Assessing the effect of indoor residual spraying (IRS) on malaria morbidity in Northern Uganda: a before and after study

BACKGROUND : Indoor residual spraying (IRS) is known to reduce malaria transmission. In northern Uganda, a high endemic area, IRS has been implemented since 2006. Limited data however, exists on the effect of IRS on the malaria burden. This study sought to assess the effect of IRS on malaria morbidity in the high intensity area of northern Uganda. Retrospective routine data from ten health facilities in three districts which had received at least five rounds of IRS in northern Uganda was analysed. The primary outcome of interest was malaria morbidity, measured by the slide positivity rate (SPR). Descriptive statistics were used to describe the malaria morbidity stratified by age and sex. The average change in the malaria morbidity, measured by the SPR was assessed according to time, measured as calendar months. A fixed-effects linear regression model was used which included a polynomial function of time and controlled for malaria seasonality and variations between districts/facilities. RESULTS : The total out-patient department attendance in the ten health facilities for the study period was 2,779,246, of which 736,034 (26.5%) malaria cases were diagnosed with 374,826 (50.9%) cases of under 5 years and an overall SPR of 37.5%. The percentage point (p.p.) changes in SPR according to time measured as calendar months following IRS, revealed a decreasing trend in malaria morbidity in the first 3 months following each round of IRS. The highest percentage point decrease in the SPR was observed in the second month following IRS (9.5 p.p., CI −17.85 to −1.16, p = 0.026), among patients above 5 years. The SPR decline however waned by the fourth month following IRS, with an increase in the SPR of 8.4 p.p. at district level by the sixth month, p = 0.510. CONCLUSION : The study results show that IRS was associated with a significant reduction in malaria morbidity in northern Uganda in the first 3 months following IRS. The malaria reduction however waned by the fourth month following IRS.Additional file 1. Details of indoor residual spraying rounds.Measure Evaluation under the post graduate programme at the University of Pretoria.http://www.malariajournal.comam2017School of Health Systems and Public Health (SHSPH

Bias correction by use of errors-in-variables regression models in studies with K-X-ray fluorescence bone lead measurements

In-vivo measurement of bone lead by means of K-X ray fluorescence (KXRF) is the preferred biological marker of chronic exposure to lead. Unfortunately, considerable measurement error associated with KXRF estimations can introduce bias in estimates of the effect of bone lead when this variable is included as the exposure in a regression model. Estimates of uncertainty reported by the KXRF instrument reflect the variance of the measurement error and, although they can be used to correct the measurement error bias, they are seldom used in epidemiological statistical analyses. Errors-in-variables regression (EIV) allows for correction of bias caused by measurement error in predictor variables, based on the knowledge of the reliability of such variables. The authors propose a way to obtain reliability coefficients for bone lead measurements from uncertainty data reported by the KXRF instrument and compare, by use of Monte Carlo simulations, results obtained using EIV regression models versus those obtained by the standard procedures. Results of the simulations show that Ordinary Least Square (OLS) regression models provide severely biased estimates of effect, and that EIV provides nearly unbiased estimates. Although EIV effect estimates are more imprecise, their mean squared error is much smaller than that of OLS estimates. In conclusion, EIV is a better alternative than OLS to estimate the effect of bone lead when measured by KXRF

Variants in Iron Metabolism Genes Predict Higher Blood Lead Levels in Young Children

Background: Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children. Objective: We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children. Methods: Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Blood lead was measured at 24, 30, 36, 42, and 48 months of age. A total of 341 subjects had at least one follow-up blood lead level available and data available on covariates of interest for inclusion in the longitudinal analyses. We used random-effects models to examine the associations between genotype (HFE, TF, and combined HFE + TF) and repeated measures of blood lead, adjusting for maternal blood lead at delivery and child’s concurrent anemia status. Results: Of 422 children genotyped, 17.7, 3.3, and 18.9% carried the HFE H63D, HFE C282Y, and TF P570S variants, respectively. One percent of children carried both the HFE C282Y and TF P570S variants, and 3% of children carried both the HFE H63D and TF P570S variants. On average, carriers of either the HFE (β = 0.11, p = 0.04) or TF (β = 0.10, p = 0.08) variant had blood lead levels that were 11% and 10% higher, respectively, than wild-type subjects. In models examining the dose effect, subjects carrying both variants (β = 0.41, p = 0.006) had blood lead 50% higher than wild-type subjects and a significantly higher odds of having a blood lead level > 10 μg/dL (odds ratio = 18.3; 95% confidence interval, 1.9–177.1). Conclusions: Iron metabolism gene variants modify lead metabolism such that HFE variants are associated with increased blood lead levels in young children. The joint presence of variant alleles in the HFE and TF genes showed the greatest effect, suggesting a gene-by-gene-by-environment interaction

Effect of calcium supplementation on bone resorption in pregnancy and the early postpartum: a randomized controlled trial in Mexican Women

Abstract Background Calcium needs are physiologically upregulated during pregnancy and lactation to meet demands of the developing fetus and breastfeeding infant. Maternal calcium homeostasis is maintained by hormonal adaptive mechanisms, thus, the role of dietary calcium supplementation in altering maternal responses to fetal-infant demand for calcium is thought to be limited. However, increased calcium absorption is directly related to maternal calcium intake and dietary supplementation has been suggested to prevent transient bone loss associated with childbearing. Methods In a double-blind, randomized placebo-controlled trial, we randomly assigned 670 women in their first trimester of pregnancy to 1,200 mg/day calcium (N = 334) or placebo (N = 336). Subjects were followed through 1-month postpartum and the effect on urinary cross-linked N-telopeptides (NTx) of type I collagen, a specific marker of bone resorption, was evaluated using an intent-to-treat analysis. Women with a baseline and at least one follow-up measurement (N = 563; 84%) were included. Subsequent analyses were conducted stratifying subjects by compliance assessed using pill counts. In random subsets of participants, bone-specific alkaline phosphatase (BAP) (N = 100) and quantitative ultrasound (QUS) (N = 290) were also measured. Results Calcium was associated with an overall reduction of 15.8% in urinary NTx relative to placebo (p < 0.001). Among those who consumed ≥50%, ≥67%, and ≥75% of pills, respectively, the effect was associated with 17.3%, 21.3%, and 22.1% reductions in bone resorption (all p < 0.001). There was no significant effect of calcium on bone formation measured by BAP. However, by 1-month postpartum, those in the calcium group had significantly lower NTx/BAP ratios than those in the placebo group (p = 0.04) indicating a net reduction in bone loss in the supplement group by the end of follow-up. Among subjects who consumed ≥50% and ≥75% of pills, respectively, calcium was also associated with an increase of 26.3 m/s (p = 0.03) and 59.0 m/s (p = 0.009) in radial SOS relative to placebo by 1-month postpartum. Conclusions Calcium administered during pregnancy and the early postpartum period, to women with intakes around adequacy, was associated with reduced bone resorption and, thus, may constitute a practical intervention to prevent transient skeletal loss associated with childbearing. Trial registration ClinicalTrials.gov Identifier NCT00558623http://deepblue.lib.umich.edu/bitstream/2027.42/110126/1/12937_2014_Article_851.pd

Fetal Lead Exposure at Each Stage of Pregnancy as a Predictor of Infant Mental Development

BACKGROUND: The impact of prenatal lead exposure on neurodevelopment remains unclear in terms of consistency, the trimester of greatest vulnerability, and the best method for estimating fetal lead exposure. OBJECTIVE: We studied prenatal lead exposure’s impact on neurodevelopment using repeated measures of fetal dose as reflected by maternal whole blood and plasma lead levels. METHODS: We measured lead in maternal plasma and whole blood during each trimester in 146 pregnant women in Mexico City. We then measured umbilical cord blood lead at delivery and, when offspring were 12 and 24 months of age, measured blood lead and administered the Bayley Scales of Infant Development. We used multivariate regression, adjusting for covariates and 24-month blood lead, to compare the impacts of our pregnancy measures of fetal lead dose. RESULTS: Maternal lead levels were moderately high with a first-trimester blood lead mean (± SD) value of 7.1 ± 5.1 μg/dL and 14% of values ≥10 μg/dL. Both maternal plasma and whole blood lead during the first trimester (but not in the second or third trimester) were significant predictors (p < 0.05) of poorer Mental Development Index (MDI) scores. In models combining all three trimester measures and using standardized coefficients, the effect of first-trimester maternal plasma lead was somewhat greater than the effect of first-trimester maternal whole blood lead and substantially greater than the effects of second- or third-trimester plasma lead, and values averaged over all three trimesters. A 1-SD change in first-trimester plasma lead was associated with a reduction in MDI score of 3.5 points. Postnatal blood lead levels in the offspring were less strongly correlated with MDI scores. CONCLUSIONS: Fetal lead exposure has an adverse effect on neurodevelopment, with an effect that may be most pronounced during the first trimester and best captured by measuring lead in either maternal plasma or whole blood

Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

Background Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility. Objective This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples. Methods We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source 109Cd K-shell X-ray fluorescence instrument. Results We found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation. Conclusions Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course

Design and efficacy of an Ecohealth competency-based course on the prevention and control of vector diseases in Latin America

Objective. To design and analyze the efficacy of an Ecohealth competency-based course on the prevention and control of vector-borne-diseases for specific stakeholders. Materials and methods. Multiple stakeholders and sectors of the region were consulted to identify Ecohealth group-specific competencies using an adjusted analysis matrix. Eight courses based on the competencies were implemented to train EA tutors. The effectiveness of the course was evaluated through the use of paired- t-tests by intervention group. Results. Strategic, tactical, academia and community stakeholder groups and their competencies were identified. An overall gain of 43 percentage points (p<0.001) was observed in terms of competencies score in trained tutors, which further trained 1 033 people. Conclusion. The identification of the stakeholders and their competencies proved to be useful to guide training courses to significantly improve the initial competencies and create a critical mass to further advance the EA in the regio

Associations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment

Background: Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals

Association between the plasma/whole blood lead ratio and history of spontaneous abortion: a nested cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Blood lead has been associated with an elevated risk of miscarriage. The plasmatic fraction of lead represents the toxicologically active fraction of lead. Women with a tendency to have a higher plasma/whole blood Pb ratio could tend towards an elevated risk of miscarriage due to a higher plasma Pb for a given whole blood Pb and would consequently have a history of spontaneous abortion.</p> <p>Methods</p> <p>We studied 207 pregnant Mexico City residents during the 1^sttrimester of pregnancy, originally recruited for two cohorts between 1997 and 2004. Criteria for inclusion in this study were having had at least one previous pregnancy, and having valid plasma and blood Pb measurements. Pb was measured in whole blood and plasma by inductively coupled plasma mass spectrometry using ultra-clean techniques. History of miscarriage in previous pregnancies was obtained by interview. The incidence rate of spontaneous abortion was defined as the proportion of previous pregnancies that resulted in miscarriage. Data were analyzed by means of Poisson regression models featuring the incidence rate of spontaneous abortion as the outcome and continuous or categorized plasma/blood Pb ratios as predictor variables. All models were adjusted for age and schooling. Additionally, logistic regression models featuring inclusion in the study sample as the outcome were fitted to assess potential selection bias.</p> <p>Results</p> <p>The mean number of miscarriages was 0.42 (range 0 to 4); mean Pb concentrations were 62.4 and 0.14 μg/L in whole blood and plasma respectively. Mean plasma/blood Pb ratio was 0.22%. We estimated that a 0.1% increment in the plasma/blood Pb ratio lead was associated to a 12% greater incidence of spontaneous abortion (p = 0.02). Women in the upper tertile of the plasma/blood Pb ratio had twice the incidence rate of those in the lower tertile (p = 0.02). Conditional on recruitment cohort, inclusion in the study sample was unrelated to observable characteristics such as number of abortions, number of pregnancies, blood Pb levels, age schooling, weight and height.</p> <p>Conclusion</p> <p>Women with a large plasma/whole blood Pb ratio may be at higher risk of miscarriage, which could be due to a greater availability of placental barrier-crossing Pb.</p