The virus

Rotavirus is a double-stranded RNA virus belonging to the family Reoviridae. It is called rotavirus because by electron microscopy the virus particle resembles a wheel (see Fig. 25.1).

Epidemiology

Route of spread

Rotavirus spreads among humans by the faecal–oral and respiratory routes. There are seven different groups (A–G). Group A rotaviruses are the major cause of human infection, but groups B and C also infect humans. Rotavirus infections occur in most animal species, and although they can infect humans, are mostly associated with mild or no human disease, and no onward transmission.

Prevalence

Rotavirus infections are common in childhood and have a high morbidity with associated mortality in poor developing countries. In the UK, by the age of 5 years 90% of children have been infected. Reinfection can occur throughout life, but only the first infection after loss of maternal protection is associated with severe symptoms, and reinfections in older children and adults tend to be mild or asymptomatic. Infection usually occurs between November and March.

Incubation period

The incubation period of rotavirus is 1–2 days.

Infectious period

Patients are most infectious when symptomatic with diarrhoea and vomiting.

Clinical

There are several viruses that can cause meningitis and/or encephalitis. Listed below are the viruses most commonly associated with these symptoms. However, it must be remembered that any virus (e.g. rubella virus and rotavirus) can cause encephalitis rarely. For more details on individual viruses, refer to virus-specific pages.

Viral encephalitis

• Herpes simplex virus encephalitis is caused by HSV type 1 or rarely type 2. Symptoms include fever, severe headache, drowsiness, fits and/or unconsciousness. Prompt antiviral treatment with intravenous aciclovir is essential, since herpes encephalitis can have a mortality rate of 70% when untreated. Patients very rarely have HSV-type vesicles on the skin. Even when prompt treatment is given, about 10–30% of patients will be left with some sort of neurological deficit.

• Varicella-zoster virus can cause meningitis or meningo-encephalitis as a result of reactivation of the virus in the brain. As with HSV, few patients have VZV lesions on the skin. Patients are usually experiencing zoster with no external manifestations. One of the most feared but rare complications of chickenpox is encephalitis, which can be fatal, especially in pregnant women, and should be treated promptly with high dose intravenous aciclovir.

• Other viruses, such as arboviruses (e.g. Japanese encephalitis virus) or rabies virus cause potentially fatal encephalitis, almost always acquired abroad. Any virus can cause encephalitis and the clue to the causal virus often lies in the other symptoms (e.g. rubella rash or rotavirus diarrhoea and vomiting) or their travel history.

Neonates can be born with encephalitis as a result of congenital infection.

The viruses

Human herpes viruses 6, 7 and 8 all are double-stranded DNA viruses and belong to the family Herpesviridae.

• HHV6 (beta herpesvirus)

• HHV7 (beta herpesvirus)

• HHV8 (gamma herpesvirus)

Epidemiology

Route of spread

• HHV6: aerosol transmission and saliva from mothers to babies and breast milk.

• HHV7: aerosol transmission and saliva from mothers to babies and breast milk.

• HHV8: there is some evidence of sexual spread via semen and possibly vertically from mother to child. HHV8 has been transmitted to transplant recipients from donor organs.

Prevalence

• HHV6 infection is ubiquitous and occurs worldwide. Infection often occurs after 4 months of age, as maternally acquired immunity wanes.

• HHV7 infection is ubiquitous and occurs worldwide. Most children (95%) acquire the infection by 5 years of age.

• HHV8 infection is more prevalent in Italy, Greece, Israel and Saudi Arabia than in northern Europe. These countries have a higher prevalence of Kaposi's sarcoma. In the UK, the HHV8 antibody prevalence is <5% in blood donors and 30–50% in HIV-positive men who have sex with men (MSM). Human herpes virus 8 antibody prevalence is 85% in patients with Kaposi's sarcoma.

At-risk groups

Immunocompromised patients are at increased risk of more severe infection and clinical disease.

The virus

Rubella virus is a single-stranded RNA virus, which is the only member of the genus Rubivirus within the family Togaviridae. The outer envelope protein E1 is the viral haemagglutinin protein responsible for binding to the cell receptors to initiate infection.

Epidemiology

Prevalence

Rubella has a worldwide prevalence. Before the introduction of vaccination, it circulated in epidemic form with an epidemic cycle every 6–8 years. In countries with effective childhood rubella vaccination programmes this pattern has been interrupted, as has been the number of reports of endemic cases. In countries without vaccination programmes it remains an infection of childhood. About 15–20% of young adults remain susceptible, putting them (especially pregnant women) at risk of acute infection as the virus is endemic and continues to circulate in the community.

Route of spread

Infection is spread via respiratory secretion droplets. The virus is highly infectious with attack rates of 50–80% in susceptible individuals in communities during outbreaks.

Incubation period

The rash usually develops 16–18 days after exposure, but the incubation period may range from 14–21 days. Infection is first initiated in the respiratory epithelium and then spreads and replicates in the regional lymph node. This is then followed by viraemia and dissemination of the virus to multiple sites.

Infectious period

Maximum viral shedding from the respiratory tract of infected individuals occurs from 5 days before to 7 days after the appearance of the rash.

This book is intended for trainee doctors, healthcare scientists, infection control nurses and other healthcare workers working in infection-related specialties (virology, microbiology, infectious diseases and public health).

It will also be useful for medical students and other healthcare professionals (doctors, nurses, general practitioners etc.) working in non-infection specialties who deal with patients with suspected virus infections.

It has easily accessible information with tables, figures and algorithms to aid easy reference for the busy clinician. It is divided into two main sections. The first is an alphabetically arranged series of chapters on the most important viruses that cause symptomatic disease in humans in the developed world; we have kept a standard chapter format throughout this section to enable the reader to access important information quickly. The second is a set of clinical syndromes (e.g. hepatitis and skin rashes), where the different viruses and their clinical symptoms are presented. Other sections provide information on diagnostic techniques, antiviral drugs, viral vaccines, occupational health issues, infection control and travel-related infections. We are aware that most virologists in the UK deal with non-viral pathogens, such as Chlamydia, toxoplasma, atypical pneumonia organisms and Creutzfeldt–Jakob disease (CJD) and variant CJD (vCJD), so a section on these pathogens is also included.

The aim of the book is for it to be a quick-reference guide to differential diagnosis, giving details of which specimens and tests are best for laboratory diagnosis, which treatments to use and what the control of infection implications are.

Clinical

There are several kinds of skin infections caused by viruses, and these are best considered in the four categories that group together similar symptoms for the purpose of differential diagnosis:

• maculopapular rashes

• vesicular rashes

• wart-like lesions

• haemorrhagic rashes.

Maculopapular rashes

These skin rashes can be caused by a variety of different viruses. Clinically it is difficult to distinguish between the viral causes of these maculopapular rashes. Studies have shown that only a small percentage of these rashes are clinically diagnosed accurately.Figure 41.1 shows a typical maculopapular rash. Table 41.1 provides information on the laboratory diagnosis of virus infections associated with maculopapular skin rashes.

Rubella

Rubella is caused by rubella virus. It produces a mild illness with a maculopapular skin rash. It causes severe congenital damage in children born to mothers who acquire infection in the first 12 weeks of pregnancy. Because of this, women should receive rubella virus vaccine before becoming pregnant. They should also seek advice from a healthcare professional if they are in contact with a rubella-like illness in the first 20 weeks of pregnancy. Patients are infectious for one week either side of the onset of rash.

The first vaccination known to humankind was against a viral infection, when Jenner, in 1796, injected material from a lesion of cowpox into an eight-year-old boy to protect him from smallpox. The culmination of this first step was in 1980 with the declaration that smallpox was the first human infection to be eradicated from the world.

Subsequently, many viral vaccines have been developed and there have been successful public health campaigns to reduce the burden of infection. The World Health Organization (WHO) has an ongoing expanded programme of immunizations (EPI) targeting the worldwide elimination of both polio and measles. Polio is now considered to be non-endemic in all but four countries of the world.

Vaccines against hepatitis B and papilloma viruses can arguably be considered as the first vaccines that protect against cancers (hepatocellular and cervical carcinomas respectively).

Viral vaccines can be divided according to whether they are attenuated or killed.

Attenuated vaccines

Attenuation of virus implies the loss of pathogenicity, but for successful vaccination the immunogenicity has to be maintained. The first example was the smallpox vaccination, which used a related non-pathogenic virus, the cowpox virus.

Attenuation is achieved by selective pressure on the virus during repeated passages in cell culture. The whole process has to be quality controlled strictly to ensure that extraneous viruses have not been introduced and that there is no wild type pathogenic virus in the vaccine.

The viruses

The main viruses associated with the common cold are rhinoviruses (over 100 types), coronaviruses, influenza viruses, respiratory syncytial virus and parainfluenza viruses.

Epidemiology

Route of spread

The mechanism of transmission of the common cold is different for different viruses. There are three main routes of transmission – direct contact (the virus is transmitted by skin contact from handling an infected object and transmission to the mouth or nose), via small particle aerosols (these hang around in the air and can be highly infectious) and/or via large particle aerosols (created by coughing and sneezing).

Prevalence

As its name suggests, the common cold occurs throughout the year. It is most prevalent in children, especially in younger children. Pre-school or primary school children have about 3–8 colds a year, whereas adults usually have 2–4 colds per year. Parents, teachers and others in frequent contact with young children have more colds than those with minimal contact. Women have more colds than men, probably reflecting their increased contact with children.

The common cold is more prevalent in winter months (usually caused by rhinoviruses or parainfluenza types 1 and 2 virus). Summer colds are more likely to be caused by coronaviruses or parainfluenza virus type 3. Quite why parainfluenza viruses type 1 and 2 cause winter infections and parainfluenza virus type 3 causes summer infections is a mystery! It is a myth that colds are more likely to be acquired in cold and wet weather.

The most successful antiviral agent to date, aciclovir, was a serendipitous discovery. It was manufactured as an anticancer drug but was found to have good in vitro activity against herpes simplex virus, and after clinical trials it was licensed for use in the 1980s. Subsequently, the antivirals have been designed and manufactured with specific viral targets in mind that will inhibit viral replication.

One disadvantage of the antivirals that act by DNA polymerase inhibition is that they affect the cellular DNA replication at the same time, and therefore can cause cytotoxic side effects such as nausea, vomiting, bone marrow suppression etc. For this reason they are not licensed to be used in pregnancy (except in life threatening situations or in HIV cases where risk to the fetus is outweighed by the benefit of treatment) because of risk of fetal teratogenesis. These side effects are limited in certain drugs, such as aciclovir, because the drug is preferentially activated in virus-infected cells and has little or no side effects on normal uninfected cells (see below).Table 50.1 gives examples of antiviral drugs targeted to different steps in the viral life cycle.

Human immunodeficiency virus (HIV)

See below under antiretrovirals.

Herpes viruses

Drugs: aciclovir, valaciclovir, penciclovir/famciclovir, ganciclovir, foscarnet, cidofavir, rituximab.

Clinical

Individual respiratory virus infections are difficult to diagnose clinically because they all cause similar symptoms. They often occur in outbreaks, at certain times of the year and in certain age groups, which increases the accuracy of clinical diagnosis. For example, respiratory syncytial virus (RSV) infection most frequently occurs in children under the age of 18 months from November to February each year and is associated with bronchiolitis, sometimes requiring hospital admission.

Several viruses, such as rhinoviruses, coronaviruses, enteroviruses, respiratory adenoviruses and parainfluenza viruses are causes of the ‘common cold’ (see Chapter 34). It is interesting that types 1 and 2 parainfluenza viruses cause outbreaks in the winter while parainfluenza 3 viruses cause summer colds.

Some of these viruses (especially parainfluenza viruses and RSV) can cause pneumonia.

Influenza

Influenza viruses are the most feared cause of respiratory viral infection. As a result of the profound malaise and myalgia associated with influenza, clinical diagnosis is more accurate than with the other viral respiratory infections. Influenza occurs each year in the UK from October to April. Nobody can predict exactly when an outbreak of influenza will occur each year, which virus will be involved, how severe it will be and which age group will be worst affected. If patients acquire a bacterial lung infection on top of influenza, this can result in severe or fatal infection. There is an extensive surveillance programme in the UK for influenza, which involves general practitioners, the Health Protection Agency (HPA) and the Department of Health. This gives impending warning of the first influenza cases of the season, and monitors each evolving national outbreak.