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Philippines halts dengue immunisation campaign owing to safety risk

BMJ 2017; 359 doi: (Published 12 December 2017) Cite this as: BMJ 2017;359:j5759

Rapid Response:

Dengue vaccine and influenza vaccine are both subject to increased illness risk via "antibody-dependent enhancement"

The Phillipine Dengvaxia scandal continues to unfold (NYT, WSJ, CIDRAP 12/18/17).....Meanwhile it reminds us that influenza vaccines also increase the risk of illness via "antibody-dependent enhancement" of infection: some vaccines evoke antibodies that are poorly matched to circulating viruses; instead of neutralizing the viruses these antibodies enhance uptake of the viruses via Fc receptors on mononuclear phagocytes, which then manufacture large numbers of virus, leading to severe illness. This seems counterintuitive, but the phenomenon is quite real. In the third year of a randomized trial the risk of hospitalization from a dengue infection was 5-fold in young vaccine recipients. (Hadinegoro, NEJM 2015;373:1195. Halstead, Am J Trop Med 6/8/16).....ADE helps account for the fact that the 2008-9 flu shot doubled the risk of illness from the 2009 H1N1 pandemic flu (Skowronski, PLoS Medicine 2010); the increased H1N1 illness risk in US children associated with the 2015-16 nasal flu vaccine (Jackson, NEJM 2017) ; and the 68% increase in H3N2 illness risk among UK elderly after the 2016-17 flu shot (Pub Health England 8/31/17).

Recent announcements that the 2016-17 flu shot was "only 10% effective " against H3N2 in Australia concealed the possibility that it increased the risk in the elderly by as much as 160%!! (VE minus 20%; minus 160 to 42). (Paules, NEJM 11/29/17. Sullivan, Euro Surveill 10/2617)

Influenza deaths do occur in vaccinated individuals, and some are likely the result of antibodies that enhance infections instead of neutralizing them. This is particularly worrisome as we wait for the next pandemic, possibly from the H7N9 virus that has emerged in China. (Skowronski, Euro Surveill 4/25/13)....Finally, one of the obstacles to the development of a universal influenza vaccine is the very real possibility of provoking ADE. (Jang, Viruses 2014;6;3159. Dutry, BMC Proceedings 2011; 5:suppl 1:P62)

Competing interests: No competing interests

21 December 2017
Allan S. Cunningham
Retired pediatrician
Cooperstown NY 13326, USA