From the microbiome to the central nervous system, an update on the epidemiology and pathogenesis of bacterial meningitis in childhood [version 1; referees: 3 approved]

In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis

The Impact of HAART on the Respiratory Complications of HIV Infection: Longitudinal Trends in the MACS and WIHS Cohorts

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women's Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2-2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3-1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8-2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02-8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3-1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5-2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. © 2013 Gingo et al

An overview of diagnostic criteria for identification of cryptococcal meningitis with special emphasis on AIDS

Fungi are common in human immunodeficiency virus (HIV)-positive patients but HIV predisposes patients to several viral and bacterial infections that can result in meningitis. Understanding the burden of cryptococcal disease is particularly important for public health officials to adequately plan and prioritize needed resources for disease prevention and control. Cryptococcal meningitis, a fungal infection caused by Cryptococcus spp. is the second most common cause of opportunistic fungal infection in patients with  acquired immunodeficiency syndrome (AIDS). It is important to define the burden of cryptococcal meningitis, as it relates to other important diseases, and to understand the need for public health attention to this infection. Frequently, HIV infection weakens the body's ability to fight disease. Infections which are rarely seen in those with normal immune systems are life-threatening to those with HIV. It is time to expand this global focus on HIV to include one of its most serious consequences, cryptococcosis. Few, if any, complications of advanced HIV disease have a greater influence on morbidity and mortality. We are likely to see little real progress in the outcome for these patients until there is a global commitment to invest in more drug availability, better access to easily used diagnostics and therapeutic devices, and more innovative clinical researches.Key words: Cryptococcal meningitis, immune system, human immunodeficiency virus (HIV), serotrypes

ESCMID postgraduate technical workshop on intracellular bacteria: from biology to clinic.

Infection by intracellular bacteria can lead to several diseases in both veterinary and human medicine. Unfortunately, the biology of these intracellular bacteria is highly complex due to their interactions with their host cells. Thus, it is very important to develop several tools in order to better understand the complex intracellular life of these pathogens, so allowing to improve the diagnosis options and the treatments of infectious diseases that they are causing. The workshop organised in Villars-sur-Ollon (Switzerland) by the ESCMID Study group on intracellular bacteria was a good opportunity to enhance our knowledge on these fastidious pathogens. During 5 days, 15 speakers gave 41 talks, covering all fields, from biology to clinic of different intracellular bacteria such as Bartonella, Chlamydia, Coxiella, Ehrlichia, Listeria, Parachlamydia, Rickettsia, and Waddlia. The format of this postgraduate course, which took place in the Swiss mountains, allowed interactive sessions and living discussions between the participants coming from all around the world. One of the major strength was to gather epidemiologists, clinical microbiologists, infectious diseases specialists, entomologists, veterinarians as well as bioinformaticians, biochemists and biologists to deliver a unique "one-health science" on intracellular bacteria. Here, we summarise the main take-home messages delivered during this meeting

Gonorrhoea

The bacterium Neisseria gonorrhoeae causes the sexually transmitted infection (STI) gonorrhoea, which has an estimated global annual incidence of 86.9 million adults. Gonorrhoea can present as urethritis in men, cervicitis or urethritis in women, and in extragenital sites (pharynx, rectum, conjunctiva and, rarely, systemically) in both sexes. Confirmation of diagnosis requires microscopy of Gram-stained samples, bacterial culture or nucleic acid amplification tests. As no gonococcal vaccine is available, prevention relies on promoting safe sexual behaviours and reducing STI-associated stigma, which hinders timely diagnosis and treatment thereby increasing transmission. Single-dose systemic therapy (usually injectable ceftriaxone plus oral azithromycin) is the recommended first-line treatment. However, a major public health concern globally is that N. gonorrhoeae is evolving high levels of antimicrobial resistance (AMR), which threatens the effectiveness of the available gonorrhoea treatments. Improved global surveillance of the emergence, evolution, fitness, and geographical and temporal spread of AMR in N. gonorrhoeae, and improved understanding of the pharmacokinetics and pharmacodynamics for current and future antimicrobials in the treatment of urogenital and extragenital gonorrhoea, are essential to inform treatment guidelines. Key priorities for gonorrhoea control include strengthening prevention, early diagnosis, and treatment of patients and their partners; decreasing stigma; expanding surveillance of AMR and treatment failures; and promoting responsible antimicrobial use and stewardship. To achieve these goals, the development of rapid and affordable point-of-care diagnostic tests that can simultaneously detect AMR, novel therapeutic antimicrobials and gonococcal vaccine(s) in particular is crucial

Epidemiology and aetiology of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 1)

Background. Pneumonia remains a major cause of morbidity and mortality among South African (SA) children. Improved immunisation regimens, strengthening of HIV programmes, better socioeconomic conditions and new preventive strategies have influenced the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis.Objectives. To summarise current information on childhood community-acquired pneumonia (CAP) epidemiology and aetiology in children as part of the revised South African Thoracic Society guidelines.Methods. The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases expert subgroup on epidemiology and aetiology revised the existing SA guidelines.The subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system, and the relevant section underwent peer review.Results. Respiratory viruses, particularly respiratory syncytial virus, are the key pathogens associated with hospitalisation for radiologically confirmed pneumonia in HIV-uninfected children. Opportunistic organisms, including Pneumocystis jirovecii, are important pathogens in HIV-infected infants, while non-typable Haemophilus influenzae and Staphylococcus aureus are important in older HIV-infected children. Co-infections with bacteria or other respiratory viruses are common in hospitalised children. Mycobacterium tuberculosis is common in children hospitalised with CAP in SA.Conclusions. Numerous public health measures, including changes in immunisation schedules and expansion of HIV prevention and treatment programmes, have influenced the epidemiology and aetiology of CAP in SA children. These changes have necessitated a revision of the South African Paediatric CAP guidelines, further sections of which will be published as part of a CME series in SAMJ

The Pathogenesis of <i>Escherichia coli</i> Urinary Tract Infection

Urinary tract infections (UTIs) are the commonest human bacterial infections and are responsible for substantial morbidity and mortality, resulting in increased healthcare costs. Most UTIs are caused by specialized Escherichia coli (E. coli) strains referred to as uropathogenic E. coli (UPEC). UPEC possess a variety of virulence factors (VFs), which the organism uses to attach, invade, and injure the host. These VFs include adhesins, toxins, iron acquisition factors, lipopolysacharide capsules, and other invasins. Most studies on UTI pathogenesis have targeted VFs. The source of UPEC is the host’s fecal flora. According to the pathogenicity theory, UPEC strains with special VFs move from the host’s fecal flora to the urogenital tract and cause UTI. However, another theory states that the numerically abundant strain is responsible for UTI. Effective UTI management is hampered by the recent rise in antibiotic resistance, specifically, the recent emergence of multidrug-resistant E. coli sequence type 131. The distribution of VFs and other bacterial characteristics among different patient groups and UTI syndromes, is crucial understanding UTI pathogenesis, which would guide clinical decision making. For ST131 clonal group, further epidemiological studies are needed to clarify transmission pathways, risk factors for spread, and reservoirs, so that effective control measures can be devised

Principles of Periodontology

Periodontal diseases are among the most common diseases affecting humans. Dental biofilm is a contributor to the etiology of most periodontal diseases. It is also widely accepted that immunological and inflammatory responses to biofilm components are manifested by signs and symptoms of periodontal disease. The outcome of such interaction is modulated by risk factors (modifiers), either inherent (genetic) or acquired (environmental), significantly affecting the initiation and progression of different periodontal disease phenotypes. While definitive genetic determinants responsible for either susceptibility or resistance to periodontal disease have yet to be identified, many factors affecting the pathogenesis have been described, including smoking, diabetes, obesity, medications, and nutrition. Currently, periodontal diseases are classified based upon clinical disease traits using radiographs and clinical examination. Advances in genomics, molecular biology, and personalized medicine may result in new guidelines for unambiguous disease definition and diagnosis in the future. Recent studies have implied relationships between periodontal diseases and systemic conditions. Answering critical questions regarding host‐parasite interactions in periodontal diseases may provide new insight in the pathogenesis of other biomedical disorders. Therapeutic efforts have focused on the microbial nature of the infection, as active treatment centers on biofilm disruption by non‐surgical mechanical debridement with antimicrobial and sometimes anti‐inflammatory adjuncts. The surgical treatment aims at gaining access to periodontal lesions and correcting unfavorable gingival/osseous contours to achieve a periodontal architecture that will provide for more effective oral hygiene and periodontal maintenance. In addition, advances in tissue engineering have provided innovative means to regenerate/repair periodontal defects, based upon principles of guided tissue regeneration and utilization of growth factors/biologic mediators. To maintain periodontal stability, these treatments need to be supplemented with long‐term maintenance (supportive periodontal therapy) programs