The Spillover Effect of Vaccine Hesitancy

Mothers register their young children for free childhood immunizations at the Corazon Aquino Health Center near Manila. From Beaubien, J. (2019), https://www.npr.org/sections/goatsandsoda/2019/05/23/725726094/the-philippines-is-fighting-one-of-the-worlds-worst-measles-outbreaks.

As of July 2019, the Philippines reported over 39,000 measles cases, which is the country’s largest measles outbreak since 2014 [1]. The reason for the outbreak may be linked to a controversy surrounding the dengue vaccine. How could a vaccine against one disease have influenced an outbreak of another? 

Dengue is a mosquito-borne virus that circulates in tropical and subtropical climates [2]. Although most infected individuals are asymptomatic, about a quarter of those experience a flu-like illness that can develop into severe dengue [2, 3]. Severe dengue is the leading cause of childhood morbidity and mortality in some countries in Latin America and Asia, and has been on the rise globally [2].

In December 2015, the Philippine Department of Health approved plans to vaccinate one million school children aged 9 years and above with three doses of Dengvaxia®, the world’s first dengue vaccine developed by the pharmaceutical company, Sanofi [4]. Globally, surveillance of adverse events following immunization found 51 fatalities, of which 15 were dengue cases and the majority were reported in the Philippines [5]. Through an immunological process called antibody-dependent enhancement, children without previous infection who were vaccinated were found to have an increased risk of severe dengue if naturally infected later in life [6]. Therefore, the World Health Organization (WHO) reissued its position paper on the vaccine in 2018, recommending it only for children with past dengue infection confirmed through laboratory testing [7]. If individual testing capacity is unavailable, vaccination could be recommended for children living in areas where previous dengue infection is estimated to affect at least 80% in children by 9 years of age [7]. Among the children who were vaccinated in the Philippines, about 80,000 are estimated to never have had previous history of dengue infection, and thus may be at an increased risk for adverse events [8].

The reported adverse events created a media frenzy. There were protests on the streets calling for accountability from the government. Parents expressed that communication around the situation was inadequate, and it caused mistrust in public institutions [9]. This resulted in a total of 20 individuals facing criminal charges for reckless imprudence resulting in homicide, including government and Sanofi officials [8]. Sanofi maintains that there is no clinical evidence that the deaths were related to Dengvaxia® [10]. During this controversy, confidence in vaccination plummeted nationally. In 2015, a study found that 82% of respondents believed that vaccines were safe and effective. However, in 2018, only 21-22% held the same belief [11]. This decline mirrors the drop in vaccination coverage for various diseases. From 2016 to 2018, vaccination coverage dropped from 80% to 67% and from 47% to 40% for the first and second dose of measles-containing-vaccine (MCV), respectively [12]. The low vaccination coverage rendered the children in the Philippines more susceptible to vaccine-preventable diseases.

In January 2019, the Philippine Department of Health declared a measles outbreak in the country [13]. As of July 2019, 39,726 measles cases were reported – more than a 200% increase compared to the same period during the previous year [1]. To control the outbreak, the government launched vaccination campaigns which has reached 5.5 million people, and hopes to reach an additional 15 million before September 2019 [14]. However, difficulties have been reported in convincing parents to allow vaccination of their children given the controversy surrounding the dengue vaccine, even in areas where the dengue vaccine was not administered [14]. Although the incidence of measles has been decreasing since the peak of the outbreak in February 2019, there is a need to rebuild vaccine confidence [1].

World Health Organization. (2019). Measles: Distribution of cases by country, year and month. [Data file]. Retrieved from https://www.who.int/immunization/monitoring_surveillance/burden/vpd/measlescasesbycountrybymonth.xls?ua=1

This situation in the Philippines highlights that vaccine hesitancy in one vaccine can potentially spill over into other vaccines. Vaccine hesitancy has been thought of as vaccine and context specific [15]. For example, the hesitancy towards the HPV vaccine is influenced by some factors that are unique to the vaccine, primarily the false perceived notion that the vaccine could encourage children to engage in sexual behaviour at an earlier age [16]. 

In some regards, vaccines are perceived to be a monolithic health intervention that groups many vaccines together. This is seen in the messaging that “vaccines are safe” by the public health community  and in the “do not vaccinate” messages by anti-vaccination groups. However, this grouping of different vaccines simplifies the risks and benefits of individual vaccines. Mistrust of the dengue vaccine led to mistrust in all vaccines. Interestingly, drugs are not viewed in the same way. Removing drugs off the market due to adverse side effects are well noted, however subsequent loss of confidence in all drugs is not common. Perhaps it is because drugs are not usually discussed as a monolithic group and reference is made to specific drug names in public discourse, especially when adverse side effects are reported. What could explain this difference? Is it because vaccines are perceived to cause harm because they are usually delivered intravenously through a needle that causes pain? Is it because vaccines primarily target healthy people to prevent diseases compared to drugs that are primarily taken to cure sick people?

In September 2019, a polio outbreak was declared in the Philippines due to vaccine-derived poliovirus type 2 [17]. Vaccine-derived polio occurs rarely when the attenuated polio virus that is in the vaccine is transmitted person to person for a long time and it develops the ability to cause disease again. In the capital, the coverage for the polio vaccine dropped from 77% in 2016 to 24% in June 2019. Given the recent history with the dengue vaccine and measles outbreak, the progression of this polio outbreak remains uncertain and transparent risk communication with the public will be key to rebuilding trust in vaccination.

References

[1] World Health Organization. (2019). Measles cases by country by month. The World Health Organization. https://www.who.int/immunization/monitoring_surveillance/burden/vpd/measlescasesbycountrybymonth.xls?ua=1.  

[2] World Health Organization. (October 23 2019). Dengue and severe dengue. The World Health Organization. Retrieved from https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue. 

[3] Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., … Hay, S. I. (2013). The global distribution and burden of dengue. Nature, 496(7446), 504–507. https://doi.org/10.1038/nature12060.

[4] Yasmin, S., & Mukerjee, M. (2019). How the world’s first dengue vaccination drive ended in disaster. Scientific American. Retrieved from https://www.scientificamerican.com/article/how-the-worlds-first-dengue-vaccination-drive-ended-in-disaster/.

[5] Thomas, S. J., & Yoon, I.-K. (2019). A review of Dengvaxia®: Development to deployment. Human Vaccines & Immunotherapeutics, 15(10), 2295–2314. https://doi.org/10.1080/21645515.2019.1658503.

[6] Dans, A. L., Dans, L. F., Lansang, M. A. D., Silvestre, M. A. A., & Guyatt, G. H. (2018). Controversy and debate on dengue vaccine series—paper 1: Review of a licensed dengue vaccine: Inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs. Journal of Clinical Epidemiology, 95(Complete), 137-139. doi:10.1016/j.jclinepi.2017.11.019.

[7] Dengue vaccine: WHO position paper, September 2018 – Recommendations. (2019). Vaccine, 37(35), 4848–4849. https://doi.org/10.1016/j.vaccine.2018.09.063.

[8] Dyer, O. (2019). Philippines to charge Sanofi staff and government officials over dengue vaccine. BMJ, 1088. https://doi.org/10.1136/bmj.l1088.

[9] Valido, E. M., Laksanawati, I. S., & Utarini, A. (2018). Acceptability of the dengue vaccination among parents in urban poor communities of Quezon City, Philippines before and after vaccine suspension. BMC Research Notes, 11(1), 661. https://doi.org/10.1186/s13104-018-3766-y.

[10] Doucleff, M. (2019). Dengue vaccine controversy in the Philippines. National Public Radio. Retrieved from https://www.npr.org/2019/05/02/719366831/dengue-vaccine-controversy-in-the-philippines.

[11] Larson, H. J., Hartigan-Go, K., & de Figueiredo, A. (2019). Vaccine confidence plummets in the Philippines following dengue vaccine scare: Why it matters to pandemic preparedness. Human Vaccines & Immunotherapeutics, 15(3), 625–627. https://doi.org/10.1080/21645515.2018.1522468.

[12]The United Nations Children’s Fund. (2018). Vaccination and Immunization Statistics. The United Nations Children’s Fund. Retrieved from https://data.unicef.org/wp-content/uploads/2016/07/Immunization-estimates-2018.xlsx.

[13] Republic of the Philippines Department of Health. (2019). DOH Expands Measles Outbreak Declaration to Other Region. (DOH Publication no. 16647). Retrieved from https://www.doh.gov.ph/node/16647

[14] Beaubien, J. (2019). How the philippines is fighting one of the world’s worst measles outbreaks. National Public Radio. Retreived from https://www.npr.org/sections/goatsandsoda/2019/05/23/725726094/the-philippines-is-fighting-one-of-the-worlds-worst-measles-outbreaks. 

[15] MacDonald, N. E. (2015). Vaccine hesitancy: Definition, scope and determinants. Vaccine, 33(34), 4161-4164. doi:10.1016/j.vaccine.2015.04.036.

[16] Holman, D. M., Benard, V., Roland, K.B, Watson, M., Liddon, N., & Stokley, S. (2014). Barriers to Human Papillomavirus Vaccination Among US Adolescents. JAMA, 168(1), 76-82. doi:10.1001/jamapediatrics.2013.2752

[17] World Health Organization. (2019). Polio-outbreak the portfolio. The World Health Organization. Retrieved from https://www.who.int/csr/don/24-september-2019-polio-outbreak-the-philippines/en/.

[18] Beaubien, J. (2019). Corazon Aquino Health Center. [Photograph]. Retrieved from https://www.npr.org/sections/goatsandsoda/2019/05/23/725726094/the-philippines-is-fighting-one-of-the-worlds-worst-measles-outbreaks.