Elena Chiappini

Pertussis re-emergence in the post-vaccination era

BackgroundResurgence of pertussis in the post-vaccination era has been reported in Western countries. A shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade, and mortality rates in infants are still sustained. We aimed to review and discuss the possible vaccination strategies which can be adopted in order to improve the pertussis control, by searches of Pubmed, and websites of US and European Centers for Disease Control and Prevention, between 1st January 2002, and 1st March 2013.DiscussionThe following vaccination strategies have been retrieved and analysed: the cocooning strategy, the immunization of pregnant women and newborns, vaccination programs for preschool children, adolescents, adults and health-care workers. Cost-effectiveness studies provide some contrasting data, mainly supporting both maternal vaccination and cocooning. Adolescent and/or adult vaccination seems to be cost-effective, however data from observational studies suggest that this vaccination strategy, used alone, leads to a reduced pertussis burden globally, but does not affect the disease incidence in infants. Moreover, substantial logistical and economic difficulties have to be overcome to vaccinate the largest number of individuals.SummaryThe simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure. The development of new highly immunogenic and efficacious pertussis vaccines continues to be a primary objective for the control of pertussis.

Interferon-Gamma Release Assay Improves the Diagnosis of Tuberculosis in Children

Background: Interferon-&ggr; release assays (IGRAs) have been recently developed for the diagnosis of tuberculosis (TB) infection. The aim of the present study was to evaluate the performance of an enzyme-linked immunosorbent assay (ELISA)-based IGRA for detecting TB in children. Methods: A prospective study in 336 children at risk for TB infection was carried out. All children were tested with tuberculin skin test (TST) and a commercial ELISA-based IGRA [QuantiFERON-TB Gold In-Tube (Cellestis)]. Results: TST were positive in 58 of 336 (17.3%) and IGRA in 60 of 336 (17.9%) children. Two (0.6%) IGRA results were indeterminate. The overall agreement between the 2 tests was intermediate (86.2%, κ = 0.533). IGRA was positive in 15 of 16 (93.8%) children with active pulmonary TB. The discordant pattern IGRA−/TST+ was significantly associated with Bacille Calmette-Guérin (BCG) vaccination. Among IGRA+ children (excluding cases of TB disease), TST− were significantly younger than TST+ children. Conclusions: The good agreement between positive IGRA and active TB disease suggests a good sensitivity of IGRA. Discrepancies between IGRA and TST can be a result of higher specificity of IGRA that is not influenced by previous BCG vaccination. IGRA may be more sensitive in children younger than 48 months.

Analysis of Different Recommendations From International Guidelines for the Management of Acute Pharyngitis in Adults and Children

BACKGROUND Streptococcal pharyngitis is a frequently observed condition, but its optimal management continues to be debated. OBJECTIVE The goal of this study was to evaluate the available guidelines, developed at the national level, for the management of streptococcal pharyngitis in Western countries, with a focus on their differences. METHODS A literature search was conducted of the Cochrane Library, EMBASE, TRIP, and MEDLINE databases from their inception (1993 for the Cochrane Library, 1980 for EMBASE, 1997 for TRIP, and 1966 for MEDLINE) through April 25, 2010. The following search terms were used: pharyngitis, sore throat, tonsillitis, pharyngotonsillitis, Streptococcus pyogenes, Group A β-haemolytic Streptococcus pyogenes, and streptococcal pharyngitis. Searches were limited to type of article or document (practice guideline or guideline) with no language restrictions or language limits. RESULTS Twelve national guidelines were identified: 6 from European countries (France, United Kingdom, Finland, Holland, Scotland, and Belgium), 5 from the United States, and 1 from Canada. Recommendations differ substantially with regard to the use of a rapid antigen diagnostic test or throat culture and the indications for antibiotic treatment. The North American, Finnish, and French guidelines recommend performing one timely microbiologic investigation in suspected cases, and prescribing antibiotics in confirmed cases to prevent suppurative complications and acute rheumatic fever. According to the remaining European guidelines, however, acute sore throat is considered a benign, self-limiting disease. Microbiologic tests are not routinely recommended by these latter guidelines, and antibiotic treatment is reserved for well-selected cases. The use of the Centor score, for evaluation of the risk of streptococcal infection, is recommended by several guidelines, but subsequent decisions on the basis of the results differ in terms of which subjects should undergo microbiologic investigation. All guidelines agree that narrow-spectrum penicillin is the first choice of antibiotic for the treatment of streptococcal pharyngitis and that treatment should last for 10 days to eradicate the microorganism. Once-daily amoxicillin was recommended by 2 US guidelines as equally effective. CONCLUSION The present review found substantial discrepancies in the recommendations for the management of pharyngitis among national guidelines in Europe and North America.

Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection.

Objective:To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. Methods:A multi-centre nationwide case–control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0–6.5 years). Results:No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13–24 (P < 0.0001), 25–36 (P < 0.0001), and 37–48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P = 0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan–Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. Conclusion:The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

Parental and medical knowledge and management of fever in Italian pre-school children

BackgroundGuidelines for the management of fever in children have been recently published, however “fever phobia” is still spreading. To provide information which may sustain educational interventions tailored to our population we investigated the parental and medical knowledge and management of fever in preschool children.MethodsA questionnaire was administered to a convenient sample of Italian parents and paediatricians. The questionnaire elicited information about definition and cause of fever, concerns about fever, method of temperature measurement, and treatment modalities.ResultsOverall, 388 parents and 480 paediatricians were interviewed. All the parents believed that fever could cause at least one harmful effect and 89.9% (n = 349) believed that, if left untreated, it can cause brain damage or seizures. Parents used multiple resources to obtain information about fever but 67.8% (n = 264) considered paediatricians as their primary resource. Several wrong behaviours were found in the same proportions among parents and paediatricians: 78.5% of paediatricians (n = 377) and 77.8% of parents (n = 302) used physical method to reduce fever (P = 0.867); 27.0% of paediatricians (n = 103) and 21.4% (n = 83) of parents declared to alternate ibuprofen and acetaminophen (P = 0.953). Differently, 73.1% (n = 351) of paediatricians preferred oral to rectal administration of antipyretics compared to 48.7% (n = 190) of parents (P < 0.0001). Worrisomely, 1.4% of paediatricians and 1.2% of parents declared to use acetylsalicylic acid or steroids as second-choice antipyretics (P = 0.937) and 6.7% (n = 26) of parents declared to use table- or teaspoons for determining the dose of drug.ConclusionsPaediatricians’ attitudes greatly influence the parental behaviours and beliefs. Implementation of educational programs regarding the management of the febrile child are needed in our setting.

Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update

BackgroundPrevious meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.MethodsWe systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.ResultsOverall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).ConclusionsBoth IGRAs showed no better performance than TST in low income countries.

Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART

Background:The introduction of HAART has decreased mortality and progression to AIDS in perinatally HIV-1-infected children, but information on modification of the rate of specific clinical events is limited. Method:An observational population study on changes in HIV-1-related morbidity was conducted on 1402 perinatally HIV-1-infected children enrolled in the Italian Register for HIV Infection in Children and prospectively followed in the pre-HAART (1985–1995) and post-HAART periods (1996–2000, and 2001–2005). Of this group, 773 children (55.1%) were followed from birth. Median observation time was 8.58 years (interquartile range, 3.71–13.72). Results:Overall, 666 (47.5%) children developed AIDS and 420 (29.9%) died. Improved survival over time was evidenced at Kaplan–Meier analysis (P < 0.0001). Poisson regression analysis indicated that Centers for Disease Control and Prevention class B and C clinical event rates and most of the HIV-1-related organ complication rates significantly decreased starting from 1996–2000. Significant reductions in rates of cancer and opportunistic infections were evidenced after 2000. Nevertheless, opportunistic infections still occurred at high rates (6.09/100 person-years) in 2001–2005, with high rate of bacterial infections (3.55/100 person-years), particularly pneumonia (1.66/100 person-years), in this period. CD4 cell percentage was > 15% in 58.5% children with pneumonia. Conclusions:Progressive reductions of both mortality and rates of class B and C clinical events, including organ complications, were evidenced in the HAART era. Nevertheless, severe bacterial infections, particularly pneumonia, still occurred at considerable high rates, even in the absence of a severe CD4 cell depletion.

Management of fever in children: Summary of the Italian pediatric society guidelines

OBJECTIVE This article summarizes the Italian Pediatric Society guideline on the management of the signs and symptoms of fever in children, prepared as part of the National Guideline Program (NGLP). METHODS Relevant publications in English and Italian were identified through searches of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through December 31, 2007. Based on the consensus of a multidisciplinary expert panel, the strength of the recommendations was categorized into 5 grades (A-E) according to NGLP methodology. SUMMARY In the health care setting, axillary measurement of body temperature using a digital thermometer is recommended in children aged <4 weeks; for children aged > or =4 weeks, axillary measurement using a digital thermometer or tympanic measurement using an infrared thermometer is recommended. When body temperature is measured at home by parents or care-givers, axillary measurement using a digital thermometer is recommended for all children. Children who are afebrile when seen by the clinician but are reported to have had fever by their caregivers should be considered febrile. In special circumstances, high fever may be a predictive factor for severe bacterial infection. Use of physical methods of reducing fever is discouraged, except in the case of hyperthermia. Use of antipyretics-paracetamol (acetaminophen) or ibuprofen-is recommended only when fever is associated with discomfort. Combined or alternating use of antipyretics is discouraged. The dose of antipyretic should be based on the childs weight rather than age. Whenever possible, oral administration of paracetamol is preferable to rectal administration. Use of ibuprofen is not recommended in febrile children with chickenpox or dehydration. Use of ibuprofen or paracetamol is not contraindicated in febrile children with asthma. There is insufficient evidence to form any recommendations concerning fever in children with other chronic conditions, but caution is advised in cases of severe hepatic/renal failure or severe malnutrition. Newborns with fever should always be hospitalized because of the elevated risk of severe disease; paracetamol may be used, with the dose adjusted to gestational age. Use of paracetamol or ibuprofen is not effective in preventing febrile convulsion or the adverse effects of vaccines.

Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children

Objective To define age at entry into Tanner stages in children with perinatal HIV-1 infection. Design Multicentre longitudinal study including 212 perinatally HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from 8 and 9 years onwards in girls and boys, respectively). Healthy children (843 girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and P2 or G2 stages in boys defined onset of puberty. Methods The cumulative probability [95% confidence limit (CI)] of entry into each stage at different ages was estimated by the Kaplan–Meier product-limit method; differences were evaluated by log rank test. Relationships were tested using the Spearmans rank correlation coefficient. Results Ages of girls [years (95%CI)] at P2 [12.9 (12.6–13.2)], P3 [13.4 (13.0–13.8)], P4 [14.6 (14.0–15.2)], B2 [12.7 (12.2–13.2)], B3 [13.3 (12.8–14.0)] and B4 [14.6 (14.0–15.2)] stages were > 97th percentile (⩾ 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1–13.1)], P3 [13.9 (13.4–14.4)], P4 [14.9 (14.2–15.6)], G2 [12.1 (11.5–12.7)], G3 [13.6 (13.1–14.1)] and G4 [14.9 (14.1–15.7)] stages were at the 75–97th percentiles (⩽ 15 month delay). Age at onset of puberty was not related to clinical and immunological condition, antiretroviral treatment, weigh for height and age at onset of severe disease or immune suppression. Conclusion Perinatal HIV-1 infection interferes with sexual maturation. The mechanisms by which this occurs should be elucidated and intervention strategies designed. Intervention could save much psychological distress, since associated linear growthfailure can exacerbate adolescents’ feelings of being different and unwell.

Tuberculosis and HIV co-infection in children

HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes.Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV.ConclusionData on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.