Wastewater-based epidemiology as a public health resource in low- and middle-income settings.

In the face of emerging and re-emerging diseases, novel and innovative approaches to population scale surveillance are necessary for the early detection and quantification of pathogens. The last decade has seen the rapid development of wastewater and environmental surveillance (WES) to address public health challenges, which has led to establishment of wastewater-based epidemiology (WBE) approaches being deployed to monitor a range of health hazards. WBE exploits the fact that excretions and secretions from urine, and from the gut are discharged in wastewater, particularly sewage, such that sampling sewage systems provides an early warning system for disease outbreaks by providing an early indication of pathogen circulation. While WBE has been mainly used in locations with networked wastewater systems, here we consider its value for less connected populations typical of lower-income settings, and in assess the opportunity afforded by pit latrines to sample communities and localities. We propose that where populations struggle to access health and diagnostic facilities, and despite several additional challenges, sampling unconnected wastewater systems remains an important means to monitor the health of large populations in a relatively cost-effective manner.

Qualitative and quantitative detection of SARS-CoV-2 RNA in untreated wastewater in Western Cape Province, South Africa.

Recent studies have shown that the detection of SARS-CoV-2 genetic material in wastewater may provide the basis for a surveillance system to track the environmental dissemination of this virus in communities. An effective wastewater-based epidemiology (WBE) system may prove critical in South Africa (SA), where health systems infrastructure, testing capacity, personal protective equipment and human resource capacity are constrained. In this proof-of-concept study, we investigated the potential of SARS-CoV-2 RNA surveillance in untreated wastewater as the basis for a system to monitor COVID-19 prevalence in the population, an early warning system for increased transmission, and a monitoring system to assess the effectiveness of interventions. The laboratory confirmed the presence (qualitative analysis) and determined the RNA copy number of SARS-CoV-2 viral RNA by reverse transcription polymerase chain reaction (quantitative) analysis from 24-hour composite samples collected on 18 June 2020 from five wastewater treatment plants in Western Cape Province, SA. The study has shown that a WBE system for monitoring the status and trends of COVID-19 mass infection in SA is viable, and its development and implementation may facilitate the rapid identification of hotspots for evidence-informed interventions.

Living conditions and respiratory health in Walmer Township and Wells Estate, Port Elizabeth, South Africa.

BACKGROUND: Many impoverished communities in South Africa (SA) simultaneously face multiple preventable socioenvironmental hazards associated with elevated burdens of ill health. One such hazard is failure to institute effective buffer zones between human settlements and point sources of pollution such as airports and industrial zones. OBJECTIVES: To gather information on living conditions, housing quality and health status in two poor communities in the SA coastal industrial city of Port Elizabeth. METHODS: The study was undertaken in Walmer Township, situated in close proximity to Port Elizabeth International Airport, and Wells Estate, which borders two industrial sites. Approximately 120 households were randomly selected from each study site. Following written informed consent, information on the neighbourhood environment and housing conditions was collected through administration of a structured questionnaire. RESULTS: The two study sites were similar in respect of household language, income, education, high levels of debt servicing and high reliance on social grants. Relative to Walmer Township, higher levels of indoor dust and bad odours in the neighbourhood were reported in Wells Estate, as were higher rates of selected respiratory ill-health symptoms. Upper respiratory tract symptoms were significantly associated with reports of high levels of indoor dust, while lower respiratory tract symptoms were significantly associated with low income, overcrowding, and having a young child in the household. CONCLUSIONS: The study highlights a scenario of a triple environmental hazard to health in the study communities: (i) poverty; (ii) poor-quality housing; and (iii) lack of an effective buffer zone between the study communities and local point sources of pollution. Respiratory ill-health conditions were significantly associated with poverty, household composition and living conditions.

Traditional health practitioners and sustainable development: a case study in South Africa.

OBJECTIVES: To highlight legal and regulatory advances relating to South African traditional health practitioners (THPs) over the past 10 years and discuss the implications for the translation of health policies into guidelines for sustainable practice supporting public health. STUDY DESIGN: This is a rapid, structured literature review. METHODS: A rapid, structured literature review was undertaken to identify relevant studies related to South African THPs involving a search of peer-reviewed literature from three databases and a grey literature internet search. The identified citations were screened, critically appraised, and narratively synthesized. RESULTS: Efforts to regulate THPs in South Africa are underway; however, the lack of a regulatory framework for traditional practices is hampering progress. Several efforts to collaborate with THPs have been made over the years, many of which were not systematically evaluated and not based on principles of mutual respect. Existing collaborative examples need to be further supported by cost-effective evidence to suit the South African public health budget. Furthermore, small collaborative research efforts do not take into consideration the scale up of interventions. CONCLUSIONS: THPs in South Africa represent an important healthcare resource. However, the current policy environment does not support indicators to describe, monitor, and/or evaluate the role of THPs in the healthcare system.

Ethnopharmacological use of potassium permanganate in South African traditional medicine.

BACKGROUND: Potassium permanganate (KMnO4), which is widely available, is often used by traditional health practitioners (THPs) in South Africa (SA) without taking its potentially harmful properties into account. The crystalline KMnO4 salt is sold at traditional medicine markets and shops throughout SA. However, to date, traditional uses of KMnO4 remain undocumented. OBJECTIVE: To describe KMnO4 use by THPs in KwaZulu-Natal, SA. METHODS: This sub-study is part of a larger study investigating substances used in SA traditional medicine that are collectively known as imikhando in isiZulu - literally translated as 'ore'. THPs (N=201) were interviewed in the local language (isiZulu) by trained interviewers. Information on the reasons for using/not using KMnO4, the source of information on its use and modes of administration were collected. RESULTS: KMnO4 was used as a constituent of traditional medicine by 158 (79%) THPs. Their knowledge of KMnO4 use was acquired predominantly from fellow THPs (n=134; 85%). Reasons for use included skin rash or wounds (n=99, 63%) and to treat aches, pains and swelling (n=74; 47%). The main modes of administration were in the bath (n=94; 60%), orally (n=67; 42%) and in herbal compresses (n=66; 42%). The principal reason of the 43 THPs for not administering KMnO4 was not knowing how to use it (n=29; 71%). CONCLUSIONS: This study has identified traditional medicine users at risk of manganese toxicity owing to commonly used sociocultural practices. In particular, reports of oral ingestion and use in enemas are cause for concern. This public health issue needs regulatory measures and education programmes to enlighten the population against possible harm caused by KMnO4 exposure.

Bibliometric trends of South African environmental health articles between 1998 and 2015: Making local research visible and retrievable.

BACKGROUND: South Africa (SA) has to grapple with multiple burdens of disease for which environmental factors have a role to play in both causation and prevention. This article describes a bibliometric review of environmental health indexed literature for SA over an 18-year period. OBJECTIVES: To provide an overview of the nature of SA-based published environmental health indexed research and to identify search challenges, frequently researched topics, and gaps and opportunities for future research. METHODS: The Web of Science, PubMed and Science Direct were used to search for original, peer-reviewed and review articles with the inclusion criteria 'environmental health' and 'South Africa' available online and published between 1998 and 2015, inclusively. RESULTS: A total of 230 journal articles were included in the bibliometric analysis. The highest number of articles (n=54) was published in 2015. The majority of the first authors were affiliated with SA institutions (n=160, 69.5%). For the articles where funding was explicitly declared (n=148), the three most frequently occurring agencies that funded the published research were the National Research Foundation in SA (n=17), the South African Medical Research Council (n=13) and the Water Research Commission (n=9). There was little inter-annual/environmental health category variation over time owing to the relatively small sample size. The largest number of retrieved journal articles was in the area of environmental pollution control (n=76), followed by environmental health lifestyle and behaviour-related topics (n=42) and then water monitoring (n=26). CONCLUSIONS: Despite the research needed to solve large environmental health challenges in SA, environmental health was only used as a keyword in title, author keywords or abstract for 230 SA-based studies over an 18-year period. This makes it extremely difficult for environmental health research to be located and used to inform the profession as well as the research agenda. Several issues that environmental health practitioners are typically tasked to implement and monitor are not indexed as environmental health topics. The need for authors to use 'environmental health' as a keyword is emphasised, particularly if research is to inform decision-making and policy support, as well as guide future research in the country.

5-Hydroxymethylation-associated epigenetic modifiers of Alzheimer's disease modulate Tau-induced neurotoxicity.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognitive function. Pathogenesis of AD is incompletely understood; evidence suggests a role for epigenetic regulation, in particular the cytosine modifications 5-methylcytosine and 5-hydroxymethylcytosine (5hmC). 5hmC is enriched in the nervous system and displays neurodevelopment and age-related changes. To determine the role of 5hmC in AD, we performed genome-wide analyses of 5hmC in DNA from prefrontal cortex of post-mortem AD patients, and RNA-Seq to correlate changes in 5hmC with transcriptional changes. We identified 325 genes containing differentially hydroxymethylated loci (DhMLs) in both discovery and replication datasets. These are enriched for pathways involved in neuron projection development and neurogenesis. Of these, 140 showed changes in gene expression. Proteins encoded by these genes form direct protein-protein interactions with AD-associated genes, expanding the network of genes implicated in AD. We identified AD-associated single nucleotide polymorphisms (SNPs) located within or near DhMLs, suggesting these SNPs may identify regions of epigenetic gene regulation that play a role in AD pathogenesis. Finally, using an existing AD fly model, we showed some of these genes modulate AD-associated toxicity. Our data implicate neuronal projection development and neurogenesis pathways as potential targets in AD. By incorporating epigenomic and transcriptomic data with genome-wide association studies data, with verification in the Drosophila model, we can expand the known network of genes involved in disease pathogenesis and identify epigenetic modifiers of Alzheimer's disease.

A minimally invasive anterior skull base approach for evacuation of a basal ganglia hemorrhage.

We describe the technical nuances of a minimally invasive anterior skull base approach for microsurgical evacuation of a large basal ganglia hematoma through an endoport. Patients who suffer from large spontaneous intracerebral hemorrhages (ICH) of the basal ganglia have a very poor prognosis. However, the benefit of surgery for the management of ICH is controversial. The development of endoport technology has allowed for minimally invasive access to subcortical lesions, and may offer unique advantages over conventional surgical techniques due to less disruption of the overlying cortex and white matter fiber tracts. A 77-year-old man presented with a hypertensive ICH of the right putamen, measuring 9 cm in maximal diameter and 168 cm(3) in volume. We planned an endoport trajectory through the long axis of the hematoma using frameless stereotactic neuronavigation. In order to access the optimal cortical entry point at the lateral aspect of the basal frontal lobe, a miniature modified orbitozygomatic skull base craniotomy was performed through an incision along the superior border of the right eyebrow. Using the BrainPath endoport system (NICO, Indianapolis, IN, USA), the putaminal hematoma was successfully evacuated, resulting in an 87% postoperative reduction in ICH volume. Thus, we show that, in appropriately selected cases, endoport-assisted microsurgery is safe and effective for the evacuation of large ICH. Furthermore, minimally invasive anterior skull base approaches can be employed to expand the therapeutic potential of endoport-assisted approaches to include subcortical lesions, such as hematomas of the basal ganglia.

Base-resolution methylation patterns accurately predict transcription factor bindings in vivo.

Detecting in vivo transcription factor (TF) binding is important for understanding gene regulatory circuitries. ChIP-seq is a powerful technique to empirically define TF binding in vivo. However, the multitude of distinct TFs makes genome-wide profiling for them all labor-intensive and costly. Algorithms for in silico prediction of TF binding have been developed, based mostly on histone modification or DNase I hypersensitivity data in conjunction with DNA motif and other genomic features. However, technical limitations of these methods prevent them from being applied broadly, especially in clinical settings. We conducted a comprehensive survey involving multiple cell lines, TFs, and methylation types and found that there are intimate relationships between TF binding and methylation level changes around the binding sites. Exploiting the connection between DNA methylation and TF binding, we proposed a novel supervised learning approach to predict TF-DNA interaction using data from base-resolution whole-genome methylation sequencing experiments. We devised beta-binomial models to characterize methylation data around TF binding sites and the background. Along with other static genomic features, we adopted a random forest framework to predict TF-DNA interaction. After conducting comprehensive tests, we saw that the proposed method accurately predicts TF binding and performs favorably versus competing methods.

Environmental enrichment modulates 5-hydroxymethylcytosine dynamics in hippocampus.

Gene-environment interactions mediated at the epigenetic level may provide an initial step in delivering an appropriate response to environmental changes. 5-Hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC), accounts for ~40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity. To identify the role of 5hmC in gene-environment interactions, we exposed both young (6-week-old) and aged (18-month-old) mice to both an enriched environment and a standard environment. Exposure to EE significantly improves learning and memory in aged mice and reduces 5hmC abundance in mouse hippocampus. Furthermore, we mapped the genome-wide distribution of 5hmC and found that the alteration of 5hmC modification occurred mainly at gene bodies. In particular, genes involved in axon guidance are enriched among the genes with altered 5hmC modification. These results together suggest that environmental enrichment could modulate the dynamics of 5hmC in hippocampus, which could potentially contribute to improved learning and memory in aged animals.

Coordination of engineered factors with TET1/2 promotes early-stage epigenetic modification during somatic cell reprogramming.

Somatic cell reprogramming toward induced pluripotent stem cells (iPSCs) holds great promise in future regenerative medicine. However, the reprogramming process mediated by the traditional defined factors (OSMK) is slow and extremely inefficient. Here, we develop a combination of modified reprogramming factors (OySyNyK) in which the transactivation domain of the Yes-associated protein is fused to defined factors and establish a highly efficient and rapid reprogramming system. We show that the efficiency of OySyNyK-induced iPSCs is up to 100-fold higher than the OSNK and the reprogramming by OySyNyK is very rapid and is initiated in 24 hr. We find that OySyNyK factors significantly increase Tet1 expression at the early stage and interact with Tet1/2 to promote reprogramming. Our studies not only establish a rapid and highly efficient iPSC reprogramming system but also uncover a mechanism by which engineered factors coordinate with TETs to regulate 5hmC-mediated epigenetic control.

Genome-wide alteration of 5-hydroxymethylcytosine in a mouse model of fragile X-associated tremor/ataxia syndrome.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder in which patients carry premutation alleles of 55-200 CGG repeats in the FMR1 gene. To date, whether alterations in epigenetic regulation modulate FXTAS has gone unexplored. 5-Hydroxymethylcytosine (5hmC) converted from 5-methylcytosine (5mC) by the ten-eleven translocation (TET) family of proteins has been found recently to play key roles in neuronal functions. Here, we undertook genome-wide profiling of cerebellar 5hmC in a FXTAS mouse model (rCGG mice) and found that rCGG mice at 16 weeks showed overall reduced 5hmC levels genome-wide compared with age-matched wild-type littermates. However, we also observed gain-of-5hmC regions in repetitive elements, as well as in cerebellum-specific enhancers, but not in general enhancers. Genomic annotation and motif prediction of wild-type- and rCGG-specific differential 5-hydroxymethylated regions (DhMRs) revealed their high correlation with genes and transcription factors that are important in neuronal developmental and functional pathways. DhMR-associated genes partially overlapped with genes that were differentially associated with ribosomes in CGG mice identified by bacTRAP ribosomal profiling. Taken together, our data strongly indicate a functional role for 5hmC-mediated epigenetic modulation in the etiology of FXTAS, possibly through the regulation of transcription.

Commonly used metal and crystalline salts in South African traditional medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional medicines in the form of plants, animals and/or minerals are used by millions of South Africans. There is currently no data regarding the commonly used mineral elements thus the potential benefits or hazards of such products remain unclear. MATERIALS AND METHODS: Metal and crystalline salts were purchased from a rural market (Nongoma, Zululand, South Africa). Information regarding the colloquial name, price and weight was recorded. Energy dispersive X-ray spectroscopy (EDX) was used to quantatively determine the unknown salts. RESULTS: Six widely available salts were analyzed. Ndonya, as it is colloquially known, refers to two products which look identical to the untrained eye-one is dyed table salt and the other is hexavalent chromium. A further product used medicinally, although not widely available, was identified as iron chromite ore. CONCLUSIONS: The array of substances documented, ranging from benign to carcinogenic, stresses the importance of documenting components used in traditional medicine and confirms the necessity to regulate South Africa traditional medicine. Healthcare workers should be aware of the complexities of using such metal salt.

Patients' intuitive judgments about surveillance endoscopy in Barrett's esophagus: a review and application to models of decision-making.

Adherence to practice guidelines for endoscopic surveillance of Barrett's esophagus is equivocal with evidence of underutilization and overutilization. While physicians report strong agreement with and adherence to recommended surveillance endoscopy (esophagogastroduodenoscopy [EGD]) guidelines, less is known about modifiable barriers and facilitators shaping patients' adherence behaviors. The aim of this study is to conduct a structured literature review of studies exploring patients' perspectives regarding surveillance EGD and to place these results within a conceptual framework. A structured literature review of PubMed, Cochrane, and Google Scholar databases with qualitative thematic analysis was performed. Six studies met eligibility criteria. Analysis of results identified five distinct themes. First, patients' objective cancer risk estimates are consistent with subjective risk perceptions, but neither is associated with EGD surveillance. Second, patients have strong beliefs in the benefits of cancer screening and surveillance and trust in their doctors. Third, anxiety and depression symptoms are related to risk perceptions and outcome expectancies of surveillance. Fourth, endoscopic surveillance itself has affective and physical consequences. Finally, health services and system variables are related to risk perception and EGD surveillance. These themes coherently fit within an integrated model of intuitive decision-making and health behaviors. Studies meeting eligibility criteria were heterogeneous in terms of their study objectives and findings. Quantitative meta-analyses of study findings could not be performed. To improve adherence, endoscopic surveillance programs should consider how patients intuitively frame risks and benefits and patients' emotional reactions to the endoscopy procedure, and focus on how physicians communicate recommendations.

South African traditional medicinal plant trade-Challenges in regulating quality, safety and efficacy.

Based on the long history of medicinal plant use, users of traditional medicines accept that they are safe for human consumption. However, the absence of regulation of the medicinal plant trade in aspects such as collection, processing and storage provides no such guarantee. Environmental pollution, misidentification and adulteration provides further grounds for concern. The potential adverse effects of South African traditional medicines are not well documented. There are only a few investigations of mutagenic properties and heavy metal contamination. In the absence of regulatory controls, the safety and quality of medicinal plants vary considerably. The current comprehension and future challenges regarding quality, safety and efficacy of South African traditional medicine are discussed.

Variation in heavy metals and microelements in South African medicinal plants obtained from street markets.

South African medicinal plants are traditionally harvested from a wide range of undisclosed locations by plant gatherers. Thus, there is a risk that plant material may be exposed to a variety of pollutants. The variation in five heavy metals (arsenic, cadmium, cobalt, nickel, and lead) and six essential elements (boron, copper, iron, manganese, molybdenum, and zinc) was determined in commonly used South African medicinal plants obtained from street markets. Elemental content was determined using inductively coupled plasma optical emission spectrophotometry. The reliability of the procedure was ensured by analysing a certified reference material. Medicinal plant samples contained arsenic and cadmium at levels exceeding the World Health Organization limits of 1 and 0.3 mg kg(-1) respectively. Lead and nickel were detected in all samples. Elevated iron and manganese levels were recorded in certain plant species. Multiple metal contamination of parts of medicinal plants gives grounds for concern. This study emphasizes the unsafe consequences of the South African practice of collecting medicinal plants from undisclosed locations and making these readily available to the public.

Fabrication of high aspect-ratio polymer microstructures for large-area electronic portal x-ray imagers.

Megavoltage x-ray imaging performed during radiotherapy is the method of choice for geometric verification of patient localization and dose delivery. Presently, such imaging is increasingly performed using electronic portal imaging devices (EPIDs) based on indirect detection active matrix flat panel imagers (AMFPIs). These devices use a scintillating phosphor screen in order to convert incident x-rays into optical photons, which are then detected by the underlying active matrix photodiode array. The use of a continuous phosphor introduces a trade-off between x-ray quantum efficiency and spatial resolution, which limits current devices to use only ∼2% of the incident x-rays. This trade-off can be circumvented by "segmented phosphor screens", comprising a two-dimensional matrix of optically-isolated cell structures filled with scintillating phosphor. In this work we describe the fabrication of millimeter-thick segmented phosphor screens using the MEMS (micro-electro-mechanical-system) polymer SU-8. This method is capable of being extended to large-area substrates.

Toxicity of metal elements on germination and seedling growth of widely used medicinal plants belonging to Hyacinthaceae.

In South Africa, pollution of agricultural soils is on the increase primarily due to excessive application of fertilizers, sewage disposal and mining activities. This study was done to determine the effect of trace elements (Cu, Zn) and heavy metals (Cd, Pb, Hg) on germination and seedling development of Bowiea volubilis, Eucomis autumnalis and Merwilla natalensis. These medicinal plant species are highly recommended for cultivation in South Africa to reduce the pressure on wild populations. Copper and Zn at 1 mg L(-1) significantly (p < 0.05) reduced the percentage germination of E. autumnalis. Low concentrations (>or=1 mg L(-1)) of Cu and Zn negatively affected the roots of all three species. Mercury concentrations of 0.5 and 1 mg L(-1) significantly (p < 0.05) decreased the percentage germination of B. volubilis and E. autumnalis respectively. Cadmium and Hg at 2 mg L(-1) showed a detrimental effect on the root growth of B. volubilis. Concentrations of 0.5 mg L(-1) of all heavy metals tested significantly (p < 0.05) decreased shoot length of M. natalensis.