Measles, mumps and rubella infections

This Update examines the incidence, mortality and prevention of measles, mumps and rubella.

Professor Dominic Fitzgerald, MBBS, PhD, FRACP
Paediatric respiratory and sleep physician at the Children’s Hospital at Westmead, NSW.

INTRODUCTION
AT ANY age, the viral infections of measles, mumps and rubella can cause severe and sometimes fatal illness, especially if contracted in utero.

Immunisations are among the most cost-effective public health strategies implemented. The safety and efficacy of immunisation against measles, mumps and rubella (MMR) is widely accepted. The introduction of the MMR vaccine has saved many lives in both the developing and developed world.

While some challenges for delivery and implementation of vaccine programs to the poorest of nations remain, medical and nursing clinicians in Australia face the First World problems of convincing a vocal minority of concerned but usually ill-informed parents about the importance of the MMR vaccine for their children.

MEASLES
Measles is rarely seen today due to effective immunisation policies.

Measles is a ribonucleic acid (RNA) paramyxovirus. It has an incubation period of 6–19 days (median 14 days); a prodrome of 2–4 days with coryza, conjunctivitis, high fevers, and Koplik’s spots on mucous membranes; and a diffuse maculopapular rash with fever that lasts for 5–6 days. Patients are listless and unwell.

Incidence
There are an estimated 21 million cases of measles annually, but most of these occur in the developing world.

In Western countries such as Australia with effective immunisation programs, the incidence is 0–10 cases per 100,000 people.

Before the introduction of vaccination programs, up to 90% of people suffered measles by the age of 15 years in the US, reflecting the highly contagious nature of the infection. Measles is spread through airborne droplets.

Morbidity
The impact of measles infection can be devastating. It was estimated to have caused almost 350,000 deaths in 2005.

In malnourished populations, the risk of death from measles is estimated to be as high as 25%, especially in those with vitamin A deficiency.

The use of vitamin A treatment in infected infants, the introduction of a slightly younger age of immunisation (older than nine months as opposed to 12 months), and the use of a second measles immunisation are three factors that have been shown to have reduced the mortality significantly in the developing world.

The better recognition and supportive treatment of diarrhoea causing severe dehydration, affecting 9–10% of malnourished children with measles, has also helped improve survival.

The WHO suggested that the estimated deaths from measles fell from 750,000 in 2000 to 197,000 in 2007 because of vitamin A treatment and the second measles vaccine.

It should also be noted that in the immunocompromised paediatric populations, primarily those with HIV/AIDS, the mortality rate is higher.

The major morbidity in the developed world relates to encephalitis and pneumonia. Seizures occur in 5:1000 people and subacute sclerosing pan-encephalitis affects 1:1000 people.

The latter condition is fatal and occurs about 4–5 times more commonly in children younger than 12 months who are infected with measles.

MUMPS
Mumps is caused by another RNA virus described as a rubulavirus from the paramyxovirus family. It has a longer incubation period than measles at 15–24 days (median 19 days), with a prodromal period with influenza-like symptoms preceding the appearance of parotitis.

The parotitis lasts for 7–10 days, with swelling of the parotid gland usually being symmetrical. There is an association with headache and abdominal pain.

Interestingly, it is suggested that up to one-third of mumps infections may be subclinical or milder illnesses, where the diagnosis of mumps is not considered.

The infectivity period extends from a couple of days before the parotid glands become swollen to five days after the swelling appears. Infection is spread by respiratory droplets, saliva and, potentially, in urine.

Incidence
The risk of infection has been believed to be lower in the first 12 months of life when infection had occurred in mothers when they were children in an analogous fashion to that of measles and rubella.

However, with younger generations who have vaccine-mediated immunity and lower levels of antibodies than from infection-generated immunity, this issue may need further consideration.

In the US, the number of cases of mumps reported before vaccination was 185,691 in 1968; this decreased to 231 cases in 2003, 14 years after the number of MMR vaccines was recommended to increase from one to two. Mumps vaccination was first recommended in 1977.

Before immunisation, mumps was primarily a childhood condition, with up to 87% of children in one UK study having serological evidence of mumps infection by the age of 10 years. Currently, most cases occur in adults who are unimmunised.

Nonetheless, there are periodic outbreaks in immunised populations such
as in a Kansas University dormitory, which was reported in 2006. In this outbreak of 174 cases at a mean age of 20.9 years,
65% of cases were women, and 96%
of people affected had had at least two MMR vaccinations confirmed on health record checks.

The authors commented that initially doctors did not consider mumps as the cause of parotitis because of the high MMR vaccination rate in current university students.

Complications
The main consequences of mumps are the subsequent neurological problems, hearing loss, orchitis with infertility and pancreatitis.

Before the introduction of MMR vaccination, mumps was responsible for about 20% of aseptic meningitis cases. The outcome was usually benign and was different to that of mumps encephalitis, which had more sequelae such as behavioural changes and ataxia occurring up to two years after infection.

Sensorineural hearing loss (usually unilateral) is described after mumps, and one Israeli report suggested an incidence of 1:3400 after a mumps outbreak in the early 1980s.

Orchitis has been reported to occur in up to 10% of males; it is more common in adults and occurs bilaterally in 17–33%. Testicular atrophy was reported in 36% of cases in one study. In females who had mumps, one study reported 15% developing mastitis.

The incidence of pancreatitis in a community-based survey was 4%, while in a case series of people hospitalised with pancreatitis it was as high as 46% as a complication of mumps.

Vaccination
Mumps vaccination is highly effective in reducing the risk of mumps in those immunised, as well as the families of those immunised.

One randomised controlled trial from the US in 1965 compared open-label live mumps vaccine with placebo and followed the children for five months. The incidence of mumps was 22 times greater in the placebo group, with an immunisation efficiency at preventing mumps (short-term) of 96% in the immunised group.

A similar study a year later in the US showed an immunisation-protect efficiency of 97% for up to nine months; when extended to include family members, it concluded an overall protective efficacy of 95%.

RUBELLA
In contrast to measles and mumps, rubella is more benign as a clinical illness but has a greater risk of affecting the fetus with maternal infection.

Rubella is another RNA virus, but it belongs to the Toga virus family. The incubation period is 15–20 days (median 17 days) and the prodromal period is often not apparent. In many cases the infection is subclinical.

Rubella is spread by direct contact or droplet spread. With clinical infection there is generalised lymphadenopathy and a generalised rash appears about a week later.

Before immunisation was introduced, the infection was uncommon before the age of five years and peaked at 5–10 years. By early adulthood it was estimated that 80% of women had been infected.

Rubella rash

Complications
Complications of rubella are most uncommon in children. Rarely, encephalitis, pneumonia, arthralgia and arthritis have been reported. Arthralgia is more common in women who are infected with rubella.

The most important issue is the risk of developing the congenital rubella syndrome (CRS), which was first reported by Gregg in 1941. In a study of 1000 pregnant women in the UK who developed rubella with a rash, 80% who had the infection in the first 12 weeks as opposed to 25% at the end of the second trimester passed the infection on to their fetus. Rubella-related defects occurred in all infants infected up to 10 weeks’ gestation, and this decreased to 35% of those infected between 13 and 16 weeks, and no infants after 16 weeks.

As would be expected, the earlier in pregnancy the fetus is infected, the more severe the defects. The most common manifestations include deafness, congenital heart disease, cataracts, growth retardation and cognitive impairment.

Immunisation
Rubella immunisation greatly reduces the risk of rubella. The incidence of CRS in the US dropped from 20 to 70 cases per year in the 1970s to two cases annually by 1985. With the widespread uptake of MMR, cases of CRS are rare in the US and when they do occur, it is usually in babies born to young women outside the US (who are presumably not immunised).

Similarly, a 2003 Melbourne study reported on a retrospective review of 65,000 hospital records to show that significantly more women born overseas were seronegative for rubella, suggesting that their babies were at an increased risk of CRS. With the changing demographic of Australia’s population reported from the 2011 census, ascertaining the rubella serological status of late-teenage girls and young adult women born in developing countries should be recommended, or, more simply, an additional dose of
MMR given.

MMR VACCINATION
The main issues are local discomfort at the injection site, fevers and occasional febrile seizures. There is no evidence of an increased risk of afebrile seizures. Moderate fever (38.6°C to 39.5°C) may occur within 21 days in up to 25% of young children (aged 14–18 months).

In a double-blind crossover trial of MMR vaccine and placebo given 21 days apart to twins, high fever (> 39.5°C) occurred in up to 7% with the vaccine. The twins received the treatments (vaccine or placebo) in the opposite order.

With febrile seizure, the risk is higher in the fortnight after immunisation, and the risk is highest if the child has had
a previous febrile seizure or has a family history (e.g. older sibling) with febrile
seizures. In one UK study, the risk of febrile seizures occurring 6–11 days after MMR immunisation put the incidence
at 1:3000 vaccinations.

Very rarely reported concerns include anaphylaxis (one estimate at 1:100,000), as well as an increased risk of aseptic meningitis, arthralgia and idiopathic thrombocytopaenic purpura. No association has been found between MMR vaccine and asthma, diabetes, Guillain-Barré syndrome, multiple sclerosis, autism or autistic spectrum disorders.

The next issue parents may wish to discuss is how effective is the vaccine against measles? Firstly, if most of the population is immunised (> 95%) then the
‘herd immunity’ consideration applies. This considers that as most people are protected by vaccination, they are less likely to be infected.

However, beyond this argument it is estimated that the introduction of vaccine programs in the US lowered the infection rate in vaccinated children from 0.5 to 17.6 cases per 100,000 compared to 5.2 to 378.3 cases per 100,000 in non-vaccinated children between 1985 and 1992. The presumption was that most children who were vaccinated received the MMR vaccine rather than the monovalent measles vaccine. This equated to a four- to 170-fold increase in the risk of developing measles if you were not vaccinated as a young child.

MMR IMMUNISATION AND AUTISM
The opportunity to engage in a constructive conversation with anti-immunisation campaigners is one of the truly exhausting challenges in preventive medicine for clinicians caring for children.

Nothing highlights this more than conversations about immunisation and autism with often ill-informed but strident opponents of immunisation.

The Lancet study
Despite the fact that English gastroenterologist Andrew Wakefield’s report in 1998 of a highly selected case series (N=8) of autism that he alleged occurred as a result of MMR vaccination has been totally discredited, and the article withdrawn by The Lancet, anti-immunisation lobbyists push this agenda to vulnerable parents of children with autistic manifestations and those who embrace alternative medicines.

Wakefield suggested that MMR vaccination caused intestinal inflammation, which manifested with lymphoid nodular hyperplasia of the gut (on endoscopy), and that this led to translocation of usually non-permeable gut proteins to the bloodstream and then into the brain where they adversely affected development, with autistic manifestations among other neurological complications.

The problem with Wakefield’s argument was that it was seen by no one else in the world and that even the rationale lacked biological plausibility. It caused a backlash against immunisation in the UK, and other parts of the developed world, and no doubt caused an increase in morbidity and possibly mortality for those communities where vaccination rates fell to less than 70% in some cases.

Epidemiological studies have clearly shown that there is no increase in the rate of diagnosis of autism related to MMR vaccination. However, complicating matters was the fact that the age of presentation of autistic features between one and two years coincided with the timing of MMR vaccination, and an increase in the diagnosis of ‘autism spectrum disorders’ with more liberal criteria was advocated. In Australia there was a push from primary school teachers and headmasters for such a label as it attracted extra school funding for the school with each case diagnosed. This is to be addressed with tighter criteria for the diagnosis of autism anticipated in the coming months.

An additional concern is that multidose vaccines may contain traces of mercury as an antibacterial agent, specifically thimerosal, which is 50% ethylmercury by weight. It has been used for more than 50 years.

There is no correlation between the neurological signs of mercury poisoning and autism. More importantly, MMR vaccine does not contain thimerosal  or any other traces of mercury.

So, 14 years later, there is no link between autism and the MMR vaccine, and Wakefield’s views on MMR vaccination. Primary care providers are left debating the indefensible with the vulnerable parents of autistic children who understandably may seek someone or something to blame for their child’s condition, as well as trying to offer rational information to the vocal lunatic fringe!


Two-year-old child with mumps

IMPROVING IMMUNISATION UPTAKE IN PRIMARY CARE
Few in the community are better placed to improve immunisation rates than GPs and early childhood nurses.

A recent systematic review of methods of improving immunisation rates was reported, which concluded that simple and inexpensive reminders, and better education of parents of young children, can improve compliance with immunisation schedules by 7–19%. The most effective strategies appear to target both the healthcare provider and those that are to be immunised in what is described as ‘multifaceted strategies’.

Reminders to families via posters in surgery waiting rooms and reminder letters to homes, or, in today’s terms, perhaps emails or SMS, have been useful. Providing feedback to the provider about immunisation rates and financial incentives for completing immunisation data registries are ways of improving provider awareness.

The most vulnerable to incomplete immunisations are the more socioeconomically disadvantaged: those from single-parent families, ethnic minorities and the more itinerant inner-city populations. Strategies to improve immunisation rates include outreach into schools and preschools with ‘catch-up’ immunisation drives.

At the heart of this in general practice is simply making questions about immunisation in all consultations part of a routine history, despite what the presenting problem is for children, and considering on-the-spot immunisation of those who present for unrelated reasons.


Measles: Koplik’s spots in mouth

KEY POINTS

• Measles, mumps and rubella can cause severe and sometimes fatal illness, especially if contracted in utero.
• The measles, mumps and rubella vaccine has saved many lives in both the developing and developed world.
• The major morbidity of measles in the developed world relates to the development of encephalitis and pneumonia.
• The main consequences of mumps are the subsequent neurological problems, hearing loss, orchitis with infertility and pancreatitis.
• The most important issue with rubella is the risk of developing the congenital rubella syndrome, with rubella-related defects occurring in all infants infected up to 10 weeks’ gestation.
• Epidemiological studies have clearly shown that there is no increase in the rate of diagnosis of autism related to MMR vaccination.