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BackgroundPrompt diagnosis and treatment prevents a mild case of malaria from developing into severe disease and death. Unfortunately, parasitological testing of febrile children is greater in the public and formal private sector than in the informal private sector in sub-Saharan Africa.MethodsA mixed method study was carried out to determine factors limiting test-based management of suspected malaria cases among caregivers of febrile children and Over-the-Counter medicine sellers (OTCMS) in eight rural communities in Ghana. Structured questionnaires were used to interview 254 adult caregivers. Fourteen in-depth interviews were conducted with OTCMS. The interviews were audio-recorded, transcribed verbatim, and analysed thematically.ResultsThe most frequently sought health providers by caregivers of febrile children in descending order were Community Health-Based Planning Services (CHPS) compounds; drug vendors; and OTCMS. Malaria parasitological testing rate of febrile children was highest (94.9%) at the CHPS compound and lowest (10.5%) at the OTCMS shops. Proportion of febrile children not subjected to malaria blood test is 28.3%. Among caregivers who did not ask for malaria blood test, 15.2% reported that healthcare provider did not offer a malaria blood test; 21.7% were financially handicapped to visit the Health Centre; and 63% lacked knowledge of malaria blood test and where to get it. From OTCMS point of view, clients’ inability to pay for malaria blood test, community perception that OTCMS are unqualified to perform malaria blood test, financial loss when unused RDT kits expires, clients’ demand for half dose of ACT, and activities of drug peddlers are factors limiting adherence to WHO recommended policy on testing before treating uncomplicated malaria cases.ConclusionThe study results suggest the need to implement community friendly interventions aimed at improving test-based management of suspected malaria in febrile children. These may include educating caregivers and community members on the need to test and confirm malaria in febrile children before treating them, and supply of subsidized RDT kits to OTCMS and re-training them to provide testing services to their clients. Further studies pertaining to influence of gender roles on healthcare seeking attitude for febrile children is also suggested.

Background The World Health Organization initiated test, treat, and track (T3) malaria strategy to support malaria-endemic countries in their efforts to achieve universal coverage with diagnostic testing, antimalarial treatment, and strengthening surveillance systems. Unfortunately, T3 is not adopted by over-the-counter medicine sellers (OTCMS) where many patients with malaria-like symptoms first seek treatment. Sub-Saharan African countries are considering introducing and scaling up RDTs in these outlets to reduce malaria burden. In this context, this study is aimed at improving implementation of the T3 among OTCMS using a number of intervention tools that could be scaled-up easily at the national level. Methods/design The interventions will be evaluated using a two-arm, cluster randomized trial across 8 rural communities (4 clusters per arm), in two adjacent districts (Fanteakwa North and Fanteakwa South districts) of Ghana. A total of 8 OTCMS in the intervention arm and 5 OTCMS in the control arm in the selected communities will participate in the study. In the intervention arm only, subsidized malaria rapid diagnostic test (mRDT) kits will be introduced after the OTCMS have been trained on how to use the kit appropriately. Supervision, technical assistance, feedbacks, and collection of data will be provided on a regular basis at the participating medicine stores. The primary outcome is the proportion of children under 10 years with fever or suspected to have malaria visiting OTCMS and tested (using mRDT) before treatment. Secondary outcomes will include adherence to national malaria treatment guidelines and recommended mRDT retail price. Outcomes will be measured using mainly a household survey supplemented by mystery client survey and a surveillance register on malaria tests conducted by the OTCMS during patient consultations. Data collected will be double entered and verified using Microsoft Access 2010 (Microsoft Inc., Redmond, Washington) and analyzed using STATA version 11.0. Discussion The trial will provide evidence on the combined effectiveness of provider and community interventions in improving adherence to the T3 initiative among OTCMS in rural Ghana. Ethical clearance NMIMR-IRB CPN 086/18-19 Trial registration ISRCTN registry ISRCTN77836926. Registered on 4 November 2019.

Osteoarthritis results in chronic pain and loss of function. Proinflammatory cytokines create both osteoarthritis pathology and pain. Current treatments are poorly effective, have significant side effects, and have not targeted the cytokines central to osteoarthritis development and maintenance. Interleukin-10 is an anti-inflammatory cytokine that potently and broadly suppresses proinflammatory cytokine activity. However, interleukin-10 protein has a short half-life in vivo and poor joint permeability. For sustained IL-10 activity, we developed a plasmid DNA-based therapy that expresses a long-acting human interleukin-10 variant (hIL-10var). Here, we describe the 6-month GLP toxicology study of this therapy. Intra-articular injections of hIL-10var pDNA into canine stifle joints up to 1.5 mg bilaterally were well-tolerated and without pathologic findings. This represents the first long-term toxicologic assessment of intra-articular pDNA therapy. We also report results of a small double-blind, placebo-controlled study of the effect of intra-articular hIL-10var pDNA on pain measures in companion (pet) dogs with naturally occurring osteoarthritis. This human IL-10-based targeted therapy reduced pain measures in the dogs, based on veterinary and owner ratings, without any adverse findings. These results with hIL-10var pDNA therapy, well-tolerated and without toxicologic effects, establish the basis for clinical trials of a new class of safe and effective therapies for OA.

Background Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). Conclusion This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation. Trial registration NCT04167566, Date 14/11/2019. Retrospective registration.

Background Mass and continuous distribution channels have significantly increased access to insecticide-treated nets (ITNs) in Ghana since 2000. Despite these gains, a large gap remains between ITN access and use. Methods A qualitative research study was carried out to explore the individual and contextual factors influencing ITN use among those with access in three sites in Ghana. Eighteen focus group discussions, and free listing and ranking activities were carried out with 174 participants; seven of those participants were selected for in-depth case study. Focus group discussions and case study interviews were audio-recorded, transcribed verbatim, and analysed thematically. Results ITN use, as described by study participants, was not binary; it varied throughout the night, across seasons, and over time. Heat was the most commonly cited barrier to consistent ITN use and contributed to low reported ITN use during the dry season. Barriers to ITN use throughout the year included skin irritation; lack of airflow in the sleeping space; and, in some cases, a lack of information on the connection between the use of ITNs and malaria prevention. Falling ill or losing a loved one to malaria was the most powerful motivator for consistent ITN use. Participants also discussed developing a habit of ITN use and the economic benefit of prevention over treatment as facilitating factors. Participants reported gender differences in ITN use, noting that men were more likely than women and children to stay outdoors late at night and more likely to sleep outdoors without an ITN. Conclusion The study results suggest the greatest gains in ITN use among those with access could be made by promoting consistent use throughout the year among occasional and seasonal users. Opportunities for improving communication messages, such as increasing the time ITNs are aired before first use, as well as structural approaches to enhance the usability of ITNs in challenging contexts, such as promoting solutions for outdoor ITN use, were identified from this work. The information from this study can be used to inform social and behaviour change messaging and innovative approaches to closing the ITN use gap in Ghana.

Traumatic brain injury (TBI) may affect the pharmacodynamics of centrally acting drugs. Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive measure of cortical gamma-aminobutyric acid (GABA)-mediated cortical inhibition. Huperzine A (HupA) is a naturally occurring acetylcholinesterase inhibitor with newly discovered potent GABA-mediated antiepileptic capacity, which is reliably detected by ppTMS. To test whether TBI alters cerebral HupA pharmacodynamics, we exposed rats to fluid percussion injury (FPI) and tested whether ppTMS metrics of cortical inhibition differ in magnitude and temporal pattern in injured rats. Anesthetized adult rats were exposed to FPI or sham injury. Ninety minutes post-TBI, rats were injected with HupA or saline (0.6 mg/kg, intraperitoneally). TBI resulted in reduced cortical inhibition 90 min after the injury (N = 18) compared to sham (N = 13) controls (p = 0.03). HupA enhanced cortical inhibition after both sham injury (N = 6; p = 0.002) and TBI (N = 6; p = 0.02). The median time to maximum HupA inhibition in sham and TBI groups were 46.4 and 76.5 min, respectively (p = 0.03). This was consistent with a quadratic trend comparison that projects HupA-mediated cortical inhibition to last longer in injured rats (p = 0.007). We show that 1) cortical GABA-mediated inhibition, as measured by ppTMS, decreases acutely post-TBI, 2) HupA restores lost post-TBI GABA-mediated inhibition, and 3) HupA-mediated enhancement of cortical inhibition is delayed post-TBI. The plausible reasons of the latter include 1) low HupA volume of distribution rendering HupA confined in the intravascular compartment, therefore vulnerable to reduced post-TBI cerebral perfusion, and 2) GABAR dysfunction and increased AChE activity post-TBI.

Background The Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission. Methods A cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Discussion It is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes. Trial registration ClinicalTrials.gov, ID: NCT03036059. Registered on 26 January 2017. Pan African Clinical Trials Registry, ID: PACTR201702002012425. Registered on 23 February 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2196-9) contains supplementary material, which is available to authorized users.

Objective Mass drug Administration (MDA) for the control of Lymphatic filariasis (LF), in Ghana, started in the year 2000. While this had great success in many implementation units, there remain areas with persistent transmission, after more than 10 years of treatment. A closer examination of the parasite populations could help understand the reasons for persistent infections, and formulatingn appropriate strategies to control LF in these areas of persistent transmission. Materials and Methods In a longitudinal study, we assessed the prevalence of microfilaraemia (mf) in two communities with 12 years of MDA in Ghana. In baseline surveys 6 months after the National MDA in 2014, 370 consenting individuals were tested for antigenaemia using immunochromatographic test (ICT) cards, and had their mf count determined through night blood surveys. 48 ICT positives, of whom 17 were positive for mf, were treated with 400 μg/kg ivermectin + 400 mg albendazole and subsequently followed for parasitological assessment at 3-month intervals for 1 year. This overlapped with the National MDA in 2015. Results There was a 68% parasite clearance 3 months after treatment. The pre-treatment mf count differed significantly from the post-treatment mf counts at 3 months (p = 0.0023), 6 months (p = 0.0051), 9 months (p = 0.0113) and 12 months (p = 0.0008). Conclusion In these settings with persistent LF transmission, twice-yearly treatment may help accelerate LF elimination. Further large-scale evaluations are required to ascertain these findings. This article is protected by copyright. All rights reserved.

BackgroundLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2020, with the main strategy being treatment of entire endemic communities. Since the inception of the Global Programme for the Elimination of LF in 2000, tremendous progress has been made in many endemic countries. However, current observations point to the need for improved treatment regimen, frequency of treatment or drug delivery strategies in order to achieve the elimination goals in certain endemic areas. In this randomised trial, we evaluate the use of twice-yearly treatment with ivermectin and albendazole in 18 LF-endemic communities in Ghana, where despite 15 years of yearly treatment the disease is still above the elimination thresholds.MethodsFollowing demographic data collection, Wuchereria bancrofti antigen, microfilaria and antibody prevalence were assessed in study participants using the Alere FTS kit, nucleopore filtration and Wb123 ELISA, respectively. The study assessed the perspectives of the communities’on persistent transmission of LF in view of implementing effective treatment uptake strategies.ResultsThe baseline assessments revealed antigen prevalence of 8.2% (95% CI=6.8–9.8), with overall microfilaria prevalence of 1.2%. Infections were higher in males and in individuals who spend significant amount of time outdoors for commercial activities. Barriers related to medication, personal, health system, disease and social structure were observed to affect mass drug administration compliance. Community members perceived that they were not susceptible to infection and this together with drug adverse effects strongly affect the ingestion of the drugs.ConclusionWhile this trial is still in an early phase, the baseline assessments reveal programmatic challenges to the implementation of a twice-yearly treatment strategy for the control of LF which must be addressed to enhance implementation success.

The development of antibody testing for the diagnosis of lymphatic filariasis (LF) is intended to enhance the monitoring and evaluation activities of the Global Program for the Elimination of LF. This is due to the fact that antibody tests are expected to be the most sensitive at detecting exposure to LF compared to antigen that takes longer to develop. To this end a new antibody-based enzyme linked immunosorbent assay (ELISA) to Wuchereria bancrofti antigen Wb123 has been developed and further designed into a point of care rapid diagnostic test, under evaluation. In pretreatment surveys, individuals were tested for antigen using the immuno-chromatographic test (ICT) card, and night blood microfilariae, after which all positives were treated using Ivermectin and Albendazole. The Wb123 ELISA was tested in antigen positive individuals, three months after they were treated. Samples were also tested for ICT and night blood microfilariae. The results revealed a reduction in microfilariae and ICT prevalence after treatment. Antigen and antibody prevalence increased with age. However, there was no correlation with the antibody responses observed. The mean WB123 antibody titers were higher among ICT positives, but not significantly different from ICT negative persons. While the Wb123 is targeted for use in untreated populations, further evaluations and guidelines will be required to define its use in populations that have undergone treatment for the control of LF.Keywords: Lymphatic filariasis, elephantiasis, antigen, antibody, Wb123, Ghana

De novo loss-of-function mutations in the voltage-gated sodium channel (VGSC) SCN1A (encoding Nav1.1) are the main cause of Dravet syndrome (DS), a catastrophic early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), refractory afebrile epilepsy, cognitive and behavioral deficits, and a 15-20% mortality rate. SCN1A mutations also lead to genetic epilepsy with febrile seizures plus (GEFS+), which is an inherited disorder characterized by early-life FSs and the development of a range of adult epilepsy subtypes. Current antiepileptic drugs often fail to protect against the severe seizures and behavioral and cognitive deficits found in patients with SCN1A mutations. To address the need for more efficacious treatments for SCN1A-derived epilepsies, we evaluated the therapeutic potential of Huperzine A, a naturally occurring reversible acetylcholinesterase inhibitor. In CF1 mice, Hup A (0.56 or 1 mg/kg) was found to confer protection against 6 Hz-, pentylenetetrazole (PTZ)-, and maximal electroshock (MES)-induced seizures. Robust protection against 6 Hz-, MES-, and hyperthermia-induced seizures was also achieved following Hup A administration in mouse models of DS (Scn1a+/-) and GEFS+ (Scn1aRH/+). Furthermore, Hup A-mediated seizure protection was sustained during 3 weeks of daily injections in Scn1aRH/+ mutants. Finally, we determined that the muscarinic and GABAA receptors play a role in Hup A-mediated seizure protection. These findings indicate that Hup A might provide a novel therapeutic strategy for increasing seizure resistance in DS and GEFS+, and more broadly, in other forms of refractory epilepsy.

Objective: A review of literature referable to management issues for women with epilepsy (WWE) was undertaken for the development of a practice parameter.Background: Epilepsy is a common neurologic condition with gender-related management implications. Although reviews of this topic often focus on pregnancy-related issues for WWE, specific health concerns for WWE are present throughout all phases of reproductive life.Methods: An OVID MEDLINE literature search was conducted for 1965 to 1997 using the following key words/phrases and cross referencing: epilepsy/seizures and pregnancy, anticonvulsants, antiepileptic drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic acid, vitamin K, metabolic bone disease, and breast-feeding.Results: Pregnancy outcome literature for WWE spans several decades. Methodology varies and interpretation is complicated by modern management strategies. Contributions of socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to adverse pregnancy outcomes have not been clearly delineated. There is a biologic basis for recommendations concerning contraception, folate supplementation, vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial epilepsy, and reproductive endocrine disorders, but no outcome studies afford a strong evidence base for practice recommendation.Conclusions: WWE face health issues for which there is no available outcome literature to guide decision making. The urgent need for studies in many of these areas is highlighted by expanded treatment options with new AEDs and epilepsy surgery.

Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

A series of LPGs with the same period was inscribed by femtosecond laser into photonic crystal fibre with various powers. All suffered post-fabrication spectral evolution at low temperatures, apparently related to inscription power.

A series of LPGs was inscribed in photonic crystal fibre by a low repetition femtosecond laser system. When subjected to bending they were found to be spectrally sensitive to bend orientation and displayed a strong polarisation dependence.

Fibre Bragg Grating (FBG) array sensors have been successfully embedded in aluminium alloy matrix by ultrasonic consolidation (UC) technique. The temperature and loading responses of the embedded FBG arrays have been systematically characterised. The embedded grating sensors exhibit an average temperature sensitivity of ~36pm/°C, which is three times higher than that of normal FBGs, and a loading responsivity of ~0.1nm/kg within the dynamic range from 0kg to 3kg. This initial experiment clearly demonstrates that FBG array sensors can be embedded in metal matrix together with other passive and active fibres to fabricate smart materials to monitor the operation and health of engineering structures.

A multicore fibre (MCF) sensor to measure the radial deformation of a compliant cylinder under compression is presented. The sensor is connectorised and need not be permanently bonded to the test object. A differential measurement technique using FBGs written into the MCF makes the sensor temperature insensitive. FBG measurement of axial strain of a cylinder under compression is also reported.

We report a distinctive polarisation mode coupling behaviour of tilted fibre Bragg gratings (TFBGs) with tilted angle exceeding 45°. The ex-45° TFBGs exhibit pronounced polarisation mode splitting resulted from grating structure asymmetry induced birefringence. We have studied and analysed the property of ex-45° TFBGs under transverse load applied to their equivalent fast- and slow-axis. The results show that the coupling between the orthogonally polarised modes takes place only when the load is applied to its fast-axis, giving a prominent directional loading response. This transverse load related polarisation property may be exploitable for implementation of optical fibre vector sensors capable of measuring the magnitude and orientation of the applied transverse load.