Toxocariasis in migrant children: A 6 years' experience in a reference pediatric unit in Spain.

BACKGROUND: Toxocariasis is a worldwide distributed zoonosis that affects characteristically children. Clinical presentation is highly variable, often asymptomatic, and treatment duration is controversial. METHODS: A retrospective descriptive study (January 2014-December 2019) was performed in a referral Unit for Pediatric Tropical Diseases. Patients younger than 18 years of age diagnosed with toxocariasis were included. RESULTS: Out of 931 children screened for toxocariasis, 49 (5.3%) were seropositive. The median age was 11.0 years, 55.1% male and 30.6% referred contact with puppies. Overall, 34.7% were Latin-American, 24.5% Asiatic, 20.4% European, and 20.4% African. Only 34.7% presented symptoms, gastrointestinal the most common (52.9%). The 57.1% of children presented eosinophilia and 50% elevated total IgE. Most cases (95.9%) corresponded to covert toxocariasis. All children were treated with albendazole for 5, 14 or 21 days, and 4 children required a second course. Follow-up data were available in 32 children (65.3%) for a median of 7 months, showing a progressive decline in eosinophils, IgE-titers and ELISA optical density. CONCLUSION: Toxocariasis is mostly asymptomatic in children and eosinophilia is not always present. Serological tests should be included in migrant health screening and in the diagnostic assessment of eosinophilia. Eosinophil count, IgE-titers and ELISA optical-density could be useful during follow-up.

Brain activity in well-controlled perinatally HIV-infected young adults: a fMRI pilot study. / Actividad cerebral en jóvenes infectados por el virus de la inmunodeficiencia humana por transmisión vertical: estudio piloto de resonancia magnética funcional.

INTRODUCTION AND AIM: Perinatal transmission of human immunodeficiency virus (PHIV) is considered a chronic disease that has highlighted several cognitive deficits. From birth to early adulthood, cognition is known to play a fundamental role. However, although neurocognitive processes associated with PHIV have been extensively described by psychometric testing, data is scarce on neural activity from functional magnetic resonance imaging (fMRI) which provides in vivo physiological information. SUBJECTS AND METHODS: We studied described impaired cognitive processes using fMRI on a group of PHIV adolescents with good immunovirological indications and healthy matched controls. Psychological status and neurocognitive functions were also assessed. RESULTS: There were no significant differences between HIV+ and HIV- groups, either on neurocognitive testing nor in fMRI activity for phonological fluency tasks. Prolonged duration of cART was positively associated with greater brain activity in left inferior frontal gyrus (LIFG) which could indicate functional compensation. CONCLUSIONS: These results suggest that neural activity through fMRI in PHIV adolescents with good daily functioning and good immunovirological control may be similar to their peers.

TITLE: Actividad cerebral en jóvenes infectados por el virus de la inmunodeficiencia humana por transmisión vertical: estudio piloto de resonancia magnética funcional.Introducción y objetivos. La infección por el virus de la inmunodeficiencia humana de transmisión vertical (VIH-TV) constituye una enfermedad crónica que puede asociar múltiples alteraciones cognitivas que pueden influenciar el desarrollo de estos pacientes desde la infancia a la vida adulta. Sin embargo, aunque las alteraciones neurocognitivas vinculadas al VIH-TV están ampliamente descritas y valoradas mediante pruebas psicométricas, no existen apenas estudios de actividad neuronal medida a través de la resonancia magnética funcional (RMf). Sujetos y métodos. Analizar la utilidad de la RMf a través de la realización de tareas motoras y de fluidez verbal en un grupo de adolescentes y jóvenes con VIH-TV con buen control inmunovirológico y compararlo con un grupo control negativo de características similares. Se evaluaron también alteraciones psicológicas y funciones neurocognitivas. Resultados. No se encontraron diferencias significativas entre el grupo VIH+ y el grupo control para las tareas ejecutadas durante la RMf ni en la evaluación neurocognitiva. Un mayor tiempo de terapia combinada antirretroviral se asoció de forma directa con una mayor actividad en el giro frontal inferior izquierdo, lo cual podría indicar una posible compensación funcional. Conclusiones. Estos resultados sugieren que la actividad neuronal medida a través de la RMf en adolescentes con VIH-TV y buen control inmunovirológico es similar a la de sus pares.

Intestinal giardiasis in children: Five years' experience in a reference unit.

BACKGROUND: Giardiasis is highly prevalent in children and is often mildly symptomatic. First-line treatment is metronidazole, but treatment failure is not uncommon. We describe a paediatric series, to identify risk factors for treatment failure and to analyse the safety and effectiveness of other treatment strategies. METHODS: Retrospective observational study, including children diagnosed with giardiasis from 2014 to 2019. Diagnosis was based on direct visualisation by microscopy after concentration using an alcohol-based fixative, antigen detection and/or DNA detection by polymerase chain reaction in stool. Treatment failure was considered when GI was detected 4 weeks after treatment. RESULTS: A total of 120 patients were included, 71.6% internationally adopted, median age 4.2 (2.3-7.3) years. Only 50% presented with symptoms, mainly diarrhoea (35%) and abdominal pain (14.1%); co-parasitism was frequent (45%). First-line treatment failure after a standard dose of metronidazole was 20%, lowering to 8.3% when a higher dose was administered (p < 0.001). Quinacrine was administered in 10 patients, with 100% effectiveness. Children <2 years were at higher risk of treatment failure (OR 3.49; 95% CI 1.06-11.53; p = 0.040). CONCLUSIONS: In children with giardiasis, treatment failure is frequent, especially before 2 years of age. Quinacrine can be considered as a second-line treatment. After treatment, eradication should be confirmed.

Actividad cerebral en jóvenes infectados por el virus de la inmunodeficiencia humana por transmisión vertical: estudio piloto de resonancia magnética funcional / Brain activity in well-controlled perinatally HIV-infected young adults: a fMRI pilot study

Introducción y objetivos: La infección por el virus de la inmunodeficiencia humana de transmisión vertical (VIH-TV) constituye una enfermedad crónica que puede asociar múltiples alteraciones cognitivas que pueden influenciar el desarrollo de estos pacientes desde la infancia a la vida adulta. Sin embargo, aunque las alteraciones neurocognitivas vinculadas al VIH-TV están ampliamente descritas y valoradas mediante pruebas psicométricas, no existen apenas estudios de actividad neuronal medida a través de la resonancia magnética funcional (RMf). Sujetos y métodos:Analizar la utilidad de la RMf a través de la realización de tareas motoras y de fluidez verbal en un grupo de adolescentes y jóvenes con VIH-TV con buen control inmunovirológico y compararlo con un grupo control negativo de características similares. Se evaluaron también alteraciones psicológicas y funciones neurocognitivas. Resultados: No se encontraron diferencias significativas entre el grupo VIH+ y el grupo control para las tareas ejecutadas durante la RMf ni en la evaluación neurocognitiva. Un mayor tiempo de terapia combinada antirretroviral se asoció de forma directa con una mayor actividad en el giro frontal inferior izquierdo, lo cual podría indicar una posible compensación funcional. Conclusiones: Estos resultados sugieren que la actividad neuronal medida a través de la RMf en adolescentes con VIH-TV y buen control inmunovirológico es similar a la de sus pares.(AU)

Introduction and aim: Perinatal transmission of human immunodeficiency virus (PHIV) is considered a chronic disease that has highlighted several cognitive deficits. From birth to early adulthood, cognition is known to play a fundamental role. However, although neurocognitive processes associated with PHIV have been extensively described by psychometric testing, data is scarce on neural activity from functional magnetic resonance imaging (fMRI) which provides in vivo physiological information. Subjects and methods: We studied described impaired cognitive processes using fMRI on a group of PHIV adolescents with good immunovirological indications and healthy matched controls. Psychological status and neurocognitive functions were also assessed. Results: There were no significant differences between HIV+ and HIV– groups, either on neurocognitive testing nor in fMRI activity for phonological fluency tasks. Prolonged duration of cART was positively associated with greater brain activity in left inferior frontal gyrus (LIFG) which could indicate functional compensation. Conclusions: These results suggest that neural activity through fMRI in PHIV adolescents with good daily functioning and good immunovirological control may be similar to their peers.(AU)

Tuberculosis in a Spanish cohort of children living with HIV: the CHOTIS study (Childhood HIV & TB study).

BACKGROUND: Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain.METHODS: Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995-1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000-2009 (P2, increase in immigration), and 2010-2016 (P3, decrease in immigration).RESULTS: We included 29 TB cases among 1183 children aged <18 years (2.4%, 243/100 000 person-years). The proportion was stable in P1 and P2 (1.3%), but decreased in P3 (0.8%). The median age at TB diagnosis was 6.4 years (IQR 4-10.6); most children in P3 were aged >10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period (P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%).CONCLUSION: In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced.

Epidemiological factors related to hospitalization due to influenza in children below 6 months of age.

The aim of this study was to address the epidemiological factors associated to hospital admissions due to influenza in infants younger than 6 months. A case-control study was performed in a tertiary hospital in Spain. Cases were infants under 6 months of age without comorbidities who were admitted due to influenza between October 2010 and March 2015. Controls were healthy infants younger than 6 months who were hospitalized due to non-respiratory illness or non-infectious diseases (urinary tract infection was included as controls). Data were retrospectively collected from medical records and phone interviews. A total of 88 cases and 122 controls we included. From univariate analysis, differences were found in relation to maternal age (43.1 ± 4.95 vs 32 ± 5.3), paternal age (37 ± 6.4 vs 34.5 ± 6.1), having siblings (79 vs 24%), siblings below 4 years old (54 vs 15%), and having vaccinated grandparents (18 vs 39%) (p < 0.05). After logistic regression, having vaccinated grandparents was an independent protective factor (OR 0.22 [CI95%; 0.05-0.91]), while having siblings was a risk factor (OR 15.8 [CI95% 3.15-79.5]). Vaccination during pregnancy was highly uncommon (3.5 vs 8.3%; p = 0.3). CONCLUSION: This study underlines the importance of increasing influenza immunization among household contacts of infants below 6 months to prevent their influenza admission. What is Known: • Infants younger than 6 months old are considered a high-risk population. • Vaccination against influenza is not licensed in infants below 6 months. What is New: • Increasing vaccination coverage in elderly people could reduce infants' hospitalization rates. • Cocoon immunization strategy may reduce the admission of infants.

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects.

Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+ viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART+) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV- controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART+ subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.

Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.

Development of tuberculosis in human immunodeficiency virus infected patients receiving antiretroviral therapy.

BACKGROUND: It is unclear whether optimal immunological recovery reduces the risk of tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients receiving antiretroviral therapy (ART), in whom it is still significantly higher than in the general population. METHODS: Retrospective cohort study in ART-treated patients without a previous diagnosis of TB. TB was microbiologically proven. Multivariate analyses were performed to identify risk factors associated with TB. RESULTS: This study included 1824 patients; the median follow-up was 473 days. The median CD4 count was 207 cells/µl (90-363.8); 339 (18.6%) were tuberculin skin test positive. Increased CD4 count gain after ART initiation was a protective factor against active TB (per each 100 cells/µl increase, OR 0.683, 95%CI 0.522-0.894). Maximal protection was observed in patients reaching increments ⩾150 cells/µl after 12 months of ART (OR 0.29, 95%CI 0.11-0.8) or ⩾300 cells/µl after 24 months (OR 0.73, 95%CI 0.71-0.75). There was no association between achieving HIV RNA <50 copies/ml and risk of active TB (OR 1.43, 95%CI 0.68-2.49). CONCLUSIONS: The risk of TB in patients starting ART is reduced among those with better immunological response, and is unrelated to the virological response. Our results emphasise the need for adjunctive strategies in immunological non-responders to minimise any residual risk of TB.

The CD4:CD8 ratio is associated with markers of age-associated disease in virally suppressed HIV-infected patients with immunological recovery.

OBJECTIVES: Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. METHODS: A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/µL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height(2) (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. RESULTS: CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2-7.1], arterial stiffness (OR 4.8; 95% CI 1.0-23.5) and lower eGFR (OR 5.2; 95% CI 1.0-64.4), but not sarcopenia (OR 0.7; 95% CI 0.2-2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/µL and those with CD4 counts > 500 cells/µL. CONCLUSIONS: The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.

Survival and characterization of Escherichia coli strains in a typical Mexican acid-fermented food.

In this study, the presence and pathogenic characteristics of Escherichia coli strains in pozol, an acid-fermented maize beverage consumed in South-eastern Mexico, were determined. Seventy-three E. coli strains were isolated at early and late times (6 and 48 h) during the pozol fermentation process, when pH values of the doughs were 6.7-4.7 (6 h) and 4.7-3.7 (48 h). Serotypes that belong to diarrheagenic E. coli serogroups O18, O88, O8, O11, O20, O173 were identified. HEp-2 cell adherence in vitro assays showed localized, diffuse and aggregative adherence patterns among some of these strains. A DNA colony hybridization analysis with different probes showed the presence of virulence genes related to diarrheal pathogenesis. Thirty-three percent of the E. coli strains were tetracycline-resistant and 95% had a 20 kb plasmid. The presence and survival of potentially pathogenic E. coli in acid-fermented pozol suggest that such foods may be a potential source of foodborne outbreaks.

Human leukocyte antigen alleles and haplotypes associated with selective immunoglobulin A deficiency in Spanish pediatric patients.

Class I and II human leukocyte antigens were determined by a standard microlymphocytotoxity test in a group of 45 pediatric patients with selective immunoglobulin A deficiency (IgA-D), 33 of them with frequent respiratory tract infections, allergic diseases, or gastrointestinal disorders (RTIAG), and 12 with celiac disease (CD). The results showed that the DR1 allele, and the A1, B8, Cw7, DR3, DQw2; B35, Cw4, DR1, DQw1; and B14, DR1, DQw1 haplotypes could be involved with IgA-D susceptibility in RTIAG patients. Among the CD-IgA-D group, the B14 allele and A1, B8, Cw7, DR3, DQw2 haplotype were found to confer a high risk of developing IgA-D. A possible protective role may be postulated for DR2 and DR4 in both types of IgA-D patients. The present study confirms some of the previous findings in other white populations and describes new possible alleles and haplotypes that could be implicated with IgA-D susceptibility and resistance.

Serum sickness-like syndrome associated with cefaclor therapy.

We describe 2 cases of paediatric patients who developed the main clinical features of a serum sickness reaction, while on treatment with cefaclor. A decrease in complement values was observed in both cases. Physicians should be aware of the possibility of such drug adverse reaction.

Allergens from rye pollen (Secale cereale). I. Study of protein release by rye pollen during a 19-hour extraction process. Allergen identification.

We have studied the proteins and allergens released by rye pollen in the course of a 19-h pollen incubation process. Nearly 40% of the total extracted proteins were collected during the first 5 min, and most of them had a molecular weight less than 28 kDa. Between 5 and 30 min, 15% of the proteins from total extract were released, showing in the SDS-PAGE analysis an increase in which components moved close to 30 kDa standard. From 30 min to 19 h several extracts were collected. Electrophoretical profile of components from these extracts reveals that bands moving below 28 kDa were practically absent and those of 28 and 23 kDa became very intense. At the end of the process there was a rise of 67 kDa proteins. Dot-immunobinding and immunoblotting techniques reveal that allergens leave the rye pollen, for the most part, after 5 min incubation and are proteins with 28 kDa, 33 kDa, 48 kDa and 67 kDa molecular weights.

Allergens from rye pollen (Secale cereale). II. Characterization and partial purification.

Rye pollen was incubated for 30 min and proteins extracted at this time were collected as extract A (EA). The same pollen grains were resuspended in buffer and incubated for 18.5 h. Proteins extracted in this period were designated extract B (EB). Both extracts were subfractionated by DEAE ion-exchange chromatography and allergen presence in peaks detected by the dot-immunobinding technique. The results reveal that unretained proteins (peaks 1 and 2) and proteins eluted at 0.2 M NaCl from extract B contain the highest proportion of allergens. SDS-PAGE of chromatographic peaks showed that peak 2 from extract B contains a highly purified 28 kDa band. On the skin of allergic patients this band gave a stronger positive prick test than for the crude extract.

Bronchial asthma caused by Lathyrus sativus flour.

A 10-year-old child with asthmatic attacks related to Lathyrus sativus flour inhalation was studied in our department. Skin test and specific bronchial provocation challenge were positive. Specific IgE antibodies to Lathyrus sativus flour was demonstrated by indirect enzyme immunoassay. We suggest that our patient's allergic symptoms were due to the development of Type I allergic reactivity to L. sativus antigens.

Peroxidase activity in human cutaneous mast cells: an ultrastructural demonstration.

An intense and reproducible peroxidase staining in the cutaneous mast cells of two patients with systemic mast cell disease and urticaria pigmentosa is demonstrated at the ultrastructural level. This enzyme activity was demonstrated by use of a cytochemical technique employing 3,3'- diaminobenzicine (DAB) as an oxidizable substrate, after fixation by a tannic acid-aldehyde mixture. Enzyme activity was localized in the perinuclear cisterna and strands of endoplasmic reticulum. Granules appeared unreactive. This peroxidase activity appears sensitive to fixation by aldehydes; it is inhibited by 3-amino-1,2,4-triazole (AMT) and by lack of H2O2 or DAB in the incubation medium. These characteristics are fundamentally different from the peroxidase activity of basophils, and the demonstration of this enzyme is therefore not a further argument for a common ontogenetic origin of both cells. On the other hand, the cytochemical characteristics of this enzyme are very similar to those of platelet peroxidase (P-PO), which has been connected to the synthesis by platelets of prostaglandins. Since the mast cell is known to generate prostaglandins, the relationship between the enzyme described and prostaglandin synthesis by mast cells is discussed.

[Purine nucleoside phosphorylase deficiency. Report of two cases]. / Déficit de purina nucleósido fosforilasa. Presentación de dos casos.

Two brothers with a PNP deficit are reported. The first case presented recurrent upper respiratory infections and died of a sepsis by pseudomonas. The second one was diagnosed when he was six months old and remains asymptomatic. Immunologic tests revealed a deficit of T cell mediated immunity. Treatment consisted on radiated erythrocytes transfusions because HLA compatible donors were not available.

Cellular basis of hyper IgM immunodeficiency.

Six patients with primary hypogammaglobulinaemia and hyper IgM were studied. All showed very low serum IgG and IgA concentrations. The in vitro pokeweed-mitogen (PWM)-induced immunoglobulin (Ig) production, including IgM, by their peripheral blood lymphocytes was low. Even when patients' B cells were cocultured with normal T cells, IgM production did not reach normal levels. These results and studies of Ig class on the surface of B lymphocytes point to a maturation arrest of these cells. T cells from all but one patient helped very little Ig production by patients' or normal B cells. Similar numbers of these T cells did not suppress Ig production by normal T plus B cells. Therefore a defect in T cell help for IgM, IgG and IgA was seen in most patients, in addition to the B cell abnormality.