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Prevalence of mental health conditions in post-conflict Kasai Province, Democratic Republic of the Congo: A repeated, cross-sectional study
Get PDFGlobally, one in five people in post-conflict areas are estimated to be living with a mental health condition. As a key public health issue, these conditions negatively affect individuals, communities, and societies to function after a conflict. Documenting the prevalence of mental health conditions amongst these populations is crucial to prioritise and guide future mental health interventions. This study was the first to use a repeated cross-sectional design and sex-disaggregated analysis, with the aim of estimating the prevalence of depression (PHQ-9) and anxiety (GAD-7) in a post-conflict population of the Kasai Province, Democratic Republic of the Congo. Several domains of Quality of life (WHO-QoL-BREF) were also assessed to gain insight into the relationship between bio-psychosocial stressors and mental health status. Using random cluster sampling, data were collected in two waves from 385 participants, with a one-year interval. The pooled prevalence across both waves was 34.3% for major depression disorder and 26.5% for generalised anxiety disorder. Multivariable linear regression analysis showed that depression and anxiety were both predicted by being female, being of older age, and by experiencing lower physical quality of life, but not by the passing of time. For both mental health outcomes, environmental quality of life served as a significant predictor for women, but not for men. In conclusion, these results suggest that a lack of mental health services and continued exposure to daily stressors are linked to a sustained high prevalence of mental health conditions in our study population. There is a significant need for the development of mental health services in the region. These services should go beyond biomedical interventions and include multi-sectoral approaches that consider the social determinants of (mental) health.</p
Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.
Get PDFBackgroundProcalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.MethodsThe BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales. Children aged 72 h to 18 years who were admitted to hospital and were being treated with intravenous antibiotics for suspected or confirmed bacterial infection and who were expected to remain on intravenous antibiotics for more than 48 h were enrolled. Participants were randomly assigned (1:1) to receive either current clinical management alone (usual care group) or clinical management with the addition of a procalcitonin test guided algorithm (procalcitonin group). Participants were randomly assigned by minimisation, with site and age group (0–6 months, 6 months to 2 years, 2–5 years, and older than 5 years) as minimisation factors and a random element to reduce predictability. Participants were randomly assigned remotely using a secure 24 h web-based randomisation programme. The coprimary outcomes were duration of intravenous antibiotic use, assessed for superiority, and a composite safety measure, assessed for non-inferiority (non-inferiority margin 5%). The primary analysis sample for each coprimary endpoint included all randomly assigned participants with available outcome data. This trial is registered with the International Standard Randomised Controlled Trial Number registry, ISRCTN11369832.FindingsBetween June 11, 2018, and Oct 12, 2022, 15 282 children were screened for eligibility, 1949 of whom were randomly assigned to receive procalcitonin-guided antibiotic therapy (n=977) or usual care (n=972). The median intravenous antibiotic duration was 96·0 h (IQR 59·5–155·5) in the procalcitonin group and 99·7 h (61·2–153·8) in the usual care group (hazard ratio 0·96 [95% CI 0·87–1·05]). 78 (9%) of 917 participants in the procalcitonin group and 85 (9%) of 904 participants in the usual care group had at least one event covered by the composite safety outcome measure (estimated adjusted risk difference –0·81% [95% CI upper bound 1·11]).InterpretationIn children with suspected or confirmed bacterial infection admitted to hospitals in England and Wales for intravenous antibiotic treatment of at least 48 h, the introduction of a procalcitonin-guided algorithm did not reduce duration of intravenous antibiotics treatment and is non-inferior to usual care for safety outcomes. Therefore, evidence does not support the use of procalcitonin-guided algorithms where robust effective paediatric antibiotic stewardship programmes are established.</p
De novo designed proteins neutralize lethal snake venom toxins
Get PDFSnakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity4. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here we used deep learning methods to de novo design proteins to bind short-chain and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtained protein designs with remarkable thermal stability, high binding affinity and near-atomic-level agreement with the computational models. The designed proteins effectively neutralized all three 3FTx subfamilies in vitro and protected mice from a lethal neurotoxin challenge. Such potent, stable and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our results highlight how computational design could help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for the development of therapies for neglected tropical diseases.</p
Availability, cost and affordability of essential medicines for smoking cessation in low-income and middle-income countries: a cross-sectional study.
Get PDFSmoking cessation is more effective when supported by medicines. Data on the availability, cost and affordability of these treatments in low-income and middle-income countries (LMIC) are limited. Cross-sectional data for smoking cessation medications were collected from pharmacies, healthcare facilities and central medicine stores in 60 LMIC (2022–2023). Medications had varying availability, large price ranges and were essentially unaffordable. Enabling access to these medications is important in reducing tobacco consumption and associated disease. Strategies for integrating smoking cessation services into health systems are needed to reach Sustainable Development Goal targets.</p
LLIN Evaluation in Uganda Project (LLINEUP2) – Effect of long-lasting insecticidal nets (LLINs) treated with pyrethroid plus pyriproxyfen vs LLINs treated with pyrethroid plus piperonyl butoxide in Uganda: A cluster-randomised trial
Get PDFBetween 2000 and 2015, intensified efforts to control malaria substantially reduced malaria case incidence and parasite prevalence across Africa, with the majority of cases averted attributed to the distribution of long-lasting insecticidal nets (LLINs) [1]. More recently, however, progress on malaria control has stalled. Globally, malaria cases increased from 230 million in 2015 to 249 million in 2022, with 95% of cases reported from Africa [2]. Four African countries, including Uganda, accounted for nearly half of all cases worldwide in 2022. In 2022, Uganda reported the third highest number of malaria cases, representing 5% of the global burden of malaria [2]. In Uganda, implementation of malaria control interventions including repeated national LLIN distribution campaigns, indoor residual spraying (IRS) of insecticides in selected high-transmission districts, case management with effective artemisinin-based combination therapy, and intermittent preventive treatment in pregnancy (IPTp) reduced the malaria burden, with parasite prevalence by microscopy in children under-five decreasing from 45% in 2009 to 9% in 2018-2019 [3]. Progress in malaria control in Uganda has been difficult to sustain, however, despite ongoing implementation of effective control interventions [4,5].In Uganda, and across Africa, LLINs are the most widely-used malaria prevention tool [6]. As recommended by the World Health Organization (WHO), the Ugandan Ministry of Health distributes LLINs through mass campaigns approximately every three years, aiming for universal coverage [7]. Currently, LLINs rely on pyrethroid insecticides, but resistance to pyrethroids has spread rapidly in malaria vectors, threatening the effectiveness of LLINs [8, 9]. The causal mechanisms of pyrethroid resistance are complex, but point mutations in the voltage-gated sodium channel where pyrethroids bind (‘knock down resistance’), and alterations in enzymes that metabolize pyrethroids, commonly cytochrome P450s, are key features [10, 11]. Pyrethroid resistance is widespread in Uganda [12, 13].To combat emerging resistance, next generation LLINs that incorporate a second chemical in addition to pyrethroids have been developed. One such net includes piperonyl butoxide (PBO), a synergist which inhibits P450 enzymes, overcoming metabolic resistance mechanisms in mosquitoes, and partially restoring susceptibility to pyrethroids [13, 14]. Supported by evidence from trials conducted in Tanzania and Uganda [15–17], demonstrating the superiority of pyrethroid-PBO LLINs over pyrethroid-only LLINs, the WHO endorsed deployment of pyrethroid-PBO LLINs in areas where malaria vectors exhibit pyrethroid resistance. The WHO’s recommendation was conditional due to uncertainty about the cost-effectiveness and durability of pyrethroid-PBO LLINs [18, 19]. Another new type of LLIN combines pyrethroids with pyriproxyfen, an insect growth regulator which acts as a sterilising agent, reducing the vector population density and lifespan of adult mosquitoes. Pyrethroid-pyriproxyfen LLINs are promising, but trials comparing these nets to pyrethroid-only LLINs in Burkina Faso and Tanzania have produced mixed results [20, 21]. Additional studies evaluating the effectiveness of nets incorporating pyriproxyfen are needed.Uganda has embraced next-generation LLINs to combat pyrethroid resistance. While only pyrethroid-only LLINs were available for distribution in 2013-2014, pyrethroid-PBO LLINs were distributed to selected areas in 2016-2017 and were found to be superior to pyrethroid-only LLINs in a large-scale cluster-randomised trial [16,17]. In 2020-2021, pyrethroid-PBO LLINs and pyrethroid-pyriproxyfen LLINs were distributed across Uganda, providing an opportunity to evaluate the effectiveness of these LLINs in a ‘real-world’ setting. With support from the Ministry of Health, donors, and partners, a large cluster-randomised trial (LLINEUP2) was embedded within this national distribution campaign, allowing us to rigorously compare the impact of these LLINs on epidemiological indicators. Leveraging mass campaigns is an innovative, pragmatic approach to evaluate the ‘real-world’ effectiveness of novel malaria control interventions, which has been applied successfully in Uganda [16,17]. We aimed to test the hypothesis that malaria incidence would be lower in intervention clusters (randomised to receive pyrethroid-pyriproxyfen LLINs) than in control clusters (randomised to receive pyrethroid-PBO LLINs). Malaria surveillance data at health facilities were collected between 17 October 2020 and 31 March 2023, and cross-sectional community survey data between 24 November 2021 to 1 April 2022 (12-months) and 23 November 2022 to 21 March 2023 (24-months) post-LLIN distribution.</p
Efficacy of prebiotic, probiotic and synbiotic administration in improving growth in children aged 0–59 months living in low and middle‑income countries: a systematic review and meta‑analysis.
Get PDFBackground Poor growth is one of the major obstacles to human development, affecting millions of children under the age of 5 years, particularly those living in low- and middle-income countries (LMICs). The objective of this review was to evaluate the efficacy of administering pre-, pro- or synbiotics on the growth of children aged 0–59 months living in LMICs.Methods Google scholar, Pubmed, clinical trial.org and Science Direct databases were searched in April 2023 for randomised controlled trials of pre-, pro- or synbiotics that evaluated growth in under fives in LMICs. The primary outcome were weight and height gain. Secondary outcomes were head circumference, body mass index gain and Zscore. Random-effects meta-analysis was used to calculate mean differences for continuous outcomes. Grading of Recommendations Assessment, Development and Evaluation criteria was used to assess certainty of the evidence.Results Eight trials involving 1375 children under 5 years of age were identified. Meta-analysis of 6 RCTs (n = 991 children) revealed a significant difference in favor of the experimental group (n = 579) compared the control group (n = 412) for weight gain: (MD = 0.33 kg, 95% CI 0.11 to 0.55); low-certainty evidence. Sub-group analysis revealed that pre-, pro, or synbiotics may be more effective in malnourished that healthy children (p = 0.003). Meta-analysisof height gain for 4 RCTs (n = 845) found that there was no significant difference between the experimental group (n = 496) and the control group (n = 349) (MD = 0.31 cm; 95% CI -0.36 to 0.98); low-certainty evidence. In sub-group analysis, prebiotics had a greater impact on height gain than synbiotics (p = 0.03). In the only study reportingan increase in head circumference (n = 32 children), this was not improved by the administration of synbiotics. However, administration of synbiotics to undernourished children significantly improved BMI gain.</p
Disinfection methods for preventing COVID-19 infections in healthcare settings: A rapid review
Get PDFBackground: Disinfectant sprays and wipes reduce the risk of infection from contaminated surfaces and materials in healthcare facilities. To support guideline updates, evidence on surface disinfection against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are needed.Aim: This study aims to compare the effect of disinfection by spraying or wiping on the risk of human infections in healthcare facilities providing coronavirus disease 2019 (COVID-19) services.Setting: Healthcare settings providing care for patients with COVID-19 or where exposure risk to COVID-19 is high.Method:We searched the Central Register of Controlled Trials (CENTRAL) and Cochrane Database of systematic review; PubMed, EMBASE and EPOC databases from 01 January 2020 to 31 August 2022. Results were screened for eligibility, the risk of bias in included studies assessed, and the certainty of evidence defined using GRADE®.Results: Three observational studies were included. Two studies reporting proportion of surfaces with residual contamination, showed contrasting results with spraying more effective (0%, [n= 0/39] vs. 25.6% [n= 23/90]) in one study but less effective (25.0% [n= 12/48] vs. 48.2% [n= 13/27]) in the other. The third study reported higher reductions from wiping (88.0%) compared to spraying (15.1%). The risk of bias ranged from moderate to serious and the certainty of the evidence was very low. No study reported a direct effect on the risk of infection in humans.Conclusion: Both spraying and wiping methods may protect against SARS-CoV-2 infections indirectly by reducing residual surface contamination</p
Mapping waste piles in an urban environment using ground surveys, manual digitization of drone imagery, and object based image classification approach.
Get PDFThere is wide recognition of the threats posed by the open dumping of waste in the environment. However, tools to surveil interventions for reducing this practice are poorly developed. This study explores the use of drone imagery for environmental surveillance. Drone images of waste piles were captured in a densely populated residential neighborhood in the Republic of Malawi. Images were processed using the Structure for Motion (SfM) technique and partitioned into segments using Orfeo Toolbox mounted in QGIS software. A total of 509 segments were manually labeled to generate data for training and testing a series of classification models. Four supervised classification algorithms (Random Forest, Artificial Neural Network, Naïve Bayes, and Support Vector Machine) were trained, and their performances were assessed regarding precision, recall, and F-1 score. Ground surveys were also conducted to map waste piles using a Global Positioning System (GPS) receiver and determine the physical composition of materials on the waste pile surface. Differences were observed between the field survey done by community-led physical mapping of waste piles and drone mapping. Drone mapping identified more waste piles than field surveys, and the spatial extent of waste piles was computed for each waste pile. The binary Support Vector Machine model predictions were the highest performing, with a precision of 0.98, recall of 0.99, and F1-score of 0.98. Drone mapping enabled the identification of waste piles in areas that cannot be accessed during ground surveys and further allowed the quantification of the total land surface area covered by waste piles. Drone imagery-based surveillance of waste piles thus has the potential to guide environmental waste policy, offer solutions for permanent monitoring, and evaluate waste reduction interventions.</p
Advances in the recombinase polymerase amplification platform for urogenital schistosomiasis diagnosis (ShDraI-RPA) towards implementation at the point-of-care
Get PDFAccurate diagnosis of schistosomiasis is crucial to achieve disease elimination as a public health problem. Rapid and highly sensitive diagnostic tools that can be used in decentralized environments and/or at the point-of-care are needed. This work optimises and simplifies an existing isothermal molecular diagnostic platform (recombinase polymerase amplification, RPA) for urogenital schistosomiasis, the ShDraI-RPA, with a focus on delivering a more accurate diagnosis in endemic settings. The standard ShDraI-RPA oligonucleotides were modified, incorporating a phosphorothioate backbone into the reverse primer and inverting the probe fluorophore and quencher, to prevent false positive results due to secondary structure formation. The sensitivity and specificity of the modified assay were evaluated on a donor urine spiked with one S. haematobium egg and an array of other schistosomes and human urinary tract pathogens. The stability of RPA reagents was assessed by storing them at ambient temperature (± 27 °C) in a dark environment for up to 90 days. Sample preparations were explored to develop a simple, rapid and low resource methodology that would complement the ShDraI-RPA platform when used in remote settings. The modified ShDraI-RPA assay was robust, sensitive and specific to S. haematobium group species, detecting down to 10 fg of gDNA and ten synthetic Dra I copies. DNA amplification was achieved at 42 °C within 20 min and results could easily be visualized using a portable fluorometer or under blue light. RPA reagents remained stable when stored in the absence of light at ± 27 °C for up to 30 days. A two-step DNA extraction method proved optimal for extracting DNA from single S. haematobium eggs in spiked urine. The optimized ShDraI-RPA platform shows improved specificity and sensitivity and has now reached several of the target product profile requirements set out by the WHO for the ideal diagnostic test for schistosomiasis.</p
Malawian Democracy Beyond Patrons and Clients: Distribution in Parliamentary Elections and the Moral Grounds of Democratic Relationships
Get PDFThe distribution of cash, resources and campaign materials is a characteristic feature of elections in Malawi and across Africa. Scholars, commentators and international bodies often describe these practices as a type of clientelism, patronage or ‘vote buying’ that corrupts the ethical integrity of the relationship between democratic representatives and the electorate by introducing a transactional logic into the formation of political relationships. Drawing on long-term ethnographic research in a rural constituency in Malawi’s Central Region, this article examines the significance of distributary practices in the 2019 parliamentary elections. It argues that distributary practices should be understood as an attempt by parliamentary candidates to establish the moral grounds of a distinctly democratic relationship with constituents in the context of socio-economic inequality and limited state resources. The article highlights two important ways that distributive practices, informed by an ethic prevalent in the broader social life of constituents, enabled political relationships to be formed on robust moral, democratic grounds. First, distribution can be understood as an enactment of a type of virtue associated with the capacity to assist others that I refer to as ‘virtuous capacity’, entailed in the demands and expectations of being a Member of Parliament. Second, these practices can be seen as an expression of a non-reciprocal moral obligation associated with a democratic mandate to serve constituents. Rather than undermining the ethical integrity of the relationship between candidates and constituents, distributary practices have enabled moral democratic relationships to be formed that might otherwise be difficult to establish.</p