Measles

Also referred to as rubeolla, or morbilli; Highly Communicable Disease principally affecting children characterized by a prominent exanthema, a high fever, an enanthem, coryza, cough, and conjunctivitis; The temporal sequence of disease manifestations can be described according to four (4) overlapping stages comprising:

• Incubation period of 10-14 days with little or no symptoms;
• Prodromal stage lasting 3-5 days characterized by catarrhal symptoms and the pathognomonic Koplik’s spots;
• Exanthematous stage characterized by the advent of (an initially facial) maculopapular rash which spreads in a cephalocaudal direction and associated with multi-systemic, but predominantly respiratory complications;
• Stage of Resolution characterized by extensive skin desquamation, post-measles stain and anergy.

Measles is almost synonymous with ‘misery’ or a miserable look of acute prostration in the affected child. In the pre-vaccine era, the disease was “once an inevitable experience during childhood” (frequently with devastating outcome) in many communities of the world!... Remember the old Indian adage, that you can only count the number of your children, after a measles epidemic)!!!!

Measles virus:

• Single-stranded, lipid-enveloped RNA virus
• Belongs to the family Paramyxoviridae, genus morbillivirus (similar to the virus that causes rinderpest virus in cattle and the common canine distemper virus)
• Human is the only host of the measles virus (with preventive implications)

Measles virus has 6 important structural proteins, of which 2 are the most immunologically relevant:

• Haemmaglutinin protein (H-protein): Induces neutralizing antibodies
• Fusion protein (F-protein): Limits virus proliferation

Global Endemicity and Impact of Immunisation:

• Measles was globally endemic in the pre-vaccine era, but its epidemiology has shifted due to widespread immunisation since 1963.
• In developed countries, decline in measles incidence before widespread immunisation was attributed to improved living conditions, sanitation, healthcare, and nutrition. That has hardly been the case in Nigeria as well as several other developing countries
• In the US, the incidence dropped from 313/100,000 (1956-1960) to 1.3/100,000 (1982-88).
• Measles remains a common cause of hospitalization and emergency room visits.

Epidemiological Factors Influencing Occurrence:

• Seasonal Factors: Outbreaks in tropical Africa coincide with the dry season.
• Age: In tropical communities, the disease primarily affects infants and toddlers aged 6-24 months, with a peak incidence between 9-18 months.
• Nutritional Status: Complications and mortality are higher in malnourished children, with vitamin A deficiency exacerbating ophthalmological complications.
• Immunisation Status: There is an inverse relationship between measles incidence and immunisation rates.
• Others: Factors such as zinc deficiency and religious beliefs may play a role in measles occurrence.

• Portal of Entry: The respiratory tract is the primary entry point, occasionally through the conjunctiva. Transmission occurs via:
• Small droplet aerosol inhalation
• Contact with large droplets
• Self-inoculation
• Infectivity Period: Infectivity starts around 3-4 days before the rash develops and lasts until the 5th to 6th day after the rash appears.
• High Infectivity Rate: Over 90% of unimmunized individuals exposed to the virus will develop symptomatic disease.
• Aerosol Transmission: Infectivity can occur even without direct contact with an affected individual. Suspended aerosols can persist in a room for up to an hour after an affected person has left.
• Secondary Transmission: Secondary cases can arise from contact with surfaces contaminated by aerosols, such as health workers' offices or hospital beds.

• Four Overlapping Phases: Measles progression is characterized by these stages:
• Incubation Period: Involves virus multiplication and migration to regional lymph nodes.
• Dissemination of the virus to the reticuloendothelial (RE) system constitutes the primary viremia.
• Secondary viremia follows, spreading the virus to the skin and epithelial surfaces.
• Prodromal Period: Involves virus replication-induced cellular necrosis.
• Giant cell formation occurs, represented by Warthin–Finkeldey Giant cells resulting from fusion of infected cells.
• Virus replication continues in various body tissues through this phase.
• Viral shedding begins during this period, leading to positive virus culture from respiratory secretions and peak infectivity.
• Exanthematous Phase: Characterized by sero-conversion and regression of virus replication.
• Antibody formation takes place, leading to subsidence of symptoms.
• At the cellular level, virus infection of CD4+T cells leads to suppression of the immune system or anergy.
• This anergic state corresponds with the recovery phase of the disease.
• Recovery Phase: Occurs as the immune system responds to the infection.
• During recovery, the immune system overcomes the suppression and mounts an effective immune response against the virus.
• At this stage, clinical symptoms gradually subside, and the patient's overall health improves.
• While the anergic state was beneficial to prevent an excessive immune response during the acute phase, recovery involves a return to immune functionality.

• Pathological Hallmark - PANMUCOSITIS: The hallmark of measles pathology is panmucositis, involving cellular necrosis across various epithelial surfaces. Microvascular involvement is observed in the skin, oro- and nasopharynx, tracheobronchial tree, buccal mucosa, and tonsils. Microvascular pathology is accompanied by lymphocytic infiltration.
• Maculopapular Rash: The maculopapular rash develops due to epithelial capillary proliferation, leading to macule formation, and lymphocytic and PMN (polymorphonuclear) infiltration resulting in papule formation.
• Histological Characteristics: The rash exhibits dyskeratosis, intracellular edema, and the presence of multi-nucleated epidermal syncytial giant cells with numerous nuclei (up to 26 or more). Some of these giant cells contain virus particles or antigens.
• Warthin-Finkeldey Giant Cells: Fusion of infected cells leads to the formation of the pathognomonic Warthin-Finkeldey giant cells, which can have up to 100 nuclei. These giant cells display intracytoplasmic and intranuclear inclusion bodies.
• Lymphoid Hyperplasia: Measles-associated lymphadenitis is due to lymphoid hyperplasia. This hyperplasia is attributed to the spread and replication of the virus within the lymphoreticular tissue.
• Respiratory Tract Affection: Panmucositis affects nearly all mucosal surfaces, particularly the respiratory tract. This results in various respiratory conditions:
• Rhinitis
• Nasopharyngitis
• Laryngotracheitis (LTB)
• Pneumonia, initially viral interstitial Hecht giant cell pneumonia
• Secondary bacterial broncho- or lobar pneumonia, sometimes with pleural effusion/empyema and pneumothorax

• Incubation Period: Occurs 10 – 14 days after virus acquisition and is generally associated with few or no symptoms.
• Prodromal Period: Lasting the next 3 – 5 days, this phase is marked by:
  • Emergence of catarrhal symptoms
  • Fever
  • Dry hacking cough
  • Conjunctival inflammation
  • Appearance of characteristic Koplik's Spots on the buccal mucosa towards the end of this phase. These spots are pathognomonic, rarely lasts for more than 18-36hrs and are found in specific locations such as the mucosal aspect of the cheek, hard or soft palate, conjunctival mucosa, or sometimes on the tear glands.
  • Cough becomes increasingly severe with high fever and breathlessness as the prodromal stage progresses.
• Exanthematous Stage: Characterized by the emergence of a maculopapular rash that spreads in a cephalo-caudal direction. The rash:
  • Starts as faint macular lesions
  • Becomes more maculopapular as it spreads downwards
  • Most of the systemic symptoms, especially those related to the respiratory system, are associated with this stage.
• Stage of Resolution: Associated with anergy, leaving the patient vulnerable to tuberculosis and other infectious diseases. The stage is characterized by:
  • Disappearance of the rash
  • Skin desquamation
  • Post-measles stain

Other viral, presumed viral exanthems, or immune-mediated diseases:

• Rubella (German Measles): Less toxicity with a temperature usually below 38.5°C; prodrome has a different course with no specific intraoral lesion.
• Roseola Infantum (Exanthem Subitum): Features centripetal distribution of rash, febrile incubation period, and less toxicity despite high temperature; fever crashes the exanthematous stage.
• Adenovirus Infection: Presents with nasopharyngeal symptoms, throat inflammation, cervical lymphadenopathy, conjunctivitis, paroxysms of cough, and occasionally haematuria (hemorrhagic cystitis) due to Adenovirus type 11.
• Non-Polio Enteroviral Exanthems: Caused by viruses like Echo virus, Coxsackievirus, and ungrouped enteroviruses (e.g., 70 & 71) virus (ref., Boston exanthem).
• Ebstein-Barr Virus Infection (Infectious Mononucleosis):
• Kawasaki Disease: Characterized by centrifugal full skin thickness desquamation, extremity oedema, thrombocytosis, and lacks a specific intraoral lesion.

Non-viral exanthems:

• Streptococcal Infection (Group A Beta-haemolytic Strept): Presents with scarlatiniform (sandpaper) rash, distinct papular lesions, pharyngitis, cervical lymphadenopathy, and increased ASO titre.
• Mycoplasma Pneumoniae: Generally mild with increased ESR and cell count.
• Rocky Mountain Spotted Fever (RMSF): Spirochaetal disease with a prominent symptom of headache.

Non-infectious skin eruptions:

• Drug Eruptions: Antecedent ingestion of the drug, e.g., ampicillin.
• Serum Sickness: Antecedent transfusion of blood and blood products.

In general, complications of measles can be categorized as immune-related (anergy) and respiratory:

General Complications:

• Anergy: Suppression of the immune system.
• Malnutrition: Affects overall health and recovery.
• Extensive Ulcerated Skin Lesions:
• Purpura Fulminans and DIC: Disseminated intravascular coagulation.

Systemic Complications:

• Respiratory Complications: Including Acute Otitis Media (AOM), Croup, Tracheobronchitis, Bronchiolitis, and Pneumonia, which can be associated with necrotizing pathogens.
• Neurologic Complications: Involvement of the nervous system, including:
• Encephalitis: Inflammation of the brain that can lead to seizures, altered consciousness, and neurological deficits.
• Subacute Sclerosing Panencephalitis (SSPE): A rare, progressive brain disorder that can develop years after measles infection, leading to intellectual and neurological deterioration.
• Alimentary/Gastrointestinal Complications: Affecting the digestive system:
• Diarrhea: Gastrointestinal symptoms such as diarrhea can occur, leading to dehydration and electrolyte imbalances.
• Cardiovascular Complications: Involving the heart and blood vessels:
• Myocarditis: Inflammation of the heart muscle, which can lead to heart rhythm abnormalities and heart failure.
• Pericarditis: Inflammation of the lining around the heart (pericardium), causing chest pain and discomfort.
• Ophthalmic Complications: Affecting the eyes:
• Conjunctivitis: Inflammation of the conjunctiva, the thin layer covering the white part of the eye and the inner eyelid.
• Keratitis: Inflammation of the cornea, the clear front surface of the eye, leading to eye redness, pain, and vision disturbances.

The diagnosis of measles is primarily clinical, characterized by:

• Acute febrile illness with a specific progression of the rash that later resolves with skin desquamation.
• Presence of pathognomonic oral lesions known as Koplik's spots.
• Seasonal dry outbreaks in tropical regions.

Laboratory corroboration can include the following microbiologic and serological methods:

1. Giant Cell (Warthin-Finkedey) Detection: Giant cells can be identified in nasal and nasopharyngeal secretions during the prodromal stage of the disease.
2. Serological Diagnosis: Measles-specific IgM antibodies appear around 2 days after the rash onset and persist for about 4 weeks. Acute and convalescent IgG titres show a 4-fold rise within 2 weeks to 1 month.
3. Viral Isolation: The virus can be isolated from blood, urine, and respiratory secretions (nasopharyngeal or respiratory) using suitable cell cultures like Human Embryonic Kidney (HEK) cells or their simian equivalents.
4. PCR: Polymerase Chain Reaction (PCR) is primarily a research tool for detecting measles virus genetic material.

Non-specific laboratory findings associated with measles include:

• Leukopenia with more pronounced reduction in lymphocytes compared to neutrophils.
• Elevated ESR (Erythrocyte Sedimentation Rate) and CRP (C-reactive protein), which can be normal in uncomplicated cases but typically increase in cases of secondary bacterial infections or bacterial pneumonia.
• Anergy-related false negative reaction in tuberculin skin test.

In uncomplicated cases of measles and those with minimal complications or modified measles, the management is mainly supportive and includes:

• Indications for admission should be assessed based on the severity of symptoms and complications.
• Fluids for satisfactory hydration, preferably oral. Caution should be exercised due to the risk of SIADH (Syndrome of Inappropriate Antidiuretic Hormone).
• Feeds with a focus on calorie-dense, protein-rich options along with added micronutrients such as Zn, Vitamins A, C, D, E, selenium, etc.
• Fever control with symptomatic management using acetaminophen (paracetamol).
• Oxygen therapy as indicated by clinical evidence of hypoxemia and SpO2 levels below 92%.

Management of Complications:

• Use of antiseptic bath lotions with the addition of chlorhexidine (such as savlon) to bath water and provision of Vitamin A supplements.
• For complications like Acute Otitis Media (AOM) or bacterial pneumonia, antibacterial agents are prescribed. There is no specific antiviral agent for measles.
• Management of febrile seizures involves differentiation from meningitic or encephalitic complications and appropriate management.
• Encephalitis cases may present with fever, irritability, lethargy, and coma associated with lymphocytic pleocytosis. About 15% may experience severe long-term sequelae like mental retardation, motor disabilities, and deafness.
• Encephalitis in immunocompromised individuals, especially those with HIV/AIDS and lymphoreticular malignancies, can lead to direct damage to the brain parenchyma by the virus.

The prognosis of measles has been significantly improved due to widespread immunization, reducing the risk of measles-associated deaths.

Immunization is the cornerstone of measles prevention:

• Considering measles as potentially 'eradicable' is grounded in the availability of the vaccine.
• Passive immunization: Early administration of immune globulin is recommended in potentially infected cases, especially those with immunocompromised status.
• Active immunization (using live vaccine):
  • MMR vaccine (Measles, Mumps, Rubella vaccine) is a key preventive measure.
  • The vaccine is contraindicated in certain situations:
  • Individuals with severe immunodeficiency.
  • Pregnant women (due to theoretical risk to the fetus).
  • Immunosuppressed individuals (e.g., those receiving high-dose corticosteroids).
  • Those with a history of anaphylactic reaction to neomycin or gelatin (as these components are present in the vaccine).
  • Specific vaccine strains have considerations:
  • Contraindicated in Edmonstein B, Shwartz, and Moraten strain: These refer to specific strains or versions of the measles virus that were used in earlier versions of the measles vaccine. If a person received any of these specific strains as part of an older measles vaccine, it might be contraindicated for them to receive the MMR vaccine due to potential interactions between the different vaccine strains.
  • The timing of vaccine administration in our NPI (National Immunization Program) is strategic:
  • The rationale for this schedule is to provide effective immunity during vulnerable periods.