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Cel pracyOcena częstości występowania zaburzeń psychicznych, behawioralnych, emocjonalnych oraz ustalenie związków ze zmiennymi klinicznymi i socjodemograficznymi u dzieci i młodzieży z wertykalnym zakażeniem HIV.MetodaW badaniu udział wzięło 56 dzieci z wrodzonym zakażeniem HIV (grupa PHIV+), 24 zdrowych dzieci urodzonych przez matki zakażone HIV (grupa PHEU) oraz 43 zdrowych dzieci zdrowych rodziców (grupa HIV-nA), w wieku 6-18 lat. Do oceny zaburzeń behawioralnych i emocjonalnych zastosowano Kwestionariusz dla Rodziców CBCL/4-18 oraz Kwestionariusz Samooceny YSR, do oceny objawów zaburzeń psychicznych półustrukturyzowany wywiad diagnostyczny K-SADS-PL.WynikiWykazano wyższą częstość występowania zaburzeń psychicznych w ciągu życia w grupie PHIV+ oraz grupie PHEU w porównaniu z grupą HIV-nA. Najczęściej diagnozowano zaburzenia lękowe oraz zaburzenia nastroju. Występowanie objawów zaburzeń emocjonalnych i behawioralnych w grupie PHIV+ oraz w grupie PHEU było związane z podobnymi zmiennymi socjodemograficznymi (m.in. płeć męska, niezamieszkiwanie z opiekunem biologicznym, doświadczenie stresującego wydarzenia w życiu). Zaburzenia psychiczne występowały częściej u osób, u których leczenie antyretrowirusowe (ARV) rozpoczęto dopiero po 12 m.ż. Stwierdzono dodatnią korelację pomiędzy wynikiem dla części skal YSR i CBCL/4-18, a liczbą limfocytów CD4 w momencie przeprowadzania badania oraz wyższym logarytmem wiremii na początku leczenia ARV i w momencie ustalenia rozpoznania zakażenia HIV.WnioskiW grupie dzieci PHIV+ oraz PHEU, stwierdzono wyższą częstość występowania zaburzeń psychicznych. Cięższy przebieg zakażenia HIV i jego nasilenie przed rozpoczęciem leczenia wiąże się z większym nasileniem problemów internalizacyjnych.

Background Although COVID-19 is associated with a mild course in children, a certain proportion requires admission to hospital due to SARS-CoV-2 infection and coexisting diseases. The prospective multicenter study aimed to analyze clinical factors influencing the length of the hospital stay (LoHS) in children with COVID-19. Methods The study included 1283 children from 14 paediatric infectious diseases departments with diagnosed SARS-CoV-2 infection. Children were assessed in respective centres regarding indications for admission to hospital and clinical condition. History data, clinical findings, laboratory parameters, treatment, and outcome, were collected in the paediatric SARSTer register. The group of children with a hospital stays longer than seven days was compared to the remaining patients. Parameters with a statistically significant difference were included in further logistic regression analysis. Results One thousand one hundred and ten children were admitted to the hospital, 763 children were hospitalized >24 h and 173 children >7 days. 268 children had comorbidities. Two hundred and eleven children had an additional diagnosis with coinfections present in 135 children (11%). Factors increasing the risk of higher LoHS included pneumonia [odds ratio—OR 3.028; 95% confidence interval—CI (1.878–4.884)], gastrointestinal symptoms [OR = 1.556; 95%CI (1.049–2.322)], or rash [OR = 2.318; 95%CI (1.216–4.418)] in initial clinical findings. Comorbidities [OR = 2.433; 95%CI (1.662–3.563)], an additional diagnosis [OR = 2.594; 95%CI (1.679–4.007)] and the necessity of the empirical antibiotic treatment [OR = 2.834; 95%CI (2.834–6.713)] were further factors related to higher LoHS. Conclusions The clinical course of COVID-19 was mild to moderate in most children. Factors increasing the risk of higher LoHS included pneumonia, gastrointestinal symptoms, comorbidities, an additional diagnosis, and the empirical antibiotic treatment.

We present the efficacy and safety of 12 weeks of therapy with a fixed dose of ledipasvir/sofosbuvir in 2 teenagers with HIV/hepatitis C virus coinfection. Patient 1 presented with compensated cirrhosis, whereas patient 2 had evidence of previous hepatitis B virus infection. Both patients achieved a sustained virologic response 12 weeks after the end of treatment. No serious adverse effects were reported.

Chronic hepatitis C (CHC) is a global health burden. Mother-to-child transmission (MTCT) accounts for most HCV infections in pediatric patients. Spontaneous viral clearance may occur in early childhood but is uncommon thereafter. Infection is usually asymptomatic during childhood, although without an effective treatment, vertically infected children may develop serious liver complications including cirrhosis and hepatocellular carcinoma in adulthood. Despite the lack of vaccine against hepatitis C and effective post-exposure methods of prevention of MTCT, treatment with direct-acting antiviral agents (DAAs) raised the prospect of eliminating HCV on a population level. Highly effective, well-tolerated, oral, and interferon-free regimens of short duration have revolutionized treatment of CHC. However, access to these therapies might be limited because of its high cost. In this review, we provide the current state of knowledge on the epidemiology, testing, monitoring and treating of HCV in children. We outline the remaining gaps in therapy and barriers to disease eradication.Chronische Hepatitis C (CHC) stellt eine globale Gesundheitsbelastung dar. Die Mutter-Kind-Übertragung (MTCT) ist für die meisten HCV-Infektionen bei pädiatrischen Patienten verantwortlich. Eine spontane Virusfreisetzung kann in der frühen Kindheit auftreten, ist danach aber selten. In der Regel verläuft die Infektion während der Kindheit asymptomatisch, obwohl unbehandelte vertikal infizierte Kinder schwere Leberkomplikationen wie Zirrhose und Leberzellkarzinom im Erwachsenenalter entwickeln können. Trotz des Fehlens eines Impfstoffs gegen Hepatitis C und wirksamer Methoden zur Prävention von MTCT nach der Exposition hat die Behandlung mit direkt wirkenden antiviralen Wirkstoffen (DAA) die Aussicht auf eine Eliminierung von HCV auf Bevölkerungsebene erhöht. Hochwirksame, gut verträgliche, orale und kurzzeitige interferonfreie Therapien haben die Behandlung von CHC revolutioniert. Der Zugang zu diesen Therapien könnte jedoch aufgrund der hohen Kosten begrenzt sein. In diesem Überblick stellen wir den aktuellen Stand des Wissens über Epidemiologie, Testung, Überwachung und Behandlung von HCV bei Kindern dar. Wir skizzieren die verbleibenden Therapielücken und Hindernisse bei der Ausrottung der Krankheit.

Background The aim of this prospective study was to analyze liver fibrosis in teenagers with chronic hepatitis C (CHC) using noninvasive methods. Methods Thirty-five patients with CHC, 12-17 years of age (mean 14.2 ± 1.8 years; 22/35, 63% male) were included. Most of them (29/35, 83%) were infected vertically, 21/35 (60%) were treatment-naive, 30/35 (86%) were infected with genotype 1 and 5/35 (14%) were infected with genotype 4 HCV. In all patients, evaluation of liver fibrosis was performed using transient elastography (TE) and measurement of the following serum biomarkers: aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 index (FIB-4). Using liver stiffness measurement (LSM) results as a reference, the diagnostic performance of APRI and FIB-4 was assessed by calculating area under the receiver operating characteristics curve. Results Transient elastography results revealed no or mild fibrosis (F0/1 in METAVIR scale) in 31/35 (89%) patients. In 4/35 (11%) patients, significant fibrosis was observed (F ≥ 2), including 3/35 (9%) with cirrhosis (F4). The median APRI was 0.32, and the median FIB-4 was 0.32. LSM was associated with both APRI and FIB-4 [r = 0.61, 95% confidence interval (CI) 0.35-0.79, P = 0.0001; and r = 0.60, 95% CI 0.32-0.78, P = 0.0002, respectively]. For the diagnosis of significant fibrosis, the area under the receiver operating characteristics (95% CI) for both APRI and FIB-4 was 0.855 (0.695-0.951). APRI, with a cutoff >0.374, predicted significant fibrosis, with 100% sensitivity and 67.7% specificity, whereas FIB-4, with a cutoff >0.402, predicted significant fibrosis, with 75.0% sensitivity and 90.3% specificity. Conclusions Significant fibrosis, including cirrhosis, may occur in teenagers with CHC. Serum biomarkers (APRI, FIB-4) correlate positively with LSM.

Background: There are limited data available on the influence of direct-acting antivirals used to treat chronic hepatitis C (CHC) on growth in children. In this study, we aimed to analyze the growth parameters in children treated with ledipasvir/sofosbuvir (LDV/SOF). Methods: We included 38 patients (16 girls and 22 boys) aged 10–17 years treated with LDV/SOF for CHC (33 infected with genotype 1 and 5 with genotype 4; 36 were treated for 12 weeks, and 2 for 24 weeks according to the current guidelines). Patient weight and height were measured at baseline, after 4 weeks of treatment, at the end of the treatment (EOT), and 12 weeks and one year after the EOT. Body mass index (BMI), BMI z and height-for-age (HA) z scores were calculated according to the WHO Child Growth Standards and Growth reference data using the WHO anthropometric calculator AnthroPlus v. 1.0.4. In addition, correlations between BMI z scores and liver fibrosis (liver stiffness measurement, LSM), the aspartate transaminase (AST)-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4) and liver steatosis (controlled attenuation parameter, CAP) were analyzed. Results: At baseline, 5/38 (13%) patients were obese (BMI z score >2 SD), 4/38 (11%) were overweight, and 29 (76%) were normal. A significant increase was observed in mean weight, height and BMI both 12 weeks and one year after the treatment compared to the baseline, whereas no differences were observed for BMI z scores and HA z scores. Baseline BMI z scores correlated with alanine aminotransferase levels (r = 0.33, 95% CI 0.01–0.58, p = 0.04), LSM (r = 0.40, 95% CI 0.09–0.65, p = 0.01), the APRI (r = 0.33, 95% CI 0.02–0.59, p = 0.03), and the CAP (r = 0.40, 95% CI 0.08–0.64, p = 0.01). No similar correlations were reported at 12 weeks posttreatment. Conclusions: Treatment with LDV/SOF in children with CHC (genotypes 1 and 4) did not negatively influence the patients’ growth. However, higher baseline BMI z scores correlated with more advanced liver fibrosis and steatosis in children with CHC.

Background Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. Methods Data on children aged Results 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) 3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens–Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. Conclusion Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

The study aimed to analyse the clinical course of COVID-19 in 300 infants, selected from 1283 children diagnosed with COVID-19 between March and December 2020, registered in the SARSTerPED multicenter database. Most of the infants were registered in October and November 2020. 44% of the group were girls, and 56% were boys. At diagnosis, the most common symptoms were fever in 77% of the children, cough in 40%, catarrh in 37%. Pneumonia associated with COVID-19 was diagnosed in 23% of the children, and gastrointestinal symptoms in 31.3%. In 52% of the infants, elevated levels of D-dimers were observed, and in 40%, elevated levels of IL-6 serum concentration were observed. During the second wave of the pandemic, 6 times more infants were hospitalized, and the children were statistically significantly younger compared to the patients during the first wave (3 months vs 8 months, p

Background Mother-to-child transmission is one of the main sources of hepatitis C virus (HCV) infection in children. However, because of the asymptomatic course of the illness, certain women may not be aware of their infection. Objectives The aim of this study was to estimate the significance of epidemiological anamnesis in diagnoses of HCV infection in women of reproductive age and to evaluate how screening among pregnant women impacts the detection of HCV infection. Material and methods Epidemiological interviews of 432 mothers infected with HCV (but free of human immunodeficiency virus (HIV)) were conducted in the Warsaw Hospital for Infectious Diseases (Poland) from 1998 to 2012. Results Complaints or abnormalities in laboratory tests were the reasons for anti-HCV antibody testing in 28.2% of mothers, whereas specific interview responses or occupational health care services group affiliation were the reasons for testing in 35.6%. However, in a large group of women, infection was only detected because of screening examinations. The introduction of routine screening for pregnant women (since 2010 in Poland) has led to the increased detection of HCV infection in women who did not present with infection risk factors (9.9% before 2010 vs 46.1% after 2010). This practice has also led to an increase in the percentage of women diagnosed during pregnancy (21.5% before 2010 vs 30.8% after 2010). Conclusions Establishing HCV infection risk factors during the interview process is the most common indicator for serological testing; however, not all infected cases can be diagnosed in this manner. Screening for anti-HCV antibodies in pregnant women increases the detection of HCV infection in this group.

Difficulties in achieving elimination targets of the World Health Organization’s Global Strategy on viral hepatitis might be overcome through a new micro-elimination approach that allows for a quick, efficient targeting of treatment and prevention services. Particular focus on identification of high-risk and so far marginalized populations, such as children and adolescents, increases chances for HCV elimination on a country, and ultimately on a population level. Therefore, a broad access to safe and highly effective direct-acting antiviral drugs is of upmost importance in the pediatric population.

BACKGROUND Therapy with pegylated interferon and ribavirin (PEG-IFN+RBV) for chronic hepatitis C (CHC) still remains the only option available for children in many Eurasian and European countries. Our aim was to evaluate the influence of host and viral factors on response to IFN-based therapy to optimize it for those in whom directly acting antivirals (DAA) are currently unavailable. METHODS Seventeen vertically infected, treatment naive children (10 male and 7 female) aged 5-16 years with CHC underwent a course of PEG-IFN+RBV. The end point was sustained virologic response (SVR). Host and virus factors were divided into pre- and ontreatment predictors of response to therapy. RESULTS Eleven patients obtained SVR (64%), 4 were nonresponders (23%), and 2 were relapsers (12%). Significant relationship was found between HCV RNA elimination and following variables: virus genotype and early virologic response (EVR) (p< .037, p< .029 respectively). Higher eradication rate was observed in patients infected with genotype 3 HCV (100% vs. 65% with genotype 1 or 4), and in those with undetectable HCV RNA by week 12 (88% vs. 66% with viremia). EVR was associated with SVR (83% vs. 0% in nonresponders; p< .004). C allele of IL28B rs12979860 was a predictor of EVR (p < .043). The SVR rates among CC, CT, and TT carriers were as follows: 75%, 67%, and 33%. CONCLUSIONS Detection of favourable HCV and IL28B genotype prior to commencement of PEG-IFN+RBV, and continuing it in patients with EVR is of major importance for those in whom DAA are still unavailable.

Data on the novel coronavirus disease 2019 (COVID-19) in children are limited, and studies from Europe are scarce. We analyzed the clinical severity and epidemiologic aspects of COVID-19 in consecutive children aged 0–18 years, referred with a suspicion of COVID-19 between February 1, and April 15, 2020. RT-PCR on a nasopharyngeal swab was used to confirm COVID-19. 319 children met the criteria of a suspected case. COVID-19 was diagnosed in 15/319 (4.7%) patients (8 male; mean age 10.5 years). All of them had household contact with an infected relative. Five (33.3%) patients were asymptomatic. In 9/15 (60.0%) children, the course of the disease was mild, and in 1/15 (6.7%), it was moderate, with the following symptoms: fever (46.7%), cough (40%), diarrhea (20%), vomiting (13.3%), rhinitis (6.7%), and shortness of breath (6.7%). In the COVID-19-negative patients, other infections were confirmed, including influenza in 32/319 (10%). The clinical course of COVID-19 and influenza differed significantly based on the clinical presentation. In conclusion, the clinical course of COVID-19 in children is usually mild or asymptomatic. In children suspected of having COVID-19, other infections should not be overlooked. The main risk factor for COVID-19 in children is household contact with an infected relative.

One-year outcomes after therapy with ledipasvir/sofosbuvir (LDV/SOF) in children with chronic hepatitis C (CHC) presenting with and without significant liver fibrosis were analyzed. We included patients aged 12–17 years treated with LDV/SOF, presenting with significant fibrosis (F ≥ 2 on the METAVIR scale) in transient elastography (TE) at the baseline and we compared the outcomes with that of patients without fibrosis. Patients were followed every 4 weeks during the treatment, at the end of the therapy, at week 12 posttreatment, and one year after the end of treatment. Liver fibrosis was established using noninvasive methods: TE, aspartate transaminase-to-platelet ratio index (APRI), and Fibrosis-4 index (FIB-4). There were four patients with significant fibrosis at baseline: one with a fibrosis score of F2 on the METAVIR scale, and three with cirrhosis (F4) at baseline. One year after the end of treatment, the hepatitis C viral load was undetectable in three of them. One patient was lost to follow-up after week 4. In two out of the four patients, a significant improvement and regression of liver fibrosis was observed (from stage F4 and F2 to F0-F1 on the METAVIR scale). In one patient, the liver stiffness measurement median increased 12 weeks after the end of the treatment and then decreased, but still correlated with stage F4. An improvement in the APRI was observed in all patients. In four patients without fibrosis, the treatment was effective and no progression of fibrosis was observed. A one-year observation of teenagers with CHC and significant fibrosis treated with LDV/SOF revealed that regression of liver fibrosis is possible, but not certain. Further observations in larger groups of patients are necessary to find predictors of liver fibrosis regression.

In a recent publication, Baer et al pointed out that there are few studies on the association between sexually transmitted infections (STIs) and prematurity.1 Similarly, there are limited data on prematurity in the setting of HIV and HCV) co-infection. Many factors can contribute to preterm delivery in this population, both related and not related to HIV. For example, gestational age may be affected by HIV-related immunosuppression or use of antiretroviral therapy (ART).2 3 There is also evidence that in vitro HCV may infect the human trophoblast and cause ultrastructure changes.4 Relation between HCV infection and preterm birth has already been studied in …

Introduction and objective In recent decades the use of orthodontic appliances in Poland has increased; however, data on their influence on changes of components of the microbiome connected with oral biofilm are scarce. The objective of this study was to evaluate oral microbiota in terms of their role as risk factors for health complications. Material and methods The study included 100 patients treated with removable or fixed appliances. Oral hygiene and gingival health were determined, and periodontal swabs taken from each patient for parasitological, bacteriological and mycological microscopic and in vitro examinations. Results Oral protists and various pathogenic and opportunistic bacterial and fungal strains were identified in the superficial layer of biofilm. A higher prevalence of bacteria, Enterococcus faecalis, E. faecium, Staphylococcus aureus and Escherichia coli, and various strains of yeast-like fungi from the Candida albicans group, occurred in patients treated with the fixed appliance than in those using a removable appliance or not treated orthodontically. In some periodontal samples from patients treated with fixed appliances, cysts of the Acanthamoeba spp. were found. Conclusions The use of orthodontic appliances alters the status of the oral cavity; it has impact on the colonization of oral biofilm by opportunistic/pathogenic strains, and increases the risk of their dissemination to various human tissues and organs. Pretreatment examination of oral microbiome, its monitoring particularly during treatment with fixed appliances, and preventive elimination of the potentially pathogenic strains to avoid health complications, are highly recommended, especially in patients with impaired immunity.

To the EditorGuidelines for antiretroviral treatment of HIV infection were recently published by the present journal, including recommendations for adults and children [1]. An additional important ...

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Histopathological features and determinants of liver disease progression were analyzed in 42 treatment-naïve children (mean age: 10.7 ±3.7) with chronic hepatitis C (14/42 infected vertically and 26/42 horizontally). Histopathological evaluation was performed according to Knodell's modified system. Predictors of necroinflammation and fibrosis were identified using linear regression analyses. Most children presented with mild necroinflammation and fibrosis (mean grade 4.3 ±2.7, mean staging 1.2 ±0.8), irrespective of the mode of transmission. Vertically infected children were younger than those infected horizontally (8.6 ±2.5 vs. 11.5 ±3.7 years, p = 0.02). Alanine and aspartate aminotransferase (ALT and AST) levels were associated with necroinflammation (p = 0.003 and p = 0.01 for ALT and AST, respectively) and fibrosis (p = 0.01 and p = 0.04, respectively). Other positive independent predictors of fibrosis included duration of infection (p = 0.03) and body mass index (BMI) z-score (p = 0.03). Children with chronic hepatitis C presented with mild liver changes over a decade after the infection, irrespective of the mode of transmission. Since fibrosis is a time-dependent process, progression of the liver disease in vertically infected children may occur at a younger age compared to patients infected horizontally. Aminotransferase levels were associated with necroinflammation and fibrosis. Longer duration of infection and a higher BMI z-score were associated with more severe fibrosis.

Background There is a need for validation of noninvasive alternatives to liver biopsy for the evaluation of fibrosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the diagnostic performance of serum biomarkers modified by the body mass index z-score (BMI z-score) for the detection of fibrosis and steatosis in children with CHC. Methods Thirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC underwent liver biopsy. Fibrosis was scored using a 5-point METAVIR scale (≥2 = significant fibrosis). For all the children, the following noninvasive markers were calculated: The aspartate transaminase (AST)-to-platelets ratio index (APRI), the modified APRI (M-APRI: BMI z-score × APRI), the Fibrosis-4 index (FIB-4), the modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The area under the receiver operator characteristic curve (AUROC) was calculated to detect significant fibrosis and steatosis. Results In the histopathological evaluation, 22/30 (73%) patients presented with fibrosis, and 8/30 (27%) presented with steatosis. For the detection of significant fibrosis, the AUROCs for M-APRI, M-FIB-4 and B-AST were 0.842, 0.823, and 0.848, respectively. For significant steatosis, the AUROCs were more than 0.9 for all markers that included the BMI z-score. B-AST, with a cut-off of 92.8, showed 71% sensitivity and 95% specificity for detecting significant fibrosis. For predicting severe steatosis, B-AST had 100% sensitivity and 92% specificity. Negative values of all three markers that included BMI z-scores excluded all patients with both significant fibrosis and significant steatosis. Conclusions Including the BMI z-score in serum biomarker formulas enhances their diagnostic ability to detect significant fibrosis and steatosis. B-AST may thus act as an effective alternative to liver biopsy.

Zidovudine (ZDV) has been associated with risk of haematological toxicity. Safety data from clinical trials is generally limited to 48 weeks. We assessed the short- and mid-term toxicity of ZDV/lamivudine (3TC) fixed-dose combination scored tablets in HIV-infected children followed in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) network.Fourteen cohorts provided data on patients18 years of age taking ZDV/3TC scored tablets between 2008 and 2012. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory adverse events (AEs) for hepatobiliary and haematological disorders were estimated by duration on drug (12, 12-24,24 months). Clinical adverse events and reasons for tablet discontinuation were described.Of 541 patients on ZDV/3TC, 388 (72%) had weight and dose data available, of whom 350 (90%) weighed ≥14 kg and were eligible for tablet use; 161 (41%) were aged10 years on an approved dose, 189 (49%) aged ≥10 years on an approved dose, and 30 (8%) were on an unapproved dose. Median age at ZDV/3TC start was 10 years, and 79% had taken ART previously (60% had prior exposure to ZDV/3TC). Overall rates of grade ≥3 AEs for absolute neutrophil counts, bilirubin, haemoglobin, platelet counts, white blood cell counts (WBC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were ≤2/100 person years (PY) for patients taking approved doses. Two hundred thirty-three (43%) patients were not on ZDV/3TC tablets at most recent follow-up; a small number (17 (7%)) discontinued due to AEs (17 (7%)), and the most common reason for discontinuation was treatment simplification (73 (31%)).Scored ZDV/3TC tablets, both approved and taken off-label, appear to be well tolerated with few side effects. Few patients discontinued treatment due to toxicity. As ZDV/3TC tablets are taken with other antiretrovirals, it is difficult to infer association between toxicities and specific agents, highlighting the importance of widening long-term pharmacovigilance to a broader spectrum of drug combinations.

The 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.

[Objective] To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment., [Design] Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts., [Methods] Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol., [Results] Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from, [Conclusion] The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment., This work was supported by funding from the EU Seventh Framework Programme (FP7/2007–2013) under EuroCoord grant agreement [no. 260694] and additional funding from Janssen.

Cytomegalovirus (CMV) infections are common and their incidence increases with age. In immunocompetent people they are usually asymptomatic or manifest as a mild, self-limiting mononucleosis syndrome. CMV infection in patients with immune deficiency as well as congenital infections may cause a considerable problem. A group of experts designated by the Polish Society of Epidemiology and Infectious Diseases has prepared recommendations on the diagnosis and treatment of CMV infections, with particular emphasis on the management of patients with immunodeficiencies and congenital infections.

Objectives The objective of this paper is to summarize the outcomes of the Euroguidelines in Central and Eastern Europe (ECEE) conference held in Warsaw in February 2016. The main aim of this conference was to facilitate a discussion on European AIDS Clinical Society (EACS) guidelines implementation across the region and neighbouring countries and to present the current obstacles in benchmarking HIV care in Europe. Methods During a 2-day meeting, there were country-based presentations using a predefined template so as to make the data comparable and focus the discussion. Areas covered were country epidemiology, surveillance, national strategy for treatment and prevention, standards of care, access to care and treatment availability. Each participant filled in a questionnaire investigating HIV guidelines usage per country. Results In total, 16 Central and Eastern Europe (CEE) and neighbouring countries were represented at the conference: Albania, Armenia, Belarus, Croatia, Czech Republic, Estonia, Georgia, Hungary, Lithuania, Moldova, Poland, Romania, Russia, Serbia, Slovakia and Turkey. EACS guidelines version 7.1 were used in 14 (87%) countries. In 11 (69%) countries, national guidelines were available, of which eight had been recently updated. Half of the countries declared that they use World Health Organization (WHO) and Department of Health and Human Services (DHHS) guidelines, over one-third the European Centre for Disease Prevention and Control (ECDC) HIV testing guidelines and one in five the International Antiviral Society−USA (IAS-USA) Panel guidelines from 2012. Conclusions Participants declared their will to promote the widespread use of EACS guidelines for HIV infection in the CEE region and neighbouring countries by signing the Warsaw Declaration. They also emphasized the need to increase publishing of data from national cohorts in that region.

Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

Cowpox Virus Infection An 11-year-old girl presented with a necrotic-appearing ulceration on her left cheek that had been present for 3 weeks. Evaluation confirmed infection with cowpox virus.

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 children's 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.

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

Aforesaid recommendations for the management of T.gondii infection, elaborated by the group of experts, are intended for physicians of various specialties in order to standardize and facilitate diagnostic and therapeutic management. Early diagnosis of congenital toxoplasmosis, both symptomatic and asymptomatic, in neonatal period, initiation of adequate treatment and long-term, multispecialist monitoring, including multi-organ rehabilitation of children may prevent or reduce the complications of congenital toxoplasmosis. Health education, whose role is often underestimated, should be targeted mainly on girls and women at reproductive age as to prevent from infection during pregnancy.

A physician has to perform a benefit-risk assessment each time acyclovir is prescribed “off label” for children. A group of Polish infectious disease experts was created to develop evidence-based guidelines on the use of acyclovir in the treatment and prevention of varicella zoster and herpes simplex infections. In primary varicella zoster virus infections, oral acyclovir treatment is recommended in children over 12 years of age and should be considered in younger children who fall into one of the groups at risk of severe varicella. Intravenous acyclovir therapy in varicella is recommended in patients with immune deficiencies, newborns and in complicated cases. When there is a justified need for prevention of varicella, oral acyclovir prophylaxis may be considered if immunoglobulin cannot be administered, and if it is too late for vaccination. Oral acyclovir treatment of herpes zoster may be beneficial to otherwise healthy patients with a rash in places other than the trunk and in patients over 50 years of age. In immunocompetent patients with herpes simplex infections, indications for treatment with oral acyclovir include primary (genital herpes, skin herpes in children with atopic dermatitis, ocular herpes simplex, severe gingivostomatitis, paronychia and pharyngitis) and recurrent infections. Intravenous acyclovir should be administered for herpes infections in neonates, immunocompromised patients and patients who develop complications including neurological.

BACKGROUND Evaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children. OBJECTIVES The aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data. MATERIAL AND METHODS The study comprised 30 treatment-naive children (mean age: 12.8 ± 2.4; mean duration of infection: 11.7 ± 2.5 years; 16/30 HBeAg-positive and 14/30 HBeAg-negative), who underwent a liver biopsy due to CHB. Liver biopsies were evaluated according to the modified Knodell score. RESULTS A histopathological evaluation revealed mild to severe necroinflammatory activity (mean grading: 5.4 ± 3.2) and fibrosis (mean staging: 1.7 ± 0.9), irrespective of the HBeAg-status, viral load and duration of infection. One case of cirrhosis was observed. A multiple regression analysis revealed that alanine and aspartate aminotransferase (ALT and AST) levels were associated with the necroinflammatory activity (p = 0.001 for ALT, and p = 0.006 for AST). No such correlation for fibrosis was observed; however, children with elevated AST were prone to more advanced fibrosis compared to children with normal AST level (p = 0.01). CONCLUSIONS Children with CHB presented a wide range of liver changes over a decade after the infection. The severity of liver lesions did not differ according to the HBeAg status, viral load and duration of the infection. ALT and AST levels correlated positively with the inflammatory activity. AST seems to be a better predictor of fibrosis compared to ALT. Liver biopsy is a useful tool in evaluating the severity of liver disease in children with chronic hepatitis B, whereas clinical and laboratory parameters are weak predictors of liver injury.

Item does not contain fulltext BACKGROUND: The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. METHODS: PENPACT-1 had a 2 x 2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, and switch at a 1000 copies/mL versus 30,000 copies/mL threshold. Switch criteria were not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or Center for Disease Control and Prevention stage C event. Resistance tests were performed on samples >/=1000 copies/mL before switch, resuppression, and at 4-years/trial end. RESULTS: Sixty-seven children started PI-based ART and were randomized to switch at 1000 copies/mL (PI-1000), 64 PIs and 30,000 copies/mL (PI-30,000), 67 NNRTIs and 1000 copies/mL (NNRTI-1000), and 65 NNRTI and 30,000 copies/mL (NNRTI-30,000). Ninety-four (36%) children reached the 1000 copies/mL switch criteria during 5-year follow-up. In 30,000 copies/mL threshold arms, median time from 1000 to 30,000 copies/mL switch criteria was 58 (PI) versus 80 (NNRTI) weeks (P = 0.81). In NNRTI-30,000, more nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000 copies/mL (23% NNRTI-1000, 27% NNRTI-30,000). Sixty-two children started abacavir + lamivudine, 166 lamivudine + zidovudine or stavudine, and 35 other NRTIs. The abacavir + lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30,000, 64% NNRTI-1000, and 100% NNRTI-30,000 were

Objectives: To carry out an epidemiological analysis of the emerging epidemic in an Eastern European country and to compare the approach to prevention of mother-to-child transmission (MTCT) with that in Western Europe. Design: Prospective cohort study established in 1985 in Western Europe and extended to Ukraine in 2000. Methods: Data on 5967 HIV-infected pregnant women and their infants (1251 from Ukraine and 4716 from Western/Central Europe) was analysed. Factors associated with transmission were identified with logistic regression. Results: HIV-infection among pregnant women enrolled in Western European centres has shifted from being largely injecting drug use (IDU)-related to heterosexually-acquired; in Ukraine IDU also gradually declined with women increasingly identified without specific risk factors. In Ukraine in 2000-2004 most (80%) women received single dose nevirapine (sdNVP) and/or short-course zidovudine prophylaxis [MTCT rate 4.2%; 95% confidence interval (CI), 1.8-8.0 for sdNVP with short-course zidovudinel; 2% (n = 27) received antenatal HAART and 33% (n = 418) delivered by elective caesarean section (CS); in Western European centres 72% of women received HAART (MTCT rate 1.0%; 95% Cl, 0.4-1.9) and 66% delivered by elective CS during the same period. Conclusions: Our findings indicate distinct differences in the epidemics in pregnant women across Europe. The evolution of the MTCT epidemic in Ukraine does not appear to be following the same pattern as that in Western Europe in the 1980s and 1990s. Although uptake of preventive MTCT prophylaxis has been rapid in both Western Europe and Ukraine, substantial challenges remain in the more resource-constrained setting in Eastern Europe. (c) 2006 Lippincott Williams & Wilkins

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.

To estimate prevalence of body fat redistribution and dyslipidaemia in HIV-infected children and to assess associated risk factors, ultimately to inform the definition of lipodystrophy in children.Cross-sectional observational study.During a 2-3 month period, 477 HIV-infected children agedor= 3 years (median 9.78; range, 3-18) in 30 paediatric HIV clinics were assessed at their first visit. Sociodemographic, clinical and immunological data were recorded and the presence or absence of clinical signs of fat redistribution (peripheral lipoatrophy and central lipohypertrophy) determined according to an agreed protocol. Laboratory indicators of lipid/glucose metabolism were recorded for all children in 18 centres.Prevalence was 26.0% [95% confidence interval (CI), 22.1-30.2] for any fat redistribution, 8.81% (95% CI, 6.42-11.7) for central lipohypertrophy, 7.55% (95% CI, 5.34-10.3) for peripheral lipoatrophy and 9.64% (95% CI, 7.15-12.7) for the combined subtype (more than one sign of each). Independent predictors of fat redistribution included Centers for Disease Control and Prevention class C disease, female gender, ever used versus never use of protease inhibitors and of stavudine. Increasing time since initiation of antiretroviral therapy was associated with increased severity of fat redistribution. In the metabolic assessment subgroup, 27% (95% CI, 21.6-32.7) of children had hypercholesterolaemia and 21% (95% CI, 16.4-26.6) hypertriglyceridaemia; however, significantly more children had fat redistribution in this subgroup than overall (31%).Approximately a quarter of children and adolescents could be taken to have signs of lipodystrophy, with clinical presentation and risk factors similar to those described in adults.

Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life (.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.

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.

1Department of Cardiology, Hypertension and Internal Medicine, Medical University of Warsaw, Brodnowski Mazowian Hospital, Warsaw, Poland 2Department of Heart Failure and Cardiac Rehabilitation, Medical University of Warsaw, 2nd Medical Faculty, Brodnowski Mazowian Hospital, Warsaw, Poland 3Department of Children’s Infectious Diseases, Medical University of Warsaw, Regional Hospital of Infectious Diseases, Warsaw, Poland

Vertical transmission is an important route of HCV infection. Infants are considered to be infected if two or more HCV-RNA results are positive and/or anti-HCV+ over 18 mo of age. HCV-RNA RT-PCR testing requires high quality certificated centers. Anti-HCV ELISA commercial tests are cheaper and may be performed in all laboratories.To estimate sufficiency of anti-HCV testing over 18 mo in the diagnostic process of HCV mother-to-child infection.317 children born to HCV infected mothers were observed for 2-4 years. HCV-RNA was determined first at the age of 2-5 mo and subsequent in 6 months intervals, anti-HCV every 3-6 months.HCV infection (HCV-RNA twice presence) was recognized in 26/317 (8.2%). Anti-HCV+ were found in: 288 (91%) children in 3-6 mo of age, 213 (67.2%) in 7-9 mo, 21 (6.6%) above 18 mo. HCV-RNA was negative during all observation in the group with anti-HCV results group in all determinations in the first year of life. Among 21 children anti-HCV+ over 18 mo there were: 18 with chronic infection (HCV-RNA+, anti-HCV+), 3 achieved HCV-RNA clearance (2 became anti-HCV-, 1 anti-HCV+ during following observation). Among 296 children anti-HCV over 18 mo there were 5 children HCV-RNA+ twice in the first year of life, but all became HCV-RNA- during follow up. In 4 of them (4/296, 1.3%) in spite of anti-HCV- we transiently found HCV-RNA+ above 18 mo of age.Anti-HCV presence in children born to HCV infected mothers: a) up to 18 mo of age do not confirm HCV infection. b) over 18 mo of age are indicative of HCV infection, but not always with active HCV replication. Negative results of anti-HCV above 18 mo of age usually allow us to exclude HCV replication, but in 1.3% we found HCV-RNA in anti-HCV- children. Anti-HCV testing over 18 mo of age as only diagnostic procedure may be not enough. Missing HCV replication in the first period of life prevents HCV microreplication follow up.

The authors present the case of a vertically HIV infected, six-year-old girl, with precocious puberty. The late diagnosis of HIV both in the mother and in the child is of significance. Different causes of adrenarche precox are also discussed. In pediatric practice vertical HIV infection should be taken into consideration in differential diagnosis. In routine care of HIV-infected children, monitoring of development including sexual development is indicated. The presence of symptoms of adrenarche precox, as in noninfected children needs in depth diagnostic investigations. The role of HIV infection and of antiretrovirus treatment in the pathogenesis of adrenarche precox remains unclear and needs further investigation.

Incidence of hepatitis B in Poland decreased significantly after implementation of routine immunization in infants. Natural boosters may influence the long-term post vaccination immunity in countries, where endemicity is high. In areas of low incidence this influence may be limited. The aim of the study was to analyze the influence of risk factors for HBV infection (potential natural boosters) on long-term post vaccination immunity against hepatitis B and the possibilityof HBVinfection in previously vaccinated individuals.In 130 children aged 10-12years, vaccinated with 4 doses ofrecombinantvaccine against hepatitis B in infancy, exposure to risk factors for HBV infection (infection in family members including mother, hospitalization, surgical interventions, blood transfusion, dental treatment, piercing, tattooing) was analyzed. Markers of HBVinfection (anti-HBc and HBsAg) and humoral immunity against hepatitis B were determined. Protective level of anti-HBs antibodies was defined asor =10 IU/1.Statistically significant influence of dental treatment (p0.02) andsurgicalinterventions (p0.05) on possessing very high anti-HBs titer (or = 1000 IU/) was revealed, which indicates that these factors act as natural boosters. Children, who previously received blood transfusion, statistically more frequently did not have protective level of anti-HBs (p0.0 I). In all 6 children with confirmed HBV infection there was exposure to risk factors for infection in anamnesis. In children with chronic hepatitis B (positive HBsAg) statistically significantly more frequently surgical interventions were performed (p0.05).I. Despite of low incidence of hepatitis B in Poland, natural boosters, especially dental and surgical treatment, may stimulate the post vaccination immunity. 2. Blood transfusion is currently not a source of infection, however, children who received blood transfusion in the neonatal period, may require control of immunization efficacy or a booster dose. 3. HBVinfection and chronic hepatitis B may occur in previously vaccinated children, especially if they underwent surgical intervention.

In the autumn 2009 in Poland there was an outbreak of influenza A(H1N1)v, approximately 1/3 of confirmed cases in children younger than 14 years. The aim of the study was an epidemiologic and clinical characteristics of pediatric patients with influenza A(H1N1)v and evaluation of antiviral treatment safety. The medical records of 100 children with confirmed influenza A(H1N1)v were reviewed. 48% of children had risk factors for severe clinical course, including 23 younger than 2 years. The most common symptoms were fever (89%) and cough (68%). In 20% children pneumonia was diagnosed, other complications were uncommon. 4 patients required mechanical ventilation and 3 died, all with severe underlying conditions. In 62% of patients oseltamivir was used and it was well tolerated.

To evaluate hepatitis B vaccination effectiveness.49 vertically HIV-infected children were enrolled. Anti-HBs antibodies were evaluated at HIV diagnosis, at evaluation (year 2004) and after primary vaccination. The following factors were analyzed: age, time since the last vaccine dose, clinical and immunological CDC category, HIV viral load, age at the beginning of ART.At HIV diagnosis 14% of children had anti-HBs antibody levelor = 100 mLU/ml. At evaluation 76% of patients had anti-HBs antibody levelor = 100 mIU/ml. Children, who were diagnosed before their first birthday, were more likely to have protective antibody level (p0.01). Percentage of lymphocyte T CD4+ count (p0.01) and time since last vaccination (p0.01) were found to be important factors of vaccination response. Primary vaccination was effective in 86% of children.Factors which influenced vaccination effectiveness included early HIV diagnosis, percentage of lymphocyte T CD4+ at evaluation and time since last vaccination. The effectiveness of primary vaccination was high.

The aim of the study was to determine the rate of transmission of drug resistant human immunodeficiency virus-1 (HIV-1) variants among therapy-naive 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 Stanford's 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. © 2010 Wiley-Liss, Inc.

vaccination is one of very important aspects in medical care of HIV infected children.to evaluate measles vaccination effectiveness based on post-vaccination antibodies in HIV infected children.45 -- vertically HIV infected children were observed between 2001-2004 in the Department of Children's Infectious Diseases, Medical University of Warsaw. Post vaccination measles antibodies were evaluated at the beginning of study and during the follow-up. Effectiveness of primary vaccination and revaccination was evaluated The analysed factors included: age, time since the last vaccine dose, age at HIV diagnosis, clinical and immunological condition, HIV viral load, age of the child at the beginning of antiretroviral treatment.post vaccination measles antibodies were detected in 47% patients. Children, who were diagnosed before vaccination, were more likely to have measles antibodies (p0,02). Age at the beginning of antiretroviral treatment (p0,005) and time since last vaccination (p0,01) were found to be important factors of measles antibody response. Primary vaccination was effective in 77% of the treated children, revaccination in 46%.factors which influenced measles vaccination effectiveness included age at the beginning of antiretroviral treatment and the time since last vaccination. The effectiveness of primary vaccination in treated children was high but lower compared to healthy children. Revaccination response is lower.

The number of HIV-infected women is increasing worldwide. A similar phenomenon has also been observed in Poland, where women constitute 30% of the HIV-infected population. Every year in Poland there are 70-100 infants born by HIV-infected mothers. Since the beginning of the epidemic, 147 HIV-infected children have been registered. The key issue in the prevention of mother-to-child transmission of HIV (PMTCT) is to identify the infection in pregnant women who report to hospitals for delivery and in breastfeeding mothers. In the majority of EU countries, the percentage of pregnant women diagnosed for HIV is over 60%, with some countries (England, Holland, France) where the percentage amounts to as much as 98%. In Poland the proportion is not greater than 10%. Almost all perinatal HIV infections in Poland occured due to the lack of timely diagnosis of the infection in a pregnant woman and the resultant failure to apply known and effective prevention measures. These recommendations present the actual system of care in that population of women in Poland.

Toxocariasis in humans is a zoonosis due to the migration of Toxocara canis or T. cati larvae in human body. This review provides basic information on pathology of infection and clinical signs and symptoms of toxocariasis in children. The cases diagnosed in the recent years in central Poland are presented. The disease was recognised accidentally based on the results of laboratory analysis performed for other reasons, when abnormalities suggesting an active helminthiasis were found (eosinophilia, elevated IgE level and/or anemia). The high rate of soil contamination in households of the patients demonstrated elevated risk of infection and reinfection in both, rural and urban areas. Presented data show the need for educational programs which should be implemented for prevention of Toxocara infection in children.