This document describes the recommendations of a group of scientific societies concerning the first-line therapeutic approach to paediatric tuberculosis (TB). The treatment of pulmonary TB should be ...based on the existence of parenchymal involvement and the risk of antibiotic resistance. The treatment of extra-pulmonary TB is based on the regimens used for severe pulmonary TB. The administration of corticosteroids is recommended only in cases of miliary TB, tuberculous meningitis and tuberculous pericarditis. Vitamin B6 may be indicated in the case of isoniazid-treated TB in breastfeeding infants, severely malnourished subjects, or patients with other diseases at high risk of vitamin deficiency. Once having started treatment, children with TB should be carefully followed up in order to evaluate compliance, the response to treatment, the need for treatment changes, and the presence of drug-related adverse events. Primary care paediatricians can support reference centres in providing family healthcare education and encouraging treatment compliance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering ...child-bearing age and experiencing motherhood is increasing.
A description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children.
Twenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2-6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/μL (IQR 275-522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36-38, median birth weight: 2550 grams, IQR 2270 - 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 - 42), with no adverse events reported. No child acquired HIV-1 infection.
Despite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess applicability of quantitative ultrasonography (QUS) for bone health assessment in HIV-infected youths.
QUS measurements of the radius and tibia and dual-energy x-ray absorptiometry (DXA) ...measurements of the lumbar spine and whole skeleton were obtained in 88 HIV-infected children and adolescents (aged 4.8-22.1 years, 43 boys and 45 girls).
Radius speed of sound was significantly associated to lumbar spine and total body DXA measurements (R values from 0.57 to 0.60), after correction for differences in sex and anthropometry. Similarly, speed of sound of the tibia was associated to all DXA measurements (R from 0.58 to 0.66). The z scores calculated for lumbar spine DXA measurements were significantly lower (P < 0.0001) than those of QUS measurements, although no differences were observed between QUS and total body z scores.
Our study shows that QUS of the peripheral skeleton is related to DXA. The ability to detect low values is similar to that of total body DXA. Our data suggest that QUS may be an additional diagnostic tool for the study of bone mass in HIV-infected youths.
Background. There is currently an experts' agreement discouraging interruption of antiretroviral treatment (ART) during the first trimester of pregnancy in women infected with human immunodeficiency ...virus type 1 (HIV-1). However, this recommendation is poorly supported by data. We evaluated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission. Methods. Logistic regression models were performed in a prospective cohort of 937 children who were perinatally exposed to HIV-1 to estimate adjusted odds ratios for confounding factors on mother-to-child transmission, including maternal interruption of ART. Results. Among 937 pregnant women infected with HIV-1, ART was interrupted in 81 (8.6%) in the first trimester and in 11 (1.2%) in the third trimester. In the first trimester, the median time at suspension of ART was 6 weeks (interquartile range IQR, 5–6 weeks) and the time without treatment was 8 weeks (IQR, 7–11 weeks). In the third trimester, the median time at suspension of ART was 32 weeks (IQR, 23–36 weeks) and the time without treatment was 6 weeks (IQR, 2–9 weeks). The plasma viral load was similar in women who had treatment interrupted in the first trimester and in those who did not have treatment interrupted. Overall, the rate of mother-to-child transmission in the whole cohort was 1.3% (95% confidence interval CI, 0.7%–2.3%), whereas it was 4.9% (95% CI, 1.9%–13.2%) when ART was interrupted in the first trimester and 18.2% (95% CI, 4.5%–72.7%) when ART was interrupted in the third trimester. In the multiple logistic regression models, only interruption of ART during either the first or the third trimester, maternal mono- or double therapy, delivery by a mode other than elective cesarean delivery, and a viral load at delivery >4.78 log10 copies/mL were independently associated with an increased rate of mother-to-child transmission. Conclusions. Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester. This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Background: Information on the use of new antiretroviral drugs in children in the real setting of clinical fields is largely unknown.
Methods: Data from 2554 combined antiretroviral therapy (cART) ...regimens administered to 911 children enrolled in the Italian Register for HIV infection in children, between 1996 and 2009, were analysed. Factors potentially associated with undetectable viral load and immunological response to cART were explored by Cox regression analysis.
Results: Proportion of protease inhibitor (PI)‐based regimens significantly decreased from 88.0% to 51.2% and 54.9%, while proportion on non‐nucleoside reverse transcriptase inhibitor (NNRTI)‐based regimens increased from 4.5% to 38.8% and 40.2% in 1996–1999, 2000–2004 and 2005–2009, respectively (p < 0.0001). Significant change in the use of each antiretroviral drug occurred over the time periods (p < 0.0001). Factors independently associated with virological and immunological success were as follows: later calendar periods, younger age at regimen (only for virological success) and higher CD4+ T‐lymphocyte percentage at baseline. Use of unboosted PI was associated with lower adjusted hazard ratio (aHR) of virological or immunological success with respect to NNRTI‐ and boosted PI‐based regimens, with no difference among these two latter types.
Conclusion: Use of new generation antiretroviral drugs in Italian HIV‐infected children is increasing. No different viro‐immunological outcomes between NNRTI‐ and boosted PI‐based cART were observed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bacillus Calmette-Guérin (BCG) vaccine is still the only vaccine approved for the prevention of tuberculosis (TB), and is widely used in highly endemic countries, where all newborns receive a single ...intradermal dose immediately after birth; however, the recommendations concerning its use in Europe vary widely from country to country. This document describes the recommendations of a group of Italian scientific societies concerning its pediatric use in Italy, the persistence of the protection it provides, its safety, its interference with tuberculin skin test (TST) responses, and the children who should be vaccinated. The experts conclude that BCG vaccination provides a good level of protection against tuberculous meningitis and disseminated forms, and a fair level of protection against pulmonary disease; the protective effective lasts at least 10 years, and revaccination offers no advantages over a single administration. The vaccine is safe in immunocompetent subjects, and affects the response to a TST for at least 6 y On the basis of these observations, we recommend its use in Italy in all TST-negative immunocompetent newborns and breastfeeding infants aged <6 months, and all TST-negative children aged between 6 months and 5 y who come from highly epidemic areas, or whose parents come from highly endemic areas, or who have been in contact with a family member with active TB without contracting the disease themselves.
Prophylactic administration of zidovudine (ZDV) to mother-child pairs reduces HIV transmission. ZDV can impair mitochondrial (mt) DNA polymerase gamma, leading to mtDNA depletion. Signs of ...mitochondrial dysfunction have been observed in a few children with prenatal exposure to nucleoside analogues, although no mtDNA depletion was demonstrated. Other studies failed to confirm mitochondrial disorders in children who were exposed to antiretroviral agents in utero. A child, whose HIV-infected mother received ZDV from the fourth month of pregnancy, developed neonatal encephalomyopathy, anaemia and hyperlactataemia. At 2 weeks of age, a muscle biopsy exhibited red-ragged-like fibres, proliferation of abnormal mitochondria and a 90% depletion of mtDNA without qualitative abnormalities. At 6 months, the depletion was less profound (about 50% of normal values). Severe psychomotor delay and visual disturbances persisted at 30 months, but they were greatly reduced at 5-year follow-up. These laboratory and clinical findings clearly demonstrated that mtDNA alteration was acquired and not consequent to an inherited disorder. Fetal exposure to ZDV may have caused the mtDNA depletion, which, although temporary, led to irreversible but not progressive brain damage.
Only a few reports of zidovudine (ZDV) overdose have been described in the literature. All cases occurred in HIV-1-infected patients, including one child. Patients presented with nausea or vomiting, ...neurologic symptoms (ataxia, lethargia, nystagmus, seizures), signs of bone marrow toxicity (anemia, leukopenia, throm-bocytopenia), or an increase in liver enzymes. Clinical and haematological abnormalities were temporary in all cases. No case of ZDV overdose has been described among uninfected children born to HIV-1-infected mothers.
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