The influenza virus, an enveloped RNA virus, is classified into types A, B, and C. It is considered as highly significant among agents causing respiratory viral infections. The infection ranges from upper respiratory tract involvement with a typical “influenza-like illness” with fever, myalgia, cough, and sore throat, to lower respiratory tract disease with pneumonitis, and occasionally severe systemic involvement. The incubation period usually is 1 to 3 days, and the virus is shed in respiratory droplets and secretions from clinical onset for a few days, and longer for children until up to a week (3). Virologically, the genome of influenza A and B viruses comprises eight RNA segments. Two of the genes, hemagglutinin (H) and neuraminidase (N), encode for surface proteins targeted by the immune system. Influenza A viruses comprise 17 designated H subtypes and 9 N subtypes. Viruses of subtypes H1 to 16, combined with different permutations of N subtypes, can be found in avian species as natural reservoirs of the viruses (4). The H17 virus was initially reported in 2012 from bats in Guatemala (5). Other animals, including humans, harbor a more limited number of subtypes of influenza A viruses. As a result of the replacement of entire gene segments, especially of the H and N genes of the influenza A virus, due to recombination events in nature, called genetic shift, viruses for which human has little immunity emerge periodically, causing pandemics (6). In the 20th century, successive influenza A pandemics have been caused by H1N1 (1918), H2N2 (1957), H3N2 (1968), and most recently H1N1 (2009). Pandemics have different characteristics in terms of morbidity and mortality rates, and the predominantly affected age groups and populations. This probably is due to a combination of viral and host immunologic factors, and the availability of medical and supportive treatment, including the use of antimicrobials for secondary bacterial infections, the development of antiviral agents, advances in life-support measures, and heightened infection control practices. The 1918 pandemic was caused by a virus likely to be entirely of avian origin (7), with around 30% of the world’s population being infected, and a mortality of 40 million people, especially among young adults (8). Secondary bacterial infections probably played a significant role (9). The 1957 and 1968 pandemics had lower mortality, probably as a result of a lesser degree of virulence of the virus, and improved medical management (10). The virus causing the 2009 pandemic likely had a swine origin (11). The overall mortality was <0.5%. In contrast to seasonal influenza, most of the serious illnesses caused by the 2009 pandemic virus have occurred among children and non-elderly adults, and ˜90% of the deaths have occurred in those <65 years of age (12). This phenomenon is postulated to be due to the related H1N1 virus having circulated from 1918 until 1950s, so that those born during this period had a degree of protective immunity due to previous infection (13). Apart from antigenic shift, influenza A and B viruses undergo antigenic drifts where cumulative mutations mainly in the H gene give rise to emergence of new strains against which there is reduced immunity in the population (14). Such strains cause outbreaks of various severity and durations in different seasons. The seasonality of influenza infections is distinct in different areas of the world; countries in temperate climates mainly have winter peaks, and tropical areas have a more even distribution throughout the year. In Hong Kong, there are two distinct peaks in winter and in summer in most years, although variations may be encountered (Figure 42.1). Influenza C causes mild sporadic infections and is not of major medical concern.

Surveillance of influenza A and B infections, both clinical and laboratory-based, is of significance on a global scale, in order to monitor for the occurrence of antigenic drift and
shifts. The World Health Organization (WHO) has a laboratory network where virus strain characterization is systematically undertaken by national and collaborating reference laboratories, in order to monitor the currently circulating influenza strains, and to make recommendations on a half-yearly basis on the strains to be included in the vaccine for the Northern and Southern hemispheres (15).

Human parainfluenza viruses (HPIVs) are enveloped RNA viruses, and are classified into types 1, 2, 3, and 4. They are the etiologic agents of various respiratory tract infections, especially in children, such as croup (laryngotracheobronchitis), which is more commonly associated with HPIV-1 and -2, and bronchiolitis, occurring mainly from infection with HPIV-3. The disease is usually self-limited, with occasional episodes of severe disease probably as a result of host factors and compromised immunity. The infection is mainly recognized in children, although the elderly are occasionally affected (26). The incubation period ranges from 2 to 6 days, and virus shedding occurs via infective respiratory secretions for around 1 week (14). Seasonal patterns are evident, with HPIV-1 and -2 occurring mainly in autumn, with HPIV-1 infections showing a cyclical peak every alternate year, whereas HPIV-3 mainly occurs during the summer months (27). The seasonal pattern in Hong Kong is shown in Figure 42.2. A definitive diagnosis for the infection may not be essential since a syndromic approach to patient management and infection control usually suffices.

RSV is an enveloped RNA virus, classically causing bronchiolitis in young children <2 years of age. The infection may predispose to future asthmatic attacks. The infection typically peaks during the winter season in temperate climates. Nevertheless, the seasonal pattern varies geographically. In Hong Kong, the virus activity occurs mainly in the spring and summer months of March to September (28). Interestingly, with the high activity of the influenza A H1N1 in 2009 and 2010, the RSV peaks were abrogated (Figure 42.3). The incubation period of the infection is 4 to 5 days, and the virus is shed from infective respiratory secretions several days to >1 week (14). Since the disease mainly occurs in infants and young children with symptoms of lower respiratory tract infection, hospital admission is common. Outbreaks of RSV infection in pediatric hospital wards, and also in institutional settings, including those for the elderly, are commonly encountered. With a definitive laboratory diagnosis, treatment with ribavirin may be administered, especially in severe and immunocompromised patients. Scrupulous implementation of droplet precautions in all episodes of respiratory tract infections in the hospital setting, with environmental decontamination using disinfectants active against these viruses, is effective in preventing outbreaks and transmission of the pathogen.

The human metapneumovirus (HMPV), an enveloped RNA virus, was first described in 2001 (29), and now is recognized as one of the viral agents causing respiratory tract infections. The incubation period is 5 to 6 days (30), and shedding of the virus can be for 1 to 2 weeks (31). The symptoms range from mild upper respiratory tract disease to lower respiratory tract and pulmonary involvement. The infection is observed in all age groups, with a high prevalence in pediatric patients. Seasonality studies suggest peak of infection occurring 1 to 2 months later than that for RSV epidemics (31). Occasionally, HMPV is shown to be the cause of clusters of respiratory tract infection in the community, but does not appear to be an important agent of hospital outbreaks.

Human coronaviruses have been described since the 1960s to be the agents of the common cold. The viruses initially recognized were OC43 and 229E (32). Sporadic and self-limited infections usually were encountered, and there was not a great deal of medical interest, compounded by the lack of readily accessible diagnostic tests. It was in 2003 that the coronavirus came under global limelight with the occurrence of severe acute respiratory syndrome (SARS).

The disease syndrome was first reported in November 2002 in Guangdong, China (33). The occurrence of infections at the level of community outbreaks first came to global attention in February 2003 in the city of Guangzhou. Epidemiologic investigations subsequently traced the spread of the virus, via Hong Kong, with extensive outbreaks to various countries including Vietnam, Singapore, and Canada. The outbreak of SARS was officially over in July 2003 as announced by the WHO. There were >8,000 infected patients, resulting in almost 800 deaths in 27 countries in a global scale (34). In Hong Kong, the infection count was 1,755 patients and 299 deaths. Nearly a quarter of the infected patients were healthcare workers. At the height of the outbreak, the virus was found to be a coronavirus first recognized to occur in humans, and the virus was named SARS-related coronavirus (SARS-CoV) (35). With genetic and epidemiologic studies, the virus was traced first to masked palm civets in game animals markets in Guangzhou, and eventually to bats as the probable natural reservoirs (36). The SARS-CoV is distinct in that the infective course was typified by shedding of low concentrations of the virus in the first week of infection, with peak shedding occurring in the second week (37). This shedding pattern enables the opportunity for infection control measures to be successfully implemented on early recognition of infection, probably contributing to the eventual successful control of the disease. In addition, there is evidence that the hygienic measures implemented on a population level during SARS resulted in a reduction in the incidence of other respiratory viruses (38). Although the SARS-CoV has now been eliminated from
circulation in humans, its recurrence is potentially possible, not only as a result of reintroduction from its natural reservoir but also of inadvertent escape from the laboratory (39).

Since 2003, there was heightened interest in coronaviruses, and an explosion in publications on the agent. New coronaviruses infecting humans were subsequently recognized, including NL63 and HKU1 (40,41,42). These agents usually cause sporadic mild respiratory tract infections, similar to the earlier coronaviruses, and were much less virulent than the SARS-CoV.

Human adenoviruses (HAdVs) are nonenveloped DNA viruses, now with >50 types recognized. HAdVs cause a plethora of diseases not limited to the respiratory tract. Respiratory adenoviruses mainly belong to types 1 to 7, and occasionally to other types. Mild upper respiratory illness is the usual presentation, although occasional episodes of pneumonitis are recognized (14). Although infection with the virus is mostly recognized in children, both young adults and the elderly can be infected. Outbreaks of HAdV infection are commonly reported in the community, with HAdV types 4 and 7, and more recently type 14, being associated with clusters of infection among military recruits (43). In recent years, new types of HAdVs continue to be described, and occasional outbreaks have been recognized (44). The seasonal occurrence of HAdV infection is not consistently reported in the literature. The seasonal pattern observed in Hong Kong is illustrated in Figure 42.4.

Human rhinoviruses are nonenveloped RNA viruses comprising >100 serotypes. They are classical causes of the common cold and are associated with mild respiratory disease. Episodes of severe infection seldom occur and are mostly confined to immunocompromised hosts (45). In terms of seasonality, infections more commonly occur from autumn to spring in temperate climates, whereas in the tropics, the incidence is highest during the rainy season (3). Distinct outbreaks are not commonly recognized. Nevertheless, due to the large number of serotypes, reinfections throughout life are frequent. The virus is mostly community-based, and rarely a problem in the hospital setting.