BACKGROUND: Hemoglobin and hematocrit are the two most common biomarkers used to identify anemia in clinical settings, but their results do not always agree. OBJECTIVE: To examine agreement between hemoglobin and hematocrit in identifying anemia among children aged 1-<5 years and pregnant persons. METHODS: Pregnant persons and children aged 1-<5 years with hemoglobin and hematocrit results from the same whole blood sample in National Health and Nutrition Examination Survey (NHANES,1999-2020) were included. We used the Centers for Disease Control and Prevention (CDC) anemia cutoff values for children, pregnancy status, trimester, and smoking adjustments. We examined concordance of anemia, sensitivity, and specificity among those with anemia based on at least one test overall and by race/ethnicity, sex, and income level. Cohen's kappa was used to measure concordance. RESULTS: Analytic samples included 7,052 children and 1,437 pregnant persons, of which 1,119 had trimester data. Among children, anemia prevalence was 3.7% (95% CI: 3.1-4.3) based on hemoglobin and 5.5% (95% CI: 4.7-6.3) based on hematocrit. Among pregnant persons, anemia prevalence based on hemoglobin was 7.7% (95% CI: 5.9-9.5) and 12.4% (95% CI: 10.1-14.6) based on hematocrit. Kappa scores overall and by sociodemographic characteristics ranged from 0.64-0.75 (moderate concordance) among children and 0.53-0.78 (weak to moderate concordance) among pregnant persons. Among those with anemia on at least one test, 53.5% of children and 61.5% of pregnant persons had anemia based on both tests. CONCLUSIONS: We found substantial discordance between the two biomarkers; about 50% of children and 40% of pregnant women were identified by only one of the two biomarkers. Because hemoglobin and hematocrit may be used interchangeably in the clinical setting, individuals with anemia may be missed, not receive treatment, and therefore be at higher risk of adverse pregnancy, birth, and developmental outcomes.

This cohort study examines the association of reuse of N95 filtering facepiece respirators and N95 filtration efficiency. | eng

INTRODUCTION: Blood source is a known preanalytical factor affecting hemoglobin (Hb) concentrations, and there is evidence that capillary and venous blood may yield disparate Hb levels and anemia prevalence. However, data from adolescents are scarce. OBJECTIVE: To compare Hb and anemia prevalence measured by venous and individual pooled capillary blood among a sample of girls aged 10-19 years from 232 schools in four regions of Ghana in 2022. METHODS: Among girls who had venous blood draws, a random subsample was selected for capillary blood. Hb was measured using HemoCue® Hb-301. We used Lin's concordance correlation coefficient (CCC) to quantify the strength of the bivariate relationship between venous and capillary Hb and a paired t-test for difference in means. We used McNemar's test for discordance in anemia cases by blood source and weighted Kappa to quantify agreement by anemia severity. A multivariate generalized estimating equation was used to quantify adjusted population anemia prevalence and assess the association between blood source and predicted anemia risk. RESULTS: We found strong concordance between Hb measures (CCC = 0.86). The difference between mean venous Hb (12.8 g/dL, ± 1.1) and capillary Hb (12.9 g/dL, ± 1.2) was not significant (p = 0.26). Crude anemia prevalence by venous and capillary blood was 20.6% and 19.5%, respectively. Adjusted population anemia prevalence was 23.5% for venous blood and 22.5% for capillary (p = 0.45). Blood source was not associated with predicted anemia risk (risk ratio: 0.99, 95% CI: 0.96, 1.02). Discordance in anemia cases by blood source was not significant (McNemar p = 0.46). Weighted Kappa demonstrated moderate agreement by severity (ĸ = 0.67). Among those with anemia by either blood source (n = 111), 59% were identified by both sources. CONCLUSION: In Ghanaian adolescent girls, there was no difference in mean Hb, anemia prevalence, or predicted anemia risk by blood source. However, only 59% of girls with anemia by either blood source were identified as having anemia by both sources. These findings suggest that pooled capillary blood may be useful for estimating Hb and anemia at the population level, but that caution is needed when interpreting individual-level data.

BACKGROUND: Diversity is a key component of diet quality and health, but no indicator exists for adolescents under the age of 15 years. OBJECTIVE: To establish a dichotomous indicator for population-level assessment of adolescent dietary diversity as a proxy for micronutrient adequacy. METHODS: We used the probability approach to construct mean probability of adequacy (MPA) of 11 micronutrients from 2 days of 24-hour dietary recall data from NHANES, 2007-2018. For each micronutrient, probability of adequacy was calculated using the best linear unbiased predictor of usual intake. Adolescent dietary diversity score (ADDS) was derived with a maximum score of 10 food groups. Generalized linear mixed models were used to examine associations between ADDS and MPA. Receiver operating characteristic analysis was used to establish a cutoff for minimum dietary diversity for adolescents (MDD-A), using an energy-adjusted logistic model with ADDS predicting MPA > 0.6. RESULTS: Probability of adequacy was greater than 80% for all nutrients except vitamin C (42.1%), folate (65.7%), and calcium (23.8%). Population MPA was 79.4%, and nearly 92% of adolescents had an MPA > 0.6. ADDS was positively associated with MPA, and energy was a significant confounder. Area under the curve was > 0.8 on both days with sensitivity and specificity ranging from 0.71-0.80. The MDD-A cutoff was calculated as 5.12 and 5.10 food groups on day 1 and 2, respectively. CONCLUSIONS: In U.S. adolescents, the best cutoff for a dichotomous indicator of dietary diversity as a proxy for micronutrient adequacy is 6 food groups in a given day. Future research could validate MDD-A and its associated cutoff for use across country contexts.

Serum ferritin (SF) concentration is the most widely used indicator for iron deficiency (ID). During pregnancy, the World Health Organization recently recommended SF thresholds for ID of <15 µg/L for the 1st trimester of pregnancy, based on expert opinion, and made no recommendations for the 2nd and 3rd trimesters. We examined the relationship of SF with two independent indicators of the onset of iron-deficient erythropoiesis, hemoglobin (Hb) and soluble transferrin receptor 1 (sTfR1), in cross-sectional data from NHANES for 1999-2010 and 2015-2018. We included 1288 pregnant women 15-49 years and excluded women with inflammation or potential liver disease. We used restricted cubic spline (RCS) regression analysis to determine SF thresholds for iron-deficient erythropoiesis. SF decreased during pregnancy; geometric mean SF was higher during the 1st and lower during the 2nd and 3rd trimesters. Using RCS analysis, the SF thresholds identified during pregnancy were <25.8 (18.1, 28.5) µg/L during 1st trimester, <18.3 (16.3, 22.9) µg/L during 2nd trimester, and <19.0 (14.4, 26.1) µg/L during 3rd trimester. These SF threshold levels track concentrations of hepcidin, the iron regulatory hormone controlling the mobilization of iron stores. A SF concentration of <15 µg/L as the criterion for ID may underestimate the true prevalence of ID throughout pregnancy. In our study, an additional one of every ten pregnant women would be recognized as iron deficient by using the physiologically based thresholds at SF of about 25 µg/L during the 1st and of about 20 µg/L during the 2nd and 3rd trimesters.

We read with interest the article by Kang et al. [1], “Hemoglobin distributions and prevalence of anemia in a multiethnic United States pregnant population,” as well as the accompanying Editorial by Merz and Achebe [2], “Iron deficiency in pregnancy: a health inequity [2].” Both Kang et al. [1] and Merz and Achebe [2] incorrectly stated that the Centers for Disease Control and Prevention (CDC) recommend use of lower race-adjusted thresholds to define anemia for Black individuals. The CDC does not recommend separate diagnostic thresholds to define anemia for Black individuals or any other race/ethnic group. Here, we clarify misinterpretations in recent American Journal of Clinical Nutrition publications regarding the CDC anemia threshold recommendations. | | The 1998 “Recommendations to prevent and control iron deficiency in the United States” [3], the most recent CDC publication providing guidance on thresholds to define anemia in individuals, did not recommend race-specific cutoff values for anemia. The 1998 recommendations included criteria for anemia threshold adjustments based on age, sex, pregnancy status, gestational age, altitude, and smoking status [3]. To guide the development of these 1998 CDC recommendations, the CDC requested that the Institute of Medicine (IOM) convene an expert committee to develop recommendations for preventing, detecting, and treating iron deficiency anemia among children and women of reproductive age in United States. The IOM report published in 1993 [4] is independent and not an official institutional CDC/federal recommendations publication. The 1998 CDC recommendations considered inputs from the IOM report [4], conclusions of a CDC expert panel convened in April 1994, and from other multidisciplinary subject matter experts [3].

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability.

Ticks are efficient vectors for transmitting pathogens that negatively affect livestock production and pose a risk to public health. In this study, Babesia and Theileria species were identified in ticks collected from cattle, sheep and goats from the Kassena-Nankana Districts of Ghana between February and December 2020. A total of 1550 ticks were collected, morphologically identified, pooled and screened for pathogens using primers that amplify a 560 bp fragment of the ssrRNA gene and Sanger sequencing. Amblyomma variegatum (62.98%) was the predominant tick species. From the 491 tick pools screened, 12/15 (2.44%) positive pools were successfully sequenced. The pathogen DNA identified were Theileria ovis in eight (15.38%) pools of Rhipicephalus evertsi evertsi, Theileria velifera in two (0.78%) pools of A. variegatum and Babesia occultans and Babesia sp. Xinjiang in one (1.72%) pool each of Hyalomma truncatum. It was further observed that T. ovis occurred in ticks collected from only sheep (p < 0.001) which were females (p = 0.023) and < =1 year old (p = 0.040). This study reports the first identification of these pathogens in ticks within Kassena-Nankana. With the constant trade of livestock, there is a need for effective tick control measures to prevent infection spread.

Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 1549 y [women of reproductive age (WRA)] and children 659 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 20172019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated. 2023

Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 15–49 y [women of reproductive age (WRA)] and children 6–59 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 2017–2019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated. © 2023

BACKGROUND: Although the importance of adolescent nutrition has gained attention in the global nutrition community, there is a gap in research focused on adolescent dietary diversity and food group consumption. OBJECTIVES: This study aimed to characterize population-level food group consumption patterns and quantify the extent of dietary diversity among United States adolescents using a large nationally representative sample of adolescents aged 10-19 y. METHODS: We used 24-h dietary recall data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 to construct the 10 food groups comprising the minimum dietary diversity for women (MDD-W) indicator and estimated the prevalence of intake of each food group. A composite metric adolescent dietary diversity score (ADDS) was derived for each adolescent where 1 point was awarded per food group. Both population scores and the distribution of individual scores were estimated. Differences in proportions of food groups consumed across sociodemographic categories were tested using the Rao-Scott χ(2) test, and pairwise comparisons were expressed as population prevalence differences and prevalence ratios. RESULTS: Food group consumption patterns were very similar across 2 d of dietary recall but varied significantly by sex, race/ethnicity, and income status. The food groups with the highest prevalence of consumption were grains, white, roots, and tubers (∼99%), milk products (∼92%), and meat, poultry, and fish (∼85%), whereas <15% of adolescents consumed key micronutrient-dense foods, such as vitamin A-rich fruits and vegetables and dark green vegetables. The mean ADDS was 4.69, with modest variation across strata. CONCLUSIONS: On average, United States youth consumed fewer than 5 food groups on a given day. The lack of dietary variety and relatively low prevalence of consumption of several micronutrient-rich plant-based foods could pose a risk for adolescents' ability to achieve micronutrient adequacy in the United States.

Micronutrient deficiency is a common global health problem, and accurately assessing micronutrient biomarkers is crucial for planning and managing effective intervention programs. However, analyzing micronutrient data and applying appropriate cutoffs to define deficiencies can be challenging, particularly when considering the confounding effects of inflammation on certain micronutrient biomarkers. To address this challenge, we developed the Statistical Apparatus of Micronutrient Biomarker Analysis (SAMBA) R package, a new tool that increases ease and accessibility of population-based micronutrient biomarker analysis. The SAMBA package can analyze various micronutrient biomarkers to assess status of iron, vitamin A, zinc, and B vitamins, adjust for inflammation, account for complex survey design when appropriate, and produce reports of summary statistics and prevalence estimates of micronutrient deficiencies using recommended age- and sex-specific cutoffs. We have provided a step-by-step procedure for how to use the SAMBA R package, including how to customize it for broader use, and made both the package and user manual publicly available on GitHub. SAMBA was validated by comparing results from analyzing 24 datasets on non-pregnant women of reproductive age from 23 countries and 30 datasets on preschool-age children from 26 countries with those obtained by an independent analyst. SAMBA generated identical means, percentiles, and prevalence of micronutrient deficiencies to those calculated by the independent analyst. In conclusion, SAMBA simplifies and standardizes the process for deriving survey-weighted and inflammation-adjusted (when appropriate) estimates of the prevalence of micronutrient deficiencies, reducing the time from data cleaning to result generation. SAMBA is a valuable tool that facilitates the accurate and rapid analysis of population-based micronutrient biomarker data, which can inform public health research, programs, and policy across contexts.

Ticks are arthropods of veterinary and medical importance which spread zoonotic pathogens that link animal and human health. In this study, ticks were collected from 448 livestock between February and December 2020 in the Kassena-Nankana Districts of Ghana and screened for the presence of zoonotic pathogens DNA using PCR and sequencing approaches. In total, 1550 ticks were collected and morphologically identified. Three tick genera were identified with Amblyomma variegatum (63%) as the predominant tick species collected. DNA was extracted from 491 tick pools and screened for the presence of DNA of Rickettsia spp. based on the 115 bp fragment of the 17 kDa surface protein and 639 bp of the Outer membrane protein A (ompA) gene and the 295 bp fragment of the transposase gene of Coxiella burnetii IS1111a element. From the 491 pools screened, the DNA of Rickettsia spp. and C. burnetii was detected in 56.8 and 3.7%, respectively. Coinfections were identified in 2.4% of the tick pools. Characterization of the Rickettsia spp. in this study based on the ompA gene showed that the DNA of Rickettsia africae and Rickettsia aeschlimannii accounted for 39.7 and 14.7%, respectively, and were 100% similar to sequences in GenBank. Most R. africae and C. burnetii infections occurred in ticks collected in the wet season, whereas R. aeschlimannii occurred mostly in the dry season. These pathogens are potential public health threats, thus there is a need to implement control measures to reduce the risk of infections in vulnerable populations.

We agree with Tamohiko Sato and colleagues that a paucity of ferritin measurements to detect iron deficiency in high-income, middle-income, and low-income countries restricts how well research can quantify the magnitude of the disease burden and prevent and treat the disease. Following Sato and colleagues’ suggestions, we reanalysed ferritin concentration data from the US National Health and Nutrition Examination Survey (NHANES) by age, body-mass index, and income and found no meaningful correlations. In our Article,1 we proposed a method to derive physiologically based ferritin thresholds for iron deficiency among apparently healthy young children and non-pregnant women. We concluded that this approach needs validation in non-US populations before specific threshold values are adopted. Although Sato and colleagues highlight the scarcity of ferritin data for Japan, there is also a paucity of data in the USA for populations at high risk of iron deficiency, hindering surveillance and clinical practice. NHANES measures ferritin but does not collect blood among infants younger than 12 months. Ferritin is an acute phase protein and should be adjusted for inflammation, but NHANES does not measure inflammation in all age groups consistently. Sample sizes for pregnant women are small, requiring the combining of data from approximately 10 years for dependable estimates; after 2013, NHANES stopped recording the trimester of pregnancy. The US Public Health Task Force has also emphasised the paucity of prevalence data for iron deficiency anaemia among pregnant women.2 Analysis of electronic health records for first-trimester pregnancies found that anaemia screening is virtually universal, but ferritin screening for iron deficiency is not,3 despite recommendations by the American College of Obstetrics and Gynecologists.4 We continue to search for suitable anonymised databases to examine the proposed method for deriving physiologically based thresholds for serum ferritin concentration for iron deficiency among apparently healthy individuals. Having found that some national datasets from other countries have prohibitive restrictions on their use, we welcome any suggestions of publicly available and representative ferritin data.

Tick-borne pathogens harm livestock production and pose a significant risk to public health. To combat these effects, it is necessary to identify the circulating pathogens to create effective control measures. This study identified Anaplasma and Ehrlichia species in ticks collected from livestock in the Kassena-Nankana Districts between February 2020 and December 2020. A total of 1550 ticks were collected from cattle, sheep and goats. The ticks were morphologically identified, pooled and screened for pathogens using primers that amplify a 345 bp fragment of the 16SrRNA gene and Sanger sequencing. The predominant tick species collected was Amblyomma variegatum (62.98%). From the 491 tick pools screened, 34 (6.92%) were positive for Ehrlichia and Anaplasma. The pathogens identified were Ehrlichia canis (4.28%), Ehrlichia minasensis (1.63%), Anaplasma capra (0.81%) and Anaplasma marginale (0.20%). This study reports the first molecular identification of the above-mentioned Ehrlichia and Anaplasma species in ticks from Ghana. With the association of human infections with the zoonotic pathogen A. capra, livestock owners are at risk of infections, calling for the development of effective control measures.

BACKGROUND: Current WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 μg/L) and women (<15 μg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 μg/L; women, <25 μg/L) were identified from physiologically based analyses. OBJECTIVE: We examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. METHODS: We analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. RESULTS: SF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 μg/L (95% confidence interval: 18.5, 26.5) and 18.7 μg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 μg/L (23.4, 26.9) and 22.5 μg/L (21.7, 23.3). CONCLUSIONS: These NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID.

OBJECTIVES: We determined pulse oximetry benefit in pediatric pneumonia mortality-risk stratification and chest indrawing pneumonia in-hospital mortality risk factors. METHODS: We report characteristics and in-hospital pneumonia-related mortality of children 2-59-months-old included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57·5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5·8%, 95% CI 5·6-5·9% vs 2·1%, 95% CI 1·9-2·4%). One in five children with chest indrawing pneumonia was hypoxemic (19·7%, 95% CI 19·0-20·4%) and the hypoxemic CFR was 10·3% (95% CI 9·1%-11·5%). Other mortality risk factors were younger age (either 2-5 months (aOR 9·94, 95% CI 6·67-14·84) or 6-11 months (aOR 2·67, 95% CI 1·71-4·16)), moderate malnutrition (aOR 2·41, 95% CI 1·87-3·09), and female sex (aOR 1·82, 95% CI 1·43-2·32). CONCLUSIONS: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest indrawing pneumonia were hypoxemic and one in ten died. Young age and moderate malnutrition were risk factors for in-hospital chest indrawing pneumonia-related mortality. Pulse oximetry should be integrated in under-five pneumonia hospital care.

The risk of pathogen transmission continues to increase significantly in the presence of tick vectors due to the trade of livestock across countries. In Ghana, there is a lack of data on the incidence of tick-borne pathogens that are of zoonotic and veterinary importance. This study, therefore, aimed to determine the prevalence of such pathogens in livestock using molecular approaches. A total of 276 dry blood spots were collected from cattle (100), sheep (95) and goats (81) in the Kassena-Nankana Districts. The samples were analyzed using Polymerase Chain Reaction (qPCR) and conventional assays and Sanger sequencing that targeted pathogens including Rickettsia, Coxiella, Babesia, Theileria, Ehrlichia and Anaplasma. An overall prevalence of 36.96% was recorded from the livestock DBS, with mixed infections seen in 7.97% samples. Furthermore, the prevalence of infections in livestock was recorded to be 19.21% in sheep, 14.13% in cattle, and 3.62% in goats. The pathogens identified were Rickettsia spp. (3.26%), Babesia sp. Lintan (8.70%), Theileria orientalis (2.17%), Theileria parva (0.36%), Anaplasma capra (18.48%), Anaplasma phagocytophilum (1.81%), Anaplasma marginale (3.26%) and Anaplasma ovis (7.25%). This study reports the first molecular identification of the above-mentioned pathogens in livestock in Ghana and highlights the use of dry blood spots in resource-limited settings. In addition, this research provides an update on tick-borne pathogens in Ghana, suggesting risks to livestock production and human health. Further studies will be essential to establish the distribution and epidemiology of these pathogens in Ghana.

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. RESULTS: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285839 children with pneumonia (244323 in the hospital and 41516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285839 episodes, 280998 occurred in children 0-59 months old, of which 129584 (46%) were 2-11 months of age and 152730 (54%) were males. CONCLUSIONS: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

BACKGROUND: In the presence of inflammation, the serum or plasma ferritin concentration ("ferritin" hereafter) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain. OBJECTIVES: We describe relationships between weight status, inflammation, and ferritin among nonpregnant women of reproductive age (WRA; 15-49 years) and preschool-age children (PSC; 6-59 months) with normal weight to overweight or obesity (OWOB) in differing geographic settings. METHODS: Cross-sectional data were separately analyzed from 18 surveys (WRA) and 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (in WRA) or BMI-for-age z-score (BAZ; in PSC), inflammatory biomarkers of C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications. RESULTS: In 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully, in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines. CONCLUSIONS: Where having OWOB is common among WRA, measurements of inflammatory biomarkers and their uses in interpreting ferritin may improve iron status assessments. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status. Included Kenyan trial data are registered at clinicaltrials.gov as NCT01088958.

Iron deficiency and the more severe sequela, iron deficiency anemia, are public health problems associated with morbidity and mortality, particularly among pregnant women and younger children. The 1998 Centers for Disease Control and Prevention recommendations for prevention and control of iron deficiency in the United States is old and does not reflect recent evidence but is a foundational reference for many federal, clinical, and program guidelines. Surveillance data for iron deficiency are sparse at all levels, with critical gaps for pregnant women and younger children. Anemia, iron deficiency, and iron deficiency anemia are often conflated but should not be. Clinical guidelines for anemia, iron deficiency, and iron deficiency anemia give inconsistent recommendations, causing nonsystematic assessment of iron deficiency. Screening for iron deficiency typically relies on identifying anemia, despite anemia's low sensitivity for iron deficiency. In the National Health and Nutrition Examination Survey, more than 70% of iron deficiency is missed among pregnant women and children by relying on hemoglobin for iron deficiency screening. To improve assessment and diagnosis and strengthen surveillance, better and more complete data and updated foundational guidance on iron deficiency and anemia are needed that consider new evidence for measuring and interpreting laboratory results. (Am J Public Health. 2022;112(S8):S826-S835. https://doi.org/10.2105/AJPH.2022.306998).

BACKGROUND: The introduction of human immunodeficiency virus (HIV) antibody rapid testing (RT) in resource-limited settings has proven to be a successful intervention to increase access to prevention measures and improve timely linkage to care. However, the quality of testing has not always kept pace with the scale-up of this testing strategy. To monitor the accuracy of HIV RT test results, a national proficiency testing (PT) program was rolled out at selected testing sites in Ghana using the dried tube specimen (DTS) approach. METHODS: Between 2015 and 2018, 635 HIV testing sites, located in five regions and supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), were enrolled in the HIV PT program of the Ghana Health Service National AIDS/STI Control Programme. These sites offered various services: HIV Testing and Counselling (HTC), prevention of mother-to-child transmission (PMTCT) and Antiretroviral Treatment (ART). The PT panels, composed of six DTS, were prepared by two regional laboratories, using fully characterized plasma obtained from the regional blood banks and distributed to the testing sites. The results were scored by the PT providers according to the predefined acceptable performance criteria which was set at ≥ 95%. RESULTS: Seven rounds of PT panels were completed successfully over three years. The number of sites enrolled increased from 205 in round 1 (June 2015) to 635 in round 7 (December 2018), with a noticeable increase in Greater Accra and Eastern regions. The average participation rates of enrolled sites ranged from 88.0% to 98.0% across the PT rounds. By round 7, HTC (257/635 (40.5%)) and PMTCT (237/635 (37.3%)) had a larger number of sites that participated in the PT program than laboratory (106/635 (16.7%)) and ART (12/635 (1.9%)) sites. The average testing performance rate improved significantly from 27% in round 1 to 80% in round 7 (p < 0.001). The highest performance rate was observed for ART (100%), HTC (92%), ANC/PMTCT (90%) and Laboratory (89%) in round 5. CONCLUSION: The DTS PT program showed a significant increase in the participation and performance rates during this period. Sub-optimal performances observed was attributed to non-compliance to the national testing algorithm and testing technique. However, the implementation of review meetings, peer-initiated corrective action, supportive supervisory training, and mentorship proved impactful. The decentralized approach to preparing the PT panels ensured ownership by the region and districts.

The highly transmissible SARS-CoV-2 Omicron variant led to increased hospitalizations, staffing shortages, and increased school closures. To reduce spread in school-aged children during the Omicron peak, the District of Columbia implemented a test-to-return strategy in public and public charter schools after a two-week break from in-person learning.

BACKGROUND: Practice-based experiences documenting development and implementation of nutrition and health surveillance systems are needed. OBJECTIVES: To describe processes, methods, and lessons learned from developing and implementing a population-based household nutrition and health surveillance system in Guatemala. METHODS: The phases and methods for the design and implementation of the surveillance system are described. Efforts to institutionalize the system in government institutions are described, and illustrative examples describing different data uses, and lessons learned are provided. RESULTS: After initial assessments of data needs and consultations with officials in government institutions and partners in the country, a population-based nutrition surveillance system prototype with complex sampling was designed and tested in 5 Guatemalan Highland departments in 2011. After dissemination of the prototype, government and partners expanded the content, and multitopic nutrition and health surveillance cycles were collected in 2013, 2015, 2016, 2017/18, and 2018/19 providing nationally representative data for households, women of reproductive age (15-49 y), and children aged 0-59 mo. For each cycle, data were to be collected from 100 clusters, 30 households in each, and 1 woman and 1 child per household. Content covered ∼25 health and nutrition topics, including coverage of all large-scale nutrition-specific interventions; the micronutrient content of fortifiable sugar, salt, and bread samples; anthropometry; and biomarkers to assess annually, or at least once, ∼25 indicators of micronutrient status and chronic disease. Data were collected by 3-5 highly trained field teams. The design was flexible and revised each cycle allowing potential changes to questionnaires, population groups, biomarkers, survey design, or other changes. Data were used to change national guidelines for vitamin A and B-12 interventions, among others, and evaluate interventions. Barriers included frequent changes of high-level government officials and heavy dependence on US funding. CONCLUSIONS: This system provides high-quality data, fills critical data gaps, and can serve as a useful model for others.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

Our objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and two independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20-49 years, who were first-time or reactivated donors in the REDS-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin <25.4 µg/L) and by hemoglobin (serum ferritin <25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin <25.5 µg/L) and hemoglobin (serum ferritin <26.6 µg/L) in a previous study of 5,442 women, 20-49 years, in the U.S. National Health and Nutrition Examination Survey 2003-2018 (NHANES) (p=0.98 and 0.83, respectively). While international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

BACKGROUND: Standardized practices are needed in the analysis of inflammation biomarker values outside limits of detection (LOD) when used for inflammation correction of nutritional biomarkers. OBJECTIVE: We assessed the direction and extent to which serum C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP) values outside LODs (<0.05 mg/L and >4.0 g/L, respectively) affect inflammation regression correction of serum ferritin and compared approaches to addressing such values when estimating inflammation-adjusted ferritin and iron deficiency (ID). METHODS: Examined 29 cross-sectional datasets from 7 countries with reproductive-age women (15-49y) (n = 12,944), preschool-age children (6-59m) (n = 18,208) and school-age children (6-14y) (n = 4,625). For each dataset, we compared 6 analytic approaches for addressing CRP <LOD: listwise deletion, single imputation (lower, middle, or upper bound; LOD/√2; random number), with multiple imputation (MI). For each approach, inflammation-adjusted ferritin and ID using BRINDA regression correction were estimated. We calculated deviance of each estimate from that given by MI within each dataset and performed fixed effects multivariate meta-regression with analytic approach as moderator to compare the reliability of each approach to MI. RESULTS: Across datasets, observations outside LOD ranged from 0.0 to 35.0% of CRP values and 0.0 to 2.5% of AGP values. Pooled deviance estimates for mean ferritin (µg/L) and ID (percentage points) were: listwise deletion -0.46 (95%CI: -0.76, -0.16) and 0.14 (-0.43, 0.72), lower bound 0.45 (0.14, 0.76) and -0.36 (-0.91, 0.20), middle bound -0.21 (-0.51, 0.09) and 0.22 (-0.34, 0.79), LOD/√(2) -0.26 (-0.57, 0.04) and 0.25 (-0.31, 0.81), upper bound -0.31 (-0.61, -0.01) and 0.30 (-0.27, 0.86), and random number -0.08 (-0.38, 0.22) and 0.11 (-0.46, 0.67). There was moderation by approach in the ferritin model (p<0.001). CONCLUSIONS: Findings demonstrate the need for standardized analyses of inflammation biomarker values outside LODs and suggest that random number single imputation may be a reliable and feasible alternative to MI for CRP <LOD.

BACKGROUND: To address the burden of anemia in adolescent girls in Ghana, the Girls' Iron-Folate Tablet Supplementation (GIFTS) program was established in 2017. An evaluation found that although iron and folic acid (IFA) supplementation reached nearly all adolescent girls in schools during year 1, most girls received fewer than the minimum effective number of tablets over the school year. Barrier analyses highlighted schools as drivers of adherence, though information was incomplete on the reasons for the disparities among schools. Information was also lacking on the implementation of health and nutrition education. OBJECTIVES: At the start of year 3 of an integrated adolescent anemia prevention program with IFA supplementation, the present study sought to illuminate differences in program fidelity among schools and across time and potential factors that drive such differences. METHODS: After stratifying by school level, size, geographic location, and intake adherence during year 1, 16 schools were purposively selected. For each school, semistructured key informant interviews were conducted with 1 coordinator at the district level, 3 educators at the school level, and 1 parent leader. Following thematic analysis methods, recorded and transcribed interviews were coded and organized into deductive and inductive themes. RESULTS: Limited training, challenges during distribution of IFA, lack of incentives, and inconsistent health and nutrition education diminished program fidelity. Strong supply chain, widespread awareness promotion, improved acceptability, and intrinsically motivated educators improved program fidelity. After 2 y of implementation, schools had made program adaptations, and widespread changes in attitudes and beliefs about the IFA tablets had improved their acceptability. However, limitations remained related to supply chain, program ownership, communication between health and education sectors, training, motivation, and resources. CONCLUSIONS: The fidelity of Ghana's GIFTS program is strengthened by its supply chain, acceptability, and motivated stakeholders; however, training, curricula, clear communication, and incentives could improve it.

BACKGROUND: Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 μg/L for children and less than 15 μg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). METHODS: In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×10(9)/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. FINDINGS: 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 μg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 μg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 μg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 μg/L (23·3-24·6; p=0·05). INTERPRETATION: The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 μg/L for children and 25 μg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. FUNDING: None.