21367 research outputs found
Sort by
An exploratory study of context and factors shaping policies for integrated management of multimorbidity in Malawi
Get PDFBackground: Malawi faces a high burden of chronic diseases. There is an increasing prevalence of multimorbidity, where individuals experience the coexistence of two or more chronic communicable and noncommunicable diseases. International organizations such as the WHO call for policy reforms that embrace integrated disease management. Our study explored the policy environment and decisions directly relevant to the delivery of integrated multimorbidity care in Malawi. Methods: This was a cross-sectional qualitative study. We used a single case-study methodology combining two sources of data: a document review of policies published between 2000 and 2023 (N = 11) and key informant interviews with policymakers (N = 13). We used the policy triangle framework to examine the context in which the policies aimed at improving management of multimorbidity were formulated, the actors involved, the policy process and the contents of the policies. Additionally, we identified barriers to the implementation of these policies. Results: Malawi advocates for integrated health promotion, screening, treatment and management of chronic conditions across key policies, with a bias towards noncommunicable disease (NCD) + NCD and NCD + human immunodeficiency virus (HIV) integration. Integrated disease management was seen as a tool to accelerate achieving global and local goals such as the Sustainable Development Goals and universal health coverage. However, the formulation and implementation of these policies have been challenged by several factors including unclear burden of multimorbidity, donor-driven priorities through vertical disease funding and inadequate number and training of healthcare workers to manage multimorbidity. Conclusions: We suggest that the timely provision of resources, creation of guidelines for multimorbidity management, building clinicians’ capacity and harmonization of donor–government goals should accompany policy rollout for integrated multimorbidity management.</p
Draft genome sequence of Flavobacterium aquidurense strain, isolated from untreated wastewater
Get PDFHere, we report the draft 5.8 Mb genome sequence of a Flavobacterium aquidurense isolate from untreated wastewater in Liverpool, United Kingdom. The reported isolate has the potential to produce both flexirubin and β-carotene pigments, and contains an additional biosynthetic gene cluster for a putative novel β-lactone. The genome also contains a gene for a putative β-lactamase blaJOHN-1 analogue, and there are multiple copies of a putative novel insertion sequence of the IS3 family. This genome adds to a growing resource of Flavobacterium spp. sequencing data which can be utilized to investigate microbial pigment production, antimicrobial resistance genes and mobile genetic elements within this genus.</p
Significant variations in tolerance to clothianidin and pirimiphos-methyl in Anopheles gambiae and Anopheles funestus populations during a dramatic malaria resurgence despite sustained indoor residual spraying in Uganda
Get PDFBackground: A dramatic malaria resurgence occurred in areas of Uganda between 2020 and 2022, coinciding with the switch to clothianidin-based formulations for indoor residual spraying. During the resurgence, Anopheles funestus sensu lato (s.l.) numbers increased more than those of Anopheles gambiae s.l., but when an alternative insecticide, pirimiphos-methyl, was reintroduced in 2023, both malaria cases and An. funestus mosquito density fell. Methods: In this study, we investigated possible causes of the resurgence by assessing (1) whether sufficient quantities of insecticide were sprayed, (2) the residual insecticide bio-efficacy against wild mosquitoes, and (3) the insecticide susceptibility of both key vector populations using standard test tube assays and wall cone assays. Results: In 2023, after adjusting for extraction efficiency, 70–80% of the houses had optimal residual concentrations of insecticides (clothianidin > 0.3g/m2; pirimiphos-methyl > 0.5g/m2), with significant variations between sampling rounds and wall types. Mud walls had the lowest residual concentration of insecticides, and the lowest observed mortality in wall cone assays, compared to burnt bricks with plaster/cement/paint. In the studies of residual bio-efficacy, by World Health Organization (WHO) definitions, An. funestus s.l. showed resistance to clothianidin (< 80% mortality) up to 11 months, and susceptibility to pirimiphos-methyl (> 90% mortality) when exposed to wall surfaces up to 7 months post-spray. In WHO tube tests, variations were observed in susceptibility to clothianidin in An. funestus s.l. populations using dose– and time–response assays (80–98% mortality). In 2022, An. gambiae s.l. was largely susceptible to the clothianidin-based formulation Sumishield (85–90% mortality), although the levels dropped slightly in 2023 (60–85% mortality), mainly in mud and pole houses. In contrast, An. gambiae s.l. was highly susceptible with mild tolerance to the pirimiphos-methyl-based formulation Actellic (~ 80% mortality), and time–response assays showed that An. gambiae s.l. populations had very low knockdown and mortality at lower exposure time compared to An. funestus s.l. Regression models showed a positive association between residual insecticide concentration (RIC) and mortality in houses sprayed with Sumishield but not Actellic houses. Conclusions: Despite the possible variations observed in spray operations, the study revealed that An. funestus s.l. exhibited a higher tolerance to clothianidin-based formulations compared to An. gambiae s.l., and this might have driven the malaria resurgence observed in Uganda. However, there are signals of An. gambiae s.l. resistance to pirimiphos-methyl, which will require further investigation and monitoring.</p
Early intensive blood pressure management after endovascular treatment in ischaemic stroke (IDENTIFY) a multicentre, open-label, blinded-endpoint, randomised controlled trial
Get PDFBackground: The optimal blood pressure (BP) management following successful endovascular treatment (EVT) in acute ischaemic stroke (AIS) patients remains unclear. This study investigated the safety and efficacy of intensive BP control in AIS patients who had received EVT within 6 h. Methods: This randomised, multicentre, open-label, blinded-endpoint clinical trial (ChiCTR2200057770) was conducted at 63 stroke centres in China. Eligible participants had AIS due to large vessel occlusion in anterior circulation, underwent EVT within 6 h, and achieved successful recanalisation. Patients were randomised to intensive (systolic BP target <130 mm Hg) or standard (systolic BP target <180 mm Hg) management, maintained until 24 h post-EVT. The primary outcome was unfavourable functional outcome (modified Rankin Scale score of 3–6) at 90 days. The trial was terminated following a neutral interim analysis results and publication of counterpart randomised trials. Findings: Between October 14, 2022 and March 18, 2024, 383 patients were randomised. Unfavourable functional outcome occurred in 71.0% (130/183) of the intensive-management group and 67.5% (135/200) of the standard-management group (risk ratio, 1.05; 95% CI, 0.92–1.20; p = 0.45). There was no significant difference in symptomatic intracerebral haemorrhage, malignant brain oedema, or all-cause death at 90 days. Interpretation: Intensive BP management to <130 mm Hg did not improve outcomes in AIS patients undergoing EVT within 6 h and achieved successful recanalisation. The optimal BP management strategies require further investigation. Funding: Sichuan University West China Hospital, National Natural Science Foundation of China, National Key R&D Programme of China, and Science and Technology Department of Sichuan Province.</p
Initial community response to a novel spatial repellent for malaria prevention in Busia County, Kenya
Get PDFBackground: Malaria transmission in Africa significantly declined between 2005 and 2015 due to widespread distribution of insecticide-treated nets (ITNs). However, since 2015, transmission has increased due to insecticide resistance and biting at times when people are not using ITNs. Spatial repellents (SRs) may help address these challenges. A double-blinded cluster-randomized controlled trial (cRCT) in Busia County, Kenya, reported that Mosquito Shield™, a transfluthrin-based SR, reduced malaria infections by 33.4% during interim analysis and 32.7% by the end of the study, among children aged 6 months to 10 years. Understanding community responses to SRs is critical for their successful deployment and long-term use. This paper reports the initial community response to MosquitoShield™ as part of the Advancing Evidence for the Global Implementation of Spatial Repellents (AEGIS) project. Methods: Longitudinal qualitative data were collected from 30 households participating in the cRCT, using modified trials of improved practices (TIPs) to assess participants’ perceptions of MosquitoShield’s utility, efficacy, appearance, and user experience with monthly product replacement. This analysis focuses on initial responses recorded one week and two months post-installation. The data were analysed using thematic coding, with researchers blinded to trial arm assignment. Results: The participants reported a positive initial response to the SR, with a significant perceived reduction in mosquito density and activity. Some also reported concerns about the product’s effectiveness over time and its comparison with existing mosquito control methods, particularly after first replacement. Participants highlighted their perception that the SR provided continuous protection in contrast with the situational protection offered by ITNs. Improvement suggestions included modified installation methods plus a longer-lasting product that protected more space. Conclusion: MosquitoShield™ shows potential as a promising malaria prevention tool among communities in Busia County, Kenya. Incorporating user feedback and addressing concerns about product installation, duration, and coverage are crucial for successful implementation. Future research exploring community perceptions, cultural factors and behavioural responses related to long-term acceptability and the impact of SRs on malaria transmission will be crucial to ensure effective SR implementation.</p
Prevalence of hepatitis B virus infection among pregnant women and cord blood hepatitis B surface antigen positive newborns in sub-Saharan Africa and South Asia
Get PDFBackground: Newborns infected with Hepatitis B Virus (HBV) are at risk of chronic liver disease and hepatocellular carcinoma. Objectives: This study investigated the prevalence of HBV infection among pregnant women and cord blood Hepatitis B surface antigen (HBsAg) positivity of their newborns in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa. Study design: Randomly selected paired maternal and cord blood samples (n = 101 each site) taken at delivery were tested for HBsAg and Hepatitis B extractable antigen (HBeAg) in the women using a chemiluminescent microparticle immunoassay. Similarly, cord blood sample of newborn was assessed for HBsAg reactivity. HBV DNA was quantified using the Xpert® HBV viral load assay, followed by genotyping. Results: The overall prevalence of maternal HBsAg positivity was 5.5 % (95 %CI: 0.4 %–7.1 %; n = 50/909). HBsAg positivity was higher in African countries (7.3 %; 95 %CI: 5.4 %–9.6 %; n = 44/606) compared to South Asian countries (2.0 %; 95 %CI: 0.8 %–4.3 %; n = 6/303; p = 0.002). Relative to South Africa, there were higher odds of HBsAg sero-positivity in women from Mozambique ((aOR): 7.7, 95 %CI: 1.6 %–37.8 %) and Mali (aOR: 5.7; 95 %CI: 1.1 %–29.7 %). The rate of HBsAg positivity in cord blood of babies born to HBsAg positive women was 28.0 % (95 %CI: 17.1 %–42.3 %; n = 14/50), including 31.8 % (95 %CI: 19.5–47.4 %; n = 14/44) in African countries. No cord blood HBsAg positivity was observed in South Asia. Genotypic analysis revealed HBV genotypes A (41.7 %) and E (58.3 %) were pre-dominant. Conclusion: The high rate of cord blood positivity (28.0 %) for HBsAg underscores the urgency of enhancing HBV prevention strategies to meet the World Health Organization's target of a 90 % reduction in new HBV infections by 2030.</p
The impact of sulfadoxine–pyrimethamine resistance on the effectiveness of intermittent preventive treatment for the prevention of malaria in pregnancy in Africa: an updated systematic review and meta-analysis
Get PDFBackground: Resistance of Plasmodium falciparum to sulfadoxine–pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine–pyrimethamine (ITPp-SP) in sub-Saharan Africa. We updated an aggregated-data meta-analysis to assess the associations between sulfadoxine–pyrimethamine resistance and the effectiveness of IPTp-SP to inform policy. Methods: We searched databases (Jan 1, 1990, to June 8, 2024) for observational studies or trials reporting data on malaria, low birthweight (<2500 g), anaemia, and other outcomes by IPTp-SP dose and matched these by year and location with studies that reported on molecular markers of sulfadoxine–pyrimethamine resistance. Studies including only women with HIV or combined interventions were excluded. We evaluated how sulfadoxine–pyrimethamine resistance influenced the adjusted risk ratio (aRR) between three and two doses of IPTp-SP for various outcomes using Poisson mixed-effects models that allowed for non-linear relationships. Initially, we performed a threshold analysis, stratified by region, to identify the resistance levels most predictive of altered effect of IPTp-SP doses on malaria parasitaemia at delivery (peripheral or placental parasitaemia by any test), our primary outcome. These resistance strata were then used in all subsequent models for other outcomes. All analyses were adjusted for malaria transmission intensity, HIV infection, percentage of paucigravidae, and insecticide-treated net use. Performance of models was evaluated using cross-validation. The trial was registered with PROSPERO (CRD42021250359). Findings: Overall, 122 studies involving 148 693 participants were included. For west and central Africa (69 studies comprising 63 745 participants), very low resistance was categorised as a prevalence of the dihydropteroate synthase (dhps) Lys540Glu mutation in the parasite population of less than 4%, and low resistance as a prevalence of Lys540Glu of 4% or higher. In east and southern Africa (53 studies comprising 84 948 participants), moderate resistance was categorised as a prevalence of the Lys540Glu mutation of less than 60% combined with a prevalence of the Ala581Gly mutation of less than 5%, high resistance as a prevalence of Lys540Glu of 60% or higher combined with a prevalence of Ala581Gly of less than 5%, and very high resistance as a prevalence of the Lys540Glu mutation of 60% or higher combined with a prevalence of Ala581Gly of 5% or higher. There was a marked trend towards lower efficacy of IPTp-SP on reducing malaria infection with increasing resistance levels. In west and central Africa, when comparing three versus two doses, the aRR was 0·71 (95% CI 0·65–0·78) in areas with very low resistance and 0·83 (0·72–0·95) in areas with low resistance (p=0·0144 for the difference between dose–response curves in very low vs low resistance). For east and southern Africa, the same trend was observed: the aRR was 0·63 (95% CI 0·57–0·69) in areas with moderate resistance, 0·89 (0·82–0·96) in areas with high resistance, and 0·93 (0·85–1·01) in areas with very high resistance (p<0·0001 for dose–response curves differences between moderate vs high and moderate vs very high resistance). This pattern was not seen for low birthweight. When comparing three versus two doses in west and central Africa, the aRR was 0·58 (95% CI 0·48–0·68) in areas with very low resistance and 0·56 (0·44–0·68) in areas with low resistance (p=0·72 for dose–response curves very low vs low resistance). For east and southern Africa, the aRR was 0·75 (95% CI 0·52–0·98) in areas with moderate resistance, 0·73 (0·69–0·78) in areas with high resistance, and 0·75 (0·63–0·87) in areas with very high resistance (p=0·80 for dose–response curves moderate vs high resistance; p=0·90 for moderate vs very high resistance). Dose comparisons in some resistance strata were limited by sample size.Interpretation: IPTp-SP antimalarial efficacy is greatly reduced in very high resistance areas. However, it remains effective at reducing low birthweight in these areas, possibly through non-malaria effects on fetal growth. While IPTp-SP use should continue in high SP-resistance areas, alternative malaria preventive strategies are urgently needed in these areas.Funding: WHO and WorldWide-Antimalarial-Resistance-Network.</p
High diversity of Escherichia coli causing invasive disease in neonates in Malawi poses challenges for O-antigen based vaccine approach
Get PDFBackground: Escherichia coli is an important cause of neonatal sepsis and the third most prevalent cause of neonatal infection in sub-Saharan Africa, often with negative outcomes. Development of maternally administered vaccines is under consideration, but to provide adequate protection, an understanding of serotypes causing invasive disease in this population is essential. We describe the genomic characteristics of a collection of neonatal E. coli isolates from a tertiary hospital in Blantyre, Malawi, with specific reference to potential protection by vaccines under development. Methods: Neonatal blood or cerebrospinal fluid cultures from 2012 to 2021 identified 208 E. coli isolates, and 169 could be recovered for sequencing. Results: Our data shows very high diversity in sequence types, LPS O-antigen-type and flagellar H-type, which all show temporal fluctuations and, as far as we are aware previously undescribed diversity, including ten putative novel O-types. Vaccines in clinical trials target the O-antigen but would only protect against less than half (37.9%) of neonatal sepsis cases in this population (EXPEC9V). An O-antigen-based vaccine would require 30 different O-types to protect against 80% of infections. Conclusions: Vaccines against neonatal sepsis in Africa are of considerable potential value, but their development requires larger studies to establish the diversity and stability over time of relevant O-types for this population.</p
Decentralized Immunization Monitoring:Lessons Learnt from a Pilot Implementation in Kumbotso LGA, Kano State, Nigeria
Get PDFBackground: Immunization coverage in Nigeria is low, with many children missing out on important lifesaving vaccines. To enable a better understanding of contextual factors towards increasing uptake, we piloted a Decentralized Immunization Monitoring (DIM) approach in the Kumbotso local government area (LGA) of Kano state, Nigeria, to identify wards with low vaccination rates and understand why this is happening. The findings were used to improve routine immunization (RI) programs and reduce the number of unvaccinated children and children yet to receive their first dose of diphtheria–pertussis–tetanus (DPT) vaccine, referred to as Zero-Dose children (ZD). Methods: This study adopted a cross-sectional design approach using the Behavioural and Social Drivers of Vaccination (BeSD) framework and the Lot Quality Assurance Sampling (LQAS). The study population comprised caregivers of children aged 0–11 months and 12–23 months across the 11 wards in Kumbotso District, Kano State, Nigeria, using a segmentation sampling approach. The study covered 209 settlements selected using probability proportionate to size (PPS) sampling from the wards. Univariate and bivariate analyses were performed to show patterns and relations across variables. Results: Out of 418 caregivers surveyed, 98.1% were female. Delayed vaccination was experienced by 21.9% of children aged 4.5–11 months, while the prevalence of ZD was estimated at 26.8% amongst the older cohort (12–23 months). A total of 71.4% of the delayed group and 89.1% of the ZD group remained unvaccinated. Caregiver education, rural residence, and home births correlated with delayed/ZD status (p < 0.05). Logistic regression associated higher caregiver education with reduced delayed vaccination odds (OR:0.34, p < 0.001) and urban residence with lower ZD odds (OR:1.89, p = 0.036). The antigen coverages of BCG (81.5%), DPT3 (63.6%), and measles 1 (59.7%) all surpassed the national dropout thresholds. Kumbotso, Unguwar Rimi, and Kureken Sani wards were all identified as underperforming and therefore targeted for intervention. Negative vaccine perceptions (50% delayed, 53.6% ZD) and distrust in health workers (46.4% delayed, 48.2% ZD) were significant barriers, though the caregiver intent to vaccinate was protective (OR: 0.27, p < 0.001). The cost of accessing immunization services appeared to have a minor effect on coverage, as the majority of caregivers of delayed and ZD children reported spending less than 200 Naira (equivalent to USD 0.15) on transport. Conclusions: This pilot study highlighted the utility of LQAS and BeSD in identifying low-performing wards, barriers, and routine immunization gaps. Barriers included low caregiver education, rural residence, and negative vaccine perceptions/safety. Caregiver education and urban residence were protective factors against delayed and ZD vaccination, suggesting social and systemic barriers, particularly in rural and less educated populations. Antigen-specific coverage showed disparities, with dropouts for multi-dose vaccines exceeding the national thresholds of 10%. Targeted measures addressing education, trust, and systemic issues are needed. Findings emphasize decentralized monitoring, community engagement, and context-specific strategies to reduce ZD children and ensure equitable vaccination in Nigeria.</p
Improving Molecular Epidemiological Surveillance of Strongyloidiasis Upon Differentiation of Strongyloides fuelleborni fuelleborni From Strongyloides stercoralis
Get PDFMolecular epidemiological surveillance for zoonotic strongyloidiasis is confounded by a genus-specific TaqMan probe assay that conflates Strongyloides fuelleborni fuelleborni with Strongyloides stercoralis. To improve surveillance, we developed and validated a novel duplex species-specific TaqMan probe assay, screening a representative collection of available clinical samples. Our assay was highly discriminatory, evidencing no cross-reactivity, and had a lowest DNA detection limit of 1 pg/µL. However, as the genus-specific DNA assay has greater detection ability, we propose a 2-step protocol where samples are first screened with this assay then, if positive, screened with our species-specific assay, discriminating (co)infections between each threadworm species