May 6, 2020

Measles Infection or Measles Vaccine?

Growing evidence that natural infection by measles, but not vaccination, results in immune-system amnesia
Natural infection by measles—but not the measles vaccine—may compromise the immune system for many years.

Reference

Mina MJ, Kula T, Leng Y, et al. Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Science. 2019;366,(6465):599-606.

Objective

To assess whether “immune amnesia,” which is a reduction in the diversity of the antibodies toward various pathogens (ie, the antibody repertoire), occurs with measles infection.

Design

The study authors analyzed the antibody repertoire in children before and after natural infection with measles virus, as well as in children before and after measles vaccination.

Participants

Researchers evaluated 77 unvaccinated children (average age 9 years) before and then 2 months after natural measles infection during the 2013 measles outbreak in the Netherlands. The 77 infected children were divided into mild (n=34) and severe (n=43) cases for analysis. The children and their families are members of an Orthodox Protestant community in which parents had opted to not vaccinate their children for religious reasons. Controls included 5 unimmunized children from this community who never contracted measles over the course of the study and who were tested at the same intervals as the infected group. Other control groups (all uninfected) used for comparison included: A) age-matched controls tested at similar intervals (n=28), B) age-matched controls with samples collected 1 year apart (n=31), and C) adults tested at time intervals similar to the measles-infected children (n=22).

Outcome Measures

Researchers used a technology called VirScan, which tests for antibody epitopes to specific organisms, to test the diversity of antibodies to known human pathogens, both viral and bacterial. They also quantified antibodies to each epitope. They did this both before and after infection.

Key Findings

After the disease, the children lost, on average, about 20% of their antibody repertoire, signaling a loss of memory of prior pathogenic exposures. Between 11% to 73% of the antibody repertoire was eliminated after infection; the biggest drops tended to occur in children with the severest cases of measles. The 5 children without infection had no drop in antibody repertoire.

This effect was not found in the other controls either. No loss of antibodies was seen in children after they received a vaccination against measles.

Practice Implications

A second closely related study was published simultaneously with this study and should also be mentioned. A research group led by Velislava Petrova analyzed blood from 26 of the same children who were part of this initial cohort.1 They used genetic sequencing to study the B cells isolated from these children. The measles virus is known to infect B cells, which make antibodies. They found that children who had a naturally acquired measles infection had a reduced diversity of memory B cells, the subset that quickly responds to infections through production of antibodies that have been made before. The diversity of a second type of B cell, the nonspecific naïve B cells in bone marrow, which normally fight infections unfamiliar to the immune system, also declined. It was as if after a measles infection, the immune system was left in an immature state with a kind of amnesia regarding infections that it had already learned to fight and was slow to respond to new infections.1

The premise that natural infection may not be optimal for immune function overall challenges basic assumptions of natural medicine. Corroborating this, however, is evidence suggesting that the vaccine may have the opposite effect. Counter to our expectations, observational studies show that there may be protection from a broad range of infections in those who receive measles vaccination.

Since 1996 there have been reports from developing nations that suggest the measles vaccine cut deaths from all other infections combined by one-third, mainly by protecting against pneumonia, sepsis, and diarrhea.2,3 In 2005, Veirum and colleagues reported that measles-vaccinated children had a 49% decreased risk of fatality from infectious disease.4 They found that in children with pneumonia, there was a 72% decreased risk of dying in those who had been vaccinated.

The premise that natural infection may not be optimal for immune function overall challenges basic assumptions of natural medicine.

In a randomized trial conducted from 2003 to 2009 in Guinea-Bissau, children received either their routine dose of measles vaccine at 9 months of age or an additional dose of measles vaccine at 4.5 months of age along with the routine dose at 9 months. The children had received 3 DPT (diphtheria, pertussis, and tetanus) shots prior to starting this study. Compared to children who received measles vaccine at 9 months of age, children who received the vaccine at 4.5 months and 9 months had a 30% decrease in all-cause mortality up to 3 years of age. Less than 5% of this reduction in mortality could be explained by measles prevention.5

One possible explanation might be simply that the measles vaccine lowered measles incidence in children between 4.5 months and 9 months old and that doing so prevented immune-memory damage.

It has become quite clear over recent years that catching measles, the actual disease, injures the immune system, leaving the patient more vulnerable to infection long afterwards. Mina wrote in 2017 that the “invisible hallmarks of measles infections [are] increased vulnerability to non-measles infections in nearly all children for weeks, months, or years following acute infections. By depleting measles incidence, vaccination has had important indirect benefits to reduce non-measles mortality.”6

Some research suggests that this immune suppression lasts as long as 30 months. An interesting paper published in June 2019 used historical medical records to look at 3 distinct periods of time when past outbreaks of measles and whooping cough overlapped.8 In a period between 1904 to 1912, risk of whooping cough in those who had contracted measles increased 85-fold. Between 1922 and 1932, whooping cough risk increased 10-fold after a measles infection. And then between 1946 and 1956, whooping cough risk increased 36-fold post measles infection.7

A study of children in the United Kingdom, published in November 2018, compared risk of infectious disease in 2,228 children who had contracted measles against nearly 20,000 children who had not. Risk of nonmeasles infections persisted for the full 5 years during which the study collected data. During the first month, risk of infection was 43% higher in the measles kids, and at 5 years it was still 15% higher.8

Parents who are wary of vaccinating their children are well represented in naturopathic patient populations, and we are likely to see their unvaccinated children after they have had measles. We should be mindful that current research has clearly associated greater infection risk in those who have had a natural infection of measles, and that this risk lasts for many years after the measles infection.

The researchers are pondering the wisdom of revaccinating children who have had measles against all childhood diseases, essentially starting the vaccination schedule over. Of course, even if such a practice were proven useful, compliance would be low.

Prior to this idea that measles causes immune amnesia, there was evidence that the measles vaccine itself might act as an immune stimulant. A 2016 paper described how the measles vaccine activated the immune system in a way similar to bacille Calmette-Guérin (BCG).10 Both lower all-cause mortality through protection against nontargeted pathogens.9

A March 2019 clinical trial reported that topical application of MMR (measles, mumps, and rubella) vaccine in children being treated for juvenile recurrent respiratory papillomatosis (RRP) significantly lowered HPV (human papillomavirus) viral load.10

These recent findings stand in stark contrast to the general understanding that many of us absorbed during our naturopathic training. I left school assuming that exposure to childhood illnesses was necessary to “train” the immune system, increasing its resilience, and was somehow beneficial to long-term health.

There was a concern raised a decade ago that such “untrained” immune systems might be more prone to autoimmune disease. There are distinct examples of specific vaccines leading to autoimmune problems: the 1976 swine flu vaccine leading to Guillain-Barré syndrome, the 2009 H1N1 vaccine Pandemrix being associated with narcolepsy,11 the MMR vaccine causing thrombocytopenic purpura, and the smallpox vaccine leading to myopericarditis. A theorized link between childhood immunization and type 1 diabetes mellitus (DM-1) now appears to be disproven.12,13

These risks certainly do not appear to apply to the measles vaccine. It may be necessary for some of us to evaluate our beliefs and check them against the evidence that is contrary to our long-held assumptions.

Again, integrative medicine physicians are more likely to see children who have been infected by measles and whose immune systems have taken a hit. At this point there is no proven approach to restore immune memory or hasten its recovery. This entire idea of immune amnesia is so new that there is not even an animal trial published to suggest any helpful interventions.

Nevertheless, there is 1 approach we might consider, and that is utilizing saponin herbs, in particular licorice, astragalus, and ginseng, to stimulate immune function. The saponin herbs act as adjuvants, enhancing immune reaction to disease antigens.14-18 Admittedly, the evidence is weak; at this point, this is a “won’t hurt, might help” category of recommendations, without any evidence or clear mechanisms elucidated. For those parents who insist on not vaccinating their children, immune support appears to be a “must do” after natural infection.

Categorized Under

References

  1. Petrova VN, Sawatsky B, Han AX, et al. Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles. Sci Immunol. 2019;4(41). pii:eaay6125.
  2. Aaby MP, Samb B, Simondon F, Seck AM, Knudsen KM, Whittle H. [A non-specific, beneficial effect of measles vaccination. Analysis of mortality studies from developing countries]. Ugeskr Laeger. 1996;158(42):5944-5948.
  3. Aaby P, Bhuiya A, Nahar L, Knudsen K, de Francisco A, Strong M. The survival benefit of measles immunization may not be explained entirely by the prevention of measles disease: a community study from rural Bangladesh. Int J Epidemiol. 2003;32(1):106-116.
  4. Veirum JE, Sodemann M, Biai S, et al. Routine vaccinations associated with divergent effects on female and male mortality at the paediatric ward in Bissau, Guinea-Bissau. Vaccine. 2005;23(9):1197-1204.
  5. Aaby P, Martins CL, Garly ML, et al. Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial. BMJ. 2010;341:c6495.
  6. Mina MJ. Measles, immune suppression and vaccination: direct and indirect nonspecific vaccine benefits. J Infect. 2017;74 Suppl 1:S10-S17.
  7. Noori N, Rohani P. Quantifying the consequences of measles-induced immune modulation for whooping cough epidemiology. Philos Trans R Soc Lond B Biol Sci. 2019;374(1775):20180270.
  8. Gadroen K, Dodd CN, Masclee GMC, et al. Impact and longevity of measles-associated immune suppression: a matched cohort study using data from the THIN general practice database in the UK. BMJ Open. 2018;8(11):e021465.
  9. Goodridge HS, Ahmed SS, Curtis N, et al. Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol. 2016;16(6):392-400.
  10. Wang Y, Dai PD, Zhang TY. Experimental research on the therapeutic effect of MMR vaccine to juvenile-onset recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol. 2019;276(3):801-803.
  11. Centers for Disease Control and Prevention. Narcolepsy following Pandemrix Influenza Vaccine in Europe. CDC.gov. https://www.cdc.gov/vaccinesafety/concerns/history/narcolepsy-flu.html. Access May 2, 2020.
  12. Toussirot É1, Bereau M. Vaccination and induction of autoimmune diseases. Inflamm Allergy Drug Targets. 2015;14(2):94-98.
  13. Salemi S1, D’Amelio R. Could autoimmunity be induced by vaccination? Int Rev Immunol. 2010;29(3):247-269.
  14. Maqbool B, Wang Y, Cui X, et al. Ginseng stem-leaf saponins in combination with selenium enhance immune responses to an attenuated pseudorabies virus vaccine. Microbiol Immunol. 2019;63(7):269-279.
  15. Zhai L, Li Y, Wang W, Wang Y, Hu S. Effect of oral administration of ginseng stem-and-leaf saponins (GSLS) on the immune responses to Newcastle disease vaccine in chickens. Vaccine. 2011;29(31):5007-5014.
  16. Alexyuk PG, Bogoyavlenskiy AP, Alexyuk MS, et al. Adjuvant activity of multimolecular complexes based on Glycyrrhiza glabra saponins, lipids, and influenza virus glycoproteins. Arch Virol. 2019;164(7):1793-1803.
  17. Pickering RJ, Smith SD, Strugnell RA, Wesselingh SL, Webster DE. Crude saponins improve the immune response to an oral plant-made measles vaccine. Vaccine. 2006;24(2):144-150.
  18. Koczurkiewicz P, Klaś K, Grabowska K, et al. Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug-minireview of in vitro studies. Phytother Res. 2019;33(9):2141-2151.