Epidemiology of pediatric schistosomiasis in hard-to-reach areas and populations: a scoping review protocol

Background: Schistosomiasis is a neglected tropical disease (NTD) that affects millions of people. Children are the most vulnerable group to developing overt disease. An estimated 779 million people are at risk of schistosomiasis and 50 million preschool-age children (PSAC) need treatment. PSAC are not currently targeted by national chemotherapy campaigns due to a lack of suitable pediatric formulations of praziquantel. The Pediatric Praziquantel Consortium has developed an orally dispersible praziquantel formulation (arpraziquantel) and is facilitating its adoption for schistosomiasis control by endemic countries through the ADOPT program - an implementation research program that paves the way for the large-scale delivery of the child-friendly formulation to treat schistosomiasis in preschool-aged children in endemic countries. A key challenge for comprehensive NTD control including schistosomiasis is reaching all at-risk populations, including those hard to reach. Main access barriers include geographic, social and economic conditions. Objective : This scoping literature review aims to document the epidemiology of schistosomiasis in children under 6 years of age living in hard-to-reach areas and populations. Methods : This review will adopt the five-stage scoping review process of identifying the research question, identifying relevant studies, study selection, charting data and collating, summarizing and reporting results. Electronic databases including Medline, Web of Science, Embase (Ovid), LILACS and African Journals OnLine (AJOL) will be searched for relevant articles. Two independent reviewers will screen identified articles using a two-stage approach of reviewing the title/abstract and then the full text of provisionally retained articles. Relevant literatures will be downloaded into EndNote X9 to maintain and manage citation and facilitate the overall review process. A meta-analysis will be conducted if indicated. Relevance : The results will provide insights into the burden of schistosomiasis among marginalized PSAC, aiming to produce evidence on the need for inclusion of this population when designing the expansion of preventive chemotherapy programs

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

Unifying low and high mass star formation through density amplified hubs of filaments

Context: Star formation takes place in giant molecular clouds, resulting in mass-segregated young stellar clusters composed of Sun-like stars, brown dwarves, and massive O-type(50-100\msun) stars. Aims: To identify candidate hub-filament systems (HFS) in the Milky-Way and examine their role in the formation of the highest mass stars and star clusters. Methods: Filaments around ~35000 HiGAL clumps that are detected using the DisPerSE algorithm. Hub is defined as a junction of three or more filaments. Column density maps were masked by the filament skeletons and averaged for HFS and non-HFS samples to compute the radial profile along the filaments into the clumps. Results: ~3700~(11\%) are candidate HFS of which, ~2150~(60\%) are pre-stellar, ~1400~(40\%) are proto-stellar. All clumps with L>10^4 Lsun and L>10^5 Lsun at distances respectively within 2kpc and 5kpc are located in the hubs of HFS. The column-densities of hubs are found to be enhanced by a factor of ~2 (pre-stellar sources) up to ~10 (proto-stellar sources). Conclusions: All high-mass stars preferentially form in the density enhanced hubs of HFS. This amplification can drive the observed longitudinal flows along filaments providing further mass accretion. Radiation pressure and feedback can escape into the inter-filamentary voids. We propose a "filaments to clusters" unified paradigm for star formation, with the following salient features: a) low-intermediate mass stars form in the filaments slowly (10^6yr) and massive stars quickly (10^5yr) in the hub, b) the initial mass function is the sum of stars continuously created in the HFS with all massive stars formed in the hub, c) Feedback dissiption and mass segregation arise naturally due to HFS properties, and c) explain age spreads within bound clusters and formation of isolated OB associations.Comment: 20 pages, 17 figures, Accepted by Astronomy and Astrophysic

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

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 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

Bird extinctions and introductions are causing taxonomic and functional homogenization in oceanic islands

Humans are quickly reshaping species assemblages through the loss and gain of species at multiple scales. Extinctions and introductions are non-random events known to be contributing to taxonomic homogenization. However, it is not yet clear if they also promote functional homogenization. Here, we assess whether extinctions and introductions are leading to taxonomic and functional homogenization of 64 oceanic island bird assemblages, belonging to 11 archipelagos. Based on island lists of extinct and extant, native and introduced species and on species traits, we use probabilistic hypervolumes in trait space to calculate functional beta-diversity before and after extinctions and introductions. Bird extinctions and introductions promoted taxonomic and functional homogenization on most oceanic islands. These results follow our expectations, considering previous studies on taxonomic homogenization, the predictable link between taxonomic and functional diversity, and the trait similarity of many introduced species, often adapted to anthropogenic habitats, linked to the non-randomness of bird introductions on islands. Taxonomic homogenization was more common across than within archipelagos, also corroborating previous studies describing stronger homogenization on islands that are further apart and thus had distinctive native assemblages. Surprisingly, the widespread loss of species with similar traits, namely large flightless birds, often led to functional differentiation across archipelagos. However, this differentiation effect tended to be offset by the homogenizing effect of introductions. Functional homogenization increases the vulnerability to global changes, by reducing the variability of responses to disturbance and thus the resilience of ecosystem services, posing a threat to human societies on islands. Our results highlight subtle variations in taxonomic and functional beta-diversity of bird assemblages in oceanic islands, providing important insights to allow a better assessment of how anthropogenic changes might alter ecosystem functioning, which is vital to develop effective long-term conservation strategies. Read the free Plain Language Summary for this article on the Journal blog.Peer reviewe

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

Combined effects of bird extinctions and introductions in oceanic islands : Decreased functional diversity despite increased species richness

Aim We analyse the consequences of species extinctions and introductions on the functional diversity and composition of island bird assemblages. Specifically, we ask if introduced species have compensated the functional loss resulting from species extinctions. Location Seventy-four oceanic islands (> 100 km(2)) in the Atlantic, Pacific and Indian Oceans. Time period Late Holocene. Major taxa studied Terrestrial and freshwater bird species. Methods We compiled a species list per island (extinct and extant, native and introduced), and then compiled traits per species. We used single-trait analyses to assess the effects of past species extinctions and introductions on functional composition. Then, we used probabilistic hypervolumes in trait space to calculate functional richness and evenness of original versus present avifaunas of each island (and net change), and to estimate how functionally unique are extinct and introduced species on each island. Results The net effects of extinctions and introductions were: an increase in average species richness per island (alpha diversity), yet a decline in diversity across all islands (gamma diversity); an average increase in the prevalence of most functional traits, yet an average decline in functional richness and evenness, associated with the fact that extinct species were functionally more unique (when compared to extant natives) than introduced species. Main conclusions Introduced species are on average offsetting (and even surpassing) the losses of extinct species per island in terms of species richness, and they are increasing the prevalence of most functional traits. However, they are not compensating for the loss of functional richness due to extinctions. Current island bird assemblages are becoming functionally poorer, having lost unique species and being composed of functionally more redundant species. This is likely to have cascading repercussions on the functioning of island ecosystems. We highlight that taxonomic and functional biodiversity should be assessed simultaneously to understand the global impacts of human activities.Peer reviewe

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