Preface

Alimuddin Zumla, FRCP, PhD(Lond), FRCPath Guest Editor

Wing-Wai Yew, MBBS, FRCP (Edinb), FCCP Guest Editor

David S.C. Hui, MD (UNSW), FRACP, FRCP Guest Editor

Respiratory infections are one of the most common causes of morbidity and mortality worldwide. As we enter the twenty-first century, several landmark events are unfolding in the area of respiratory infections. Some of these, by assuming the form of formidable disasters, have abruptly claimed lives and led to economic loss. Examples include severe acute respiratory syndrome (SARS) and bird and swine influenza. Viral and bacterial resistance to currently available antimicrobial drugs is thwarting efforts in the management of influenza and pulmonary sepsis. Newer and emerging viral lung infections are seen more frequently in clinical practice, including post-transplant viral infections other than cytomegalovirus and Epstein-Barr virus. The frequency and diversity of serious fungal infections are increasing. Persons who are severely immunocompromised are particularly vulnerable to infection from unusual molds and yeasts that are often found naturally in the environment. Other respiratory infections pose continuous health care challenges. Examples include the changing demography of tuberculosis (TB) and emerging deadly drug-resistant forms of TB worldwide. Pediatric TB and elderly TB are on the rise and the problem of coinfection with HIV is proving difficult to diagnose and manage. Anti–tumor necrosis factor (TNF)-α therapy for autoimmune conditions results in reactivation of TB. In addition, occupational lung diseases due to airborne microbes constitute another problematic issue. Protozoal and helminthic lung infestations continue to be important clinical problems in many parts of the world. This issue of Infectious Diseases Clinics of North America is aimed at giving an up-to-date and comprehensive overview of emerging respiratory infections in the twenty-first century through 14 articles written by authoritative experts from all around the globe.

David Hui and Paul Chan review SARS and coronavirus in detail, remind us of the enormous threat it posed to international health and the global economy, and state that at the end of the epidemic in July 2003, 8098 probable cases were reported in 29 countries and regions, with 774 deaths (9.6% mortality rate).

The recent panic over avian and swine influenza outbreaks has focused research-sequencing technologies and phylogenetic methods on how novel influenza viruses arise, usually from animal reservoirs. Julian Tang and colleagues describe how such knowledge allows more effective public health surveillance of seasonal human influenza viruses as well as candidate pandemic viruses that may cross the species barrier from animal to man. Of the 3 known serotypes of influenza (A, B, and C), only influenza types A and B cause frequent and occasionally severe disease in humans. Although there is only one type of influenza B, influenza A has multiple subtypes, characterized by a combination of the 16 known hemagglutinin and 9 neuraminidase genes that code for these viral envelope or surface proteins. So far, only 3 subtypes of hemagglutinin (H1, H2, and H3) and 2 subtypes of neuraminidase (N1 and N2) have caused pandemics in humans. Influenza viruses will continue to pose a persistent and variable threat to human health for the foreseeable future.

Lower respiratory tract infections were ranked the third leading cause of death worldwide in 2004. The increasing prevalence of antimicrobial resistance in major respiratory pathogens has become a serious threat to clinical medicine with increased morbidity and mortality due to treatment failures. Antimicrobial resistance is a critical issue not only in community-acquired pneumonia due to resistance in Streptococcus pneumoniae but also in hospital-acquired pneumonia or ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) or drug-resistant gram-negative bacilli. Jae-Hoon Song and Doo Ryeon Chung review current knowledge of respiratory infections caused by antibiotic-resistant pathogens and the treatment options available.

TB causes 1.8 million deaths annually, 5000 every day, and is one of the most common causes of death from an infectious disease. The emergence of multidrug-resistant TB and extensively drug-resistant TB (XDR-TB) in Eastern Europe, Asia, and South Africa now poses an ominous threat to global TB control. We review the insights provided by clinical and molecular epidemiology about global trends and transmission dynamics of XDR-TB and the challenges faced by clinicians in diagnosing and managing cases of XDR-TB. Keertan Dheda and colleagues review the clinical, management, and epidemiologic dilemmas posed by drug-resistant TB. Pediatric TB is now regarded as an emerging epidemic in areas where the adult epidemic remains out of control and Mycobacterium tuberculosis transmission is ongoing. Childhood TB remains a neglected disease in many resource-limited settings and the number of cases of pediatric TB is increasing. Ben Marais and Simon Schaaf emphasize in their article that children contribute significantly to the global TB disease burden and suffer severe TB-related morbidity and mortality. They describe current issues in the diagnosis, management, and prevention relevant to pediatric TB.

One third (over 2 billion people) of the world's population is latently infected with M tuberculosis. Although the risk of developing active TB disease is highest in the first two years after infection, considerable magnitude of risk persists in patients for the rest of their lives.

With waning immunity associated with advancing age and increasing use of immunosuppressants, there is an excess risk for the development of active clinical TB disease. Toru Mori and Chi Chiu Leung review TB in the ageing population, emphasizing that TB presents atypically among the elderly leading to delays in diagnosis and treatment.

Non-tuberculous mycobacteria (NTM) are environmental mycobacteria that are distinct from members of the Mycobacterium tuberculosis complex. Due to the advent of the HIV/AIDS epidemic and the increasing use of immunosuppressive drugs, infections due to NTM are increasingly being seen in clinical practice. Babafemi Taiwo and Jeff Glassroth describe the spectrum of NTM causing human disease. Lung involvement ranges from isolation of mycobacteria that may be benignly colonizing an individual, to benign nodules, disease in ostensibly healthy immune competent persons, disease in immune compromised hosts who may be infected with unusual or rarely encountered NTM, and hypersensitivity syndrome.

Other risk factors for development of TB are discussed in two articles. TNF antagonists for treatment of rheumatoid disorders were first introduced 10 years ago. Robert Wallis and Neil Schluger review the risk of TB reactivation posed by TNF antibodies. Current recommendations for withdrawal of anti-TNF therapy when TB is diagnosed place patients at risk for paradoxic worsening due to recovery of TNF-dependent inflammation. Further research is needed to determine how best to prevent and manage their infectious complications. Richard N. van Zyl-Smit and coworkers attempt to link the interactions between smoking, TB, HIV infection, and chronic obstructive pulmonary disease (COPD), suggesting these epidemics interact by means of increased susceptibility or worsening outcomes. For example, tobacco smoking increases the risk of TB, and this in turn increases the risk of subsequent COPD. They warn of the possibility that new global influenza pandemics are more likely to occur in those with predisposing factors, such as smoking, COPD, or HIV infection.

With increasing use of immunosuppressive therapy and the advent of the HIV epidemic, fungal pulmonary infections are increasingly seen in clinical practice. Li Yang Hsu and colleagues give a succinct overview of the diagnosis, treatment, and prevention of common and emerging new fungal infections causing respiratory illness.

Occupational pulmonary infectious diseases are also important causes of morbidity worldwide and these include TB and many viral pathogens, including influenza, varicella, respiratory syncytial virus, and hantavirus. Daphne Ling and Dick Menzies focus on TB, influenza, and SARS. The lessons from these three are relevant for all nosocomial pulmonary infectious diseases. TB is the most important occupational infectious disease worldwide. Rates of infection are 5- to 10-fold higher in health care workers than in the general population whereas rates of disease are 2- to 5-fold higher. Risk is increased among occupations associated with performance of aerosol-producing procedures, such as sputum induction, bronchoscopy, or autopsy. SARS was unusual because of the severity of illness and high rate of nosocomial transmission via the droplet (and perhaps also airborne) route, so that health care workers accounted for 21% of all known cases. Hence, infection control measures are of primary importance. This means identification of patients (or workers) with these illnesses and their immediate separation from other patients. Personal protective equipment recommended for influenza and SARS include gown, gloves, and masks with eye-shields, whereas for TB, only masks (personal respirators) are recommended.

Kidney, liver, heart, pancreas, lung, and small intestine transplantations are now viable therapeutic options for patients with end-stage organ failure. Infections still contribute to substantial morbidity and mortality, limiting long-term success rates of these procedures. Immunosuppressive regimens are necessary to limit allograft rejection and also weaken host immune responses to exogenously acquired pathogens and enable endogenous reactivation of latent infection. Frequent medical care of newly transplanted patients exposes recipients to potentially drug-resistant pathogens. To help prevent the occurrence of common opportunistic infections in transplant recipients, prophylactic strategies have been used; despite these efforts, emerging pathogens continue to pose unique challenges for clinicians to recognize, diagnose, and treat. Shawn Nishi and colleagues describe some of these organisms responsible for emerging respiratory infections in transplantation recipients.

A decline in parasitic infestations was observed in the past century, especially in developed countries, due to improved socioeconomic conditions, good vector control, and excellent hygiene practices. Vannan Kandi Vijayan and Tarek Kilani review the emerging problems of respiratory parasitic infections, particularly due to protozoa and helminths. The increasing occurrence of immunosuppression in individuals due to HIV infection, organ transplantations, and use of immunosuppressive drugs has made these individuals prone to the development of parasitic pulmonary infestations de novo from the environment or recrudescence from dormant infestations.

Rapid and accurate diagnosis of respiratory pathogens can lead to effective and specific treatment resulting in low morbidity and mortality rates. David Murdoch and colleagues review recent developments in rapid diagnostics for respiratory infections, particularly in the areas of antigen and nucleic acid detection. They conclude that new approaches for respiratory pathogen detection are needed, and breath analysis is an exciting new area with enormous potential. Their review provides encouragement that recent developments in technology will eventually yield point-of-care, rapid diagnostic tests for screening of multiple pathogens in resource-poor developing countries where current technologic equipment could be run on solar-powered computers.