Management of HIV-1 infection in the paediatric age

Introduction of Highly Active Antiretroviral Therapy (HAART) and implementation of preventive strategies during pregnancy have resulted in a dramatic reduction of the mortality rate in HIV-1 infected children by over 80-90% and in a decrease in the risk of mother-to-child transmission (MCTC) of HIV-1 to approximately 1-2%. However the MCTC remains the main source of HIV-1 infection within the paediatric population. The risk of disease progression is inversely correlated with the age of the child, with the youngest children at greatest risk of rapid disease progression, but in the first year of life it is not possible to identify infants at greatest risk; therefore, according to all the international guidelines, it is necessary to start antiretroviral therapy in all infants < 12 months of age. This article provides a summary of the clinical features of the infection and of the methods for diagnosis. Furthermore it offers an overview of antiretroviral therapy in HIV-1 infected children, including a description of the main classes of antiretroviral drugs, the most common side effects and some issues concerning the disclosure of diagnosis. The objectives of this study are to make a set of practical suggestions to paediatricians for the optimum management of the infection and the antiretroviral therapy

Congenital syphilis in a two-month-old infant

This report describes a rare case of congenital syphilis in a two-month-old Romanian infant. Diagnosis was possible when the baby showed decrease in the left upper limb movements and a papular rash. Her father had been infected and transmitted the infection to the mother, who had two non-treponemal serological tests during pregnancy, both with negative results. Congenital syphilis was confirmed by serological tests and the newborn was successfully treated. A global overview on diagnosis and treatment of children with suspected congenital syphilis is presented

Significant impact of pneumococcal conjugate vaccination on pediatric parapneumonic effusion: Italy 2006-2018

Abstract Etiology and serotyping of parapneumonic effusion (PPE) and the impact of vaccination was evaluated over a 12-year period, before and after the PCV13 introduction (2011) for Italian children From 0 to 16 years of age. Five hundred and two children were evaluated; 226 blood and 356 pleural fluid samples were obtained and tested using Realtime-PCR and culture. In the pre-PCV13 era S. pneumoniae was the most frequent pathogen identified (64/90; 71.1%) with a large predominance of serotypes 1 (42.4%), 3 (23.7%), 7F (5.1%) and 19A (11.9%). The impact of vaccination, calculated on children 0–8 years of age, demonstrated a significant reduction of PPE: with an incidence rate of 2.82 (95%CL 2.32–3.41) in the pre-PCV13 era and an age-standardized rate (ASR) of 0.66 (95% CL 0.37–1.99) in the post-PCV13 era, p  In conclusion, our findings indicate that routine immunization with PCV13 has significantly reduced the burden of childhood PPE in vaccinated children, without increasing PPE due to other bacteria and without serotype shift. Moreover, the impact of PCV13 may be underestimated due to the increase in pneumococcal surveillance in Italy. Data has also shown that Real-time PCR is an essential tool to better define the etiology of PPE and to monitor vaccination plans. Longer studies will be necessary to evaluate the role of herd protection in PPE prevention

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background &amp; Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p &lt;0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p &lt;0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.</p

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. Homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC), in contrast to patients with two predicted protein truncating mutations (PPTM). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n=31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n=30), and with two PPTMs (BSEP3/3; n=77). We compared presentation, native liver survival (NLS), and effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (P<0.001). Without siEHC in their follow-up, NLS of BSEP1/3 was similar to BSEP3/3 patients, but considerably lower than BSEP1/1 patients (at age 10 years: 38%, 30%, and 71%, resp; P=0.003). After siEHC, BSEP1/3 and BSEP3/3 patients had similarly low NLS, while this was much higher in BSEP1/1 patients (10 years after siEHC, 27%, 14%, and 92%, resp.; P<0.001). Conclusions: BSEP deficiency patients with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as patients with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment

Congenital syphilis in a two-month-old infant

This report describes a rare case of congenital syphilis in a two-month-old Romanian infant. Diagnosis was possible when the baby showed decrease in the left upper limb movements and a papular rash. Her father had been infected and transmitted the infection to the mother, who had two non-treponemal serological tests during pregnancy, both with negative results. Congenital syphilis was confirmed by serological tests and the newborn was successfully treated. A global overview on diagnosis and treatment of children with suspected congenital syphilis is presented

Management of HIV-1 infection in the paediatric age

Introduction of Highly Active Antiretroviral Therapy (HAART) and implementation of preventive strategies during pregnancy have resulted in a dramatic reduction of the mortality rate in HIV-1 infected children by over 80-90% and in a decrease in the risk of mother-to-child transmission (MCTC) of HIV-1 to approximately 1-2%. However the MCTC remains the main source of HIV-1 infection within the paediatric population. The risk of disease progression is inversely correlated with the age of the child, with the youngest children at greatest risk of rapid disease progression, but in the first year of life it is not possible to identify infants at greatest risk; therefore, according to all the international guidelines, it is necessary to start antiretroviral therapy in all infants < 12 months of age. This article provides a summary of the clinical features of the infection and of the methods for diagnosis. Furthermore it offers an overview of antiretroviral therapy in HIV-1 infected children, including a description of the main classes of antiretroviral drugs, the most common side effects and some issues concerning the disclosure of diagnosis. The objectives of this study are to make a set of practical suggestions to paediatricians for the optimum management of the infection and the antiretroviral therapy

Congenital toxoplasmosis treatment

Objectives: Congenital toxoplasmosis is a particular manifestation of T. gondii infection, which may present as a mild or severe neonatal disease. This pathology remains a difficult challenge in terms of therapy for the pediatrician and gynecologist. In this article we have set ourselves the objective to provide an overview of the main aspects of the disease, with particular attention to the treatment, based on the information in the literature. Results: Two kinds of treatment are currently available: prenatal and postnatal. When pregnant women seroconvert, spiramycin is administered in order to prevent the mother-to-child transmission. When the fetal infection is confirmed the association of pyrimethamine and sulfadiazine is prescribed. After the birth the specific therapy is based on the administration of pyrimethamine and sulfadiazine. However, to date, there is not strong evidence on the effectiveness of treatment, whether prenatal or postnatal. Conclusions: The studies undertaken so far have not given satisfactory answers. Doubleblind randomized controlled trials would be required, but for obvious ethical reasons they cannot be achieved

How to manage TB in children? Problems and solutions in four cases

Children bear a substantial part of the tuberculosis (TB) epidemic worldwide, and it is estimated that there were ≅ 500.000 childhood TB cases globally in 2010, although accurate data are problematic to obtain given the many difficulties associated with TB diagnosis in children and the weaknesses of surveillance systems in countries where TB is endemic. The World Health Organization is working hard in order to reduce the TB prevalence rates and deaths by half by 2015. In this challenge, general practitioners and pediatricians play a key role in detecting early cases of suspected TB and sending them to experts in infectious diseases. This will reduce delayed diagnosis and the spread of disease, which is especially important now that the prevalence of multidrug resistant TB is increasing. For this reason, the purpose of this report was to delineate the characteristic clinical features of the most common forms of pediatric TB and to suggest a rational and practical approach to the disease underlining the role of patients and parents personal and clinical history