Magdalena Marczyńska

Mother to child transmission of HIV infection in the era of highly active antiretroviral therapy

BACKGROUND Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. METHODS Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. RESULTS Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001-2003. The overall MTCT rate in this period was 2.87% (95% confidence interval [CI], 2.11%-3.81%), but it was 0.99% (95% CI, 0.32%-2.30%) during 2001-2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1; P=.003) and elective Caesarean section (AOR, 0.33; P=.04). Detection of maternal HIV RNA was significantly associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03-0.33), compared with vaginal delivery or emergency Caesarean section. CONCLUSIONS Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important.

Body fat abnormality in HIV-infected children and adolescents living in europe: Prevalence and risk factors

Objectives: To estimate the prevalence of and identify risk factors for lipodystrophy syndrome (LS) and body fat abnormality in a population of HIV-infected children and adolescents. Design: Cross-sectional observational study. Methods: HIV-infected subjects aged 2–18 years were recruited from 15 HIV centers in Belgium, Italy, and Poland between January 2007 and December 2008. Standardized assessments by the patients long-term clinician were performed to establish the presence of abnormality. Risk factors were explored in logistic regression models for fat abnormality outcomes and LS (abnormality plus dyslipidemia). Results: Among 426 subjects (70% white), median age was 12.2 years (interquartile range: 9.0–15.0 years) and median duration of antiretroviral therapy was 5.2 years (interquartile range: 2.2–8.8 years). Prevalence was 57% (n = 235) for LS and 42% (n = 176) for fat abnormality; 90 subjects with abnormality were affected in ≥3 locations. Lipoatrophy occurred in 28% (n = 117) of subjects and lipohypertrophy in 27% (n = 115), most commonly in the face and trunk, respectively. In multivariable analysis, white ethnicity, body mass index, ritonavir/lopinavir, and nonnucleoside reverse transcriptase inhibitors were each associated with an increased risk of LS (P < 0.05). White ethnicity, history of Centers for Disease Control and Prevention–defined disease, and stavudine were associated with risk of lipoatrophy (P < 0.05). Increased risk of lipohypertrophy was associated with body mass index and prior HIV disease. Conclusions: Fat abnormality was prevalent in close to half of children and adolescents, who had accumulated long treatment durations. Risk of fat abnormality was associated with specific drugs, including stavudine and ritonavir, and other variables. Our results underline the importance of continued surveillance of children treated with antiretroviral therapy.

Age related standards for total lymphocyte, CD4+ and CD8+ T cell counts in children born in Europe

Objective: Currently used reference values for immunologic markers in children are largely derived from cross-sectional data from historic, small sample size studies in predominantly white children. There is a lack of reliable age-related standards for immunologic markers, such as CD4+ cell counts, in particular in black children whose values according to recent reports may differ from those in white children. Standards are essential for diagnosing and monitoring childhood diseases such as pediatric human immunodeficiency virus (HIV) infection. Design: Prospective cohort study with data on 1781 uninfected children born to HIV-infected mothers in the European Collaborative Study. Methods: Age-related standards (centiles) for immunologic markers (CD4+ and CD8+ cell counts and total lymphocyte counts) up to 5 years in black and up to 10 years in white children were constructed using Generalized Additive Models for Location, Scale and Shape method, which allows for variability and skewness of the data. The optimal model was chosen according to the Akaike Information Criterion. Results: Patterns and values of total lymphocyte, CD4+ and CD8+ cell counts varied with age, especially in the first 3 years of life, but less so thereafter. Values of all 3 immunologic markers were substantially and significantly lower in black than in white children of the same age. Conclusions: We present age-related standards separately for black and white children to aid clinicians in the monitoring of childhood diseases. These standards may also contribute to the decision on an accurate cutoff for CD4+ cell counts for initiating treatment of HIV-infected children.

Environmental and personal risk factors for toxocariasis in children with diagnosed disease in urban and rural areas of central Poland.

To investigate the epidemiology of human toxocariasis a field survey was carried out at homes of 194 children (80 of rural and 114 of urban origin) with diagnosed disease from central Poland. A questionnaire referring to the possible risk factors was directed to their parents. Overall contamination rate of soil by Toxocara eggs was 27.5% in rural and 21.1% in urban environment in the households examined, with difference not significant (chi2=1.08, p=0.2986). In rural settlements 29.3% of yards surrounding houses were found contaminated, whereas in urban 25.0% of family gardens, 26.4% of private yards and 10.7% of public sandpits were positive. Frequency of positive samples differs only for rural yards and urban sandpits (chi2=3.85, p=0.0499). The study showed a high risk of reinfection for the ill children in sites of their residence. Despite diagnosed toxocariasis kids were not adequately supervised by their parents with no measures undertaken to avoid further infection. These data present strong need for educational programs which should be implemented for prevention of Toxocara infections in children.

Guidance on vaccination of HIV‐infected children in Europe

EN Menson,1 MJ Mellado,2 A Bamford,3 G Castelli,4 D Duiculescu,5 M Marczyńska,6 ML Navarro,7 HJ Scherpbier8 and PT Heath9 on behalf of the Paediatric European Network for Treatment of AIDS (PENTA) Vaccines Group, PENTA Steering Committee and Children’s HIV Association (CHIVA) 1Department of General Paediatrics, Evelina Children’s Hospital @St Thomas’ Hospital, London, UK, 2Paediatric Infectious Disease and Tropical Diseases Unit, Paediatric Department, Carlos III Hospital, Madrid, Spain, 3Section of Paediatrics, Division of Infectious Diseases, Imperial College London, London, UK, 4Infectious Diseases Paediatric Unit, “Bambino Jesu” Hospital, Rome, Italy, 5HIV Department, ‘Dr. Victor Babes’ Hospital for Infectious and Tropical Diseases, Bucharest, Romania, 6Children’s Infectious Diseases Department, Infectious Diseases Hospital, Medical University of Warsaw, Warsaw, Poland, 7Section of Infectious Diseases, Paediatric Department, Gregorio Marañon Hospital, Madrid, Spain, 8Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children’s Hospital/Academic Medical Center, Amsterdam, the Netherlands and 9Division of Clinical Sciences & Vaccine Institute, St George’s, University of London, London, UK

Evolving patterns of HIV-1 transmitted drug resistance in Poland in the years 2000-2008.

The aim of the study was to determine the rate of transmission of drug resistant human immunodeficiency virus‐1 (HIV‐1) variants among therapy‐naïve HIV positive patients in Poland in the year 2008, to compare the data with the results from the years 2000 to 2007 and to monitor patterns of HIV‐1 subtypes present in Polish population and their evolution. Complete protease and part of reverse transcriptase regions were sequenced from the sera of patients directed to the laboratory for drug resistance testing. The Stanfords HIVdb program was used for the interpretation of results and subtyping. The variants scoring at least “intermediate resistance” for at least one drug were considered as resistant. The results obtained were compared to those obtained in the years 2000–2007. A total of 95 patients were enrolled in the 2008 study. Homosexual transmission of infection was documented in more than 55% of all cases. The overall prevalence of transmitted drug resistance (TDR) was 5.3% (3.9% in 2007, 5.8% in 2006, and 14.1% in the years 2002–2005). The study from the years 2000 to 2001 revealed 28.7% prevalence. Preliminary analysis of the first half of 2009 shows the ratio of 7.8%. In four (4.2%) cases drug resistance was associated with protease inhibitors class, in one case (1.1%) with resistance to non‐nucleoside reverse transcriptase inhibitors class. In four cases (4.2%) non‐B subtype was identified (C, G, CRF01_AE, CRF02_AG). An increase of percentage of drug resistant mutants—from 3.9% (2007) to 5.3% (2008)—was recognized. In this study, TDR was limited to single classes of antiretroviral drugs. HIV‐1 subtype B prevails in Poland. J. Med. Virol. 82:1291–1294, 2010.

A serological and epidemiological evaluation of risk factors for toxocariasis in children in central Poland

The level of specific anti-Toxocara IgG was examined in 343 children from central Poland with suspected Toxocara infection. Based on the presence of specific IgG antibodies and clinical signs and symptoms, toxocariasis was confirmed in 249 patients. The serological results of diagnosed cases were analysed in connection with epidemiological data (contamination of soil around the childrens homes and presence of a dog or a cat). A higher prevalence of soil contamination with Toxocara eggs was found in suburban and rural areas (30.9% and 24.6%, respectively) whereas it was lower in urban areas (10.3%). In about 40% of the children whose households were not contaminated, a decrease in the antibody level was observed 2 years after treatment for toxocariasis, while there was no such decline in those living in contaminated places. The logistic regression model employed to determine the correlation between seropositivity in the children and selected epidemiological risk factors showed a statistically significant relationship in connection only with dog ownership (P = 0.0238). The present results have demonstrated the high risk of toxocariasis for children from rural and suburban areas in Poland. The sero-epidemiological investigations indicated that re-infection might be the reason for persistence of seropositivity after treatment.

The influence of hepatitis B and C virus coinfection on liver histopathology in children.

AbstractThe influence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on liver histology in children remains unknown. We analyzed histopathological features in 70 treatment-naïve children: 10 with HBV/HCV coinfection (case group A), 30 with HBV (control group B), and 30 with HCV (control group C). Liver biopsies were scored for grading and staging according to Knodell’s modified system and were tested for an association with demographic and laboratory data. The mean grade was higher in coinfected children compared to control group C (6.2 ± 3.0 vs. 4.2 ± 2.5, p = 0.04), but not control group B (p = 0.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (p = 0.05). Mean staging did not differ between the case and control groups. Multivariate analysis revealed that HBV/HCV coinfection and aminotransferase activity were independently associated with moderate to severe necroinflammatory activity Conclusion: HBV/HCV coinfection was associated with moderate to severe necroinflammation irrespective of age at biopsy or duration of infection and led to significantly higher necroinflammatory activity than HCV monoinfection. HBV/HCV coinfection did not enhance fibrosis. High aminotransferase levels were positively associated with moderate to severe necroinflammation.

Risk of human toxocarosis in Poland due to Toxocara infection of dogs and cats

The purpose of this paper was to present the current data on the risk of toxocarosis in humans in Poland and to give an overview of the clinical and diagnostic aspects of the disease. The number of reported clinical cases of Toxocara infection in children in Poland in medical literature has increased recently. The results of field surveys aimed to evaluate the soil contamination with geohelminth eggs conducted during the last few years showed that Toxocara is the most common zoonotic agent in urban public sites and in rural settlements. The questionnaire revealed rural inhabitants’ low awareness of zoonotic parasite threats to humans. In particular parents should be advised as to what proper preventive measures to undertake to eliminate the toxocarosis risk factors for children in rural environment. Prevention of initial environment contamination with Toxocara canis and T. cati eggs, which includes proper treatment regimes to eliminate patent infections in dogs and cats and preventing pets from defecating in public areas and private households is vital. To provide the public with suitably presented information as well as pet owners with uniform recommendations, a close collaboration between veterinary and public health professionals is crucial.

Early vs deferred highly active antiretroviral therapy in HIV infected infants: a European Collaborative Cohort Study

Without antiretroviral therapy (ART), approximately 20% of HIV-1 vertically infected infants develop severe disease manifestations before the age of 1 year [1] and surrogate markers poorly predict infants at higher risk of rapid disease progression. Several small prospective and retrospective studies in developed countries have suggested that ART initiated early in life could prevent this rapid clinical and immunologic deterioration [2-6].