (11%). The main drivers of in-country survey costs were personnel (49%) and transportation (44%). Global support expenditure for all surveyed districts amounted to $5.1m, which included grant management, epidemiological support, and data stewardship. Conclusion: This study provides the most extensive analysis of the cost of conducting trachoma prevalence surveys to date. The findings can aid planning and budgeting for future trachoma surveys required to measure the impact of trachoma elimination activities. Furthermore, the results of this study can also be used as a cost basis for other disease mapping programmes, where disease or context-specific survey cost data are not available. [ABSTRACT FROM AUTHOR]

Introduction: The 2014/2015 West African Ebola Virus Disease (EVD) outbreak attracted global attention. Numerous opinions claimed that the global response was impaired, in part because, the EVD research was neglected, although quantitative or qualitative studies did not exist. Our objective was to analyse how the EVD research landscape evolved by exploring the existing research network and its communities before and during the outbreak in West Africa. Methods/ Principal findings: Social network analysis (SNA) was used to analyse collaborations between institutions named by co-authors as affiliations in publications on EVD. Bibliometric data of publications on EVD between 1976 and 2015 was collected from Thomson Reuters’ Web of Science Core Collection (WoS). Freely available software was used for network analysis at a global-level and for 10-year periods. The networks are presented as undirected-weighted graphs. Rankings by degree and betweenness were calculated to identify central and powerful network positions; modularity function was used to identify research communities. Overall 4,587 publications were identified, of which 2,528 were original research articles. Those yielded 1,644 authors’ affiliated institutions and 9,907 connections for co-authorship network construction. The majority of institutions were from the USA, Canada and Europe. Collaborations with research partners on the African continent did exist, but less frequently. Around six highly connected organisations in the network were identified with powerful and broker positions. Network characteristics varied widely among the 10-year periods and evolved from 30 to 1,489 institutions and 60 to 9,176 connections respectively. Most influential actors are from public or governmental institutions whereas private sector actors, in particular the pharmaceutical industry, are largely absent. Conclusion/ Significance: Research output on EVD has increased over time and surged during the 2014/2015 outbreak. The overall EVD research network is organised around a few key actors, signalling a concentration of expertise but leaving room for increased cooperation with other institutions especially from affected countries. Finding innovative ways to maintain support for these pivotal actors while steering the global EVD research network towards an agenda driven by agreed, prioritized needs and finding ways to better integrate currently peripheral and newer expertise may accelerate the translation of research into the development of necessary live saving products for EVD ahead of the next outbreak. [ABSTRACT FROM AUTHOR]

African trypanosomes of the sub-genus Trypanozoon) are eukaryotic parasitesthat cause disease in either humans or livestock. The development of genomic resources can be of great use to those interested in studying and controlling the spread of these trypanosomes. Here we present a large comparative analysis of Trypanozoon whole genomes, 83 in total, including human and animal infective African trypanosomes: 21 T. brucei brucei, 22 T. b. gambiense, 35 T. b. rhodesiense and 4 T. evansi strains, of which 21 were from Uganda. We constructed a maximum likelihood phylogeny based on 162,210 single nucleotide polymorphisms (SNPs.) The three Trypanosoma brucei sub-species and Trypanosoma evansi are not monophyletic, confirming earlier studies that indicated high similarity among Trypanosoma “sub-species”. We also used discriminant analysis of principal components (DAPC) on the same set of SNPs, identifying seven genetic clusters. These clusters do not correspond well with existing taxonomic classifications, in agreement with the phylogenetic analysis. Geographic origin is reflected in both the phylogeny and clustering analysis. Finally, we used sparse linear discriminant analysis to rank SNPs by their informativeness in differentiating the strains in our data set. As few as 84 SNPs can completely distinguish the strains used in our study, and discriminant analysis was still able to detect genetic structure using as few as 10 SNPs. Our results reinforce earlier results of high genetic similarity between the African Trypanozoon. Despite this, a small subset of SNPs can be used to identify genetic markers that can be used for strain identification or other epidemiological investigations. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. Methodology/Principal findings: In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV. Conclusions/Significance: Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia. [ABSTRACT FROM AUTHOR]

Background: The fight against onchocerciasis in Africa has boomed thanks to the Community Directed Treatment with Ivermectin (CDTI) program. However, in Cameroon, after more than 15 years of mass treatment, onchocerciasis prevalence is still above the non-transmission threshold. This study aimed to explore a possible association between people’s beliefs/perceptions of onchocerciasis and of CDTI program, and their adherence to ivermectin in three regions of Cameroon. Methodology/Principal findings: A cross sectional survey was carried out in three health districts with persistent high onchocerciasis prevalence. Participants were randomly selected in 30 clusters per district. Adherence to ivermectin was comparable between Bafang and Bafia (55.0% and 48.8%, respectively, p>0.05) and lower in Yabassi (40.7%). Among all factors related to program perceptions and disease representations that were studied, perceptions of the program are the ones that were most determinant in adherence to ivermectin. People who had a “not positive” opinion of ivermectin distribution campaigns were less compliant than those who had a positive opinion about the campaigns (40% vs 55% in Bafang, and 48% vs 62% in Bafia, p<0.01), as well as those who had a negative appreciation of community drug distributors’ commitment (22% vs 53% in Bafang, 33% vs 59% in Bafia, 27% vs 47% in Yabassi; p<0.01). The most common misconception about onchocerciasis transmission was the lack of hygiene, especially in Bafia and Yabassi. In Bafang, high proportions of people believed that onchocerciasis was due to high consumption of sugar (31% vs less than 5% in Bafia and Yabassi, p<0.001). Conclusion/Significance: There are still frequent misconceptions about onchocerciasis transmission in Cameroon. Perceptions of ivermectin distribution campaigns are more strongly associated to adherence. In addition to education/sensitisation on onchocerciasis during the implementation of the CDTI program, local health authorities should strive to better involve communities and more encourage community distributors’ work. [ABSTRACT FROM AUTHOR]

Introduction: Leishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now. Methodology/Principles findings: We subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%–23.5%) across the entire sequence except for highly conserved motifs within the 5’ untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five distinct clusters. They further showed a species-dependent clustering between viral genomes of L. (V.) guyanensis and L. (V.) braziliensis, confirming a long-term co-evolutionary history. Noteworthy, we identified cases of multiple LRV1 infections in three of the 20 Leishmania isolates. Conclusions/Significance: Here, we present the first-ever estimate of LRV1 genomic diversity that exists in Leishmania (V.) guyanensis parasites. Genetic characterization and phylogenetic analyses of these viruses has shed light on their evolutionary relationships. To our knowledge, this study is also the first to report cases of multiple LRV1 infections in some parasites. Finally, this work has made it possible to develop molecular tools for adequate identification and genotyping of LRV1 strains for diagnostic purposes. Given the suspected worsening role of LRV1 infection in the pathogenesis of human leishmaniasis, these data have a major impact from a clinical viewpoint and for the management of Leishmania-infected patients. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is best known for the disabling and disfiguring clinical conditions that infected patients can develop; providing care for these individuals is a major goal of the Global Programme to Eliminate LF. Methods of locating these patients, knowing their true number and thus providing care for them, remains a challenge for national medical systems, particularly when the endemic zone is a large urban area. Methodology/Principle findings: A health community-led door-to-door survey approach using the SMS reporting tool MeasureSMS-Morbidity was used to rapidly collate and monitor data on LF patients in real-time (location, sex, age, clinical condition) in Dar es Salaam, Tanzania. Each stage of the phased study carried out in the three urban districts of city consisted of a training period, a patient identification and reporting period, and a data verification period, with refinements to the system being made after each phase. A total of 6889 patients were reported (133.6 per 100,000 population), of which 4169 were reported to have hydrocoele (80.9 per 100,000), 2251 lymphoedema-elephantiasis (LE) (43.7 per 100,000) and 469 with both conditions (9.1 per 100,000). Kinondoni had the highest number of reported patients in absolute terms (2846, 138.9 per 100,000), followed by Temeke (2550, 157.3 per 100,000) and Ilala (1493, 100.5 per 100,000). The number of hydrocoele patients was almost twice that of LE in all three districts. Severe LE patients accounted for approximately a quarter (26.9%) of those reported, with the number of acute attacks increasing with reported LE severity (1.34 in mild cases, 1.78 in moderate cases, 2.52 in severe). Verification checks supported these findings. Conclusions/Significance: This system of identifying, recording and mapping patients affected by LF greatly assists in planning, locating and prioritising, as well as initiating, appropriate morbidity management and disability prevention (MMDP) activities. The approach is a feasible framework that could be used in other large urban environments in the LF endemic areas. [ABSTRACT FROM AUTHOR]

Background: Contact tracing is one of the key response activities necessary for halting Ebola Virus Disease (EVD) transmission. Key elements of contact tracing include identification of persons who have been in contact with confirmed EVD cases and careful monitoring for EVD symptoms, but the details of implementation likely influence their effectiveness. In November 2015, several months after a major Ebola outbreak was controlled in Liberia, three members of a family were confirmed positive for EVD in the Duport Road area of Monrovia. The cluster provided an opportunity to implement and evaluate modified approaches to contact tracing. Methods: The approaches employed for improved contact tracing included classification and risk-based management of identified contacts (including facility based isolation of some high risk contacts, provision of support to persons being monitored, and school-based surveillance for some persons with potential exposure but not listed as contacts), use of phone records to help locate missing contacts, and modifications to data management tools. We recorded details about the implementation of these approaches, report the overall outcomes of the contact tracing efforts and the challenges encountered, and provide recommendations for management of future outbreaks. Results: 165 contacts were identified (with over 150 identified within 48 hours of confirmation of the EVD cases) and all initially missing contacts were located. Contacts were closely monitored and promptly tested if symptomatic; no contacts developed disease. Encountered challenges related to knowledge gaps among contact tracing staff, data management, and coordination of contact tracing activities with efforts to offer Ebola vaccine. Conclusions: The Duport Road EVD cluster was promptly controlled. Missing contacts were effectively identified, and identified contacts were effectively monitored and rapidly tested. There is a persistent risk of EVD reemergence in Liberia; the experience controlling each cluster can help inform future Ebola control efforts in Liberia and elsewhere. [ABSTRACT FROM AUTHOR]

Bartonella infections were investigated in seven species of bats from four regions of the Republic of Georgia. Of the 236 bats that were captured, 212 (90%) specimens were tested for Bartonella infection. Colonies identified as Bartonella were isolated from 105 (49.5%) of 212 bats Phylogenetic analysis based on sequence variation of the gltA gene differentiated 22 unique Bartonella genogroups. Genetic distances between these diverse genogroups were at the level of those observed between different Bartonella species described previously. Twenty-one reference strains from 19 representative genogroups were characterized using four additional genetic markers. Host specificity to bat genera or families was reported for several Bartonella genogroups. Some Bartonella genotypes found in bats clustered with those identified in dogs from Thailand and humans from Poland. [ABSTRACT FROM AUTHOR]