5.1 Clinical aspects

5.1.1 Incubation

The average incubation period is 10 days (10 to 14 days) from the date of exposure to the virus to the onset of the first clinical signs. It can be as short as 7 days and in very rare cases can be up to 23 days. 

5.1.2 Clinical presentation

Prodromal phase

This phase lasts 2 to 4 days.

• Fever with temperature over 38 °C, often over 39 °C
• Cold-like symptoms: non-productive cough and/or coryza (runny nose) and/or conjunctivitis (red eyes with discharge);
• Koplik’s spots: tiny bluish-white spots (2 to 3 mm) on an erythematous base, found on the inside of the cheeks. They appear 1 to 2 days before the rash, and last 2 to 3 days. This sign is specific of measles infection but is not always present. Observation of Koplik's spots is not required for diagnosing measles.

Eruptive phase

Begins an average of 14 days after exposure and lasts 4 to 6 days.

• Erythematous, nonpruritic maculopapules that blanch under pressure; they may coalesce into patches separated by healthy skin
• The rash starts at the forehead and spreads progressively downward to the face, neck, trunk, abdomen, and lower limbs over 3 to 4 days

At the same time, the cold-like symptoms improve. If there are no complications, the fever disappears once the rash reaches the feet. The rash then gradually disappears, and the skin desquamates.

Recovery phase

Pigmented skin takes on a striped appearance and then desquamates intensely for 1 to 2 weeks. 

5.1.3 Differential diagnosis

Rubella [1]Citation 1.World Health Organization (WHO). Rubella vaccines: WHO position paper – July 2020. Wkly Epidemiol Rec. 2020;95(27):301-324. https://iris.who.int/bitstream/handle/10665/332950/WER9527-eng-fre.pdf?sequence=1  (accompanied by posterior cervical lymphadenopathy), erythema infectiosum, roseola infantum (transient rash involving mainly the trunk), infectious mononucleosis, scarlet fever, epidemic typhus, certain rickettsial infections, medication-related erythema, etc.

5.1.4 Acute complications

Measles can have several complications aCitation a.Complications are related to epithelial changes (pulmonary and gastrointestinal) and to temporary, measles-related immune suppression. , [2]Citation 2.Perry RT, Halsey NA. The clinical significance of measles: a review. Orenstein WA, ed. J Infect Dis. 2004;189 (Suppl 1):S4-S16. doi: 10.1086/377712 , [3]Citation 3.World Health Organization (WHO). The Child, Measles and the Eye. Geneva, Switzerland: WHO; 2004. WHO/EPI/TRAM/93.05. 
https://s3.amazonaws.com/wp-agility2/measles/wp-content/uploads/2013/06/Child-Measles-Eye.pdf . 75% of measles cases experience at least one complication. Deaths are due to the most severe complications.

Respiratory and ENT complications (viral or bacterial)

In children under 5 years, these are the most common complications, both during and after the disease.

In adults, pulmonary complications are less common, but more severe than in children.

• Acute otitis media

5 to 15% of measles cases are complicated by acute otitis media [2]Citation 2.Perry RT, Halsey NA. The clinical significance of measles: a review. Orenstein WA, ed. J Infect Dis. 2004;189 (Suppl 1):S4-S16. doi: 10.1086/377712 .  

• Pneumonia

5 to 10% of measles patients develop pneumonia.

The pneumonia may be complicated by empyema (collection of pus between the lung and the pleura). 

• Croup (acute laryngotracheobronchitis)

Croup is a potential complication in children. Most children have moderate, self-limited disease lasting 2 to 5 days, but it is important to stay vigilant and continue monitoring children during this period, because their general and respiratory status can deteriorate rapidly.
Symptoms of croup include a characteristic "barking" cough, hoarse crying or voice, difficulty breathing, and a high-pitched inspiratory wheeze (inspiratory stridor) caused by inflammation and narrowing of the larynx.
Croup is considered mild if the stridor occurs when the child is agitated or crying but disappears when the child is calm, there are no signs of respiratory distress, the child is able to drink, and the oxygen saturation (SpO₂) is > 94%.
Croup is considered moderate or severe if there is stridor at rest (continuous) and/or is accompanied by signs of respiratory distress and/or the child is unable to drink and/or is hypoxic (SpO₂ ≤ 94%).   

Ocular complications [2]Citation 2.Perry RT, Halsey NA. The clinical significance of measles: a review. Orenstein WA, ed. J Infect Dis. 2004;189 (Suppl 1):S4-S16. doi: 10.1086/377712

Eyes are usually red with a watery discharge. These symptoms are typical and benign and are not considered a complication.

The most common ocular complications are bacterial infections and xerophthalmia due to vitamin A deficiency bCitation b.In addition to ocular lesions, vitamin A deficiency weakens the immune system. .

Diseases that cause corneal lesions (keratoconjunctivitis, keratitis, and xerophthalmia) may compromise the eye integrity and can progress to irreversible blindness. 

• Purulent conjunctivitis
  Purulent conjunctivitis is the most common – and most benign – complication.
• Infectious keratitis and keratoconjunctivitis 
  These infections are less common. They cause the cornea to lose its transparency or shininess. When a fluorescein test can be done to confirm the diagnosis, the exam shows a single corneal erosion or ulcer cCitation c.The normal cornea does not stain with fluorescein; if there is epithelial loss, fluorescein stains the lesion green. .
• Xerophthalmia 
  Xerophthalmia can be detected in any of the following stages: Bitot’s spots (whitish deposits of keratin on the bulbar conjunctiva of the eye), corneal xerosis (dry, dull cornea), keratomalacia (opaque, softened, or perforated cornea). 

Gastrointestinal complications

• Diarrhoea
  Diarrhoea is a common complication during and after the disease. It can rapidly lead to dehydration, especially in children.
• Oral lesions (stomatitis)
  Stomatitis is usually due to Candida albicans. Herpetic gingivostomatitis may occur.

Neurological complications

• Seizures
  Seizures are the most common neurological complication. They are in most cases simple febrile seizures.
• Acute measles encephalitis 
  This is a rare complication, occurring in 1 out of every 1000 to 2000 cases, about 3 to 6 days after the rash first appears [2]Citation 2.Perry RT, Halsey NA. The clinical significance of measles: a review. Orenstein WA, ed. J Infect Dis. 2004;189 (Suppl 1):S4-S16. doi: 10.1086/377712 . Symptoms include: recurrence or persistence of the fever, meningeal symptoms, impaired consciousness and seizures. 

5.1.5 Other complications

Immediate

Thrombocytopenic purpura may develop 3 to 15 days after the rash appears.

Post-measles

• Measles can lead to malnutrition in the weeks following infection.
• Children are at higher risk of death for several years, due to the temporary immune depression following measles (See Section 1.1.4).
• Noma (gangrenous gingivostomatitis) is a rare but extremely serious complication in malnourished children under age 4 years; it is not specific to measles. It begins with severe, foul-smelling oral ulcers.

Delayed

Subacute sclerosing pan-encephalitis is a very rare complication (1/100,000 cases) that occurs long after the initial infection (an average of 7 years) [4]Citation 4.Moss WJ. Measles. Lancet. 2017;390(10111):2490-2502. 
doi: 10.1016/S0140-6736(17)31463-0 .

Special case: pregnant women

Measles can increase the risk of complications – in particular, miscarriage, premature birth, low birth weight, and even maternal death.

5.1.6 Co-morbidities

Acute malnutrition

Malnourished children are at risk of developing severe complications.

HIV infection

Measles tends to be severe and prolonged in immunocompromised individuals. The skin rash may be absent [5]Citation 5.World Health Organization (WHO). Measles Outbreak Guide. Geneva: WHO; 2022. https://www.who.int/publications/i/item/9789240052079 .

There are two particularly serious complications: giant cell interstitial pneumonia and measles inclusion-body encephalitis. The main cause of death in children is pneumonia, and in adults, encephalitis.