A variety of clinical syndromes in children are caused by viral infections. These viruses circulate freely either because there is no vaccine or else because vaccination is not part of EPI. Infections occur predominantly in childhood and are usually followed by life long immunity.
Togaviridae family, Rubivirus genus
Enveloped, ssRNA, positive sense
There is no immunization in the public sector against this virus in South Africa and it circulates freely. Most people are exposed in childhood. However, around 5% women of childbearing age in South Africa are still susceptible.
Virus is shed in respiratory tract and spread by droplets.
Incubation period: 14-18 days
Rubella causes a mild febrile illness with a blotchy (maculo-papular) rash. Enlarged posterior auricular lymphadenopathy is highly characteristic. This clinical picture is more distinct in adults than in children. Women in particular may develop arthralgia/arthritis during infection. Infection is followed by life long immunity.
Women who have rubella in the first trimester of pregnancy are likely to transmit the infection to the foetus. The virus can replicate in foetal cells causing damage to rapidly developing organs. The consequences to the baby depend on the timing of exposure to the virus:
Before 12 weeks:
>80% fetuses die (spontaneous abortion) or are born with severe defects to eye (cataracts), heart, brain (micro-cephaly, mental retardation), ear (sensori-neural deafness).
Deafness, learning disorders
No consequence to foetus
Acute rubella: rubella IgM
Congenital rubella: rubella IgM, rubella PCR (urine)
Immunity: rubella IgG
A live attenuated vaccine to rubella was developed in the 1960s. Universal infant immunization with measles mumps rubella (MMR) vaccine in many first world countries has eliminated CRS in those countries. Vaccine is not part of EPI in South Africa, but is available in the private sector. MMR is usually given in the 2nd year (around 15 months)
Morbillivirus (Paramyxoviridae family, Paramyxovirinae subfamily)
Enveloped, ss RNA, negative sense
Incubation period: 7-14 days
Illness begins with a prodrome of fever, conjunctivitis, cough, coryza. 3-5 days into the illness a macular popular rash erupts on the face and spreads to involve the rest of the body. Patients are most ill during the first 2 days of the rash. The virus is highly cytopathic causing widespread damage to respiratory and gut epithelium and transient immunosuppression. These factors put the patient at risk of secondary bacterial and viral complications such as otitis media, pneumonia, diarrhoeal disease. The virus also invades the brain during the acute phase of the illness. Various neurological complications may occur during and after infection (acute measles encephalitis, post-infectious measles encephalitis, sub-acute measles encephalitis and sub-acute sclerosing pan encephalitis).
This virus is not known to be teratogenic, but intra-uterine deaths can occur in pregnant women with measles.
Measles is one of the most infectious diseases known. Infection is spread by respiratory droplets and the airbourne route.
In the pre-vaccine era, the virus circulated freely in humans. Globally, it was a leading infectious cause of death in children under the age of five years.
Since the introduction of universal infant immunization, its incidence has reduced dramatically world wide. However, very high vaccine coverage (>90%) is required to stop the circulation of this virus. Ongoing epidemics still occur in under-developed countries. In South Africa, measles epidemics occurred in 2005 and again in 2009/10.
The measles vaccine is a live attenuated virus. All infants are required by law to be immunized against measles. Two doses of vaccine are given (at 9 and 18 months). The vaccine cannot be given earlier because maternal antibody interferes with vaccine replication and no immune response develops.
Post exposure prophylaxis:
Non immune individuals who are exposed to a patient with measles have a very high chance of acquiring infection. Measles vaccine should be given to non immune contacts. Individuals in whom vaccine is contra-indicated (infants < 1 year, pregnant women and severely immuno-compromised patients) should be given normal human immunoglobulin.
Acute infection: Measles IgM, culture or PCR of virus from urine or respiratory secretions.
Immunity: Measles IgG
Rubulavirus (Paramyxoviridae family, Paramyxovirinae subfamily)
Enveloped, ss RNA, negative sense
The classic picture is of parotitis, which occurs in 95% of symptomatic infections. Subclinical infection is about 30%. The incubation period is 16-18 days. There may be a prodromal stage, with malaise, headache, fever, and myalgia. Swelling of the one parotid gland is usually (75% of cases) followed by the other parotid gland between 1 and 5 days later. Sometimes other glands are involved and sublingual and laryngeal swelling caused by lymphatic obstruction may cause problems. The parotid swelling subsides after about 7-8 days.
Mumps is also a common cause of aseptic meningitis. The onset varies from 1 week before the onset of parotitis to 3 weeks afterwards. Symptoms subside 3-10 days later, and recovery is usually complete. Some patients (1 in 6000 mumps cases) also show signs of encephalitis, such as convulsions, abnormal movement, abnormal sensory perception, and focal neurological signs. Hearing loss is a less common complication of mumps, about 1 in 15000 cases of mumps having permanent hearing loss.
About a quarter of mumps cases in males after puberty are complicated by orchitis, with 20-40% of these being bilateral. There is acute pain and tenderness, with testicular enlargement. Nausea and vomiting may also occur. Late complications include infertility secondary to testicular atrophy (only if orchitis is bilateral). Oophoritis (inflammation of the ovary) is less common in post-pubertal females than orchitis is in males, and it is not associated with female infertility.
Other complications: involvement of other glands, such as the pancreas, prostate, lacrimal glands, and other salivary glands; arthritis; myocarditis; transient renal dysfunction; nephritis; thrombocytopenia; abortion (there is, however, no evidence of an increased risk of congenital abnormalities.)
Infection is transmitted by respiratory droplets. The primary site for replication is the mucosal epithelium of the upper respiratory tract and the eye. From there the virus spreads to the local lymphoid tissues, and then the primary viraemia occurs, where the virus spreads to other organs - usually the parotid, but also the pancreas, testis, ovary, and central nervous system. A secondary viraemia occurs, with further spread. Virus is excreted in urine and breast milk, but the main source of spread is via droplets from the respiratory system. Interferon appears to play a significant role in the pathogenesis, and stimulates IgG, IgM, and IgA, as well as a cell-mediated response. There doesn't seem to be a higher risk for children with an immune deficiency.
The highest incidence of mumps is in children between the ages of 5 and 9. However, because the disease is less contagious than other childhood diseases, many people only get it later in life, when they are more likely to be symptomatic - 90% of those between the ages of 10 and 14 are symptomatic, while all those over the age of 60 are. Some complications are more common after puberty - notably orchitis, oophoritis, and meningoencephalitis, the latter being 2-3 times more common in males than in females.
There is no immunization in the public sector against this virus in South Africa. The vaccine is a live attenuated virus, and usually forms part of the MMR vaccine (against measles, mumps, and rubella).
Serology: IgG and IgM; IgG levels correspond to levels of neutralising antibodies.
Isolation: Mumps can be cultured from saliva and urine.
Molecular: PCR provides a more rapid diagnosis, and is of use on CSF for a rapid diagnosis of meningitis.
Parvoviridae family, Erythrovirus genus
Small, unenveloped, ssDNA virus
The acute infection is a bi-phasic illness with fever followed by a macular-papular rash and arthralgia/arthritis (joint symptoms are commoner in women). The rash is prominent on the cheeks in small children (slapped cheek disease). Infection is followed by clearance of the virus and immunity. There is no vaccine.
Complications of this infection relate to the cell tropism of the virus. B19 replicates in red blood cell precursors and transient arrest of red cell syntheses occurs during the acute infection. This is not a problem for healthy people, but can cause an aplastic crisis in patients with shortened RBC survival (such as in patients with congenital RBC disorders).
In addition, patients with B cell deficiencies, haematological malignancies and patients with AIDS may fail to clear B19 infection and infection becomes chronic. There is ongoing virus replication in RBC precursors causing life threatening anaemia (the haemoglobin concentration in the blood can fall to below 3g/dl). These patients can be treated with large doses IV human immunoglobulin which contains anti-B19 antibodies. This helps to clear the infection.
AIDS patients with parvovirus infections need to be put on ARV therapy.
Parvovirus B19 also can cross the placenta leading to foetal infection. The foetus is at risk if the mother develops infection during the 2nd or early 3rd trimester of pregnancy. The virus replicates in the RBC precursors of the developing foetus causing severe anaemia and heart failure (hydrops foetalis). This can result in intra-uterine death. Intra-uterine transfusions can be given to save these babies.
Infection is spread by respiratory droplets. Virus circulates freely as there is no vaccine. Most infections occur in childhood. 50-80% adults have evidence of previous exposure (IgG positive).
Acute infection: Parvovirus IgM
Immunity: parvovirus IgG
Chronic infection (in immuno-compromised patient): Parvovirus PCR on blood. Parvovirus antibodies are negative in these patients.
Human herpesvirus 6
Large enveloped dsDNA virus
Primary infection with human herpesvirus 6 in infancy is usually asymptomatic. However, in 20% cases infants may develop a high fever, followed by eruption of a generalized macular popular rash as the fever subsides. Following the primary infection, the virus persists for life by establishment of latency.
Most people are exposed in the first few years of life. Virus is shed intermittently in saliva and body fluids by healthy carriers. It is readily transmitted in families from mother to child or between siblings. By adulthood, close to 100% of people have evidence of past exposure (positive anti-HHV6 IgG antibodies).
The enteroviruses are a large family of viruses transmitted by faecal oral route that cause a range of clinical syndromes, most commonly in children. Asymptomatic infections are common, but infections may be associated with a variety of clinical conditions. Clinical syndromes associated with enterovirus infection include: febrile illnesses with a rash, upper respiratory tract infections, conjunctivitis, aseptic meningitis, epidemic myositis, hand foot and mouth disease and acute flaccid paralysis (polioviruses)
Repeated infections with different enteroviruses occur as each is antigenically different. Other than for polioviruses, there are no vaccines.
Picornaviridae family, Enterovirus genus
Small un-enveloped ssRNA (positive sense)
>100 antigenically distinct viruses (previously classified into 4 groups: polioviruses 1-3, Coxsakie A, Coxsakie B and Echoviruses)
1. Aseptic meningitis (see notes on acute viral neurological syndromes)
2. Hand, foot and mouth disease:
Acute febrile illness, associated with a blistering rash on hands, feet and around the mouth. Outbreaks commonly occur in crèches, day care centres.
3. Febrile illness with rash:
Many enterovirus types can cause febrile illnesses with a macular-papular rash, much like rubella. They are most commonly seen in children.
Enteroviruses are the commonest cause of viral myocarditis (infection and inflammation of heart muscle). Cardiac symptoms are usually preceded by a febrile upper respiratory tract infection.
5. Epidemic myositis (Bornholm disease)
This is an enteroviral infection of abdominal or intercostal muscles. Illness presents with fever and chest or abdominal pain and lasts about a week. Outbreaks in families are common. Pain in the affected muscle group may be very severe and can mimic a myocardial infarction.
6. Neonatal sepsis:
Disseminated enteroviral infection (meningo-encephalitis, myocarditis, hepatitis, pneumonia) may occur in young infants who have been exposed to an enterovirus type that the mother has no pre-existing immunity to. Thus the infant has no passive protection from maternal antibody and can develop extensive disease.
8. Acute flaccid paralysis: (see notes on poliomyelitis in acute viral CNS syndromes)
Enteroviruses replicate in the gut and are shed in the stools. Thus transmission is by the faecal oral route. Infections have a seasonal prevalence during the summer months. Family and community wide outbreaks are common due to the ease of transmission.
Virus detection in stool, throat swab by culture or PCR
Serology (antibody assays) are available to identify certain enteroviral infections. There are no IgM assays. Acute and convalescent blood samples are needed confirm an acute infection. A rising titre of IgG antibody in acute and convalescent samples provides evidence of infection.