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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: Two surgical options are available for cystic echinococcosis (CE). The two principal approaches are radical (resection of the cyst) and conservative (evacuation of the cyst content and partial removal of the cyst capsule). Here, we describe a standardized endocystectomy technique for hepatic echinococcosis. Subjects and methods: Twenty-one patients (male/female: 4/3; median age: 28 years) with uncomplicated, isolated hepatic CE (cyst stages WHO CE1, 2, 3a, and 3b) that were treated with the standardized endocystectomy described in this paper. Before the operation and during the follow-up period (mean: 33.8 months, median: 24 months), patients underwent clinical and sonographical and/or magnetic resonance imaging assessment during regular visits managed by an interdisciplinary team. Results: Forty-seven cysts were treated with the standardized endocystectomy technique. The median number of cysts per patient was two (range: 1–8). Nine patients (43%) had a single cystic lesion. The median operation time was 165 minutes and the median intraoperative bleeding volume was 200 mL. The median hospital stay was nine days (range: 6–28 days). Morbidity (Clavien-Dindo III) occurred in four patients (19%). No mortality and no recurrence were found during the median follow-up time of 24 months. Conclusions: The standardized endocystectomy technique presented is a safe procedure with acceptable morbidity, no mortality, and without recurrences in our patient series. Important components of our CE management are interdisciplinary patient care, adequate diagnostic work-ups, and regular pre- and postoperative visits, including long-term follow-up for early and reliable capture of recurrences. [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]

The article presents a case study of a 26-year-old female who was brought to the local schistosomiasis-specialized hospital in China for diagnosis and treatment after complaining of distention and abdominal pain for over a month. The patient was suspected to have advanced schistosomiasis due to her symptoms and blood test results as well as contact history. Early operation and effective decompression are also considered the major factors resulting in reversal of liver fibrosis for the case.

Background: Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria. Methods: Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012–2014. These data were used in conjunction with epidemiological data from Austria’s national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE. Results: In Austria, total modelled direct costs were 486,598€ (95%CI 341,825€ – 631,372€) per year for CE, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832€ (25th– 75th percentile: 23,197€ - 31,220€) and 62,777€ (25th– 75th percentile: 60,806€ - 67,867€) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253€ (25th– 75th percentile: 8,555€ - 24,832€) and 1,786€ (25th– 75th percentile: 736€ - 2,146€) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs. Conclusions: This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs. [ABSTRACT FROM AUTHOR]

Background: Trachomatous trichiasis (TT) will continue to develop among those people who have had repeated infections after active trachoma is controlled. Detecting and treating affected individuals will remain necessary for years; a long “tail” of incident cases is anticipated. As the prevalence of TT declines, there will be fewer cases available for training trachoma graders (TG), necessitating alternative methods. Methodology/Principal findings: Prospective, diagnostic accuracy study assessing sensitivity and specificity of 3D and 2D photography as a tool for training TG to detect TT. Individuals with TT in Ethiopia were examined, and 2D and 3D clinical images taken. Images were independently graded by four graders for presence or absence of trichiasis and compared to field grading. We recruited 153 participants. Clinical assessments and images were available for 306 eyes. Trichiasis was identified in 204 eyes by field grading. Image grading was performed on a selection of 262 eyes (131 with trichiasis). Most eyes with trichiasis had minor trichiasis (94/131). Pooled sensitivity was 88.3% (3D) and 98.0% (2D); pooled specificity was 59.8% (3D) and 26.8% (2D). 3D photo grading was 33.0% more specific than the 2D photo grading (p = 0.0002). The overall Kappa scores were 0.48 (3D) and 0.25 (2D). We trained 26 novice TG in Ethiopia using 3D images. They were tested on a 3D images set and had 71.4% agreement (kappa 0.46), relative to an expert. They were then tested examining 50 people, and had 86.8% agreement (kappa 0.75). We also tested 27 experienced TG on the same cases (86.4% agreement, kappa 0.75). There was no difference in performance between groups (p = 0.76). All participants preferred 3D over 2D images for training. Conclusions/Significance: The slightly higher sensitivity of 2D photos comes at considerable cost in specificity. Training with 3D images enabled novice TG to identify cases as well as experienced TG. 3D were preferred to conventional 2D photos for training. Standardized 3D images of TT could be a useful tool for training TG, in settings where there are now few TT cases. [ABSTRACT FROM AUTHOR]

Background: ARFI elastrography has been used as a noninvasive method to assess the severity of liver fibrosis in viral hepatitis, although with few studies in schistosomiasis mansoni. We aimed to evaluate the performance of point shear wave elastography (pSWE) for predicting significant periportal fibrosis (PPF) in schistosomotic patients and to determine its best cutoff point. Methodology/principal findings: This cross-sectional study included 358 adult schistosomotic patients subjected to US and pSWE on the right lobe. Two hundred two patients (62.0%) were women, with a median age of 54 (ranging 18–92) years. The pSWE measurements were compared to the US patterns of PPF, as gold standard, according to the Niamey classification. The performance of pSWE was calculated as the area under the ROC curve (AUC). Patients were further classified into two groups: 86 patients with mild PPF and 272 patients with significant PPF. The median pSWE of the significant fibrosis group was higher (1.40 m/s) than that of mild fibrosis group (1.14 m/s, p<0.001). AUC was 0.719 with ≤1.11 m/s as the best cutoff value for excluding significant PPF. Sensitivity and negative predictive values were 80.5% and 40.5%, respectively. Whereas, for confirming significant PPF, the best cutoff value was >1.39 m/s, with specificity of 86.1% and positive predictive value of 92.0%. Conclusions/significance: pSWE was able to differentiate significant from mild PPF, with better performance to predict significant PPF. [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]

Manipulation of natural mosquito populations using the endosymbiotic bacteria Wolbachia is being investigated as a novel strategy to reduce the burden of mosquito-borne viruses. To evaluate the efficacy of these interventions, it will be critical to determine Wolbachia infection frequencies in Aedes aegypti mosquito populations. However, current diagnostic tools are not well-suited to fit this need. Morphological methods cannot identify Wolbachia, immunoassays often suffer from low sensitivity and poor throughput, while PCR and spectroscopy require complex instruments and technical expertise, which restrict their use to centralized laboratories. To address this unmet need, we have used loop-mediated isothermal amplification (LAMP) and oligonucleotide strand displacement (OSD) probes to create a one-pot sample-to-answer nucleic acid diagnostic platform for vector and symbiont surveillance. LAMP-OSD assays can directly amplify target nucleic acids from macerated mosquitoes without requiring nucleic acid purification and yield specific single endpoint yes/no fluorescence signals that are observable to eye or by cellphone camera. We demonstrate cellphone-imaged LAMP-OSD tests for two targets, the Aedes aegypti cytochrome oxidase I (coi) gene and the Wolbachia surface protein (wsp) gene, and show a limit of detection of 4 and 40 target DNA copies, respectively. In a blinded test of 90 field-caught mosquitoes, the coi LAMP-OSD assay demonstrated 98% specificity and 97% sensitivity in identifying Ae. aegypti mosquitoes even after 3 weeks of storage without desiccant at 37°C. Similarly, the wsp LAMP-OSD assay readily identified the wAlbB Wolbachia strain in field-collected Aedes albopictus mosquitoes without generating any false positive signals. Modest technology requirements, minimal execution steps, simple binary readout, and robust accuracy make the LAMP-OSD-to-cellphone assay platform well suited for field vector surveillance in austere or resource-limited conditions. [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: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. Methods: Children aged 5–18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. Findings: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. Interpretation: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. Trial registration: ClinicalTrials.gov No [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: European liver fluke Opisthorchis felineus, causing opisthorchiasis disease, is widespread in Russia, Ukraine, Kazakhstan and sporadically detected in the EU countries. O. felineus infection leads to hepatobiliary pathological changes, cholangitis, fibrosis and, in severe cases, malignant transformation of bile ducts. Due to absence of specific symptoms, the infection is frequently neglected for a long period. The association of opisthorchiasis with almost incurable bile duct cancer and rising international migration of people that increases the risk of the parasitic etiology of liver fibrosis in non-endemic regions determine high demand for development of approaches to opisthorchiasis detection. Methodology/Principal findings: In vivo magnetic resonance imaging and spectroscopy (MRI and MRS) were applied for differential assessment of hepatic abnormalities induced by O. felineus in an experimental animal model. Correlations of the MR-findings with the histological data as well as the data of the biochemical analysis of liver tissue were found. MRI provides valuable information about the severity of liver impairments induced by opisthorchiasis. An MR image of O. felineus infected liver has a characteristic pattern that differs from that of closely related liver fluke infections. 1H and 31P MRS in combination with biochemical analysis data showed that O. felineus infection disturbed hepatic metabolism of the host, which was accompanied by cholesterol accumulation in the liver. Conclusions: A non-invasive approach based on the magnetic resonance technique is very advantageous and may be successfully used not only for diagnosing and evaluating liver damage induced by O. felineus, but also for investigating metabolic changes arising in the infected organ. Since damages induced by the liver fluke take place in different liver lobes, MRI has the potential to overcome liver biopsy sampling variability that limits predictive validity of biopsy analysis for staging liver fluke-induced fibrosis. [ABSTRACT FROM AUTHOR]

Background: The globally important Zika, dengue and chikungunya viruses are primarily transmitted by the invasive mosquitoes, Aedes aegypti and Aedes albopictus. In Australia, there is an increasing risk that these species may invade highly urbanized regions and trigger outbreaks. We describe the development of a Rapid Surveillance for Vector Presence (RSVP) system to expedite presence- absence surveys for both species. Methodology/Principal findings: We developed a methodology that uses molecular assays to efficiently screen pooled ovitrap (egg trap) samples for traces of target species ribosomal RNA. Firstly, specific real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were developed which detect a single Ae. aegypti or Ae. albopictus first instar larva in samples containing 4,999 and 999 non-target mosquitoes, respectively. ImageJ software was evaluated as an automated egg counting tool using ovitrap collections obtained from Brisbane, Australia. Qualitative assessment of ovistrips was required prior to automation because ImageJ did not differentiate between Aedes eggs and other objects or contaminants on 44.5% of ovistrips assessed, thus compromising the accuracy of egg counts. As a proof of concept, the RSVP was evaluated in Brisbane, Rockhampton and Goomeri, locations where Ae. aegypti is considered absent, present, and at the margin of its range, respectively. In Brisbane, Ae. aegypti was not detected in 25 pools formed from 477 ovitraps, comprising ≈ 54,300 eggs. In Rockhampton, Ae. aegypti was detected in 4/6 pools derived from 45 ovitraps, comprising ≈ 1,700 eggs. In Goomeri, Ae. aegypti was detected in 5/8 pools derived from 62 ovitraps, comprising ≈ 4,200 eggs. Conclusions/Significance: RSVP can rapidly detect nucleic acids from low numbers of target species within large samples of endemic species aggregated from multiple ovitraps. This screening capability facilitates deployment of ovitrap configurations of varying spatial scales, from a single residential block to entire suburbs or towns. RSVP is a powerful tool for surveillance of invasive Aedes spp., validation of species eradication and quality assurance for vector control operations implemented during disease outbreaks. [ABSTRACT FROM AUTHOR]

The dispersal patterns of mosquito vectors are important drivers of vector-borne infectious disease dynamics and understanding movement patterns is pivotal to devise successful intervention strategies. Here, we investigate the dispersal patterns of two globally important mosquito vectors, Aedes albopictus and Culex quinquefasciatus, by marking naturally-occurring larvae with stable isotopes (13C or 15N). Marked individuals were captured with 32 CDC light trap, 32 gravid trap, and 16 BG Sentinel at different locations within two-kilometer radii of six larval habitats enriched with either 13C or 15N. In total, 720 trap nights from July to August 2013 yielded a total of 32,140 Cx. quinquefasciatus and 7,722 Ae. albopictus. Overall, 69 marked female mosquitoes and 24 marked male mosquitoes were captured throughout the study period. The distance that Cx. quinquefasciatus females traveled differed for host-seeking and oviposition-seeking traps, with females seeking oviposition sites traveling further than those seeking hosts. Our analysis suggests that 41% of Cx. quinquefasciatus females that were host-seeking occurred 1–2 kilometer from their respective natal site, while 59% remained within a kilometer of their natal site. In contrast, 59% of Cx. quinquefasciatus females that were seeking oviposition sites occurred between 1–2 kilometer away from their larval habitat, while 15% occurred > 2 kilometer away from their natal site. Our analysis estimated that approximately 100% of Ae. albopictus females remained within 1 km of their respective natal site, with 79% occurring within 250m. In addition, we found that male Ae. albopictus dispersed farther than females, suggesting male-biased dispersal in this Ae. albopictus population. This study provides important insights on the dispersal patterns of two globally relevant vector species, and will be important in planning next generation vector control strategies that mitigate mosquito-borne disease through sterile insect techniques, novel Wolbachia infection, and gene drive strategies. [ABSTRACT FROM AUTHOR]

Background: Taenia solium inflicts substantial neurologic disease and economic losses on rural communities in many developing nations. “Ring-strategy” is a control intervention that targets treatment of humans and pigs among clusters of households (rings) that surround pigs heavily infected with cysticerci. These pigs are typically identified by examining the animal’s tongue for cysts. However, as prevalence decreases in intervened communities, more sensitive methods may be needed to identify these animals and to maintain control pressure. The purpose of this study was to evaluate ultrasonography as an alternative method to detect pigs heavily infected with T. solium cysts. Methodology/Principal Findings: We purchased 152 pigs representing all seropositive animals villagers were willing to sell from eight communities (pop. 2085) in Piura, Peru, where T. solium is endemic. Tongue and ultrasound examinations of the fore and hind-limbs were performed in these animals, followed by necropsy with fine dissection as gold standard to determine cyst burden. We compared the sensitivity and specificity of ultrasonography with tongue examination for their ability to detect heavy infection (≥ 100 viable cysts) in pigs. Compared to tongue examination, ultrasonography was more sensitive (100% vs. 91%) but less specific (90% vs. 98%), although these differences were not statistically significant. The greater sensitivity of ultrasound resulted in detection of one additional heavily infected pig compared to tongue examination (11/11 vs. 10/11), but resulted in more false positives (14/141 vs. 3/141) due to poor specificity. Conclusions/Significance: Ultrasonography was highly sensitive in detecting heavily infected pigs and may identify more rings for screening or treatment compared to tongue examination. However, the high false positive rate using ultrasound would result in substantial unnecessary treatment. If specificity can be improved with greater operator experience, ultrasonography may benefit ring interventions where control efforts have stalled due to inadequate sensitivity of tongue examination. [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]

Extraparenchymal neurocysticercosis has an aggressive course because cysts in the cerebrospinal fluid compartments induce acute inflammatory reactions. The relationships between symptoms, imaging findings, lesion type and location remain poorly understood. In this retrospective clinical records-based study, we describe the clinical symptoms, magnetic resonance imaging features, and cyst distribution in the CSF compartments of 36 patients with extraparenchymal neurocysticercosis. Patients were recruited between 1995 and 2010 and median follow up was 38 months. During all the follow up time we found that 75% (27/36) of the patients had symptoms related to raised intracranial pressure sometime, 72.2% (26/36) cysticercotic meningitis, 61.1% (22/36) seizures, and 50.0% (18/36) headaches unrelated to intracranial pressure. Regarding lesion types, 77.8% (28/36) of patients presented with grape-like cysts, 22.2% (8/36) giant cysts, and 61.1% (22/36) contrast-enhancing lesions. Hydrocephalus occurred in 72.2% (26/36) of patients during the follow-up period. All patients had cysts in the subarachnoid space and 41.7% (15/36) had at least one cyst in some ventricle. Cysts were predominantly located in the posterior fossa (31 patients) and supratentorial basal cisterns (19 patients). The fourth ventricle was the main compromised ventricle (10 patients). Spinal cysts were more frequent than previously reported (11.1%, 4/36). Our findings are useful for both diagnosis and treatment selection in patients with neurocysticercosis. [ABSTRACT FROM AUTHOR]

Background: Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols. Results: Here, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK). AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus. Conclusion: The present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses. [ABSTRACT FROM AUTHOR]

Mycetoma is a devastating, neglected tropical disease characterised by extensive tissue involvement resulting in destruction, deformities and disabilities in the affected patients. The hand is commonly affected by mycetoma thus compromises its functionality and hinder the patient’s daily activities of living. In this communication, we report on 533 patients with hand mycetoma managed over a period of 24 years at the Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan. Eumycetoma was the commonest type of mycetoma (83.3%) encountered. Males were predominately affected (69.2%) with a sex ratio of 2.2:1. The majority of the patients (84%) were young adult below the age of 40 years old at presentation. The generality of patients (86.4%) were from the Sudan mycetoma belt. Children and adolescents (28.1%), farmers (18.2%) and workers (17.4%) were more frequently affected. The majority of patients (67.4%) had disease duration of less than 5 years at presentation. The study, did not document significant history of local trauma, familial tendency, concomitant medical diseases or other predisposing cause for mycetoma in this population. Pain (23.1%) was not a disease feature in this series and 52% of patients had past surgery for mycetoma and recurrence. The right hand was affected most (60.4%), and 64% of them had small lesion at presentation. Conventional x-ray was only helpful in patients with advanced disease and the MRI accurately determined the disease extension. Cytological smears, surgical biopsies histopathological examination and grains culture were the principal diagnostic tools for causative organisms’ identification. In the present series it was difficult to determine the treatment outcome due to high patients follow up dropout. [ABSTRACT FROM AUTHOR]

Background: Disease manifestations in neurocysticercosis (NCC) are frequently due to inflammation of degenerating Taenia solium brain cysts. Exacerbated inflammation post anthelmintic treatment is associated with leakage of the blood brain barrier (BBB) using Evans blue (EB) staining. How well EB extravasation into the brain correlates with magnetic resonance imaging (MRI) using gadolinium (Gd) enhancement as a contrast agent and pericystic inflammation was analyzed in pigs harboring brain cysts of Taenia solium. Methodology/Principal Findings: Three groups of 4 naturally infected pigs were assessed. The first and second groups were treated with both praziquantel plus albendazole and sacrificed two and five days post treatment, respectively. A third untreated group remained untreated. Pigs were injected with EB two hours prior to evaluation by Gd-enhanced T1-MRI, and euthanized. The EB staining for each cyst capsule was scored (EB grades were 0: 0%; 1: up to 50%; 2: over 50% but less than 100%; 3: 100%). Similarly, the Gd enhancement around each cyst was qualitatively and quantitatively scored from the MRI. The extent of pericystic inflammation on histology was scored in increasing severity as IS1, IS2, IS3 and IS4. Grade 3 EB staining and enhancement was only seen in treated capsules. Also, treated groups had higher Gd intensity than the untreated group. Grades of enhancement correlated significantly with Gd enhancement intensity. EB staining was correlated with Gd enhancement intensity and with IS4 in the treated groups. These correlations were stronger in internally located cysts compared to superficial cysts in treated groups. Significance: EB staining and Gd enhancement strongly correlate. The intensity of enhancement determined by MRI is a good indication of the degree of inflammation. Similarly, EB staining highly correlates with the degree of inflammation and may be applied to study inflammation in the pig model of NCC. [ABSTRACT FROM AUTHOR]

Scabies is a common, highly contagious skin parasitosis caused by Sarcoptes scabiei var. hominis. Early identification and prompt treatment of infested subjects is essential, as missed diagnosis may result in outbreaks, considerable morbidity, and significantly increased economic burden. The standard diagnostic technique consists of mites’ identification by microscopic examination of scales obtained by skin scraping. This is a time-consuming and risk-associated procedure that is also not suitable to a busy practice. In recent years, some advanced and noninvasive techniques such as videodermatoscopy, dermatoscopy, reflectance confocal microscopy, and optical coherence tomography have demonstrated improved efficacy in the diagnosis of scabies. Their advantages include rapid, noninvasive mass screening and post-therapeutic follow-up, with no physical risk. A greater knowledge of these techniques among general practitioners and other specialists involved in the intake care of overcrowded populations vulnerable to scabies infestations is now viewed as urgent and important in the management of outbreaks, as well as in consideration of the recent growing inflow of migrants in Europe from North Africa. [ABSTRACT FROM AUTHOR]

Background: Echocardiographic screening for detection of latent RHD has shown potential as a strategy to decrease the burden of disease. However, further research is needed to determine optimal implementation strategies. RHD results from a complex interplay between environment and host susceptibility. Family members share both and relatives of children with latent RHD may represent a high-risk group. The objective of this study was to use echocardiographic family screening to determine the relative risk of RHD among first-degree relatives of children with latent RHD compared to the risk in first-degree relatives of healthy peers. Methodology/Principal Findings: Previous school-based screening data were used to identify RHD positive children and RHD negative peers. All first-degree relatives ≥ 5 years were invited for echocardiography screening (2012 World Heart Federation Criteria). Sixty RHD positive cases (30 borderline/30 definite RHD) and 67 RHD negative cases were recruited. A total of 455/667 (68%) family members were screened. Definite RHD was more common in childhood siblings of RHD positive compared to RHD negative (p = 0.05). Children with any RHD were 4.5 times as likely to have a sibling with definite RHD, a risk that increased to 5.6 times when considering only cases with definite RHD. Mothers of RHD positive and RHD negative cases had an unexpectedly high rate of latent RHD (9.3%). Conclusions/Significance: Siblings of RHD positive cases with RHD are more likely to have definite RHD and the relative risk is highest if the index case has definite RHD. Future screening programs should consider implementation of sibling screening following detection of an RHD positive child. Larger screening studies of adults are needed, as data on prevalence of latent RHD outside of childhood are sparse. Future studies should prioritize implementation research to answer questions of how RHD screening can best be integrated into existing healthcare structures, ensuring practical and sustainable screening programs. [ABSTRACT FROM AUTHOR]

Background: Tapeworms of the order Diphyllobothriidea are parasites of tetrapods and several species may infect man and cause neglected human disease called diphyllobothriosis. Identification of human-infecting diphyllobothriid cestodes is difficult because of their morphological uniformity, which concerns also their eggs in stool samples. Methods: In the present study, we analysed by far the largest dataset of more than 2,000 eggs of 8 species of diphyllobothriid cestodes that may infect humans, including the most frequent human parasites Diphyllobothrium latum, D. nihonkaiense and Adenocephalus pacificus (syn. Diphyllobothrium pacificum). Size (length, width and length/width ratio) and the surface of the egg shell from naturally and experimentally infected hosts were studied using light and scanning electron microscopy. Results: A high degree of intraspecific and host-related size variability has been detected, but combination of morphometrical and ultrastructural data made it possible to distinguish all of the studied species, including otherwise quite similar eggs of the 3 most common species infecting man, i.e. D. latum, D. nihonkaiense and D. dendriticum. The surface of all marine species is covered by numerous deep pits with species-specific density, whereas the surface of freshwater species is smooth or with isolated shallow hollows or wrinkles. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica causes intestinal disease in endemic settings throughout the world. Diagnosis of E. histolytica infection would be improved by the identification of biomarkers that are expressed by cysts of E. histolytica, but not by cysts of closely related commensal species of Entamoeba. Herein, we describe two novel monoclonal antibodies (1A4 and 1D3) produced against a spacer region of the E. histolytica Jacob2 lectin, an outer cyst wall protein. These reagents demonstrated no cross-reaction to E. dispar recombinant antigen and low picomolar molecular detection limits when paired in ELISA sandwich assays. In an immunofluorescence microscopy assay, the α-Jacob2 murine antibodies labeled cysts of three xenically cultured E. histolytica isolates but did not label cysts of three E. bangladeshi isolates. Monoclonal antibody 1A4 did not cross-react with xenic cultures of three E. dispar isolates, demonstrating specificity to E. histolytica, while monoclonal antibody 1D3 cross-reacted with two out of three E. dispar isolates. Both antibodies labeled cysts in formalin-fixed slides, a potential logistical advantage in some settings. The monoclonal antibody 1A4 was also used in an immunofluorescence microscopy assay with formalin-fixed stool specimens. Seven out of ten ELISA-positive stool specimens exhibited 1A4-labeled cyst-like objects, compared to one out of seven ELISA-negative specimens. These results demonstrate that antibodies generated against the flexible spacer of E. histolytica Jacob2 lectin recognize and bind to Jacob2 protein in whole cysts and are capable of differentiating Entamoeba species in fixed specimens. Thus, Jacob2 is a promising biomarker for use in diagnosing E. histolytica infection. [ABSTRACT FROM AUTHOR]

Introduction: Human angiostrongyliasis (HA) is a neurological helminthic disease caused by the lung worm Angiostrongylus cantonensis. It is suspected in the combination of travel or a residence in an endemic area and eosinophilic meningitis. In Mayotte, an island in the Indian Ocean, cases are rare but regular. The main objective of our study was to describe the epidemiological and diagnosis clues of HA in Mayotte. The secondary objectives were to evaluate the contribution of Real-Time Polymerase Chain Reaction (RT- PCR) for the diagnosis of HA, delineate the characteristics of the local transmission and ascertain the presence of A. cantonensis in Achatina fulica, the potential vector of the disease. Materials and Methods: Between 2007 and 2012, all cases of eosinophilic meningitis were retrospectively included and investigated by RT- PCR in the CSF. Descriptive analysis was conducted for clinical, biological and radiological features, and were analyzed for all patients together with the search for prognostic factors for mortality. Concurrently, geolocalization and temporal parameters were studied to correlate the occurrence of the cases with rainfall seasons and snails were collected to enhance a parasitic carriage with real time PCR. Results: During the 6-year period of the study, 14 cases were identified (2.3 cases/year) and 9 among 10 remaining CSF were positive in PCR. Among 14 cases of EM, 13 were less than 2 year-old children. The 1 year mortality rate was 5/14 (35.7%). Among survivors, 3/7 (42.8%) presented neurological sequelae. Factors associated with mortality were dysfunction of cranial nerves, abnormal brain imaging, and CSF glucose level inferior to 2 mmol/l. Occurrence of cases was temporarily and spatially correlated to the rainy season. Among the 64 collected giant snails, 6 (9.4%) were positive with A. cantonensis PCR. The likely main route of transmission was the children licking snails, carriers of the parasite. Conclusion: In Mayotte, HA was mainly found in paediatric cases under 2 years old, and evidenced a life-threatening disease. PCR seems to be a promising tool in the definitive diagnosis of HA. Population should be aware of the role of A. fulica, and not let the children have direct contact with the snails. [ABSTRACT FROM AUTHOR]

Background: The mucosal changes associated with female genital schistosomiasis (FGS) encompass abnormal blood vessels. These have been described as circular, reticular, branched, convoluted and having uneven calibre. However, these characteristics are subjective descriptions and it has not been explored which of them are specific to FGS. Methods: In colposcopic images of young women from a schistosomiasis endemic area, we performed computerised morphologic analyses of the cervical vasculature appearing on the mucosal surface. Study participants where the cervix was classified as normal served as negative controls, women with clinically diagnosed FGS and presence of typical abnormal blood vessels visible on the cervical surface served as positive cases. We also included women with cervical inflammatory conditions for reasons other than schistosomiasis. By automating morphological analyses, we explored circular configurations, vascular density, fractal dimensions and fractal lacunarity as parameters of interest. Results: We found that the blood vessels typical of FGS are characterised by the presence of circular configurations (p < 0.001), increased vascular density (p = 0.015) and increased local connected fractal dimensions (p = 0.071). Using these features, we were able to correctly classify 78% of the FGS-positive cases with an accuracy of 80%. Conclusions: The blood vessels typical of FGS have circular configurations, increased vascular density and increased local connected fractal dimensions. These specific morphological features could be used diagnostically. Combined with colourimetric analyses, this represents a step towards making a diagnostic tool for FGS based on computerised image analysis. [ABSTRACT FROM AUTHOR]

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE. [ABSTRACT FROM AUTHOR]

Background: The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses. Methodology/Principal Findings: We report a case of a 20-year-old pregnant woman who was referred to our service after a large Zika virus outbreak in the city of Salvador, Brazil with an ultrasound examination that showed intrauterine growth retardation of the fetus at the 18th gestational week. Ultrasound examinations in the 2nd and 3rd trimesters demonstrated severe microcephaly, hydranencephaly, intracranial calcifications and destructive lesions of posterior fossa, in addition to hydrothorax, ascites and subcutaneous edema. An induced labor was performed at the 32nd gestational week due to fetal demise and delivered a female fetus. ZIKV-specific real-time polymerase chain reaction amplification products were obtained from extracts of cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid, while extracts of heart, lung, liver, vitreous body of the eye and placenta did not yield detectable products. Conclusions/Significance: This case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes. [ABSTRACT FROM AUTHOR]

Background: Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. Methods and Principal Findings: PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Conclusions: Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available. [ABSTRACT FROM AUTHOR]

Background: Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC) is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility. Methodology/Principal Findings: We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum. Conclusions/Significance: The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite. [ABSTRACT FROM AUTHOR]

Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele. The mechanisms driving worm migration and retention within the lymphatics are currently unknown. We have developed an integrated in vitro imaging platform capable of quantifying B. malayi migration and behavior in a multicellular microenvironment relevant to the initial site of worm injection by incorporating the worm in a Polydimethylsiloxane (PDMS) microchannel in the presence of human dermal lymphatic endothelial cells (LECs) and human dermal fibroblasts (HDFs). The platform utilizes a motorized controllable microscope with CO2 and temperature regulation to allow for worm tracking experiments with high resolution over large length and time scales. Using post-acquisition algorithms, we quantified four parameters: 1) speed, 2) thrashing intensity, 3) percentage of time spent in a given cell region and 4) persistence ratio. We demonstrated the utility of our system by quantifying these parameters for L3 B. malayi in the presence of LECs and HDFs. Speed and thrashing increased in the presence of both cell types and were altered within minutes upon exposure to the anthelmintic drug, tetramisole. The worms displayed no targeted migration towards either cell type for the time course of this study (3 hours). When cells were not present in the chamber, worm thrashing correlated directly with worm speed. However, this correlation was lost in the presence of cells. The described platform provides the ability to further study B. malayi migration and behavior. [ABSTRACT FROM AUTHOR]

Tungiasis (sand flea disease) is a neglected tropical disease, prevalent in resource-poor communities in South America and sub-Saharan Africa. It is caused by an inflammatory response against penetrated female sand fleas (Tunga penetrans) embedded in the skin of the host. Although associated with debilitating acute and chronic morbidity, there is no proven effective drug treatment. By consequence patients attempt to remove embedded sand fleas with non-sterile sharp instruments, such as safety pins, a procedure that represents a health threat by itself. In this proof-of-principle study we compared the topical application of a mixture of two dimeticones of low viscosity (NYDA) to the topical application of a 0.05% solution of KMnO4 in 47 school children in an endemic area in rural Kenya. The efficacy of the treatment was assessed during a follow up period of seven days using viability signs of the embedded parasites, alterations in the natural development of lesion morphology and the degree of local inflammation as outcome measures. Seven days after treatment, in the dimeticone group 78% (95% CI 67–86%) of the parasites had lost all signs of viability as compared to 39% (95% CI 28–52%) in the KMnO4 group (p<0.001). In the dimeticone group 90% (95% CI 80–95%) of the penetrated sand fleas showed an abnormal development already after 5 days, compared to 53% (95% CI 40–66%; p<0.001) in the KMnO4 group. Seven days after treatment, signs of local skin inflammation had significantly decreased in the dimeticone group (p<0.001). This study identified the topical application of dimeticones of low viscosity (NYDA) as an effective means to kill embedded sand fleas. In view of the efficacy and safety of the topical treatment with dimeticone, the mechanical extraction of embedded sand fleas using hazardous instruments is no longer warranted. [ABSTRACT FROM AUTHOR]