Sunday, July 27, 2014

Demographic transition: do vaccines reduce fertility?

First, what is fertility? To most people, fertility is the ability to have children; the opposite of infertility. To demographers and epidemiologists, fertility is the number of children a person has. According the U.S. Census Bureau, fertility is the number of children ever born to a person (referring to the number of live births). "Typically it is asked of women age 15 to 50, or women of all ages but some surveys ask men how many children they have fathered." A fertility rate is the number of children born in a population over a period of time, usually per 1,000 people per year. To demographers and epidemiologists, the ability to have children in known as fecundity rather than fertility.

In his book, The End of Poverty, Jeffery Sachs wrote, "I have been asked dozens of times if help for Africa would ultimately backfire in an even greater population explosion. Would greater child survival rates not translate into more adult hunger and suffering?"

I've been asked similar questions about my interest in tropical medicine and my volunteer work in Africa. Sachs goes on to discuss the demographic transition, a phenomenon that has occurred in every industrialized country and is occurring in developing countries; that is, as standards of living improve, people have fewer children.

There are a several theories about why the demographic transition occurs. The primary theory links decreasing fertility to decreases in child mortality; parents have fewer children when more of their children survive to adulthood.

We can see this occurring today. In the graph below, I've used World Bank data from 2012 to plot child mortality rates (the number of deaths of children under 5 years of age per 1,000 population per year) against fertility rates. Each dot represents a country. In countries in which child mortality is low, women have fewer children. In countries with high death rates for children under 5 five years of age, fertility rates are higher.


Childhood vaccines are associated with improved child survival. Measles immunization has been shown to decrease all cause mortality. In the graph below I've plotted mortality of children less than 5 years of age against the percent of children 12 to 23 months of age who have received measles vaccines. Under 5 mortality is higher in countries with lower measles immunization coverage than in countries with high measles vaccine coverage.


Of course, there are a number of other factors associated with both decreasing child mortality and decreasing fertility including higher costs of raising a child (e.g., education), transitioning from agricultural to manufacturing markets and urbanization (people who live in cities tend to have fewer children than those living in rural areas), more women working outside of the home, changes in social norms, and, of course, access to contraception.

Although there have been improvements in the prevention and treatment of malaria, most malaria deaths occur in children under 5 years in sub-Saharan Africa. This is one of the reasons fertility remains high in Africa.

In 2010, Bill Gates made a passing reference to the demographic transition during a TED Talk on energy and climate:

First, we've got population. The world today has 6.8 billion people. That's headed up to about nine billion. Now, if we do a really great job on new vaccines, health care, reproductive health services, we could lower that by, perhaps, 10 or 15 percent, but there we see an increase of about 1.3.

Gates had discussed the demographic transition in the Bill and Melinda Gates Foundation 2009 annual letter:

Two things caused this huge reduction in the death rate. First, incomes went up, and with that increase, nutrition, medical care, and living conditions improved. The second factor is that even where incomes did not go up, the availability of life-saving vaccines reduced the number of deaths. For example, measles accounted for 4 million children’s deaths in 1990, but fewer than 250,000 in 2006.

A surprising but critical fact we learned was that reducing the number of deaths actually reduces population growth. Chart 3 shows the strong connection between infant mortality rates and fertility rates. Contrary to the Malthusian view that population will grow to the limit of however many kids can be fed, in fact parents choose to have enough kids to give them a high chance that several will survive to support them as they grow old. As the number of kids who survive to adulthood goes up, parents can achieve this goal without having as many children.

Bill and Melinda Gates Foundation, 2009

Unfortunately, Gates' TED Talk comments were misinterpreted by several people in the blogosphere to mean that vaccines cause infertility.

To answer the question in the title of this post, "do vaccines reduce fertility?" I will violate Betteridge's law of headlines and say, yes, vaccines reduce fertility, but not in the way some people would like you to believe.


Bloom, D. E., Canning, D., & Weston, M. (2005). The value of vaccination. World Economics, 6(3), 15-39.

Brauner-Otto, S., Axinn, W., & Ghimire, D. (2007). The spread of health services and fertility transition. Population Studies Center Research Report 07-619.

Conley, D., McCord, G. C., & Sachs, J. D. (2007). Africa's lagging demographic transition: evidence from exogenous impacts of malaria ecology and agricultural technology. National Bureau of Economic Research Working Paper Series No. 12892.

Gates, B. (2009). Bill and Melinda Gates Foundation annual letter 2009.

Greenwood, J. & Sesharid, A. (2001). The U.S. demographic transition. AEA Papers and Proceedings, 92(2), 153-159.

Newson, L., Postmes, T., Lea, S. E. G., & Webley, P. (2005). Why are modern families small? Toward an evolutionary and cultural explanation for the demographic transition. Personality and Social Psychology Review, 9(4), 360-373.

Omran, A R. (1971). The epidemiologic transition. Milbank Memorial Fund Quarterly, 49(4), 509-538.

Sachs, J. D. (2005). The end of poverty: economic possibilities for our time. New York: The Penguin Press.

van den Ent, M. M. V. X., Brown, D. W., Hoelstra, E. J., Christie, A., & Cochi, S. L. (2011). Measles mortality reduction contributes substantially to reduction of all cause mortality among children less than five years of age, 1990-2008. Journal of Infectious Diseases, 204(Supple. 1), S18-S23.

World Bank. (2014). Data.


Sunday, July 13, 2014

Modified measles

Happy birthday Andrew!

Our little boy is two years old today. Seeing Andrew grow up has been one of the greatest joys of my life. I have been enthralled by watching our little scientist learn about the world. Watching him learn new skills and challenge himself has made me a very proud daddy!

Measles vaccine is highly effective; so effective that high immunization coverage has resulted in the elimination of measles from the U.S. Nevertheless, a small proportion of people who receive measles vaccine do not develop an immune response sufficient to prevent infection. This is known as primary vaccine failure. There is evidence that measles antibody levels (titers) wane over time allowing some people to become susceptible to measles. Infection in a person who initially developed an adequate immune response to the vaccine but later became susceptible is called secondary vaccine failure.

One of the factors that contributes to waning immunity to measles is the loss of natural boosting. In the past, people in the U.S. were periodically exposed to measles virus during epidemics. Since measles has been eliminated from the U.S., exposure to the virus in this country has become rare.

Secondary measles vaccine failure is more likely to occur with intense exposure to the measles virus. This can occur during an outbreak or among household contacts of a person with measles. For this reason, it's not unusual to find vaccinated people with measles during an outbreak.

Modified measles, measles in a vaccinated person, is much milder than measles in an unvaccinated person; fever and rash are less severe and a person with modified measles is much less likely to develop complications of measles than an unvaccinated person with measles. In contrast to unvaccinated people with measles, vaccinated people who develop modified measles have high avidity antibodies, meaning, their antibodies are mature and bind tightly to the virus.

People with modified measles are also much less likely to infect other people than unvaccinated people with measles. There have been numerous cases of modified measles in previously vaccinated people with no evidence of transmission to close contacts reported in the medical literature. There have even been reports of vaccinated doctors who developed modified measles but did not infect their patients (Lee et al., 2008; Rota et al., 2011).

Earlier this year, Jennifer Rosen and colleagues published the first report of transmission of measles from a previously vaccinated person. In 2011, a 22-year-old woman in New York City who had received two doses of MMR as a child who developed measles. Out of 88 people who had contact with her, 4 people developed measles. One was her coworker and the other three were health care workers at a clinic. Two of the secondary cases had received two doses of MMR as children and the other two had previous evidence of immunity (positive immunoglobulin G titer). None of the contacts to the four secondary cases developed measles. The authors wrote, "this outbreak probably represents a series of rare events" and that it "does not justify a change in current measles control and elimination strategies."


Centers for Disease Control and Prevention. (2013). Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 62(4), 1-34.

Gershon, A. A. (2009). Measles virus (rubeola). In G. L. Mandell, J. E. Bennett, & R. Dolin (Eds.). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. (7th Ed.) [Electronic version].

Hickman, C. J., Hyde, T. B., Sowers, S. B., Mercader, S., McGrew, M., Williams, N. J. et al. (2011). Laboratory characterization of measles virus infection in previously vaccinated and unvaccinated individuals. Journal of Infectious Diseases, 204(Suppl. 1), S549-S558.

Lee, N. Y., Lee, H. C., Chang, C. M., Wu, C. J., Ko, N. Y., Ko, C. (2008). Modified measles in a healthcare worker after return from travel. Infection Control and Hospital Epidemiology, 29(4), 380-381.

Mercader, S., Garcia, P., & Bellini, W. J. (2012). Measles virus avidity assay for use in classification of measles vaccine failure in measles elimination settings. Clinical and Vaccine Immunology, 19(11), 1810-1817.

Mitchell, P., Turner, N., Jennings, L., & Dong, H. (2013). Previous vaccination modifies both the clinical disease and immunological features in children with measles. Journal of Primary Health Care, 5(2), 93-98.

Rosen, J. B., Rota, J. S., Hickman, C. J., Sowers, S. B., Mercader, S., Rota, P. A. et al. (2014). Outbreak of measles among persons with prior evidence of immunity, New York City, 2011. Clinical Infectious Diseases, 58(9), 1205-1210.

Rota, J. S., Hickman, C. J., Sowers, S. B., Rota, P. A., Mercader, S., & Bellini, W. J. (2011). Two case studies of modified measles in vaccinated physicians exposed to primary measles cases: high risk of infection but low risk of transmission. Journal of Infectious Diseases, 204(Suppl. 1), S559-S563.