Why measles is the master childhood infection
By Michael Mina
Measles was once so common it was considered a near right-of-passage into adulthood. Until the introduction of the measles containing vaccine in the 1960’s, the measles virus, arguably the most transmissible pathogen to infect humans, infected nearly 100% of children. Today, approximately 7 million cases continue to occur annually, or about 5% of the annual global birth cohort, reflecting a massive reduction in expected measles incidence of approximately 95%.
Though most children who become infected with measles recover within a few weeks after infection, physicians and public health experts have long recognized the dangers of becoming infected with the virus. Case fatality rates range from about 1 death per 5000 cases in high income countries to 1 death per 50 in low income countries.
Measles increases risk of other infectious diseases for 2-3 years
Although these mortality estimates are very high, particularly in low-income settings, recent research suggests that deaths associated with measles may be far higher. In a report (https://science.sciencemag.org/content/348/6235/694) we published in 2015, we looked at measles incidence data across countries and decades (spanning vaccine introduction) and compared measles incidence with rates of death from other non-measles infections. Surprisingly, we discovered that after large measles epidemics, the numbers of deaths from other infections (not including measles) were increased for 2-3 years. We concluded that measles may have long-term immune consequences that place children at elevated risk from other infectious diseases for years. In addition, we measured that measles virus infections may have been associated with as many as 50% of all childhood infectious disease deaths – a controversial finding that would place measles elimination and prevention of a measles resurgence as a top global priority.
With our interest piqued by that study, we later evaluated over 2200 measles cases in the UK via a retrospective review using the UK THIN database. We found (https://bmjopen.bmj.com/content/8/11/e021465) that after a measles infection, children had increased risk of requiring medical visits and being prescribed antibiotics for up to 5 years after measles.
These findings brought us to ask the obvious question – how? How could a famously acute viral infection like measles result in a years-long increased risk of other infectious diseases?
Measles is a lymphotropic virus – meaning it likes to infect and kill off lymphocytes – key immune cells that harbor our protective immune memories. We hypothesized that by killing off immune memory cells, measles could cause an “immunological amnesia” – whereby the immune system might recover functionally from measles but might forget the protective immunological memories it had previously acquired.
Measles causes immunological-amnesia
To test for immune amnesia, we looked towards the Netherlands. During an ongoing measles outbreak among a community who refuse vaccines on religious grounds, we collected a small blood sample at baseline and, if / when children became infected with measles during the epidemic, we returned and collected a follow up sample. By the end, we had 77 paired blood samples before and after measles. We then used a novel technology we have developed called VirScan that measures the presence and amounts of thousands of antibodies against hundreds of different pathogens, simultaneously. We found (https://science.sciencemag.org/content/366/6465/599) that measles was associated with large (20% - 70%) reductions of antibodies that protect against other infectious diseases. The most affected children lost over half of all of their pre-existing antibodies. We additionally tested this in measles infected macaques and found 50% declines in antibodies that lasted at least 5 months post-measles. Because antibodies are produced by long-lived memory cells that do not automatically return once lost, we believe that reacquisition of immune memory would require re-infections or revaccinations – which could take years, during which time children would be at elevated risk for other infectious diseases.
Measles, therefore, is a master childhood infection – orchestrating excess susceptibility to other diseases – and highlighting measles elimination as a key public health priority and measles vaccines as a “best buy” for public health, preventing not just measles but preserving immunity to all other infectious diseases at the same time.
Michael Mina is an Assistant Professor of Epidemiology and of Immunology & Infectious Diseases at the Harvard T.H. Chan School of Public Health and is an associate medical director in clinical pathology, focusing on infectious disease diagnostics, at the Brigham and Women’s Hospital / Harvard Medical School. His work aims to understand the interface of immunity and public health, particularly surrounding vaccines and childhood infectious diseases.