Positive impact of preventative chemotherapy during a national helminth control program:Perception and KAP

Helminth control at the national level is currently based on mass drug administration (MDA) programs. Perception of the MDA programs for helminth control by the affected populations influences compliance and future designs of the programs. We determined the perception of Zimbabwe's National Helminth Control Program (2012-2017) with a specific focus on schistosomiasis in the school children treated with praziquantel, schoolteachers and village health workers (VHW). The study enrolled 409 children from Grades 6 and 7 who had the full benefit of the 6 years of MDA from 2012 to 2017. Thirty-six schoolteachers and 22 VHW serving the schools were also recruited. A structured questionnaire developed in English, translated into the local language Shona, and validated prior to the study was administered to the children and the adults. The questions focused on the perceived impact on health, school attendance and performance and Knowledge Attitudes and Practice (KAP) among the school children. Data were captured electronically on android platforms using the Open Data Kit. Overall, 84% of the children responded that their awareness of schistosomiasis (transmission, disease, treatment and infection avoidance) had improved because of participating in the MDAs. Of the 151 children self-diagnosed with schistosomiasis, 74% reported that their health had improved following treatment with praziquantel. This included resolution of haematuria, painful urination, sore stomach, tiredness and falling asleep during class lessons. The children and teachers reported improvements in both pupil school attendance and performance at school while the VHW and teachers reported an increase in health-seeking behaviour amongst the school children for schistosomiasis treatment in-between MDAs. The majority of VHW (96%) reported improvement in handwashing behaviour, schistosomiasis awareness (96%) and treatment uptake (91%) within the communities where the school children belonged. However, only 59% of the VHW reported improvement in toilet use while only 50% of the VHW reported improvement in clean water use within their communities. This study indicated that the surveyed children perceived the MDA program had improved their health, school attendance, school performance and awareness of schistosomiasis. The VHW also perceived that the MDA program had improved the community KAP

Investigating a strategy for quantifying schistosome infection levels in preschool-aged children using prevalence data from school-aged children

In 2012, the World Health Organisation (WHO) set out a roadmap for eliminating schistosomiasis as a public health problem by 2025. To achieve this target, preschool-aged children (PSAC; aged 6 years and below) will need to be included in schistosomiasis treatment programmes. As the global community discusses the tools and approaches for treating this group, one of the main questions that remains unanswered is how to quantify infection in this age group to inform treatment strategies. The aim of this study was thus to determine whether a relationship exists between levels of schistosome infection in PSAC and school-aged children (SAC), that can be used to determine unknown schistosome infection prevalence levels in PSAC. A systematic search of publications reporting schistosomiasis prevalence in African PSAC and SAC was conducted. The search strategy was formulated using the PRISMA guidelines and SPIDER search strategy tool. The published data was subjected to regression analysis to determine if a relationship exists between infection levels in PSAC and SAC. The interaction between SAC and community treatment history was also entered in the regression model to determine if treatment history significantly affected the relationship between PSAC and SAC prevalence. The results showed that a significant positive relationship exists between infection prevalence levels in PSAC and SAC for Schistosoma mansoni (r = 0.812, df (88, 1), p = <0.0001) and S. haematobium (r = 0.786, df (53, 1), p = <0.0001). The relationship was still significant after allowing for diagnostic method, treatment history, and the African sub-region where the study was conducted (S. mansoni: F = 25.63, df (88, 9), p = <0.0001; S. haematobium: F = 10.20, df (53, 10), p = <0.0001). Using the regression equation for PSAC and SAC prevalence, over 90% of the PSAC prevalence studies were placed in the correct WHO classifications category based on the SAC levels, regardless of treatment history. The study indicated that schistosome prevalence in SAC can be extended as a proxy for infection levels in PSAC, extending on its current use in the adult population. SAC prevalence data could identify where there is a need to accelerate and facilitate the treatment of PSAC for schistosomiasis in Africa

Identification of a major causative agent of human cercarial dermatitis, Trichobilharzia franki (Muller and Kimmig 1994), in southern England and its evolutionary relationships with other European populations.

Background Trichobilharzia is the most species rich and widely distributed genus of schistosomes and is known throughout Europe and North America as an agent of human cercarial dermatitis. The disease is caused by an acute allergic reaction in the skin that develops as a consequence of repeated contact with water containing schistosomatid cercariae. However, despite historical outbreaks of the disease, there are no published records of accurately identified Trichobilharzia species from the UK. Methods Two hundred Radix auricularia (L.) were sampled from a recreational fishing lake in Hampshire and emerging schistosomatid cercariae were collected for microscopy and DNA extraction. General morphological description of the cercariae was performed, alongside sequencing and phylogenetic analysis of the 28S ribosomal DNA for accurate species identification as well as comparisons of ITS1 in order to identify evolutionary affinities with other European populations. All molecular comparisons were performed using published sequences. Results The phylogenetic analysis of 28S sequences identified the cercariae as Trichobilharzia franki. Two unique British ITS1 haplotypes were identified which were most closely related to haplotypes of T. franki populations from France. Haplotype network analysis indicated the mixing of T. franki populations throughout Europe. It is suggested that parasite distribution is the probable result of the movement of migratory waterfowl. Conclusions This is the first accurate record of T. franki in the UK. The movement of T. franki with waterfowl could pose a considerable human health risk, as in mainland Europe, and signifies T. franki-associated human cercarial dermatitis as a re-emerging disease in the UK

Six rounds of annual praziquantel treatment during a national helminth control program significantly reduced schistosome infection and morbidity levels in a cohort of schoolchildren in Zimbabwe

BackgroundThe World Health Organization recommends that schistosomiasis be treated through Mass Drug Administration (MDA). In line with this recommendation, Zimbabwe commenced a national helminth control program in 2012 targeting schoolchildren throughout the country for 6 years. This study, part of a larger investigation of the impact of helminth treatment on the overall health of the children, determined the effect of annual praziquantel treatment on schistosome infection and morbidity in a cohort of children during Zimbabwe's 6-year national helminth control program.Methodology/principal findingsA school-based longitudinal study was carried out in 35 sentinel sites across Zimbabwe from September 2012 to November 2017. The sentinel sites were selected following a countrywide survey conducted in 280 primary schools. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni was diagnosed using both the Kato-Katz and formol-ether concentration techniques. S. haematobium morbidity was determined through detection of macro and microhaematuria. A cohort of children aged 6-15 years old was surveyed annually before MDA and 6 weeks post treatment. Maximum treatment coverage reached 90% over the 6 rounds of MDA. At baseline S. haematobium infection prevalence and intensity were 31.7% (95% CI = 31.1-32.2) and 28.75 eggs/10ml urine (SEM = 0.81) respectively, while S. mansoni prevalence and intensity were 4.6% (95% CI = 4.4-4.8) and 0.28 eggs/25mg (SEM = 0.02). Prior to the 6th round of MDA, S. haematobium infection prevalence had reduced to 1.56% (pConclusionZimbabwe's helminth control program significantly reduced schistosome infection intensity and prevalence and urogenital schistosomiasis morbidity prevalence in a cohort of school-aged children, moving the schistosome prevalence in the children from moderate to low by WHO classification. These findings will inform the design of the country's next stage interventions for helminth control and eventual elimination

Assessing early child development and its association with stunting and schistosome infections in rural Zimbabwean children using the griffiths scales of child development

There is a paucity of reference early childhood development (ECD) data at community level in rural Africa. Our objective was to conduct a comprehensive assessment of ECD in rural Zimbabwe and determine the impact of stunting and schistosome infections on ECD. Using the Griffiths Scales of Child Development, we conducted a cross sectional assessment of Eye and Hand Coordination (EHC), Personal-Social-Emotional (PSE), Language and Communication (LC), Foundations of Learning (FL) and Gross Motor (GM) domains and the summary General Development (GD) in 166 children aged 6-72 months. The effects of stunting, malnutrition and Schistosoma haematobium infection on ECD was determined. The impact of praziquantel curative treatment of schistosome infection on the developmental scores was determined through a longitudinal follow up at 6 and 12 months. From an initial 166 children, 11 were found to have developmental deficits warranting further investigation. Of the remaining 155, 58.7% recorded a good (≥ average) score for the overall General Development (GD). Proportions of children scoring above the cut-off (≥ average) for each domain were GM (84.5%), PSE (80.6%), EHC (61.9%), FL (43.9%) and LC (44.5%). The prevalence of stunting was 26.8% (95% CI = 20.1%-34.8%) Scores for stunted children were significantly lower for EHC (p = 0.0042), GM (p = 0.0099), and GD (p = 0.0014) with the fraction of lower scores attributable to stunting being GM = 63.4%, GD = 46.6%, EHC = 45%, and LC = 21%. S. haematobium infection prevalence was 39.7% and mean infection intensity was 5.4 eggs/10 ml urine. Infected children had poorer cognitive performance scores for the FL (p = 0.0005) with 30.8% of poor FL attributable to the infection. Performance in all domains improved to the expected normal or above reference levels at 6 and 12 months post curative treatment of schistosome infections. Our study documented reference values for ECD in rural Zimbabwean children. The study detected deficiencies in the FL domain, which were more pronounced in children, infected with schistosomes, highlighting the need for provision of cognitive stimulation tools and access to early childhood foundation education. There is also need for improved child nutrition and treatment of schistosome infections to improve child development outcomes

SARS-CoV-2 serological testing in front line health workers in Zimbabwe

BackgroundIn order to protect health workers from SARS-CoV-2, there is need to characterise the different types of patient facing health workers. Our first aim was to determine both the infection status and seroprevalence of SARS-CoV-2 in health workers. Our second aim was to evaluate the occupational and demographic predictors of seropositivity to inform the country's infection prevention and control (IPC) strategy.Methods and principal findingsWe invited 713 staff members at 24 out of 35 health facilities in the City of Bulawayo in Zimbabwe. Compliance to testing was defined as the willingness to uptake COVID-19 testing by answering a questionnaire and providing samples for both antibody testing and PCR testing. SARS-COV-2 antibodies were detected using a rapid diagnostic test kit and SAR-COV-2 infection was determined by real-time (RT)-PCR. Of the 713 participants, 635(89%) consented to answering the questionnaire and providing blood sample for antibody testing while 560 (78.5%) agreed to provide nasopharyngeal swabs for the PCR SARS-CoV-2 testing. Of the 635 people (aged 18-73) providing a blood sample 39.1% reported a history of past COVID-19 symptoms while 14.2% reported having current symptoms of COVID-19. The most-prevalent co-morbidity among this group was hypertension (22.0%) followed by asthma (7.0%) and diabetes (6.0%). The SARS-CoV-2 sero-prevalence was 8.9%. Of the 560 participants tested for SARS-CoV-2 infection, 2 participants (0.36%) were positive for SAR-CoV-2 infection by PCR testing. None of the SARS-CoV-2 antibody positive people were positive for SAR-CoV-2 infection by PCR testing.Conclusion and interpretationIn addition to clinical staff, several patient-facing health workers were characterised within Zimbabwe's health system and the seroprevalence data indicated that previous exposure to SAR-CoV-2 had occurred across the full spectrum of patient-facing staff with nurses and nurse aides having the highest seroprevalence. Our results highlight the need for including the various health workers in IPC strategies in health centres to ensure effective biosecurity and biosafety

Intestinal inflammation and increased intestinal permeability in Plasmodium chabaudi AS infected mice

Background: Gastrointestinal symptoms are commonly associated with acute Plasmodium spp infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. Methods: To investigate whether intestinal pathology also occurs during infection with a murine model of mild and resolving malaria, C57BL/6J mice were inoculated with recently mosquito-transmitted Plasmodium chabaudi AS. At schizogony, intestinal tissues were collected for quantification and localisation of immune mediators and malaria parasites, by PCR and immunohistochemistry. Inflammatory proteins were measured in plasma and faeces and intestinal permeability was assessed by FITC-dextran translocation after oral administration. Results: Parasitaemia peaked at approx. 1.5% at day 9 and resolved by day 14, with mice experiencing significant and transient anaemia but no weight loss. Plasma IFNγ, TNFα and IL10 were significantly elevated during peak infection and quantitative RT-PCR of the intestine revealed a significant increase in transcripts for ifng and cxcl10. Histological analysis revealed parasites within blood vessels of both the submucosa and intestinal villi and evidence of mild crypt hyperplasia. In faeces, concentrations of the inflammatory marker lactoferrin were significantly raised on days 9 and 11 and FITC-dextran was detected in plasma on days 7 to 14. At day 11, plasma FITC-dextran concentration was significantly positively correlated with peripheral parasitemia and faecal lactoferrin concentration. Conclusions: In summary, using a relevant, attenuated model of malaria, we have found that acute infection is associated with intestinal inflammation and increased intestinal permeability. This model can now be used to explore the mechanisms of parasite-induced intestinal inflammation and to assess the impact of increased intestinal permeability on translocation of enteropathogens

miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics

Background: The tumor suppressor PTEN (phosphatase and tensin homolog) is a lipid phosphatase that converts PIP3 into PIP2 and downregulates the kinase AKT and its proliferative and anti-apoptotic activities. The FoxO transcription factors are PTEN downstream effectors whose activity is negatively regulated by AKT-mediated phosphorylation. PTEN activity is frequently lost in many types of cancer, leading to increased cell survival and cell cycle progression. Principal Findings: Here we characterize the widely expressed miR-22 and report that miR-22 is a novel regulatory molecule in the PTEN/AKT pathway. miR-22 downregulates PTEN levels acting directly through a specific site on PTEN 39UTR. Interestingly, miR-22 itself is upregulated by AKT, suggesting that miR-22 forms a feed-forward circuit in this pathway. Timeresolved live imaging of AKT-dependent FoxO1 phosphorylation revealed that miR-22 accelerated AKT activity upon growth factor stimulation, and attenuated its down regulation by serum withdrawal. Conclusions: Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway

Anti-Neuroinflammatory effects of the extract of Achillea fragrantissima

<p>Abstract</p> <p>Background</p> <p>The neuroinflammatory process plays a central role in the initiation and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, and involves the activation of brain microglial cells. During the neuroinflammatory process, microglial cells release proinflammatory mediators such as cytokines, matrix metalloproteinases (MMP), Reactive oxygen species (ROS) and nitric oxide (NO). In the present study, extracts from 66 different desert plants were tested for their effect on lipopolysaccharide (LPS) - induced production of NO by primary microglial cells. The extract of <it>Achillea fragrantissima </it>(<it>Af</it>)<it/>, which is a desert plant that has been used for many years in traditional medicine for the treatment of various diseases, was the most efficient extract, and was further studied for additional anti-neuroinflammatory effects in these cells.</p> <p>Methods</p> <p>In the present study, the ethanolic extract prepared from <it>Af </it>was tested for its anti-inflammatory effects on lipopolysaccharide (LPS)-activated primary cultures of brain microglial cells. The levels of the proinflammatory cytokines interleukin1β (IL-1β) and tumor necrosis factor-α (TNFα) secreted by the cells were determined by reverse transcriptase-PCR and Enzyme-linked immunosorbent assay (ELISA), respectively. NO levels secreted by the activate cells were measured using Griess reagent, ROS levels were measured by 2'7'-dichlorofluorescein diacetate (DCF-DA), MMP-9 activity was measured using gel zymography, and the protein levels of the proinflammatory enzymes cyclooxygenase-2 (COX-2) and induced nitric oxide synthase (iNOS) were measured by Western blot analysis. Cell viability was assessed using Lactate dehydrogenase (LDH) activity in the media conditioned by the cells or by the crystal violet cell staining.</p> <p>Results</p> <p>We have found that out of the 66 desert plants tested, the extract of <it>Af </it>was the most efficient extract and inhibited ~70% of the NO produced by the LPS-activated microglial cells, without affecting cell viability. In addition, this extract inhibited the LPS - elicited expression of the proinflammatory mediators IL-1β, TNFα, MMP-9, COX-2 and iNOS in these cells.</p> <p>Conclusions</p> <p>Thus, phytochemicals present in the <it>Af </it>extract could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.</p

Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme

Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM.Based on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution.The top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was PERIOSTIN (POSTN). The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (P<0.001). High POSTN and low miR-219 expression were significantly associated with the mesenchymal GBM subtype (P<0.0001).Here, we propose a novel diagnostic method to screen for molecular cancer subtypes and genomic correlates of cellular invasion. Our findings also have potential therapeutic significance since successful molecular inhibition of invasion will improve therapy and patient survival in GBM