Measles – A brief historical & clinical review

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Bella, 11m, is brought to your emergency department by her parents. She’s had 3 days of cough with fears over 40oC, conjunctivitis and just today has developed a bright red rash along her hairline.

Although you’ve never seen a case before, you suspect measles.

Bottom Line:

  • Measles is one of the classic febrile exanthematous illnesses.
  • Although rare in the developed world, thanks to a good vaccination program & a historically well understood disease process, is still a major cause of childhood mortality worldwide.
  • Measles outbreaks occur sporadically in areas with close contact and lower rates of vaccination.
  • Measles may be the cause of fever & rash in a recently returned traveller from an endemic area.
  • It is very contagious and there may be a need for large-scale post-exposure prophylaxis after a confirmed case.
  • Children under five and immunocompromised patients are the most vulnerable to measles and complications thereof.

“It would be unfortunate if the classic sign of Koplik spots passed into history without a good facsimile of their appearance and a historical record of their description. As the use of measles vaccine grows more frequent and world-wide, future generations of physicians may not often see this important prodromal sign of measles. Already, many young North American physicians answer in the negative when asked ig they have ever actually seen these spots.” – Brem 1972

Measles is caused by a paramyxoviridae. It was considered the ‘first’ in the classical list of childhood febrile exanthems (along with Scarlet fever, rubella, ‘fifth disease’ et al), and was first described by the Persian physician ar-Razi (Razes) in 910 AD, in his “Treatise on the Small Pox and Measles”.

Measles was traditionally a disease of the city, with smaller outbreaks in rural or regional communities often more severe. There was a long held tradition of describing measles as ‘mild’ or ‘mortal’- some outbreaks, notably the 1875 Fiji Measles outbreak have had death rates in excess of 30%.

Since the introduction of a measles vaccine in 1963, the rates in the developed world have plummeted, approaching zero. Unfortunately, in the developing world, measles still kills about 400 people a day, mostly children.

Measles occurs in several phases:

Incubation

 After infection, the virus spreads to local lymphatics and then disseminates via the haematology route to other lymph nodes and the spleen (viremia #1). Incubation averages around 13 days (6-19 days). This is usually an asymptomatic period, however upper respiratory symptoms, fever and rash are occasionally described.

Prodrome

 The usual onset of symptoms accompanied by a second viremia. Symptoms include a fever (up to 40oC) and malaise, then a cough, conductivity and coryza symptoms. Respiratory symptoms may occur, but this two to three day prodrome generally precedes any rash, at which symptoms increase in severity.

Also around this time the pathognomic feature of measles, Koplik spots, can be seen. Koplik himself described them as “one of the most, if not the most, reliable sign of the invasion of measles”. In addition to preceding the exanthem, Koplik spots are said to appear prior to maximum infectivity. Interestingly, Koplik’s original paper quotes Osler’s description of the spots, but implies it is insufficient and, along with Henoch’s description is overly focussed on the pharynx.

“On the buccal mucous membrane and the inside of the lips, we invariably see a distinct eruption. It consists of small, irregular spots, of a bright red color. In the centre of each spot, there is noted, in strong daylight, a minute bluish white speck.” … “[I]t will be seen that the buccal eruption is of greatest diagnostic value at the outset of the disease, before the appearance of the skin eruption and at the outset and height of the skin eruption.” – Koplik, 1896

Koplik Spots

Exanthem

 Described as morbiliform, the measles rash typically begins at the hairline & face and spreads cephalocaudally to involve the neck, trunk then extremities. The palms and soles are spared. The rash blanches initially, but can include petechiae and occasionally appears hemorrhagic. Severity of the illness generally correlates with the rash coverage and confluence. It fades in the same direction. This phase of Measles also entails a fever which peaks on day two of rash, as well as lymphadenopathy (which may be generalised), pharyngitis, non purulent conjunctivitis and occasionally splenomegaly. After three days, the rash darkens, and may desquamate. By this time there has usually been a clinical improvement. The rash typically lasts for a total of seven days. 

The period of contagiousness is taken from the appearance of the rash. It is thought to be from (day minus five) to (day plus four) of the onset of rash.

Recovery

 Further fever after the fourth day is suggestive of a secondary infection or additional complication. The cough may persist for several weeks. 

“But,” Bella’s parents say, “she’s immunised as per the Australian schedule!”

As per the Australian Immunisation schedule, the first dose of measles vaccine is given at 12 months. Seroconversion rates are described as 95% after the first vaccine, increasing to approximately 99% after a second vaccine. Irrespective of her immunisation status, Bella is not yet currently immune to measles, relying instead on herd immunity. This is also important for children whose immune status precludes immunisation with MMR, as it is a live attenuated vaccine. These patients include children on high-dose steroids, those with HIV (and a CD4+ count <15%), those receiving chemo- or radiation-therapy.

The Australian Immunisation Handbook specifically mentions that, if given <12 months of age, there is still a need for two doses >12 months, as persistent maternal antibodies to measles (up to 11 months) may interfere with active immunisation.

Complications

Complications of measles are more common in children, especially <5 years. About 1 in 5 children with measles will have at least one complication.

Acute otitis media occurs in 10%.

Lower respiratory tract infection occurs in 6% of measles cases; pneumonia is the most common cause of death.

1 in 1000 children will have a measles encephalitis, with a high mortality rate (greater than 10%). Survivors have neurologic sequelae.

Measles-associated immune suppression, particularly in the developing world, confers an increased risk of mortality for three years post-infection.

Subacute sclerosing pan encephalitis occurs in about 1/10,000 cases of measles, manifesting as a progressive, eventually fatal, deterioration including ataxia and seizures, typically seven years after infection.

Differential diagnoses

What else could it be?

Having just described a petechial rash in a febrile child, we need to consider bacterial sepsis. Also recall the childhood febrile exanthems:

Exanthem 2 – Group A Streptococcus

Exanthem 3 – Rubella

Exanthem 4 – likely enterovirus

Exanthem 5 – B19 parvovirus

Exanthem 6 – Roseola infantum (HHV6)

Also, mycoplasma pneumonia (the great mimic!), EBV, adenovirus or other viruses should be considered, and it is reasonable to entertain the possibility of Kawasaki disease, Henoch-Schonlein purpura or other vasculitides too.

It’s particularly worth noting that a significant number of measles cases are contracted from measles endemic areas. That is, for cases in the developed world, it is (as always) essential to elicit a travel history. Likewise, consider measles as a differential diagnosis for the suspected Ebola patient in your isolation room (!).

Do we need to do any tests?

 Measles IgM serology is not an unreasonable test if measles is high up your list of differentials. Additionally, the measles virus can be found in blood, throat swabs or urine via PCR. Although they might not change management, the results will give public health some leads and some diagnostic clarity for the patient and their family.

If you’ve done a FBC and LFTs, you might see a leukopenia, a lymphopenia, and mildly raised transaminases.

Infectivity:

We’ve mentioned several times above the period for which measles is contagious. Most notably, measles can survive for up to 2 hours in air, but is rapidly inactivated by heat, light, and extremes of pH. It is reasonable to assume that each case will have associated a number of contacts. Measles is likely to be a notifiable disease in your jurisdiction; and the Public Health Unit may refer contacts for post-exposure prophylaxis, thus:

Post-exposure prophylaxis:

Immunocompromised patients or those patients <9 months should receive a dose of ‘Normal Human Immunoglobulin’ (NHIG). Patients over 9 months who have yet to receive their first does of MMR vaccine should receive a vaccine, as should those over 12 months if they’re yet to receive a second MMR vaccine, provided their first dose was greater than four weeks previously. Pregnant patients should be offered NHIG.

 

References:

Brem, J. Koplik Spots for the Record: An Illustrated Historical Note CLIN PEDIATR March 1972 11: 161-163,

Dobson, M. Disease. Oxford: BCS Publishing (2007) pp140-6.

Baxby, Derrick (July 1997). “Classic Paper: The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal mucous membrane”. Reviews in Medical Virology 7 (2): 71–74.

Koplik, H.: The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal mucous membrane. Arch. Pediat. 13: 918, 1896.

Kliegman R. (Ed.) Measles. Nelson essentials of pediatrics. Philadelphia, PA: Saunders/Elsevier. (2013)

Tasker, RC (Ed.) Exanthema 1; measles. Oxford Handbook of Paediatrics. Oxford: Oxford University Press. (2008) pp684

The Australian Immunisation Handbook 10th Edition (2013) via: www.immunise.health.gov.au

Measles – World Health Ogranisation. http://www.who.int/topics/measles/en/

Measles images via Center for Control of Disease – Public Health Image Library. http://phil.cdc.gov/phil/details.asp?pid=3168 & http://phil.cdc.gov/phil/details.asp?pid=3167 (Public domain)

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A Paediatric Trainee based in Queensland, Australia, Henry is passionate about Adolescent Medicine & General Paediatrics, with a strong interest in Medical Education & Clinical Teaching. An admitted nerd & ironman with a penchant for Rubik's Cubes & 'Dad jokes'.

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