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Infecciones por VIH , Hospitalización , Femenino , VIH , Humanos , Renta , Lactante , Parto , EmbarazoRESUMEN
BACKGROUND: Epidemiological studies conducted in low- and high-income countries showed that infants exposed to maternal human immunodeficiency virus (HIV) have a high risk of severe infections. Immune alterations during fetal life have been proposed as a possible mechanism. METHODS: This prospective study assessed the relative risk of hospitalization for infection in HIV-exposed uninfected (HEU) infants as compared to HIV-unexposed (HU) infants born in a high-income country (HIC). Markers of monocyte activation and levels of pathogen-specific antibodies were measured at birth to identify correlates of infant susceptibility. RESULTS: There were 27 of 132 HEU infants and 14 of 123 HU infants hospitalized for infection during the first year of life (adjusted hazard ratio [aHR] 2.33, 95% confidence interval [CI] 1.10-4.97). Most of this increased risk was associated with the time of initiation of maternal antiretroviral therapy (ART). As compared to HU infants, the risk of hospitalization for infection of HEU infants was 4-fold higher when mothers initiated ART during pregnancy (aHR 3.84, 95% CI 1.69-8.71) and was not significantly increased when ART was initiated before pregnancy (aHR 1.42, 95% CI 0.58-3.48). The activation of newborn monocytes and the reduced transfer of maternal antibodies were most intense following ART initiation during pregnancy, and predicted the risk of infant hospitalization. CONCLUSIONS: These observations indicate that initiation of maternal ART before pregnancy reduces the susceptibility of HEU infants born in a HIC to severe infections, and that this effect could be related to the prevention of immune alterations during fetal life.
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Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Enfermedades del Recién Nacido/epidemiología , Exposición Materna , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Bélgica/epidemiología , Países Desarrollados , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , Medición de Riesgo , Adulto JovenRESUMEN
Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-naïve adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4+ T cells 14days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4+ T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy naïve adults. The results summary for this study (GSK study number 112115 - NCT# NCT00805389) is available on the GSK Clinical Study Register and can be accessed at www.gsk-clinicalstudyregister.com.
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Formación de Anticuerpos/inmunología , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adulto , Método Doble Ciego , Femenino , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/inmunología , Humanos , Inmunoensayo/métodos , Mediciones Luminiscentes , Masculino , Vacunación/métodos , Vacunas/administración & dosificaciónRESUMEN
BACKGROUND: Following primary human cytomegalovirus (HCMV) infection, the production of antibodies against envelope glycoprotein B (gB) is delayed, compared with production of antibodies against tegument proteins, and this likely reduces the control of HCMV dissemination. METHODS: The frequency and the phenotype of gB-specific and tegument protein-specific B cells were studied in a cohort of pregnant women with primary HCMV infection. Healthy adults who had chronic HCMV infection or were recently immunized with tetanus toxoid (TT) were included as controls. RESULTS: Primary HCMV infection was associated with high and similar frequencies of gB-specific and tegument protein-specific B cells following primary HCMV infection. During primary infection, tegument protein-specific B cells expressed an activated (CD21(low)) memory B-cell (MBC) phenotype. Activated MBCs were also induced by TT booster immunization, indicating that the expansion of this subset is part of the physiological B-cell response to protein antigens. In contrast, gB-specific B cells had a predominant classical (CD21(+)) MBC phenotype during both primary and chronic infections. CONCLUSIONS: The delayed production of gB-specific immunoglobulin G (IgG) during primary HCMV infection is associated with a limited induction of MBCs with effector potential. This novel mechanism by which HCMV may interfere with the production of neutralizing antibodies could represent a target for therapeutic immunization.
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Anticuerpos Antivirales/inmunología , Subgrupos de Linfocitos B/inmunología , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Proteínas del Envoltorio Viral/inmunología , Anticuerpos Neutralizantes/inmunología , Infecciones por Citomegalovirus/virología , Femenino , Humanos , Inmunoglobulina G/inmunología , Fenotipo , EmbarazoRESUMEN
BACKGROUND: Several studies indicate that HIV-exposed uninfected (HEU) children have a high infectious morbidity. We previously reported an increased incidence of group B streptococcus (GBS) infections in HEU infants born in Belgium. METHODS: This study was undertaken to evaluate the incidence and risk factors of all cause severe infections in HEU infants born in Belgium between 1985 and 2006, including the pre-antiretroviral (ARV) prophylaxis era (1985 to 1994). The medical charts of 537 HEU infants followed in a single center were reviewed. RESULTS: The incidence rate of severe infections during the first year of life was 16.8/100 HEU infant-years. The rates of invasive S. pneumoniae (0.62/100 infant-years) and GBS infections (1.05/100 infant-years) were, respectively, 4 and 13-fold higher in HEU infants than in the general infant population. Preterm birth was a risk factor for severe infections in the neonatal period (aOR = 21.34, 95%CI:7.12-63.93) and post-neonatal period (aHR = 3.00, 95%CI:1.53-5.88). As compared to the pre-ARV prophylaxis era, infants born in the ARV prophylaxis era (i.e., after April 1994) had a greater risk of severe infections (aHR = 2.93; 95%CI:1.07-8.05). This risk excess was present in those who received ARV prophylaxis (aHR 2.01, 95%CI 0.72-5.65) and also in those born in the ARV prophylaxis era who did not benefit from ARV prophylaxis as a result of poor access to antenatal care or lack of compliance (aHR 3.06, 95%CI 0.88-10.66). CONCLUSIONS: In HEU infants born in an industrialized country, preterm birth and being born during the ARV prophylaxis era were risk factors of severe infections throughout the first year of life. These observations have important implications for the clinical management of HIV-infected mothers and their infants.
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Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Intercambio Materno-Fetal , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición Prenatal , Infecciones Estreptocócicas/epidemiología , Streptococcus agalactiae/patogenicidad , Adolescente , Adulto , Bélgica/epidemiología , Susceptibilidad a Enfermedades , Femenino , Edad Gestacional , VIH-1/patogenicidad , Humanos , Incidencia , Recién Nacido , Masculino , Morbilidad , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
We assessed the safety, reactogenicity and immunogenicity of a staphylococcal vaccine combining capsular polysaccharides types 5 and 8 (CPS5/8), conjugated to tetanus toxoid (TT), with mutated detoxified α-toxin (AT) and clumping factor A (ClfA). In this phase I, randomized, placebo-controlled, observer-blind trial (NCT01160172), 88 healthy 18- to 40-year-olds received CPS5-TT/CPS8-TT/AT/ClfA vaccine (5/5/10/10 µg or 10/10/30/30 µg dose, each with or without AS03B adjuvant) or saline, at months 0, 1, 6. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 d post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded throughout the study. Humoral and antigen-specific CD4(+)/CD8(+) T-cell immunity were assessed from Day (D) 0 to D540 post-vaccination. The most frequently reported solicited local and general AEs were pain (78.6%-100% of subjects), fatigue (36.4%-93.3% of subjects post-dose 1-2) and headache (20%-44.4% of subjects post-dose 3). Overall, 4 SAEs and 2 potential immune-mediated diseases (pIMDs) (none fatal or vaccine-related) were reported. For each antigen, pre-vaccination seropositivity rates were high (85.7%-100%) and geometric mean concentrations (GMCs) in vaccine recipients sharply increased from D0 to D14, then plateaued to study end. Exploratory group comparisons suggested higher GMCs with higher dosage, without AS03B effect. Vaccine-induced antibodies were functional (CPS5 opsonophagocytic assays, and AT/ClfA inhibition assays). AT- and ClfA-specific CD4(+) T-cells with Th0/Th1 cytokine profile were induced at low levels (median <0.05%) by each formulation (intracellular cytokine staining). In conclusion, no safety concerns were identified and each vaccine formulation induced robust humoral immune responses after the first vaccine dose.
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Infecciones Estafilocócicas/prevención & control , Vacunas Estafilocócicas/efectos adversos , Vacunas Estafilocócicas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adolescente , Adulto , Anticuerpos Antibacterianos/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Combinación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Voluntarios Sanos , Humanos , Masculino , Placebos/administración & dosificación , Polisorbatos/administración & dosificación , Método Simple Ciego , Escualeno/administración & dosificación , Infecciones Estafilocócicas/inmunología , Adulto Joven , alfa-Tocoferol/administración & dosificaciónRESUMEN
OBJECTIVES: Perinatal mortality rates vary between ethnic groups but the relation with immigrant status is unclear. Previous research suggested that birth outcomes may either improve or deteriorate with duration of residence, depending on the migrant group. The objectives of this study are to describe and measure inequalities in pregnancy outcomes, perinatal mortality and causes of perinatal deaths according to current citizenship versus national origin of the mother, in Brussels. STUDY DESIGN: This is a population-based cohort study using data from linked birth and death certificates from the Belgian civil registration system. The data relate to all babies born between 1998 and 2008, whose mothers were living in Brussels, irrespective of the place of delivery. We used a logistic regression to estimate the odds ratios (ORs) for the association between mortality, causes of deaths and nationality. RESULTS: Women from Morocco, sub-Saharan Africa and Turkey experience an 80% excess in perinatal mortality (p<0.0001) compared to Belgians, but this excess of perinatal mortality is not observed for mothers with Belgian citizenship at delivery. For sub-Saharan African women, this excess is caused mainly by immaturity-related conditions and reflects a high rate of preterm deliveries, low birth weight and a low socio-economic level. Moroccan and Turkish mothers have favourable pregnancy outcomes that persist after adopting Belgian nationality, but they experience a strong excess of perinatal mortality, mainly due to congenital anomalies and asphyxia or unexplained deaths prior to the onset of labour. CONCLUSION: In Brussels, perinatal mortality varies according to nationality but those differences do not persist after adopting Belgian nationality. The explanation of this positive effect is probably due to a mix of determinants such as acculturation, use of health services or cultural contexts. Further analysis should help to better understand the results observed.
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Aculturación , Causas de Muerte , Emigrantes e Inmigrantes , Disparidades en el Estado de Salud , Mortalidad Perinatal/etnología , Adulto , África del Sur del Sahara/etnología , Bélgica/epidemiología , Estudios de Cohortes , Anomalías Congénitas/epidemiología , Anomalías Congénitas/etnología , Anomalías Congénitas/mortalidad , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/etnología , Enfermedades del Prematuro/mortalidad , Masculino , Marruecos/etnología , Embarazo , Resultado del Embarazo/etnología , Turquía/etnología , Adulto JovenRESUMEN
BACKGROUND: Paradoxical reaction (PR) during antituberculosis (TB) therapy, defined as clinical or radiologic worsening of preexisting TB lesions or the development of new lesions, has not been widely studied in immunocompetent children. METHODS: All children (<17 years) with the diagnosis of TB who sought care at our center between 1994 and 2007 were included in this retrospective study. Data on demographic characteristics, bacteriologic results, medical imaging, treatment regimens and outcomes were abstracted from medical records. Patients with and without PR were compared. RESULTS: Of 115 TB cases, 12 (10.3%) developed PR. Children with PR were younger than those with TB without complication: median age at diagnosis was 26 months (range, 5-148) compared with 66 months (range, 6-205) for those without complications (P = 0.013). None of the children in the PR group had received Calmette-Guérin bacillus vaccination, compared with 34 of 103 (33%) children without PR (P = 0.017). Children with a diagnosis of PR were more frequently symptomatic at diagnosis of TB disease when compared with children without PR (P = 0.028). PR occurred at a median interval of 39 days (range, 15-75) after initiation of antituberculosis treatment. The most common PR was worsening of preexisting pulmonary lesions (75%). New lesions in anatomical sites other than those observed at initial presentation developed in 3 children. CONCLUSION: Paradoxical deterioration during treatment of TB disease is common in immunocompetent children. Young age and absence of Calmette-Guérin bacillus vaccination appeared to be associated with PR.
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Tuberculosis/tratamiento farmacológico , Tuberculosis/inmunología , Adolescente , Antituberculosos/uso terapéutico , Vacuna BCG/uso terapéutico , Distribución de Chi-Cuadrado , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Inmunocompetencia , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Tuberculosis/diagnósticoRESUMEN
OBJECTIVE: We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE. METHODS: We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 µg, 60 µg, 120 µg, or 240 µg of IFN-K or placebo in 28 women with mild to moderate SLE. RESULTS: IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers. CONCLUSION: These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted.
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Regulación hacia Abajo/efectos de los fármacos , Interferón-alfa/inmunología , Interferón-alfa/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Vacunación/métodos , Adulto , Método Doble Ciego , Femenino , Expresión Génica , Hemocianinas/inmunología , Humanos , Interferón-alfa/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both groups.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Carga Viral , Factores de Edad , Recuento de Linfocito CD4 , Humanos , Lactante , Estimación de Kaplan-Meier , Método de Montecarlo , Modelos de Riesgos Proporcionales , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The human papillomavirus type 16/18 (HPV-16/18) AS04-adjuvanted cervical cancer vaccine is licensed for females aged 10 years and above and is therefore likely to be coadministered with other licensed vaccines, such as hepatitis B. In this randomized, open-label study, we compared the immunogenicity of the hepatitis B vaccine administered alone (HepB group) or with the HPV-16/18 AS04-adjuvanted vaccine (HepB+HPV group) in healthy women aged 20 to 25 years (clinical trial NCT00637195). The hepatitis B vaccine was given at 0, 1, 2, and 12 months (an accelerated schedule which may be required by women at high risk), and the HPV-16/18 vaccine was given at 0, 1, and 6 months. One month after the third dose of hepatitis B vaccine, in the according-to-protocol cohort (n = 72 HepB+HPV; n = 76 HepB), hepatitis B seroprotection rates (titer of ≥10 mIU/ml) were 96.4% (95% confidence interval [CI], 87.5 to 99.6) and 96.9% (CI, 89.2 to 99.6) in the HepB+HPV and HepB groups, respectively, in women initially seronegative for anti-hepatitis B surface antigen (HBs) and anti-hepatitis B core antigen (HBc). Corresponding geometric mean titers of anti-HBs antibodies were 60.2 mIU/ml (CI, 40.0 to 90.5) and 71.3 mIU/ml (CI, 53.9 to 94.3). Anti-HBs antibody titers rose substantially after the fourth dose of hepatitis B vaccine. All women initially seronegative for anti-HPV-16 and anti-HPV-18 antibodies seroconverted after the second HPV-16/18 vaccine dose and remained seropositive up to 1 month after the third dose. Both vaccines were generally well tolerated, with no difference in reactogenicity between groups. In conclusion, coadministration of the HPV-16/18 AS04-adjuvanted vaccine did not affect the immunogenicity or safety of the hepatitis B vaccine administered in an accelerated schedule in young women.
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Vacunas contra el Cáncer/administración & dosificación , Vacunas contra Hepatitis B , Hepatitis B/prevención & control , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Neoplasias del Cuello Uterino/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Adulto , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Anticuerpos Antivirales/sangre , Vacunas contra el Cáncer/inmunología , Femenino , Hepatitis B/inmunología , Hepatitis B/virología , Anticuerpos contra la Hepatitis B/sangre , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Lípido A/administración & dosificación , Lípido A/análogos & derivados , Lípido A/inmunología , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/inmunología , Resultado del Tratamiento , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/virología , Adulto JovenRESUMEN
BACKGROUND: Repeat digital cervical assessment (RDCA - examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). OBJECTIVES: To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL (The Cochrane Library 2009, Issue 3). SELECTION CRITERIA: All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. DATA COLLECTION AND ANALYSIS: We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. MAIN RESULTS: We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. AUTHORS' CONCLUSIONS: We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention.
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Cuello del Útero , Trabajo de Parto Prematuro/diagnóstico , Palpación/métodos , Femenino , Humanos , Trabajo de Parto Prematuro/prevención & control , Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The relation between immigration status and perinatal mortality is unclear. The objective of this study is to describe and measure inequalities in perinatal mortality and causes of perinatal deaths according to maternal nationality and socioeconomic status. METHODS: A population-based cohort study related to all babies born during the period of 1998-2006 whose mothers were living in Brussels, irrespective of the place of delivery. Perinatal and post-perinatal mortality were analysed according to the nationality and sociodemographic characteristics of the mothers at birth. We used logistic regression to estimate the odds ratios (ORs) for the association between mortality and nationality. RESULTS: The women of sub-Saharan Africa experience a 50% excess in perinatal mortality, which primarily reflects a high rate of preterm deliveries and low birth weight, as well as a low socioeconomic level. Paradoxically, despite their favourable rates of preterm and low-birth-weight births, Maghrebian and Turkish women experience a strong excess (50-70%) of perinatal mortality caused primarily by congenital anomalies. Differences in age, parity distributions and multiple births play no significant role, and the excess does not reflect low socioeconomic levels. This excess of perinatal mortality contrasts with the absence of an excess of post-perinatal mortality. CONCLUSION: In Brussels, patterns of inequalities in perinatal mortality and causes of perinatal deaths vary according to nationality; perinatal mortality is increased in particular ethnic groups independently of socioeconomic status and maternal characteristics.
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Emigración e Inmigración/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Mortalidad Perinatal/etnología , Resultado del Embarazo/etnología , Adulto , Bélgica/epidemiología , Causas de Muerte , Estudios de Cohortes , Femenino , Edad Gestacional , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Recién Nacido , Vigilancia de la Población , Embarazo , Características de la Residencia , Clase Social , Mortinato/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: In the absence of treatment, rapid progression to AIDS occurs in approximately 20% of HIV-1-infected infants over the first year of life. The prognosis of these children has considerably improved with highly active antiretroviral therapy. As data from well resourced countries are lacking, the objective of this collaborative study was to evaluate the impact of early treatment in vertically infected infants. DESIGN: Children born to HIV-infected mothers between 1 September 1996 and 31 December 2004, who were diagnosed with HIV and free of AIDS before 3 months, were eligible. Demographics and pregnancy data, details of antiretroviral therapy, and clinical outcome were collected from 11 European countries. METHODS: The risk of AIDS or death, by whether or not an infant started treatment before 3 months of age, was estimated by Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Among 210 children, 21 developed AIDS and three died. Baseline characteristics of the 124 infants treated before 3 months were similar to those of the 86 infants treated later. The risk of developing AIDS/death at 1 year was 1.6 and 11.7% in the two groups, respectively (P < 0.001). Deferring treatment was associated with increased risk of progression [crude hazard ratio 5.0; 95% confidence interval (CI) 2.0-12.6; P = 0.001] that persisted after adjusting for cohort in multivariate models (adjusted hazard ratio 3.0; 95% CI 1.2-7.9; P = 0.021). CONCLUSION: In HIV-1 vertically infected infants, starting antiretroviral therapy before the age of 3 months is associated with a significant reduction in progression to AIDS and death.
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Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Progresión de la Enfermedad , Esquema de Medicación , Métodos Epidemiológicos , Europa (Continente)/epidemiología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , MasculinoRESUMEN
Prophylactic interventions have lead to the reduction of the mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) to less than 2% in industrialized countries. The aim of this study was to evaluate the changes over time in vertical transmission according to the standard care of prophylaxis in the practice of a single large reference center and to identify the risk factors for failure. The rate of MTCT decreased progressively from 10% in 1986-1993 to 4.7% in 1999-2002, reflecting the progressive implementation of newly available means of prevention. During the last period evaluated (1999-2002), where highly active antiretroviral therapy (HAART) prophylaxis was the standard of care, 17% of women had a viral load between 400 and 20,000 copies/ml around delivery and 5% had a viral load above 20,000 copies/ml. High viral load and low CD4 lymphocyte count were strongly associated with vertical transmission. The rate of MTCT in women who received HAART for more than one month during pregnancy was 1.7%, compared to 13.3% in women treated with HAART for less than one month. The risk of vertical transmission in the absence of therapy was four times higher than before the era of antiretroviral therapy (ART; p=0.05). In conclusion, since the prevention of MTCT of HIV with HAART is the standard of care, a short duration or absence of ART during pregnancy linked to late or absent prenatal care is associated with a high risk of transmission. The early detection of HIV-1 infection in pregnant women, and close follow up and support during pregnancy are crucial to the success of the prevention of transmission.
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Antirretrovirales/uso terapéutico , Infecciones por VIH/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Zidovudina/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Bélgica/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Incidencia , Recién Nacido , Masculino , Prevalencia , Estudios RetrospectivosRESUMEN
OBJECTIVES: Preeclampsia is a leading cause of maternal and perinatal morbidity. Work-related factors may influence the occurrence of this disorder. This case-control study estimated the associations between work-related physical and psychosocial factors and the risk of preeclampsia and gestational hypertension. METHODS: The eligible women consisted of a random sample of the women who delivered a singleton live birth in 1997-1999 in six regions of Quebec and worked during pregnancy. Cases of preeclampsia (N=102) and gestational hypertension (N=99) were compared with normotensive controls (N=4381). Information on occupational exposures at the onset of pregnancy was collected during phone interviews a few weeks after delivery. Detailed information was obtained on work schedule, postures, physical exertion, work organization, noise, vibration, and extreme temperature. Adjusted odds ratios (aOR) were estimated through polytomous logistic regression. RESULTS: Women standing daily at least 1 hour consecutively without walking experienced a higher risk of preeclampsia [aOR 2.5, 95% confidence interval (95% CI) 1.4-4.6], as well as women climbing stairs frequently (aOR 2.3, 95% CI 1.2-4.1) and women working more than 5 consecutive days without a day-off (aOR 3.0, 95% CI 1.0-9.5). Squatting or kneeling, pushing or pulling objects, whole-body vibration, forced pace, job strain, and no control on breaks were positively, but nonsignificantly, associated with preeclampsia. The associations were weaker for gestational hypertension. CONCLUSIONS: These findings suggest that being exposed to physically demanding and stressful occupational conditions at the onset of pregnancy increases the risk of preeclampsia.
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Hipertensión Inducida en el Embarazo/etiología , Exposición Profesional , Preeclampsia/etiología , Adulto , Estudios Epidemiológicos , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Entrevistas como Asunto , Exposición Profesional/efectos adversos , Vigilancia de la Población , Preeclampsia/epidemiología , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Quebec/epidemiología , Factores de Riesgo , Estrés PsicológicoRESUMEN
Each of the 17 vertically infected infants born to HIV-1-infected mothers in Belgian HIV reference centers since 1996 was treated with a combination of 3 reverse transcription inhibitors as soon as the diagnosis was established. Treatment was initiated in all patients before 66 days of life. Twelve patients, including 11/13 infants treated with the combination of zidovudine, lamivudine and nevirapine, experienced a complete viral suppression (<50 copies/mL) with their first drug regimen. At last follow-up, 12 patients were asymptomatic, 2 were CDC stage A and 3 were stage B; 15 had HIV-1 RNA levels of <50 copies/mL and 14 had >or=25% CD4 lymphocytes. These results suggest that early initiation of treatment with 3 reverse transcription inhibitors is highly effective to inhibit viral replication and to prevent clinical and immunologic progression of HIV infection in vertically infected infants.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Enfermedades del Prematuro/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Lactante , Recién Nacido , Enfermedades del Prematuro/virología , ARN Viral/sangre , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Replicación Viral/efectos de los fármacosRESUMEN
OBJECTIVE: To estimate the associations between biomedical, social and health care factors and the occurrence of severe pre-eclampsia, eclampsia or HELLP syndrome. STUDY DESIGN: A case-control study conducted in 14 of the 15 maternity hospitals of Brussels. Cases were all 99 women who delivered in these hospitals in 1996 and who had severe pre-eclampsia, eclampsia or HELLP syndrome. Controls were 200 women without these severe maternal conditions, randomly selected among women who delivered in the same hospitals during the same period. Crude odds ratios were computed and adjusted odds ratios were derived from logistic regression. RESULTS: Indicators of social deprivation such as low educational level, poverty and illegal residence or asylum request, were strongly associated with the outcome in univariate analysis. So were African or Turkish ethnicity, obesity, chronic hypertension and primiparity. Logistic regression showed that no access to national health insurance and history of residence in another country were strongly and independently associated with the outcome (adjusted odds ratio = 4.0 (95% confidence interval 1.1, 14.0) and 3.7 (95% confidence interval 1.9, 7.3), respectively). CONCLUSIONS: The burden of pre-eclampsia is concentrated in socially disadvantaged women. Health services should be more responsive to the specific needs of these women. Low access to health care may contribute to the occurrence of severe pre-eclampsia in our setting.