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Influenza viruses: update on epidemiology, clinical features, treatment and vaccination

imagePurpose of reviewIn the last decade, sporadic and lethal human disease caused by zoonotic avian influenza viruses, and the seasonal activity of human H1N1 2009 pandemic type have driven intense epidemiological and laboratory studies into the virus life cycle. This article highlights major developments from mid-2012 to early 2014. Recent findingsAdvances in molecular techniques and efficient rollout of diagnostic tests have enabled the rapid identification of clinical cases and detailed genetic sequencing of viral genomes. Studies have contributed widely to the understanding of how and when influenza viruses circulate, what determines their innate pathogenicity in particular hosts and whether host cofactors influence disease severity. Other imperatives include investigations into how influenza can be better prevented by vaccination, or treated with antiviral drugs. SummaryAvian influenza viruses present a continuous threat to human populations. There is a need for sustained surveillance and downstream research to evaluate the potential for future pandemics.

Severe acute respiratory syndrome vs. the Middle East respiratory syndrome

imagePurpose of reviewThis review compares the clinical features, laboratory aspects and treatment options of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). Recent findingsBats are the natural reservoirs of SARS-like coronaviruses (CoVs) and are likely the reservoir of MERS coronavirus (MERS-CoV). Although a small number of camels have been found to have positive nasal swabs by real-time polymerase chain reaction and to carry antibody against MERS-CoV, the transmission route and the intermediary animal source remain uncertain amongst the sporadic primary cases. Both SARS-CoV and MERS-CoV may cause severe respiratory failure and extrapulmonary features such as diarrhoea, whereas mild or asymptomatic cases also occur in both conditions. In comparison with SARS, patients with MERS are older with male predominance, more comorbid illness and relatively lower human-to-human transmission potential. Although the viral kinetics of MERS-CoV remain unknown, nosocomial infections of MERS occur early within the first week of illness of the index case, whereas those of SARS occurred mainly in the second week of illness when the patient's upper airway viral load peaks on day 10 of illness. In-vitro data suggest that interferon (IFN) with or without ribavirin and mycophenolic acid may inhibit MERS-CoV, whereas protease inhibitors and IFN have inhibitory activity against SARS-CoV. SummaryAlthough there are some similarities in the clinical features, MERS progresses to respiratory failure much more rapidly than SARS. The higher case fatality rate of MERS is likely related to older age and comorbid illness. More studies are needed to understand MERS-CoV in order to guide public health infection control measures and treatment.

Aetiology of hospital-acquired pneumonia and trends in antimicrobial resistance

imagePurpose of reviewHospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to present very significant diagnostic and management challenges. The development, introduction and use of a wider range of immunosuppressive therapies are leading to a broader spectrum of microorganisms causing HAP and VAP. The persistent clinical dilemma regarding their cause is that detection of a microorganism from a respiratory tract sample does not necessarily signify it is the causative agent of the pneumonia. The ever-increasing antibiotic resistance problem means that HAP and VAP are becoming progressively more difficult to treat. In this article, we review the cause, antimicrobial resistance, diagnosis and treatment of HAP and VAP and encapsulate recent developments and concepts in this rapidly moving field. Recent findingsAlthough the microbial causes of HAP and VAP remain at present similar to those identified in previous studies, there are marked geographical differences. Resistance rates among Gram-negative bacteria are continually increasing, and for any species, multiresistance is the norm rather than the exception. The development and introduction of rapid point-of-care diagnostics may improve understanding of the cause of HAP and VAP and has immense potential to influence the treatment and clinical outcomes in HAP/VAP, with patients likely to receive much faster, microorganism-specific treatment with obvious downstream improvements to clinical outcome and antimicrobial stewardship. SummaryWe describe recent trends in aetiology of HAP and VAP and recent trends in antimicrobial resistance, including resistance mechanisms causing particular concern. The potential for novel molecular diagnostics to revolutionize the diagnosis and treatment of HAP/VAP is discussed.

Viral lung infections: Epidemiology, virology, clinical features, and management of avian influenza A(H7N9)

imagePurpose of reviewThe avian influenza A(H7N9) virus has jumped species barrier and caused severe human infections. Here, we present the virological features relevant to clinical practice, and summarize the epidemiology, clinical findings, diagnosis, treatment, and preventive strategies of A(H7N9) infection. Recent findingsAs of 18 February 2014, A(H7N9) virus has caused 354 infections in mainland China, Taiwan, and Hong Kong with a case-fatality rate of 32%. Elderly men were most affected. Most patients acquired the infection from direct contact with poultry or from a contaminated environment, although person-to-person transmission has likely occurred. A(H7N9) infection has usually presented with severe pneumonia, often complicated by acute respiratory distress syndrome and multiorgan failure. Mild infections have been reported in children and young adults. Nasopharyngeal aspirate and sputum samples should be collected for diagnosis, preferably using reverse transcriptase-PCR. Early treatment with neuraminidase inhibitors improved survival, but the efficacy of antivirals was hampered by resistant mutants. The closure of live poultry markets in affected areas has significantly contributed to the decline in the incidence of human cases. SummaryThe emergence of A(H7N9) virus represents a significant health threat. High vigilance is necessary so that appropriate treatment can be instituted for the patient and preventive measures can be implemented.

Tuberculosis vaccine development at a divide

imagePurpose of reviewTuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette–Guérin (BCG), protects against extrapulmonary TB in infants. Recent findingsNovel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB–protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. SummaryWith increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

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