Analogous to the section on bacterial respiratory pathogens, in this section, several disparate types of viruses will be discussed. Their commonality is that the diseases they cause are predominantly respiratory, and they are generally acquired through contact with the respiratory secretions of infected individuals. Focus will be on specific viruses causing severe disease — in particular Influenza virus.
The “Common Cold”
All of us are familiar with cold symptoms. With the average young child experiencing 6 to 8 and average adult suffering between 2 and 4 colds a year this condition is, by far, the most common infection of humans. Rhinoviruses predominate with greater than 100 different serotypes identified. Other viruses known to cause this syndrome are coronaviruses, adenoviruses, parainfluenzaviruses and respiratory syncitial virus (RSV).
Influenza is one of the most important epidemic diseases of humans. This importance is derived from the worldwide scope, the rapidity of spread of epidemics, the seriousness of disease and the potential for development of devastating worldwide pandemics as were seen in 1958 (the “Asian flu”), 1967 (the “Hong Kong flu”) and most notably 1918 (the “Spanish flu”) from which, at least 20 million people succumbed. Please read this letter written during the 1918 epidemic by an army medic at Camp Devens, Massachusetts to get an understanding of why the next big influenza pandemic is so feared.
Influenza A, B, and C are the only members of the Orthomyxoviridae, of which only Influenza A and B cause significant human disease. The virion is generally rounded but may be long and filamentous. In Influenza A a single stranded RNA genome is closely associated with a helical nucleoprotein (NP), and is present in eight separate segments of ribonucleoprotein (RNP), each of which has to be present for successful replication. This unique segmented genome is enclosed within an outer lipoprotein envelope and facilitates development of new strains by reassortment of the gene segments between different human and animal (in particular bird and pig) strains of virus. Co-infection with two distinct strains in a single animal is thought to be the mechanism. This genetic instability is, at least in part, responsible for the annual influenza epidemics (mutation: drift) and periodic pandemics (reassortment: shift) of influenza infection worldwide.
The most important structures from the pathogenesis and immune response perspectives are two types of protruding spikes. One is neuraminidase (N), of which there are nine major antigenic types, and which has enzymic properties as the name implies. The other type of envelope spike the haemagglutinin (H) of which there are 13 major antigenic types. The haemagglutinin functions during attachment of the virus particle to the cell membrane, and can combine with specific receptors on a variety of cells including red blood cells. Influenza strains are characterized and named based on the specifics of antigenic makeup of these two proteins.
Changes in antigenic character of Hemagglutinin and Neuraminidase are responsible for the unusual epidemic behaviour of this virus. In temperate climates epidemics always occur in the winter months, usually yearly and tend to follow specific geographic patterns of spread. For instance, in North America, the first isolates of Influenza almost always come from the west and the epidemic spreads eastward. In Newfoundland, it is usual for Influenza epidemics to start in late January or February. In Alberta it is usual for Influenza epidemics to begin in November or December.
Influenza is spread from person to person by the droplet route, by direct contact with respiratory secretions and articles contaminated by secretions. It is highly contagious. Susceptibility is universal, however the experience of the population with prior influenza epidemics influences extent of current population at risk.
Influenza epidemics are associated with increases in overall morbidity and mortality rates (especially in the elderly and debilitated) and put a strain on hospitals. It is always a difficult time to work as a primary care physician because the volume of acutely unwell patients abruptly increases and distinguishing those suffering from influenza from those with serious bacterial infections (e.g., meningococcal septicemia) is challenging.
After an incubation period of 1 to 4 days, influenza begins with a brief prodrome of malaise and headache lasting a few hours. This is followed by the abrupt onset of fever, severe myalgia often followed by a nonproductive cough. During this acute phase of illness, most of those affected will be “off of their feet” and feel generally miserable. Fever persists for approximately 3 days, followed by respiratory symptoms for several more days and then, unless a complication occurs, recovery is complete. Coryza (runny nose) is very uncommon in influenza helping to distinguish it from a “bad cold”. In young children influenza can be difficult to distinguish from other severe respiratory infections. It is associated with bronchiolitis, croup, otitis media, and rarely, febrile convulsions. Complications of influenza include bacterial pneumonia, myositis, central nervous system involvement, and Reye’s syndrome.
During the winter months, “sentinel” physicians submit samples for testing on patients presenting with “flu like illness”. Nasopharyngeal swabs and throat gargles are preferred specimens. In the laboratory, virus culture is performed by inoculating cell cultures or fertilized chicken’s eggs. When virus is first isolated it confirms the epidemiological suspicions that the yearly influenza epidemic has started. Virus isolates are forwarded to national authorities and the detailed characterization of the circulating viruses are used by international authorities to determine the make—up of future vaccines.
Once it has been confirmed that influenza is present in a community laboratory confirmation of infection is usually unnecessary and impractical as the clinical syndrome is easily recognizable. Rapid antigen detection tests are available and are occasionally utilized in institutions to make decisions about isolation of patients or with difficult clinical scenarios.
As with other specific antiviral therapies the drugs that are active against influenza are only effective when started very early in clinical course. This has hindered the widespread use of these specific therapies as patients, quite correctly, do not seek medical attention within 24—48 hours of the start of their illness. Those hospitalized with influenza and its complications have usually been ill for several days limiting the utility of antivirals. However, prophylactic use of antivirals is an effective means of preventing influenza especially in institutions for the elderly where epidemics can be devastating.
Two classes of agent are active against Influenza viruses. Amantadine and its analogue, rimantadine have been available for many years. Recently, two related agents zanamivir and oseltamavir have become available.
It is very difficult to limit the spread of influenza viruses during epidemics. However, efforts are made in institutions. Visitations may be limited and attention to barrier precautions (e.g., personal respirators) and hand washing encouraged.
Immunization is the most important strategy employed to limit susceptibility to Influenza. It is advocated for all people over the age of 65 and anyone with a chronic medical condition (e.g., coronary artery disease, diabetes, kidney disease). Particular attention to residents of chronic care facilities should be made.
Killed (formalin inactivated) influenza vaccine is available each year. Based on the experience of the past season and the current circumstances in the other hemisphere, an international panel decides upon the component strains in the spring to allow lead-in time for the production of vaccine for administration in the fall. Ideally, the vaccine incorporates antigens of the A and B influenza strains that will be prevalent in the community during the upcoming winter. Two Influenza A and one Influenza B strain are included in each year’s vaccine.
Measles virus a member of the Paramyxoviridae family. Other important members of the Paramyxoviridae family include mumps, parainfluenza virus and respiratory syncitial virus (RSV) that are discussed below.
Measles is very infectious. It is one of very few pathogens of humans that is transmitted via the airborne route. Special attention must be made to engineering controls of air flow in hospital rooms that house measles patients.
Measles is an acute disease characterized by fever, cough, coryza, conjunctivitis, an erythematous maculopapular rash, and a pathognomonic enanthem on the buccal mucosa (Koplik spots). It is also called Rubeola (not to be confused with Rubella or “German Measles”). Complications such as otitis media, bronchopneumonia, laryngotracheobronchitis (croup), and diarrhea occur more commonly in young children. Acute encephalitis, which frequently results in permanent brain damage, occurs in approximately 1 of every 1000 cases. Death, predominantly due to respiratory and neurologic complications, occurs in 1 to 2 of every 1000 cases reported in the United States. Case fatality rates are increased in immunocompromised children in particular those that are malnourished. Several million children still die annually.
Subacute sclerosing panencephalitis (SSPE) is a degenerative nervous system disease characterized by behavioral and intellectual deterioration and convulsions. It occurs is a result of a persistent measles virus infection with symptoms developing years after the original infection. Once a rare, but very feared complication of Measles, vaccination has lead to its virtual disappearance in industrialized nations.
Measles vaccine is a component of all childhood vaccination programs in developed countries. It is usually administered as part of a trivalent vaccine that includes Mumps and Rubella and referred to as MMR. For years MMR was given only once at one year of age. However, recent limited outbreaks of measles have resulted in a booster dose of vaccine to be advocated for routine administration. In Newfoundland the booster dose is given at 18 months.
Mumps is caused by a paramyxovirus that is spread by contact with respiratory secretions. Universal immunization appeared to have eliminated this infection in Canada until recent large scale outbreaks among university students prompted an active revaccination program and change in childhood immunization schedules.
Mumps is a systemic infection characterized by swelling of the salivary glands, particularly the parotid glands. Orchitis (inflammation of the testes) is a common complication of mumps acquired after puberty. Overall the morbidity of this infection is low.
Parainfluenza viruses are very prominent pathogens of children and the major cause of laryngotracheobronchitis (croup). The four distinct serotypes designated 1 to 4 are responsible for approximately one third of the lower respiratory infections occurring in children under the age of 5 years. No specific antiviral therapies are available for parainfluenza viruses and while vaccines are actively studied, none have become available.
Adenoviruses are icosahedral, DNA containing viruses. There are 47 recognized serotypes and although many serotypes have been associated with specific clinical syndromes, a role in disease causation remains obscure for at least half. Several types of respiratory symptoms can be caused by adenoviruses including cough, fever, sore throat and rhinorrhea. Lower respiratory tract involvement is not uncommon. They are not infrequent causes of “severe colds”.
Respiratory Syncytial Virus
Disease caused by respiratory syncytial virus (RSV) occurs in annual epidemics during the winter and early spring affecting essentially all children at some time during their first 3 years of life. Immunity, however, is not complete and reinfection is quite common. Spread among household and childcare contacts, including adults, is common. The period of infectivity is usually 3 to 8 days, but it may be longer, especially in young infants in whom viral shedding may continue for as long as 3 to 4 weeks.
In infants and young children RSV is the most important cause of lower respiratory tract infections (bronchiolitis and pneumonia). These infections may be life threatening and are a prominent reason for hospitalization in this age group. Infections in later life tend to be much more mild and predominantly involve the upper respiratory tract.
RSV is a problem organism in pediatric hospitals and many outbreaks of nosocomial RSV have been described. Special attention to control spread to immunocompromised patients must be undertaken. Transmission in hospital is curtailed through good hand washing practices and through cohorting of patients who are infected. There is no active vaccine. However, an RSV hyperimmune globulin preparation has recently become available and is advocated for infants at high risk for serious disease such as those that were very premature.