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Adv Exp Med Biol [journal]
- Management of severe malaria: results from recent trials. [Journal Article]
- Adv Exp Med Biol 2013.:241-50.
Globally, malaria remains a substantial public health burden with an estimated 349-552 million clinical cases of P. falciparum malaria each year--leading to 780,000 deaths directly attributable to the disease. Whilst the outcome from severe malaria in Africa children remains poor, recent developments in the management of malaria have come from two key sources--the introduction of new, safe and rapidly-effective anti-malarials and high quality evidence from two of the largest clinical trials ever conducted in African children with severe malaria. As a result, the time-honoured anti-malarial treatment for severe malaria, quinine, will now be replaced by artesunate, a water-soluble artemisinin derivative. Supportive care, specifically the management of shock, has been informed by a large late phase clinical trial which concluded that bolus resuscitation is harmful and therefore should be avoided in children with severe malaria, including the high risk group with severe metabolic acidosis and advanced shock.
- How to get and get rid of gonorrhea. [Journal Article]
- Adv Exp Med Biol 2013.:219-39.
Gonorrhea remains as a significant public health concern with an estimated 88 million new cases per year globally. Gonorrhea is a disease of sexual networks and is most prevalent in youth, men who have sex with men, and the socioeconomically disadvantaged. Highly adaptive through years of co-evolution, gonorrhea has developed multiple ways of evading the human immune system. Although new molecular-based strategies have opened avenues for less invasive testing, education and accessibility issues persist. Novel strategies, including use of the internet and social media, are required to better target high risk groups for education, testing, and treatment. Increasing the availability of youth-friendly health services will also help foster earlier gonorrhea diagnosis and management. The inappropriate and overuse of antibiotics and propensity of gonococcus for mutation has led to growing microbe resistance. Treatment failures now include both oral and intravenous formulations of third generation cephalosporins; key front line recommended gonococcal treatment in many countries. With treatment options dwindling, the need for better preventative strategies has never been more important. This overview highlights some of the major aspects of gonococcal infection, including the epidemiology of the disease with an emphasis on sexual networks, new diagnostic techniques, treatment options in the face of evolving gonococcal resistance, and notes potential new preventative strategies.
- Preventing urinary tract infections in early childhood. [Journal Article]
- Adv Exp Med Biol 2013.:211-8.
Urinary tract infection (UTI) is common in children, causes them considerable discomfort, as well as distress to parents and has a tendency to recur. Approximately 20% of those children who experience one infection will have a repeat episode. Since 1975, 11 trials of long-term antibiotics compared with placebo or no treatment in 1,550 children have been published. Results have been heterogeneous, but the largest trial demonstrated a small reduction (6% absolute risk reduction, risk ratio 0.65) in the risk of repeat symptomatic UTI over 12 months of treatment. This effect was consistent across sub groups of children based upon age, gender, vesicoureteric reflux status and number of prior infections. Trials involving re-implantation surgery (and antibiotics compared with antibiotics alone) for the sub-group of children with vesicoureteric reflux have not shown a reduction in repeat UTI, with the possible exception of a very small benefit for febrile UTI. Systematic reviews have shown that circumcision reduces the risk of repeat infection but 111 circumcisions would need to be performed to prevent one UTI in unpredisposed boys. Given the need for anaesthesia and the risk of surgical complication, net clinical benefit is probably restricted to those who are predisposed (such as those with recurrent infection). Many small trials in complementary therapies have been published and many suggest some benefit, however inclusion of children is limited. Only three trials involving 394 children for cranberry products, two trials with a total of 252 children for probiotics and one trial with 24 children for vitamin A are published. Estimates of efficacy vary widely and imprecision is evident. Multiple interventions to prevent UTI in children exist. Of those, long-term low dose antibiotics has the strongest evidence base, but the benefit is small. Circumcision in boys reduces the risk substantially, but should be restricted to those at risk. There is little evidence of benefit of re-implantation alone, and the benefit of this procedure over antibiotics alone is very small. Cranberry concentrate is probably effective.
- Urinary tract infections in children: microbial virulence versus host susceptibility. [Journal Article]
- Adv Exp Med Biol 2013.:205-10.
Urinary tract infections (UTI) are common, dangerous and interesting. This review includes a general background on UTIs and molecular mechanisms of pathogenesis. In addition, we discuss UTI susceptibility and especially the effect of genetic variation on innate immunity. The symptoms of acute pyelonephritis are caused by the innate immune response and inflammation in the urinary tract decreases renal tubular function and may give rise to renal scarring, especially in childhood. The disease severity is explained by pathogens and their virulence factors triggering signaling through Toll-like receptors (TLRs), interferon regulatory factors (IRFs) and type 1 interferons, and the activation of a host response mediating disease or pathology or clearance of infection. In children with asymptomatic bacteriuria (ABU), in contrast, bacteria persist without causing symptoms or pathology. ABU strains mostly lack virulence factors, and the lack of symptoms has largely been attributed to their lack of virulence. Recently, rapid progress has been made in the understanding of host susceptibility mechanisms. For example, genetic alterations that reduce TLR4 function are associated with ABU while polymorphisms reducing IRF3 or CXCR1 expression are associated with acute pyelonephritis and an increased risk for renal scarring. Understanding bacterial virulence and host resistance promises new tools to improve the diagnostic accuracy in children with UTI. By combining information on bacterial virulence and the host response, it should be possible to start individualizing diagnosis and therapy. Finally, we propose that the prediction of future disease risk and decisions on prophylaxis and invasive diagnostic procedures might be improved by genetic analysis.
- Elucidation and clinical role of emerging viral respiratory tract infections in children. [Journal Article]
- Adv Exp Med Biol 2013.:191-204.
Acute respiratory viral infections (ARVI's) are the most common infectious disease in humans. With the appearance of molecular techniques the recovery of viruses has dramatically increased. Nowadays virologists can quickly discriminate virological families and related viruses from emerging viruses and consequently identify novel viruses. Many new respiratory viruses have been identified in children in the past 15 years. In this review we shortly discuss novel respiratory viruses and their pathogenic role in pediatric respiratory disease. Advantages and drawbacks of the technique and our current knowledge will be discussed. We will conclude this review with a general discussion on the future role of molecular diagnostic virology in the clinic.
- Mycetoma caused by Madurella mycetomatis: a completely neglected medico-social dilemma. [Journal Article, Research Support, Non-U.S. Gov't]
- Adv Exp Med Biol 2013.:179-89.
Mycetoma is a debilitating disease with a highly particular geographical distribution. The mycetoma belt circles the entire world just above the equator and defines the region with the highest prevalence and incidence. Although the disease is seen in Central America, India and all across Africa, Sudan seems to be the homeland of mycetoma. Mycetoma is an infectious disease caused either by bacteria (actinomycetoma) or true fungi (eumycetoma). In Sudan most cases are caused by the fungal species Madurella mycetomatis. The precise natural habitat of this fungus is still an enigma, but its DNA can easily be found in soil and plant samples in endemic areas. Although the entire human population in these areas are in regular contact with the fungus, most individuals are unaffected. Thus mycetoma is an ideal clinical and experimental model system for the study of host-pathogen interactions. Also, given its relative importance locally, improvements in clinical and laboratory diagnostics and knowledge of the epidemiology of the disease are badly needed. This chapter describes the current state of affairs in the field of eumycetoma caused by M. mycetomatis. The value of laboratory research on this disease and future perspective for control and prevention of the infection are discussed.
- When to think of immunodeficiency? [Journal Article]
- Adv Exp Med Biol 2013.:167-77.
Primary Immunodeficiencies (PIDs), although rare, are serious and heightened clinical suspicion leads to earlier diagnosis and improved outcome. Recognition of PIDs may be difficult as infections are common in young children in particular. Clues to the diagnosis of PID may be found in history, examination and initial basic investigations such as lymphocyte count. Age at presentation, type of infective organism and family history help focus on likely PIDs. Type of infective organism may indicate a specific PID, for example Aspergillus and Chronic Granulomatous Disease and Pneumocystis Jiroveci and SCID amongst others. Diagnostic aids such as 'The 10 Warning Signs of Primary Immunodeficiency' can be useful with failure to thrive, need for IV antibiotics, and family history of severe or unusual infections being the most discriminating. Systemic examination including the recognition of dysmorphic features may also support a particular diagnosis.
- Cat scratch disease and other Bartonella infections. [Journal Article]
- Adv Exp Med Biol 2013.:159-66.
First described in 1931, cat scratch disease remains the most commonly identified clinical syndrome associated with Bartonella infection. Over the last 20 years, however, the discovery and use of modern diagnostic tests has greatly expanded our understanding of the pathogenesis, clinical spectrum, and treatment options for Bartonella infections of all types. Indeed, each varies substantially depending on the infecting species and the immune status of the host.
- Infectious risks associated with biologics. [Journal Article]
- Adv Exp Med Biol 2013.:151-8.
Biologics are generally either custom-designed monoclonal antibodies against specific target cells (e.g. B-cells) or target cytokines (e.g. tumour necrosis factor, TNF) or they are receptor constructs (fusion proteins) based on naturally-occurring cytokine or cell receptors. Biologics are mostly used in adult rheumatology but are increasingly used in paediatrics. There are significant concerns about safety and also about cost. The main safety concerns are about increased risk of infection and malignancy. The use of TNF antagonists is associated with increased risk of serious infections with intracellular organisms, particularly mycobacteria, but also intracellular bacteria, fungi and Pneumocystis. B-cell antagonists like rituximab can cause progressive multifocal leukoencephalopathy. IL-6 antagonists are associated with increased rates of common bacterial infections and the complement pathway antagonist eculizumab with meningococcal infection. The risk of some infections associated with biologics can be reduced, by screening patients starting TNF antagonists for latent tuberculosis and giving them cotrimoxazole prophylaxis against Pneumocystis, and by immunising against VZV, hepatitis B, meningococci and pneumococci. However, the risk of the biologics causing serious infection in children is unknown and needs study. Children should not be started on the biologics without careful consideration of the risks and without fully informed consent.
- The evidence behind prophylaxis and treatment of wound infection after surgery. [Journal Article]
- Adv Exp Med Biol 2013.:141-50.
Surgical site infections (SSIs) represent a serious post surgical complication. They are the leading cause of healthcare-related infections in developing countries and the second most common healthcare-related infection in developed countries. Here we discuss the epidemiology of and risk factors for SSIs together with the current evidence supporting the use of antibiotic prophylaxis for the prevention of wound infection after surgery.