Evaluation of retinal structure and function in prediabetes.

Purpose: Alterations in retinal structure and function have been well documented in type 2 diabetes (T2DM). However, few studies have evaluated the eye in prediabetes (preDM), a precursor to T2DM. It is unknown which retinal deficits, if any, occur before T2DM diagnosis. This study evaluates retinal structure via optical coherence tomography (OCT) and retinal function via multifocal electroretinogram (mfERG) N1 and P1 in those with PreDM. The goal is to evaluate associations between structure and function across glucose dysfunction. Methods: 85 subjects (aged 28-69yrs) were tested with VERIS mfERG and Heidelberg Spectralis OCT. Demographic and health information was collected. Subjects were grouped by HbA1c: 33 controls (HbA1c <5.7%), 31 with preDM (HbA1c 5.7-6.4%), and 21 with T2DM (HbA1c >6.4% at the time of testing or diagnosed by physician) and mild or no retinopathy. mfERG N1 and P1 latency and amplitude were measured for the right eye in the foveal hexagon (central 2.4°). Average macular thickness was also measured over the central 3.3°. Groups were compared with ANOVA and corrected t-tests. Models of these associations with diabetes diagnosis (in groups above) were created with backward multivariate regression. Results: The T2DM group was exceptionally well-controlled with an HbA1c of 7.0% ± 0.68 but also had elevated systolic blood pressure compared to other groups (P<0.01). The age of the control group was younger (P<0.01), so other testing was age controlled. There was a borderline but statistically significant difference in P1 between the control group and both the preDM and T2DM groups after Bonferroni corrections (P<0.03). There was also a difference in N1 latency between the control and other groups (P<0.001). A multivariate model demonstrated a significant relationship between T2DM/PreDM diagnosis and delayed N1 latency, reduced foveal thickness, and age. Conclusions: Structure and function together can provide an associative model of preDM or T2DM changes for patients. Based on this multivariate model, N1 is strongly associated with preDM and T2DM. N1 findings and decreasing foveal thickness are additive and can together inform ocular health related to preDM. Future longitudinal studies are needed to understand changes in function and structure in preDM and T2DM.

Test-retest repeatability in macular retinal oximetry.

CLINICAL RELEVANCE: Evaluation of retinal macular oxygen saturation in healthy controls can aid in understanding the pathological changes seen in similar locations of those with vascular diseases like diabetes. BACKGROUND: The aim of this study was to determine the test-retest repeatability of localised retinal oximetry measurements in the macula on the Zilia Oximeter within healthy subjects of different races, 18-40 years old. Oxygen saturation was measured between three time points within the same locations of the right eye. METHODS: Twenty seven subjects were included (aged 26.3 ± 3.6 years). All were confirmed to have healthy retinas and at least 6/9 vision. Oximetry measurements were taken using the Zilia to acquire local oxygen saturation measurements (300 µm diameter) at four points 3.1 degrees from the fovea in the superior/temporal, superior/nasal, inferior/temporal, and inferior/nasal locations. Oximetry measurements were taken twice on the same day 20 minutes apart and then again 1-2 weeks later. Oximetry data was analysed with intraclass correlation between visits. To assess intrasubject repeatability, the Bland-Altman repeatability coefficient and coefficient of variation were calculated. RESULTS: Average Intraclass correlation for the three acquisition times of the right eye was 0.78. The averaged intrasubject repeatability coefficient for the three acquisition times was 8.4. The averaged coefficient of variation was 5.4%. CONCLUSION: The Zilia oximeter has good macular test-retest repeatability; however, multiple measurements may be needed to ensure accuracy.

Twenty-four hour diurnal variation in retinal oxygen saturation.

Retinal oxygen saturation is influenced by systemic and local vasculature, intraocular pressure (IOP), and individual cellular function. In numerous retinal pathologies, early changes take place at the level of the microvasculature, thereby affecting retinal oxygenation. The purpose of this study was to investigate diurnal variations in retinal oximetry measures and evaluate the relationship with other ocular and systemic physiological processes. Healthy adults (n = 18, mean age 27 ± 5.5 years) participated. Ocular and systemic measures were collected every four hours over 24 h and included retinal oximetry, IOP, optical coherence tomography (OCT), OCT-angiography (OCTA), biometry, blood pressure, and partial pressure of oxygen. Amplitude and acrophase for retinal oxygen saturation, axial length, retinal and choroidal thickness, OCTA parameters, and mean arterial and ocular perfusion pressure (MAP, MOPP) were determined were determined using cosine fits, and multiple regression analysis was performed to compare metrics. Retinal oxygenation saturation demonstrated a significant diurnal variation with an amplitude of 5.84 ± 3.86% and acrophase of 2.35 h. Other parameters that demonstrated significant diurnal variation included IOP, MOPP, axial length, choroidal thickness, superficial vessel density, heart rate, systolic blood pressure, and MAP. Diurnal variations in retinal oxygen saturation were in-phase with choroidal thickness, IOP, and density of the superficial vascular plexus and out-of-phase with axial length and MOPP. In conclusion, retinal oxygenation saturation undergoes diurnal variations over 24 h. These findings contribute to a better understanding of intrinsic and extrinsic factors influencing oxygenation of the area surrounding the fovea.

Foveal avascular zone size and mfERG metrics in diabetes and prediabetes: a pilot study of the relationship between structure and function.

PURPOSE: Previous studies have demonstrated functional and structural retinal changes in type 2 diabetes (T2DM). However, less is understood in prediabetes, which is an important precursor to T2DM. Here, we evaluate the microvasculature structure of the foveal avascular zone (FAZ) and how it is correlated with retinal function as measured by the multifocal electroretinogram (mfERG) across levels of glucose dysfunction to uncover how T2DM and prediabetes alter this structure-function relationship. METHODS: 33 subjects were included: 9 controls, 12 prediabetes, 12 T2DM with no retinopathy or edema. Subjects were aged 30-70 years, had BCVA of 20/25 or better, and had no confounding ocular conditions. Blood was collected via fingerstick to determine Hemoglobin A1c (HbA1c), which was used along with previous diagnosis, to determine study grouping. Optical coherence tomography angiography (OCTA) was used to analyze the FAZ area and was corrected for refractive error. FAZ area was measured by hand using the Heidelberg Spectralis software. mfERG (VERIS 6.3) metrics implicit time (IT) and amplitude were evaluated in the foveal region, macular region, and averaged over the posterior pole of the right eye. Regression analysis was performed between each study group parameter to determine relationships, and t tests with corrections were used to compare groups. RESULTS: FAZ area (superficial plexus) was negatively correlated with mfERG posterior pole amplitude (p < 0.01, R2 = 0.30), foveal amp (p = 0.02 R2 = 0.17) and macular amplitude (p = 0.02 R2 = 0.18) across all 33 study subjects. FAZ and mfERG metrics were not significantly different between study groups in this cohort except for IT, which was more delayed in the diabetes group compared to other groups. CONCLUSION: FAZ area is correlated with mfERG amplitudes but not IT. This suggests a link between the structural metrics and retinal function. Longitudinal follow-up work would be helpful to determine the timing of these changes in prediabetes.

Correction: Characteristics of people with epilepsy and Neurocysticercosis in three eastern African countries-A pooled analysis.

[This corrects the article DOI: 10.1371/journal.pntd.0010870.].

Characteristics of people with epilepsy and Neurocysticercosis in three eastern African countries-A pooled analysis.

BACKGROUND: Neurocysticercosis (NCC), a zoonotic disease caused by the pork tapeworm T. solium, represents one of the most common causes of secondary epilepsy but remains often undiagnosed due to lack of awareness and diagnostic facilities. METHODOLOGY: We pooled data from four cross-sectional studies on epilepsy and NCC in eastern Africa. Study sites were in Uganda, Malawi and in Tanzania (Dar es Salaam and Haydom). The study in Uganda and Malawi were community-based, the two studies in Tanzania were hospital-based. The same questionnaire was used for assessment of clinical characteristics of patients with epilepsy. Computed tomography (CT) scans and serological testing were performed in order to diagnose NCC. RESULTS: Overall, 1,179 people with epilepsy were included in our analysis. Of those, 941 PWE underwent CT scanning and were pooled for NCC analysis. Seventy patients were diagnosed with NCC, but NCC prevalence differed considerably between sites ranging from 2.0% (95%CI 0.4% to 3.6%) in Dar es Salaam to 17.5% (95%CI 12.4% to 22.6%) in Haydom. NCC prevalence did not show any association with sex but increased with age and was higher in rural than urban settings. In addition, being a farmer, non-Muslim, eating pork and living with pigs close by was associated with a higher NCC prevalence. PWE with NCC experienced their first epileptic seizure around 3 years later in life compared to PWE without NCC and their epileptic seizures seemed to be better controlled (p<0.001). There was no difference between focal onset seizures and focal signs on neurological examination in both groups (p = 0.49 and p = 0.92, respectively). The rT24H-EITB had a sensitivity for the detection of NCC of 70% (95% confidence interval [CI] 51 to 84%), the LLGP of 76% (95%CI 58 to 89%) and the antigen ELISA of 36% (95% CI 20 to 55%). CONCLUSIONS: NCC is prevalent among PWE in eastern Africa, although it may not be as common as previously stated. Demographic characteristics of PWE with NCC differed from those without NCC, but semiological characteristics and results on neurological examination did not differ compared to PWE without NCC. Interestingly, seizures seemed to be less frequent in PWE with NCC. Being aware of those differences and similarities may help triaging PWE for neuroimaging in order to establish a diagnosis of NCC.

Community-level prevalence of epilepsy and of neurocysticercosis among people with epilepsy in the Balaka district of Malawi: A cross-sectional study.

BACKGROUND: Epilepsy and neurocysticercosis (NCC) prevalence estimates in sub-Saharan Africa are still scarce but show important variation due to the population studied and different screening and diagnosis strategies used. The aims of this study were to estimate the prevalence of epileptic seizures and epilepsy in the sampled population, and the proportion of NCC among people with epilepsy (PWE) in a large cross-sectional study in a rural district of southern Malawi. METHODS: We conducted a community-based door-to-door screening study for epileptic seizures in Balaka, Malawi between October and December 2012. Past epileptic seizures were reported through a 15-item questionnaire answered by at least one person per household generating five major criteria. People who screened positive were further examined by a neurologist to establish diagnosis. Patients diagnosed with epilepsy were examined and offered Taenia solium cyst antigen and antibody serological tests, and a CT scan for the diagnosis of NCC. RESULTS: In total, screening information on 69,595 individuals was obtained for lifetime occurrence of epileptic seizures. 3,100 (4.5%) participants screened positive, of whom 1,913 (62%) could be followed-up and underwent further assessment. Lifetime prevalence was 3.0% (95% Bayesian credible interval [CI] 2.8 to 3.1%) and 1.2% (95%BCI 0.9 to 1.6%) for epileptic seizures and epilepsy, respectively. NCC prevalence among PWE was estimated to be 4.4% (95%BCI 0.8 to 8.5%). A diagnosis of epilepsy was ultimately reached for 455 participants. CONCLUSION: The results of this large community-based study contribute to the evaluation and understanding of the burden of epilepsy in the population and of NCC among PWE in sub-Saharan Africa.

Global variation in force-of-infection trends for human Taenia solium taeniasis/cysticercosis.

Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021-2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic areas by 2030. Understanding geographical variation in age-prevalence profiles and force-of-infection (FoI) estimates will inform intervention designs across settings. Human taeniasis (HTT) and human cysticercosis (HCC) age-prevalence data from 16 studies in Latin America, Africa, and Asia were extracted through a systematic review. Catalytic models, incorporating diagnostic performance uncertainty, were fitted to the data using Bayesian methods, to estimate rates of antibody (Ab)-seroconversion, infection acquisition and Ab-seroreversion or infection loss. HCC FoI and Ab-seroreversion rates were also estimated across 23 departments in Colombia from 28,100 individuals. Across settings, there was extensive variation in all-ages seroprevalence. Evidence for Ab-seroreversion or infection loss was found in most settings for both HTT and HCC and for HCC Ab-seroreversion in Colombia. The average duration until humans became Ab-seropositive/infected decreased as all-age (sero)prevalence increased. There was no clear relationship between the average duration humans remain Ab-seropositive and all-age seroprevalence. Marked geographical heterogeneity in T. solium transmission rates indicate the need for setting-specific intervention strategies to achieve the WHO goals.

Characteristics of people with epilepsy in three Eastern African countries - a pooled analysis.

BACKGROUND: Epilepsy is one of the most common neurological disorders worldwide. Yet, its treatment gap is large in some areas and especially in sub-Saharan Africa data on clinical, radiological and semiological characteristics, as well as on treatment of persons with epilepsy (PWE) are still scarce. METHODS: We pooled data from four cross-sectional studies on epilepsy in eastern Africa. Two studies from Malawi and Uganda were community-based; two studies in Tanzania (urban Dar es Salaam and rural Haydom) were hospital-based. Clinical characteristics of PWE were assessed by the same questionnaire. Additionally, data on treatment were collected and computed tomography (CT) scans were performed. RESULTS: Overall, 1179 PWE were included in our analysis (581 (49.3%) female, median age 22 years (IQR 15-32 years)). Up to 25% of the patients had focal onset seizures. Those showed a higher rate of remarkable CT scan findings, with especially post-ischaemic and neurocysticercosis-associated lesions, compared to PWE with generalized onset seizures (35.1% vs. 20%). The majority of the patients experienced tonic-clonic seizures (70-85%). Only 67-78% of PWE received anti-seizure medication (ASM) treatment in the community-based studies, mostly monotherapy with phenobarbital, phenytoin or carbamazepine. Yet, underdosage was frequent and a large proportion of PWE received alternative non-ASM treatment consisting of herbal treatment (up to 83%) and/or scarification (up to 20%). CONCLUSIONS: Epilepsy is common in sub-Saharan Africa, often caused by neurocysticercosis or ischaemic strokes. PWE suffer from high seizure rates and subsequent injuries, as well as from socio-economic consequences due to insufficient ASM treatment. This pooled analysis illustrates the need for structural programmes for adequate identification, education, assessment and treatment of PWE in sub-Saharan Africa.

Comparative incidence of early and late bloodstream and respiratory tract co-infection in patients admitted to ICU with COVID-19 pneumonia versus Influenza A or B pneumonia versus no viral pneumonia: wales multicentre ICU cohort study.

OBJECTIVE: The aim is to characterise early and late respiratory and bloodstream co-infection in patients admitted to intensive care units (ICUs) with SARS-CoV-2-related acute hypoxemic respiratory failure (AHRF) needing respiratory support in seven ICUs within Wales, during the first wave of the COVID-19 pandemic. We compare the rate of positivity of different secondary pathogens and their antimicrobial sensitivity in three different patient groups: patients admitted to ICU with COVID-19 pneumonia, Influenza A or B pneumonia, and patients without viral pneumonia. DESIGN: Multicentre, retrospective, observational cohort study with rapid microbiology data from Public Health Wales, sharing of clinical and demographic data from seven participating ICUs. SETTING: Seven Welsh ICUs participated between 10 March and 31 July 2020. Clinical and demographic data for COVID-19 disease were shared by each participating centres, and microbiology data were extracted from a data repository within Public Health Wales. Comparative data were taken from a cohort of patients without viral pneumonia admitted to ICU during the same period as the COVID-19 cohort (referred to as no viral pneumonia or 'no viral' group), and to a retrospective non-matched cohort of consecutive patients with Influenza A or B admitted to ICUs from 20 November 2017. The comparative data for Influenza pneumonia and no viral pneumonia were taken from one of the seven participating ICUs. PARTICIPANTS: A total of 299 consecutive patients admitted to ICUs with COVID-19 pneumonia were compared with 173 and 48 patients admitted with no viral pneumonia or Influenza A or B pneumonia, respectively. MAIN OUTCOME MEASURES: Primary outcome was to calculate comparative incidence of early and late co-infection in patients admitted to ICU with COVID-19, Influenza A or B pneumonia and no viral pneumonia. Secondary outcome was to calculate the individual group of early and late co-infection rate on a per-patient and per-sample basis, with their antimicrobial susceptibility and thirdly to ascertain any statistical correlation between clinical and demographic variables with rate of acquiring co-infection following ICU admission. RESULTS: A total of 299 adults (median age 57, M/F 2:1) were included in the COVID-19 ICU cohort. The incidence of respiratory and bloodstream co-infection was 40.5% and 15.1%, respectively. Staphylococcus aureus was the predominant bacterial pathogen within the first 48 h. Gram-negative organisms from Enterobacterales group were predominantly seen after 48 h in COVID-19 cohort. Comparative no viral pneumonia cohort had lower rates of respiratory tract infection and bloodstream infection. The influenza cohort had similar rates respiratory tract infection and bloodstream infection. Mortality in all three groups was similar, and no clinical or demographic variables were found to increase the rate of co-infection and ICU mortality. CONCLUSIONS: Higher incidence of bacterial co-infection was found in COVID-19 cohort as compared to the no viral pneumonia cohort admitted to ICUs for respiratory support.

PRAISE: providing a roadmap for automated infection surveillance in Europe.

INTRODUCTION: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. METHODS: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. RESULTS: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. CONCLUSIONS: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists.

Taenia solium taeniasis/cysticercosis: From parasite biology and immunology to diagnosis and control.

Infection with the pork tapeworm (Taenia solium) is responsible for a substantial global burden of disease, not only restricted to its impact on human health, but also resulting in a considerable economic burden to smallholder pig farmers due to pig cysticercosis infection. The life-cycle, parasitology and immunology of T. solium are complex, involving pigs (the intermediate host, harbouring the larval metacestode stage), humans (the definitive host, harbouring the adult tapeworm, in addition to acting as accidental intermediate hosts) and the environment (the source of infection with eggs/proglottids). We review the parasitology, immunology, and epidemiology of the infection associated with each of the T. solium life-cycle stages, including the pre-adult/adult tapeworm responsible for human taeniasis; post-oncosphere and cysticercus associated with porcine and human cysticercosis, and the biological characteristics of eggs in the environment. We discuss the burden associated, in endemic settings, with neurocysticercosis (NCC) in humans, and the broader cross-sectoral economic impact associated both with NCC and porcine cysticercosis, the latter impacting food-value chains. Existing tools for diagnostics and control interventions that target different stages of the T. solium transmission cycle are reviewed and their limitations discussed. Currently, no national T. solium control programmes have been established in endemic areas, with further work required to identify optimal strategies according to epidemiological setting. There is increasing evidence suggesting that cross-sectoral interventions which target the parasite in both the human and pig host provide the most effective approaches for achieving control and ultimately elimination. We discuss future avenues for research on T. solium to support the attainment of the goals proposed in the revised World Health Organisation neglected tropical diseases roadmap for 2021-2030 adopted at the 73rd World Health Assembly in November 2020.

Fundus motion during mfERG testing.

PURPOSE: The purpose of this study was to assess eye movements during a multifocal ERG (mfERG) recording. This study evaluated the relationship between bivariate contour ellipse areas (BCEAs), mfERG amplitudes (Amps) and mfERG implicit times (ITs) with repeat testing and experienced subjects. METHODS: Thirty subjects were selected (15 experienced to ocular procedures and 15 novices). All were confirmed to have healthy retinas and at least 20/25 vision. MfERGs with a stimulus near 100% contrast and 4-min m-sequence were recorded on two different days using our common clinical technique, which did not constrain the head. VERIS with fundus monitoring system was used for recording with a Burian-Allen electrode. An external camera captured the fundus during each mfERG recording. The optic nerve head position was tracked in each video using a custom algorithm in order to determine BCEAs. Each subject performed one mfERG on two different days. MfERGs were analyzed for Amps and ITs for the fovea and whole eye. RESULTS: There was no correlation between the mfERG metrics and BCEAs with repeat testing. There were also no differences between the experienced and novice subjects for mfERG Amps, ITs or BCEAs. Eye movements between visits were highly correlated (multiple r = 0.67). BCEAs were larger during mfERGs (1.04 ± 0.8 deg2) than those observed in previous literature using brief viewing tasks (< 0.3 deg2). The proportion of time spent fixating within 1.0 and 2.0 degrees of the central hexagon was 68 and 93%, respectively. CONCLUSIONS: This study is the first to evaluate the stability of the retina while recording a mfERG in healthy subjects and indicates that the center of fixation during a mfERG stays within the central hexagon. Eye stability during an initial recording is the best indicator of stability on the second recording. The amount of movement during these recordings did not seem to affect the mfERG Amps or ITs. These data suggest clinical confidence with mfERGs when recording novice patients.

Diagnosis of colorectal and emergency surgical site infections in the era of enhanced recovery: an all-Wales prospective study.

AIM: Surgical site infections (SSIs) are associated with increased morbidity, hospital stay and cost. The literature reports that 25% of patients who undergo colorectal surgical procedures develop a SSI. Due to the enhanced recovery programme, patients are being discharged earlier with some SSIs presenting in primary care, making accurate recording of SSIs difficult. The aim of this study was to accurately record the 30-day SSI rate after surgery performed by colorectal surgeons nationally within Wales. METHOD: During March 2019, a national prospective snapshot study of all patients undergoing elective or emergency colorectal and general surgical procedures under the care of a colorectal consultant at 12 Welsh hospitals was completed. There was a multimodal 30-day follow-up using electronic records, clinic visits and/or telephone calls. Diagnosis of SSI was based on Centers for Disease Control and Prevention diagnostic criteria. RESULTS: Within Wales, of the 545 patients included, 13% developed a SSI within 30 days, with SSI rates of 14.3% for elective surgery and 11.7% for emergency surgery. Of these SSIs, 49.3% were diagnosed in primary care, with 28.2% of patients being managed exclusively in the community. There were two peaks of diagnosis at days 5-7 and days 22-28. SSI rates between laparoscopic (8.6%) and open (16.2%) surgeries were significantly different (p = 0.028), and there was also a significantly different rate of SSI between procedure groups (p = 0.001), with high SSI rates for colon (22%) and rectal (18.9%) surgery compared with general surgical procedures. CONCLUSION: This first all-Wales prospective study demonstrated an overall SSI rate of 13%. By incorporating accurate primary care follow-up it was found that 49.3% of these SSIs were diagnosed in primary care.

Use of directed acyclic graphs (DAGs) to identify confounders in applied health research: review and recommendations.

BACKGROUND: Directed acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require conditioning when estimating causal effects. This review examined the use of DAGs in applied health research to inform recommendations for improving their transparency and utility in future research. METHODS: Original health research articles published during 1999-2017 mentioning 'directed acyclic graphs' (or similar) or citing DAGitty were identified from Scopus, Web of Science, Medline and Embase. Data were extracted on the reporting of: estimands, DAGs and adjustment sets, alongside the characteristics of each article's largest DAG. RESULTS: A total of 234 articles were identified that reported using DAGs. A fifth (n = 48, 21%) reported their target estimand(s) and half (n = 115, 48%) reported the adjustment set(s) implied by their DAG(s). Two-thirds of the articles (n = 144, 62%) made at least one DAG available. DAGs varied in size but averaged 12 nodes [interquartile range (IQR): 9-16, range: 3-28] and 29 arcs (IQR: 19-42, range: 3-99). The median saturation (i.e. percentage of total possible arcs) was 46% (IQR: 31-67, range: 12-100). 37% (n = 53) of the DAGs included unobserved variables, 17% (n = 25) included 'super-nodes' (i.e. nodes containing more than one variable) and 34% (n = 49) were visually arranged so that the constituent arcs flowed in the same direction (e.g. top-to-bottom). CONCLUSION: There is substantial variation in the use and reporting of DAGs in applied health research. Although this partly reflects their flexibility, it also highlights some potential areas for improvement. This review hence offers several recommendations to improve the reporting and use of DAGs in future research.

One Health for neglected tropical diseases.

The forthcoming World Health Organization road map for neglected tropical diseases (NTDs) 2021-2030 recognises the complexity surrounding control and elimination of these 20 diseases of poverty. It emphasises the need for a paradigm shift from disease-specific interventions to holistic cross-cutting approaches coordinating with adjacent disciplines. The One Health approach exemplifies this shift, extending beyond a conventional model of zoonotic disease control to consider the interactions of human and animal health systems within their shared environment and the wider social and economic context. This approach can also promote sustainability and resilience within these systems. To achieve the global ambition on NTD elimination and control, political will, along with contextualised innovative scientific strategies, is required.

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer.

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women's empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and women.

La schistosomiase génitale féminine, résultant d'une infection chronique à Schistosoma haematobium (également connue sous le nom de bilharziose), continue d'être largement ignorée par les responsables des politiques de santé nationales et internationales. Si le monde lui accorde son attention en vue de mener une action à grande échelle contre la maladie, c'est surtout pour déterminer s'il s'agit d'un facteur de risque pour la transmission du virus de l'immunodéficience humaine (VIH). Pourtant, la schistosomiase génitale féminine est associée à des douleurs, des saignements et peut engendrer l'hypofertilité, voire la stérilité. Par conséquent, celles qui en souffrent sont souvent stigmatisées, et le problème est courant dans les régions endémiques d'Afrique subsaharienne. Cette maladie doit donc être considérée comme composante à part entière d'une approche globale de la santé et des droits humains pour les femmes et filles africaines, à l'instar du VIH et du cancer du col de l'utérus. Chacune de ces trois maladies fait l'objet d'une intervention préventive ciblée qui a déjà fait ses preuves: le traitement antirétroviral et la prophylaxie pré-exposition pour le VIH; le vaccin contre le papillomavirus humain pour le cancer du col de l'utérus; et l'administration de praziquantel pour la schistosomiase génitale féminine. Le présent document se penche sur la manière d'intégrer la schistosomiase génitale féminine dans la prise en charge du VIH et du cancer du col de l'utérus. Un tel programme fera partie d'un cadre plus vaste consacré aux droits et à la santé sexuelle et reproductive, à l'émancipation des femmes et à la justice sociale en Afrique. Les approches intégrées qui regroupent plusieurs programmes de santé publique permettent d'élargir des perspectives ou de créer des opportunités visant à atteindre un plus grand nombre de filles et de femmes tout au long de leur vie. Nous exposons les grandes lignes d'un programme de recherches pragmatiques et opérationnelles capable d'optimiser la mise en œuvre conjointe d'une série de mesures qui répondent aux besoins spécifiques des filles et des femmes.

Los responsables de formular las políticas sanitarias nacionales y globales siguen ignorando en gran medida la esquistosomiasis genital femenina como consecuencia de la infección crónica por Schistosoma haematobium (conocida comúnmente como bilharziasis). La atención internacional para adoptar medidas de gran alcance contra la enfermedad se centra en determinar si es un factor de riesgo para la transmisión del virus de la inmunodeficiencia humana (VIH). Sin embargo, la propia esquistosomiasis genital femenina está vinculada al dolor, las hemorragias y la infertilidad o subfertilidad, lo que conduce al estigma social, además de ser un problema común para las mujeres de las áreas en donde la esquistosomiasis es endémica en el África subsahariana. Por consiguiente, la enfermedad debe ser reconocida como otro componente de un programa integral de salud y de derechos humanos para las mujeres y las niñas de África, junto con el VIH y el cáncer de cuello uterino. Cada una de estas tres enfermedades tiene una intervención preventiva específica y comprobada: la terapia antirretroviral y la profilaxis previa a la exposición para el VIH; la vacuna contra el virus del papiloma humano para el cáncer de cuello uterino; y el tratamiento con praziquantel para la esquistosomiasis genital femenina. Se analiza cómo el control de la esquistosomiasis genital femenina se puede integrar con la atención del VIH y el cáncer de cuello uterino. Ese programa formará parte de un marco más amplio de salud y de derechos sexuales y reproductivos, de empoderamiento de la mujer y de justicia social en África. Los enfoques integrados que unen múltiples programas de salud pública tienen el potencial de ampliar o crear oportunidades para llegar a más niñas y mujeres a lo largo de sus vidas. Se describe a grandes rasgos un programa de investigación operacional pragmático que tiene el potencial de optimizar la implementación conjunta de una serie de medidas que respondan a las necesidades específicas de las niñas y de las mujeres.

Force-of-infection of Taenia solium porcine cysticercosis: a modelling analysis to assess global incidence and prevalence trends.

The World Health Organization (WHO) called, in 2012, for a validated strategy towards Taenia solium taeniasis/cysticercosis control and elimination. Estimating pig force-of-infection (FoI, the average rate at which susceptible pigs become infected) across geographical settings will help understand local epidemiology and inform effective intervention design. Porcine cysticercosis (PCC) age-prevalence data (from 15 studies in Latin America, Africa and Asia) were identified through systematic review. Catalytic models were fitted to the data using Bayesian methods, incorporating uncertainty in diagnostic performance, to estimate rates of antibody seroconversion, viable metacestode acquisition, and seroreversion/infection loss. There was evidence of antibody seroreversion across 5 studies, and of infection loss in 6 studies measured by antigen or necropsy, indicating transient serological responses and natural resolution of infection. Concerted efforts should be made to collect robust data using improved diagnostics to better understand geographical heterogeneities in T. solium transmission to support post-2020 WHO targets.