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Beyond Failure: Exploring the Heart of the Malawian State
Get PDFFollowing a national referendum in 1993, Malawi transitioned from the 30-year autocratic regime of Hastings Kamuzu Banda and the Malawi Congress Party (MCP) to become a democratic state.Footnote1 While sustained pressure from a wide variety of actors contributed to this transition, of particular importance was the 1992 Lenten pastoral letter from the Catholic bishops of the Episcopal Conference of Malawi, entitled ‘Living our Faith’, which famously expressed open criticism of the MCP regime in a number of areas, ranging from limitations on press freedom to access to education and health care.Footnote2 The Malawian Catholic bishops’ Lenten letter of 25 February 2024 also sought to make political waves. Although unlikely to cause as great a political shift as the 1992 letter, the bishops similarly attempted to intervene in Malawian politics by publicly calling the state’s leaders to account. In the letter, entitled ‘The Sad Story of Malawi’, they vehemently declared that the Tonse Alliance governmentFootnote3 has so far failed to deliver, with its leaders having ‘resorted to being salesmen of words, with no serious attempt at keeping any promises they made to the people’.Footnote4 The letter subsequently outlined ten areas of failure, including corruption, concerns about press freedom and politically motivated violence.</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
‘You can sleep hungry just to buy the medicine’: Applying a patient-centred model of cumulative complexity to explore how patients manage the lifelong workload of hypertension care in Kenya
Get PDFThis research applies the Cumulative Complexity model to examine patient experiences of hypertension management following prescription of anti-hypertensive medication in the public health system in Kenya. Set in Kiambu County, central Kenya, it draws on abductive analysis of interviews with patients (n = 24), caregivers (n = 7) and non-participant observation in four purposively selected public facilities conducted between November 2022 and April 2023. Patients undertook three kinds of ‘work’ to reduce their blood pressure: processing work to accept hypertension diagnosis and its chronic dimension; practical work managing care and medications, and work of managing emotions. Four inter-related domains of patient capacity influenced patients' ability to do this work: individual financial resources; physical functioning; social support and religious faith. Variations in treatment cost and medicine availability increased patient workload. When workload overwhelmed capacity treatment adherence was interrupted. Interruptions in treatment resulted in negative feedback loops further reducing patient capacity. Recognising temporal variability in workload and capacity is key to understand treatment adherence in resource constrained settings. Consideration of adaptive counter-agency can strengthen treatment burden models. We encourage policy makers to prioritise addressing treatment burdens to support treatment adherence and sustained hypertension control.</p
Optimizing maternal health facility locations in Ethiopia: A geospatial approach for upgrading to emergency obstetric and newborn care
Get PDFBackground: Emergency Obstetric and Newborn Care (EmONC) facilities are scarce in Ethiopia and concentrated in bigger cities. Using geospatial analysis, this study modeled the optimal locations for new EmONC facilities such that a maximum number of women could access them. Methods: We used data from the 2016 EmONC Assessment encompassing 3804 health facilities (including 370 EmONC facilities). Using OpenStreetMap data, we created a road network with different speed assumptions for different road types. We assumed women would walk to the nearest available road and use public transport afterward. We modeled the upgrade of health facilities using a location-allocation analysis based on the existing distribution of facilities and population and road conditions. Three scenarios—conservative (25 % gap closure), moderate (50 % gap closure), and ideal (100 % gap closure)—were modeled to enhance EmONC facility numbers to recommended levels. Findings: The majority of Ethiopian women live over two hours, the maximum suggested travel time, away from EmONC facilities, with significant regional variations. In all three scenarios, upgrades mostly targeted facilities in Oromia, Amhara, and Southern Nations Nationalities and Peoples regions, with minimal facilities selected in Addis Ababa, Dire Dawa, and Harari. Conclusion: Optimizing the location of new facilities using geospatial analysis has shown considerable potential in enhancing geographic accessibility and reducing regional disparities. Nonetheless, even under the most favorable scenario, a substantial portion of the country still lacks geographic access to EmONC facilities. Therefore, strategic health facility upgrades should be complemented by expanding or enhancing road infrastructure
Adaptive Design for Phase II/III Platform Trial of Lassa Fever Therapeutics
Get PDFThe current recommendation for treating Lassa fever with ribavirin is supported only by weak evidence. Given the persistent effects in areas with endemic transmission and epidemic potential, there is an urgent need to reassess ribavirin and investigate other potential therapeutic candidates; however, a robust clinical trial method adapted to Lassa fever epidemiology has not yet been established. We propose an adaptive phase II/III multicenter randomized controlled platform trial that uses a superiority framework with an equal allocation ratio and accounts for challenges selecting the primary end point and estimating the target sample size by using an interim analysis
Incidence of diabetes mellitus following hospitalisation for COVID-19 in the United Kingdom: A prospective observational study: A prospective observational study
No full textBackground: People hospitalised for coronavirus disease 2019 (COVID-19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness. Methods: We analysed a multicentre prospective cohort study (PHOSP-COVID) of people ≥18 years discharged from NHS hospitals across the United Kingdom following COVID-19. Individuals were included if they attended at least one research visit with a HbA1c measurement within 14 months of discharge and had no history of diabetes at baseline. The primary outcome was new onset diabetes (any type), as defined by a first glycated haemoglobin (HbA1c) measurement ≥6.5% (≥48 mmol/mol). Follow-up was censored at the last HbA1c measurement. Age-standardised incidence rates and incidence rate ratios (adjusted for age, sex, ethnicity, length of hospital stay, body mass index, smoking, physical activity, deprivation, hypertension, hyperlipidaemia/hypercholesterolaemia, intensive therapy unit admission, invasive mechanical ventilation, corticosteroid use and C-reactive protein score) were calculated using Poisson regression. Incidence rates were compared with the control groups of published clinical trials in the United Kingdom by applying the same inclusion and exclusion criteria, where possible. Results: Incidence of diabetes was 91.4 per 1000 person-years and was higher in South Asian (incidence rate ratios [IRR] = 3.60; 1.77, 7.32; p < 0.001) and Black ethnic groups (IRR = 2.36; 1.07, 5.21; p = 0.03) compared with White ethnic groups. When restricted to similar characteristics, the incidence rates were similar to those in UK clinical trials data. Conclusion: Diabetes incidence following hospitalisation for COVID-19 is high, but it remains uncertain whether it is disproportionately higher than pre-pandemic levels
Statistical analysis plan for the “empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia” clinical trial
Get PDFBackground: The EMPIRICAL trial aims to assess safety and efficacy of an empirical treatment against cytomegalovirus (CMV) and tuberculosis (TB) compared to standard of care (SoC), on adverse events and 15-day and 1-year mortality among infants living with HIV hospitalized with severe pneumonia in Africa. Methods and design: The EMPIRICAL trial (NCT03915366) is an international multicenter phase II-III, open-label randomized factorial clinical trial conducted in six African countries. The trial has four randomization arms in a 1:1:1:1 fashion with patients allocated to (i) TB-Treatment plus SoC, (ii) valganciclovir plus SoC, (iii) both TB-Treatment and valganciclovir plus SoC, and (iv) SoC only. Discussion: This paper describes the statistical analysis plan (SAP) for the trial which, per the study publication plan, needs to be published prior to the database lock and final analysis results. The SAP includes details of the analyses to be undertaken and unpopulated tables that will be reported to address primary and secondary endpoints. The database will be locked on 31st January 2025. </p
Parallel in vitro ion channel and in vivo zebrafish assaying of elapid snake venoms following chromatographic separation of toxin components
Get PDFSnake venoms are complex bioactive mixtures designed to paralyse, kill, or digest prey. These venoms are of pharmacological interest due to their ability to modulate molecular targets such as ion channels and receptors with high specificity and potency. Traditional studies often focus on in vitro molecular analysis or in vivo behavioural effects, limiting comprehensive understanding. Here, we present a high-throughput screening platform that combines in vitro ion channel assays with in vivo zebrafish larval bioassays using nanofractionation analytics. This method integrates post-column calcium flux assays, zebrafish paralytic bioassays, toxin mass spectrometry, and proteomics to link bioactivity with toxin identification. Using elapid snake venoms (genus Dendroaspis, Naja, and Hemachatus) as a proof of concept, we identified several toxins modulating ion channels with paralytic effects on zebrafish larvae. Our approach enables parallel acquisition of in vitro and in vivo data, offering a robust guide for identifying and characterising ion channel modulators with defined molecular targets.</p
180-day efficacy of nirsevimab against hospitalisation for respiratory syncytial virus lower respiratory tract infections in infants (HARMONIE): a randomised, controlled, phase 3b trial
Get PDFBackground: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalisations in infants worldwide. The primary analyses of HARMONIE showed that nirsevimab reduced infant hospitalisations due to RSV-associated lower respiratory tract infection through the RSV season. This analysis aims to evaluate nirsevimab's efficacy at 180 days after dosing, a period exceeding the typical 5-month RSV season. Methods: HARMONIE is an ongoing, open-label, parallel arm, randomised, controlled, phase 3b study conducted in France, Germany, and the UK. Infants aged 12 months or younger, born at a gestational age of at least 29 weeks, were randomly assigned (1:1) to receive either a single intramuscular dose of nirsevimab (50 mg for children <5 kg or 100 mg for children ≥5 kg) or standard care (without RSV prophylaxis) before or during their first RSV season. Randomisation was electronically done, stratified by country and age-group. The primary efficacy endpoint for this analysis was the incidence of hospitalisations due to RSV-associated lower respiratory tract infection up to 180 days after nirsevimab administration or randomisation in all randomised participants. Safety up to 365 days following nirsevimab administration was also assessed. This trial is ongoing and registered with ClinicalTrials.gov, number NCT05437510. Findings: Between Aug 8, 2022, and Feb 28, 2023, 8057 infants were randomly assigned to either the nirsevimab group (n=4038) or the standard care group (n=4019). The median age at randomisation was 4·00 months (IQR 1·0–7·0; range 0·0–12·0, and 4195 (52·1%) were male and 3862 (47·9%) were female. Up to 180 days, 12 (0·3%) of 4038 infants in the nirsevimab group and 68 (1·7%) of 4019 infants in the standard care group had been hospitalised for RSV-associated lower respiratory tract infection, corresponding to a nirsevimab efficacy of 82·7% (95% CI 67·8–91·5; p<0·0001). Most participants experienced grade 1 (2759 [68·7%] of 4016 in the nirsevimab group; 2696 [67·1%] of 4018 in the standard care group) or grade 2 (1447 [36·0%] of 4016 in the nirsevimab group; 1436 [35·7%] of 4018 in the standard care group) treatment-emergent adverse events, and no apparent safety concerns were raised up to 365 days after dosing. Interpretation: Nirsevimab offers consistent and sustained protection against hospitalisation due to RSV-associated lower respiratory tract infection for at least 6 months. This finding provides global health systems greater flexibility when implementing nirsevimab, providing substantial benefit in the ongoing effort to reduce the burden of infant RSV and the potential wider public health value. Funding: Sanofi and AstraZeneca.</p
The potential impacts of vector host species fidelity on zoonotic arbovirus transmission
Get PDFThe interaction between vector host preference and host availability on vector blood feeding behaviour has important implications for the transmission of vector-borne pathogens. However, to our knowledge, the effect of bias towards feeding on the same host species from which a first meal was taken, termed fidelity, has not been quantified. Using a mathematical model we showed that vector fidelity to the host species they take a first blood meal from leads to non-homogeneous mixing between hosts and vectors. Taking Japanese encephalitis virus (JEV) as a case study, we investigated how vector preference for amplifying vs dead-end hosts and fidelity can influence JEV transmission. We show that in regions where pigs (amplifying hosts) are scarce compared to cattle (dead-end hosts preferred by common JEV vectors), JEV could still be maintained through vector fidelity. Our findings demonstrate the importance of considering fidelity as a potential driver of transmission, particularly in scenarios such as Bangladesh and India where the composition of the host community might initially suggest that transmission is not possible.</p