Compliance with anthelmintic treatment in the neglected tropical diseases control programmes: a systematic review

PRISMA checklist. (PDF 223 kb

Epidemiological surveys of, and research on, soil-transmitted helminths in Southeast Asia: a systematic review

PRISMA checklist, full list of search terms and Supporting Figure 1. (DOCX 1462 kb

What is required in terms of mass drug administration to interrupt the transmission of schistosome parasites in regions of endemic infection?

Supplementary information. (PDF 445 kb

An economic evaluation of expanding hookworm control strategies to target the whole community.

Background: The WHO treatment guidelines for the soil-transmitted helminths (STH) focus on targeting children for the control of morbidity induced by heavy infections. However, unlike the other STHs, the majority of hookworm infections are harboured by adults. This untreated burden may have important implications for controlling both hookworm’s morbidity and transmission. This is particularly significant in the context of the increased interest in investigating STH elimination strategies. Methods We used a deterministic STH transmission model and parameter estimates derived from field epidemiological studies to evaluate the impact of child-targeted (2–14 year olds) versus community-wide treatment against hookworm in terms of preventing morbidity and the timeframe for breaking transmission. Furthermore, we investigated how mass treatment may influence the long-term programmatic costs of preventive chemotherapy for hookworm. Results: The model projected that a large proportion of the overall morbidity due to hookworm was unaffected by the current child-targeted strategy. Furthermore, driving worm burdens to levels low enough to potentially break transmission was only possible when using community-wide treatment. Due to these projected reductions in programme duration, it was possible for community-wide treatment to generate cost savings – even if it notably increases the annual distribution costs. Conclusions: Community-wide treatment is notably more cost-effective for controlling hookworm’s morbidity and transmission than the current child-targeted strategies and could even be cost-saving in many settings in the longer term. These calculations suggest that it is not optimum to treat using the same treatment strategies as other STH. Hookworm morbidity and transmission control require community-wide treatment.</p

Data-driven inference for the spatial scan statistic

<p>Abstract</p> <p>Background</p> <p>Kulldorff's spatial scan statistic for aggregated area maps searches for clusters of cases without specifying their size (number of areas) or geographic location in advance. Their statistical significance is tested while adjusting for the multiple testing inherent in such a procedure. However, as is shown in this work, this adjustment is not done in an even manner for all possible cluster sizes.</p> <p>Results</p> <p>A modification is proposed to the usual inference test of the spatial scan statistic, incorporating additional information about the size of the most likely cluster found. A new interpretation of the results of the spatial scan statistic is done, posing a modified inference question: what is the probability that the null hypothesis is rejected for the original observed cases map with a most likely cluster of size k, taking into account only those most likely clusters of size k found under null hypothesis for comparison? This question is especially important when the p-value computed by the usual inference process is near the alpha significance level, regarding the correctness of the decision based in this inference.</p> <p>Conclusions</p> <p>A practical procedure is provided to make more accurate inferences about the most likely cluster found by the spatial scan statistic.</p

Achieving elimination as a public health problem for schistosoma mansoni and S. haematobium: when is community-wide treatment required?

The World Health Organization (WHO) has set elimination as a public health problem (EPHP) as a goal for schistosomiasis. As the WHO treatment guidelines for schistosomiasis are currently under revision, we investigate whether school-based or community-wide treatment strategies are required for achieving the EPHP goal. In low- to moderate-transmission settings with good school enrolment, we find that school-based treatment is sufficient for achieving EPHP. However, community-wide treatment is projected to be necessary in certain high-transmission settings as well as settings with low school enrolment. Hence, the optimal treatment strategy depends on setting-specific factors such as the species present, prevalence prior to treatment, and the age profile of infection

Nano-Hydroxyapatite and Nano-Hydroxyapatite/Zinc Oxide Scaffold for Bone Tissue Engineering Application

This research aims to evaluate the mechanical properties, biocompatibility, and degradation behavior of scaffolds made of pure hydroxyapatite (HA) and HA‐modified by ZnO for bone tissue engineering applications. HA and ZnO were developed using sol‐gel and precipitation methods respectively. The scaffolds properties were characterized using X‐ray diffraction (XRD), Fourier transform spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), atomic absorption (AA), and atomic force microscopy (AFM). The interaction of scaffold with cells was assessed using in vitro cell proliferation and alkaline phosphatase (ALP) assays. The obtained results indicate that the HA/ZnO scaffolds possess higher compressive strength, fracture toughness, and density—but lower hardness—when compared to the pure HA scaffolds. After immersing the scaffold in the SBF solution, more deposited apatite appeared on the HA/ZnO, which results in the rougher surface on this scaffold compared to the pure HA scaffold. Finally, the in vitro biological analysis using human osteoblast cells reveals that scaffolds are biocompatible with adequate ALP activity

Wnt4 and LAP2alpha as pacemakers of Thymic Epithelial Senescence

Age-associated thymic involution has considerable physiological impact by inhibiting de novo T-cell selection. This impaired T-cell production leads to weakened immune responses. Yet the molecular mechanisms of thymic stromal adipose involution are not clear. Age-related alterations also occur in the murine thymus providing an excellent model system. In the present work structural and molecular changes of the murine thymic stroma were investigated during aging. We show that thymic epithelial senescence correlates with significant destruction of epithelial network followed by adipose involution. We also show in purified thymic epithelial cells the age-related down-regulation of Wnt4 (and subsequently FoxN1), and the prominent increase in LAP2α expression. These senescence-related changes of gene expression are strikingly similar to those observed during mesenchymal to pre-adipocyte differentiation of fibroblast cells suggesting similar molecular background in epithelial cells. For molecular level proof-of-principle stable LAP2α and Wnt4-over-expressing thymic epithelial cell lines were established. LAP2α over-expression provoked a surge of PPARγ expression, a transcription factor expressed in pre-adipocytes. In contrast, additional Wnt4 decreased the mRNA level of ADRP, a target gene of PPARγ. Murine embryonic thymic lobes have also been transfected with LAP2α- or Wnt4-encoding lentiviral vectors. As expected LAP2α over-expression increased, while additional Wnt4 secretion suppressed PPARγ expression. Based on these pioneer experiments we propose that decreased Wnt activity and increased LAP2α expression provide the molecular basis during thymic senescence. We suggest that these molecular changes trigger thymic epithelial senescence accompanied by adipose involution. This process may either occur directly where epithelium can trans-differentiate into pre-adipocytes; or indirectly where first epithelial to mesenchymal transition (EMT) occurs followed by subsequent pre-adipocyte differentiation. The latter version fits better with literature data and is supported by the observed histological and molecular level changes