Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite.

Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasite Plasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection. In addition, PfPK2 may also be involved in the maturation of the parasite post-invasion. PfPK2 regulates the release of microneme proteins like Apical Membrane Antigen 1 (AMA1), which facilitates the formation of Tight Junction between the merozoite and host erythrocyte- a key step in the process of invasion. Comparative phosphoproteomics studies revealed that PfPK2 may be involved in regulation of several key proteins involved in invasion and signalling. Furthermore, PfPK2 regulates the generation of cGMP and the release of calcium in the parasite, which are key second messengers for the process of invasion. These and other studies have shed light on a novel signalling pathway in which PfPK2 acts as an upstream regulator of important cGMP-calcium signalling, which plays an important role in parasite invasion.

A VPS15-like kinase regulates apicoplast biogenesis and autophagy by promoting PI3P generation in Toxoplasma gondii.

Phosphoinositides are important second messengers that regulate key cellular processes in eukaryotes. While it is known that a single phosphoinositol-3 kinase (PI3K) catalyses the formation of 3'-phosphorylated phosphoinositides (PIPs) in apicomplexan parasites like Plasmodium and Toxoplasma, how its activity and PI3P formation is regulated has remained unknown. Present studies involving a unique Vps15 like protein (TgVPS15) in Toxoplasma gondii provides insight into the regulation of phosphatidyl-3-phosphate (PI3P) generation and unravels a novel pathway that regulates parasite development. Detailed investigations suggested that TgVPS15 regulates PI3P formation in Toxoplasma gondii, which is important for the inheritance of the apicoplast-a plastid like organelle present in most apicomplexans and parasite replication. Interestingly, TgVPS15 also regulates autophagy in T. gondii under nutrient-limiting conditions as it promotes autophagosome formation. For both these processes, TgVPS15 uses PI3P-binding protein TgATG18 and regulates trafficking and conjugation of TgATG8 to the apicoplast and autophagosomes, which is important for biogenesis of these organelles. TgVPS15 has a protein kinase domain but lacks several key residues conserved in conventional protein kinases. Interestingly, two critical residues in its active site are important for PI3P formation and parasitic functions of this kinase. Collectively, these studies unravel a signalling cascade involving TgVPS15, a novel effector of PI3-kinase in T. gondii and possibly other Apicomplexa, that regulate critical processes like apicoplast biogenesis and autophagy.

Mapping child growth failure in Africa between 2000 and 2015.

Insufficient growth during childhood is associated with poor health outcomes and an increased risk of death. Between 2000 and 2015, nearly all African countries demonstrated improvements for children under 5 years old for stunting, wasting, and underweight, the core components of child growth failure. Here we show that striking subnational heterogeneity in levels and trends of child growth remains. If current rates of progress are sustained, many areas of Africa will meet the World Health Organization Global Targets 2025 to improve maternal, infant and young child nutrition, but high levels of growth failure will persist across the Sahel. At these rates, much, if not all of the continent will fail to meet the Sustainable Development Goal target-to end malnutrition by 2030. Geospatial estimates of child growth failure provide a baseline for measuring progress as well as a precision public health platform to target interventions to those populations with the greatest need, in order to reduce health disparities and accelerate progress.

Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii.

Apicomplexan parasites are causative agents of major human diseases. Calcium Dependent Protein Kinases (CDPKs) are crucial components for the intracellular development of apicomplexan parasites and are thus considered attractive drug targets. CDPK7 is an atypical member of this family, which initial characterization suggested to be critical for intracellular development of both Apicomplexa Plasmodium falciparum and Toxoplasma gondii. However, the mechanisms via which it regulates parasite replication have remained unknown. We performed quantitative phosphoproteomics of T. gondii lacking TgCDPK7 to identify its parasitic targets. Our analysis lead to the identification of several putative TgCDPK7 substrates implicated in critical processes like phospholipid (PL) synthesis and vesicular trafficking. Strikingly, phosphorylation of TgRab11a via TgCDPK7 was critical for parasite intracellular development and protein trafficking. Lipidomic analysis combined with biochemical and cellular studies confirmed that TgCDPK7 regulates phosphatidylethanolamine (PE) levels in T. gondii. These studies provide novel insights into the regulation of these processes that are critical for parasite development by TgCDPK7.

Magnetic Stress-Driven Metal-Insulator Transition in Strongly Correlated Antiferromagnetic CrN.

Traditionally, the Coulomb repulsion or Peierls instability causes the metal-insulator phase transitions in strongly correlated quantum materials. In comparison, magnetic stress is predicted to drive the metal-insulator transition in materials exhibiting strong spin-lattice coupling. However, this mechanism lacks experimental validation and an in-depth understanding. Here we demonstrate the existence of the magnetic stress-driven metal-insulator transition in an archetypal material, chromium nitride. Structural, magnetic, electronic transport characterization, and first-principles modeling analysis show that the phase transition temperature in CrN is directly proportional to the strain-controlled anisotropic magnetic stress. The compressive strain increases the magnetic stress, leading to the much-coveted room-temperature transition. In contrast, tensile strain and the inclusion of nonmagnetic cations weaken the magnetic stress and reduce the transition temperature. This discovery of a new physical origin of metal-insulator phase transition that unifies spin, charge, and lattice degrees of freedom in correlated materials marks a new paradigm and could lead to novel device functionalities.

The use of commercial wrist-worn technology to track physiological outcomes in behavioral interventions.

PURPOSE OF REVIEW: The aim of this review is to provide an overview of the use of commercial wrist-worn mobile health devices to track and monitor physiological outcomes in behavioral interventions as well as discuss considerations for selecting the optimal device. RECENT FINDINGS: Wearable technology can enhance intervention design and implementation. The use of wrist-worn wearables provides the opportunity for tracking physiological outcomes, thus providing a unique approach for assessment and delivery of remote interventions. Recent findings support the utility, acceptability, and benefits of commercial wrist-worn wearables in interventions, and they can be used to continuously monitor outcomes, remotely administer assessments, track adherence, and personalize interventions. Wrist-worn devices show acceptable accuracy when measuring heart rate, blood pressure, step counts, and physical activity; however, accuracy is dependent on activity type, intensity, and device brand. These factors should be considered when designing behavioral interventions that utilize wearable technology. SUMMARY: With the continuous advancement in technology and frequent product upgrades, the capabilities of commercial wrist-worn devices will continue to expand, thus increasing their potential use in intervention research. Continued research is needed to examine and validate the most recent devices on the market to better inform intervention design and implementation.

Making programmes worth their salt: Assessing the context, fidelity and outcomes of implementation of the double fortified salt programme in Uttar Pradesh, India.

Double fortified salt (DFS) has proven efficacy in addressing iron deficiency and anaemia, thus improving maternal and child nutrition outcomes. However, DFS delivery in large-scale settings is less understood, with limited documentation of its fidelity of implementation (FOI). We assessed the FOI of the DFS intervention in Uttar Pradesh, India, to improve the design and implementation of such programmes that aim to reduce the anaemia burden, especially in women of reproductive age (WRA). We conducted in-depth interviews with DFS programme staff (n = 25) and end-user WRAs (23), guided by a programme impact pathway. We transcribed and thematically analysed the interviews and used an adapted analytic framework to document FOI across four domains-objects of intervention, implementation staff, implementation context and target of implementation. DFS utilisation remained low due to a combination of factors including poor product quality, distribution challenges, ineffective promotion and low awareness amongst end-user WRAs. Motivation levels were higher amongst district-level staff compared to frontline staff, who lacked supervisory support and effective incentives to promote DFS. Three typologies of DFS users emerged-'believers', 'thrifters' and 'naysayers'-who indicated differing reasons for DFS purchase and its use or nonuse. The implementation of the DFS programme varied significantly from its theorised programme impact pathway. The adapted analytic framework helped document FOI and assess the programme's readiness for impact assessments and subsequent scale-up. The programme needs product quality improvements, incentivised distribution and stronger promotion to effectively deliver and improve the realisation of its potential as an anaemia prevention strategy.

Impact on child acute malnutrition of integrating a preventive nutrition package into facility-based screening for acute malnutrition during well-baby consultation: A cluster-randomized controlled trial in Burkina Faso.

BACKGROUND: Community management of acute malnutrition (CMAM) is a highly efficacious approach for treating acute malnutrition (AM) in children who would otherwise be at significantly increased risk of mortality. In program settings, however, CMAM's effectiveness is limited because of low screening coverage of AM, in part because of the lack of perceived benefits for caregivers. In Burkina Faso, monthly screening for AM of children <2 years of age is conducted during well-baby consultations (consultation du nourrisson sain [CNS]) at health centers. We hypothesized that the integration of a preventive package including age-appropriate behavior change communication (BCC) on nutrition, health, and hygiene practices and a monthly supply of small-quantity lipid-based nutrient supplements (SQ-LNSs) to the monthly screening would increase AM screening and treatment coverage and decrease the incidence and prevalence of AM. METHODS AND FINDINGS: We used a cluster-randomized controlled trial and allocated 16 health centers to the intervention group and 16 to a comparison group. Both groups had access to standard CMAM and CNS services; caregivers in the intervention group also received age-appropriate monthly BCC and SQ-LNS for children >6 months of age. We used two study designs: (1) a repeated cross-sectional study of children 0-17 months old (n = 2,318 and 2,317 at baseline and endline 2 years later) to assess impacts on AM screening coverage, treatment coverage, and prevalence; (2) a longitudinal study of 2,113 children enrolled soon after birth and followed up monthly for 18 months to assess impacts on AM screening coverage, treatment coverage, and incidence. Data were analyzed as intent to treat. Level of significance for primary outcomes was α = 0.016 after adjustment for multiple testing. Children's average age was 8.8 ± 4.9 months in the intervention group and 8.9 ± 5.0 months in the comparison group at baseline and, respectively, 0.66 ± 0.32 and 0.67 ± 0.33 months at enrollment in the longitudinal study. Relative to the comparison group, the intervention group had significantly higher monthly AM screening coverage (cross-sectional study: +18 percentage points [pp], 95% CI 10-26, P < 0.001; longitudinal study: +23 pp, 95% CI 17-29, P < 0.001). There were no impacts on either AM treatment coverage (cross-sectional study: +8.0 pp, 95% CI 0.09-16, P = 0.047; longitudinal study: +7.7 pp, 95% CI -1.2 to 17, P = 0.090), AM incidence (longitudinal study: incidence rate ratio = 0.98, 95% CI 0.75-1.3, P = 0.88), or AM prevalence (cross-sectional study: -0.46 pp, 95% CI -4.4 to 3.5, P = 0.82). A study limitation is the referral of AM cases (for ethical reasons) by study enumerators as part of the monthly measurement in the longitudinal study that may have attenuated the detectable impact on AM treatment coverage. CONCLUSIONS: Adding a preventive package to CMAM delivered at health facilities in Burkina Faso increased participation in monthly AM screening, thus overcoming a major impediment to CMAM effectiveness. The lack of impact on AM treatment coverage and on AM prevalence and incidence calls for research to address the remaining barriers to uptake of preventive and treatment services at the health center and to identify and test complementary approaches to bring integrated preventive and CMAM services closer to the community while ensuring high-quality implementation and service delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02245152.

Impact on child acute malnutrition of integrating small-quantity lipid-based nutrient supplements into community-level screening for acute malnutrition: A cluster-randomized controlled trial in Mali.

BACKGROUND: Community-based management of acute malnutrition (CMAM) has been widely adopted to treat childhood acute malnutrition (AM), but its effectiveness in program settings is often limited by implementation constraints, low screening coverage, and poor treatment uptake and adherence. This study addresses the problem of low screening coverage by testing the impact of distributing small-quantity lipid-based nutrient supplements (SQ-LNSs) at monthly screenings held by community health volunteers (CHVs). Screening sessions included behavior change communication (BCC) on nutrition, health, and hygiene practices (both study arms) and SQ-LNSs (one study arm). Impact was assessed on AM screening and treatment coverage and on AM incidence and prevalence. METHODS AND FINDINGS: A two-arm cluster-randomized controlled trial in 48 health center catchment areas in the Bla and San health districts in Mali was conducted from February 2015 to April 2017. In both arms, CHVs led monthly AM screenings in children 6-23 months of age and provided BCC to caregivers. The intervention arm also received a monthly supply of SQ-LNSs to stimulate caregivers' participation and supplement children's diet. We used two study designs: i) a repeated cross-sectional study (n = approximately 2,300) with baseline and endline surveys to examine impacts on AM screening and treatment coverage and prevalence (primary study outcomes) and ii) a longitudinal study of children enrolled at 6 months of age (n = 1,132) and followed monthly for 18 months to assess impact on AM screening and treatment coverage and incidence (primary study outcomes). All analyses were done by intent to treat. The intervention significantly increased AM screening coverage (cross-sectional study: +40 percentage points [pp], 95% confidence interval [CI]: 32, 49, p < 0.001; longitudinal study: +28 pp, 95% CI: 23, 33, p < 0.001). No impact on treatment coverage or AM prevalence was found. Children in the intervention arm, however, were 29% (95% CI: 8, 46; p = 0.017) less likely to develop a first AM episode (incidence) and, compared to children in comparison arm, their overall risk of AM (longitudinal prevalence) was 30% (95% CI: 12, 44; p = 0.002) lower. The intervention lowered CMAM enrollment by 10 pp (95% CI: 1.9, 18; p = 0.016), an unintended negative impact likely due to CHVs handing out preventive SQ-LNSs to caregivers of AM children instead of referring them to the CMAM program. Study limitations were i) the referral of AM cases by our research team (for ethical reasons) during monthly measurements in the longitudinal study might have interfered with usual CMAM activities and ii) the outcomes presented by child age also reflect seasonal variations because of the closed cohort design. CONCLUSIONS: Incorporating SQ-LNSs into monthly community-level AM screenings and BCC sessions was highly effective at improving screening coverage and reducing AM incidence, but it did not improve AM prevalence or treatment coverage. Future evaluation and implementation research on CMAM should carefully assess and tackle the remaining barriers that prevent AM cases from being correctly diagnosed, referred, and adequately treated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02323815.

Changes in Underlying Determinants Explain Rapid Increases in Child Linear Growth in Alive & Thrive Study Areas between 2010 and 2014 in Bangladesh and Vietnam.

Background: Child linear growth sometimes improves in both intervention and comparison groups in evaluations of nutrition interventions, possibly because of spillover intervention effects to nonintervention areas or improvements in underlying determinants of nutritional change in both areas.Objective: We aimed to understand what changes in underlying socioeconomic characteristics and behavioral factors are important in explaining improvements in child linear growth.Methods: Baseline (2010) and endline (2014) surveys from the Alive & Thrive impact evaluation were used to identify the underlying determinants of height-for-age z scores (HAZs) among children aged 24-48 mo in Bangladesh (n = 4311) and 24-59 mo in Vietnam (n = 4002). Oaxaca-Blinder regression decompositions were used to examine which underlying determinants contributed to HAZ changes over time.Results: HAZs improved significantly between 2010 and 2014 in Bangladesh (∼0.18 SDs) and Vietnam (0.25 SDs). Underlying determinants improved substantially over time and were larger in Vietnam than in Bangladesh. Multiple regression models revealed significant associations between changes in HAZs and socioeconomic status (SES), food security, maternal education, hygiene, and birth weight in both countries. Changes in HAZs were significantly associated with maternal nutrition knowledge and child dietary diversity in Bangladesh, and with prenatal visits in Vietnam. Improvements in maternal nutrition knowledge in Bangladesh accounted for 20% of the total HAZ change, followed by maternal education (13%), SES (12%), hygiene (10%), and food security (9%). HAZ improvements in Vietnam were accounted for by changes in SES (26%), prenatal visits (25%), hygiene (19%), child birth weight (10%), and maternal education (7%). The decomposition models in both countries performed well, explaining >75% of the HAZ changes.Conclusions: Decomposition is a useful and simple technique for analyzing nonintervention drivers of nutritional change in intervention and comparison areas. Improvements in underlying determinants explained rapid improvements in HAZs between 2010 and 2014 in Bangladesh and Vietnam.

Large-Scale Behavior-Change Initiative for Infant and Young Child Feeding Advanced Language and Motor Development in a Cluster-Randomized Program Evaluation in Bangladesh.

BACKGROUND: Promoting adequate nutrition through interventions to improve infant and young child feeding (IYCF) has the potential to contribute to child development. OBJECTIVE: We examined whether an intensive intervention package that was aimed at improving IYCF at scale through the Alive & Thrive initiative in Bangladesh also advanced language and gross motor development, and whether advancements in language and gross motor development were explained through improved complementary feeding. METHODS: A cluster-randomized design compared 2 intervention packages: intensive interpersonal counseling on IYCF, mass media campaign, and community mobilization (intensive) compared with usual nutrition counseling and mass media campaign (nonintensive). Twenty subdistricts were randomly assigned to receive either the intensive or the nonintensive intervention. Household surveys were conducted at baseline (2010) and at endline (2014) in the same communities (n = ∼4000 children aged 0-47.9 mo for each round). Child development was measured by asking mothers if their child had reached each of multiple milestones, with some observed. Linear regression accounting for clustering was used to derive difference-in-differences (DID) impact estimates, and path analysis was used to examine developmental advancement through indicators of improved IYCF and other factors. RESULTS: The DID in language development between intensive and nonintensive groups was 1.05 milestones (P = 0.001) among children aged 6-23.9 mo and 0.76 milestones (P = 0.038) among children aged 24-47.9 mo. For gross motor development, the DID was 0.85 milestones (P = 0.035) among children aged 6-23.9 mo. The differences observed corresponded to age- and sex-adjusted effect sizes of 0.35 for language and 0.23 for gross motor development. Developmental advancement at 6-23.9 mo was partially explained through improved minimum dietary diversity and the consumption of iron-rich food. CONCLUSIONS: Intensive IYCF intervention differentially advanced language and gross motor development, which was partially explained through improved complementary feeding. Measuring a diverse set of child outcomes, including functional outcomes such as child development, is important when evaluating integrated nutrition programs. This trial was registered at clinicaltrials.gov as NCT01678716.

Social Franchising and a Nationwide Mass Media Campaign Increased the Prevalence of Adequate Complementary Feeding in Vietnam: A Cluster-Randomized Program Evaluation.

Background: Rigorous evaluations of health system-based interventions in large-scale programs to improve complementary feeding (CF) practices are limited. Alive & Thrive applied principles of social franchising within the government health system in Vietnam to improve the quality of interpersonal counseling (IPC) for infant and young child feeding combined with a national mass media (MM) campaign and community mobilization (CM).Objective: We evaluated the impact of enhanced IPC + MM + CM (intensive) compared with standard IPC + less-intensive MM and CM (nonintensive) on CF practices and anthropometric indicators.Methods: A cluster-randomized, nonblinded evaluation design with cross-sectional surveys (n = ∼500 children aged 6-23.9 mo and ∼1000 children aged 24-59.9 mo/group) implemented at baseline (2010) and endline (2014) was used. Difference-in-difference estimates (DDEs) of impact were calculated for intent-to-treat (ITT) analyses and modified per-protocol analyses (MPAs; mothers who attended the social franchising at least once: 62%).Results: Groups were similar at baseline. In ITT analyses, there were no significant differences between groups in changes in CF practices over time. In the MPAs, greater improvements in the intensive than in the nonintensive group were seen for minimum dietary diversity [DDE: 6.4 percentage points (pps); P < 0.05] and minimum acceptable diet (8.0 pps; P < 0.05). Significant stunting declines occurred in both intensive (7.1 pps) and nonintensive (5.4 pps) groups among children aged 24-59.9 mo, with no differential decline.Conclusions: When combined with MM and CM, an at-scale social franchising approach to improve IPC, delivered through the existing health care system, significantly improved CF practices, but not child growth, among mothers who used counseling services at least once. A greater impact may be achieved with strategies designed to increase service utilization. This trial was registered at clinicaltrials.gov as NCT01676623.

Assessing the Impact of Food Assistance on Stigma Among People Living with HIV in Uganda Using the HIV/AIDS Stigma Instrument-PLWA (HASI-P).

HIV-related stigma among persons living with HIV/AIDS (PLHIV) is prevalent throughout sub-Saharan Africa. There is limited evidence, however, on which interventions are effective in reducing it. We used data from a prospective impact evaluation of a 12-month food assistance intervention among 904 antiretroviral therapy (ART)- naïve PLHIV in Uganda to examine the program impact on stigma. Stigma was measured using the comprehensive HASI-P scale, which demonstrated good internal consistency (Cronbach's alpha = 0.87) and was correlated with several related constructs including physical and mental health-related quality of life, disclosure, and physical health symptoms in the sample. Using quasi-experimental difference-in-difference matching methods to better infer causality, we tested whether the intervention improved the overall stigma scale and its subscales. The food assistance intervention had a significant effect on reported internalized (but not external) stigma of approximately 0.2 SD (p < 0.01). The HASI-P stigma scale is a useful tool for measuring and tracking stigma. Food assistance interventions, embedded in an HIV care program, can reduce internalized stigma.

The impact of integrated prevention and treatment on child malnutrition and health: the PROMIS project, a randomized control trial in Burkina Faso and Mali.

BACKGROUND: Evidence suggests that both preventive and curative nutrition interventions are needed to tackle child acute malnutrition (AM) in developing countries. In addition to reducing the incidence of AM, providing preventive interventions may also help increase attendance (and coverage) of AM screening, a major constraint in the community-based management of child acute malnutrition (CMAM) model. There is a paucity of evidence-based strategies to deliver integrated preventive and curative interventions effectively and affordably at scale. The aim of the Innovative Approaches for the Prevention of Childhood Malnutrition (PROMIS) study is to assess the feasibility, quality of implementation, effectiveness and cost-effectiveness of an integrated child malnutrition prevention and treatment intervention package implemented through a community-based platform in Mali and a facility-based platform in Burkina Faso. METHODS/DESIGN: The PROMIS intervention entails a comprehensive preventive package offered on a monthly basis to caregivers of children, while children are screened for acute malnutrition (AM). The package consists of behavior change communication on essential nutrition and hygiene actions, and monthly preventive doses of small quantity lipid-based nutrient supplements (SQ-LNS) for children aged 6 to 23.9 months. Positive AM cases are referred to treatment services offered by first-line health services according to the CMAM model. The PROMIS intervention will be evaluated using a mixed methods approach. The impact study encompasses two types of study design: i) repeated cross-sectional surveys conducted at baseline and at endline after 24 months of program implementation and ii) a longitudinal study with a monthly follow-up for 18 months. Primary study impact measures include the incidence and endpoint prevalence of AM, AM screening coverage and treatment compliance. A process evaluation will assess the feasibility and quality of implementation of the intervention guided by country specific program impact pathways (PIPs). Cost-effectiveness analysis will assess the economic feasibility of the intervention. DISCUSSION: The PROMIS study assesses the effectiveness of an innovative model to integrate prevention and treatment interventions for greater and more sustainable impacts on the incidence and prevalence of AM using a rigorous, theory-based randomized control trial approach. This type of programmatic research is urgently needed to help program implementers, policy makers, and investors prioritize, select and scale-up the best program models to prevent and treat AM and achieve the World Health Assembly goal of reducing childhood wasting to less than 5% globally by the year 2025. TRIAL REGISTRATION: Clinicaltrials.gov NCT02323815 (registered on December 18, 2014) and NCT02245152 (registered on September 16, 2014).

Executive summary for the Micronutrient Powders Consultation: Lessons Learned for Operational Guidance.

Iron deficiency anaemia is estimated to be the leading cause of years lived with disability among children. Young children's diets are often inadequate in iron and other micronutrients, and provision of essential vitamin and minerals has long been recommended. With the limited programmatic success of iron drop/syrup interventions, interest in micronutrient powders (MNP) has increased. MNP are a mixture of vitamins and minerals, enclosed in single-dose sachets, which are stirred into a child's portion of food immediately before consumption. MNP are an efficacious intervention for reducing iron deficiency anaemia and filling important nutrient gaps in children 6-23 months of age. As of 2014, 50 countries have implemented MNP programmes including 9 at a national level. This paper provides an overview of a 3-paper series, based on findings from the "Micronutrient Powders Consultation: Lessons Learned for Operational Guidance" held by the USAID-funded Strengthening Partnerships, Results, and Innovations in Nutrition Globally (SPRING) Project. The objectives of the Consultation were to identify and summarize the most recent MNP programme experiences and lessons learned for operationalizing MNP for young children and prioritize an implementation research agenda. The Consultation was composed of 3 working groups that used the following methods: deliberations among 49 MNP programme implementers and experts, a review of published and grey literature, questionnaires, and key informant interviews, described in this overview. The following articles summarize findings in 3 broad programme areas: planning, implementation, and continual programme improvement. The papers also outline priorities for implementation research to inform improved operationalization of MNP.

Experiences and lessons learned for delivery of micronutrient powders interventions.

An effective delivery strategy coupled with relevant social and behaviour change communication (SBCC) have been identified as central to the implementation of micronutrient powders (MNP) interventions, but there has been limited documentation of what works. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," three working groups were formed to summarize experiences and lessons across countries regarding MNP interventions for young children. This paper focuses on programmatic experiences related to MNP delivery (models, platforms, and channels), SBCC, and training. Methods included a review of published and grey literature, interviews with key informants, and deliberations throughout the consultation process. We found that most countries distributed MNP free of charge via the health sector, although distribution through other platforms and using subsidized fee for product or mixed payment models have also been used. Community-based distribution channels have generally shown higher coverage and when part of an infant and young child feeding approach, may provide additional benefit given their complementarity. SBCC for MNP has worked best when focused on meeting the MNP behavioural objectives (appropriate use, intake adherence, and related infant and young child feeding behaviours). Programmers have learned that reincorporating SBCC and training throughout the intervention life cycle has allowed for much needed adaptations. Diverse experiences delivering MNP exist, and although no one-size-fits-all approach emerged, well-established delivery platforms, community involvement, and SBCC-centred designs tended to have more success. Much still needs to be learned on MNP delivery, and we propose a set of implementation research questions that require further investigation.

Impacts on Breastfeeding Practices of At-Scale Strategies That Combine Intensive Interpersonal Counseling, Mass Media, and Community Mobilization: Results of Cluster-Randomized Program Evaluations in Bangladesh and Viet Nam.

BACKGROUND: Despite recommendations supporting optimal breastfeeding, the number of women practicing exclusive breastfeeding (EBF) remains low, and few interventions have demonstrated implementation and impact at scale. Alive & Thrive was implemented over a period of 6 y (2009-2014) and aimed to improve breastfeeding practices through intensified interpersonal counseling (IPC), mass media (MM), and community mobilization (CM) intervention components delivered at scale in the context of policy advocacy (PA) in Bangladesh and Viet Nam. In Bangladesh, IPC was delivered through a large non-governmental health program; in Viet Nam, it was integrated into government health facilities. This study evaluated the population-level impact of intensified IPC, MM, CM, and PA (intensive) compared to standard nutrition counseling and less intensive MM, CM, and PA (non-intensive) on breastfeeding practices in these two countries. METHODS AND FINDINGS: A cluster-randomized evaluation design was employed in each country. For the evaluation sample, 20 sub-districts in Bangladesh and 40 communes in Viet Nam were randomized to either the intensive or the non-intensive group. Cross-sectional surveys (n ~ 500 children 0-5.9 mo old per group per country) were implemented at baseline (June 7-August 29, 2010, in Viet Nam; April 28-June 26, 2010, in Bangladesh) and endline (June 16-August 30, 2014, in Viet Nam; April 20-June 23, 2014, in Bangladesh). Difference-in-differences estimates (DDEs) of impact were calculated, adjusting for clustering. In Bangladesh, improvements were significantly greater in the intensive compared to the non-intensive group for the proportion of women who reported practicing EBF in the previous 24 h (DDE 36.2 percentage points [pp], 95% CI 21.0-51.5, p < 0.001; prevalence in intensive group rose from 48.5% to 87.6%) and engaging in early initiation of breastfeeding (EIBF) (16.7 pp, 95% CI 2.8-30.6, p = 0.021; 63.7% to 94.2%). In Viet Nam, EBF increases were greater in the intensive group (27.9 pp, 95% CI 17.7-38.1, p < 0.001; 18.9% to 57.8%); EIBF declined (60.0% to 53.2%) in the intensive group, but less than in the non-intensive group (57.4% to 40.6%; DDE 10.0 pp, 95% CI -1.3 to 21.4, p = 0.072). Our impact estimates may underestimate the full potential of such a multipronged intervention because the evaluation lacked a "pure control" area with no MM or national/provincial PA. CONCLUSIONS: At-scale interventions combining intensive IPC with MM, CM, and PA had greater positive impacts on breastfeeding practices in Bangladesh and Viet Nam than standard counseling with less intensive MM, CM, and PA. To our knowledge, this study is the first to document implementation and impacts of breastfeeding promotion at scale using rigorous evaluation designs. Strategies to design and deliver similar programs could improve breastfeeding practices in other contexts. TRIAL REGISTRATION: ClinicalTrials.gov NCT01678716 (Bangladesh) and NCT01676623 (Viet Nam).

Combining Intensive Counseling by Frontline Workers with a Nationwide Mass Media Campaign Has Large Differential Impacts on Complementary Feeding Practices but Not on Child Growth: Results of a Cluster-Randomized Program Evaluation in Bangladesh.

BACKGROUND: Complementary feeding (CF) contributes to child growth and development, but few CF programs are delivered at scale. Alive & Thrive addressed this in Bangladesh through intensified interpersonal counseling (IPC), mass media (MM), and community mobilization (CM). OBJECTIVE: The objective was to evaluate the impact of providing IPC + MM + CM (intensive) compared with standard nutrition counseling + less intensive MM + CM (nonintensive) on CF practices and anthropometric measurements. METHODS: We used a cluster-randomized, nonblinded evaluation with cross-sectional surveys [n = ∼600 and 1090 children 6-23.9 mo and 24-47.9 mo/group, respectively, at baseline (2010) and n = ∼500 and 1100 children of the same age, respectively, at endline (2014)]. We derived difference-in-difference impact estimates (DDEs), adjusting for geographic clustering, infant age, sex, differences in baseline characteristics, and differential change in characteristics over time. RESULTS: Groups were similar at baseline. CF improvements were significantly greater in the intensive than in the nonintensive group [DDEs: 16.3, 14.7, 22.0, and 24.6 percentage points (pp) for minimum dietary diversity, minimum meal frequency, minimum acceptable diet, and consumption of iron-rich foods, respectively]. In the intensive group, CF practices were high: 50.4% for minimum acceptable diet, 63.8% for minimum diet diversity, 75.1% for minimum meal frequency, and 78.5% for consumption of iron-rich foods. Timely introduction of foods improved. Significant, nondifferential stunting declines occurred in intensive (6.2 pp) and nonintensive (5.2 pp) groups in children 24-47.9 mo. CONCLUSIONS: The intensive program substantially improved CF practices compared with the nonintensive program. Large-scale program delivery was feasible and, with the use of multiple platforms, reached 1.7 million households. Nondifferential impacts on stunting were likely due to rapid positive secular trends in Bangladesh. Accelerating linear growth further could require accompanying interventions. This study establishes proof of concept for large-scale behavior change interventions to improve child feeding. This trial was registered at clinicaltrials.gov as NCT01678716.

Exposure to mass media and interpersonal counseling has additive effects on exclusive breastfeeding and its psychosocial determinants among Vietnamese mothers.

The pathways through which behavior change interventions impact breastfeeding practices have not been well studied. This study aimed to examine: (1) the effects of exposure to mass media and interpersonal counseling on exclusive breastfeeding (EBF) and hypothesized psychosocial determinants (i.e. knowledge, intention, beliefs, social norms, and self-efficacy); and (2) the pathways through which exposure to mass media and interpersonal counseling are associated with EBF. We used survey data from mothers with children < 2 year (n = 2045) from the 2013 process evaluation of Alive & Thrive's program in Viet Nam. Multiple linear regression analyses and structural equation modeling were used to estimate effects. Exposure to mass media only, interpersonal counseling only, both or neither was 51%, 5%, 19% and 25%, respectively. Exposure to both mass media and interpersonal counseling had additive effects on EBF as well as on related psychosocial factors, compared with no exposure. For example, EBF prevalence was 26.1 percentage points (pp) higher in the group that received interpersonal counseling only, 3.9 pp higher in the mass media group and 31.8 pp higher in the group that received both interventions. As hypothesized, more than 90% of the total effect of the two interventions on EBF was explained by the psychosocial factors measured. Our findings suggest that combining different behavior change interventions leads to greater changes in psychosocial factors, which in turn positively affects breastfeeding behaviors.

Assessing implementation fidelity of a community-based infant and young child feeding intervention in Ethiopia identifies delivery challenges that limit reach to communities: a mixed-method process evaluation study.

BACKGROUND: Program effectiveness is influenced by the degree and quality of implementation, thus requiring careful examination of delivery processes and how the program is or is not being implemented as intended. Implementation fidelity is defined by adherence to intervention design, exposure or dose, quality of delivery, and participant responsiveness. As part of the process evaluation (PE) of Alive & Thrive in Ethiopia, a large-scale initiative to improve infant and young child feeding (IYCF), we assessed these four fidelity elements along three components of its community-based intervention: training of frontline workers (FLWs), delivery of program tools and messages, and supportive supervision. METHODS: Data from a qualitative study among three levels of FLWs (n = 54), i.e. supervisors, health extension workers (HEWs), and community volunteers, and among mothers with children under two years of age (n = 60); and cross-sectional PE surveys with FLWs (n = 504) and mothers (n = 750) in two regions (Tigray and SNNPR) were analyzed to examine program fidelity. RESULTS: There was strong adherence to the intended cascading design (i.e. transfer of knowledge and information from higher to lower FLW levels) and high exposure to training (95% HEWs and 94% volunteers in Tigray, 68% and 81% respectively in SNNPR). Training quality, assessed by IYCF knowledge and self-reported capacity, was high and increased since baseline. Job aids were used regularly by most supervisors and HEWs, but only 54% of volunteers in Tigray and 39% in SNNPR received them. Quality of program message delivery was lower among volunteers, and aided recall of key messages among mothers was also low. Although FLW supervision exposure was high, content and frequency were irregular. CONCLUSIONS: There is evidence of strong fidelity in training and delivery of program tools and messages at higher FLW levels, but gaps in the reach of these to community volunteers and mothers and variability between regions could limit the potential for impact. Strengthening the linkages between HEWs and volunteers further can help to reach the target households and deliver IYCF results at scale.