Increased Iron Status during a Feeding Trial of Iron-Biofortified Beans Increases Physical Work Efficiency in Rwandan Women.

BACKGROUND: Iron-biofortified staple foods can improve iron status and resolve iron deficiency. However, whether improved iron status from iron biofortification can improve physical performance remains unclear. OBJECTIVE: This study aimed to examine whether changes in iron status from an iron-biofortified bean intervention affect work efficiency. METHODS: A total of 125 iron-depleted (ferritin <20 µg/L) female Rwandan university students (18-26 y) were selected from a larger sample randomly assigned to consume iron-biofortified beans (Fe-Bean; 86.1 mg Fe/kg) or conventional beans (control: 50.6 mg Fe/kg) twice daily for 18 wk (average of 314 g beans consumed/d). Blood biomarkers of iron status (primary outcome) and physical work efficiency (secondary outcome) were measured before and after the intervention. Work performed was assessed during 5-min steady-state periods at 0-, 25-, and 40-W workloads using a mechanically braked cycle ergometer. Work efficiency was calculated at 25 W and 40 W as the work accomplished divided by the energy expended at that workload above that expended at 0 W. General linear models were used to evaluate the relation between changes in iron status biomarkers and work efficiency. RESULTS: The Fe-Bean intervention had significant positive effects on hemoglobin, serum ferritin, and body iron stores but did not affect work efficiency. However, 18-wk change in hemoglobin was positively related to work efficiency at 40 W in the full sample (n = 119; estimate: 0.24 g/L; 95% CI: 0.01, 0.48 g/L; P = 0.044) and among women who were anemic (hemoglobin <120 g/L) at baseline (n = 43; estimate: 0.64 g/L; 95% CI: 0.05, 1.23 g/L; P = 0.036). Among women who were nonanemic at baseline, change in serum ferritin was positively related to change in work efficiency at 40 W (n = 60; estimate: 0.50 µg/L; 95% CI: 0.06, 0.95 µg/L; P = 0.027). CONCLUSIONS: Increasing iron status during an iron-biofortified bean feeding trial improves work efficiency in iron-depleted, sedentary women. This trial was registered at clinicaltrials.gov as NCT01594359.

Changes in Iron Status Are Related to Changes in Brain Activity and Behavior in Rwandan Female University Students: Results from a Randomized Controlled Efficacy Trial Involving Iron-Biofortified Beans.

BACKGROUND: Evidence suggests that iron deficiency (ID) affects cognitive performance, as measured in behavior. Although such effects must be mediated by changes in the brain, very few studies have included measures of brain activity to assess this relation. OBJECTIVE: We tested the hypothesis that provision of iron-biofortified beans would result in improvements in measures of iron status, brain dynamics, and behavior. METHODS: A double-blind, randomized, intervention study was conducted in 55 women aged 18-27 y with low iron status (serum ferritin <20 µg/L). Women were randomly assigned to consume iron-biofortified (86.1 ppm iron) or comparison beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed by hemoglobin, ferritin, transferrin receptor, and body iron; cognitive performance with 5 computerized tasks; and brain dynamics by concurrent electroencephalography (EEG). All measures were taken at baseline and endline. RESULTS: The groups did not differ on any measures at baseline. Intention-to-treat analyses revealed significant (all P < 0.05) improvements in hemoglobin (partial effect size attributable to the independent variable, η2 = 0.16), ferritin (η2 = 0.17), and body iron (η2 = 0.10), speed of responding in attentional and mnemonic tasks (η2 = 0.04-0.29), sensitivity and efficiency of memory retrieval (η2 = 0.12-0.55), and measures of EEG amplitude and spectral power (η2 = 0.08 to 0.49). Mediation models provided evidence in support of the hypothesis that changes in iron status produce changes in behavior by way of changes in brain activity. CONCLUSIONS: Behavioral performance and brain activity, as measured by EEG, are sensitive to iron status, and the consumption of iron-biofortified beans for 18 wk resulted in improvements in measures of both, relative to what was obtained with a comparison bean, in a sample of female university students. Furthermore, the results support the conclusion that changes in brain activity resulting from consumption of biofortified beans mediate the relations between changes in iron biomarkers and changes in cognition. Clinical trial registry: ClinicalTrials.gov Reg No. NCT01594359.

Co-infections with Plasmodium, Ascaris and Giardia among Rwandan schoolchildren.

OBJECTIVES: Co-infections with Plasmodium, Ascaris and Giardia are common in sub-Saharan Africa but epidemiological and clinical data are rare. We examined factors associated with co-infections and their clinical manifestation among Rwandan schoolchildren. METHODS: Schoolchildren aged 6-10 years attending 12 schools in Huye district, Rwanda, were recruited preceding routine deworming. Data on socioeconomic status (SES) and children's histories were obtained, and children were clinically and anthropometrically examined. Blood and stool samples were collected, and infections with Plasmodium, Ascaris and Giardia were determined by microscopy and PCR assays. RESULTS: Among 878 schoolchildren, Plasmodium, Ascaris and Giardia were present in 22%, 35% and 36%, respectively. Co-infections with two or more parasites were found in 24%; only one-third of the children did not harbour any of the parasites examined. Factors associated with parasite (co-)infections largely overlapped and reflected low SES, in addition to a few specific risk factors. Clinically, most children were asymptomatic but anaemia (38%), underweight (17%), and reported signs and symptoms in the preceding 2 weeks (46%) were common. Many of the reported and assessed signs and symptoms were associated with Plasmodium infection, and co-infection with Ascaris and/or Giardia did basically not modify the clinical picture. One exception was malnutrition, which was pronounced in Ascaris-Giardia co-infection vs. individual mono-infections. CONCLUSIONS: Parasitic co-infections are common in Rwandan schoolchildren, and are associated with a rather silent clinical manifestation that nevertheless may affect school performance and long-term development. School-based health interventions should target such co-infections in an integrated manner.

OBJECTIFS: Les coinfections par Plasmodium, Ascaris et Giardia sont courantes en Afrique subsaharienne, mais les données épidémiologiques et cliniques sont rares. Nous avons examiné les facteurs associés aux coinfections et leurs manifestations cliniques chez les écoliers rwandais. MÉTHODES: Des écoliers âgés de 6 à 10 ans fréquentant 12 écoles du district de Huye au Rwanda ont été recrutés avant le déparasitage de routine. Les données sur le statut socioéconomique (SSE) et les antécédents des enfants ont été obtenues et les enfants ont été examinés cliniquement et anthropométriquement. Des échantillons de sang et de selles ont été recueillis et les infections à Plasmodium, Ascaris et Giardia ont été déterminées par microscopie et par PCR. RÉSULTATS: sur 878 écoliers, Plasmodium, Ascaris et Giardia étaient présents chez 22%, 35% et 36%, respectivement. Des coinfections avec deux parasites ou plus ont été trouvées chez 24%; seul un tiers des enfants n'hébergeait aucun des parasites examinés. Les facteurs associés aux (co)infections parasitaires se chevauchaient largement et reflétaient un faible statut SSE, en plus de quelques facteurs de risque spécifiques. Sur le plan clinique, la plupart des enfants étaient asymptomatiques mais l'anémie (38%), l'insuffisance pondérale (17%) et les signes et symptômes rapportés au cours des deux semaines précédentes (46%) étaient fréquents. De nombreux signes et symptômes rapportés et évalués étaient associés à l'infection au Plasmodium et la coinfection par Ascaris et/ou Giardia n'a fondamentalement pas modifié le tableau clinique. Une exception était la malnutrition, qui était prononcée dans la coinfection Ascaris-Giardia par rapport aux mono-infections individuelles. CONCLUSIONS: Les coinfections parasitaires sont courantes chez les écoliers rwandais et sont associées à une manifestation clinique plutôt silencieuse qui peut néanmoins affecter les performances scolaires et le développement à long terme. Les interventions de santé en milieu scolaire devraient cibler ces coinfections de manière intégrée.

Intense pre-admission carriage and further acquisition of ESBL-producing Enterobacteriaceae among patients and their caregivers in a tertiary hospital in Rwanda.

OBJECTIVES: To assess the presence and risk factors of intestinal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) among patients admitted to the University Teaching Hospital of Butare and among their attending caregivers, and to analyse the acquisition of ESBL-PE carriage during hospital stay and associated factors. METHODS: We screened 392 patients and their attending caregivers at admission and discharge for ESBL-PE carriage. Bacterial species were determined using the API-20E system, and antimicrobial susceptibility testing was performed by agar disc diffusion. Data on socio-economic status, diet, behaviour, household assets, livestock and hospital procedures were collected. RESULTS: At admission, 50% of the patients showed intestinal ESBL-PE carriage (Escherichia coli, 51%; Klebsiella pneumoniae, 39%; Enterobacter cloacae, 19%) as did 37% of their caregivers. Co-resistance was common but no carbapenem resistance was detected. At discharge, the proportion of ESBL-PE-colonised patients increased to 65% (caregivers, 47%) with almost complete carriage in paediatric patients (93%). The acquisition rate among initially non-colonised patients was 55% (or, 71/1000 patient days). Independent predictors of admission carriage included a colonised caregiver, prior antibiotic intake, egg consumption and neglecting to boil drinking water, whereas being a paediatric patient, undergoing surgery and male gender predicted acquisition during hospitalisation. CONCLUSIONS: Abundant admission carriage of ESBL-PE and a high acquisition rate in a Rwandan university hospital point to potential intrahospital transmission and community dissemination. Caregivers are an additional source of possible spread. Risk factors of colonisation such as diet and water source need to be tackled to prevent the further emergence and spread of ESBL-PE.

Consuming Iron Biofortified Beans Increases Iron Status in Rwandan Women after 128 Days in a Randomized Controlled Feeding Trial.

BACKGROUND: Food-based strategies to reduce nutritional iron deficiency have not been universally successful. Biofortification has the potential to become a sustainable, inexpensive, and effective solution. OBJECTIVE: This randomized controlled trial was conducted to determine the efficacy of iron-biofortified beans (Fe-Beans) to improve iron status in Rwandan women. METHODS: A total of 195 women (aged 18-27 y) with serum ferritin <20 µg/L were randomly assigned to receive either Fe-Beans, with 86 mg Fe/kg, or standard unfortified beans (Control-Beans), with 50 mg Fe/kg, 2 times/d for 128 d in Huye, Rwanda. Iron status was assessed by hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), and body iron (BI); inflammation was assessed by serum C-reactive protein (CRP) and serum α1-acid glycoprotein (AGP). Anthropometric measurements were performed at baseline and at end line. Random weekly serial sampling was used to collect blood during the middle 8 wk of the feeding trial. Mixed-effects regression analysis with repeated measurements was used to evaluate the effect of Fe-Beans compared with Control-Beans on iron biomarkers throughout the course of the study. RESULTS: At baseline, 86% of subjects were iron-deficient (serum ferritin <15 µg/L) and 37% were anemic (hemoglobin <120 g/L). Both groups consumed an average of 336 g wet beans/d. The Fe-Beans group consumed 14.5 ± 1.6 mg Fe/d from biofortified beans, whereas the Control-Beans group consumed 8.6 ± 0.8 mg Fe/d from standard beans (P < 0.05). Repeated-measures analyses showed significant time-by-treatment interactions for hemoglobin, log serum ferritin, and BI (P < 0.05). The Fe-Beans group had significantly greater increases in hemoglobin (3.8 g/L), log serum ferritin (0.1 log µg/L), and BI (0.5 mg/kg) than did controls after 128 d. For every 1 g Fe consumed from beans over the 128 study days, there was a significant 4.2-g/L increase in hemoglobin (P < 0.05). CONCLUSION: The consumption of iron-biofortified beans significantly improved iron status in Rwandan women. This trial was registered at clinicaltrials.gov as NCT01594359.

In Rwandese Women with Low Iron Status, Iron Absorption from Low-Phytic Acid Beans and Biofortified Beans Is Comparable, but Low-Phytic Acid Beans Cause Adverse Gastrointestinal Symptoms.

BACKGROUND: Phytic acid (PA) is a major inhibitor of iron bioavailability from beans, and high PA concentrations might limit the positive effect of biofortified beans (BBs) on iron status. Low-phytic acid (lpa) bean varieties could increase iron bioavailability. OBJECTIVE: We set out to test whether lpa beans provide more bioavailable iron than a BB variety when served as part of a composite meal in a bean-consuming population with low iron status. METHODS: Dietary iron absorption from lpa, iron-biofortified, and control beans (CBs) (regular iron and PA concentrations) was compared in 25 nonpregnant young women with low iron status with the use of a multiple-meal crossover design. Iron absorption was measured with stable iron isotopes. RESULTS: PA concentration in lpa beans was ∼10% of BBs and CBs, and iron concentration in BBs was ∼2- and 1.5-fold compared with CBs and lpa beans, respectively. Fractional iron absorption from lpa beans [8.6% (95% CI: 4.8%, 15.5%)], BBs [7.3% (95% CI: 4.0%, 13.4%)], and CBs [8.0% (95% CI: 4.4%, 14.6%)] did not significantly differ. The total amount of iron absorbed from lpa beans and BBs was 421 µg (95% CI: 234, 756 µg) and 431 µg (95% CI: 237, 786 µg), respectively, and did not significantly differ, but was >50% higher (P < 0.005) than from CBs (278 µg; 95% CI: 150, 499 µg). In our trial, the lpa beans were hard to cook, and their consumption caused transient adverse digestive side effects in ∼95% of participants. Gel electrophoresis analysis showed phytohemagglutinin L (PHA-L) residues in cooked lpa beans. CONCLUSION: BBs and lpa beans provided more bioavailable iron than control beans and could reduce dietary iron deficiency. Digestive side effects of lpa beans were likely caused by PHA-L, but it is unclear to what extent the associated digestive problems reduced iron bioavailability. This trial was registered at clinicaltrials.gov as NCT02215278.

Reduced prevalence of Giardia duodenalis in iron-deficient Rwandan children.

OBJECTIVE: Acute symptomatic infection with Giardia duodenalis impairs iron absorption, but iron deficiency may protect against infections caused by various micro-organisms including parasites. We therefore examined the association of G. duodenalis infection and iron deficiency in 575 Rwandan children under 5 years of age. METHODS: Giardia duodenalis infection was diagnosed by triplicate microscopy and PCR assays, and iron deficiency was defined as a ferritin concentration <12 ng/ml. RESULTS: Largely asymptomatic G. duodenalis infection was seen in 65.3% of the children and iron deficiency in 17.4%. G. duodenalis infection was less common in iron-deficient children (51%) than in non-deficient children (68%, P = 0.002). In multivariate analysis, the odds of G. duodenalis infection were almost halved in iron-deficient children (adjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86). CONCLUSION: In this highly endemic setting, there was no evidence that Giardia infection impairs iron status. Rather, iron deficiency appeared to protect against infection with this parasite.

No association of the p53 codon 72 polymorphism with malaria in Ghanaian primiparae and Rwandan children.

The p53 protein is a key cell-signaling mediator integrating host responses to various types of stress. A common polymorphism of the encoding TP53 gene (codon 72, Pro > Arg, rs1042522) is associated with susceptibility to virus-related and other cancers. The p53 has also been shown to be central for successful Plasmodium liver stage infection. We examined whether the polymorphism is associated with P. falciparum infection in Ghanaian primiparae and Rwandan children. The allele frequency of TP53 codon 72 Arg was 0.30 among 314 Ghanaian primiparae and 0.31 among 545 Rwandan children, respectively, and it was not associated with infection prevalence or parasite density. This does not exclude p53 to be of pathophysiological relevance in malaria but argues against a major respective role of the TP53 codon 72 polymorphism.

Anaemia, iron deficiency and a common polymorphism of iron-regulation, TMPRSS6 rs855791, in Rwandan children.

Anaemia in children living in sub-Saharan Africa is common, but its causes are diverse. In 545 children below 5 years of age from rural southern Rwanda, we assessed the role of iron deficiency (ID) and of the TMPRSS6 736(V) (rs855791) allele, known to reduce iron status and haemoglobin (Hb) levels, in anaemia and Hb concentrations. Anaemia (Hb <11 g/dl) was present in 34.4% of the children and ID (ferritin <12 ng/ml) in 17.6%. The TMPRSS6 736(V) allele was uncommon (allele frequency, 0.096) and not associated with ID. In multivariate analysis, ID was positively associated with anaemia (adjusted odds ratio, 1.67) to an extent comparable with α(+) -thalassaemia, breastfeeding, inflammation and low household income, but the odds were substantially higher in Plasmodium falciparum infection (adjusted odds ratio, 10.3). These findings were verified in a multivariate analysis of Hb concentrations. The TMPRSS6 736(V) allele only tended to be associated with low Hb levels. TMPRSS6 736(V) is comparatively rare among Rwandan children and may only slightly contribute to low Hb concentrations. Preventable causes of anaemia, notably ID and P. falciparum infection, largely outweigh its impact and need to be addressed to improve the haematological status of children in the study area.

High prevalence of cysticercosis in people with epilepsy in southern Rwanda.

BACKGROUND: Neurocysticercosis (NCC), the central nervous system infection by Taenia solium larvae, is a preventable and treatable cause of epilepsy. In Sub-Saharan Africa, the role of NCC in epilepsy differs geographically and, overall, is poorly defined. We aimed at contributing specific, first data for Rwanda, assessing factors associated with NCC, and evaluating a real-time PCR assay to diagnose NCC in cerebrospinal fluid (CSF). METHODOLOGY/PRINCIPAL FINDINGS: At three healthcare facilities in southern Rwanda, 215 people with epilepsy (PWE) and 51 controls were clinically examined, interviewed, and tested by immunoblot for cysticerci-specific serum antibodies. Additionally, CSF samples from PWE were tested for anticysticercal antibodies by ELISA and for parasite DNA by PCR. Cranial computer tomography (CT) scans were available for 12.1% of PWE with additional symptoms suggestive of NCC. The Del Brutto criteria were applied for NCC diagnosis. Cysticerci-specific serum antibodies were found in 21.8% of PWE and 4% of controls (odds ratio (OR), 6.69; 95% confidence interval (95%CI), 1.6-58.7). Seropositivity was associated with age and lack of safe drinking water. Fifty (23.3%) PWE were considered NCC cases (definitive, based on CT scans, 7.4%; probable, mainly based on positive immunoblots, 15.8%). In CSF samples from NCC cases, anticysticercal antibodies were detected in 10% (definitive cases, 25%) and parasite DNA in 16% (definitive cases, 44%). Immunoblot-positive PWE were older (medians, 30 vs. 22 years), more frequently had late-onset epilepsy (at age >25 years; 43.5% vs. 8.5%; OR, 8.30; 95%CI, 3.5-20.0), and suffered from significantly fewer episodes of seizures in the preceding six months than immunoblot-negative PWE. CONCLUSIONS/SIGNIFICANCE: NCC is present and contributes to epilepsy in southern Rwanda. Systematic investigations into porcine and human cysticercosis as well as health education and hygiene measures for T. solium control are needed. PCR might provide an additional, highly specific tool in NCC diagnosis.