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Melinda Hergert,1 Kevin le Roux,2 Louis H Nel3,4 1Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Pretoria, 2KwaZulu-Natal Department of Environment, Agriculture and Rural Development, Government Veterinary Services, Pietermaritzburg, 3Department of Microbiology and Plant Pathology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa; 4Global Alliance for Rabies Control, Manhattan, KS, USA Abstract: Canine rabies has been enzootic in the dog population of the KwaZulu-Natal ­province of South Africa since the mid-1970s and has been associated with high rates of human exposures and frequent transmissions to other domestic animal species. Several decades of control efforts, consisting primarily of mass vaccination programs, failed to sufficiently curb rabies in this province. For meaningful progression toward better control and elimination, the factors contributing to the persistence of this disease need to be elucidated and addressed. This paper reports evaluated observations from survey records captured through a cross-sectional observational study regarding owned canine populations in this South African province. We used logistic regression modeling to predict variables associated with risk of nonvaccination of rabies in owned dogs. The study indicated that husbandry practices, rabies knowledge, geographical area/location, and the ages of dogs were important factors associated with the risk of nonvaccination. High population turnover, together with large free roaming dog populations, compromised the levels of vaccination achieved and contributed to the persistence of dog rabies in the province. Dog owners in this study also reported that they were more likely to present their dogs for vaccination when the vaccines were free of charge (52%) and less than a kilometer from their homes (91%). It has been suggested that effective dog rabies control requires 70% or more of the dog population to be vaccinated. Our data showed that this figure was not reached in the surveyed dog population. Keywords: dog population, canine rabies, rabies vaccination, vaccination campaigns, ­KwaZulu-Natal, South Africa, dog owners more...

BackgroundImmunisations are one of the most cost-effective public health interventions available and South Africa (SA) has implemented a comprehensive immunisation schedule. However, there is disagreement about the level of immunisation coverage in the country and few studies document the immunisation coverage in rural areas.ObjectiveTo examine the successful and timely delivery of immunisations to children during the first 2 years of life in a deeply rural part of the Eastern Cape Province of SA.MethodsFrom January to April 2013, a cohort of sequential births (N=470) in the area surrounding Zithulele Hospital in the OR Tambo District of the Eastern Cape was recruited and followed up at home at 3, 6, 9, 12 and 24 months post birth, up to May 2015. Immunisation coverage was determined using Road-to-Health cards.ResultsThe percentages of children with all immunisations up to date at the time of interview were: 48.6% at 3 months, 73.3% at 6 months, 83.9% at 9 months, 73.3% at 12 months and 73.2% at 24 months. Incomplete immunisations were attributed to stock-outs (56%), lack of awareness of the immunisation schedule or of missed immunisations by the mother (16%) and lack of clinic attendance by the mother (19%). Of the mothers who had visited the clinic for baby immunisations, 49.8% had to make multiple visits because of stock-outs. Measles coverage (of at least one dose) was 85.2% at 1 year and 96.3% by 2 years, but 20.6% of babies had not received a second measles dose (due at 18 months) by 2 years. Immunisations were often given late, particularly the 14-week immunisations.ConclusionsImmunisation rates in the rural Eastern Cape are well below government targets and indicate inadequate provision of basic primary care. Stock-outs of basic childhood immunisations are common and are, according to mothers, the main reason for their children's immunisations not being up to date. There is still much work to be done to ensure that the basics of disease prevention are being delivered at rural clinics in the Eastern Cape, despite attempts to re-engineer primary healthcare in SA. more...

Chrysotherapeutics are under investigation as new or additional treatments for different types of cancers. In this study, gold complexes were investigated for their anticancer potential using Raman spectroscopy. The aim of the study was to determine whether Raman spectroscopy could be used for the characterization of metallodrug-induced cell death. Symptoms of cell death such as decreased peak intensities of proteins bonds and phosphodiester bonds found in deoxyribose nucleic acids were evident in the principal component analysis of the spectra. Vibrational bands around 761cm-1 and 1300cm-1 (tryptophan, ethanolamine group, and phosphatidylethanolamine) and 1720cm-1 (ester bonds associated with phospholipids) appeared in the Raman spectra of cervical adenocarcinoma (HeLa) cells after metallodrug treatment. The significantly (p<0.05, one way analysis of variance) increased intensity of phosphatidylethanolamine after metallodrug treatment could be a molecular signature of induced apoptosis since both the co-regulated phosphatidylserine and phosphatidylethanolamine are externalized during cell death. Treated cells had significantly higher levels of glucose and glycogen vibrational peaks, indicative of a survival mechanism of cancer cells under chemical stress. Cancer cells excrete chemotherapeutics to improve their chances of survival and utilize glucose to achieve this. Raman spectroscopy was able to monitor a survival strategy of cancer cells in the form of glucose uptake to alleviate chemical stress. Raman spectroscopy was invaluable in obtaining molecular information generated by biomolecules affected by anticancer metallodrug treatments and presents an alternative to less reproducible, conventional biochemical assays for cytotoxicity analyses. [ABSTRACT FROM AUTHOR] more...

A rapid immunodiagnostic test kit was evaluated against a selection of isolates of lyssavirus genotypes occurring in Africa. The test was carried out in parallel comparison with the fluorescent antibody test (FAT) and isolates representing previously established phylogenetic groups from each genotype were included. The specificity of the rapid immunodiagnostic test compared favourably with the FAT and was found to detect all representatives of genotypes 1, 2, 3 and 4 in brain samples of either field cases or suckling mouse brain inoculates. [ABSTRACT FROM AUTHOR] more...

Abstract: Introduction: In 2005–2006, during the Chikungunya virus outbreak in La Réunion (Indian Ocean), we urgently established the molecular and serological methods for the diagnosis of Chikungunya virus (CHIKV) from various types of samples. Methods: CHIKV RNA was detected using a highly sensitive real-time RT PCR assay. A co-extracted and co-amplified internal control RNA was used to identify RT PCR inhibitors. Depending on their nature samples were pretreated before nucleic acid extraction. Viral loads were measured using a synthetic RNA calibrator. CHIKV immunoglobulin (Ig) G and M antibodies were detected by ELISA either from sera or from blood absorbed on filter paper. Results: CHIKV RNA was found in various types of samples such as plasma, cerebrospinal fluid, and placenta, but was not found in some samples including maternal milk and synovial samples. Detection of IgG from filter paper absorbed blood is specific and sensitive. Routine data showed that maternally transferred IgG and naturally acquired IgM persist at least 12 and 18 months, respectively. Discussion: The techniques enabled the diagnosis of chikungunya in known and newly described forms of the disease. They are used for routine diagnosis and large scale surveys. [Copyright &y& Elsevier] more...

Abstract Background Child and infant malnourishment is a significant and growing problem in the developing world. Malnourished children are at high risk for negative health outcomes over their lifespans. Philani, a paraprofessional home visiting program, was developed to improve childhood nourishment. The objective of this study is to evaluate whether the Philani program can rehabilitate malnourished children in a timely manner. Methods Mentor Mothers were trained to conduct home visits. Mentor Mothers went from house to house in assigned neighborhoods, weighed children age 5 and younger, and recruited mother-child dyads where there was an underweight child. Participating dyads were assigned in a 2:1 random sequence to the Philani intervention condition (n = 536) or a control condition (n = 252). Mentor Mothers visited dyads in the intervention condition for one year, supporting mothers' problem-solving around nutrition. All children were weighed by Mentor Mothers at baseline and three, six, nine and twelve month follow-ups. Results By three months, children in the intervention condition were five times more likely to rehabilitate (reach a healthy weight for their ages) than children in the control condition. Throughout the course of the study, 43% (n = 233 of 536) of children in the intervention condition were rehabilitated while 31% (n = 78 of 252) of children in the control condition were rehabilitated. Conclusions Paraprofessional Mentor Mothers are an effective strategy for delivering home visiting programs by providing the knowledge and support necessary to change the behavior of families at risk. more...

Abstract Background Pseudomonas fluorescens is present in low number in the intestinal lumen and has been proposed to play a role in Crohn's disease (CD). Indeed, a highly specific antigen, I2, has been detected in CD patients and correlated to the severity of the disease. We aimed to determine whether P. fluorescens was able to adhere to human intestinal epithelial cells (IECs), induce cytotoxicity and activate a proinflammatory response. Results Behaviour of the clinical strain P. fluorescens MFN1032 was compared to that of the psychrotrophic strain P. fluorescens MF37 and the opportunistic pathogen P. aeruginosa PAO1. Both strains of P. fluorescens were found to adhere on Caco-2/TC7 and HT-29 cells. Their cytotoxicity towards these two cell lines determined by LDH release assays was dose-dependent and higher for the clinical strain MFN1032 than for MF37 but lower than P. aeruginosa PAO1. The two strains of P. fluorescens also induced IL-8 secretion by Caco-2/TC7 and HT-29 cells via the AP-1 signaling pathway whereas P. aeruginosa PAO1 potentially used the NF-κB pathway. Conclusions The present work shows, for the first time, that P. fluorescens MFN1032 is able to adhere to IECs, exert cytotoxic effects and induce a proinflammatory reaction. Our results are consistent with a possible contribution of P. fluorescens in CD and could explain the presence of specific antibodies against this bacterium in the blood of patients. more...

Abstract Background Chikungunya virus (CHIKV) caused a major two-wave seventeen-month-long outbreak in La Réunion Island in 2005–2006. The aim of this study was to refine clinical estimates provided by a regional surveillance-system using a two-stage serological assessment as gold standard. Methods Two serosurveys were implemented: first, a rapid survey using stored sera of pregnant women, in order to assess the attack rate at the epidemic upsurge (s1, February 2006; n = 888); second, a population-based survey among a random sample of the community, to assess the herd immunity in the post-epidemic era (s2, October 2006; n = 2442). Sera were screened for anti-CHIKV specific antibodies (IgM and IgG in s1, IgG only in s2) using enzyme-linked immunosorbent assays. Seroprevalence rates were compared to clinical estimates of attack rates. Results In s1, 18.2% of the pregnant women were tested positive for CHIKV specific antibodies (13.8% for both IgM and IgG, 4.3% for IgM, 0.1% for IgG only) which provided a congruent estimate with the 16.5% attack rate calculated from the surveillance-system. In s2, the seroprevalence in community was estimated to 38.2% (95% CI, 35.9 to 40.6%). Extrapolations of seroprevalence rates led to estimate, at 143,000 and at 300,000 (95% CI, 283,000 to 320,000), the number of people infected in s1 and in s2, respectively. In comparison, the surveillance-system estimated at 130,000 and 266,000 the number of people infected for the same periods. Conclusion A rapid serosurvey in pregnant women can be helpful to assess the attack rate when large seroprevalence studies cannot be done. On the other hand, a population-based serosurvey is useful to refine the estimate when clinical diagnosis underestimates it. Our findings give valuable insights to assess the herd immunity along the course of epidemics. more...

Purpose To evaluate the various clinical presentations, etiological diagnosis and prognosis of patients with scleritis at a tertiary care eye center. Methods Retrospective, monocentric and analytical study on a series of 32 patients with scleritis seen in the departments of Ophthalmology and Internal Medicine at Croix‐Rousse University Hospital, Lyon, France from 2004 through 2011. Results The mean age of patients with scleritis was 46.8 years (range 22‐77years). Nineteen of the patients were women and 13 were men. Twenty‐six patients (81%) had anterior scleritis (15 nodular, 8 diffuse and 3 necrotizing), six (19%) had posterior scleritis. Unilateral inflammation was present in 24 patients (75%). Twelve of the 32 patients (37.5%) had a systemic disease : Wegener's granulomatosis (n = 3),Behçet's disease (n = 2), unspecified inflammatory arthritis (n = 2), psoriatic arthritis (n = 1),ankylosing spondylitis (n = 1), sarcoidosis (n = 1), Cogan's syndrome (n = 1), ulcerative colitis (n = 1). Six patients (18.8%) were suspected of having infectious disease with herpes : clinical context and positive treatment response with oral valacyclovir. Systemic agents and topical agents were required in 28 patients (87.5%). The first line therapy was mainly oral non steroidal anti‐inflammatory drugs in 15 patients (47%) and oral corticosteroids in 8 (25%). Immunosuppressive drugs were required in 6 patients, 4 with systemic disease. The mean follow‐up was 16.3 months. Conclusion The number of systemic disease in our series is similar to the main series in the literature. Treatment with valacyclovir might be effective in patients with suspected herpes simplex scleritis. [ABSTRACT FROM AUTHOR] more...

Background: An outbreak of chikungunya virus affected over one-third of the population of La Réunion Island between March 2005 and December 2006. In June 2005, we identified the first case of mother-to-child chikungunya virus transmission at the Groupe Hospitalier Sud-Réunion level-3 maternity department. The goal of this prospective study was to characterize the epidemiological, clinical, biological, and radiological features and outcomes of all the cases of vertically transmitted chikungunya infections recorded at our institution during this outbreak.Methods and Findings: Over 22 mo, 7,504 women delivered 7,629 viable neonates; 678 (9.0%) of these parturient women were infected (positive RT-PCR or IgM serology) during antepartum, and 61 (0.8%) in pre- or intrapartum. With the exception of three early fetal deaths, vertical transmission was exclusively observed in near-term deliveries (median duration of gestation: 38 wk, range 35-40 wk) in the context of intrapartum viremia (19 cases of vertical transmission out of 39 women with intrapartum viremia, prevalence rate 0.25%, vertical transmission rate 48.7%). Cesarean section had no protective effect on transmission. All infected neonates were asymptomatic at birth, and median onset of neonatal disease was 4 d (range 3-7 d). Pain, prostration, and fever were present in 100% of cases and thrombocytopenia in 89%. Severe illness was observed in ten cases (52.6%) and mainly consisted of encephalopathy (n = 9; 90%). These nine children had pathologic MRI findings (brain swelling, n = 9; cerebral hemorrhages, n = 2), and four evolved towards persistent disabilities.Conclusions: Mother-to-child chikungunya virus transmission is frequent in the context of intrapartum maternal viremia, and often leads to severe neonatal infection. Chikungunya represents a substantial risk for neonates born to viremic parturients that should be taken into account by clinicians and public health authorities in the event of a chikungunya outbreak. [ABSTRACT FROM AUTHOR] more...

Background: Chikungunya virus (CHIKV) caused a major two-wave seventeen-month-long outbreak in La Réunion Island in 2005-2006. The aim of this study was to refine clinical estimates provided by a regional surveillance-system using a two-stage serological assessment as gold standard.Methods: Two serosurveys were implemented: first, a rapid survey using stored sera of pregnant women, in order to assess the attack rate at the epidemic upsurge (s1, February 2006; n = 888); second, a population-based survey among a random sample of the community, to assess the herd immunity in the post-epidemic era (s2, October 2006; n = 2442). Sera were screened for anti-CHIKV specific antibodies (IgM and IgG in s1, IgG only in s2) using enzyme-linked immunosorbent assays. Seroprevalence rates were compared to clinical estimates of attack rates.Results: In s1, 18.2% of the pregnant women were tested positive for CHIKV specific antibodies (13.8% for both IgM and IgG, 4.3% for IgM, 0.1% for IgG only) which provided a congruent estimate with the 16.5% attack rate calculated from the surveillance-system. In s2, the seroprevalence in community was estimated to 38.2% (95% CI, 35.9 to 40.6%). Extrapolations of seroprevalence rates led to estimate, at 143,000 and at 300,000 (95% CI, 283,000 to 320,000), the number of people infected in s1 and in s2, respectively. In comparison, the surveillance-system estimated at 130,000 and 266,000 the number of people infected for the same periods.Conclusion: A rapid serosurvey in pregnant women can be helpful to assess the attack rate when large seroprevalence studies cannot be done. On the other hand, a population-based serosurvey is useful to refine the estimate when clinical diagnosis underestimates it. Our findings give valuable insights to assess the herd immunity along the course of epidemics. [ABSTRACT FROM AUTHOR] more...

Four clinics implemented an intervention to increase TB household contact identification and evaluation in rural Eastern Cape, South Africa. We applied a care cascade framework to assess gaps in evaluation and treatment initiation from April 2021 to June 2023. We identified 1,698 contacts of 287 individuals with TB. The majority of contacts (71%) were screened; 9% of those with symptoms were fully evaluated, and of these, 14% were diagnosed with active TB. This intervention substantially increased TB contact identification and evaluation compared to prior efforts in the same area; however, additional barriers limited the ability to identify and treat secondary cases., (© 2024 The Authors.) more...

Students often seek opportunities to enrich their classroom learning. Providing students the chance to engage in research studies or global health projects allows for experiential enrichment. However, the impact on partners and partner sites, financial implications, and equity of student opportunity, as well as the logistical burden potentially placed on multiple parties, all need to be considered. If challenges are minimized, students can make meaningful contributions to projects, be a catalyst for partner engagement, and allow for formative learning., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).) more...

We have recently identified the uncharacterized ZNF555 protein as a component of a productive complex involved in the morbid function of the 4qA locus in facioscapulohumeral dystrophy. Subsequently named DiPRO1 (Death, Differentiation, and PROliferation related PROtein 1), our study provides substantial evidence of its role in the differentiation and proliferation of human myoblasts. DiPRO1 operates through the regulatory binding regions of SIX1, a master regulator of myogenesis. Its relevance extends to mesenchymal tumors, such as rhabdomyosarcoma (RMS) and Ewing sarcoma, where DiPRO1 acts as a repressor via the epigenetic regulators TIF1B and UHRF1, maintaining methylation of cis-regulatory elements and gene promoters. Loss of DiPRO1 mimics the host defense response to virus, awakening retrotransposable repeats and the ZNF/KZFP gene family. This enables the eradication of cancer cells, reprogramming the cellular decision balance towards inflammation and/or apoptosis by controlling TNF-α via NF-kappaB signaling. Finally, our results highlight the vulnerability of mesenchymal cancer tumors to si/shDiPRO1-based nanomedicines, positioning DiPRO1 as a potential therapeutic target., (© 2024. The Author(s).) more...

Deploying Community Health Workers is a crucial strategy to improve health at a community level in low and middle income countries. While there is substantial evidence for CHW effectiveness, there is a need for more research on the mechanisms through which these programs work. Understanding CHWs experiences of how programmes function is important. This article examines CHW's experiences of three key programmatic domains; training, logistical support and supervision. Data were gathered using a qualitative study embedded within a cluster randomized controlled trial of an enhanced supervision package delivered to government-employed CHWs in the rural Eastern Cape, South Africa. We interviewed CHWs (n = 16) and two supervisors. Three overarching areas and five sub-themes emerged from our interviews. CHW knowledge and confidence increased through additional training, that CHW motivation and community acceptance improved because of added logistical support, and that CHW supervision led to improved sense of accountability, feelings of respect, and sense of being supported. Our findings highlight the importance of a functional support system within which CHWs can operate, in a context where most CHWs operate in isolation and without support. CHWs receiving supportive supervision reported positive impacts on their motivation and ability to carry out their work effectively., Competing Interests: Conflicts of interest/Competing interests: The authors have no relevant financial or non-financial interests to disclose. more...

Background: South African national tuberculosis (TB) guidelines, in accordance with the World Health Organization, recommend conducting routine household TB contact investigation with provision of TB preventive therapy (TPT) for those who qualify. However, implementation of TPT has been suboptimal in rural South Africa. We sought to identify barriers and facilitators to TB contact investigations and TPT management in rural Eastern Cape, South Africa, to inform the development of an implementation strategy to launch a comprehensive TB program., Methods: We collected qualitative data through individual semi-structured interviews with 19 healthcare workers at a district hospital and four surrounding primary-care clinics referring to the hospital. The consolidated framework for implementation research (CFIR) was used to develop interview questions as well as guide deductive content analysis to determine potential drivers of implementation success or failure., Results: A total of 19 healthcare workers were interviewed. Identified common barriers included lack of provider knowledge regarding efficacy of TPT, lack of TPT documentation workflows for clinicians, and widespread community resource constraints. Facilitators identified included healthcare workers high interest to learn more about the effectiveness of TPT, interest in problem-solving logistical barriers in provision of comprehensive TB care (including TPT), and desire for clinic and nurse-led TB prevention efforts., Conclusion: The use of the CFIR, a validated implementation determinants framework, provided a systematic approach to identify barriers and facilitators to TB household contact investigation, specifically the provision and management of TPT in this rural, high TB burden setting. Specific resources-time, trainings, and evidence-are necessary to ensure healthcare providers feel knowledgeable and competent about TPT prior to prescribing it more broadly. Tangible resources such as improved data systems coupled with political coordination and funding for TPT programming are essential for sustainability., (© 2023. BioMed Central Ltd.) more...

Background: South African national tuberculosis (TB) guidelines, in accordance with the World Health Organization, recommend conducting routine household TB contact investigation with provision of TB preventive therapy (TPT) for those who qualify. However, implementation of TPT has been suboptimal in rural South Africa. We sought to identify barriers and facilitators to TB contact investigations and TPT management in rural Eastern Cape, South Africa to inform the development of an implementation strategy to launch a comprehensive TB program., Methods: We collected qualitative data through individual semi-structured interviews with 19 healthcare workers at a district hospital and four surrounding primary-care clinics referring to the hospital. The consolidated framework for implementation research (CFIR) was used to develop interview questions as well as guide deductive content analysis to determine potential drivers of implementation success or failure., Results: A total of 19 healthcare workers were interviewed. Identified common barriers included lack of provider knowledge regarding efficacy of TPT, lack of TPT documentation workflows for clinicians, and widespread community resource constraints. Facilitators identified included healthcare workers high interest to learn more about the effectiveness of TPT, interest in problem-solving logistical barriers in provision of comprehensive TB care (including TPT), and desire for clinic and nurse-led TB prevention efforts., Conclusion: The use of the CFIR, a validated implementation determinants framework, provided a systematic approach to identify barriers and facilitators to TB household contact investigation, specifically the provision and management of TPT in this rural, high TB burden setting. Specific resources - time, trainings, and evidence - are necessary to ensure healthcare providers feel knowledgeable and competent about TPT prior to prescribing it more broadly. Tangible resources such as improved data systems coupled with political coordination and funding for TPT programming are essential for sustainability. more...

Self-testing for COVID-19 may be a preferable strategy for identifying SARS-CoV-2 infection among populations in low- and middle-income settings. To determine South Africans' values related to COVID-19 self-testing should it become widely available, a cross-sectional survey was administered in Durban, KwaZulu-Natal Province and the King Sabata Dalindyebo sub-district of the Eastern Cape. A 35-question survey was administered to 531 participants (268 female) in one urban and one rural setting of South Africa. Survey participants were randomly selected by household in the rural setting, while in the urban setting participants were approached in randomly selected public places. The survey assessed participants' likelihood of using and willingness to pay for a COVID-19 self-test and actions they would take following a COVID-19 self-test. The results were analysed using descriptive statistics and bivariate and multivariate regression. Overall, 93.03% of participants supported COVID-19 self-testing, 61.62% of participants were willing to pay for self-testing, and 90.15% indicated they would communicate their results if they tested positive. Rural participants were more positively associated with each of these outcomes compared with urban-based participants. Should they test positive, most participants said they would: go in-person to a health facility for counselling (76.45%), self-isolate (95.85%), notify close contacts (97.74%), and inform their employer (95.14%). COVID-19 self-testing was a preferable option for most participants, although this varied with setting and demographic characteristics. Self-testing may overcome barriers to care for South Africans, but to achieve this, policies for self-testing and delivery methods must not exacerbate individuals' underlying economic vulnerabilities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.) more...

Competing Interests: Declaration of interests We declare no competing interests.

Maternal and child health programmes often use Community Health Workers (CHWs) to help address poor access to health care, particularly in low- and middle-income countries (LMIC). Supervision has long been recognised as a critical ingredient of successful CHW programmes, yet it is often reported as either of poor quality or absent. There is little research on CHWs' own perception of supervision and to the best of our knowledge, there are no reviews synthesising the evidence of CHWs' experiences of supervision. This review identified and synthesised qualitative research evidence about the experiences and perceptions of supervision by CHWs in programmes targeting maternal and child health (MCH) in LMIC. Electronic searches were performed in the following databases: EMBASE, Medline, PsycINFO, ASSIA, ERIC and CINAHL. This review included studies during the period from 2000 to 2021. In total, 10,505 titles were screened for inclusion, of which 177 full-text articles were retrieved and assessed. Ultimately, 19 articles were included in this review. Data extraction was based on the thematic synthesis approach: coding the text of included studies line-by-line; developing descriptive themes; and generating analytical themes. Four themes emerged: (1) frequency of supervision, (2) type of supervision, (3) supervision and motivation and (4) supportive supervision. Careful consideration needs to be taken of the model of supervision used, as primary care facility-based supervisors (usually nurses), although skilled, may not have sufficient time to supervise. Employing supervisors whose sole responsibility is to supervise CHWs may be a good strategy to alleviate these issues. Sufficient time and resources need to be allocated to supervisors and they should be expected to perform regular in-the-field supervision. Involving some aspects of community oversight should also be considered. Supervisor skills and training and the long-term retention of trained supervisors also need to be an important area of focus., (© 2022 John Wiley & Sons Ltd.) more...

Background: hPSC-derived endothelial and hematopoietic cells (ECs and HCs) are an interesting source of cells for tissue engineering. Despite their close spatial and temporal embryonic development, current hPSC differentiation protocols are specialized in only one of these lineages. In this study, we generated a hematoendothelial population that could be further differentiated in vitro to both lineages., Methods: Two hESCs and one hiPSC lines were differentiated into a hematoendothelial population, hPSC-ECs and blast colonies (hPSC-BCs) via CD144 + -embryoid bodies (hPSC-EBs). hPSC-ECs were characterized by endothelial colony-forming assay, LDL uptake assay, endothelial activation by TNF-α, nitric oxide detection and Matrigel-based tube formation. Hematopoietic colony-forming cell assay was performed from hPSC-BCs. Interestingly, we identified a hPSC-BC population characterized by the expression of both CD144 and CD45. hPSC-ECs and hPSC-BCs were analyzed by flow cytometry and RT-qPCR; in vivo experiments have been realized by ischemic tissue injury model on a mouse dorsal skinfold chamber and hematopoietic reconstitution in irradiated immunosuppressed mouse from hPSC-ECs and hPSC-EB-CD144 + , respectively. Transcriptomic analyses were performed to confirm the endothelial and hematopoietic identity of hESC-derived cell populations by comparing them against undifferentiated hESC, among each other's (e.g. hPSC-ECs vs. hPSC-EB-CD144 + ) and against human embryonic liver (EL) endothelial, hematoendothelial and hematopoietic cell subpopulations., Results: A hematoendothelial population was obtained after 84 h of hPSC-EBs formation under serum-free conditions and isolated based on CD144 expression. Intrafemorally injection of hPSC-EB-CD144 + contributed to the generation of CD45 + human cells in immunodeficient mice suggesting the existence of hemogenic ECs within hPSC-EB-CD144 + . Endothelial differentiation of hPSC-EB-CD144 + yields a population of > 95% functional ECs in vitro. hPSC-ECs derived through this protocol participated at the formation of new vessels in vivo in a mouse ischemia model. In vitro, hematopoietic differentiation of hPSC-EB-CD144 + generated an intermediate population of > 90% CD43 + hPSC-BCs capable to generate myeloid and erythroid colonies. Finally, the transcriptomic analyses confirmed the hematoendothelial, endothelial and hematopoietic identity of hPSC-EB-CD144 + , hPSC-ECs and hPSC-BCs, respectively, and the similarities between hPSC-BC-CD144 + CD45 + , a subpopulation of hPSC-BCs, and human EL hematopoietic stem cells/hematopoietic progenitors., Conclusion: The present work reports a hPSC differentiation protocol into functional hematopoietic and endothelial cells through a hematoendothelial population. Both lineages were proven to display characteristics of physiological human cells, and therefore, they represent an interesting rapid source of cells for future cell therapy and tissue engineering., (© 2022. The Author(s).) more...

Access to healthcare in developing countries remains a challenge. As a result, task-shifting to community health workers (CHWs) is increasingly used to mitigate healthcare worker shortages. Although there is solid evidence of CHW program effectiveness, less is known about CHWs' experiences of becoming and then working daily as CHWs-information that should play an important role in the design of CHW programs. We examined the experiences of a group of CHWs working in a government-run CHW program in South Africa's rural Eastern Cape Province. Semistructured qualitative interviews (N = 9) and focus groups (N = 2) focusing on motivations for becoming a CHW and experiences of working as CHWs were conducted and thematically analyzed. Three themes were identified: (1) becoming a CHW, (2) facing challenges in the field, and (3) gaining community acceptance through respect and legitimacy. In this study, CHWs were motivated by altruism and a desire to help their community. They faced a range of challenges such as limited training, lack of supervision, equipment shortages, logistical issues, and clinics with limited services. Respect and legitimacy through community acceptance and trust is crucial for effective CHW work. CHWs in this study described how confidentiality and their own persistence facilitated the process of gaining respect and legitimacy. CHWs have a unique knowledge of contexts and requirements for successful programs and greater efforts are needed to include their perspectives to improve and develop programs. Recognition is needed to acknowledge the significant personal input required by CHWs for programs to be successful., (© 2022 Wiley Periodicals LLC.) more...