Introduction

Measles is known to be a single-stranded RNA virus in the genus Morbillivirus of the family Paramyxoviridae that can be transmitted via droplets in the air. This is then transported into the respiratory epithelium, home to its duplication. Consequently, this leads to the lymphoid tissues and the entire body. Measles’ key property in distorting the immune system, attacking the host severely to allow the virus to occupy in the body. Patients with measles are expected to sustain a fever for up to 10 days and rashes to appear for 14 days.¹

Before the vaccination for measles was discovered, there were an estimated 30 million cases worldwide with more than 2 million deaths. Measles is often seasonal, it outbreaks peaking late winter and early spring.²

The measles virus (MV) is part of a group of viruses that includes several animal-infecting members, like the Canine Distemper Virus. Although primates can be infected with the measles virus in vitro, humans are the sole natural reservoir, presenting a unique opportunity for potential global eradication. The complete sequencing of the measles virus genome has enabled the identification of distinct wild-virus lineages, each associated with specific geographical distributions. This genomic information is crucial for tracing the origins of outbreaks. Despite genetic diversity among strains, the measles virus is classified as monotypic, and immunity from vaccination is effective against all variants.³

The measles virus can remain infectious in the air or on surfaces for up to two hours, making it highly transmissible. An infected person can spread the virus to 90% of their unvaccinated close contacts, and the period of infectivity ranges from four days before to four days after the rash appears. Measles outbreaks often result in severe complications and fatalities, especially among malnourished children. In countries approaching measles elimination, imported cases from other regions still pose a significant risk for new infections.⁴

The measles virus can impact the central nervous system (CNS) both during an active infection and after the infection has become latent. The CNS complications associated with measles include primary measles encephalitis (PME), acute post-infectious measles encephalomyelitis (APME), measles inclusion body encephalitis (MIBE), and subacute sclerosing panencephalitis (SSPE).

There are several ways in which measles can enter the human brain. They may enter through receptors, known as the signalling lymphocytic activation molecule (SLAM) receptor, present on immune cells such as dendritic cells, thymocytes and lymphocytes. Alternatively, a mutated version of the measles virus can tend to enter the brain without the necessity of using receptors. Lastly, measles can enter the brain through the bloodstream by infecting the cells that form the blood-brain barrier (BBB) and then crossing into the CNS, or by infected lymphocytes carrying the virus through the BBB into the brain.⁵

Pathophysiology of measles

A particularly notable and hazardous feature of measles pathogenesis is its ability to alter the immune system in infected individuals. During the acute infection phase, measles leads to immunosuppression through immune amnesia. 

Research by Rory D. de Vries on non-human primates revealed that the MV replaces the host’s pre-existing memory cells with new, MV-specific lymphocytes. This results in strong immunity against MV but increased susceptibility to other pathogens that can impair immune function. For instance, the influenza virus damages the cells lining the airways, heightening the risk of secondary bacterial infections, such as pneumonia.

MV infects host cells by fusing with their plasma membranes in a receptor-dependent manner. In the respiratory tract, MV first targets alveolar macrophages in the lungs, which typically engulf and destroy foreign particles, also known as phagocytosis. 

These macrophages have a glycoprotein called SLAM that MV exploits to bypass phagocytosis, allowing the virus to release its genome directly into the cell cytoplasm. Instead of destroying MV, infected macrophages transport it to nearby lymph nodes. There, the virus encounters memory T-cells and B-cells – crucial components of the adaptive immune system, which detect antigens and create long-lived memory cells for future protection, enabling a faster and stronger immune response upon re-exposure. 

However, following measles infection, the immune system's memory cells are drastically altered. Pre-existing memory cells are wiped out, replaced by new MV-specific lymphocytes.⁶

Common symptoms of measles

Initial symptoms of measles include the following:

1. Fever
2. Cough
3. Runny nose
4. Conjunctivitis
5. Sore eyes
6. Loss of appetite

Additionally, apparent spots in the mouth may be present, usually lasting for a few days. Then the rash would also appear two to four days after initial symptoms. If there is any kind of suspicion or others have measles, going to a doctor and consulting is advisable to prevent transmission of the disease as it could be fatal. 

Neurological complications of measles

Measles can lead to several neurological complications, Encephalitis could be the most significant. Encephalitis refers to inflammation of the brain, and in some cases, the spinal cord is also affected. This condition can arise through several mechanisms:

1. Infectious Encephalitis – MV can directly invade the brain tissue, harming neurons and brain cells
2. The immune system produces antibodies that mistakenly attack healthy brain cells, leading to inflammation
3. Reactivation of dormant infections – dormant infections can reactivate and target the brain, contributing to infectious encephalitis
4. Immune response triggered by viruses or vaccines may result in the immune system unintentionally targeting healthy brain tissue, causing inflammation and damage to the nervous system
5. Acute disseminated encephalomyelitis (ADEM) causes inflammation but targets the myelin, which is responsible for conducting electrical signalling between neurons, typically affecting younger individuals

Long-term neurological complications

Subacute sclerosing panencephalitis (SSPE) is another complication of measles that directly affects the central nervous system. It typically affects younger children when their immune system is more vulnerable. 

In the later stages of SSPE, individuals may find themselves unable to walk due to increasing muscle stiffness or spasms. As the condition progresses, there is a gradual decline in physical health, eventually leading to a coma and ultimately a persistent vegetative state. Fatal outcomes often occur due to complications like fever, heart failure, or the inability of the brain to regulate the autonomic nervous system.⁷

Lastly, measles inclusion body encephalitis (MIBE) can develop in individuals who have previously had measles, particularly those with compromised immune systems. It typically emerges months to years after the initial measles infection. MIBE involves inflammation in the brain, causing progressive neurological symptoms such as confusion, seizures, and paralysis. The condition occurs when the MV persists in the brain, damaging neurons and forming distinct inclusion bodies. Unfortunately, MIBE often carries a poor prognosis, with most cases resulting in severe disability or death.⁸

Diagnosis of measles and its neurological complications

Measles is characterised by a generalised maculopapular rash lasting for at least three days, a fever of 38.3°C or higher, and a result of the following symptoms: 

• Cough
• Conjunctivitis
• Koplik's spots
• Rash spreads from the head to the entire body 

To diagnose viruses via labs, the confirmation involves detecting measles-specific IgM antibodies. However, this criterion is excluded if the patient was vaccinated with a measles-containing vaccine 8 days to 6 weeks before the sample collection. Additionally, another less commonly used method is detection of the wild-type measles virus genome in an appropriate clinical specimen to confirm the diagnosis. These criteria help ensure accurate diagnosis and differentiation from vaccine-related responses.⁹

The Figure below highlights the progression of measles in MRI scans with the span across 1,7, 15, and 26th day.

Figure 1: MRI scans illustrating changes in the brain caused by measles over the course of 26 days.

Treatment and management

Presently, there is no universally accepted treatment for measles. Nonetheless, antivirals such as ribavirin and interferon-α are occasionally given either separately or in combination. The existing literature on these treatments is sparse, primarily consisting of clinical case studies. These studies often advocate for ribavirin, particularly at elevated doses. Another possible treatment strategy involves the administration of immunoglobulins, especially those targeting measles. 

Prevention

As there is no current treatment, the most effective way to combat measles is through prevention by vaccination.¹⁰ It is recommended to boost self with two doses, as research has shown that the measles, mumps, rubella (MMR) vaccine is approximately 97% effective at preventing measles, while a single dose is 93% effective. Additionally, the measles, mumps, rubella, and varicella (MMRV) vaccine is also available and approved for children between the ages of 12 months and 12 years.¹¹

 Vaccination not only protects individuals but also contributes to herd immunity, reducing the risk of outbreaks and making measles eradication a global public health goal.

Summary

• Measles is a single-stranded RNA virus transmitted through the air with genus Morbillivirus and the family Paramyxoviridae. It infects the respiratory epithelium and spreads throughout the body, causing significant disruption to the immune system.
• The measles virus can remain infectious in the air or on surfaces for up to two hours. It can infect 90% of unvaccinated close contacts, with a period of infectivity ranging from four days before to four days after the rash appears.
• Measles can cause several CNS complications, including primary measles encephalitis, acute post-infectious measles encephalomyelitis, measles inclusion body encephalitis, and SSPE.
• Measles causes immunosuppression through immune amnesia, replacing pre-existing memory cells with new, measles-specific lymphocytes, increasing susceptibility to other infections.
• The virus infects host cells via the SLAM receptor, bypassing phagocytosis in alveolar macrophages, and spreads to lymph nodes altering memory T-cells and B-cells.
• Initial symptoms include fever, cough, runny nose, conjunctivitis, sore eyes, and loss of appetite, followed by a rash appearing 2-4 days later. Koplik's spots may also be present.
• There is no standardised treatment for measles, but antivirals like ribavirin and interferon-α may be used. Vaccination is the primary prevention method, with the MMR vaccine being 97% effective with two doses and 93% effective with one dose. The MMRV vaccine is also available for children aged 12 months to 12 years.