Hookworm infection in infants: a case report and review of literature.

BACKGROUND: Hookworm infections (Necator americanus, Ancylostoma duodenale) are common in rural areas of tropical and subtropical countries. Human acquisition results from direct percutaneous invasion of infective larvae from contaminated soil. Overall, almost 472 million people in developing rural countries are infected. According to simulation models, hookworm disease has a global financial impact of over US$100 billion a year. Hookworm infection in newborn or infancy is rare, and most of the cases reported in literature are from endemic countries. Here, we describe the case of an infant with an Ancylostoma duodenale infection and review the literature currently available on this topic. CASE PRESENTATION: An Italian 2-month-old infant presented with vomit and weight loss. Her blood exams showed anemia and eosinophilia and stool analysis resulted positive for hookworms' eggs, identified as Ancylostoma duodenale with real time-PCR. Parasite research on parents' stools resulted negative, and since the mother travelled to Vietnam and Thailand during pregnancy, we assumed a transplacental transmission of the infection. The patient was treated successfully with oral Mebendazole and discharged in good conditions. DISCUSSION: Hookworm helminthiasis is a major cause of morbidity in children in the tropics and subtropics, but rare in developed countries. Despite most of the patients is usually asymptomatic, children are highly exposed to negative sequelae such as malnutrition, retarded growth and impaired cognitive development. In infants and newborns, the mechanism of infection remains unclear. Although infrequent, vertical transmission of larvae can occur through breastfeeding and transplacentally. Hookworm infection should be taken into account in children with abdominal symptoms and unexplained persistent eosinophilia. The treatment of infants infected by hookworm has potential benefit, but further studies are needed to define the best clinical management of these cases.

Meningococcal disease in childhood: epidemiology, clinical features and prevention.

Invasive meningococcal disease (IMD) represents a public health problem and a leading cause of morbidity and mortality worldwide. IMD can occur as an endemic disease with sporadic cases or epidemics with outbreaks. Neisseria meningitis strains are divided into 13 serogroups, but only five (A, B, C, W-135, and Y) are responsible for most IMD across the world. All age groups are at risk for IMD, but infants and adolescents are particularly vulnerable. The most common clinical manifestations of IMD are meningitis and septicemia, although in some cases both clinical pictures are present. The clinical pattern can differ according to age; in young children, the clinical manifestations may be more insidious and the diagnosis may be more difficult compared to older children or adolescents. Death occurs in 6-10% of cases and sequelae in 4.3-11.2% of cases. Early recognition of children with meningococcal infection is important in order to initiate systemic antibiotic therapy, although vaccination remains the best strategy to control meningococcal disease. Recently, different meningococcal vaccines have been introduced worldwide, resulting in a reduction in the overall burden of the disease. The goal of the next few years should be to increase vaccination coverage against meningococcal diseases, continue to monitor IMD and develop a unique vaccine able to cover all of the main meningococcal strains.

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.

Hexavalent vaccines for immunization in paediatric age.

Despite the potential for protection against a broad spectrum of pathogens, the availability of an increased number of effective vaccines could lead to a significant reduction in vaccination coverage as the result of issues with implementation of new vaccines within existing protocols. To overcome these problems, the development of combined vaccines has been promoted. The use of combined vaccines offers a number of potential benefits, including a reduction in the number of patient visits, reduced complications associated with multiple intramuscular injections, decreased costs of stocking and administering separate vaccines, and a lowering of the risk of delayed or missed vaccinations. The hexavalent vaccine includes antigens against diphtheria, tetanus, acellular pertussis (DTaP), hepatitis B (HBsAg), poliomyelitis (P1, P2, P3) and Haemophilus influenzae type B (Hib) infections. The primary goal of this review is to discuss the immunogenicity, efficacy, safety and tolerability of several hexavalent preparations that are either commercially available or still under development.

Current advances in the understanding and treatment of mevalonate kinase deficiency.

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired mevalonate kinase activity. Complete impairment results in the severe metabolic disease, mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum IgD levels and inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs, corticosteroids, and biological agents that target specific cytokine pathways. In recent years, some studies have reported promising results for new biological drugs; however, these cases have failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management.

Management of paediatric Lyme disease in non-endemic and endemic areas: data from the Registry of the Italian Society for Pediatric Infectious Diseases.

The purpose of this investigation was to determine how specialists in paediatric infectious diseases (PIDs) manage children with suspected Lyme disease (LD) by comparing their approaches in Italian endemic and non-endemic areas. A cross-sectional survey of the PID specialists participating in the Italian Society for Pediatric Infectious Disease (SITIP) Registry of LD was carried out between 1 January and 30 April 2012. A total of 160 children (80 living in endemic areas and 80 living in non-endemic areas) were diagnosed as having LD between 1 January 2005 and 31 December 2011. The clinical manifestations were erythema migrans in 130 cases (81.3 %), arthritis in 24 (15.0 %) and neuroborreliosis in six (3.8 %). Significant differences from the recommendations concerning serology and the tests to undertake were mainly observed in the children with erythema migrans, especially those living in non-endemic areas (p < 0.05). The children with erythema migrans who lived in non-endemic areas were treated with antibiotics significantly less frequently than those living in endemic areas (p < 0.05), and significantly fewer children with erythema migrans or arthritis living in non-endemic areas were treated with amoxicillin in comparison with those living in endemic regions (p < 0.05). The duration of antimicrobial therapy was significantly shorter than recommended in the children with erythema migrans or arthritis, especially those living in non-endemic areas (p < 0.05). Paediatric LD is also present in areas of Italy in which it is not considered endemic, but knowledge concerning its management is generally poor among PID specialists and characterised by enormous gaps in non-endemic areas.

Meningitis complicated by subdural empyema and deafness caused by pneumoccoccal serotype 7F in a 17-month-old child: a case report.

Despite the availability of effective antibacterial agents and vaccines, pneumococcal meningitis and sepsis are still associated with high mortality rates and a high risk of neurological sequelae. We describe the case of a 17-month-old boy vaccinated with heptavalent pneumococcal conjugate vaccine (PCV7) who developed bacterial meningitis complicated by subdural empyema and deafness caused by Streptococcus pneumoniae serotype 7F. The 7F strain is not contained in PCV7 (the only vaccine on the market at the time of the onset of meningitis) but is included in the new pediatric 13-valent PCV, which may therefore prevent cases such as this in the future.

Clinical presentation of meningococcal disease in childhood.

Although relatively rare, meningococcal disease represents a global health problem being still the leading infectious cause of death in childhood with an overall mortality around 8%. Meningococcal meningitis is the most commonly recognized presentation, accounting for 80% to 85% of all reported cases of meningococcal disease (in half of these cases sepsis is also present concomitantly). The remaining 15-20% of cases are most commonly bloodstream infections only. Meningococcal serogroups A, B, and C account for most cases of meningococcal disease throughout the world. Recently, serogroups W-135 and X (predominantly in Africa) and group Y (in the United States and European countries) have emerged as important disease-causing isolates. Despite recent advances in medical management, the mortality rate of fulminant meningococcemia ranges from 15% to 30%. However, among survivors, 10-30% could have long term sequelae (i.e. sensoneural hearing loss, seizure, motor problems, hydrocephalus, mental retardation, and cognitive and behavioral problems). Considering the clinical severity of meningococcal disease, prevention represents the first approach for avoiding serious complications and possible deaths. The availability of new vaccines able to cover the emerging serotypes including A and Y as well as the availability on the market of new products that could prevent meningococcal B infection represent a great opportunity for the decrease of the burden of this complicated disease.

Can infants be protected by means of maternal vaccination?

The administration of vaccines is not usually recommended in pregnant women because of a fear of severe adverse events for the fetus. However, contraindication to vaccination applies only to vaccines based on live attenuated viruses for the theoretical possibility that they might infect the fetus. In contrast, the use of several inactivated vaccines is useful and recommended. As a result of the transplacental passage of antibodies, maternal immunization can reduce the risk of vaccine-preventable diseases that may occur in the first months of life before the start or completion of the suggested vaccination schedule. One of the best examples is vaccination against influenza that can protect pregnant women from a disease that can lead to hospitalization and death in a significantly higher number of cases than in the general population and can induce protective specific antibody levels as well as being effective in infants in the first months of life. Other examples are vaccinations against tetanus, pertussis, pneumococcal infections and Haemophilus influenzae type b infection. This review analyses the advantages and limitations of maternal immunization as revealed by experience and the main publications.

Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences.

In order to evaluate the infectious agents associated with the first episode of severe acute wheezing in otherwise healthy infants and to define the role of each of them in recurrences, 85 patients in Italy, aged <12 months, hospitalized because of a first acute episode of wheezing, were prospectively enrolled between 1 October 2005 and 31 March 2006. Upon enrollment, nasopharyngeal swabs were collected for the real-time PCR detection of respiratory syncytial virus (RSV) types A and B, influenza virus types A and B, adenovirus, parainfluenza viruses types 1, 2, 3 and 4, rhinovirus, human metapneumovirus, human coronavirus types 229E, OC43, NL63, and HKU1, bocavirus, enterovirus, and paraechovirus; nasopharyngeal aspirates were also obtained to detect atypical bacteria. At least one infectious agent was identified in 76 children (89.4%). RSV was the most frequently detected pathogen and its prevalence was significantly higher than that of the other pathogens in both age groups, and significantly higher in the children aged 3-12 months than in those aged <3 months. Only the children with RSV infection experienced recurrent wheezing. Viral load was significantly higher in children with than in those without recurrent wheezing. This study shows that RSV is the main reason for hospitalization during the first wheezing episode in infants, and that it appears to be the only pathogen associated with a high frequency of recurrences. A high viral load seems to be strictly related to the likelihood of recurrence.

From clinical practice to guidelines: how to recognize rhinosinusitis in children.

Rhinosinusitis is a common childhood respiratory infection. Children have approximately six to eight viral infections of the upper respiratory tract each year, 5-13% of which may be complicated by a secondary bacterial infection of the paranasal sinuses. The diagnosis of acute bacterial rhinosinusitis in children is established by the persistence of purulent nasal or post-nasal draining lasting at least 10 days, especially if accompanied by supporting symptoms and signs, at which point antibiotic treatment has to be recommended. Appropriate antibacterial therapy should also be recommended if the draining has been present for less time, but is concomitantly associated with significant fever and localized signs of sinus inflammation in a child who appears ill. Imaging studies are not necessary to confirm the diagnosis of clinical rhinosinusitis for the purposes of treatment, but should be reserved for cases in which the diagnosis is in doubt or a complication is suspected, and for patients with recurrent or chronic rhinosinusitis. Under these circumstances, computed tomography is the preferred evaluation. Together with their clinical judgment, these suggestions may be useful for pediatricians in diagnosing this common condition.

Human metapneumovirus in paediatric patients.

Acute respiratory tract infections (ARTIs) are a leading cause of morbidity and mortality in children worldwide, but the aetiology of many ARTIs is still unknown. In 2001, researchers in The Netherlands reported the discovery of a previously unidentified pathogen called human metapneumovirus (hMPV). Since its initial description, hMPV has been associated with ARTI in Europe (Italy, France, Spain, the UK, Germany, Denmark, Finland and Norway), America (the USA, Canada, Argentina and Brazil), Asia (India, Japan, China and Singapore), Australia and South Africa in individuals of all ages. The incidence of infection varies from 1.5% to 25%, indicating that hMPV is a ubiquitous virus with a worldwide distribution. hMPV seems to play an important role as a cause of paediatric upper and lower respiratory tract infection, with similar, but not identical, epidemiological and clinical features to those of respiratory syncytial virus and influenza virus. Moreover, the socio-economic impact of hMPV-infected children on their families seems to be considerable, which suggests that, like influenza virus, hMPV infection may be a substantial public health problem for the community. It may be associated with significant morbidity and mortality in pre-term infants and children with underlying clinical conditions, although more adequately controlled studies are needed to confirm its importance in such patients. Many fundamental questions concerning the pathogenesis of hMPV disease and the host's specific immune response remain to be answered. Further studies are also required to properly define hMPV diagnosis, treatment and prevention strategies.

Clinical and socio-economic impact of influenza and respiratory syncytial virus infection on healthy children and their households.

This prospective study compared the clinical and socio-economic impact of laboratory-confirmed influenza and respiratory syncytial virus (RSV) infection on healthy children and their families. Among 1,520 otherwise healthy children aged< 15 years attending the Emergency Department for acute conditions other than trauma, influenza viruses and RSV were found in 234 (15.4%) and 116 (7.6%; p<0.0001) patients, respectively. The fact that influenza has a similar global clinical impact on the community to that of RSV infection, but represents a greater socio-economic burden, may contribute to broadening the acceptance of influenza vaccination.

Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides.

In order to evaluate the efficacy of macrolides in pediatric patients with recurrent respiratory tract infections (RRTIs), we enrolled 1,706 children (783 females) aged between 6 months and 14 years (median: 4 years) with an acute respiratory infection and a history of RRTIs (> or = 8 episodes per year if aged < 3 years; > or = 6 episodes per year if aged > or = 3 years). The therapies were chosen by the primary care pediatricians and their effects on respiratory relapses were blindly analyzed. Regardless of age and clinical diagnosis, the children treated with macrolides showed a significantly higher rate of short- and long-term clinical success than those receiving beta-lactams (p<0.0001) or symptomatics alone (p<0.0001). These data show that macrolide therapy of acute respiratory infections influences the natural history of RRTIs, probably because of their elective activity on atypical bacteria. They also suggest the possible importance of these pathogens in causing recurrences of respiratory infections in children and show that the infections they cause may have a more complicated course unless treated with adequate antibacterial drugs.

Emerging role of Mycoplasma pneumoniae in children with acute pharyngitis.

In order to define the role, the risk factors, and the clinical and laboratory characteristics of Mycoplasma pneumoniae infection in children with pharyngitis, 184 patients with acute non-streptococcal pharyngitis (102 males; median age, 5.33 years) were studied. Acute Mycoplasma pneumoniae infection was demonstrated in 44 (23.9%) patients. A history of recurrent episodes of pharyngitis (defined as at least 3 acute episodes of pharyngitis in the 6 months preceding enrollment) appeared to be the more useful parameter for differentiating Mycoplasma pneumoniae pharyngitis from non-streptococcal non- Mycoplasma pneumoniae pharyngitis ( P<0.05 in multivariate analysis). These data, which highlight the emerging role of Mycoplasma pneumoniae in acute pharyngitis, must be taken into account in the diagnosis and treatment of this clinical manifestation in children.

Long-term pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine in comparison with that after natural infection.

The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers against Bordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. After 5 years, only a small proportion of vaccinated and infected children had significant specific concentrations of IgG in serum against all three B. pertussis antigens, and T-cell responses persisted in a minority of subjects. A preferential type 1 cytokine response with the secretion of gamma interferon was observed in the pertussis group, whereas a type 2 skewed response was observed in the vaccinated children; however, the quantitative differences in the cytokines produced by DTaP-HBV and natural infection were minimal. In conclusion, our results show that the immune responses induced by primary pertussis vaccination are qualitatively and quantitatively similar to those seen in children who recovered from natural infection and highlight the need for booster immunization with pertussis vaccines in order to maintain adequate levels of a specific immune response to B. pertussis.

Immunoendocrinologic abnormalities in human immunodeficiency virus infection.

Alterations in the production of adrenal steroids and a complex pattern of dysregulation in cytokine profiles accompany the progression of HIV infection. Cortisol levels increase in HIV infection, while those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. A shift from type-1 to type-2 cytokine production is also detected in most patients during disease progression. This shift is summarized as a defective production of interferon gamma (IFN gamma), interleukin-2 (IL), and IL-12 accompained by increased production of IL-4, IL-5, IL-6, and IL-10. IFN gamma and IL-2 are suppressed, while the generation of IL-4 is stimulated by cortisol and pharmacological doses of glucocorticoids (GC). GC and IL-4 stimulate the differentiation of B lymphocytes into IgE-producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induces programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes. Because (1) TH1 but not TH2 undergo rapid Fas-mediated PCD upon antigen-stimulation, and (2) TH2 clones preferentially survive in vitro cell cultures, the progressive shift from type-1 to type-2 cytokine production observed in HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. Progression of HIV infection to AIDS can be controlled by highly active antiretroviral therapy (HAART); HAART drastically reduces HIV plasma viremia, but is less effective in immune reconstitution. Additionally HAART is associated in a sizable portion of patients by complex lypodistropyc phenomena that often involve the endocrine system.