Efficacy, safety and acceptability of a new chewable formulationversusthe solid tablet of mebendazole against hookworm infections in children: an open-label, randomized controlled trial

Background; : Soil-transmitted helminths (STHs) infect almost 1·5 billion people worldwide. The control of STH infections is based on preventive chemotherapy using either albendazole or mebendazole. Before being widely used, a sufficient body of evidence on efficacy, safety and acceptability is warranted for the new chewable child-friendly formulation of mebendazole that was recently developed.; Methods; : We conducted a randomised controlled superiority trial in four primary schools and kindergartens on Pemba Island, Tanzania. We considered eligible children aged 3 to 12 years with a hookworm infection intensity of at least 50 eggs per gram (EPG) of stool and no chronic diseases. Participants were allocated to treatment arms (ratio 1:1) using a computer generated random sequence. Our primary outcome was geometric mean based egg reduction rate (ERR) against hookworm assessed 14-21 days post-treatment. This trial complete and is registered with ClinicalTrials.gov, number NCT03995680 (June 24, 2019).; Findings; : 397 children were eligible and randomised into the solid (198) or chewable (199) tablet arms, of whom 393 were analysed. We found no significant difference between both formulations in terms of ERR (solid 70·8% versus chewable 68·5%, difference in ERRgeometric mean 2·3%-points, 95% CI -7·8 to 12·6, p = 0.65) and CR (11·2 versus 12·7%, 95% CI -4·9 to 7·9, p = 0.65) against hookworm infections. Adverse events were mild in both treatment arms.; Interpretations; : Though we could not demonstrate superiority in terms of efficacy of the new formulation, the difference between arms was small and therefore, the chewable formulation could be safely used as an alternative to swallowable tablets, in particular in young children who may have swallowing difficulties. This might help increase compliance and, consequently, enhance the effect of preventive chemotherapy

Current Knowledge and Conservation of the Wild Mammals of the Gulf of Guinea Oceanic Islands

Oceanic islands are usually difficult for mammals to colonize; consequently, the native mammal fauna is typically species-poor, often consisting of just a few species of bats. The oceanic islands of the Gulf of Guinea are no exception to this pattern. Still, the known mammal richness is relatively high for the small size of the islands. Out of a total of 13 native species, including 11 bats and 2 shrews, at least 7 species and 3 subspecies are single-island endemics. In addition to native species, at least 6 other wild mammals have been introduced to the islands purposely or accidentally by humans. Some of these are among the world’s most notorious invasive species and cause damage to native species, ecosystems, and humans. Predation by exotic species can threaten native island mammals, which are especially sensitive due to their small populations and limited ranges. These impacts are likely worsened by other threats, such as forest degradation and climate change, and a general lack of knowledge about the natural history of most species also hampers the implementation of conservation measures. Therefore, fostering further research on the endemic-rich mammal fauna of these islands is vital to ensure their persistence.info:eu-repo/semantics/publishedVersio

Malnutrition, anemia, micronutrient deficiency and parasitic infections among schoolchildren in rural Tanzania

BACKGROUND: Malnutrition, anemia, micronutrient deficiency and parasitic infections continue to impact the nutritional status and health of children in lower-income countries, however not enough data concerning this issue is available. The aim of this study was to assess the distribution of nutritional indicators, anemia and micronutrient deficiency and their underlying risk factors among schoolchildren in south-eastern Tanzania. METHOD/PRINCIPAL FINDINGS: This cross-sectional study enrolled primary schoolchildren aged 6-12 years from Kikwawila and Kiberege wards, Tanzania. In total 471 schoolchildren underwent physical examination and provided blood, stool and urine samples for micronutrient level assessment, nutritional and anemia status, and parasitic infection status. We employed bivariate and multivariate logistic regression to determine the association between nutritional statuses, anemia, micronutrient deficiency and parasitic infections. We found that 23.90%, 12.60% and 16.20% of schoolchildren were stunted, underweight and wasted, respectively. About 14% of schoolchildren were found to be anemic and were more likely to be diagnosed with Plasmodium falciparum infection (aOR: 3.95, 95% CI: 2.73-5.67). Vitamin A (34.70%) and vitamin B12 (8.80%) were the most prevalent micronutrients found to be deficient in diagnosed children. Finally, we found that schoolchildren attending the most rural schools were five times more likely to be diagnosed with at least one micronutrient deficiency (aOR: 5.04, 95% CI: 2.38-11.44). CONCLUSIONS/SIGNIFICANCE: Malnutrition, anemia and micronutrient deficiency still pose a significant health burden among schoolchildren living in rural Tanzania. To effectively tackle this burden, health interventions such as deworming, micronutrient supplementation, vector control, health education and access to clean water and improved sanitation should be strengthened and made sustainable

Efficacy of drugs against clonorchiasis and opisthorchiasis: a systematic review and network meta-analysis

BACKGROUND: Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three most important human liver fluke species in the Opisthorchiidae family, infecting approximately 25 million people worldwide. Drug treatment is needed to control morbidity and is also useful in lowering transmission. Several drugs used in various regimens are available to treat these infections, but their comparative efficacy is uncertain. We aimed to compare the efficacy in terms of cure rate and egg reduction rate of currently registered drugs against human liver fluke infection. METHODS: We conducted a systematic review using readily available electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, KoreaMed, China National Knowledge Infrastructure, and Wanfang Data) without language restrictions from inception until June 29, 2021. Clinical trials with pairwise comparison of drugs (praziquantel, albendazole, mebendazole, tribendimidine, or combinations of these drugs) against C sinensis, O viverrini, and O felineus were eligible, including trials comparing these drugs or their combinations with placebo. We compared efficacy in terms of cure rate by network meta-analysis. We conducted mixed binomial regression analyses for each species to derive predicted median cure rates for each drug regimen. The models included treatment and infection intensity as fixed factors, year of publication as covariate, and random effects of the different studies assumed to be normally distributed. We also assessed the quality of the included studies. This study was registered with PROSPERO (CRD42018109232). FINDINGS: Overall, 26 trials from 25 studies were included, of which 18 involved C sinensis, seven studied O viverrini, and one focused on O felineus. These trials included a total of 3340 participants. The two long-term treatment courses against C sinensis infection using 400 mg of albendazole (400 mg twice a day for 5 days and 400 mg twice a day for 7 days) resulted in cure rates of 100%, while two other multiple-dose regimens of albendazole resulted in high predicted cure rates: 300 mg twice a day for 5 days (93.9% [95% CI 49.6-99.6]) and 400 mg twice a day for 3 days (91.0% [50.9-99.0]). The WHO-recommended praziquantel regimen (25 mg/kg three times a day for 2 days) also showed a high predicted cure rate (98.5% [85.4-99.9]) in C sinensis infection, and predicted cure rates were above 90% for several other multiple-dose praziquantel regimens, including 20 mg/kg three times a day for 3 days (97.6% [74.7-99.8]), 14 mg/kg three times a day for 5 days (93.9% [44.8-99.7]), and 20 mg/kg twice a day for 3 days (91.0% [50.9-99.0]). In O viverrini infection, the regimen of 50 mg/kg and 25 mg/kg of praziquantel given in a single day showed the highest predicted cure rate (93.8% [85.7-97.5]), while a single dose of 50 mg/kg praziquantel also resulted in a high predicted cure rate (92.1% [64.9-98.6]). The single dose of 400 mg tribendimidine showed a high predicted cure rate of 89.8% (77.5-95.8). A low quality of evidence was demonstrated in most studies, especially those published before 2000. Selection bias due to poor random sequence generation and allocation concealment was high, and performance and detection biases were frequently unreported. INTERPRETATION: Praziquantel shows high efficacy against clonorchiasis and opisthorchiasis. Tribendimidine might serve as a treatment alternative and warrants further investigation. Although albendazole is efficacious when long treatment schedules (5 days or 7 days) are applied, limited size of studies and high risk of bias affect the interpretation of results. More high-quality studies are needed to promote the establishment of treatment guidelines for human liver fluke infection. FUNDING: Fourth Round of Three-Year Public Health Action Plan (2015-2017; Shanghai, China) and Swiss National Science Foundation

Informed consent procedure in a double blind randomized anthelminthic trial on Pemba Island, Tanzania: do pamphlet and information session increase caregivers knowledge?

Background In clinical research, obtaining informed consent from participants is an ethical and legal requirement. Conveying the information concerning the study can be done using multiple methods yet this step commonly relies exclusively on the informed consent form alone. While this is legal, it does not ensure the participant’s true comprehension. New effective methods of conveying consent information should be tested. In this study we compared the effect of different methods on the knowledge of caregivers of participants of a clinical trial on Pemba Island, Tanzania. Methods A total of 254 caregivers were assigned to receive (i) a pamphlet (n = 63), (ii) an oral information session (n = 62) or (iii) a pamphlet and an oral information session (n = 64) about the clinical trial procedures, their rights, benefits and potential risks. Their post-intervention knowledge was assessed using a questionnaire. One group of caregivers had not received any information when they were interviewed (n = 65). Results In contrast to the pamphlet, attending an information session significantly increased caregivers’ knowledge for some of the questions. Most of these questions were either related to the parasite (hookworm) or to the trial design (study procedures). Conclusions In conclusion, within our trial on Pemba Island, a pamphlet was found to not be a good form of conveying clinical trial information while an oral information session improved knowledge. Not all caregivers attending an information session responded correctly to all questions; therefore, better forms of communicating information need to be found to achieve a truly informed consent

Efficacy and safety of a single dose versus a multiple dose regimen of mebendazole against hookworm infections in children : a randomised, double-blind trial

Background: Single-dose mebendazole is widely used in preventive chemotherapy against the soil-transmitted helminths (STHs) Ascaris lumbricoides, hookworm and Trichuris trichiura, yet it shows limited efficacy against hookworm and T. trichiura infections. The use of adapted treatment regimens might provide a strategy to control and eliminate STH infections in STH-persistent settings. We evaluated the safety and efficacy of the multiple dose mebendazole regimen (3 days 100 mg bid) versus a single dose of 500 mg mebendazole in a setting with high STH prevalence and high drug pressure. Methods: This randomised, double-blind clinical trial took place in a primary school on Pemba Island, Tanzania, in school-aged children (6–12 years). Using a computer random number generator (block size 10), hookworm-positive children were randomly assigned (1:1) to either a single or multiple dose regimen of mebendazole by an independent statistician. Two stool samples were collected at baseline and follow-up (18 to 22 days after treatment) for Kato-Katz analysis. The primary outcome was cure rate (CR) against hookworm. Secondary outcomes were egg reduction rate (ERR) against hookworm, CRs and ERRs against A. lumbricoides and T. trichiura, and tolerability assessed 3, 24 and 48 h post-treatment. Participants, investigators, caregivers, outcome assessors and the trial statistician were blinded. This trial is registered with ClinicalTrials.gov, number NCT03245398. Findings: 93 children were assigned to each treatment arm. 185 children completed treatment and provided follow-up stool samples. CR against hookworm was significantly higher in the multiple dose (98%) than in the single dose arm (13%, OR 389.1, 95% CI 95.2 to 2885.7%, p < 0.001). 34 and 42 children reported mild adverse events in the single and multiple dose arms, respectively. The most common events were abdominal pain, headache and diarrhoea. Interpretation: The poor performance of single dose mebendazole against hookworm infections was confirmed, but the multiple dose treatment regimen of mebendazole showed high efficacy. Hence, multiple dose mebendazole might provide a treatment strategy in given epidemiological situations to boost control and elimination of STH infections. Funding: PATH

What determines the density structure of molecular clouds? A case study of Orion B with <i>Herschel</i>

A key parameter to the description of all star formation processes is the density structure of the gas. In this Letter, we make use of probability distribution functions (PDFs) of Herschel column density maps of Orion B, Aquila, and Polaris, obtained with the Herschel Gould Belt survey (HGBS). We aim to understand which physical processes influence the PDF shape, and with which signatures. The PDFs of Orion B (Aquila) show a lognormal distribution for low column densities until AV ~ 3 (6), and a power-law tail for high column densities, consistent with a ρα r-2 profile for the equivalent spherical density distribution. The PDF of Orion B is broadened by external compression due to the nearby OB stellar aggregates. The PDF of a quiescent subregion of the non-star-forming Polaris cloud is nearly lognormal, indicating that supersonic turbulence governs the density distribution. But we also observe a deviation from the lognormal shape at AV > 1 for a subregion in Polaris that includes a prominent filament. We conclude that (1) the point where the PDF deviates from the lognormal form does not trace a universal AV -threshold for star formation, (2) statistical density fluctuations, intermittency, and magnetic fields can cause excess from the lognormal PDF at an early cloud formation stage, (3) core formation and/or global collapse of filaments and a non-isothermal gas distribution lead to a power-law tail, and (4) external compression broadens the column density PDF, consistent with numerical simulations

How a haemosporidian parasite of bats gets around: the genetic structure of a parasite, vector and host compared.

Parasite population structure is often thought to be largely shaped by that of its host. In the case of a parasite with a complex life cycle, two host species, each with their own patterns of demography and migration, spread the parasite. However, the population structure of the parasite is predicted to resemble only that of the most vagile host species. In this study, we tested this prediction in the context of a vector-transmitted parasite. We sampled the haemosporidian parasite Polychromophilus melanipherus across its European range, together with its bat fly vector Nycteribia schmidlii and its host, the bent-winged bat Miniopterus schreibersii. Based on microsatellite analyses, the wingless vector, and not the bat host, was identified as the least structured population and should therefore be considered the most vagile host. Genetic distance matrices were compared for all three species based on a mitochondrial DNA fragment. Both host and vector populations followed an isolation-by-distance pattern across the Mediterranean, but not the parasite. Mantel tests found no correlation between the parasite and either the host or vector populations. We therefore found no support for our hypothesis; the parasite population structure matched neither vector nor host. Instead, we propose a model where the parasite's gene flow is represented by the added effects of host and vector dispersal patterns

Profiling filaments: comparing near-infrared extinction and submillimetre data in TMC-1

Interstellar filaments are an important part of star formation. To understand the structure of filaments, cross-section profiles are often fitted with Plummer profiles. This profiling is often done with submm studies, such as Herschel. It would be convenient if filament properties could also be studied using groundbased NIR data. We compare the filament profiles obtained by NIR extinction and submm observations to find out if reliable profiles can be derived using NIR data. We use J-, H-, and K-band data of a filament north of TMC-1 to derive an extinction map from colour excesses of background stars. We compare the Plummer profiles obtained from extinction maps with Herschel dust emission maps. We present 2 methods to estimate profiles from NIR: Plummer profile fits to median Av of stars or directly to the Av of individual stars. We compare the methods by simulations. In simulations extinction maps and the new methods give correct results to within ~10-20 for modest densities. Direct fit to data on individual stars gives more accurate results than extinction map, and can work in higher density. In profile fits to real observations, values of Plummer parameters are generally similar to within a factor of ~2. Although parameter values can vary significantly, estimates of filament mass usually remain accurate to within some tens of per cent. Our results for TMC-1 are in agreement with earlier results. High resolution NIR data give more details, but 2MASS data can be used to estimate profiles. NIR extinction can be used as an alternative to submm observations to profile filaments. Direct fits of stars can also be a valuable tool. Plummer profile parameters are not always well constrained, and caution should be taken when making fits. In the evaluation of Plummer parameters, one can use the independence of dust emission and NIR data and the difference in the shapes of the confidence regions.Comment: accepted to Astronomy & Astrophysics; abstract has been shortened for astrop

Secondary forest regeneration benefits old-growth specialist bats in a fragmented tropical landscape

Tropical forest loss and fragmentation are due to increase in coming decades. Understanding how matrix dynamics, especially secondary forest regrowth, can lessen fragmentation impacts is key to understanding species persistence in modified landscapes. Here, we use a whole-ecosystem fragmentation experiment to investigate how bat assemblages are influenced by the regeneration of the secondary forest matrix. We surveyed bats in continuous forest, forest fragments and secondary forest matrix habitats, similar to 15 and similar to 30 years after forest clearance, to investigate temporal changes in the occupancy and abundance of old-growth specialist and habitat generalist species. The regeneration of the second growth matrix had overall positive effects on the occupancy and abundance of specialists across all sampled habitats. Conversely, effects on generalist species were negligible for forest fragments and negative for secondary forest. Our results show that the conservation potential of secondary forests for reverting faunal declines in fragmented tropical landscapes increases with secondary forest age and that old-growth specialists, which are often of most conservation concern, are the greatest beneficiaries of secondary forest maturation. Our findings emphasize that the transposition of patterns of biodiversity persistence in island ecosystems to fragmented terrestrial settings can be hampered by the dynamic nature of human-dominated landscapes.Peer reviewe