Current Pediatric Reviews - Volume 9, Issue 4, 2013

Mycoplasma pneumoniae is a common cause of respiratory infections in children and adults, but the most severe presentations tend to be in older children and adolescents. The organism causes up to 30% of primary atypical pneumonia (PAP), but it is now recognized that these severe manifestations of infection represent only a small percentage of respiratory infections due to this species of bacteria. Typical incubation times until the development of symptoms are remarkably slow for a bacterial infection, usually between 2 and 3 weeks. The typical presentation includes flulike symptoms with cough, often with sore throat, headache, malaise, and fever. Symptoms, particularly cough, may be very prolonged despite appropriate antibiotic therapy, sometimes lasting up to 3 months. Cough, initially dry, may become productive of purulent sputum as the illness progresses. Examination of the throat may reveal some erythema but usually no exudates or associated lymphadenopathy. Auscultation of the chest in patients with PAP often demonstrates fine inspiratory rales, particularly at the lung bases, and occasionally expiratory wheezing. Chest films may show streaky unilateral or bibasilar infiltrates, peribronchial thickening, and not infrequently small pleural effusions. Computed tomographs of the chest are very likely to show peribronchial thickening and centrilobular nodules with a tree-in-bud pattern and patchy areas of airspace consolidation. Accurate diagnosis of M. pneumoniae infections is complicated by a current lack of rapid diagnostic techniques with appropriate sensitivity and specificity.

Mycoplasma pneumoniae causes upper and lower respiratory-tract disease. In addition, extra-pulmonary diseases may occur at the same time as the pulmonary infection or soon after. These complications may involve neurological, dermatological, musculoskeletal, cardiovascular, gastrointestinal, renal and hematological systems, or more than one of these. Complications which are dermatological, musculoskeletal and gastrointestinal are seen most frequently (15-50%) but are not as serious as nervous, cardiac and blood disorders. The mechanism behind the development of these complications is largely immunological. The extent to which autoimmune phenomena are responsible varies, evidence for this being greatest for hematological disorders and least for gastrointestinal ones.

Mycoplasma pneumoniae is an important pathogen of the upper and lower respiratory tracts of children and adults. Historically, it has been susceptible in vitro to macrolides, tetracyclines, and fluoroquinolones. Standardized methods for performance and interpretation of in vitro susceptibility tests have now been published for M. pneumoniae and mechanisms of acquired resistance to macrolides have been shown to be due to mutations in the 23S rRNA gene. Emergence and widespread dissemination of clinically significant high-level macrolide resistance in Asia and documentation of its occurrence to a lesser extent in several European countries and the United States during the past decade is worrisome since treatment options for children are limited. This article summarizes the current status of antimicrobial susceptibility testing, mechanisms of antimicrobial resistance, epidemiology of macrolide resistance and treatment alternatives for pediatric infections caused by M. pneumoniae.

Asthma is a chronic inflammatory airway disease characterized by reversible obstruction. The cause(s) of asthma are still an area of active investigation in many laboratories across the world, but to date the pathogenesis has remained obscure. It is likely that asthma is the final common pulmonary expression of multiple factors that lead to airway hyperresponsiveness, some inherited and some environmental, which differ in different individuals. It is clear that respiratory infections play a major role in the development of asthma during childhood. However there are seemingly contradictory data suggesting on the one hand that exposure to bacterial products, e.g. lipopolysaccharide, and viral infections, e.g. participation in daycare, during early childhood can be protective, but on the other hand there is well-documented association of the development of airway hyperreactivity following infections with viruses such as respiratory syncytial virus and atypical bacterial infections, particularly with Mycoplasma pneumoniae. New studies, suggest that M. pneumoniae is present in the airways of a substantial proportion of the population, bringing up the possibility that the persistent presence of the organism may contribute to the asthmatic phenotype in a subset of patients. This review will examine the current data regarding a possible role for M. pneumoniae in chronic asthma.

In order to cause disease, Mycoplasma pneumoniae must adhere to host cells and produce cytotoxic molecules. Despite its small genome, M. pneumoniae achieves cytadherence through the synthesis of a complex cellular structure, the terminal organelle or attachment organelle, which initiates binding to host cells through carbohydrate moieties associated with protein and lipid molecules on their surfaces. The construction of this organelle is remarkable, making use of proteins that are generally dissimilar in composition to those found in organisms other than the closest relatives of M. pneumoniae. The attachment organelle also plays an essential role in the crucial but poorly understood process of gliding motility. Cytadherence is also carried out by other proteins involved in binding to ligands found on host cell surfaces. Having accomplished cytadherence, M. pneumoniae damages host cells though various means. One is production of hydrogen peroxide, which occurs via metabolism of glycerol. Another is the production of CARDS toxin, an ADPribosyltransferase that induces vacuolation and, when administered on its own, mimics many of the clinical symptoms of M. pneumoniae-associated disease. A nuclease has been implicated in promoting apoptosis of host cells. Finally, certain M. pneumoniae lipoproteins elicit host immunologic responses that contribute significantly to cytokine production and concomitant inflammation. These various virulence factors make M. pneumoniae difficult to clear, resulting in not just acute but also chronic disease.

Mycoplasma pneumoniae (M. pneumoniae) is recognized as common cause of respiratory tract infections occurring worldwide both in children and in adults. Prevalences of M. pneumoniae infection range from 0% to 50%, influenced by age and geographic location of the patients, the stage of the disease but also with the diagnostic methods applied. Correct and rapid diagnosis of M. pneumoniae infections is however critical to initiate appropriate antibiotic treatment. Because of the widespread availability of commercial tests, and the ease of obtaining a serum specimen, serological methods still play a predominant role in clinical practice to diagnose M. pneumoniae infections. However, the performances of these tests depend on several factors resulting in a poor agreement between different tests. Consequently, the choice of the serological test has important implications when performing seroepidemiological studies and when using these tests for the management of individual patients. Over the past few years, nucleic acid amplification techniques (NAATs), especially real-time PCR, have provided significant improvements in the diagnosis of RTI, resulting from both improved sensitivity and specificity, and the production of very rapid results. However, as for serology, lack of standardization has resulted in a wide variation of interlaboratory test performances. The availability of the very sensitive NAATs has in recent years also put the serological tests in their right perspective. Data from recent studies using PCR based methods and serology published during the last 5 years in different patient populations from around the world are summarized and the role of both techniques will be discussed.

Despite being a member of the smallest and perhaps simplest group of organisms, the mechanisms involved in the pathogenesis of Mycoplasma pneumoniae disease have proven complex. Much of the work that is the basis of our current understanding of each of these steps of M. pneumoniae respiratory disease pathogenesis is from studies using animal models, which have proven valuable in understanding mycoplasma-host interactions, and provide a foundation for studies in humans. Soon after infection, airway epithelial cells can sense mycoplasma infection via TLR2 and produce factors that resist infection and initiate events that lead to recruitment and activation of inflammatory cells. Innate immunity is recognized to have an important role in the progression of mycoplasma respiratory disease. Adaptive immunity, characterized by both B and T lymphocyte responses, has a major impact on the progression of M. pneumoniae respiratory disease. B and T cell responses can have two competing impacts. They can contribute to mycoplasma diseases immunopathology or prevent infection and subsequent spread of mycoplasma infection from lung to other tissues. Murine and other models have also proven critical in the development of new antibiotics, therapeutic approaches and vaccine development. This review is not intended to be exhaustive, but will focus on aspects of each of the above areas and the animal studies that have lead to improving our understanding of M. pneumoniae disease pathogenesis.

A worldwide cause of atypical bacterial pneumonia, Mycoplasma pneumoniae affects all populations and age groups and is especially common in young adults and children. In the United States alone, M. pneumoniae causes up to 40% of community-acquired pneumonia (CAP) cases in some populations and is characterized by relatively long incubation periods and a wide spectrum of clinical symptoms and disease manifestations. The varied presentation and limited diagnostic methods available present unique challenges for accurately identifying M. pneumoniae cases, which can lead to inappropriate treatment of patients and/or an ineffective (or nonexistent) public health response to outbreaks. Recent advancements in diagnostics, laboratory techniques, and whole genome sequence information are addressing these issues. Newly developed and highly innovative approaches and techniques have allowed for unprecedented characterization of this organism and have led to improved awareness of many facets of M. pneumoniae. Still, considerable challenges remain for gaining a comprehensive understanding of the epidemiology and pathogenesis of this organism. Lack of standardized and reliable diagnostic tests for use in clinical laboratories and in state and local public health laboratories continues to impede efficient detection of clusters and outbreaks. Clear recommendations for outbreak control are also lacking. Worldwide emergence of macrolide resistance is a particular area of concern facing physicians who seek safe and effective alternative treatment regimens, especially for children. This review summarizes the current state of understanding of the many aspects surrounding M. pneumoniae infection and addresses outstanding domestic issues still confronting public health. A unique prospective and overview of the many features involved in conducting an outbreak investigation and effective public health response is also reported.

Genotyping of Mycoplasma pneumoniae, a pathogen responsible for community-acquired pneumonia that occurs both endemically and epidemically worldwide, is essential for understanding M. pneumoniae distribution and relatedness and for determining the epidemiology of infection caused by this pathogen. It may also explain most phenotypic variability, such as geographic distribution, host specificity, antibiotic resistance, and virulence. However, the molecular typing is hampered by the fact that M. pneumoniae is a genetically homogeneous species in which large genomic rearrangements do not frequently occur. For these reasons, it has been difficult to develop a typing method with a good discriminatory power below the species level. Many molecular methods have been used for genotyping M. pneumoniae. Some of them are based on studying the banding pattern profiles resulting from endonuclease restriction, or from PCR amplification combined with or without restriction, while some others study DNA sequence polymorphisms by sequencing. According to the method used, the target can be a single gene, multiple genes, or the whole genome. In this review, we describe these methods following the classification mentioned above. We also discuss the epidemiological value of M. pneumoniae genotyping particularly for the most commonly used techniques.

An intracranial aneurysm in a child or adolescent is a rare, but potentially devastating condition. As little as approximately 1200 cases are reported between 1939 and 2011, with many of the reports presenting diverting results. There is consensus, though, in that pediatric aneurysms represent a pathophysiological entity different from their adult counterparts. In children, there is a male predominance. About two-thirds of pediatric intracranial aneurysms become symptomatic with hemorrhage and the rate of re-hemorrhage is higher than in adults. The rate of hemorrhage from an intracranial aneurysm peaks in girls around menarche. The most common aneurysm site in children is the internal carotid artery, in particular at its terminal ending. Aneurysms in the posterior circulation are more common in children than adults. Children more often develop giant aneurysms, and may become symptomatic from the mass effect of the aneurysm (tumorlike symptoms). The more complex nature of pediatric aneurysms poses a larger challenge to treatment alongside with higher demands to the durability of treatment. Outcome and mortality are similar in children and adults, but long-term outcome in the pediatric population is influenced by the high rate of aneurysm recurrences and de novo formation of intracranial aneurysms. This urges the need for life-long follow-up and screening protocols.

Introduction: Many childhood-onset diseases and developmental disorders have a strong genetic basis. However, up till now, the knowledge of this genetic component within multifactorial diseases is not frequently used in paediatric practice. A good family history collection can facilitate the link between the present paediatric practice and the advances in genetics. This paper explores the benefits and drawbacks of the existing validated family history tools from the viewpoint of paediatric primary practice, with special attention for the mental health issues. Methodology: A literature search was conducted in the following directories: PubMed, Cochrane, Embase and Google Scholar. The timeframe was 01.01.2000 – 01.09.2011. The articles meeting the following criteria were included: original research papers in English, containing description or validation of the family history tool, for multifactorial/complex common disorders. The data were extracted from the full text of the articles. They were classified according to 14 criteria including diseases in question, level of healthcare, validation sample characteristics and results of usability analysis. Results: The majority of the family history tools, described in the literature, deal with a narrow range of diseases (some cancers, diabetes and coronary heart disease). None were tested in the paediatric healthcare. The cost-effectiveness analysis was never reported. Conclusions: The major finding of the present study is the absence of the validated tools for the family history collection for the paediatric primary care in general and in mental health in particular. The existing advances create a solid base for composition of the unified tool for paediatric primary care.

The topic of meningitis has received considerable media interest. Despite great strides in medical development, meningitis remains one of the leading causes of death by infection in children. Dental abnormalities secondary to meningococcal septicaemia have been described but information is scarce. This report aims to add weight to existing literature by describing a series of three cases which presented with a number of dental anomalies including hypodontia, abnormal tooth–shaped calcifications, impacted and ectopic teeth, hypoplasia, delayed development and eruption. Dental management of these cases encompassed a multidisciplinary approach, including prevention, restoration of carious teeth, improvement of aesthetics and orthodontic treatment. The dental features in these cases were comparable to those previously described and support links demonstrated between meningococcal septicaemia and dental abnormalities. Although immunisation offers hope, complete eradication of meningitis is not yet on the horizon. While the potential of meningitis remains, health professionals should be aware of its impact on the dentition.

Background: Adolescents experience elevated rates of STDs and HIV. STD/HIV prevention interventions for young men are crucial to decrease their STD/HIV rates and reduce disease transmission to female partners. To advance sexual health promotion interventions for young men, this paper reviewed the efficacy of STD/HIV prevention interventions conducted in North and Central America in the past 20 years. Method: PubMed, Google Scholar, and EBSCO Host databases were used to locate STD/HIV interventions. Eligible interventions were limited to STD/HIV interventions for young men between the ages of 10 and 18. We review 8 STD/HIV prevention interventions targeting heterosexual adolescent males and summarize key intervention components and content, overview intervention efficacy outcome data, and provide directions for future research. Results: The majority of interventions were guided by health behavior change theory. Interventions employed interactive group-based education and behavioral skills training to reduce risky sexual behaviors. All interventions used a randomized controlled trial design with a comparison or control group. Follow-up times varied markedly, ranging from 3 weeks to 36 months. All but one intervention improved at least one behavioral outcome (e.g., increased frequency of condom use). Conclusions: Findings suggest that male adolescent interventions can effectively curtail the STD/HIV epidemic. Major weaknesses of the reviewed studies include the reliance on self-report behavioral measures, lack of biological endpoints, and short follow-ups. Study strengths include use of randomized control trial design and theory-based content. Future research should increase the dissemination of effective sexual risk reduction interventions to decrease STD/HIV among adolescent males and their female partners.