A trial of intermittent preventive treatment and home-based management of malaria in a rural area of The Gambia

BACKGROUND: Individual malaria interventions provide only partial protection in most epidemiological situations. Thus, there is a need to investigate whether combining interventions provides added benefit in reducing mortality and morbidity from malaria. The potential benefits of combining IPT in children (IPTc) with home management of malaria (HMM) was investigated. METHODS: During the 2008 malaria transmission season, 1,277 children under five years of age resident in villages within the rural Farafenni demographic surveillance system (DSS) in North Bank Region, The Gambia were randomized to receive monthly IPTc with a single dose of sulphadoxine/pyrimethamine (SP) plus three doses of amodiaquine (AQ) or SP and AQ placebos given by village health workers (VHWs) on three occasions during the months of September, October and November, in a double-blind trial. Children in all study villages who developed an acute febrile illness suggestive of malaria were treated by VHWs who had been taught how to manage malaria with artemether-lumefantrine (Coartem™). The primary aims of the project were to determine whether IPTc added significant benefit to HMM and whether VHWs could effectively combine the delivery of both interventions. RESULTS: The incidence of clinical attacks of malaria was very low in both study groups. The incidence rate of malaria in children who received IPTc was 0.44 clinical attacks per 1,000 child months at risk while that for control children was 1.32 per 1,000 child months at risk, a protective efficacy of 66% (95% CI -23% to 96%; p = 0.35). The mean (standard deviation) haemoglobin concentration at the end of the malaria transmission season was similar in the two treatment groups: 10.2 (1.6) g/dL in the IPTc group compared to 10.3 (1.5) g/dL in the placebo group. Coverage with IPTc was high, with 94% of children receiving all three treatments during the study period. CONCLUSION: Due to the very low incidence of malaria, no firm conclusion can be drawn on the added benefit of IPTc in preventing clinical episodes of malaria among children who had access to HMM in The Gambia. However, the study showed that VHWs can successfully combine provision of HMM with provision of IPTc

Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings

Day case complex devices: the state of the UK.

Objective: Complex cardiac devices including implantable cardioverter defibrillator (ICD) and cardiac resynchronisation therapy (CRT) devices can safely be implanted as a day case procedure as opposed to overnight stay. We assess how common day case complex device therapy is and the cost implications of more widespread adoption across the UK. Methods: A freedom of information request was sent to all centres performing complex cardiac devices across the UK to assess the adoption of this technique. Cost implications were assessed using Department of Health National Schedule of Reference Costs 2016-2017. Results: 100 UK centres were surveyed, 80% replied. Eighty per cent of UK centres already implant complex cardiac devices as a day case to some extent. 64.06% of centres have a protocol for this. 12.82% of centres do 75% as day case. There was no relationship between centre volume and the proportion of devices done as a day case as opposed to overnight stay. The cost saving of performing a complex device as a day case as opposed to overnight stay was £412 per ICD, £525 per CRT-pacemaker and £2169 per CRT-defibrillator. Conclusions: Day case complex devices are already widespread across the UK, however, there is scope for increase. An increase in proportion of day case devices could translate to £5 583 265 in savings annually for the National Health Service if all centres performed 75% of devices as a day case

Investigating the Influence of High-Speed Gantry Rotation in Cardiac CT on Motion Artifacts in Aortic Stenosis Patients Not Premedicated with β-Blockers: The FAST-CCT Randomized Trial Protocol.

Coronary CT angiography (CCTA) is increasingly used as a non-invasive tool to assess coronary artery disease (CAD). However, CCTA is subject to motion artifacts, potentially limiting its clinical utility. Despite faster (0.35 and 0.28 s/rot) gantry rotation times, low (60-65 bpm) heartbeat is recommended, and the use of β-blockers is often needed. Technological advancements have resulted in the development of faster rotation speeds (0.23 s/rot). However, their added value in patients not premedicated with β-blockers remains unclear. This prospective single-center, two-arm, randomized, controlled trial aims to assess the influence of fast rotation on coronary motion artifacts, diagnostic accuracy of CCTA for CAD, and patient safety. We will randomize a total of 142 patients aged ≥ 50 scheduled for an aortic stenosis work-up to receive CCTA with either a fast (0.23) or standard (0.28 s/rot) gantry speed. rate of CCTAs with coronary motion artifacts hindering interpretation. assessable coronary segments rate, diagnostic accuracy against invasive coronary angiography (ICA), motion artifact magnitude per segment, contrast-to-noise ratio (CNR), and patient ionizing radiation dose. The local ethics committee has approved the protocol. Potential significance: FAST-CCT may improve motion artifact reduction and diagnosis quality, thus eliminating the need for rate control and β-blocker administration. gov identifier: NCT05709652

Indiscriminate ingestion of entomopathogenic nematodes and their symbiotic bacteria by Aedes aegypti larvae: a novel strategy to control the vector of Chikungunya, dengue and yellow fever

Third and fourth instar larvae of Aedes aegypti actively ingested entomopathogenic nematodes (EPNs) and their symbiotic bacteria, resulting in larval mortality. All six EPN species evaluated in this study were pathogenic to Ae. aegypti but varied significantly in their virulence. Heterorhabditis bacteriophora and Steinernema carpocapsae were most virulent, H. megidis and S. kraussei showed the least virulence, whereas H. downesi and S. feltiae had intermediate virulence. Larval mortality was dose dependent for all EPN species. When using a dose of 100 infective juveniles (IJs) per larva, H. bacteriophora and S. carpocapsae caused 90%-100% mortality, whereas H. downesi and S. feltiae caused only 40%-60% mortality. Even when using 200 IJs/larva, H. megidis and S. kraussei caused a maximum of 30%-40% mortality. Some of the invasive EPNs were melanized, suggesting a strong humoral defense response by the Aedes larvae. The degree of melanization was quite variable; some EPNs were totally enveloped in a melanin sheath while others were partially coated with melanin. Melanization did not stop the EPN from multiplying and killing the Aedes larvae. IJs released from infected larvae would have the potential to infect healthy mosquito larvae. Also, both bacterial supernatant and bacterial cell suspension of Xenorhabdus nematophila caused >91% larval mortality after 48 h, whereas only the bacterial cell suspension of Photorhabdus laumondii was effective against the mosquito larvae. These data provides useful information on the potential use of EPNs and/or formulated bacterial cell suspensions in the control of the important urban and container-breeding mosquito, Ae. aegypti, and are a starting point for future simulated and actual field studies

A Plasmodium Whole-Genome Synteny Map: Indels and Synteny Breakpoints as Foci for Species-Specific Genes

Whole-genome comparisons are highly informative regarding genome evolution and can reveal the conservation of genome organization and gene content, gene regulatory elements, and presence of species-specific genes. Initial comparative genome analyses of the human malaria parasite Plasmodium falciparum and rodent malaria parasites (RMPs) revealed a core set of 4,500 Plasmodium orthologs located in the highly syntenic central regions of the chromosomes that sharply defined the boundaries of the variable subtelomeric regions. We used composite RMP contigs, based on partial DNA sequences of three RMPs, to generate a whole-genome synteny map of P. falciparum and the RMPs. The core regions of the 14 chromosomes of P. falciparum and the RMPs are organized in 36 synteny blocks, representing groups of genes that have been stably inherited since these malaria species diverged, but whose relative organization has altered as a result of a predicted minimum of 15 recombination events. P. falciparum-specific genes and gene families are found in the variable subtelomeric regions (575 genes), at synteny breakpoints (42 genes), and as intrasyntenic indels (126 genes). Of the 168 non-subtelomeric P. falciparum genes, including two newly discovered gene families, 68% are predicted to be exported to the surface of the blood stage parasite or infected erythrocyte. Chromosomal rearrangements are implicated in the generation and dispersal of P. falciparum-specific gene families, including one encoding receptor-associated protein kinases. The data show that both synteny breakpoints and intrasyntenic indels can be foci for species-specific genes with a predicted role in host-parasite interactions and suggest that, besides rearrangements in the subtelomeric regions, chromosomal rearrangements may also be involved in the generation of species-specific gene families. A majority of these genes are expressed in blood stages, suggesting that the vertebrate host exerts a greater selective pressure than the mosquito vector, resulting in the acquisition of diversity

Designing a mHealth clinical decision support system for Parkinson's disease: a theoretically grounded user needs approach.

BACKGROUND: Despite the established evidence and theoretical advances explaining human judgments under uncertainty, developments of mobile health (mHealth) Clinical Decision Support Systems (CDSS) have not explicitly applied the psychology of decision making to the study of user needs. We report on a user needs approach to develop a prototype of a mHealth CDSS for Parkinson's disease (PD), which is theoretically grounded in the psychological literature about expert decision making and judgement under uncertainty. METHODS: A suite of user needs studies was conducted in 4 European countries (Greece, Italy, Slovenia, the UK) prior to the development of PD_Manager, a mHealth-based CDSS designed for Parkinson's disease, using wireless technology. Study 1 undertook Hierarchical Task Analysis (HTA) including elicitation of user needs, cognitive demands and perceived risks/benefits (ethical considerations) associated with the proposed CDSS, through structured interviews of prescribing clinicians (N = 47). Study 2 carried out computational modelling of prescribing clinicians' (N = 12) decision strategies based on social judgment theory. Study 3 was a vignette study of prescribing clinicians' (N = 18) willingness to change treatment based on either self-reported symptoms data, devices-generated symptoms data or combinations of both. RESULTS: Study 1 indicated that system development should move away from the traditional silos of 'motor' and 'non-motor' symptom evaluations and suggest that presenting data on symptoms according to goal-based domains would be the most beneficial approach, the most important being patients' overall Quality of Life (QoL). The computational modelling in Study 2 extrapolated different factor combinations when making judgements about different questions. Study 3 indicated that the clinicians were equally likely to change the care plan based on information about the change in the patient's condition from the patient's self-report and the wearable devices. CONCLUSIONS: Based on our approach, we could formulate the following principles of mHealth design: 1) enabling shared decision making between the clinician, patient and the carer; 2) flexibility that accounts for diagnostic and treatment variation among clinicians; 3) monitoring of information integration from multiple sources. Our approach highlighted the central importance of the patient-clinician relationship in clinical decision making and the relevance of theoretical as opposed to algorithm (technology)-based modelling of human judgment

Beliefs surrounding the use of inhaled asthma medication in The Gambia: a qualitative study of asthma patients and healthcare workers

Asthma-related mortality is high in low- and middle-income countries. Little is known about public perceptions of inhaled medicines. We conducted semi-structured interviews with asthma patients and healthcare workers at three secondary care facilities in The Gambia, between August and November 2022. Thematic analysis was used to interpret these data. A total of 20 patients and 15 healthcare workers were interviewed. Both groups noted limited access to inhalers was an issue resulting in continued use of oral medications. Some patients recognised the benefits of inhalers, yet beliefs that inhalers were dangerous were common. Reliance on oral short-acting beta agonists meant patients saw asthma as a recurrent acute condition resulting in an emphasis on hospital management with little awareness of inhaled preventative medicines. Increasing access to inhaled medicines has the potential to reduce costly avoidable admissions, but socio-cultural factors, in addition to medication supply, need addressing