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    Biofortification is the process of increasing the concentrations and/or bioavailability of micronutrients in staple crops and has the potential to mitigate micronutrient deficiencies globally. Efficacy trials have demonstrated benefits of... more
    Biofortification is the process of increasing the concentrations and/or bioavailability of micronutrients in staple crops and has the potential to mitigate micronutrient deficiencies globally. Efficacy trials have demonstrated benefits of consuming biofortified crops (BFCs); and in this paper, we report on the results of a systematic review of biofortified crops effectiveness in real-world settings. We synthesized the evidence on biofortified crops consumption through four Impact Pathways: (1) purchased directly; (2) in informal settings; (3) in formal settings; or (4) in farmer households, from their own production. Twenty-five studies, covering Impact Pathway 1 (five studies), Impact Pathway 2 (three), Impact Pathway 3 (three), Impact Pathway 4 (21) were included. The review found evidence of an improvement in micronutrient status via Impact Pathway 4 (mainly in terms of vitamin A from orange sweet potato) in controlled interventions that involved the creation of demand, the exten...
    BACKGROUND Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However,... more
    BACKGROUND Maternal serum alpha-fetoprotein (MSAFP) concentration typically increases during pregnancy and is routinely measured during the second trimester as a part of screening for fetal neural tube defects and Down syndrome. However, most pregnancy screening tests are not available in the settings they are needed the most. A mobile device–enabled technology based on MSAFP for screening birth defects could enable the rapid screening and triage of high-risk pregnancies, especially where maternal serum screening and fetal ultrasound scan facilities are not easily accessible. Shifting the approach from clinic- and laboratory-dependent care to a mobile platform based on our point-of-care approach will enable translation to resource-limited settings and the global health care market. OBJECTIVE The objective of this study is to develop and perform proof-of-concept testing of a lateral flow immunoassay on a mobile platform for rapid, point-of-care quantification of serum alpha-fetoprote...
    Governments often rely on school infrastructure to implement programs targeting children, but whether and to what extent managerial capacity constraints affect the implementation of these programs are important, open questions. We... more
    Governments often rely on school infrastructure to implement programs targeting children, but whether and to what extent managerial capacity constraints affect the implementation of these programs are important, open questions. We consider these questions in the context of India’s school meals program and iron and folic acid (IFA) supplementation program. Using a randomized controlled trial in a rural district in the state of Odisha, we evaluate the impact of two interventions on child health and on how these government-run programs are implemented. First, we distribute a micronutrient mix (MNM) to be added to the school meal to complement the existing IFA program. Second, we monitor school meals with increased frequency early in the intervention. While we find significant positive effects of distributing the MNM on micronutrient levels in the meals, we find no detectable effects on child health. Increased monitoring of school meals, on the other hand, does improve hemoglobin levels...
    chapter 1. Justification for Biofortification Introduction Biofortification is a process of increasing the density of minerals and vitamins in a food crop through conventional plant breeding, genetic engineering, or agronomic practices... more
    chapter 1. Justification for Biofortification Introduction Biofortification is a process of increasing the density of minerals and vitamins in a food crop through conventional plant breeding, genetic engineering, or agronomic practices (primarily use of fertilizers and foliar sprays). Biofortified staple food crops, when substituted consistently for non-biofortified staple food crops, can generate measurable improvements in human nutrition and health. This monograph describes the progress made in developing, testing, and disseminating biofortified staple food crops, primarily through the use of conventional plant breeding, summarizing the activities of two consortiums of inter-disciplinary collaborating institutions led the HarvestPlus program and the International Potato Center (CIP). We focus on laying out the evidence base proving the effectiveness and impact to date of biofortified crops. Results of a large number of nutritional bioavailability and efficacy trials are summarized...
    India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less... more
    India has the highest rates of tuberculosis (TB) globally and a high prevalence of malnutrition; however, the interplay between host nutritional status, inflammation, and the gut microbiome in active tuberculosis disease (ATBD) is less well-studied. We examined differences in gut microbial composition and diversity based on undernutrition and inflammation status among outpatients with ATBD at the time of treatment initiation. During this exploratory cross-sectional study, outpatients (N = 32) with ATBD (confirmed by Xpert MTB/RIF) were enrolled in anti-TB treatment initiated at a hospital in rural southern India. The 16S rRNA sequencing was used to assess the composition of the gut microbiome. We assessed multiple markers of nutritional status, including micronutrient status concentrations (vitamin D [25(OH)D], vitamin B12, ferritin), anthropometry (body mass index, mid-upper arm circumference, and height), and C-reactive protein (CRP), as indicators of inflammation. We found that 2...
    This review provides an insight into current rapid diagnostics for antimicrobial resistance, their technical aspects and benefits/limitations on their application.
    To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate... more
    To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and w...
    The pandemic of coronavirus disease 2019 (COVID‐19) is caused by infection with a novel coronavirus strain, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). At present, there is limited information on potential... more
    The pandemic of coronavirus disease 2019 (COVID‐19) is caused by infection with a novel coronavirus strain, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). At present, there is limited information on potential transmission of the infection from mother to child, particularly through breast milk and breastfeeding. Here, we provide a living systematic review to capture information that might necessitate changes in the guidance on breast milk and breastfeeding given the uncertainty in this area. Our search retrieved 19,414 total records; 605 were considered for full‐text eligibility and no ongoing trials were identified. Our review includes 340 records, 37 with breast milk samples and 303 without. The 37 articles with analyzed breast milk samples reported on 77 mothers who were breastfeeding their children; among them, 19 of 77 children were confirmed COVID‐19 cases based on RT‐PCR assays, including 14 neonates and five older infants. Nine of the 68 analyzed breast milk samples from mothers with COVID‐19 were positive for SARS‐CoV‐2 RNA; of the exposed infants, four were positive and two were negative for COVID‐19. Currently, there is no evidence of SARS‐CoV‐2 transmission through breast milk. Studies are needed with longer follow‐up periods that collect data on infant feeding practices and on viral presence in breast milk.
    To help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the Ebola virus (EBOV) in breast milk and its potential risk of viral transmission to the infant when... more
    To help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the Ebola virus (EBOV) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. We relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed EBOV infection, intending to breastfeed or give breast milk to an infant. Our search identified 10,454 records, and after deduplication and screening, we assessed 148 full texts. We included eight studies reporting on 10 breastfeeding mothers and their children (one mother with twins), who provided breast milk samples for assessment. EBOV was detected via RT‐PCR or viral culture in seven out of ten breast milk samples. Four out of the five‐breastfed infants with EBOV‐positive breast milk were found positive for EBOV infection, and all of these EBOV‐positive infants died. Since previous reports have detected EBOV in tears, saliva, sweat, and contaminated surfaces, with the current evidence, it is not possible to conclude with certainty that breast milk was the main route of EBOV transmission.
    ABSTRACTPregnancy and lactation are critical life stages with unique nutritional requirements, including for vitamin A (VA). Current DRIs for VA were published in 2001. The objective of this review was to identify and categorize evidence... more
    ABSTRACTPregnancy and lactation are critical life stages with unique nutritional requirements, including for vitamin A (VA). Current DRIs for VA were published in 2001. The objective of this review was to identify and categorize evidence related to VA requirements in pregnancy and lactation since these DRIs were formulated. We searched MEDLINE and included articles according to an analytic framework of maternal VA exposure on status and health outcomes in the mother-child dyad. Intermediate and indirect evidence supports that maternal VA intakes can impact the mother's VA status, breastmilk, and health outcomes, as well as the child's VA status and select health outcomes. Food-based approaches can lead to more sustained, sufficient VA status in mothers and children. Research needs include further study linking maternal VA intakes on maternal and child VA status, and further associations with outcomes to determine intake requirements to optimize health.
    In this cross-sectional study, we describe the composition and diversity of the gut microbiota among undernourished children living in urban slums of Mumbai, India, and determine how nutritional status, including anthropometric... more
    In this cross-sectional study, we describe the composition and diversity of the gut microbiota among undernourished children living in urban slums of Mumbai, India, and determine how nutritional status, including anthropometric measurements, dietary intakes from complementary foods, feeding practices, and micronutrient concentrations, is associated with their gut microbiota. We collected rectal swabs from children aged 10 to 18 months living in urban slums of Mumbai participating in a randomized controlled feeding trial and conducted 16S rRNA sequencing to determine the composition of the gut microbiota. Across the study cohort, Proteobacteria dominated the gut microbiota at over 80% relative abundance, with Actinobacteria representation at <4%, suggesting immaturity of the gut. Increased microbial α-diversity was associated with current breastfeeding, greater head circumference, higher fat intake, and lower hemoglobin concentration and weight-for-length Z-score. In redundancy an...
    BACKGROUND When we were unable to identify an electronic data capture (EDC) package that supported our requirements for clinical research in resource-limited regions, we set out to build our own reusable EDC framework. We needed to... more
    BACKGROUND When we were unable to identify an electronic data capture (EDC) package that supported our requirements for clinical research in resource-limited regions, we set out to build our own reusable EDC framework. We needed to capture data when offline, synchronize data on demand, and enforce strict eligibility requirements and complex longitudinal protocols. Based on previous experience, the geographical areas in which we conduct our research often have unreliable, slow internet access that would make web-based EDC platforms impractical. We were unwilling to fall back on paper-based data capture as we wanted other benefits of EDC. Therefore, we decided to build our own reusable software platform. In this paper, we describe our customizable EDC framework and highlight how we have used it in our ongoing surveillance programs, clinic-based cross-sectional studies, and randomized controlled trials (RCTs) in various settings in India and Ecuador. OBJECTIVE This paper describes the ...
    Objectives Despite the multitude of evaluations of nutrition intervention trials in low-income settings, documented practice to operate such trials is scarce. We aimed to fill this gap by outlining key steps and resources required to run... more
    Objectives Despite the multitude of evaluations of nutrition intervention trials in low-income settings, documented practice to operate such trials is scarce. We aimed to fill this gap by outlining key steps and resources required to run a small-scale intensive feeding trial such as establishing collaborations, developing an operational infrastructure, and daily orchestration of logistics for food preparation, delivery, and administration. Methods A randomized controlled feeding trial among 223 children in urban slums of Mumbai, India was completed in 2018. We established partnerships to facilitate the acquisition and proper storage of the study intervention, biofortified and conventional pearl millet. Feeding centers (FC) were identified based on a census. Two staff per FC managed daily operations: weighing and dispensing individual portions to participants based on their group allocation, recording of leftovers and adverse events. The study team developed and standardized recipes ...
    Iron deficiency is a major public health problem worldwide, with the highest burden among children. The objective of this randomized efficacy feeding trial was to determine the effects of consuming iron-biofortified beans (Fe-Beans) on... more
    Iron deficiency is a major public health problem worldwide, with the highest burden among children. The objective of this randomized efficacy feeding trial was to determine the effects of consuming iron-biofortified beans (Fe-Beans) on the iron status in children, compared to control beans (Control-Beans). A cluster-randomized trial of biofortified beans (Phaseolus vulgaris L), bred to enhance iron content, was conducted over 6 months. The participants were school-aged children (n = 574; 5–12 years), attending 20 rural public boarding schools in the Mexican state of Oaxaca. Double-blind randomization was conducted at the school level; 20 schools were randomized to receive either Fe-Beans (n = 10 schools, n = 304 students) or Control-Beans (n = 10 schools, n = 366 students). School administrators, children, and research and laboratory staff were blinded to the intervention group. Iron status (hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), total body iron (...
    Background Inflammation is a key component of immune response to infections and pathogenesis of metabolic and cardiovascular diseases. Inflammatory biomarkers, including alpha-1-acid glycoprotein (AGP), are considered prognostic tools for... more
    Background Inflammation is a key component of immune response to infections and pathogenesis of metabolic and cardiovascular diseases. Inflammatory biomarkers, including alpha-1-acid glycoprotein (AGP), are considered prognostic tools for predicting risk, monitoring response to therapy, and adjusting nutritional biomarkers for accurate interpretation. Serum is considered a primary source of biomarkers; urine and saliva are increasingly being explored and utilized as rapidly accessible, noninvasive biofluids requiring minimal sample processing and posing fewer biohazard risks. Methods A lateral flow immunoassay was developed for an established mobile-based platform to quantify AGP in human serum, urine, and saliva. Assay performance was assessed with purified AGP in buffer, diluted human serum samples (n = 16) banked from a trial in people living with HIV, and saliva and urine (n = 15 each) from healthy participants. Reference methods were conventional clinical chemistry analyzer or commercial ELISA. Bootstrap analysis was used to train and validate sample calibration. Findings The correlation between the assay and reference method for serum was 0.97 (P < 0.001). Mean (95% CI) best fit line slope was 1.0 (0.88, 1.15) and intercept was -0.003 (-0.08, 0.09). The correlation for urine was 0.93, and for saliva was 0.97 (both P < 0.001). The median CV for the LFIA for AGP in buffer was 13.2% and for all samples was 28.7%. Interpretation The performance of the assay indicated potential use as a rapid, low sample volume input, and easy method to quantify AGP that can be licensed and adopted by commercial manufacturers for regulatory approvals and production. This has future applications for determining inflammatory status either alone or in conjunction with other inflammatory proteins such as C-reactive protein for prognostic, monitoring, or nutritional status applications, including large-scale country level surveys conducted by the DHS and those recommended by the WHO.
    Background Malaria continues to impose a tremendous burden in terms of global morbidity and mortality, yet even today, a large number of diagnoses are presumptive resulting in lack of or inappropriate treatment. Methods In this work, a... more
    Background Malaria continues to impose a tremendous burden in terms of global morbidity and mortality, yet even today, a large number of diagnoses are presumptive resulting in lack of or inappropriate treatment. Methods In this work, a two-colour lateral flow immunoassay (LFA) system was developed to identify infections by Plasmodium spp. and differentiate Plasmodium falciparum infection from the other three human malaria species (Plasmodium vivax, Plasmodium ovale, Plasmodium malariae). To achieve this goal, red and blue colours were encoded to two markers on a single test line of strips, for simultaneous detection of PfHRP2 (red), a marker specific for P. falciparum infection, and pLDH (blue), a pan-specific marker for infections by all species of Plasmodium. The assay performance was first optimized and evaluated with recombinant malarial proteins spiked in washing buffer at various concentrations from 0 to 1000 ng mL−1. The colour profiles developed on the single test line were ...
    Background Micronutrients are known to modulate host immunity and there is limited literature on this association in the context of dengue virus infection (DENV). Methods Using a nested case-control design in a surveillance program, we... more
    Background Micronutrients are known to modulate host immunity and there is limited literature on this association in the context of dengue virus infection (DENV). Methods Using a nested case-control design in a surveillance program, we measured anthropometry; nutritional biomarkers including serum ferritin, soluble transferrin receptor, retinol-binding protein (RBP), 25-hydroxy vitamin D, folate, and vitamin B12; and a panel of immune response markers and compared these measures across four illness categories: healthy control, non-febrile DENV, other febrile illness (OFI), and apparent DENV using multivariate polytomous logistic regression models. Results Among 142 participants, serum ferritin (ng/mL) was associated with apparent DENV compared to healthy controls (OR 2.66; CI 1.53, 4.62; p=0.001), and RBP concentrations (µmol/L) were associated with apparent DENV (OR 0.03; CI 0.00, 0.30; p=0.003) and OFI (OR 0.02; CI 0.00, 0.24; p=0.003). In a subset of 71 participants, IL-15 levels...
    Objectives 1. To characterize the gut microbiome and 2. explore associations between dietary intake and gut microbiome composition and predicted function among children at screening for participation in a randomized controlled feeding... more
    Objectives 1. To characterize the gut microbiome and 2. explore associations between dietary intake and gut microbiome composition and predicted function among children at screening for participation in a randomized controlled feeding trial in urban slums of Mumbai, India. Methods Young children (10–18 months old) living in urban slums of Mumbai were screened from March to November 2017 after obtaining informed consent from caregivers. Nutrient intakes from 24-hour dietary recall were analyzed as absolute intakes, % of RDA, and using the nutrient residual to adjust for energy intake. DNA extracted from rectal swabs was sequenced (16S rRNA V3-V4 region; Illumina MiSeq) and further processed using QIIME2 and PICRUSt algorithm. Linear regression was used to estimate associations between nutrient intakes (adjusted for age and sex) and measures of gut microbiome α-diversity, including Shannon Index, Chao1 estimator, observed OTUs, Proteobacteria relative abundance, Firmicutes: Bacteroide...
    Objectives To examine the burden of anemia and deficiencies of iron, vitamin B12, and folate in women of reproductive age (WRA) in Ecuador. Methods Data from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) were... more
    Objectives To examine the burden of anemia and deficiencies of iron, vitamin B12, and folate in women of reproductive age (WRA) in Ecuador. Methods Data from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) were analyzed to examine the burden of anemia and micronutrient deficiencies among 7658 women of reproductive age (12–49 y; n = 7383 non-pregnant, n = 275 pregnant). Venous blood samples were collected, and hemoglobin (Hb) was assessed viathe sodium lauryl sulfate method. Samples were centrifuged, processed, and stored 
    Background Insulin regulates fatty acids (FAs) in the blood; conversely, FAs may mediate insulin sensitivity and are potentially modifiable risk factors of the diabetogenic state. Objective The objective of our study was to examine the... more
    Background Insulin regulates fatty acids (FAs) in the blood; conversely, FAs may mediate insulin sensitivity and are potentially modifiable risk factors of the diabetogenic state. Objective The objective of our study was to examine the associations between plasma concentrations of FAs, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) among individuals (n = 1433) in the NHANES (2003–2004). Design Plasma concentrations of 24 individual FAs were considered individually and in subgroups, per chemical structure. Study participants were categorized in diabetogenic groups: Group 1 (HbA1c ≥6.5% or FPG ≥126 mg/dL), Group 2 (HbA1c 5.7% to <6.5% or FPG 100 to <126 mg/dL), and Group 3 (HbA1c <5.7% and FPG <100 mg/dL). We assessed associations between diabetogenic groups and plasma FAs in multivariate multinomial regressions (with Group 3 as the reference). Results Overall, 7.0% of study participants were in Group 1; 33.3% were in Group 2. Plasma concentrations of severa...
    Interest in developing paper-based devices for point-of-care diagnostics in resource-limited settings has risen remarkably in recent decades. In this paper, we demonstrate what we refer to as “High Yield Passive...
    Biofortified crops represent a sustainable agricultural solution for the widespread micronutrient malnutrition in India and other resource-limited settings. This study aims to investigate the effect of the consumption of foods prepared... more
    Biofortified crops represent a sustainable agricultural solution for the widespread micronutrient malnutrition in India and other resource-limited settings. This study aims to investigate the effect of the consumption of foods prepared with iron- and zinc-biofortified pearl millet (FeZn-PM) by children on biomarkers of iron and zinc status, growth, and immune function. We will conduct a randomised controlled feeding trial in identified slums of Mumbai, India among 200 children aged between 12 and 18 months. Children will be randomised to receive foods prepared with the biofortified PM (FeZn-PM, ICTP8203-Fe) or non-biofortified PM. Anthropometric and morbidity data will be gathered every month for 9 months. Biological samples will be collected at baseline, midline and endline to assess iron and zinc status, including haemoglobin, serum ferritin, serum transferrin receptor, serum zinc, C-reactive protein and alpha-1 acid glycoprotein. Biological samples will be archived for future ana...
    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans.Objective: This study sought to advance the current understanding of placental vitamin D metabolism... more
    Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans.Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy.Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes.Results: In placental tissue, 25-hydroxyvitamin D3 [25(OH)D3] was strongly correlated (r = 0.83, P < 0.001) wi...
    The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following... more
    The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10), latent TB infection (LTBI, n = 10), and previous active TB disease (after successful treatment; PTBD, n = 10), relative to controls (n = 10). Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α). ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3,...
    The need for improving methods of nutritional assessment and delivering primary health care globally cannot be overemphasized. While advances in medical technology typically create more disparities because of access being limited to... more
    The need for improving methods of nutritional assessment and delivering primary health care globally cannot be overemphasized. While advances in medical technology typically create more disparities because of access being limited to resource-rich settings, a transition of health care to a mobile platform is increasingly leveling the field. Technological advances offer opportunities to scale laboratory procedures down to mobile devices, such as smartphones and tablets. Globalization also provides the required infrastructure and network capacity to support the use of mobile health devices in developing settings where nutritional deficiencies are most prevalent. Here, we discuss some of the applications and advantages provided by expanding markets of biomarker measurement coupled with primary health care and public health systems and how this is enhancing access and delivery of health services with significant global impact.
    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the... more
    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malariain utero. Levels of EBV- and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no de...
    Vitamin E is an essential nutrient for human health, with an established function as a lipid-soluble antioxidant that protects cell membranes from free radical damage. Low vitamin E status has been linked to multiple health outcomes,... more
    Vitamin E is an essential nutrient for human health, with an established function as a lipid-soluble antioxidant that protects cell membranes from free radical damage. Low vitamin E status has been linked to multiple health outcomes, including total mortality. With vitamin E being identified as a 'shortfall nutrient' because >90% of American adults are not consuming recommended amounts of vitamin E, we aimed to determine the prevalence of both clinical vitamin E deficiency (serum α-tocopherol concentration < 12 μmol/L) and failure to meet a criterion of vitamin E adequacy, serum α-tocopherol concentration of 30 μmol/L, based on the Estimated Average Requirement (EAR) and lowest mortality rate in the Alpha-Tocopherol Beta-Carotene (ATBC) study. The most recent nationally-representative cross-sectional data (2003-2006) among non-institutionalized US citizens with available serum concentrations of α-tocopherol from the National Health and Nutrition Examination Survey (NHA...
    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the... more
    Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences en-demic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV-and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd an-tibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P 0.0234 and P 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection.
    Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with... more
    Maternal plasma 25-hydroxyvitamin D (25(OH)D) status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OH)D status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63). Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OH)D and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L) and 21% had deficient (<50 nmol/L) plasma 25(OH)D concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OH)D concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI) at enrollment and gestational age at delivery found that deficient plasma 25(OH)D levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04). These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.
    The quantification of analyte concentrations using lateral flow assays is a low-cost and user-friendly alternative to traditional lab-based assays. However, sandwich-type immunoassays are often limited by the high-dose hook effect, which... more
    The quantification of analyte concentrations using lateral flow assays is a low-cost and user-friendly alternative to traditional lab-based assays. However, sandwich-type immunoassays are often limited by the high-dose hook effect, which causes falsely low results when analytes are present at very high concentrations. In this paper, we present a reaction kinetics-based technique that solves this problem, significantly increasing the dynamic range of these devices. With the use of a traditional sandwich lateral flow immunoassay, a portable imaging device, and a mobile interface, we demonstrate the technique by quantifying C-reactive protein concentrations in human serum over a large portion of the physiological range. The technique could be applied to any hook effect-limited sandwich lateral flow assay and has a high level of accuracy even in the hook effect range.
    Acute undifferentiated febrile illnesses (AFIs) represent a significant health burden worldwide. AFIs can be caused by infection with a number of different pathogens including dengue (DENV) and Chikungunya viruses (CHIKV), and their... more
    Acute undifferentiated febrile illnesses (AFIs) represent a significant health burden worldwide. AFIs can be caused by infection with a number of different pathogens including dengue (DENV) and Chikungunya viruses (CHIKV), and their differential diagnosis is critical to the proper patient management. While rapid diagnostic tests (RDTs) for the detection of IgG/IgM against a single pathogen have played a significant role in enabling the rapid diagnosis in the point-of-care settings, the state-of-the-art assay scheme is incompatible with the multiplex detection of IgG/IgM to more than one pathogen. In this paper, we present a novel assay scheme that uses two-color latex labels for rapid multiplex detection of IgG/IgM. Adapting this assay scheme, we show that 4-plex detection of the IgG/IgM antibodies to DENV and CHIKV is possible in 10 min by using it to correctly identify 12 different diagnostic scenarios. We also show that blue, mixed, and red colorimetric signals corresponding to I...

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