Margherita Semino

Procalcitonin measurements for guiding antibiotic treatment in pediatric pneumonia

In order to evaluate the use of an algorithm based on a procalcitonin (PCT) cut-off value as a means of guiding antibiotic therapy, 319 hospitalised children with uncomplicated community-acquired pneumonia (CAP) were randomised 1:1 to be treated on the basis of the algorithm or in accordance with standard guidelines. The children in the PCT group did not receive antibiotics if their PCT level upon admission was <0.25 ng/mL, and those receiving antibiotics from the time of admission were treated until their PCT level was ≥ 0.25 ng/mL. The final analysis was based on 155 patients in the PCT group and 155 in the control group. In comparison with the controls, the PCT group received significantly fewer antibiotic prescriptions (85.8% vs 100%; p < 0.05), were exposed to antibiotics for a shorter time (5.37 vs 10.96 days; p < 0.05), and experienced fewer antibiotic-related adverse events (3.9% vs 25.2%; p < 0.05), regardless of CAP severity. There was no significant between-group difference in recurrence of respiratory symptoms and new antibiotic prescription in the month following enrollment. The results of this first prospective study using a PCT cut-off value to guide antibiotic therapy for pediatric CAP showed that this approach can significantly reduce antibiotic use and antibiotic-related adverse events in children with uncomplicated disease. However, because the study included mainly children with mild to moderate CAP and the risk of the use of the algorithm-based approach was not validated in a relevant number of severe cases, further studies are needed before it can be used in routine clinical practice.

Infections and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that presents a protean spectrum of clinical manifestations, and may affect any organ. The typical course of SLE is insidious, slow, and progressive, with potential exacerbations and remissions, and even dramatically acute and rapidly fatal outcomes. Recently, infections have been shown to be highly associated with the onset and/or exacerbations of SLE, and their possible causative and/or protective role has been largely emphasized in the medical literature. However, the etiopathogenesis of SLE is still obscure and far from being completely elucidated. Among infections, particularly Epstein–Barr virus (EBV), parvovirus B19, retrovirus, and cytomegalovirus (CMV) infections might play a pivotal pathogenetic role. The multifaceted interactions between infections and autoimmunity reveal many possibilities for either causative or protective associations. Indeed, some infections, primarily protozoan infections, might confer protection from autoimmune processes, depending on the unique interaction between the microorganism and host. Further studies are needed in order to demonstrate that infectious agents might, indeed, be causative of SLE, and to address the potential clinical sequelae of infections in the field of autoimmunity.

Role of polymorphisms of toll-like receptor (TLR) 4, TLR9, toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children

BackgroundMalaria caused by Plasmodium falciparum is one of the leading causes of human morbidity and mortality from infectious diseases, predominantly in tropical and sub-tropical countries. As genetic variations in the toll-like receptors (TLRs)-signalling pathway have been associated with either susceptibility or resistance to several infectious and inflammatory diseases, the supposition is that single nucleotide polymorphisms (SNPs) of TLR2, TLR4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A could modulate malaria susceptibility and severity.MethodsThis study was planned to make a further contribution to solving the problem of the real role of the most common polymorphisms of TLR4, TLR9, TIRAP and FCGR2A genes in modulating the risk of malaria and disease severity in children from Burundi, Central Africa. All the paediatric patients aged six months to 10 years admitted to the hospital of Kiremba, Burundi, between February 2011 and September 2011, for fever and suspicion of acute malaria were screened for malaria parasitaemia by light microscopy of thick and thin blood smears. In children with malaria and in uninfected controls enrolled during the study period in the same hospital, blood samples were obtained on filter paper and TLR4 Asp299Gly rs4986790, TLR9 G1174A rs352139, T-1486 C rs187084 TLR9 T-1237 C rs5743836, TIRAP Ser180Leu rs8177374 and the FCGR2A His131Arg rs1801274 polymorphisms were studied using an ABI PRISM 7900 HT Fast Real-time instrument.ResultsA total of 602 patients and 337 controls were enrolled. Among the malaria cases, 553 (91.9 %) were considered as suffering from uncomplicated and 49 (8.1 %) from severe malaria. TLR9 T1237C rs5743836CC was associated with an increased risk of developing malaria (p = 0.03), although it was found with the same frequency in uncomplicated and severe malaria cases. No other differences were found in all alleles studied and in genotype frequencies between malaria cases and uninfected controls as well as between uncomplicated and severe malaria cases.ConclusionsTLR9 T1237C seems to condition susceptibility to malaria in Burundian children but not its severity, whereas none of the assessed SNPs of TLR4, TIRAP and FCGR2A seem to influence susceptibility to malaria and disease severity in this population.

Live attenuated intranasal influenza vaccine

Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

Factors conditioning effectiveness of a reminder/recall system to improve influenza vaccination in asthmatic children.

In order to verify whether a telephone recall system directly managed by pediatricians who usually follow up children for their asthma is more effective than an anonymous recall system, we randomly assigned 285 asthmatic children (177 males; mean age 10.3+/-3.4 years) to one of three groups: those whose mothers were to be called by a pediatrician not previously involved in caring for their asthmatic children and who received the vaccine in our immunisation clinic (group 1); those whose mothers were to be called by a pediatrician from our asthma clinic and who received the vaccine in the immunisation clinic (group 2); and those whose mothers were to be called by a pediatrician from our asthma clinic and who received the vaccine in the same clinic (group 3). Our findings highlight that the use of a reminder/recall system increases vaccination rates in asthmatic children, and show that the best results are obtained when the mothers are contacted and the vaccine administered by the pediatricians who usually follow up the child for asthma.

Should corticosteroids be used in bacterial meningitis in children

Bacterial meningitis is one of the most serious infections in infants and children, with considerable morbidity and mortality. Despite the spreading of conjugated vaccines against Haemophilus influenzae type b (Hib), the most important pneumococcal serotypes and serogroup C meningococcus has reduced the incidence of this infection in developed countries, it still remains a global public health problem and an important cause of mortality and disability. Whether corticosteroids should be used as a complementary therapy to antibacterials is still not clear because of the disparate findings from clinical trials and clinical evidence. The aim of this review is to analyze the available evidence on the impact of corticosteroid therapy in infants and children with bacterial meningitis in developed countries in order to define whether they should be added routinely in the empiric therapy of such disease. Our analysis concluded that in high-income countries dexamethasone has shown good results to prevent hearing loss in Hib meningitis if administered before or at the same time as the first dose of antibiotics. Dexamethasone should be evaluated in pneumococcal meningitis: it may be less beneficial in children with delayed presentation to medical attention and may be unfavourable in case of cephalosporin-resistant pneumococci. On the contrary, there is no evidence to recommend the use of corticosteroids in meningococcal meningitis. Further studies that take into account the epidemiologic changes of recent years, consider enrolment based on the onset of symptoms and evaluate outcomes such as hearing loss and neurologic sequelae with advanced techniques are urgently needed.

Preventing influenza in younger children

Influenza is common in infants and children: attack rates vary from 23% to 48% each year during inter-pandemic periods, and are even higher during pandemics. Severe cases occur more frequently in children with underlying chronic diseases; however, epidemiological studies have clearly shown that influenza also causes an excess of medical examinations, drug prescriptions and hospitalizations in otherwise healthy children (particularly those aged <5 years), as well as a considerable number of paediatric deaths. Childhood influenza also has a number of social and economic consequences. However, many European health authorities are still reluctant to include influenza vaccinations in their national vaccination programmes for healthy children because, among other things, there are doubts concerning their real ability to evoke a protective immune response, especially in children in the first years of life. New hope for the solution of these problems has come from the introduction of vaccines containing more antigens and the possibility of intradermal administration. However, further studies are needed to establish whether universal influenza vaccination in the first years of life should be recommended, and with which vaccine.

Risk factors for bacteremia during and after adenoidectomy and/or adenotonsillectomy

OBJECTIVE To evaluate the incidence and persistence of bacteremia in children undergoing adenoidectomy or adenotonsillectomy for different medical reasons. METHODS We enrolled 130 children scheduled for adenoidectomy because of recurrent acute otitis media (rAOM, 15) or persistent otitis media with effusion (pOME, 33), or for adenotonsillectomy because of obstructive sleep apnea syndrome (OSAS, 41) or recurrent tonsillopharyngitis (rTF, 41). Nasopharyngeal aspirates taken just before surgery, swabs of the ablated central adenoidal and tonsillar tissues, and blood samples taken within the first 30s of beginning the operation and 20min after its end were used for bacterial cultures. RESULTS The incidence of positive blood cultures after the beginning of the operation was significantly higher in the children who underwent adenotonsillectomy than in those who underwent adenoidectomy, and in those with rAOM or rTF than in those with pOME or OSAS. Children with nasopharyngeal colonisation were significantly more likely to have a positive blood culture than those without. Twenty of the 25 children with a positive blood culture (80.0%), had the same bacteria in their nasopharyngeal and adenoidal/tonsillar tissues. CONCLUSIONS Our results show that bacteremia is significantly more frequently associated with adenotonsillectomy than with adenoidectomy, and significantly more frequent in patients with a history of rAOM or rTF.

Steroids and childhood encephalitis.

G (GS) have both antiinflammatory and immunosuppressive property, which explains why pediatricians tend to prescribe them for all pediatric clinical conditions in which it is thought or known that inflammation and/or autoimmunity are the main cause of disease signs and symptoms. However, such prescriptions are sometimes questionable because the efficacy of GS has not been demonstrated by controlled trials, and the risk of adverse events following high-dose or prolonged administration has not been adequately evaluated. Encephalitis is one of the syndromes for which GS are frequently used. However, the importance of this treatment remains unclear because a diagnosis of encephalitis covers a range of clinical conditions whose etiology, pathogenesis, clinical picture and spontaneous evolution vary. Furthermore, it has been tested in very few studies involving children. The aim of this article is to review what is currently known about the real impact of GS treatment in children with acute infectious encephalitis (AIE) and acute disseminated encephalomyelitis (ADEM), the 2 major types of encephalitis.

Chapter 41 – Infections and Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that may affect any organ and presents a protean spectrum of clinical manifestations. The etiology and pathogenesis of SLE remain unknown. It is believed that SLE represents a complex multifactorial disease arising from a combination of genetic susceptibility and hormonal and environmental factors, which lead to the production and perpetuation of aberrant autoimmune responses. Infections were recently shown to be highly associated with the onset and/or exacerbations of SLE, and their causative and/or protective role has been largely emphasized in the medical literature. The aim of this review is to screen the medical literature from the past 15 years and investigate the role of infectious agents in the pathogenesis of SLE. This analysis of the literature shows that the aetiopathogenesis of SLE is still obscure and remains far from completely elucidated. Environmental and genetic factors have been implicated in the induction and progression of this disease. Among infections, Epstein-Barr virus, parvovirus B19, retrovirus and cytomegalovirus infections in particular might play a pivotal role in the pathogenesis of SLE. The multifaceted interactions between infections and autoimmunity reveal many possibilities for either causative or protective associations. Indeed, some infections (primarily protozoan infections) might confer protection from autoimmune processes, depending on the unique interaction between microorganisms and the host. Further studies are needed to conclude that infectious agents are indeed one of the causes of SLE and to address the potential clinical sequelae of infections in the field of autoimmunity.