High frequency of skin reactions in patients with leishmaniasis treated with meglumine antimoniate contaminated with heavy metals: a comparative approach using historical controls

We analyzed data from historical controls treated with meglumine antimoniate to compare the frequency of adverse events observed in patients with cutaneous leishmaniasis treated with the same dose of meglumine antimoniate contaminated with heavy metals in an endemic area of the State of Bahia, Brazil. Group A patients were treated in 2000 with the drug produced by Eurofarma Laboratórios Ltda., São Paulo, Brazil (lot A) and group B patients were treated in 1996 with the reference drug produced by Rhodia Farma Ltda., São Paulo, Brazil (lot B). We observed an unusual higher frequency of skin reactions in group A patients. However, all type of adverse events observed in group A were also observed in group B. The physico-chemical analysis of these lots revealed that lot A had lower pH and higher concentration of total and trivalent antimony, lead, cadmium, and arsenic. Our findings suggest that the skin reactions could be attributed to heavy metal contamination of lot A.

Role of genetic and social factors in modulating the efficiency of division of labour in social insects

Summary : Division of labour is one of the most fascinating aspects of social insects. The efficient allocation of individuals to a multitude of different tasks requires a dynamic adjustment in response to the demands of a changing environment. A considerable number of theoretical models have focussed on identifying the mechanisms allowing colonies to perform efficient task allocation. The large majority of these models are built on the observation that individuals in a colony vary in their propensity (response threshold) to perform different tasks. Since individuals with a low threshold for a given task stimulus are more likely to perform that task than individuals with a high threshold, infra-colony variation in individual thresholds results in colony division of labour. These theoretical models suggest that variation in individual thresholds is affected by the within-colony genetic diversity. However, the models have not considered the genetic architecture underlying the individual response thresholds. This is important because a better understanding of division of labour requires determining how genotypic variation relates to differences in infra-colony response threshold distributions. In this thesis, we investigated the combined influence on task allocation efficiency of both, the within-colony genetic variability (stemming from variation in the number of matings by queens) and the number of genes underlying the response thresholds. We used an agent-based simulator to model a situation where workers in a colony had to perform either a regulatory task (where the amount of a given food item in the colony had to be maintained within predefined bounds) or a foraging task (where the quantity of a second type of food item collected had to be the highest possible). The performance of colonies was a function of workers being able to perform both tasks efficiently. To study the effect of within-colony genetic diversity, we compared the performance of colonies with queens mated with varying number of males. On the other hand, the influence of genetic architecture was investigated by varying the number of loci underlying the response threshold of the foraging and regulatory tasks. Artificial evolution was used to evolve the allelic values underlying the tasks thresholds. The results revealed that multiple matings always translated into higher colony performance, whatever the number of loci encoding the thresholds of the regulatory and foraging tasks. However, the beneficial effect of additional matings was particularly important when the genetic architecture of queens comprised one or few genes for the foraging task's threshold. By contrast, higher number of genes encoding the foraging task reduced colony performance with the detrimental effect being stronger when queens had mated with several males. Finally, the number of genes determining the threshold for the regulatory task only had a minor but incremental effect on colony performance. Overall, our numerical experiments indicate the importance of considering the effects of queen mating frequency, genetic architecture underlying task thresholds and the type of task performed when investigating the factors regulating the efficiency of division of labour in social insects. In this thesis we also investigate the task allocation efficiency of response threshold models and compare them with neural networks. While response threshold models are widely used amongst theoretical biologists interested in division of labour in social insects, our simulation reveals that they perform poorly compared to a neural network model. A major shortcoming of response thresholds is that they fail at one of the most crucial requirement of division of labour, the ability of individuals in a colony to efficiently switch between tasks under varying environmental conditions. Moreover, the intrinsic properties of the threshold models are that they lead to a large proportion of idle workers. Our results highlight these limitations of the response threshold models and provide an adequate substitute. Altogether, the experiments presented in this thesis provide novel contributions to the understanding of how division of labour in social insects is influenced by queen mating frequency and genetic architecture underlying worker task thresholds. Moreover, the thesis also provides a novel model of the mechanisms underlying worker task allocation that maybe more generally applicable than the widely used response threshold models. Resumé : La répartition du travail est l'un des aspects les plus fascinants des insectes vivant en société. Une allocation efficace de la multitude de différentes tâches entre individus demande un ajustement dynamique afin de répondre aux exigences d'un environnement en constant changement. Un nombre considérable de modèles théoriques se sont attachés à identifier les mécanismes permettant aux colonies d'effectuer une allocation efficace des tâches. La grande majorité des ces modèles sont basés sur le constat que les individus d'une même colonie diffèrent dans leur propension (inclination à répondre) à effectuer différentes tâches. Etant donné que les individus possédant un faible seuil de réponse à un stimulus associé à une tâche donnée sont plus disposés à effectuer cette dernière que les individus possédant un seuil élevé, les différences de seuils parmi les individus vivant au sein d'une même colonie mènent à une certaine répartition du travail. Ces modèles théoriques suggèrent que la variation des seuils des individus est affectée par la diversité génétique propre à la colonie. Cependant, ces modèles ne considèrent pas la structure génétique qui est à la base des seuils de réponse individuels. Ceci est très important car une meilleure compréhension de la répartition du travail requière de déterminer de quelle manière les variations génotypiques sont associées aux différentes distributions de seuils de réponse à l'intérieur d'une même colonie. Dans le cadre de cette thèse, nous étudions l'influence combinée de la variabilité génétique d'une colonie (qui prend son origine dans la variation du nombre d'accouplements des reines) avec le nombre de gènes supportant les seuils de réponse, vis-à-vis de la performance de l'allocation des tâches. Nous avons utilisé un simulateur basé sur des agents pour modéliser une situation où les travailleurs d'une colonie devaient accomplir une tâche de régulation (1a quantité d'une nourriture donnée doit être maintenue à l'intérieur d'un certain intervalle) ou une tâche de recherche de nourriture (la quantité d'une certaine nourriture doit être accumulée autant que possible). Dans ce contexte, 'efficacité des colonies tient en partie des travailleurs qui sont capable d'effectuer les deux tâches de manière efficace. Pour étudier l'effet de la diversité génétique d'une colonie, nous comparons l'efficacité des colonies possédant des reines qui s'accouplent avec un nombre variant de mâles. D'autre part, l'influence de la structure génétique a été étudiée en variant le nombre de loci à la base du seuil de réponse des deux tâches de régulation et de recherche de nourriture. Une évolution artificielle a été réalisée pour évoluer les valeurs alléliques qui sont à l'origine de ces seuils de réponse. Les résultats ont révélé que de nombreux accouplements se traduisaient toujours en une plus grande performance de la colonie, quelque soit le nombre de loci encodant les seuils des tâches de régulation et de recherche de nourriture. Cependant, les effets bénéfiques d'accouplements additionnels ont été particulièrement important lorsque la structure génétique des reines comprenait un ou quelques gènes pour le seuil de réponse pour la tâche de recherche de nourriture. D'autre part, un nombre plus élevé de gènes encodant la tâche de recherche de nourriture a diminué la performance de la colonie avec un effet nuisible d'autant plus fort lorsque les reines s'accouplent avec plusieurs mâles. Finalement, le nombre de gènes déterminant le seuil pour la tâche de régulation eu seulement un effet mineur mais incrémental sur la performance de la colonie. Pour conclure, nos expériences numériques révèlent l'importance de considérer les effets associés à la fréquence d'accouplement des reines, à la structure génétique qui est à l'origine des seuils de réponse pour les tâches ainsi qu'au type de tâche effectué au moment d'étudier les facteurs qui régulent l'efficacité de la répartition du travail chez les insectes vivant en communauté. Dans cette thèse, nous étudions l'efficacité de l'allocation des tâches des modèles prenant en compte des seuils de réponses, et les comparons à des réseaux de neurones. Alors que les modèles basés sur des seuils de réponse sont couramment utilisés parmi les biologistes intéressés par la répartition des tâches chez les insectes vivant en société, notre simulation montre qu'ils se révèlent peu efficace comparé à un modèle faisant usage de réseaux de neurones. Un point faible majeur des seuils de réponse est qu'ils échouent sur un point crucial nécessaire à la répartition des tâches, la capacité des individus d'une colonie à commuter efficacement entre des tâches soumises à des conditions environnementales changeantes. De plus, les propriétés intrinsèques des modèles basés sur l'utilisation de seuils conduisent à de larges populations de travailleurs inactifs. Nos résultats mettent en évidence les limites de ces modèles basés sur l'utilisation de seuils et fournissent un substitut adéquat. Ensemble, les expériences présentées dans cette thèse fournissent de nouvelles contributions pour comprendre comment la répartition du travail chez les insectes vivant en société est influencée par la fréquence d'accouplements des reines ainsi que par la structure génétique qui est à l'origine, pour un travailleur, du seuil de réponse pour une tâche. De plus, cette thèse fournit également un nouveau modèle décrivant les mécanismes qui sont à l'origine de l'allocation des tâches entre travailleurs, mécanismes qui peuvent être appliqué de manière plus générale que ceux couramment utilisés et basés sur des seuils de réponse.

Bats of Borneo: diversity, distributions and representation in protected areas

Protected areas are valuable in conserving tropical biodiversity, but an insufficient understanding of species diversity and distributions makes it difficult to evaluate their effectiveness. This is especially true on Borneo, a species rich island shared by three countries, and is particularly concerning for bats, a poorly known component of mammal diversity that may be highly susceptible to landscape changes. We reviewed the diversity, distributions and conservation status of 54 bat species to determine the representation of these taxa in Borneo's protected areas, and whether these reserves complement each other in terms of bat diversity. Lower and upper bound estimates of bat species composition were characterised in 23 protected areas and the proposed boundaries of the Heart of Borneo conservation area. We used lower and upper bound estimates of species composition. By using actual inventories, species representation was highly irregular, and even if some reserves were included in the Heart of Borneo, the protected area network would still exhibit low complementarity. By inferring species presence from distributions, composition between most reserves was similar, and complementarity was much higher. Predicting species richness using abundance information suggested that bat species representation in reserves may lie between these two extremes. We recommend that researchers better sample biodiversity over the island and address the conservation threats faced in Borneo both within and outside protected areas. While the Heart of Borneo Initiative is commendable, it should not divert attention from other conservation areas.

Nodular typhlitis associated with the nematodes Heterakis gallinarum and Heterakis isolonche in pheasants: frequency and pathology with evidence of neoplasia

An investigation related to the frequency and pathology of Heterakis gallinarum and pathology of Heterakis isolonche in pheasants from Rio de Janeiro, Brazil was conducted by means of clinical examinations, necropsies, and histopathological analysis in 50 ring-necked pheasants from backyard flocks of 11 localities; also, histological sections of caeca of golden pheasants deposited in the Helminthological Collection of the Oswaldo Cruz Institute (CHIOC) have been considered in the present study. During necropsies, only specimens of H. gallinarum were recovered with a prevalence of 90%, mean intensity of 81.9 and range of infection of 1-413. Gross lesions were characterized by congestion, thickening, petechial haemorrhages of the mucosa, intussusception, and nodules in the cecal wall. Under microscopy, chronic difuse typhlitis, haemosiderosis, granulomas with necrotic center in the submucosa and leiomyomas in the submucosa, muscular and serosa associated with immature H. gallinarum worms were observed. The examination of histological sections previously deposited in the CHIOC, revealed more severe alterations associated with concomitant infections with H. gallinarum and H. isolonche in golden pheasants, and were characterized by several necrotic areas with cholesterol clefts in the submucosa, giant cell granulomas in the submucosa, and serosa centralized by necrosis and worm sections and neoplastic nodules in the muscular and submucosa.

Parasitism, the diversity of life, and paleoparasitology

The parasite-host-environment system is dynamic, with several points of equilibrium. This makes it difficult to trace the thresholds between benefit and damage, and therefore, the definitions of commensalism, mutualism, and symbiosis become worthless. Therefore, the same concept of parasitism may encompass commensalism, mutualism, and symbiosis. Parasitism is essential for life. Life emerged as a consequence of parasitism at the molecular level, and intracellular parasitism created evolutive events that allowed species to diversify. An ecological and evolutive approach to the study of parasitism is presented here. Studies of the origin and evolution of parasitism have new perspectives with the development of molecular paleoparasitology, by which ancient parasite and host genomes can be recovered from disappeared populations. Molecular paleoparasitology points to host-parasite co-evolutive mechanisms of evolution traceable through genome retrospective studies.

Comparative population genomics in animals uncovers the determinants of genetic diversity.

Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.

Malaria during pregnancy in a reference centre from the Brazilian Amazon: unexpected increase in the frequency of Plasmodium falciparum infections

Malaria remains globally the most important parasitic disease of man. Data on its deleterious effects during pregnancy have been extensively documented in hyperendemic, holoendemic, and mesoendemic areas from Africa and Asia where Plasmodium falciparum is responsible for almost all infections. However, knowledge about malaria during pregnancy in areas where transmission is unstable and P. vivax is the most prevalent species, such as the Brazilian Amazon, is scarce. Here, we report a preliminary cross sectional descriptive study, carried out at the Fundação de Medicina Tropical do Amazonas, a reference centre for diagnosis and treatment of tropical diseases in the west-Amazon (Manaus, Brazil). A total of 1699 febrile childbearing age women had positive thick blood smears to Plasmodium species, between January and November 1997: 1401 (82.5%) were positive for P. vivax , 286 (16.8%) for P. falciparum and 12 (0.07%) carried mixed infections. From the malarious patients, 195 were pregnant. The ratio of P. falciparum to P. vivax infections in the group of non-pregnant infected women was 1:5.6 while it was 1:2.3 in that of pregnant infected ones. Similar rates or even proportionally more vivax infections during pregnancy were expected to occur, in function of the contraindication of primaquine with the resulting increased P. vivax relapse rates. Such an observation suggests that the mechanism of resistance/susceptibility to infection and/or malaria pathogenesis in pregnant women may differ according to Plasmodium species and that the extensively described increase in the frequencies of malaria infection during pregnancy may be specifically due to P. falciparum infection.

The frequency of Toxocara infection in mental retarded children

Human toxocariasis is commonly seen in places where stray and Toxocara canis-infected dog population is high. There is a strong correlation between frequency of Toxocara infection, life style, and infection risk. Institutionalization of mental retarded patients increases to risk of toxocariasis. In this study, we aimed at investigating the frequency of Toxocara infection among children with mental retardation not requiring institutionalization. The study included 96 cases, who had educatable mental retardation and 85 healthy subjects who comprised the control group. Anti-Toxocara IgG or IgM antibodies were investigated in all serum samples, using ELISA method. The frequency of Toxocara infection was found significantly higher in mental retarded cases than in those in the control group (18.8% and 7.1% respectively) (p < 0.05). There was no significant difference between mental retarded children and the control group in terms of mean age, age groups, gender, owning dogs and cats and duration of their ownership, socio-economic level and behavioural factors, and personal hygiene (p > 0.05). We did not find any significant difference between Toxocara seropositive and seronegative mental retarded children in terms of demographic factors and epidemiological factors that could increase the risk of Toxocara infection (p > 0.05). The present study is the first seroprevalence study carried out with a mental retarded group not requiring institutionalization. Determination of high frequency of Toxocara infection suggests that these subjects constitute a risk factor for Toxocara infection, which may be attributed to their behavioural patterns.

Evaluation of high frequency jet ventilation in patients undergoing percutaneous thermal ablation

Purpose: To evaluate the use of high frequency jet ventilation (HFJV) in patients undergoing percutanous thermal ablation procedures.Materials: From may to september 2011 patients with lung, liver or kidney tumors suitable for percutanous thermal ablation were prospectively enrolled to be treated under general anesthesia using HFJV instead of conventional positive pressure ventilation (PPV). Our primary endpoint was feasability of HFJV during percutanous ablation, our secondary endpoints were assessment of breathing related movements by image fusion (CT/US), precision and ease of needle placement by number of CT aquisition/needle reposition and procedure related complications.Results: Twenty-nine patients (21 males, 8 females mean age 66.2 years) with 30 liver tumors, 1 kidney tumors and 6 lung tumors were included. Tumor ablation was performed by radiofrequency (RFA) in 26 cases, microwaves ( MWA) in 2 and cryoablation (CRA) in 1. The ablation procedure could be completed under HFJV in 22 patients. In 2 patients HFVJ had to be stopped in favor of PPV because the tumor was better seen under PPV. HFJV was not performed in 5. Breathing related movements of the target lesion in the cranio-caudal direction as estimated by image fusion were always inferior to 5mm compared to 20mm when patients are under PPV. Needle placement was straightforward under CT as well as US. No patient needed needle repositionning before ablation. We did not observe any HFJV related complications.Conclusions: HFJV significantly reduces breathing movements of target lesion during percutaneous ablation procedures. It does not seem to cause any particular complication. However in some cases such as tumors located at the base of the lungs or in the dome of the liver, the target may be best seen under PPV.

Risky single occasion drinking frequency and alcohol-related consequences: can abstinence during early adulthood lead to alcohol problems?

QUESTIONS UNDER STUDY: the main purpose of this longitudinal study was to determine the impact of risky single occasion drinking (RSOD) frequency on alcohol dependence and drinking consequences reported 15 months later. METHODS: As a baseline sample, 5,990 young men were assessed on their drinking habits including the frequency of RSOD. Of them, 5,196 were reassessed at follow-up 15 months later on RSOD frequency, alcohol dependence and alcohol related consequences in thze interceding year. Drop out biases were investigated. RESULTS: Around 45% of the baseline participants reported regular RSOD (every month or more frequently). Despite the fact that RSOD distribution was generally stable during the initial sample, 47.4% reported a variation of their RSOD frequency 15 months later. Around 25% of the sample reported reduced RSOD frequency. Nonetheless, occasional RS drinkers were more likely to become regular (monthly) RSO drinkers at follow up. Daily and weekly RSOD were associated with high proportions of alcohol dependence and detrimental consequences of drinking. Surprisingly, abstainers at baseline were more likely to be at risk of alcohol dependence and consequences at follow up than non-RSO drinkers. CONCLUSIONS: Despite the fact that alcohol abstinence is logically the best way to avoid the detrimental consequences of alcohol drinking, abstainers at baseline reported as many problems due to alcohol use at follow up as occasional or monthly RSO drinkers. The few participants who had become RSO drinkers during the follow up period were indeed likely to engage in detrimental behaviour. Non-RSO drinkers had the fewest problems due to alcohol use. This substantiates the early occurrence of drinking consequences among inexperienced RSO drinkers.

Trichurid nematodes in ring-necked pheasants from backyard flocks of the State of Rio de Janeiro, Brazil: frequency and pathology

The present investigation is related to the frequency of infection and to the gross and microscopic lesions associated to the presence of trichurid worms in 50 ring-necked pheasants (Phasianus colchicus) from backyard flocks in the state of Rio de Janeiro, Brazil. In the investigated birds, the overall infection rate was of 74%, with the presence of Eucoleus perforans with 72% of prevalence and 21.2 of mean intensity, in the esophageal and crop mucosa and rarely in the junction of the proventriculus and esophagus, E. annulatus with 2% and 3 in the crop mucosa, Capillaria phasianina, with 12% and 4.3 in the cecum and small intestine and Baruscapillaria obsignata, for the first time referred in this host, with 2% and 1 in the small intestine. Clinical signs were absent. The gross lesions observed in the crop and esophagus of 14 (38.9%) pheasants parasitized with E. perforans were thickening, small nodules, congestion, and petechial haemorrhages in the mucosa. These birds presented a mean infection of 37.5 and a range of infection of 10-82. The microscopic lesions revealed chronic esophagitis with diffuse inflammatory process in the lamina propria characterized mostly by a mononuclear cell infiltrate and also with the presence of granulocytes. In the case of the parasitism of pheasants with C. phasianina, the gross lesions were absent; microscopic lesions were characterized by chronic typhlitis with mononuclear infiltrate. Gross and microscopic lesions were absent in the pheasants parasitized with E. annulatus and B. obsignata.

Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil

In the context of universal access to antiretroviral therapy, the surveillance of human immunodeficiency virus type 1 (HIV-1) genetic diversity and resistance becomes pivotal. In this work our purpose was to describe the genetic variability; prevalence of drug-resistance mutations; and genotypic resistance profiles in HIV-1 infected individuals under antiretroviral treatment, from the Federal District, Brasília, Central Brazil. The entire viral protease and codons 19 to 234 of the reverse transcriptase gene from 45 HIV-1 isolates were amplified and sequenced for subtyping and genotyping. By phylogenetic analysis, 96% of the samples clustered with subtype B and the remaining 4% with HIV-1 subtype F sequences. One major protease inhibitor resistance-associated mutation, I50V, was detected in 38% of the samples. Minor mutations were also found at the protease gene: L10I/V (7%), K20M (2%), M36I (11%), L63P (20%), A71T (2%), and V77I (7%). Many mutations associated with reduced susceptibility to nucleoside or non-nucleoside reverse transcriptase inhibitors were detected: M41L (11%), E44D (4%), D67N (11%), T69D (2%), K70R (11%), L74V (2%), L100I (4%), K103N (18%), V118I (9%), Y181C (11%), M184V (18%), G190A (4%), T215Y (4%), and K219E (4%). This study has shown that 84% of the studied population from the Federal District, showing evidences of therapy failure, presented viral genomic mutations associated with drug resistance. The main antiretrovirals to which this population showed resistance were the PI amprenavir (38%), the NNRTIs delavirdine, nevirapine (31%), and efavirenz (24%), and the NRTIs lamivudine (18%), abacavir, and zidovudine (13%).

Pre-mRNA trans-splicing: from kinetoplastids to mammals, an easy language for life diversity

Since the discovery that genes are split into intron and exons, the studies of the mechanisms involved in splicing pointed to presence of consensus signals in an attempt to generalize the process for all living cells. However, as discussed in the present review, splicing is a theme full of variations. The trans-splicing of pre-mRNAs, the joining of exons from distinct transcripts, is one of these variations with broad distribution in the phylogenetic tree. The biological meaning of this phenomenon is discussed encompassing reactions resembling a possible noise to mechanisms of gene expression regulation. All of them however, can contribute to the generation of life diversity.

Recognising diversity in Public Health NI

The fifth Director of Public Health Annual Report for Northern Ireland, launched on 16 June 2014, celebrates diversity in the population.��The report recognises the opportunities and challenges posed by population diversity and highlights some of the key programmes introduced to meet these needs.The presentation slides from key speakers from the launch event on 16 June 2014 and all parallel sessions will be��appended below.��Please note:��The PHA cannot be held responsible for any breach of copyright that may exist within individual presentations.Read more here>>

Prevalence and genetic diversity of astroviruses in children with and without diarrhea in São Luís, Maranhão, Brazil

Human astroviruses (HAstV) have been increasingly identified as important etiological agents of acute gastroenteritis in children up to five years old. The aim of this study was to determine the prevalence and genotype diversity of HAstV in children with symptomatic and asymptomatic infections in São Luís, Maranhão, Brazil. From June 1997 to July 1999 a total of 183 fecal samples 84 from symptomatic and 99 from asymptomatic children were tested by enzyme immunoassay for HAstV. Prevalence rates were found to be 11 and 3% for symptomatic and asymptomatic children, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was carried out in 46 specimens (26 symptomatic and 20 asymptomatic) including the 12 samples that were positive by enzyme immunoassay (EIA). The overall positivity yielded by both methods was 8% (15/184); of these, 11% (9/84) for symptomatic and 5% (5/99) for those without symptoms or signs. Sequence analysis of amplicons revealed that HAstV-1 genotype was the most prevalent, accounting for 60% of isolates. Genotypes 2, 3, 4, and 5 were also detected, as one single isolate (10%) for each type. Variations in the sequences were observed when Brazilian isolates were compared to prototype strains identified in the United Kingdom. No seasonal pattern of occurrence was observed during these two years of study, and peak detection rate was observed in children aged between 3 and 6 months in the symptomatic group, and between 18 and 24 months in the controls.