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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]

Background: Phlebotomine sand flies are vectors of human leishmaniases, important neglected tropical diseases. In this study, we investigated diel patterns of oviposition behavior, effects of visual cues on oviposition-site selection, and whether these affect the attraction of gravid Phlebotomus papatasi (Scopoli), the vector of old-world cutaneous leishmaniasis, to olfactory cues from oviposition sites. Methodology/principal findings: To evaluate these questions, we conducted a series of experiments using attraction and oviposition assays within free-flight test chambers containing gravid females entrained under a 14:10 hrs light:dark photoperiod. By replacing sticky-screens or moist filter papers every three hours, we showed that oviposition site search occurs mainly in the latest part of the night whereas peak oviposition occurs during the early part of the night. Behavioral responses to olfactory oviposition cues are regulated by time-of-day and can be disrupted by transient exposure to a constant darkness photoperiod. Gravid females, but not any other stage, age, or sex, were attracted to dark, round oviposition jars, possibly resembling rodent burrow openings. This visual attraction disappeared in the absence of an illumination source. Egg deposition rate was not affected by jar color. Olfactory cues had the strongest effect when the visual cues were minimal. Conclusion and significance: Our study showed, for the first time, that visual cues in the form of oviposition-site color, lighting level, and photoperiod are important in guiding the oviposition behavior of phlebotomine sand flies. Furthermore, such visual cues could modify the flies’ sensitivity to olfactory oviposition cues. Our results suggest that chemosensory and visual cues are complementary, with visual cues used to orient gravid females towards oviposition sites, possibly at long- to medium-ranges during crepuscular periods, while olfactory cues are used to approach the burrow in darkness and assess its suitability at close-range. Implications to sand fly control are discussed. [ABSTRACT FROM AUTHOR]

Background: Up to 1.45 billion people currently suffer from soil transmitted helminth infection, with the largest burden occurring in Africa and Asia. Safe and cost effective deworming treatment exists, but there is a debate about mass distribution of this treatment in high prevalence settings. While the World Health Organization recommends mass administration of anthelmintic drugs for preschool and school-aged children in high (>20%) prevalence settings, and several long run follow up studies of an influential trial have suggested large benefits that persist over time, recent systematic reviews have called this recommendation into question. Methods and findings: This paper analyzes the long-term impact of a cluster-randomized trial in eastern Uganda that provided mass deworming treatment to preschool aged children from 2000 to 2003 on the numeracy and literacy skills of children and young adults living in those villages in 2010-2015. This study uses numeracy and literacy data collected seven to twelve years after the end of the deworming trial in a randomly selected subset of communities from the original trial, by an education-focused survey that had no relationship to the deworming study. Building on an earlier working paper which used data from 2010 and 2011 survey rounds, this paper uses an additional four years of numeracy and literacy data (2012, 2013, 2014, and 2015). Aggregating data from all survey rounds, the difference between numeracy scores in treatment versus control communities is 0.07 standard deviations (SD) (95% CI -0.10, 0.24, p = 0.40), the difference in literacy scores is 0.05 SD (95% CI -0.16, 0.27, p = 0.62), and the difference in total scores is 0.07 SD (95% CI -0.11, 0.25, p = 0.44). There are significant differences in program impact by gender, with numeracy and literacy differentially positively affected for girls, and by age, with treatment effects larger for the primary school aged subsample. There are also significant treatment interactions for those living in households with more treatment-eligible children. There is no evidence of differential treatment effects on age at program eligibility or number of years of program eligibility. Conclusions: Mass deworming of preschool aged children in high prevalence communities in Uganda resulted in no statistically significant gains in numeracy or literacy 7-12 years after program completion. Point estimates were positive but imprecise; the study lacked sufficient power to rule out substantial positive effects or more modest negative effects. However, there is suggestive evidence that deworming was relatively more beneficial for girls, primary school aged children, and children living in households with other treated children. Research approval: As this analysis was conducted on secondary data which is publicly available, no research approval was sought or received. All individual records were anonymized by the data provider prior to public release. [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]

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: Leprosy is a condition that has long been associated with stigma and discrimination, even when infected persons have been cured. This paper describes stigma and discrimination as viewed by caregivers who are associated with people affected by leprosy in Ghana. Methods: A qualitative interview with semi-structured interviews were conducted for twenty caregivers. Results: Findings indicated that caregivers were of the view that people affected by leprosy in Ghana are stigmatized and discriminated against by the larger society thus making their movements and interactions restricted to the Leprosarium. Besides, employments opportunities are unavailable to them thus making them exposed to financial challenges. The livelihood Empowerment Against poverty (LEAP) money given them is not sufficient for their daily upkeep. Conclusion: People affected by leprosy in Ghana are stigmatized and therefore find it difficult to interact freely with the public. The associated physical deformities with the disease also tend to impede their ability to relate to the general public. The LEAP cash given to people affected by leprosy is helpful however, it could be enhanced to keep pace with prevailing economic conditions in the country. [ABSTRACT FROM AUTHOR]

Scabies is an infestation of the skin by the mite Sarcoptes scabiei. It manifests with pruritic erythematous papules and excoriations, in addition to the pathognomonic burrows. Multiple drugs can be used for treatment, but resistance to conventional therapy is increasing throughout the years. This paper will review the mechanisms of resistance proposed in the literature and some of the potential solutions to this problem. [ABSTRACT FROM AUTHOR]

The West African Ebola epidemic of 2013–2016 was by far the largest outbreak of the disease on record. Sierra Leone suffered nearly half of the 28,646 reported cases. This paper presents a set of culturally contextualized Ebola messages that are based on the findings of qualitative interviews and focus group discussions conducted in 'hotspot' areas of rural Bombali District and urban Freetown in Sierra Leone, between January and March 2015. An iterative approach was taken in the message development process, whereby (i) data from formative research was subjected to thematic analysis to identify areas of community concern about Ebola and the national response; (ii) draft messages to address these concerns were produced; (iii) the messages were field tested; (iv) the messages were refined; and (v) a final set of messages on 14 topics was disseminated to relevant national and international stakeholders. Each message included details of its rationale, audience, dissemination channels, messengers, and associated operational issues that need to be taken into account. While developing the 14 messages, a set of recommendations emerged that could be adopted in future public health emergencies. These included the importance of embedding systematic, iterative qualitative research fully into the message development process; communication of the subsequent messages through a two-way dialogue with communities, using trusted messengers, and not only through a one-way, top-down communication process; provision of good, parallel operational services; and engagement with senior policy makers and managers as well as people in key operational positions to ensure national ownership of the messages, and to maximize the chance of their being utilised. The methodological approach that we used to develop our messages along with our suggested recommendations constitute a set of tools that could be incorporated into international and national public health emergency preparedness and response plans. [ABSTRACT FROM AUTHOR]

Background: Socioeconomically deprived children are at increased risk of ill-health associated with sedentary behavior, malnutrition, and helminth infection. The resulting reduced physical fitness, growth retardation, and impaired cognitive abilities may impede children’s capacity to pay attention. The present study examines how socioeconomic status (SES), parasitic worm infections, stunting, food insecurity, and physical fitness are associated with selective attention and academic achievement in school-aged children. Methodology: The study cohort included 835 children, aged 8–12 years, from eight primary schools in socioeconomically disadvantaged neighborhoods of Port Elizabeth, South Africa. The d2-test was utilized to assess selective attention. This is a paper and pencil letter-cancellation test consisting of randomly mixed letters d and p with one to four single and/or double quotation marks either over and/or under each letter. Children were invited to mark only the letters d that have double quotation marks. Cardiorespiratory fitness was assessed via the 20 m shuttle run test and muscle strength using the grip strength test. The Kato-Katz thick smear technique was employed to detect helminth eggs in stool samples. SES and food insecurity were determined with a pre-tested questionnaire, while end of year school results were used as an indicator of academic achievement. Principal findings: Children infected with soil-transmitted helminths had lower selective attention, lower school grades (academic achievement scores), and lower grip strength (all p<0.05). In a multiple regression model, low selective attention was associated with soil-transmitted helminth infection (p<0.05) and low shuttle run performance (p<0.001), whereas higher academic achievement was observed in children without soil-transmitted helminth infection (p<0.001) and with higher shuttle run performance (p<0.05). Conclusions/Significance: Soil-transmitted helminth infections and low physical fitness appear to hamper children’s capacity to pay attention and thereby impede their academic performance. Poor academic achievement will make it difficult for children to realize their full potential, perpetuating a vicious cycle of poverty and poor health. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Onchocerca volvulus infection can result in blindness, itching and skin lesions. Previous research concentrated on blindness. Methods: A clinical classification system of the cutaneous changes in onchocerciasis was used for the first time in this study within the context of an early ivermectin drug trial in the savanna region of Kaduna State, northern Nigeria. Skin examinations were performed in 6,790 individuals aged 5+ years in endemic communities and 1,343 individuals in nonendemic communities. Results / Discussion: There was increased risk for all forms of onchocercal skin disease in endemic communities with the most common finding being the presence of nodules (1,438 individuals, 21.2%), followed by atrophy (367, 6.1% of those < 50 years), acute papular onchodermatitis, APOD (233, 3.4%), depigmentation (216, 3.2%) and chronic papular onchodermatitis, CPOD (155, 2.3%). A further 645 individuals (9.5%) complained of pruritus but had completely normal skin. APOD was more common in males whereas atrophy, hanging groin and nodules were more common in females. After controlling for age and sex, microfilarial positivity was a risk factor for CPOD, depigmentation, hanging groin and nodules (OR 1.54, p = 0.046; OR 2.29, p = 0.002; OR 2.18, p = 0.002 and OR 3.80, p <0.01 respectively). Comparable results were found using presence of nodules as the marker for infection. Microfilarial load showed similar, though weaker, results. A total of 2621(38.6%) endemic residents had itching with normal skin, or had one or more types of onchocercal skin disease including nodules, which may be considered as a composite index of the overall prevalence of onchocercal skin disease. Conclusion: Significant levels of onchocercal skin disease were documented in this savanna area, which subsequently resulted in a reassessment of the true burden of skin disease in onchocerciasis. This paper represents the first detailed report of the association of onchocercal skin disease with markers for onchocercal infection. [ABSTRACT FROM AUTHOR]

Riverine tsetse transmit the parasites that cause the most prevalent form of human African trypanosomiasis, Gambian HAT. In response to the imperative for cheap and efficient tsetse control, insecticide-treated ‘tiny targets’ have been developed through refinement of tsetse attractants based on blue fabric panels. However, modern blue polyesters used for this purpose attract many less tsetse than traditional phthalogen blue cottons. Therefore, colour engineering polyesters for improved attractiveness has great potential for tiny target development. Because flies have markedly different photoreceptor spectral sensitivities from humans, and the responses of these photoreceptors provide the inputs to their visually guided behaviours, it is essential that polyester colour engineering be guided by fly photoreceptor-based explanations of tsetse attraction. To this end, tsetse attraction to differently coloured fabrics was recently modelled using the calculated excitations elicited in a generic set of fly photoreceptors as predictors. However, electrophysiological data from tsetse indicate the potential for modified spectral sensitivities versus the generic pattern, and processing of fly photoreceptor responses within segregated achromatic and chromatic channels has long been hypothesised. Thus, I constructed photoreceptor-based models explaining the attraction of G. f. fuscipes to differently coloured tiny targets recorded in a previously published investigation, under differing assumptions about tsetse spectral sensitivities and organisation of visual processing. Models separating photoreceptor responses into achromatic and chromatic channels explained attraction better than earlier models combining weighted photoreceptor responses in a single mechanism, regardless of the spectral sensitivities assumed. However, common principles for fabric colour engineering were evident across the complete set of models examined, and were consistent with earlier work. Tools for the calculation of fly photoreceptor excitations are available with this paper, and the ways in which these and photoreceptor-based models of attraction can provide colorimetric values for the engineering of more-attractively coloured polyester fabrics are discussed. [ABSTRACT FROM AUTHOR]

Background: The leishmanicidal action of tricyclic antidepressants has been studied and evidences have pointed that their action is linked to inhibition of trypanothione reductase, a key enzyme in the redox metabolism of pathogenic trypanosomes. Cyclobenzaprine (CBP) is a tricyclic structurally related to the antidepressant amitriptyline, differing only by the presence of a double bond in the central ring. This paper describes the effect of CBP in experimental visceral leishmaniasis, its inhibitory effect in trypanothione reductase and the potential immunomodulatory activity. Methodology/Principal Findings: In vitro antileishmanial activity was determined in promastigotes and in L. infantum-infected macrophages. For in vivo studies, L. infantum-infected BALB/c mice were treated with CBP by oral gavage for five days and the parasite load was estimated. Trypanothione reductase activity was assessed in the soluble fraction of promastigotes of L. infantum. For evaluation of cytokines, L. infantum-infected macrophages were co-cultured with BALB/c splenocytes and treated with CBP for 48 h. The supernatant was analyzed for IL-6, IL-10, MCP-1, IFN-γ and TNF-α. CBP demonstrated an IC50 of 14.5±1.1μM and an IC90 of 74.5±1.2 μM in promastigotes and an IC50 of 12.6±1.05 μM and an IC90 of 28.7±1.3 μM in intracellular amastigotes. CBP also reduced the parasite load in L. infantum-infected mice by 40.4±10.3% and 66.7±10.5% in spleen at 24.64 and 49.28 mg/kg, respectively and by 85.6±5.0 and 89.3±4.8% in liver at 24.64 and 49.28mg/kg, after a short-term treatment. CBP inhibited the trypanothione reductase activity with a Ki of 86 ± 7.7 μM and increased the ROS production in promastigotes. CBP inhibited in 53% the production of IL-6 in infected macrophages co-culture. Conclusion/Significance: To the best of our knowledge, this study is the first report of the in vivo antileishmanial activity of the FDA-approved drug CBP. Modulation of immune response and induction of oxidative stress in parasite seem to contribute to this efficacy. [ABSTRACT FROM AUTHOR]

Background: This paper assesses the impact of a counselling intervention on reducing leprosy-related stigma in Cirebon District, Indonesia. The unique features of this intervention are its rights-based approach, the underlying Cognitive Behavioural Therapy (CBT) model, the three types of counselling and the lay and peer counsellors who were involved. Methodology/principal findings: Mixed methods (e.g. three scales, interviews, focus group discussions and reflection notes) were used to assess the impact of the intervention, which ran over a two-year period. There was a control area with no interventions. The study participants were people affected by leprosy and other key persons (e.g. family members). The sample size differs per method, for example, data regarding 67 counselling clients and 57 controls from a cohort, and notes from 207 counselling clients were examined. The notes showed that most clients faced stigma on a daily basis, whether internalized, anticipated and/or enacted. A significant reduction was found between the before and after total scores of the SARI Stigma Scale (p-value < 0.001), Participation Scale Short (p-value < 0.001) and WHO Quality of Life score (p-value < 0.001) among the counselling clients. While there is also an effect in the control group, it is much larger in the intervention group. Qualitative data indicates that knowledge and rights trigger change. Clients took steps to improve their life such as re-connecting with neighbours, helping in household activities and applying for jobs. Challenges include the wish to conceal their condition. Conclusion/significance: The findings show that the counselling intervention was effective in reducing stigma, promoting the rights of people with leprosy and facilitating their social participation. More research is needed on how to create a more sustainable intervention, preferably structurally embedded in the health or social services. [ABSTRACT FROM AUTHOR]

Epidemics of communicable diseases place a huge burden on public health infrastructures across the world. Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks. However, scientists and public health officials face many obstacles in trying to create such real-time forecasts of infectious disease incidence. Dengue is a mosquito-borne virus that annually infects over 400 million people worldwide. We developed a real-time forecasting model for dengue hemorrhagic fever in the 77 provinces of Thailand. We created a practical computational infrastructure that generated multi-step predictions of dengue incidence in Thai provinces every two weeks throughout 2014. These predictions show mixed performance across provinces, out-performing seasonal baseline models in over half of provinces at a 1.5 month horizon. Additionally, to assess the degree to which delays in case reporting make long-range prediction a challenging task, we compared the performance of our real-time predictions with predictions made with fully reported data. This paper provides valuable lessons for the implementation of real-time predictions in the context of public health decision making. [ABSTRACT FROM AUTHOR]

Background: Schistosomal myeloradiculopathy (SMR), the most severe and disabling ectopic form of Schistosoma mansoni infection, is caused by embolized ova eliciting local inflammation in the spinal cord and nerve roots. The treatment involves the use of praziquantel and long-term corticotherapy. The assessment of therapeutic response relies on neurological examination. Supplementary electrophysiological exams may improve prediction and monitoring of functional outcome. Vestibular evoked myogenic potential (VEMP) triggered by galvanic vestibular stimulation (GVS) is a simple, safe, low-cost and noninvasive electrophysiological technique that has been used to test the vestibulospinal tract in motor myelopathies. This paper reports the results of VEMP with GVS in patients with SMR. Methods: A cross-sectional comparative study enrolled 22 patients with definite SMR and 22 healthy controls that were submitted to clinical, neurological examination and GVS. Galvanic stimulus was applied in the mastoid bones in a transcranial configuration for testing VEMP, which was recorded by electromyography (EMG) in the gastrocnemii muscles. The VEMP variables of interest were blindly measured by two independent examiners. They were the short-latency (SL) and the medium-latency (ML) components of the biphasic EMG wave. Results: VEMP showed the components SL (p = 0.001) and ML (p<0.001) delayed in SMR compared to controls. The delay of SL (p = 0.010) and of ML (p = 0.020) was associated with gait dysfunction. Conclusion: VEMP triggered by GVS identified alterations in patients with SMR and provided additional functional information that justifies its use as a supplementary test in motor myelopathies. [ABSTRACT FROM AUTHOR]

Palpalis group tsetse flies are the major vectors of human African trypanosomiasis, and visually-attractive targets and traps are important tools for their control. Considerable efforts are underway to optimise these visual baits, and one factor that has been investigated is coloration. Analyses of the link between visual bait coloration and tsetse fly catches have used methods which poorly replicate sensory processing in the fly visual system, but doing so would allow the visual information driving tsetse attraction to these baits to be more fully understood, and the reflectance spectra of candidate visual baits to be more completely analysed. Following methods well established for other species, I reanalyse the numbers of tsetse flies caught at visual baits based upon the calculated photoreceptor excitations elicited by those baits. I do this for large sets of previously published data for Glossina fuscipes fuscipes (Lindh et al. (2012). PLoS Negl Trop Dis 6: e1661), G. palpalis palpalis (Green (1988). Bull Ent Res 78: 591), and G. pallidipes (Green and Flint (1986). Bull Ent Res 76: 409). Tsetse attraction to visual baits in these studies can be explained by a colour opponent mechanism to which the UV-blue photoreceptor R7y contributes positively, and both the green-yellow photoreceptor R8y, and the low-wavelength UV photoreceptor R7p, contribute negatively. A tool for calculating fly photoreceptor excitations is made available with this paper, and this will facilitate a complete and biologically authentic description of visual bait reflectance spectra that can be employed in the search for more efficacious visual baits, or the analysis of future studies of tsetse fly attraction. [ABSTRACT FROM AUTHOR]

Author summary: During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community’s communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted. [ABSTRACT FROM AUTHOR]

Background: Triatomine bugs are the insect vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. These insects are known to aggregate inside shelters during daylight hours and it has been demonstrated that within shelters, the aggregation is induced by volatiles emitted from bug feces. These signals promote inter-species aggregation among most species studied, but the chemical composition is unknown. Methodology/Principal Findings: In the present work, feces from larvae of the three species were obtained and volatile compounds were identified by solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS). We identified five compounds, all present in feces of all of the three species: Triatoma infestans, Panstrongylus megistus and Triatoma brasiliensis. These substances were tested for attractivity and ability to recruit insects into shelters. Behaviorally active doses of the five substances were obtained for all three triatomine species. The bugs were significantly attracted to shelters baited with blends of 160 ng or 1.6 µg of each substance. Conclusions/Significance: Common compounds were found in the feces of vectors of Chagas disease that actively recruited insects into shelters, which suggests that this blend of compounds could be used for the development of baits for early detection of reinfestation with triatomine bugs. [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]

Viroporins like influenza A virus M2, hepatitis C virus p7, HIV-1 Vpu and picornavirus 2B associate with host membranes, and create hydrophilic corridors, which are critical for viral entry, replication and egress. The 6K proteins from alphaviruses are conjectured to be viroporins, essential during egress of progeny viruses from host membranes, although the analogue in Chikungunya Virus (CHIKV) remains relatively uncharacterized. Using a combination of electrophysiology, confocal and electron microscopy, and molecular dynamics simulations we show for the first time that CHIKV 6K is an ion channel forming protein that primarily associates with endoplasmic reticulum (ER) membranes. The ion channel activity of 6K can be inhibited by amantadine, an antiviral developed against the M2 protein of Influenza A virus; and CHIKV infection of cultured cells can be effectively inhibited in presence of this drug. Our study provides crucial mechanistic insights into the functionality of 6K during CHIKV-host interaction and suggests that 6K is a potential therapeutic drug target, with amantadine and its derivatives being strong candidates for further development. [ABSTRACT FROM AUTHOR]

Background: High epilepsy prevalence and incidence were observed in onchocerciasis-endemic villages in the Democratic Republic of Congo (DRC). We investigated the clinical characteristics of onchocerciasis-associated epilepsy (OAE), and the relationship between seizure severity and microfilarial density. Methods: In October 2017, ivermectin-naive persons with epilepsy (PWE) were recruited from onchocerciasis-endemic areas in the Logo health zone in the DRC. Additional PWE were enrolled in the Aketi health zone, where ivermectin had been distributed annually for 14 years. Past medical history, clinical characteristics and skin snips for Onchocerca volvulus detection were obtained from participants. Bivariate and multivariable analyses were used to investigate associations with microfilarial density. Results: Of the 420 PWE in the Logo health zone, 392 were skin snipped (36.5% positive). Generalized motor seizures were most frequent (392 PWE, 93.3%), and nodding seizures were reported in 32 (7.6%) participants. Twelve PWE (3.1%) presented Nakalanga features. Sixty-three (44.1%) skin snip-positive PWE had a family history of epilepsy, compared to only 82 (32.9%) skin snip-negative PWE (p = 0.027). Eighty-one onchocerciasis-infected PWE were recruited in the Aketi health zone. Positive correlations between seizure frequency and microfilarial density were observed in Logo (Spearman-rho = 0.175; p<0.001) and Aketi (Spearman-rho = 0.249; p = 0.029). In the multivariable model adjusted for age, gender, and previous treatment, high seizure frequency was associated with increasing microfilarial density in Aketi (p = 0.025) but not in Logo (p = 0.148). Conclusion: In onchocerciasis-endemic regions in the DRC, a wide spectrum of seizures was observed. The occurrence of Nodding seizures and Nakalanga features, as well as an association between seizure severity and O. volvulus microfilarial density suggest a high OAE prevalence in the study villages. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Sustainable dengue intervention requires the participation of communities. Therefore, understanding the health beliefs, knowledge and perceptions of dengue among the local people can help to design locally appropriate strategies for effective interventions. A combination of qualitative semi-structured in-depth interviews (SDIs) and quantitative household questionnaire surveys (HHSs) was used to investigate the beliefs, knowledge and perceptions of dengue among the Shan people in Eastern Shan Special Region IV (ESSR4), Myanmar. The SDI was administered to 18 key informants, and the HHS was administered to 259 respondents. Only 14.7% (95% CI: 10.6–19.6%) of the HHS respondents could confirm that mosquitoes transmit dengue; 14.3% (95% CI: 10.3–19.1%) knew that piebald or Aedes mosquitoes transmit dengue; and 24.3% (95% CI: 19.2–30.0%) believed that dengue-transmitting mosquitoes mainly lived in small ponds. Merely ten (0.4%) of the 259 respondents of the HHS thought that dengue-transmitting mosquitoes bite in the day time. The people in the villages where there were outbreaks of dengue had more knowledge about dengue. This study demonstrates that the health beliefs of the Shan people were closely associated with their lifestyles, social and natural environments. To stay healthy, the Shan people clean their houses and surroundings regularly. However, their knowledge about dengue was not adequate for effective dengue control because it was mostly learned from previous dengue experiences and in a context that lacks systematic health education. Thus, in this setting, with a weak public health structure, more international support should be provided to promote the knowledge of the Shan people about dengue and to increase their sensitive awareness to dengue, which might be beneficial for social mobilization and community participation during future dengue prevention. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminth (STH) infections remain highly endemic across the Philippines, and are believed to be important contributors to delayed cognitive development of school-aged children. Identification of communities where children are at risk of functional illiteracy is important for the attainment of Sustainable Development Goals target for literacy. We aimed to quantify the associations between the spatial variation of STH infections and functional literacy indicators adjusting for other important contributors, and identify priority areas in the Philippines in need of interventions. Methodology/Principal findings: We used data from 11,313 school-aged children on functional literacy indicators collected in 2008. Nested fixed-effects multinomial regression models were built to determine associations between STH endemicity and geographical distribution of functional literacy, adjusting for demographics, household level variables, and the prevalence of malaria. Bayesian multinomial geostatistical models were built to geographically predict the prevalence of each level of functional literacy. The number of school-aged children belonging to each of the functional literacy indicator classes was forecast for 2017. We estimated 4.20% of functional illiteracy burden among school-aged children in Mindanao might be averted by preventing T. trichiura infections. Areas predicted with the highest prevalence of functional illiteracy were observed in localised areas of the eastern region of the Visayas, and the south-eastern portion of Mindanao. Conclusions/Significance: The study demonstrates significant geographical variation in burden of functional illiteracy in school-aged children associated with STH infections suggesting that targeted helminth control could potentially promote the development of cognitive function of school-aged children in the Philippines. The benefits of a spatially targeted strategy should be tested by future studies. [ABSTRACT FROM AUTHOR]

Soil-transmitted helminths (STHs) affect more than 1.5 billion people. The global strategy to control STH infections requires periodic mass drug administration (MDA) based on prevalence among populations at risk determined by diagnostic testing. Widely used copromicroscopy methods to detect infection, however, have low sensitivity as the prevalence and intensity of STH infections decline with repeated MDA. More sensitive diagnostic tools are needed to inform program decision-making. Using an integrated product development process, PATH conducted qualitative and quantitative formative research to inform the design and development of a more sensitive test for STH infections. The research, grounded in a conceptual framework for ensuring access to health products, involved stakeholder analysis, key opinion leader interviews, observational site visits of ongoing STH surveillance programs, and market research including market sizing, costing and willingness-to-pay analyses. Stakeholder analysis identified key groups and proposed strategic engagement of stakeholders during product development. Interviews highlighted features, motivations and concerns that are important for guiding design and implementation of new STH diagnostics. Process mapping outlined current STH surveillance workflows in Kenya and the Philippines. Market sizing in 2016 was estimated around half a million tests for lower STH burden countries, and 1–2 million tests for higher STH burden countries. The cost of commodities per patient for a molecular STH diagnostic may be around $10, 3–4 times higher than copromicroscopy methods, though savings may be possible in time and staffing requirements. The market is highly price sensitive as even at $5 per test, only 27% of respondents thought the test would be used by surveillance programs. A largely subsidized STH control strategy and a semi-functional Kato-Katz test may have created few incentives for manufacturers to innovate in STH diagnostics. Diverse partnerships, as well as balancing needs and expectations for new STH diagnostics are necessary to ensure access to needed products. [ABSTRACT FROM AUTHOR]

Objectives: We contribute a new methodological approach to the ongoing efforts towards evaluating public health surveillance. Specifically, we apply a descriptive framework, grounded in prospect theory (PT), for the evaluation of decisions on disease surveillance deployment. We focus on two attributes of any surveillance system: timeliness, and false positive rate (FPR). Methods: In a sample of 69 health professionals from a number of health related networks polled online, we elicited PT preferences, specifically respondents’ attitudes towards gains, losses and probabilities (i.e., if they overweight or underweight extreme probabilities) by means of a series of lotteries for either timeliness or FPR. Moreover, we estimated willingness to pay (WTP) for improvements in the two surveillance attributes. For contextualization, we apply our framework to rabies surveillance. Results: Our data reveal considerable probability weighting, both for gains and losses. In other words, respondents underestimate their chances of getting a good outcome in uncertain situations, and they overestimate their chances of bad outcomes. Moreover, there is convex utility for losses and loss aversion, that is, losses loom larger than gains of the same absolute magnitude to the respondents. We find no differences between the estimated parameters for timeliness and FPR. The median WTP is $7,250 per day gained in detection time and $30 per 1/10,000 reduction in FPR. Conclusion: Our results indicate that the biases described by PT are present among public health professionals, which highlights the need to incorporate a PT framework when eliciting their preferences for surveillance systems. [ABSTRACT FROM AUTHOR]

Background: Clonorchis sinensis is a group I bio-carcinogen responsible for cholangiocarcinoma (CHCA) in humans. However, the mechanism by which C. sinensis promotes carcinogenesis is unclear. Methodology: Using the human cholangiocyte line H69, we investigated cell proliferation and gap junction protein expression after stimulation with the hepatotoxin N-nitrosodimethylamine (NDMA) and/or excretory-secretory products (ESP) of C. sinensis, which induce inflammation. NDMA and ESP treatment increased proliferation by 146% and the proportion of cells in the G2/M phase by 37%. Moreover, the expression of the cell proliferation-related proteins E2F1, Ki-67, and cancer related protein cytokeratin 19 and Cox-2 increased in response to combined treatment with NDMA and ESP. The gap-junction proteins connexin (Cx) 43 and Cx26 increased. In contrast, Cx32 expression decreased in cells treated with NDMA and ESP. Silencing of Cx43 reduced cell proliferation and significantly suppressed Cx26 and Cox-2 expression. Conclusions: These results suggest that Cx43 is an important factor in CHCA induced by C. sinensis ESP and NDMA and further investigations targeting this pathway may allow prevention of this deadly disease. [ABSTRACT FROM AUTHOR]

Prevalence is a common epidemiological measure for assessing soil-transmitted helminth burden and forms the basis for much public-health decision-making. Standard diagnostic techniques are based on egg detection in stool samples through microscopy and these techniques are known to have poor sensitivity for individuals with low infection intensity, leading to poor sensitivity in low prevalence populations. PCR diagnostic techniques offer very high sensitivities even at low prevalence, but at a greater cost for each diagnostic test in terms of equipment needed and technician time and training. Pooling of samples can allow prevalence to be estimated while minimizing the number of tests performed. We develop a model of the relative cost of pooling to estimate prevalence, compared to the direct approach of testing all samples individually. Analysis shows how expected relative cost depends on both the underlying prevalence in the population and the size of the pools constructed. A critical prevalence level (approx. 31%) above which pooling is never cost effective, independent of pool size. When no prevalence information is available, there is no basis on which to choose between pooling and testing all samples individually. We recast our model of relative cost in a Bayesian framework in order to investigate how prior information about prevalence in a given population can be used to inform the decision to choose either pooling or full testing. Results suggest that if prevalence is below 10%, a relatively small exploratory prevalence survey (10–15 samples) can be sufficient to give a high degree of certainty that pooling may be relatively cost effective. [ABSTRACT FROM AUTHOR]

As part of a study to investigate drivers of dengue virus (DENV) transmission dynamics, this qualitative study explored whether DENV-infected residents of Iquitos, Peru, considered it acceptable (1) to participate in direct mosquito feeding experiments (lab-reared Aedes aegypti mosquitoes fed directly on human volunteers) and (2) to provide blood meals indirectly (Ae. aegypti fed on blood drawn from participants by venipuncture). Twelve focus group discussions (FGDs; 94 participants: 82 females and 12 males) were conducted in January 2014 to explore six themes: (1) concerns and preferences regarding direct mosquito feeds and blood draws, (2) comprehension of and misconceptions about study procedures, (3) motivating factors for participation, (4) acceptability of children’s participation, (5) willingness to provide multiple samples over several days, and (6) preference for direct feedings in homes versus the study laboratory. Results of FGDs, including one with 5 of 53 past direct mosquito feed participants, indicated that mosquito feeding procedures are acceptable to Iquitos residents when they are provided with information and a few key messages are properly reinforced. FGD participants’ concerns focused primarily on safety issues rather than discomfort associated with mosquito bites. A video explaining the study dramatically increased comprehension of the study procedures. The majority of participants expressed a preference for mosquito feeding over venipuncture. Adults supported child participation if the children themselves assented. For most participants, home feedings were preferred over those in a laboratory. A major impetus for participation was the idea that results would contribute to an improved understanding of DENV transmission in Iquitos. Findings from our study will support future large-scale studies that employ direct mosquito feeding, a low-risk, non-invasive procedure that is experimentally superior to artificial mosquito feeding methods. [ABSTRACT FROM AUTHOR]

Background: Tick feeding causes extreme morbidity and mortality to humans through transmission of pathogens and causes severe economic losses to the agricultural industry by reducing livestock yield. Salivary gland secretions are essential for tick feeding and thus, reducing or preventing saliva secretions into the vertebrate host is likely to reduce feeding and hinder pathogen life cycles. Unfortunately, the membrane physiology of tick salivary glands is underexplored and this gap in knowledge limits the development of novel therapeutics for inducing cessation of tick feeding. Methodology: We studied the influence of inward rectifier potassium (Kir) channel subtypes to the functional capacity of the isolated tick salivary gland through the use of a modified Ramsay assay. The secreted saliva was subsequently used for quantification of the elemental composition of the secreted saliva after the glands were exposed to K+ channel modulators as a measure of osmoregulatory capacity. Lastly, changes to blood feeding behavior and mortality were measured with the use of a membrane feeding system. Principal findings: In this study, we characterized the fundamental role of Kir channel subtypes in tick salivary gland function and provide evidence that pharmacological inhibition of these ion channels reduces the secretory activity of the salivary gland of Amblyomma americanum. The reduced secretory capacity of the salivary gland was directly correlated with a dramatic reduction of blood ingestion during feeding. Further, exposure to small-molecule modulators of Kir channel subtypes induced mortality to ticks that is likely resultant from an altered osmoregulatory capacity. Conclusions: Our data contribute to understanding of tick salivary gland function and could guide future campaigns aiming to develop chemical or reverse vaccinology technologies to reduce the worldwide burden of tick feeding and tick-vectored pathogens. [ABSTRACT FROM AUTHOR]

Background: Loa loa infection is endemic in limited areas of West-Central Africa. Loiasis has been associated with excess mortality, but clinical studies on its treatment are scant, particularly outside endemic areas, due to the rarity of cases diagnosed. Methodology/Principal findings: With this retrospective TropNet (European Network for Tropical Medicine and Travel Health) study, we aimed at outlining the treatment schedules followed by different reference centers for tropical medicine across Europe. We gathered information about 238 cases of loiasis, 165 of which had follow up data. The regimens followed by the different centers were heterogeneous. The drugs most frequently administered were: diethylcarbamazine alone (74/165, 45.1%), ivermectin alone (41/165, 25%), albendazole + ivermectin (21/164, 11.6%), ivermectin + diethylcarbamazine (16/165, 9.7%). Conclusions/Significance: The management of loiasis substantially differs across specialized travel clinics in Europe. These discrepancies could be due to different local protocols as well as to (un)availability of the drugs. An harmonization of clinical protocols for the treatment of loiasis would be suggested across reference centers for tropical medicine in Europe. [ABSTRACT FROM AUTHOR]

Background: HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals. Methodology: This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF). Principal Findings: 18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model. Conclusions: 18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP. Significance: Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls. [ABSTRACT FROM AUTHOR]

We conducted a retrospective study on mortality trends and risk factors in 781 naïve cases of advanced stage-2 sleeping sickness admitted between 1989 and 2012 at the National Reference Center for Human African Trypanosomiasis (HAT), Department of Neurology, Kinshasa University, Democratic Republic of Congo (DRC). Death was the outcome variable whereas age, gender, duration of disease, location of trypanosomes in body fluids, cytorachy, protidorachy, clinical status (assessed on a syndromic and functional basis) on admission, and treatment regimen were predictors in logistic regression models run at the 0.05 significance level. Death proportions were 17.2% in the standard melarsoprol schedule (3-series of intravenous melarsoprol on 3 successive days at 3.6 mg/kg/d, with a one-week interval between the series, ARS 9); 12.1% in the short schedule melarsoprol (10 consecutive days of intravenous melarsoprol at 2.2 mg/kg/d, ARS 10), 5.4% in the first-line eflornithine (14 days of eflornithine at 400 mg/kg/d in 4 infusions a day DFMO B), 9.1% in the NECT treatment regimen (eflornithine for 7 days at 400, mg/kg/d in 2 infusions a day combined with oral nifurtimox for 10 days at 15 mg/kg/d in 3 doses a day); and high (36%) in the group with select severely affected patients given eflornithine because of their clinical status on admission, at the time when this expensive drug was kept for treatment of relapses (14 days at 400 mg/kg/d in 4 infusions a day, DFMO A). After adjusting for treatment, death odds ratios were as follows: 10.40 [(95% CI: 6.55–16.51); p = .000] for clinical dysfunction (severely impaired clinical status) on admission, 2.14 [(95% CI: 1.35–3.39); p = .001] for high protidorachy, 1.99 [(95% CI: 1.18–3.37); p = .010] for the presence of parasites in the CSF and 1.70 [(95% CI: 1.03–2.81); p = .038] for high cytorachy. A multivariable analysis within treatment groups retained clinical status on admission (in ARS 9, ARS 10 and DFMO B groups) and high protidorachy (in ARS 10 and DFMO B groups) as significant predictors of death. The algorithm for initial clinical status assessment used in the present study may serve as the basis for further development of standardized assessment tools relevant to the clinical management of HAT and information exchange in epidemiological reports. [ABSTRACT FROM AUTHOR]

Background: Adult schistosomes have a well-developed alimentary tract comprising an oral sucker around the mouth, a short esophagus and a blind ending gut. The esophagus is not simply a muscular tube for conducting blood from the mouth to gut but is divided into compartments, surrounded by anterior and posterior glands, where processing of ingested blood is initiated. Self-cure of rhesus macaques from a Schistosoma japonicum infection appears to operate by blocking the secretory functions of these glands so that the worms cease feeding and slowly starve to death. Here we use subtractive RNASeq to characterise the genes encoding the principal secretory products of S. japonicum esophageal glands, preparatory to evaluating their relevance as targets of the self-cure process. Methodology/Principal findings: The heads and a small portion of the rear end of male and female S. japonicum worms were separately enriched by microdissection, for mRNA isolation and library construction. The sequence reads were then assembled de novo using Trinity and those genes enriched more than eightfold in the head preparation were subjected to detailed bioinformatics analysis. Of the 62 genes selected from the male heads, more than one third comprised MEGs encoding secreted or membrane-anchored proteins. Database searching using conserved motifs revealed that the MEG-4 and MEG-8/9 families had counterparts in the bird schistosome Trichobilharzia regenti, indicating an ancient association with blood processing. A second group of MEGs, including a MEG-26 family, encoded short peptides with amphipathic properties that most likely interact with ingested host cell membranes to destabilise them. A number of lysosomal hydrolases, two protease inhibitors, a secreted VAL and a putative natterin complete the line-up. There was surprisingly little difference between expression patterns in males and females despite the latter processing much more blood. Significance/Conclusions: The mixture of approximately 40 proteins specifically secreted by the esophageal glands is responsible for initiating blood processing in the adult worm esophagus. They comprise the potential targets for the self-cure process in the rhesus macaque, and thus represent a completely new cohort of secreted proteins that can be investigated as vaccine candidates. [ABSTRACT FROM AUTHOR]

Background: By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. Methodology/Principal findings: This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design. Conclusion/Significance: Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Evidence of an adverse influence of soil transmitted helminth (STH) infections on cognitive function and educational loss is equivocal. Prior meta-analyses have focused on randomized controlled trials only and have not sufficiently explored the potential for disparate influence of STH infection by cognitive domain. We re-examine the hypothesis that STH infection is associated with cognitive deficit and educational loss using data from all primary epidemiologic studies published between 1992 and 2016. Methods: Medline, Biosis and Web of Science were searched for original studies published in the English language. Cognitive function was defined in four domains (learning, memory, reaction time and innate intelligence) and educational loss in two domains (attendance and scholastic achievement). Pooled effect across studies were calculated as standardized mean differences (SMD) to compare cognitive and educational measures for STH infected/non-dewormed children versus STH uninfected /dewormed children using Review Manager 5.3. Sub-group analyses were implemented by study design, risk of bias (ROB) and co-prevalence of Schistosoma species infection. Influential studies were excluded in sensitivity analysis to examine stability of pooled estimates. Findings: We included 36 studies of 12,920 children. STH infected/non-dewormed children had small to moderate deficits in three domains—learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01–0.03) compared to STH-uninfected/dewormed children. There were no differences by infection/treatment status for reaction time, school attendance and scholastic achievement (SMD: -0.26 to -0.16, P = 0.06–0.19). Heterogeneity of the pooled effects in all six domains was high (P<0.01; I2 = 66–99%). Application of outlier treatment reduced heterogeneity in learning domain (P = 0.12; I2 = 33%) and strengthened STH-related associations in all domains but intelligence (SMD: -0.20, P = 0.09). Results varied by study design and ROB. Among experimental intervention studies, there was no association between STH treatment and educational loss/performance in tests of memory, reaction time and innate intelligence (SMD: -0.27 to 0.17, P = 0.18–0.69). Infection-related deficits in learning persisted within design/ROB levels (SMD: -0.37 to -52, P<0.01) except for pre-vs post intervention design (n = 3 studies, SMD = -0.43, P = 0.47). Deficits in memory, reaction time and innate intelligence persisted within observational studies (SMD: -0.23 to -0.38, all P<0.01) and high ROB strata (SMD:-0.37 to -0.83, P = 0.07 to <0.01). Further, in Schistosoma infection co-prevalent settings, associations were generally stronger and statistically robust for STH-related deficits in learning, memory and reaction time tests(SMD:-0.36 to -0.55, P = 0.003–0.02). STH-related deficits in school attendance and scholastic achievement was noted in low (SMD:-0.57, P = 0.05) and high ROB strata respectively. Interpretation: We provide evidence of superior performance in five of six educational and cognitive domains assessed for STH uninfected/dewormed versus STH infected/not-dewormed school-aged children from helminth endemic regions. Cautious interpretation is warranted due to high ROB in some of the primary literature and high between study variability in most domains. Notwithstanding, this synthesis provides empirical support for a cognitive and educational benefit of deworming. The benefit of deworming will be enhanced by strategically employing, integrated interventions. Thus, multi-pronged inter-sectoral strategies that holistically address the environmental and structural roots of child cognitive impairment and educational loss in the developing world may be needed to fully realize the benefit of mass deworming programs. [ABSTRACT FROM AUTHOR]

Background: Within the context of a field trial conducted by the Cuban vector control program (AaCP), we assessed acceptability of insecticide-treated curtains (ITCs) and residual insecticide treatment (RIT) with deltamethrin by the community. We also assessed the potential influence of interviewees’ risk perceptions for getting dengue and disease severity. Methodology/principal findings: We embedded a qualitative study using in-depth interviews in a cluster randomized trial (CRT) testing the effectiveness of ITCs and RIT in Santiago de Cuba. In-depth interviews (N = 38) were conducted four and twelve months after deployment of the tools with people who accepted the tools, who stopped using them and who did not accept the tools. Data analysis was deductive. Main reasons for accepting ITCs at the start of the trial were perceived efficacy and not being harmful to health. Constraints linked to manufacturer instructions were the main reason for not using ITCs. People stopped using the ITCs due to perceived allergy, toxicity and low efficacy. Few heads of households refused RIT despite the noting reasons for rejection, such as allergy, health hazard and toxicity. Positive opinions of the vector control program influenced acceptability of both tools. However, frequent insecticide fogging as part of routine AaCP vector control actions diminished perceived efficacy of both tools and, therefore, acceptability. Fifty percent of interviewees did feel at risk for getting dengue and considered dengue a severe disease. However, this did not appear to influence acceptability of ITCs or RIT. Conclusion/significance: Acceptability of ITCs and RIT was linked to acceptability of AaCP routine vector control activities. However, uptake and use were not always an indication of acceptability. Factors leading to acceptability may be best identified using qualitative methods, but more research is needed on the concept of acceptability and its measurement. [ABSTRACT FROM AUTHOR]

The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation. A comprehensive survey questionnaire was developed and sent to a group of 117 trainees supported by TDR who had completed their degree (masters or PhD) between 2000 and 2012; of these, seventy seven (77) responded. Most of the respondents (80%) rated TDR support as a very important factor that influenced their professional career achievements. The “brain drain” phenomenon towards high-income countries was particularly low amongst TDR grantees: the rate of return to their region of origin upon completion of their degree was 96%. A vast majority of respondents are still working in research (89%), with 81% of respondents having participated in multidisciplinary research activities; women engaged in multidisciplinary collaboration to a higher extent than men. However, only a minority of all have engaged in intersectoral collaboration, an aspect that would require further study. The post-degree career choices made by the respondents were strongly influenced by academic considerations. At the time of the survey, 92% of all respondents hold full-time positions, mainly in the public sector. Almost 25% of the respondents reported that they had influenced policy and practice changes. Some of the challenges and opportunities faced by trainees at various stages of their research career have been identified. Modalities to overcome these will require further investigation. The survey evidenced how TDR’s research capacity grant programmes made a difference on researchers’ career development and on south-south collaborations, by strengthening and localizing research capacity in lower income regions, and also showed there is more that needs to be done. The factors involved, challenges and lessons learnt may help donors and policy makers improve their future interventions with regard to designing capacity strengthening programmes and setting funding priorities. [ABSTRACT FROM AUTHOR]

Background: Community drug distributors or neglected tropical disease (NTD) volunteers have played a crucial role in ensuring the success of mass drug administration (MDA) programs using preventive chemotherapy (PC) for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminths. In recent years however, a noticeable decline in motivation of some of these volunteers has been perceived, potentially negatively impacting the success of these programs. Potential hypotheses for this change in motivation include the long duration of many MDA programs, the change in sociocultural environments as well as the changes to the programs over time. This literature review identifies factors that affect NTD volunteer performance and motivation, which may be used to influence and improve future programming. Methodology/Principal findings: A systematic search was conducted to identify studies published between January 1995 and September 2016 that investigate factors pertaining to volunteer motivation and performance in NTD drug distribution programs. Searches from several databases and grey literature yielded 400 records, of which 28 articles from 10 countries met the inclusion criteria. Quality assessment of studies was performed using the Critical Appraisal Skills Programme(CASP) checklist. Data pertaining to motivation, performance, retention and satisfaction was extracted and examined for themes. Recurring themes in the literature included monetary and material incentives, intrinsic motivation, gender, cost to participate, and health systems and community support. Of these, community support and the health system were found to be particularly impactful. Very few studies were found to explicitly look at novel incentives for volunteers and very few studies have considered the out of pocket and opportunity costs that NTD volunteers bear carrying out their tasks. Conclusions/Significance: There is currently great interest in incorporating more attractive incentive schemes for NTD volunteers. However, our results show that the important challenges that volunteers face (cultural, health systems, financial and community related) may have less to do with financial incentives and may actually have a larger impact on their motivation than has previously been understood. Further integration of NTD programs into existing health systems is expected to improve the NTD volunteer working environment. Relevant community engagement related to the MDA program should also provide the supportive environment needed in the community to support NTD volunteers. Programs need to consider these issues to improve working conditions for NTD volunteers. [ABSTRACT FROM AUTHOR]

Target Product Profiles (TPPs) are process tools providing product requirements to guide researchers, developers and manufacturers in their efforts to develop effective and useful products such as biologicals, drugs or diagnostics. During a WHO Stakeholders Meeting on Taenia solium diagnostics, several TPPs were initiated to address diagnostic needs for different stages in the parasite’s transmission (taeniasis, human and porcine cysticercosis). Following the meeting, draft TPPs were completed and distributed for consultation to 100 people/organizations, including experts in parasitology, human and pig cysticercosis, diagnostic researchers and manufacturers, international organizations working with neglected or zoonotic diseases, Ministries of Health and Ministries of Livestock in some of the endemic countries, WHO regional offices and other interested parties. There were 53 respondents. All comments and feedback received were considered and discussions were held with different experts according to their area of expertise. The comments were consolidated and final TPPs are presented here. They are considered to be live documents which are likely to undergo review and updating in the future when new knowledge and technologies become available. [ABSTRACT FROM AUTHOR]

The article presents profile of scientist Margaret A. Stirewalt, who is dedicated to the study of tropical medicine. Topics include obtaining a doctorate degree in 1938 from the University of Virginia; Stirewalt's seminal research on the study of schistosomiasis; and establishment of a schistosomiasis laboratory at the Biomedical Research Institute.

Background: Neuroinvasive larvae of the worldwide occurring zoonotic roundworms Toxocara canis and T. cati may induce neurotoxocarosis (NT) in humans, provoking a variety of symptoms including cognitive deficits as well as neurological dysfunctions. An association with neuropsychological disorders has been discussed. Similar symptoms have been described in T. canis-infected mice, whereas data on T. cati-induced NT are rare. Therefore, it was aimed to obtain insights into the impact on neurobehaviour as well as progression of neurological symptoms and behavioural alterations during the course of NT directly comparing T. canis- and T. cati-infected mice as models for human NT. Methodology/Principal findings: C57BL/6 mice were orally infected with 2000 embryonated T. canis or T. cati eggs, respectively, the control group received tap water. Mice were screened weekly for neurobehavioural alterations and memory function starting one day prior infection until 97 days post infection (pi; T. canis-infection) and day 118 pi (T. cati-infection, uninfected control). Mostly motoric and neurological parameters were affected in T. canis-infected mice starting day 20 pi with severe progression accompanied by stereotypical circling. In contrast, T. cati-infected mice mostly showed reduced response to sudden sound stimulus (indicator for excitability) and flight behaviour starting day 6 pi. Interestingly, enhanced grooming behaviour was observed exclusively in T. cati-infected mice, indicating a possible role of neurotransmitter dysregulation. Reduced exploratory behaviour and memory impairment was observed in both infection groups with delayed onset and less severe progression in T. cati- compared to T. canis-infected mice. Conclusions/Significance: Results highlight the need to consider T. cati beside T. canis as causative agent of human NT. Findings provide valuable hints towards differences in key regulatory mechanisms during T. canis- and T. cati-induced NT, contributing to a comprehensive picture and consequently a broader understanding of NT, which will aid in developing strategies towards prevention in addition to novel diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei (Bp) causes the disease melioidosis. The main cause of mortality in this disease is septic shock triggered by the host responding to lipopolysaccharide (LPS) components of the Gram-negative outer membrane. Bp LPS is thought to be a weak inducer of the host immune system. LPS from several strains of Bp were purified and their ability to induce the inflammatory mediators TNF-α and iNOS in murine macrophages at low concentrations was investigated. Innate and adaptive immunity qPCR arrays were used to profile expression patterns of 84 gene targets in response to the different LPS types. Additional qPCR validation confirmed large differences in macrophage response. LPS from a high-virulence serotype B strain 576a and a virulent rough central nervous system tropic strain MSHR435 greatly induced the innate immune response indicating that the immunopathogenesis of these strains is different than in infections with strains similar to the prototype strain 1026b. The accumulation of autophagic vesicles was also increased in macrophages challenged with highly immunogenic Bp LPS. Gene induction and concomitant cytokine secretion profiles of human PBMCs in response to the various LPS were also investigated. MALDI-TOF/TOF was used to probe the lipid A portions of the LPS, indicating substantial structural differences that likely play a role in host response to LPS. These findings add to the evolving knowledge of host-response to bacterial LPS, which can be used to better understand septic shock in melioidosis patients and in the rational design of vaccines. [ABSTRACT FROM AUTHOR]

Background: Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. Methodology: Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. Principal findings: 345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. Conclusions: Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve damage do not improve. Future studies should test giving azathioprine in the treatment of nerve damage and giving a higher dose for 48 weeks to patients. These findings highlight the difficulty in switching off leprosy inflammation and the need for better treatments for reactions and nerve damage. There is also a research need to identify patients who have recurrences and optimize treatments for them. Patients with recurrences may benefit from combined treatment with steroids and azathioprine. We have also shown that significant numbers of patients treated with steroids develop adverse effects and this needs to be highlighted in leprosy programmes. Research is needed to identify patients who do not respond to steroid treatment and develop alternative treatments for them. Trial Registration: ClinicalTrials.gov This trial was registered with the Indian Council of Medical research clinical Trial register as a clinical trial Number— [ABSTRACT FROM AUTHOR]

Background: Trachomatous trichiasis (TT), inturned eyelashes from repeated infection with Chlamydia trachomatis, is the leading infectious cause of blindness in the world. Though surgery will correct entropion caused by trachoma, uptake of TT surgery remains low. In this case-control study, we identify barriers that prevent TT patients from receiving sight-saving surgery. Methodology/Principal Findings: Participants were selected from a database of TT cases who did (acceptors) and did not (non-acceptors) have surgery as of August 2015. We developed an in-home interview questionnaire, using open and closed-ended questions on perceived barriers to accessing surgical services. We compared responses between the acceptors and non-acceptors, examining differences in reasons for and against surgery, sources of TT information, and suggestions for improving surgical delivery. 167 participants (mean age 61 years, 79.7% females) were interviewed. Compared to acceptors, non-acceptors were more likely to report they had no one to accompany them to surgery (75.3% vs. 42.6%, p<0.0001), they could manage TT on their own (69.9% vs. 31.5%, p<0.0001), and the surgery camp was too far (53.4% vs. 28.7%, p = 0.001). Over 90% of both acceptors and non-acceptors agreed on the benefits of having surgery. Fear of surgery was the biggest barrier stated by both groups. Despite this fear, acceptors were more likely than non-acceptors to also report fear of losing further vision without surgery. Conclusions/Significance: Barriers included access issues, familial and/or work responsibilities, the perception that self-management was sufficient, and lack of education about surgery. Fear of surgery was the biggest barrier facing both acceptors and non-acceptors. Increasing uptake will require addressing how surgery is presented to community residents, including outlining treatment logistics, surgical outcomes, and stressing the risk of vision loss. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis is a common helminthic infection of the central nervous system and an important cause of adult-onset epilepsy in endemic countries. However, few studies have examined associations between neurologic symptoms, serology and radiographic findings on a community-level. Methodology: We conducted a population-based study of resident’s ≥2 years old in a highly endemic village in Peru (pop. 454). We applied a 14 -question neurologic screening tool and evaluated serum for antibodies against Taenia solium cysticercosis using enzyme-linked immunoelectrotransfer blot (LLGP-EITB). We invited all residents ≥18 years old to have non-contrast computerized tomography (CT) of the head. Principal findings: Of the 385 residents who provided serum samples, 142 (36.9%) were seropositive. Of the 256 residents who underwent CT scan, 48 (18.8%) had brain calcifications consistent with NCC; 8/48 (17.0%) reported a history of headache and/or seizures. Exposure to T. solium is very common in this endemic community where 1 out of 5 residents had brain calcifications. However, the vast majority of people with calcifications were asymptomatic. Conclusion: This study reports a high prevalence of NCC infection in an endemic community in Peru and confirms that a large proportion of apparently asymptomatic residents have brain calcifications that could provoke seizures in the future. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that leprosy multi-drug therapy (MDT) does not stop the progression of nerve function impairment. There are no prospective studies investigating the evolution of nerve anatomic abnormalities after treatment. We examined leprosy patients aiming to investigate the evolution of nerve ultrasonography (US) abnormalities and the risk factors for poor outcomes after MDT. Methodology/Principal findings: We performed bilateral US of the ulnar (U), median (M) and common fibular (CF) nerves in 9 paucibacillary (PB) and 64 multibacillary (MB) patients before and after MDT. Forty-two patients had leprosy reactions (type 1, type 2, acute neuritis) during the study. We analyzed nerve maximum cross-sectional areas (CSA), echogenicity and Doppler signal. Poor outcomes included a post-treatment CSA above normal limits with a reduction of less than 30% (U, M) or 40% (CF) from the baseline, echogenicity abnormalities or intraneural Doppler in the post-treatment study. We found that PB and patients without reactions showed significant increases in CSA at CF, whereas MB and patients with reactions had CSA reduction in some nerves after treatment (p<0.05). Despite this reduction, we observed a greater frequency of poor CSA outcomes in the MB compared to the PB (77.8% and 40.6%; p>0.05) and in the patients with reactions compared to those without (66.7% and 38.7%; p<0.05). There was significantly higher odds ratio (7.75; 95%CI: 1.56–38.45) for poor CSA outcomes only for M nerve in patients with reactions. Poor echogenicity outcomes were more frequent in MB (59.4%) compared to PB (22.2%) (p<0.05). There was significant association between poor Doppler outcomes and neuritis. Gender, disease duration, and leprosy classification were not significant risk factors for poor outcomes in CSA, echogenicity or Doppler. Conclusions/Significance: US nerve abnormalities can worsen after treatment despite the leprosy classification or the presence of reactions. [ABSTRACT FROM AUTHOR]