The burden of bacteremia and invasive diseases in children aged less than five years with fever in Italy.

BACKGROUND: Invasive diseases (ID) caused by Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis are a major public health problem worldwide. Comprehensive data on the burden of bacteremia and ID in Italy, including data based on molecular techniques, are needed. METHODS: We conducted a prospective, multi-centre, hospital-based study (GSK study identifier: 111334) to assess the burden of bacteremia and ID among children less than five years old with a fever of 39 °C or greater. Study participation involved a single medical examination, collection of blood for polymerase chain reaction (PCR) and blood culture, and collection of an oropharyngeal swab for colonization analysis by PCR. RESULTS: Between May 2008 and June 2009, 4536 patients were screened, 944 were selected and 920 were enrolled in the study. There were 225 clinical diagnoses of ID, 9.8 % (22) of which were bacteremic. A diagnosis of sepsis was made for 38 cases, 5.3 % (2) of which were bacteremic. Among the 629 non-ID diagnoses, 1.6 % (10) were bacteremic. Among the 34 bacteremic cases, the most common diagnoses were community-acquired pneumonia (15/34), pleural effusion (4/34) and meningitis (4/34). S. pneumoniae was the most frequently detected bacteria among bacteremic cases (29/34) followed by H. influenzae (3/34). Ninety percent (27/30) of bacteremic patients with oropharyngeal swab results were colonized with the studied bacterial pathogens compared to 46.1 % (402/872) of non-bacteremic cases (p < 0.001). PCV7 (7-valent pneumococcal conjugate vaccine) vaccination was reported for 55.9 % (19/34) of bacteremic cases. S. pneumoniae serotypes were non-vaccine serotypes in children who had been vaccinated. Mean duration of hospitalization was longer for bacteremic cases versus non-bacteremic cases (13.6 versus 5.8 days). CONCLUSIONS: These results confirm that S. pneumoniae is one of the pathogens frequently responsible for invasive disease.

Antiretroviral use in Italian children with perinatal HIV infection over a 14-year period.

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.

Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy.

BACKGROUND: Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking. METHODS: We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21-7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided. RESULTS: Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71-5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4+ T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4+ T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001). CONCLUSION: Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.

HIV-1 subtypes and circulating recombinant forms (CRFs) from HIV-infected patients residing in two regions of central and southern Italy.

A total of 347 pol gene sequences from 88 Tuscan and 259 Apulian subjects (including 52 non-Italians and 9 children) were analyzed phylogenetically. Forty-four (12.6%) non-B subtypes were found, including 3.4% C, 1.4% F1, 0.8% G, and 0.3% each for J and A pure subtypes, and 3.7% CRF02_AG, 1.4% CRF01_AE, 0.6% BF, and 0.3% CRF06-cpx recombinant forms. An additional sample close-matched the pol gene of an unique recombinant form (URF AGK 99GR303). The non-B subtypes were from 40 adults and 4 children; 12 of these 44 patients were epidemiologically linked. Thirty-three of the 44 non-B viruses pertained to non-Italian immigrants and 11 to Italians, signifying that 63.4% immigrants and 3.7% Italians harbored non-B subtypes. The overall frequency of non-B subtypes was higher in Tuscany than in Apulia (18.1% vs. 10.8%). Moreover, 6.1% and 3.0% non-B subtypes were found among Italians from Florence and Apulia, respectively, while 52.1% and 72.4% of immigrants living in Tuscany and Apulia harbored non-B subtypes. Women infected by means of sexual contact prevailed among non-Italian adults; the majority of Italians were males and admitted high-risk sexual behavior. Four Italians had a history of extensive travel in countries of high endemicity. Social and epidemiological changes are responsible for an increasing circulation of non-B subtypes in Italy. Although non-B subtypes principally infect non-Italian patients, in Italy they can no longer be considered exclusively restricted to subjects from endemic areas.