Edwige Haelterman

Somali women and their pregnancy outcomes postmigration: data from six receiving countries

Objective  This study aimed to investigate pregnancy outcomes in Somali‐born women compared with those women born in each of the six receiving countries: Australia, Belgium, Canada, Finland, Norway and Sweden.

Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected infants

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.

Social deprivation and poor access to care as risk factors for severe pre-eclampsia

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.

Impact of adjuvants on CD4+ T cell and B cell responses to a protein antigen vaccine: Results from a phase II, randomized, multicenter trial

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.

Severe Infections in HIV-Exposed Uninfected Infants Born in a European Country

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.

Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial

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.

Randomized Trial of the Immunogenicity and Safety of the Hepatitis B Vaccine Given in an Accelerated Schedule Coadministered with the Human Papillomavirus Type 16/18 AS04-Adjuvanted Cervical Cancer Vaccine

ABSTRACT 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.

Short- and Long-term Immunological and Virological Outcome in HIV-Infected Infants According to the Age at Antiretroviral Treatment Initiation

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.

Paradoxical reaction during tuberculosis treatment in immunocompetent children: Clinical spectrum and risk factors

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.

Effect of adopting host-country nationality on perinatal mortality rates and causes among immigrants in Brussels

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.