Metabolic Rewiring of Mycobacterium tuberculosis upon Drug Treatment and Antibiotics Resistance.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, further compounded by the issue of antimicrobial resistance (AMR). AMR is a result of several system-level molecular rearrangements enabling bacteria to evolve with better survival capacities: metabolic rewiring is one of them. In this review, we present a detailed analysis of the metabolic rewiring of Mtb in response to anti-TB drugs and elucidate the dynamic mechanisms of bacterial metabolism contributing to drug efficacy and resistance. We have discussed the current state of AMR, its role in the prevalence of the disease, and the limitations of current anti-TB drug regimens. Further, the concept of metabolic rewiring is defined, underscoring its relevance in understanding drug resistance and the biotransformation of drugs by Mtb. The review proceeds to discuss the metabolic adaptations of Mtb to drug treatment, and the pleiotropic effects of anti-TB drugs on Mtb metabolism. Next, the association between metabolic changes and antimycobacterial resistance, including intrinsic and acquired drug resistance, is discussed. The review concludes by summarizing the challenges of anti-TB treatment from a metabolic viewpoint, justifying the need for this discussion in the context of novel drug discovery, repositioning, and repurposing to control AMR in TB.

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.

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.

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.

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.

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.

Challenges for Estimating the Global Prevalence of Micronutrient Deficiencies and Related Disease Burden: A Case Study of the Global Burden of Disease Study.

Information on the prevalence of micronutrient deficiencies is needed to determine related disease burden; underpin evidence-based advocacy; and design, deliver, and monitor safe, effective interventions. Assessing the global prevalence of deficiency requires a valid micronutrient status biomarker with an appropriate cutoff to define deficiency and relevant data from representative surveys across multiple locations and years. The Global Burden of Disease Study includes prevalence estimates for iodine, iron, zinc, and vitamin A deficiencies, for which recommended biomarkers and appropriate deficiency cutoffs exist. Because representative survey data are lacking, only retinol concentration is used to model vitamin A deficiency, and proxy indicators are used for the other micronutrients (goiter for iodine, hemoglobin for iron, and dietary food adequacy for zinc). Because of data limitations, complex statistical modeling is required to produce current estimates, relying on assumptions and proxies that likely understate the extent of micronutrient deficiencies and the consequent global health burden.

Nutrition data use and needs: Findings from an online survey of global nutrition stakeholders.

BACKGROUND: There is growing global demand for country-specific information to track nutritional status and its determinants, including intervention coverage. Periodic population-based surveys form the backbone of most national nutrition information systems. However, data on the coverage of many nutrition specific and sensitive interventions remain sparse. METHODS: An online survey was administered to the international nutrition community in 2018 through relevant listservs and professional networks to characterize their use of nutrition-related indicators and data sources. Respondents were asked about their professional background, access and use of specific indicators and data sources in the previous year, and unmet data needs. Results were tabulated by respondent characteristics and χ2 tests used for statistical testing. RESULTS: Complete survey responses were received from 235 respondents, the majority from non-governmental organizations and research communities, and few from governments. Demographic Health Surveys (DHS) were the most frequently accessed country-specific data source and the Global Nutrition Report (GNR) was the most accessed consolidated data source, each accessed by approximately 75% of respondents. Respondents with a multi-country focus were more likely to have accessed DHS than those with a single-country focus (85% vs 60%, P < 0.001). Similarly, respondents with a multi-country focus were more likely to have accessed the GNR compared to those with a single-country focus (82% vs 66%, P < 0.05). The most commonly accessed indicators overall were the prevalence of exclusive breastfeeding (69%), child minimum dietary diversity (66%), under-5 stunting (65%), and under-5 wasting (65%). Reported data gaps included adult and household diet quality indicators (n = 32), nutrition-sensitive intervention coverage (n = 25), and infant and young child feeding promotion coverage (n = 11). Lack of data availability for the desired geographic level (82%) or demographic group of interest (82%) and out-of-date data (77%) were common data challenges experienced by respondents. CONCLUSIONS: The survey results highlight the continued need for high-quality, actionable nutrition data to help facilitate progress towards national and global nutrition targets.

Building Implementation Science in Nutrition.

The field of nutrition has been investing in the development of many nutrition-specific and -sensitive policies and programs aimed at improving population-level malnutrition in all its forms. When there is a need to learn about a new system, programmatic context, or target population to understand how to effectively deploy an intervention to help improve nutrition, it is important to be able to ask a broad range of questions, both in topic and in scope. Our aim is to provide a simple and conceptually clear definition and principles to elaborate the science of implementation for nutrition to distinguish it from other ways of knowing and learning and to serve as a guide to the articulation of implementation science questions and methods. Implementation science is a body of systematized knowledge about how to improve implementation that 1) is distinguished by its aims to learn about the process of implementation, 2) uses methods that derive from and fit with the aims, and 3) is built with tacit (as well as expert) knowledge and experiential learning. Implementation science aims to generate the learning needed to improve implementation through facilitating collaboration among stakeholders to articulate and pursue the aims; capturing and using tacit knowledge and experiential learning from stakeholders, systems, providers, and recipients; and applying a mix of methods suited to the aims. This elaboration of the science provides a simple way to help those who already do, or want to do, implementation science understand and communicate how this science is unique and the value that it adds to the current landscape of nutrition priorities, innovations, and the attendant complex learning needs that follow. Implementation science encompasses both discovery- and mission-oriented research, and centers implementation as the object of study for the purposes of broad-based learning.

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.

Publisher Correction: Mapping exclusive breastfeeding in Africa between 2000 and 2017.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Measuring the coverage of nutrition interventions along the continuum of care: time to act at scale.

The global community is committed to addressing malnutrition. And yet, coverage data for high-impact interventions along the continuum of care remain scarce due to several measurement and data collection challenges. In this analysis paper, we identify 24 nutrition interventions that should be tracked by all countries, and determine if their coverage is currently measured by major household nutrition and health surveys. We then present three case studies, using published literature and empirical data from large-scale initiatives, to illustrate the kind of data collection innovations that are feasible. We find that data are not routinely collected in a standardised way across countries for most of the core set of interventions. Case studies-of growth monitoring and screening for acute malnutrition, infant and young child feeding counselling, and nutrition monitoring in India-highlight both challenges and potential solutions. Advancing the nutrition intervention coverage measurement agenda is essential for sustained progress in driving down rates of malnutrition. It will require (1) global consensus on a core set of validated coverage indicators on proven, high-impact nutrition-specific interventions; (2) the inclusion of coverage measurement and indicator guidance in WHO intervention recommendations; (3) the incorporation of these indicators into data collection mechanisms and relevant intervention delivery platforms; and (4) an agenda for continuous measurement improvement.

Mapping exclusive breastfeeding in Africa between 2000 and 2017.

Exclusive breastfeeding (EBF)-giving infants only breast-milk (and medications, oral rehydration salts and vitamins as needed) with no additional food or drink for their first six months of life-is one of the most effective strategies for preventing child mortality1-4. Despite these advantages, only 37% of infants under 6 months of age in Africa were exclusively breastfed in 20175, and the practice of EBF varies by population. Here, we present a fine-scale geospatial analysis of EBF prevalence and trends in 49 African countries from 2000-2017, providing policy-relevant administrative- and national-level estimates. Previous national-level analyses found that most countries will not meet the World Health Organization's Global Nutrition Target of 50% EBF prevalence by 20256. Our analyses show that even fewer will achieve this ambition in all subnational areas. Our estimates provide the ability to visualize subnational EBF variability and identify populations in need of additional breastfeeding support.

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.

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.

Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations.Objectives: We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects.Design: Cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 11,913 PSC in 11 surveys and from 11,173 WRA in 7 surveys were analyzed individually and combined with the use of a meta-analysis. The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration >8.3 mg/L): 1) the exclusion of individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of regression approaches.Results: The prevalence of elevated sTfR concentrations incrementally decreased as CRP and AGP deciles decreased for PSC and WRA, but the effect was more pronounced for AGP than for CRP. Depending on the approach used to adjust for inflammation, the estimated prevalence of iron-deficient erythropoiesis decreased by 4.4-14.6 and 0.3-9.5 percentage points in PSC and WRA, respectively, compared with unadjusted values. The correction-factor approach yielded a more modest reduction in the estimated prevalence of iron-deficient erythropoiesis than did the regression approach. Mostly, adjustment for malaria in addition to AGP did not significantly change the estimated prevalence of iron-deficient erythropoiesis.Conclusions: sTfR may be useful to assess iron-deficient erythropoiesis, but inflammation influences its interpretation, and adjustment of sTfR for inflammation and malaria should be considered. More research is warranted to evaluate the proposed approaches in different settings, but this study contributes to the evidence on how and when to adjust sTfR for inflammation and malaria.