Q fever presenting as miliary pneumonia: Case imagery and differential diagnosis

Abstract: Case/imagery description: A 56-year-old immunocompetent male consulted for one month of relapsing fever, moderate dyspnea, non-productive cough, headaches, and myalgias. Past medical history was unremarkable except for exposure to a variety of livestock carcasses. A computed tomographic scan revealed innumerable randomly distributed 1-3mm micronodules. Initial diagnostic workup including bronchoalveolar lavage (BAL) was inconclusive. STUDY QUESTIONS: Is this miliary pneumonia? What diagnosis must initially be considered? In this specific case with negative BAL analysis/cultures, what would your differential diagnosis be? Is Q fever a possibility

Étude de cohorte sur les fonctions neurocomportementales de travailleurs 14 ans après la fin de l'exposition au manganèse

L'inhalation de particules de manganèse (Mn) peut causer des effets neurotoxiques qui se manifestent par des altérations des fonctions neurocomportementales, nommément des symptômes psychologiques et des déficits cognitifs et moteurs. Une première étude fut menée en 1990 sur les fonctions neurocomportementales de travailleurs exposés au Mn dans une usine de production d'alliages ferro-Mn et silico-Mn; des hommes cols bleus non-exposés au Mn servirent de groupe de comparaison (référents). Pour chaque travailleur, l'exposition aux poussières et aux fumées de Mn dans l'air au moment de l'étude a été estimée et un indice d'exposition cumulée sur toute la durée d'emploi dans l'usine a été calculé. L'usine a arrêté ses opérations quelques mois après la fin de cette étude, mais cette fermeture n'était pas liée aux résultats de l'étude. Dans la première partie de la thèse, l'objectif était d'examiner l'effet modificateur de l'âge dans les altérations neurocomportementales. L'analyse des données appariées (74 paires) a montré que les différences de scores aux tests neurocomportementaux entre les travailleurs exposés au Mn et les référents (ces différences représentant l'effet du Mn) augmentaient significativement avec l'âge pour la mémoire, la concentration, la flexibilité cognitive, la stabilité des mains et la sensibilité tactile. L'âge n'était pas associé à la concentration de Mn dans l'air au moment de l'étude, ni à l'exposition cumulée, indiquant que les déficits plus prononcés les travailleurs plus âgés ne peuvent pas être expliqués par une exposition supérieure chez ces derniers. Ces résultats indiquent que, à exposition égale, les travailleurs plus âgés sont davantage affectés que les plus jeunes par les effets du Mn sur certaines fonctions nerveuses. Pour la seconde partie de la thèse, nous avons mené une étude de suivi auprès de 78 anciens employés de l'usine et 81 référents afin de vérifier le degré de réversibilité ou d'aggravation des atteintes neurofonctionnelles 14 ans après la fin de l'exposition. Les travailleurs ayant été exposés au Mn ainsi que les référents ayant accepté de participer à l'étude de suivi ont complété une batterie de tests similaire à celle utilisée en 1990. Nous avons émis l'hypothèse que ces atteintes s'aggraveraient avec le temps, et qu'elles seraient donc plus marquées au moment du suivi (2004) que lors de l'étude initiale (1990). En effet, la progression des signes neurologiques a été rapportée lors d'études longitudinales portant sur des travailleurs gravement intoxiqués au Mn, ainsi que des travailleurs exposés à d'autres substances neurotoxiques, notamment les solvants organiques et le plomb. Globalement, les résultats indiquent que la performance pour plusieurs des tests que les travailleurs exposés avaient moins bien réussi en 1990 n'était pas différente entre les exposés et les référents en 2004. Néanmoins, les déficits de vitesse motrice (membres supérieurs) observés en 1990 étaient toujours présents en 2004. Par ailleurs, les travailleurs ayant été exposés au Mn et qui étaient âgés de plus de 45 ans lorsque l'exposition a cessée ont obtenu une performance significativement inférieure aux référents d'âge similaire à trois tests de flexibilité cognitive. Ensuite, pour certains tests moteurs et cognitifs, la performance était significativement et inversement associée à l'exposition cumulée au Mn. En somme, les résultats révèlent deux trajectoires possibles : i) un maintien des déficits, ou ii) une récupération des fonctions, particulièrement pour les moins exposés. L'hypothèse d'aggravation des déficits n'a donc pas été retenue, mais un autre suivi de la cohorte à un âge plus avancé (ici, l'âge moyen était 57 ans au moment du suivi) serait souhaitable pour connaître l'évolution des fonctions neurocomportementales en fonction de l'exposition au cours du vieillissement. Ensuite, un questionnaire portant sur les symptômes neuropsychiatriques a été ajouté à la batterie de tests administrée en 2004 afin d'examiner plus profondément ce domaine neurofonctionnel. En effet, certaines données dans la littérature indiquent que les questionnaires de symptômes neuropsychiatriques sont particulièrement sensibles aux effets du Mn sur le système nerveux. Le résultat des analyses a montré une relation significative entre l'exposition cumulée au Mn et les scores aux échelles Somatisation, Dépression, Anxiété et Hostilité. Les travailleurs dans les deux tertiles supérieurs d'exposition cumulée avaient un risque significatif d'avoir un score élevé aux échelles Hostilité, Dépression et Anxiété. Ces résultats suggèrent que l'exposition cumulée au Mn est associée à la gravité des symptômes neuropsychiatriques jusqu'à 14 ans après la fin de l'exposition. Nos travaux ont mis en évidence la vulnérabilité des travailleurs plus âgés aux effets neurotoxiques du Mn. Le suivi de cette cohorte de travailleurs plusieurs années après la fin de l'exposition a montré un portrait complexe de changements des atteintes neurofonctionnelles, où certaines atteintes sont partiellement réversibles, particulièrement chez les moins exposés, alors que d'autres atteintes persistent, particulièrement chez les plus âgés. Nous estimons que la possibilité de récupération neurofonctionnelle après la fin de l'exposition devrait encourager les mesures de réduction des concentrations de Mn dans les milieux de travail concernés par ce risque. En même temps, la persistance de certaines atteintes associées à l'exposition au Mn, et cela jusqu'à 14 ans après la fin de l'exposition, montre l'importance de prévenir celles-ci. Il semble que l'exposition cumulée à ce métal soit déterminante dans l'apparition des signes de neurotoxicité. La concentration de Mn dans l'air de l'usine où étaient employés les travailleurs à l'étude ici respectait la norme d'exposition, norme toujours en vigueur aujourd'hui. L'exposition cumulée au Mn était en deçà de 100 mg/m3 x année et a néanmoins été associée à des effets néfastes durables sur certaines fonctions neurocomportementales. Or, un travailleur exposé à la valeur maximale légalement admise pendant 35 ans aurait un indice d'exposition cumulée encore plus élevé, soit de 175 mg/m3 x année, ce qui suggère que la norme actuelle d'exposition ne protège probablement pas la santé de tous les travailleurs.\ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : manganèse, travailleurs, neurotoxique, neurocomportemental, exposition cumulé

Hair Manganese and Hyperactive Behaviors: Pilot Study of School-Age Children Exposed through Tap Water

BACKGROUND: Neurotoxic effects are known to occur with inhalation of manganese particulates, but very few data are available on exposure to Mn in water. We undertook a pilot study in a community in Québec (Canada) where naturally occurring high Mn levels were present in the public water system. Our objective was to test the hypothesis that greater exposure to Mn via drinking water would be reflected in higher Mn content in hair which, in turn, would be associated with increased level of hyperactive behaviors. METHODS: Forty-six children participated in the study, 24 boys and 22 girls, 6–15 years of age (median, 11 years). Their homes received water from one of two wells (W) with different Mn concentrations: W1: mean 610 μg/L; W2: mean 160 μg/L. The Revised Conners’ Rating Scale for parents (CPRS-R) and for teachers (CTRS-R) were administered, providing T-scores on the following subscales: Oppositional, Hyperactivity, Cognitive Problems/Inattention, and ADHD Index. RESULTS: Children whose houses were supplied by W1 had higher hair Mn (MnH) than those supplied by W2 (mean 6.2 ± 4.7 μg/g vs. 3.3 ± 3.0 μg/g, p = 0.025). MnH was significantly associated with T-scores on the CTRS-R Oppositional (p = 0.020) and Hyperactivity (p = 0.002) subscales, after adjustment for age, sex, and income. All children with Oppositional and Hyperactivity T-scores ≥ 65 had MnH > 3.0 μg/g. CONCLUSIONS: The findings of this pilot study are sufficiently compelling to warrant more extensive investigations into the risks of Mn exposure in drinking water

Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada — Results from the MIREC study

AbstractOrganophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56–62) and 21 (95% CI 20–22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment

Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children

Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development

Manganese concentrations in drinking water from villages near banana plantations with aerial mancozeb spraying in Costa Rica: Results from the Infants' Environmental Health Study (ISA)

AbstractElevated manganese (Mn) in drinking water has been reported worldwide. While, naturally occurring Mn in groundwater is generally the major source, anthropogenic contamination by Mn-containing fungicides such as mancozeb may also occur. The main objective of this study was to examine factors associated with Mn and ethylenethiourea (ETU), a degradation product of mancozeb, in drinking water samples from villages situated near banana plantations with aerial spraying of mancozeb. Drinking water samples (n = 126) were obtained from 124 homes of women participating in the Infants' Environmental Health Study (ISA, for its acronym in Spanish), living nearby large-scale banana plantations. Concentrations of Mn, iron (Fe), arsenic (As), lead (Pb), cadmium (Cd) and ethylenethiourea (ETU), a degradation product of mancozeb, were measured in water samples. Only six percent of samples had detectable ETU concentrations (limit of detection (LOD) = 0.15 μg/L), whereas 94% of the samples had detectable Mn (LOD = 0.05 μg/L). Mn concentrations were higher than 100 and 500 μg/L in 22% and 7% of the samples, respectively. Mn was highest in samples from private and banana farm wells. Distance from a banana plantation was inversely associated with Mn concentrations, with a 61.5% decrease (95% CI: −97.0, −26.0) in Mn concentrations for each km increase in distance. Mn concentrations in water transported with trucks from one village to another were almost 1000 times higher than Mn in water obtained from taps in houses supplied by the same well but not transported, indicating environmental Mn contamination. Elevated Mn in drinking water may be partly explained by aerial spraying of mancozeb; however, naturally occurring Mn in groundwater, and intensive agriculture may also contribute. Drinking water risk assessment for mancozeb should consider Mn as a health hazard. The findings of this study evidence the need for health-based World Health Organization (WHO) guidelines on Mn in drinking water

Neurobehavioral Function in School-Age Children Exposed to Manganese in Drinking Water

Background: Manganese neurotoxicity is well documented in individuals occupationally exposed to airborne particulates, but few data are available on risks from drinking-water exposure. Objective: We examined associations of exposure from concentrations of manganese in water and hair with memory, attention, motor function, and parent- and teacher-reported hyperactive behaviors. Methods: We recruited 375 children and measured manganese in home tap water (MnW) and hair (MnH). We estimated manganese intake from water ingestion. Using structural equation modeling, we estimated associations between neurobehavioral functions and MnH, MnW, and manganese intake from water. We evaluated exposure–response relationships using generalized additive models. Results: After adjusting for potential confounders, a 1-SD increase in log10 MnH was associated with a significant difference of –24% (95% CI: –36, –12%) SD in memory and –25% (95% CI: –41, –9%) SD in attention. The relations between log10 MnH and poorer memory and attention were linear. A 1-SD increase in log10 MnW was associated with a significant difference of –14% (95% CI: –24, –4%) SD in memory, and this relation was nonlinear, with a steeper decline in performance at MnW > 100 μg/L. A 1-SD increase in log10 manganese intake from water was associated with a significant difference of –11% (95% CI: –21, –0.4%) SD in motor function. The relation between log10 manganese intake and poorer motor function was linear. There was no significant association between manganese exposure and hyperactivity. Conclusion: Exposure to manganese in water was associated with poorer neurobehavioral performances in children, even at low levels commonly encountered in North America. Citation: Oulhote Y, Mergler D, Barbeau B, Bellinger DC, Bouffard T, Brodeur ME, Saint-Amour D, Legrand M, Sauvé S, Bouchard MF. 2014. Neurobehavioral function in school-age children exposed to manganese in drinking water. Environ Health Perspect 122:1343–1350; http://dx.doi.org/10.1289/ehp.130791

Lead Exposure and Behavior among Young Children in Chennai, India

Background: Lead exposure has long been associated with deficits in IQ among children. However, few studies have assessed the impact of lead on specific domains of behavior and cognition. Objective: We evaluated the associations between lead and different domains of neurobehavior and their relative sensitivity to lead. Methods: We determined blood lead levels using a LeadCare instrument in 756 children 3–7 years of age attending pre- and elementary schools in Chennai, India. Anxiety, social problems, inattention, hyperactivity, and attention deficit hyperactivity disorder (ADHD), as well as executive function were assessed in children by their schoolteachers using Conners’ Teacher Rating Scales-39, Conners’ ADHD/Diagnostic and Statistical Manual for Mental Disorders, 4th Edition Scales (CADS), and the Behavior Rating Inventory of Executive Function questionnaires, with higher scores denoting worse behavior. Analyses were carried out using multivariate generalized estimating equations with comparisons of outcome Z-scores to assess the relative strengths of the associations between log-blood lead and the different domains of behavior. Results: Mean blood lead level was 11.4 ± 5.3 μg/dL. Blood lead was associated with higher anxiety (β = 0.27, p = 0.01), social problems (β = 0.20, p = 0.02), and higher scores in the ADHD index (β = 0.17; p = 0.05). The effect estimate was highest for global executive function (β = 0.42; p < 0.001). Conclusions: Higher blood lead levels in this population of young children is associated with increased risk of neurobehavioral deficits and ADHD, with executive function and attention being particularly vulnerable domains to the effects of lead

Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water

ABSTRACT: BACKGROUND: Manganese is an essential nutrient, but in excess it can be a potent neurotoxicant. Despite the common occurrence of manganese in groundwater, the risks associated with this source of exposure are largely unknown. OBJECTIVES: Our first aim was to assess the relations between exposure to manganese from drinking water and children's intelligence quotient (IQ). Second, we examined the relations between manganese exposures from water consumption and from the diet with children's hair manganese concentration. METHODS: This cross-sectional study included 362 children 6-13 years of age living in communities supplied by groundwater. Manganese concentration was measured in home tap water (MnW) and children's hair (MnH). We estimated manganese intake from water ingestion and the diet using a food frequency questionnaire and assessed IQ with the Wechsler Abbreviated Scale of Intelligence. RESULTS: The median MnW in children's home tap water was 34 microg/L (range, 1-2,700 microg/L). MnH increased with manganese intake from water consumption, but not with dietary manganese intake. Higher MnW and MnH were significantly associated with lower IQ scores. A 10-fold increase in MnW was associated with a decrease of 2.4 IQ points (95% confidence interval: -3.9 to -0.9; p < 0.01), adjusting for maternal intelligence, family income, and other potential confounders. There was a 6.2-point difference in IQ between children in the lowest and highest MnW quintiles. MnW was more strongly associated with Performance IQ than Verbal IQ. CONCLUSIONS: The findings of this cross-sectional study suggest that exposure to manganese at levels common in groundwater is associated with intellectual impairment in children