As the 21st century unfolds, a number of landmark events are occurring in the area of respiratory infections. Some of these, by assuming the form of formidable disasters, abruptly claim lives and lead to economic loss. Examples include severe acute respiratory syndrome (due to coronavirus) and the avian influenza . Avian influenza A H5N1 is transmitted from avian species to humans, without clear evidence of transmission from human to human . Antiviral drug resistance is thwarting efforts in the management of influenza . Antiviral agents for the treatment of influenza are urgently needed to circumvent the limitations of current antiviral drugs in the areas of: high frequencies of resistance to M2 inhibitors among currently circulating strains and variable frequencies of resistance to oseltamivir among A (H1N1) strains; limited efficacy of treatment and treatment-emergent antiviral resistance in cases of avian influenza A (H5N1) illness in humans; and lack of parenteral agents for seriously ill patients .
Newer and emerging viral lung infections are being seen more frequently in clinical practice, including posttransplant viral infections other than cytomegalovirus (CMV) and Epstein–Barr virus (EBV) . More posttransplantation respiratory viral, bacterial, protozoal and fungal infections are being recognized, including West Nile, lymphocytic choriomeningitis (LCM), adenovirus, bocavirus, coronavirus and metapneumovirus infections .
The frequency and diversity of serious fungal infections are increasing . Persons who are severely immunocompromised are particularly vulnerable to infection from unusual moulds and yeasts that are often found naturally in the environment. Infections with less virulent fungi, such as Trichosporon, Fusarium, Alternaria, Pseudallescheria and dematiaceous fungi, are being recognized more frequently. In addition, occupational lung diseases due to airborne microbes constitute another problematic issue [7,8]. Protozoal and helminthic lung infestations continue to be important clinical problems in many parts of the world .
Other infections are providing continuous healthcare challenges resulting in additional mortality and morbidity. Examples include the changing demography of tuberculosis (TB) and emergent deadly forms of the disease, multidrug-resistant and extensively drug-resistant TB (MDR-TB and XDR-TB) that are now prevalent worldwide . Paediatric TB is on the rise, and the problem of coinfection with HIV is proving difficult to diagnose and manage .
There is an increased frequency of drug-resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), pneumococci, Klebsiella spp. and Haemophilus influenze type b causing respiratory infections [12,13]. Increase in the number of staphylococcal infections caused by MRSA has resulted in a large increase in cases of MRSA pneumonia in the healthcare setting [14,15]. Furthermore, community-acquired MRSA pneumonia is becoming more prevalent. This type of pneumonia historically affects younger patients, usually following infection with influenza virus. It is severe, requiring hospitalization and causing the death of a significant proportion of patients.
In Vietnam, genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) possessing altered penicillin-binding protein (PBP) genes, pbp1a, pbp2x and pbp2b, have been described in children with lower respiratory tract infections. Increasing rates of drug resistance in pneumococcal strains emphasize the necessity of prevention by use of pneumococcal vaccines. Serotypeable strains of H. influenzae, which can cause invasive infections, are found in the respiratory tract at low frequencies. Serotypes and the antibiotic susceptibilities of clinical H. influenzae strains isolated from respiratory tract specimens from Japanese patients were examined for prevalence of genotypes that are associated with β-lactam resistance. H. influenzae type b strains shared more β-lactam-resistant mechanisms than nontypeable and other serotype strains.
With increasing use of immunomodulators in medical practice, an increased risk of infections is being observed in patients using them . For example, patients with rheumatoid arthritis have been shown to have an increased risk of infection, including TB. Clinical data and postmarketing studies indicate that anakinra and the tumour necrosis factor (TNF) inhibitors are associated with an increased risk of infections versus conventional disease-modifying antirheumatic drugs in the course of treatment. The most common sites of infection are the respiratory tract (including pneumonia), skin and soft tissue and the urinary tract. The risk of TB also appears higher with TNF inhibitors (in particular, infliximab), although this can be reduced by screening for latent Mycobacterium tuberculosis infections and instituting anti-TB prophylaxis. TNF inhibitors do not appear to significantly increase the risk of reactivating chronic viral infections. Influenza and pneumococcal vaccinations are generally effective in the face of TNF inhibitors or abatacept.
The 21st century presents the medical community with major challenges in dealing with emerging new bacterial, viral, fungal and protozoal infections, viral and bacterial antibiotic resistance and opportunistic infections following immunomodulator usage. These now present new diagnostic, therapeutic and preventive challenges. Watchful surveillance, rapid detection, treatment and effective control measures for these diseases become imperative if we are to avoid global pandemics.
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