Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial.

BACKGROUND: Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. METHODS: We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5-36 months) were enrolled and randomly assigned (2:1) to receive 5 µg R21 plus 50 µg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. FINDINGS: From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71-79; p<0·0001) at the seasonal sites and 68% (61-74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71-78; p<0·0001) at the seasonal sites and 67% (59-73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762-974) cases per 1000 children-years at seasonal sites and 296 (231-362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5-17 month age group compared with 18-36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73-84]; p<0·001) and standard (75% [65-83]; p<0·001) sites. INTERPRETATION: R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. FUNDING: The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.

SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was inhibited by interferon-γ (IFN-γ). IFN-γ production was strongest in BAL NKG2r+CD8+ T cells and NKG2Alo natural killer (NK) cells and was further increased in NKG2Alo NK cells after spike protein stimulation. However, IFN-γ production was impaired in NK cells from macaques with persisting virus. Moreover, IFN-γ also enhanced the expression of major histocompatibility complex (MHC)-E on BAL macrophages, possibly inhibiting NK cell-mediated killing. Macaques with less persisting virus mounted adaptive NK cells that escaped the MHC-E-dependent inhibition. Our findings reveal an interplay between NK cells and macrophages that regulated SARS-CoV-2 persistence in macrophages and was mediated by IFN-γ.

Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study.

BACKGROUND: Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. METHODS: DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. FINDINGS: From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference -23%, 95% CI -33 to -13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (-13%, -24 to -3; p=0·01). INTERPRETATION: DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. FUNDING: European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

The Impact of the Covid-19 Pandemic on Recovery from Cardiac Surgery Over Time: Results of the Cardiaccovid Study from three Uk National Lockdowns.

This prospective study (clinicaltrials.gov NCT04366167) explores health-related quality of life (EQ-5D-5L), event-related distress (IES-R) and depression (CES-D) after cardiac surgery during the three UK national COVID-19 lockdowns. Overall, 253 patients participated (lockdown one n = 196; two n = 45; three n = 12) completing the above-mentioned questionnaires at baseline, one week after discharge and six weeks, six and 12 months after surgery. While EQ-5D-5L values were similar across all cohorts, those having surgery in lockdowns two and three had higher IES-R scores at 1-year and higher IES-R and CES-D baseline scores, respectively. Generally, increased distress, worse depression and poorer HRQoL were observed in women.

Intrahousehold power inequalities and cooperation: Unpacking household responses to nutrition-sensitive agriculture interventions in rural India.

Nutrition-sensitive agriculture (NSA) interventions offer a means to improve the dietary quality of rural, undernourished populations. Their effectiveness could be further increased by understanding how household dynamics enable or inhibit the uptake of NSA behaviours. We used a convergent parallel mixed-methods design to describe the links between household dynamics-specifically intrahousehold power inequalities and intrahousehold cooperation-and dietary quality and to explore whether household dynamics mediated or modified the effects of NSA interventions tested in a cluster-randomized trial, Upscaling Participatory Action and Videos for Agriculture and Nutrition (UPAVAN). We use quantitative data from cross-sectional surveys in 148 village clusters at UPAVAN's baseline and 32 months afterwards (endline), and qualitative data from family case studies and focus group discussions with intervention participants and facilitators. We found that households cooperated to grow and buy nutritious foods, and gendered power inequalities were associated with women's dietary quality, but cooperation and women's use of power was inhibited by several interlinked factors. UPAVAN interventions were more successful in more supportive, cooperative households, and in some cases, the interventions increased women's decision-making power. However, women's decisions to enter into negotiations with family members depended on whether women deemed the practices promoted by UPAVAN interventions to be feasible, as well as women's confidence and previous cultivation success. We conclude that interventions may be more effective if they can elicit cooperation from the whole household. This will require a move towards more family-centric intervention models that empower women while involving other family members and accounting for the varied ways that families cooperate and negotiate.

The impact of the COVID-19 pandemic on recovery from cardiac surgery: 1-year outcomes.

AIMS: The outbreak of COVID-19 was potentially stressful for everyone and possibly heightened in those having surgery. We sought to explore the impact of the pandemic on recovery from cardiac surgery. METHODS AND RESULTS: A prospective observational study of 196 patients who were ≥18years old undergoing cardiac surgery between March 23 and July 4, 2020 (UK lockdown) was conducted. Those too unwell or unable to give consent/complete the questionnaires were excluded. Participants completed (on paper or electronically) the impact of event [Impact of Events Scale-revised (IES-R)] (distress related to COVID-19), depression [Centre for Epidemiological Studies Depression Scale (CES-D)], and EQ-5D-5L [(quality of life, health-related quality of life (HRQoL)] questionnaires at baseline, 1 week after hospital discharge, and 6 weeks, 6 months and 1 year post-surgery. Questionnaire completion was >75.0% at all timepoints, except at 1 week (67.3%). Most participants were male [147 (75.0%)], white British [156 (79.6%)] with an average age 63.4years. No patients had COVID-19. IES-R sand CES-D were above average at baseline (indicating higher levels of anxiety and depression) decreasing over time. HRQoL pre-surgery was high, reducing at 1 week but increasing to almost pre-operative levels at 6 weeks and exceeding pre-operative levels at 6 months and 1 year. IES-R and CES-D scores were consistently higher in women and younger patients with women also having poorer HRQoL up to 1-year after surgery. CONCLUSIONS: High levels of distress were observed in patients undergoing cardiac surgery during the COVID-19 pandemic with women and younger participants particularly affected. Psychological support pre- and post-operatively in further crises or traumatic times should be considered to aid recovery. REGISTRATION: Clinicaltrials.gov ID:NCT04366167.

Socioeconomic inequity in coverage and quality of maternal postnatal care in Ethiopia.

OBJECTIVE: High-quality postnatal care is vital for improving maternal health. This study examined the relationship between household socioeconomic status and both coverage and quality of postnatal care in Ethiopia. METHOD: Cross-sectional household survey data were collected in October-November 2013 from 12 zones in 4 regions of Ethiopia. Women reporting a live birth in the 3-24 months prior to the survey were interviewed about the care they received before, during and after delivery and their demographic characteristics. Using mixed effect logistic and linear regression, the associations between household socioeconomic status and receiving postnatal care, location of postnatal care (health facility vs. non-health facility), cadre of person providing care and the number of seven key services (including physical checks and advice) provided at a postnatal visit, were estimated. RESULTS: A total of 16% (358/2189) of women interviewed reported receiving at least one postnatal care visit within 6 weeks of delivery. Receiving a postnatal care visit was strongly associated with socioeconomic status with women from the highest socioeconomic group having twice the odds of receiving postnatal care compared to women in the poorest quintile (OR [95% CI]: 1.98 [1.29, 3.05]). For each increasing socioeconomic status quintile there was a mean increase of 0.24 postnatal care services provided (95% CI: 0.06-0.43, p = 0.009) among women who did not give birth in a facility. There was no evidence that number of postnatal care services was associated with socioeconomic status for women who gave birth in a facility. There was no evidence that socioeconomic status was associated with the provider or location of postnatal care visits. CONCLUSION: Postnatal care in Ethiopia shows evidence of socio-economic inequity in both coverage and quality. This demonstrates the need to focus on quality improvement as well as coverage, particularly among the poorest women who did not deliver in a facility.

The nurse apprentice and fundamental bedside care: An historical perspective.

This historical study aims to explain how the transition from student nurse service to fully qualified "graduate nurse" service in the United States in the 20th century affected assumptions about fundamental patient care in hospital wards and provide historical context for current apprenticeship programs. Through analysis of documents from 1920 when student nurse service, a nurse apprentice model, was the norm to 1960 when the nurse apprentice model was waning in favor of registered nurse service, this study found that the replacement of student nurses with registered nurses led to weakened standardization of fundamental bedside care and the introduction of large numbers of unlicensed nursing assistants. While student nurses could perform all the functions of fully qualified graduate nurses, nursing assistants could not, resulting in a separation of fundamental nursing care from the professional nurse role and changes in assumptions and attitudes toward fundamental care. These changes had a negative effect on fundamental nursing care. New apprenticeship programs provide opportunities for improvement.

Understanding the effects of nutrition-sensitive agriculture interventions with participatory videos and women's group meetings on maternal and child nutrition in rural Odisha, India: A mixed-methods process evaluation.

A trial of three nutrition-sensitive agriculture interventions with participatory videos and women's group meetings in rural Odisha, India, found improvements in maternal and child dietary diversity, limited effects on agricultural production, and no effects on women and children's nutritional status. Our process evaluation explored fidelity, reach, and mechanisms behind interventions' effects. We also examined how context affected implementation, mechanisms, and outcomes. We used data from intervention monitoring systems, review notes, trial surveys, 32 case studies with families (n = 91 family members), and 20 group discussions with women's group members and intervention workers (n = 181 and 32, respectively). We found that interventions were implemented with high fidelity. Groups reached around half of the mothers of children under 2 years. Videos and meetings increased women's knowledge, motivation and confidence to suggest or make changes to their diets and agricultural production. Families responded in diverse ways. Many adopted or improved rainfed homestead garden cultivation for consumption, which could explain gains in maternal and child dietary diversity seen in the impact evaluation. Cultivation for income was less common. This was often due to small landholdings, poor access to irrigation and decision-making dominated by men. Interventions helped change norms about heavy work during pregnancy, but young women with little family support still did considerable work. Women's ability to shape cultivation, income and workload decisions was strongly influenced by support from male relatives. Future nutrition-sensitive agriculture interventions could include additional flexibility to address families' land, water, labour and time constraints, as well as actively engage with spouses and in-laws.

Improving maternal and newborn health services in Northeast Nigeria through a government-led partnership of stakeholders: a quasi-experimental study.

OBJECTIVES: This study aimed to quantify change in the coverage, quality and equity of essential maternal and newborn healthcare interventions in Gombe state, Northeast Nigeria, following a four year, government-led, maternal and newborn health intervention. DESIGN: Quasi-experimental plausibility study. Repeat cross-sectional household and linked health facility surveys were implemented in intervention and comparison areas. SETTING: Gombe state, Northeast Nigeria. PARTICIPANTS: Each household survey included a sample of 1000 women aged 13-49 years with a live birth in the previous 12 months. Health facility surveys comprised a readiness assessment and birth attendant interview. INTERVENTIONS: Between 2016-2019 a complex package of evidence-based interventions was implemented to increase access, use and quality of maternal and newborn healthcare, spanning the six WHO health system building blocks. OUTCOME MEASURES: Eighteen indicators of maternal and newborn healthcare. RESULTS: Between 2016 and 2019, the coverage of all indicators improved in intervention areas, with the exception of postnatal and postpartum contacts, which remained below 15%. Greater improvements were observed in intervention than comparison areas for eight indicators, including coverage of at least one antenatal visit (71% (95% CI 62 to 68) to 88% (95% CI 82 to 93)), at least four antenatal visits (46% (95% CI 39 to 53) to 69% (95% CI 60 to 75)), facility birth (48% (95% CI 37 to 59) to 64% (95% CI 54 to 73)), administration of uterotonics (44% (95% CI 34 to 54) to 59% (95% CI 50 to 67)), delayed newborn bathing (44% (95% CI 36 to 52) to 62% (95% CI 52 to 71)) and clean cord care (42% (95% CI 34 to 49) to 73% (95% CI 66 to 79)). Wide-spread inequities persisted however; only at least one antenatal visit saw pro-poor improvement. CONCLUSIONS: This intervention achieved improvements in life-saving behaviours for mothers and newborns, demonstrating that multipartner action, coordinated through government leadership, can shift the needle in the right direction, even in resource-constrained settings.

Embedding Community-Based Newborn Care in the Ethiopian health system: lessons from a 4-year programme evaluation.

Despite remarkable gains, improving neonatal survival globally remains slow paced. Innovative service-delivery packages have been developed for community health workers (CHWs) to maximize system efficiency and increase the reach of services. However, embedding these in health systems needs structural and procedural alignment. The Community-Based Newborn Care (CBNC) programme was a response to high neonatal mortality in Ethiopia. Key aspects include simplified treatment for neonatal illness, integrated outreach services and task-shifting. Using the CHW functionality model by WHO, this study evaluates the health system response to the programme, including quality of care. A before-and-after study was conducted with three survey time points: baseline (November 2013), midline (December 2015) and follow-up (December 2017-4 years after the programme started). Data were collected at a sample of primary healthcare facilities from 101 districts across four regions. Analysis took two perspectives: (1) health system response, through supplies, infrastructure support and supervision, assessed through interviews and observations at health facilities and (2) quality of care, through CHWs' theoretical capacity to deliver services, as well as their performance, assessed through functional health literacy and direct observation of young infant case management. Results showed gains in services for young infants, with antibiotics and job aids available at over 90% of health centres. However, services at health posts remained inadequate in 2017. In terms of quality of care, only 37% of CHWs correctly diagnosed key conditions in sick young infants at midline. CHWs' functional health literacy declined by over 70% in basic aspects of case management during the study. Although the frequency of quarterly supportive supervision visits was above 80% during 2013-2017, visits lacked support for managing sick young infants. Infrastructure and resources improved over the course of the CBNC programme implementation. However, embedding and scaling up the programme lacked the systems-thinking and attention to health system building-blocks needed to optimize service delivery.

Malnutrition in Infants Aged under 6 Months Attending Community Health Centres: A Cross Sectional Survey.

A poor understanding of malnutrition burden is a common reason for not prioritizing the care of small and nutritionally at-risk infants aged under-six months (infants u6m). We aimed to estimate the anthropometric deficit prevalence in infants u6m attending health centres, using the Composite Index of Anthropometric Failure (CIAF), and to assess the overlap of different individual indicators. We undertook a two-week survey of all infants u6m visiting 18 health centres in two zones of the Oromia region, Ethiopia. We measured weight, length, and MUAC (mid-upper arm circumference) and calculated weight-for-length (WLZ), length-for-age (LAZ), and weight-for-age z-scores (WAZ). Overall, 21.7% (95% CI: 19.2; 24.3) of infants u6m presented CIAF, and of these, 10.7% (95% CI: 8.93; 12.7) had multiple anthropometric deficits. Low MUAC overlapped with 47.5% (95% CI: 38.0; 57.3), 43.8% (95% CI: 34.9; 53.1), and 42.6% (95% CI: 36.3; 49.2) of the stunted, wasted, and CIAF prevalence, respectively. Underweight overlapped with 63.4% (95% CI: 53.6; 72.2), 52.7% (95% CI: 43.4; 61.7), and 59.6% (95% CI: 53.1; 65.9) of the stunted, wasted, and CIAF prevalence, respectively. Anthropometric deficits, single and multiple, are prevalent in infants attending health centres. WAZ overlaps more with other forms of anthropometric deficits than MUAC.

Extracellular Vesicles in Advanced Prostate Cancer: Tools to Predict and Thwart Therapeutic Resistance.

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death among men worldwide. At first, advanced PCa is treated by androgen deprivation therapy with a good initial response. Nevertheless, recurrences occur, leading to Castrate-Resistance Prostate Cancer (CRPC). During the last decade, new therapies based on inhibition of the androgen receptor pathway or taxane chemotherapies have been used to treat CRPC patients leading to an increase in overall survival, but the occurrence of resistances limits their benefits. Numerous studies have demonstrated the implication of extracellular vesicles (EVs) in different cancer cellular mechanisms. Thus, the possibility to isolate and explore EVs produced by tumor cells in plasma/sera represents an important opportunity for the deciphering of those mechanisms and the discovery of biomarkers. Herein, we summarized the role of EVs in therapeutic resistance of advanced prostate cancer and their use to find biomarkers able to predict these resistances.

Coverage of antenatal, intrapartum, and newborn care in 104 districts of Ethiopia: A before and after study four years after the launch of the national Community-Based Newborn Care programme.

BACKGROUND: Access to health services across the continuum of care improves maternal and newborn health outcomes. Ethiopia launched the Community-Based Newborn Care programme in 2013 to increase the coverage of antenatal care, institutional delivery, postnatal care and newborn care. The programme also introduced gentamicin and amoxicillin treatment by health extension workers for young infants with possible serious bacterial infection when referral was not possible. This study aimed to assess the extent to which the coverage of health services for mothers and their young infants increased after the initiation of the programme. METHODS: A baseline survey was conducted in October-December 2013 and a follow-up survey four years later in November-December 2017. At baseline, 10,224 households and 1,016 women who had a live birth in the 3-15 months prior to the survey were included. In the follow-up survey, 10,270 households and 1,057 women with a recent live birth were included. Women were asked about their experience of care during pregnancy, delivery and postpartum periods, as well as the treatment provided for their child's illness in the first 59 days of life. RESULTS: Between baseline and follow-up surveys the proportion of women reporting at least one antenatal care visit increased by 15 percentage points (95% CI: 10,19), four or more antenatal care visits increased by 17 percentage points (95%CI: 13,22), and institutional delivery increased by 40 percentage points (95% CI: 35,44). In contrast, the proportion of newborns with a postnatal care visit within 48 hours of birth decreased by 6 percentage points (95% CI: -10, -3) for home deliveries and by 14 percentage points (95% CI: -21, -7) for facility deliveries. The proportion of mothers reporting that their young infant with possible serious bacterial infection received amoxicillin for seven days increased by 50 percentage points (95% CI: 37,62) and gentamicin for seven days increased by 15 percentage points (95% CI: 5,25). Concurrent use of both antibiotics increased by 12 percentage points (95% CI: 4,19). CONCLUSION: The Community-Based Newborn Care programme was an ambitious initiative to enhance the access to services for pregnant women and newborns. Major improvements were seen for the number of antenatal care visits and institutional delivery, while postnatal care remained alarmingly low. Antibiotic treatment for young infants with possible serious bacterial infection increased, although most treatment did not follow national guidelines. Improving postnatal care coverage and using a simplified antibiotic regimen following recent World Health Organization guidelines could address gaps in the care provided for sick young infants.

Colistin Treatment Affects Lipid Composition of Acinetobacter baumannii.

Multidrug-resistant Acinetobacter baumannii (A. baumannii) causes severe and often fatal healthcare-associated infections due partly to antibiotic resistance. There are no studies on A. baumannii lipidomics of susceptible and resistant strains grown at lethal and sublethal concentrations. Therefore, we analyzed the impact of colistin resistance on glycerolipids' content by using untargeted lipidomics on clinical isolate. Nine lipid sub-classes were annotated, including phosphatidylcholine, rarely detected in the bacterial membrane among 130 different lipid species. The other lipid sub-classes detected are phosphatidylethanolamine (PE), phosphatidylglycerol (PG), lysophosphatidylethanolamine, hemibismonoacylglycerophosphate, cardiolipin, monolysocardiolipin, diacylglycerol, and triacylglycerol. Under lethal and sublethal concentrations of colistin, significant reduction of PE was observed on the resistant and susceptible strain, respectively. Palmitic acid percentage was higher at colistin at low concentration but only for the susceptible strain. When looking at individual lipid species, the most abundant PE and PG species (PE 34:1 and PG 34:1) are significantly upregulated when the susceptible and the resistant strains are cultivated with colistin. This is, to date, the most exhaustive lipidomics data compilation of A. baumannii cultivated in the presence of colistin. This work is highlighting the plasma membrane plasticity used by this gram-negative bacterium to survive colistin treatment.

Effect of nutrition-sensitive agriculture interventions with participatory videos and women's group meetings on maternal and child nutritional outcomes in rural Odisha, India (UPAVAN trial): a four-arm, observer-blind, cluster-randomised controlled trial.

BACKGROUND: Almost a quarter of the world's undernourished people live in India. We tested the effects of three nutrition-sensitive agriculture (NSA) interventions on maternal and child nutrition in India. METHODS: We did a parallel, four-arm, observer-blind, cluster-randomised trial in Keonjhar district, Odisha, India. A cluster was one or more villages with a combined minimum population of 800 residents. The clusters were allocated 1:1:1:1 to a control group or an intervention group of fortnightly women's groups meetings and household visits over 32 months using: NSA videos (AGRI group); NSA and nutrition-specific videos (AGRI-NUT group); or NSA videos and a nutrition-specific participatory learning and action (PLA) cycle meetings and videos (AGRI-NUT+PLA group). Primary outcomes were the proportion of children aged 6-23 months consuming at least four of seven food groups the previous day and mean maternal body-mass index (BMI). Secondary outcomes were proportion of mothers consuming at least five of ten food groups and child wasting (proportion of children with weight-for-height Z score SD <-2). Outcomes were assessed in children and mothers through cross-sectional surveys at baseline and at endline, 36 months later. Analyses were by intention to treat. Participants and intervention facilitators were not blinded to allocation; the research team were. This trial is registered at ISRCTN, ISRCTN65922679. FINDINGS: 148 of 162 clusters assessed for eligibility were enrolled and randomly allocated to trial groups (37 clusters per group). Baseline surveys took place from Nov 24, 2016, to Jan 24, 2017; clusters were randomised from December, 2016, to January, 2017; and interventions were implemented from March 20, 2017, to Oct 31, 2019, and endline surveys done from Nov 19, 2019, to Jan 12, 2020, in an average of 32 households per cluster. All clusters were included in the analyses. There was an increase in the proportion of children consuming at least four of seven food groups in the AGRI-NUT (adjusted relative risk [RR] 1·19, 95% CI 1·03 to 1·37, p=0·02) and AGRI-NUT+PLA (1·27, 1·11 to 1·46, p=0·001) groups, but not AGRI (1·06, 0·91 to 1·23, p=0·44), compared with the control group. We found no effects on mean maternal BMI (adjusted mean differences vs control, AGRI -0·05, -0·34 to 0·24; AGRI-NUT 0·04, -0·26 to 0·33; AGRI-NUT+PLA -0·03, -0·3 to 0·23). An increase in the proportion of mothers consuming at least five of ten food groups was seen in the AGRI (adjusted RR 1·21, 1·01 to 1·45) and AGRI-NUT+PLA (1·30, 1·10 to 1·53) groups compared with the control group, but not in AGRI-NUT (1·16, 0·98 to 1·38). We found no effects on child wasting (adjusted RR vs control, AGRI 0·95, 0·73 to 1·24; AGRI-NUT 0·96, 0·72 to 1·29; AGRI-NUT+PLA 0·96, 0·73 to 1·26). INTERPRETATION: Women's groups using combinations of NSA videos, nutrition-specific videos, and PLA cycle meetings improved maternal and child diet quality in rural Odisha, India. These components have been implemented separately in several low-income settings; effects could be increased by scaling up together. FUNDING: Bill & Melinda Gates Foundation, UK AID from the UK Government, and US Agency for International Development.

Agricultural and empowerment pathways from land ownership to women's nutrition in India.

Land size is an important equity concern for the design of 'nutrition-sensitive' agricultural interventions. We unpack some of the pathways between land and nutrition using a cross-sectional baseline survey data set of 4,480 women from 148 clusters from the 'Upscaling Participatory Action and Videos for Agriculture and Nutrition' trial in Keonjhar district in Odisha, India. Variables used are household ln-land size owned (exposure) and maternal dietary diversity score out of 10 food groups and body mass index (BMI; kg/m2 ) (outcomes); and mediators investigated are production diversity score, value of agricultural production, and indicators for women's empowerment (decision-making in agriculture, group participation, work-free time and land ownership). We assessed mediation using a non-parametric potential outcomes framework method. Land size positively affects maternal dietary diversity scores [ß 0.047; 95% confidence interval (CI) (0.011, 0.082)] but not BMI. Production diversity, but not value of production, accounts for 17.6% of total effect mediated. We observe suppression of the effect of land size on BMI, with no evidence of a direct effect for either of the agricultural mediators but indirect effects of ß -0.031 [95% CI (-0.048, -0.017)] through production diversity and ß -0.047 [95% CI (-0.075, -0.021)] through value of production. An increase in land size positively affects women's decision-making, which in turn negatively affects maternal BMI. The positive effect of work-free time on maternal BMI is suppressed by the negative effect of household land size on work-free time. Agriculture interventions must consider land quality, women's decision-making and implications for women's workload in their design.

Coverage and equity of maternal and newborn health care in rural Nigeria, Ethiopia and India.

BACKGROUND: Despite progress toward meeting the Sustainable Development Goals, a large burden of maternal and neonatal mortality persists for the most vulnerable people in rural areas. We assessed coverage, coverage change and inequity for 8 maternal and newborn health care indicators in parts of rural Nigeria, Ethiopia and India. METHODS: We examined coverage changes and inequity in 2012 and 2015 in 3 high-burden populations where multiple actors were attempting to improve outcomes. We conducted cluster-based household surveys using a structured questionnaire to collect 8 priority indicators, disaggregated by relative household socioeconomic status. Where there was evidence of a change in coverage between 2012 and 2015, we used binomial regression models to assess whether the change reduced inequity. RESULTS: In 2015, we interviewed women with a birth in the previous 12 months in Gombe, Nigeria (n = 1100 women), Ethiopia (n = 404) and Uttar Pradesh, India (n = 584). Among the 8 indicators, 2 positive coverage changes were observed in each of Gombe and Uttar Pradesh, and 5 in Ethiopia. Coverage improvements occurred equally for all socioeconomic groups, with little improvement in inequity. For example, in Ethiopia, coverage of facility delivery almost tripled, increasing from 15% (95% confidence interval [CI] 9%-25%) to 43% (95% CI 33%-54%). This change was similar across socioeconomic groups (p = 0.2). By 2015, the poorest women had about the same facility delivery coverage as the least poor women had had in 2012 (32% and 36%, respectively), but coverage for the least poor had increased to 60%. INTERPRETATION: Although coverage increased equitably because of various community-based interventions, underlying inequities persisted. Action is needed to address the needs of the most vulnerable women, particularly those living in the most rural areas.

Community-level epidemiology of soil-transmitted helminths in the context of school-based deworming: Baseline results of a cluster randomised trial on the coast of Kenya.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02397772.

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial.

BACKGROUND: School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. METHODS: In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2-14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. FINDINGS: After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9-23·2) to 13·8% (10·5-17·0) in the annual school-based treatment group, 17·9% (13·7-22·1) to 8·0% (6·0-10·1) in the annual community-wide treatment group, and 20·6% (15·8-25·5) to 6·2% (4·9-7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42-0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33-0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. INTERPRETATION: Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. FUNDING: Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children's Investment Fund Foundation.