Current Pediatric Reviews (v.9, #4)

Editorial ( Thematic Issue: Mycoplasma pneumoniae) by Thomas Prescott Atkinson (267-267).

Mycoplasma pneumoniae is a common cause of respiratory infections in children and adults, but the most severepresentations 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 ofrespiratory infections due to this species of bacteria. Typical incubation times until the development of symptoms are remarkablyslow for a bacterial infection, usually between 2 and 3 weeks. The typical presentation includes flulike symptomswith cough, often with sore throat, headache, malaise, and fever. Symptoms, particularly cough, may be very prolongeddespite appropriate antibiotic therapy, sometimes lasting up to 3 months. Cough, initially dry, may become productiveof purulent sputum as the illness progresses. Examination of the throat may reveal some erythema but usually noexudates or associated lymphadenopathy. Auscultation of the chest in patients with PAP often demonstrates fine inspiratoryrales, particularly at the lung bases, and occasionally expiratory wheezing. Chest films may show streaky unilateral orbibasilar infiltrates, peribronchial thickening, and not infrequently small pleural effusions. Computed tomographs of thechest are very likely to show peribronchial thickening and centrilobular nodules with a tree-in-bud pattern and patchyareas of airspace consolidation. Accurate diagnosis of M. pneumoniae infections is complicated by a current lack of rapiddiagnostic techniques with appropriate sensitivity and specificity.

Mycoplasma pneumoniae causes upper and lower respiratory-tract disease. In addition, extra-pulmonary diseasesmay 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 ofthese. 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 complicationsis largely immunological. The extent to which autoimmune phenomena are responsible varies, evidence for this beinggreatest for hematological disorders and least for gastrointestinal ones.

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

Asthma is a chronic inflammatory airway disease characterized by reversible obstruction. The cause(s) ofasthma are still an area of active investigation in many laboratories across the world, but to date the pathogenesis has remainedobscure. It is likely that asthma is the final common pulmonary expression of multiple factors that lead to airwayhyperresponsiveness, some inherited and some environmental, which differ in different individuals. It is clear that respiratoryinfections play a major role in the development of asthma during childhood. However there are seemingly contradictorydata 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 associationof the development of airway hyperreactivity following infections with viruses such as respiratory syncytial virus andatypical bacterial infections, particularly with Mycoplasma pneumoniae. New studies, suggest that M. pneumoniae ispresent in the airways of a substantial proportion of the population, bringing up the possibility that the persistent presenceof the organism may contribute to the asthmatic phenotype in a subset of patients. This review will examine the currentdata 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, theterminal organelle or attachment organelle, which initiates binding to host cells through carbohydrate moieties associatedwith protein and lipid molecules on their surfaces. The construction of this organelle is remarkable, making use of proteinsthat 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. Havingaccomplished cytadherence, M. pneumoniae damages host cells though various means. One is production of hydrogenperoxide, which occurs via metabolism of glycerol. Another is the production of CARDS toxin, an ADPribosyltransferasethat induces vacuolation and, when administered on its own, mimics many of the clinical symptoms ofM. pneumoniae-associated disease. A nuclease has been implicated in promoting apoptosis of host cells. Finally, certainM. pneumoniae lipoproteins elicit host immunologic responses that contribute significantly to cytokine production andconcomitant inflammation. These various virulence factors make M. pneumoniae difficult to clear, resulting in not justacute but also chronic disease.

Mycoplasma pneumoniae (M. pneumoniae) is recognized as common cause of respiratory tract infections occurringworldwide 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. pneumoniaeinfections 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 methodsstill play a predominant role in clinical practice to diagnose M. pneumoniae infections. However, the performances ofthese tests depend on several factors resulting in a poor agreement between different tests. Consequently, the choice of theserological test has important implications when performing seroepidemiological studies and when using these tests forthe management of individual patients.;Over the past few years, nucleic acid amplification techniques (NAATs), especially real-time PCR, have provided significantimprovements in the diagnosis of RTI, resulting from both improved sensitivity and specificity, and the production ofvery rapid results. However, as for serology, lack of standardization has resulted in a wide variation of interlaboratory testperformances. The availability of the very sensitive NAATs has in recent years also put the serological tests in their rightperspective.;Data from recent studies using PCR based methods and serology published during the last 5 years in different patientpopulations 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 inthe pathogenesis of Mycoplasma pneumoniae disease have proven complex. Much of the work that is the basis of our currentunderstanding of each of these steps of M. pneumoniae respiratory disease pathogenesis is from studies using animalmodels, which have proven valuable in understanding mycoplasma-host interactions, and provide a foundation for studiesin humans. Soon after infection, airway epithelial cells can sense mycoplasma infection via TLR2 and produce factors thatresist infection and initiate events that lead to recruitment and activation of inflammatory cells. Innate immunity is recognizedto have an important role in the progression of mycoplasma respiratory disease. Adaptive immunity, characterizedby both B and T lymphocyte responses, has a major impact on the progression of M. pneumoniae respiratory disease. Band T cell responses can have two competing impacts. They can contribute to mycoplasma diseases immunopathology orprevent infection and subsequent spread of mycoplasma infection from lung to other tissues. Murine and other modelshave also proven critical in the development of new antibiotics, therapeutic approaches and vaccine development. This reviewis not intended to be exhaustive, but will focus on aspects of each of the above areas and the animal studies that havelead to improving our understanding of M. pneumoniae disease pathogenesis.

A worldwide cause of atypical bacterial pneumonia, Mycoplasma pneumoniae affects all populations and agegroups and is especially common in young adults and children. In the United States alone, M. pneumoniae causes up to40% of community-acquired pneumonia (CAP) cases in some populations and is characterized by relatively long incubationperiods and a wide spectrum of clinical symptoms and disease manifestations. The varied presentation and limited diagnosticmethods available present unique challenges for accurately identifying M. pneumoniae cases, which can lead toinappropriate treatment of patients and/or an ineffective (or nonexistent) public health response to outbreaks. Recent advancementsin 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 ofthis organism and have led to improved awareness of many facets of M. pneumoniae. Still, considerable challenges remainfor gaining a comprehensive understanding of the epidemiology and pathogenesis of this organism. Lack of standardizedand reliable diagnostic tests for use in clinical laboratories and in state and local public health laboratories continuesto 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 effectivealternative treatment regimens, especially for children. This review summarizes the current state of understandingof the many aspects surrounding M. pneumoniae infection and addresses outstanding domestic issues still confrontingpublic health. A unique prospective and overview of the many features involved in conducting an outbreak investigationand effective public health response is also reported.

Strain Typing of Mycoplasma pneumoniae and its Value in Epidemiology by Arabella Touati, Charles Cazanave, Cécile Bébéar (334-342).
Genotyping of Mycoplasma pneumoniae, a pathogen responsible for community-acquired pneumonia that occursboth endemically and epidemically worldwide, is essential for understanding M. pneumoniae distribution and relatednessand for determining the epidemiology of infection caused by this pathogen. It may also explain most phenotypicvariability, such as geographic distribution, host specificity, antibiotic resistance, and virulence. However, the moleculartyping is hampered by the fact that M. pneumoniae is a genetically homogeneous species in which large genomic rearrangementsdo not frequently occur. For these reasons, it has been difficult to develop a typing method with a good discriminatorypower 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 PCRamplification 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.

Intracranial Non-traumatic Aneurysms in Children and Adolescents by Angelika Sorteberg, Daniel Dahlberg (343-352).
An intracranial aneurysm in a child or adolescent is a rare, but potentially devastating condition. As little as approximately1200 cases are reported between 1939 and 2011, with many of the reports presenting diverting results. Thereis 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 symptomaticwith hemorrhage and the rate of re-hemorrhage is higher than in adults. The rate of hemorrhage from an intracranialaneurysm peaks in girls around menarche. The most common aneurysm site in children is the internal carotid artery, inparticular at its terminal ending. Aneurysms in the posterior circulation are more common in children than adults. Childrenmore often develop giant aneurysms, and may become symptomatic from the mass effect of the aneurysm (tumorlikesymptoms). The more complex nature of pediatric aneurysms poses a larger challenge to treatment alongside withhigher demands to the durability of treatment. Outcome and mortality are similar in children and adults, but long-termoutcome in the pediatric population is influenced by the high rate of aneurysm recurrences and de novo formation of intracranialaneurysms. 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 paediatricpractice. A good family history collection can facilitate the link between the present paediatric practice and the advancesin genetics.;This paper explores the benefits and drawbacks of the existing validated family history tools from the viewpoint of paediatricprimary practice, with special attention for the mental health issues.;Methodology: A literature search was conducted in the following directories: PubMed, Cochrane, Embase and GoogleScholar. The timeframe was 01.01.2000 - 01.09.2011.;The articles meeting the following criteria were included: original research papers in English, containing description orvalidation 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 diseasesin 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 (somecancers, diabetes and coronary heart disease). None were tested in the paediatric healthcare. The cost-effectiveness analysiswas never reported.;Conclusions: The major finding of the present study is the absence of the validated tools for the family history collectionfor the paediatric primary care in general and in mental health in particular. The existing advances create a solid base forcomposition of the unified tool for paediatric primary care.

The Dental Effects of Meningococcal Septicaemia: A Case Series by Sheena Kotecha, Catriona J. Brown (373-375).
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 tomeningococcal septicaemia have been described but information is scarce. This report aims to add weight to existing literatureby describing a series of three cases which presented with a number of dental anomalies including hypodontia, abnormaltooth-shaped calcifications, impacted and ectopic teeth, hypoplasia, delayed development and eruption.;Dental management of these cases encompassed a multidisciplinary approach, including prevention, restoration of cariousteeth, improvement of aesthetics and orthodontic treatment.;The dental features in these cases were comparable to those previously described and support links demonstrated betweenmeningococcal septicaemia and dental abnormalities. Although immunisation offers hope, complete eradication of meningitisis not yet on the horizon. While the potential of meningitis remains, health professionals should be aware of its impacton the dentition.

Background: Adolescents experience elevated rates of STDs and HIV. STD/HIV prevention interventions foryoung men are crucial to decrease their STD/HIV rates and reduce disease transmission to female partners. To advancesexual health promotion interventions for young men, this paper reviewed the efficacy of STD/HIV prevention interventionsconducted 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. Eligibleinterventions were limited to STD/HIV interventions for young men between the ages of 10 and 18. We review 8STD/HIV prevention interventions targeting heterosexual adolescent males and summarize key intervention componentsand 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 interactivegroup-based education and behavioral skills training to reduce risky sexual behaviors. All interventions used a randomizedcontrolled trial design with a comparison or control group. Follow-up times varied markedly, ranging from 3weeks to 36 months. All but one intervention improved at least one behavioral outcome (e.g., increased frequency of condomuse).;Conclusions: Findings suggest that male adolescent interventions can effectively curtail the STD/HIV epidemic. Majorweaknesses 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 researchshould increase the dissemination of effective sexual risk reduction interventions to decrease STD/HIV among adolescentmales and their female partners.