More on measles and the impact of the Lancet retraction

May 2004

---Philip A. Brunell, MD

Too often articles appear only to be retracted later. Unfortunately, the retractions rarely make the first page, despite the fact that this may have been where the original article appeared. In a recent issue of The Lancet (2004;363:750), there was a retraction of the Wakefield article on the link between measles immunization and autism. The original article (Lancet. 1998;351:637), which received much notoriety, was retracted by 10 of the original 12 authors. Dr. Wakefield was one of the two who failed to join in the retraction. The other could not be reached.

Although those of us who were skeptical of the findings originally and those who were concerned about the impact of the Wakefield article on vaccine acceptance by parents were gleeful, one should read between the lines to see what the retraction actually stated and, more importantly, hear the warnings that are implied. At stake is public confidence in the “vaccine establishment,” journal publishers, universities’ management of research activities and the investigators themselves. The influence of trial lawyers and the press in this affair is also of interest. That the original article shook public confidence in vaccines can be attested to by the decrease in acceptance of vaccines in Great Britain (See chart below). What effect the retraction will have on the latter, if any, is still to be determined.

The retraction states that “in this paper no causal link was established between MMR vaccine and autism as the data were insufficient.” The retractors go on to say that “it is important that such work continues.” Autism is an important problem, and one of the virtues of public dialogue is that it focuses attention on important issues. The work certainly has continued, and I call your attention to a Web site by the Immunization Action Coalition, www.immunize.org, which cites a list of articles supporting and rejecting the link between MMR and autism. Even more important is the greater interest in the problem of autism and all its possible causes.

In a prior commentary (April 2001), I expressed concern about the methodology. “Measles antigen,” which Dr. Wakefield had thought he detected in gut samples of patients with bowel disease, appears to be a closely related human protein, rather than measles protein, that is present in many inflammatory lesions of the bowel (Gut. 2000;46:163-169). Most have failed to confirm his polymerase chain reaction (PCR) finding of measles RNA in the bowel of patients with Crohn’s disease (J Med Virol. 2000;62[3]:377).

“Full context”

The main issues of the Lancet retraction are selection bias and ethics. There is some conflict between Wakefield and the other protagonists on the influence of the legal community. Admittedly, they did fund some of these studies. There are serious concerns about the influence that patients being referred by attorneys may have had on the outcome of the studies and the selection bias. What is perfectly clear from subsequent studies of large populations selected without similar bias is that a relationship between autism and MMR has not been found (N Engl J Med. 2002;347:1477; Lancet. 1998;110:957; Arch Dis Pediatr Adol Med. 2001;155:354). One study rejected the thesis that there may be a subset of autism related to measles-containing vaccines (Pediatrics. 2001;108[e58]).

Richard Horton, editor of The Lancet, concluded that “had we appreciated the full context in which the work reported was done, publication would not have taken place in the way that it did.” He offers some sobering lessons learned from this experience (Lancet. 2004;363:747). The essence of his message is maintenance of public confidence not only in vaccines but also in the conduct of research. He acknowledges that the public now has a seat at the public debate. Lay members of the public, including vaccine protagonists, sit on the Advisory Committee on Immunization Practices (ACIP), institution research review boards and other important scientific committees in this country. He also concedes that the public is not as accepting of governmental information as it once was. The lay press is not too subtly admonished. As editor of The Lancet, he iterates the responsibility of publishing new ideas, even ones that are not likely to be in line with current thinking

Effect on measles vaccination rates

The notoriety achieved by the initial publication has not been without cost, as there has been a drop in MMR vaccination from 92% in 1995-1996, before the publication, to 84% in 2001-2002, with a concomitant increase in measles cases (Science. 2003;301:804). England had about 10 times the number of cases as the United States, with a population about one-fourth the size (See chart above). There has been concern expressed by Catherine Peckham, an English rubella expert, that congenital rubella may be on the rise in London, as rubella as well as measles immunization has fallen because of the combined vaccine. The measles epidemic in Dublin was attributed by the researchers to the reports of the relationship of measles vaccine to autism in addition to erosion of confidence in vaccines. In one area, the immunization rate of 2-year-olds fell to 66%. This epidemic claimed the lives of three children and resulted in hospital and intensive care admissions of others (Pediatr Infect Dis J. 2003;22:580). One of my English colleagues who came away from a public debate on the measles autism issue came away discouraged. He remarked that it will take a few deaths before immunization is again accepted. This is exactly what occurred in Ireland, as immunization rates that were 76% nationally rose to 81% in the next quarter. Unfortunately, when disease is not visible, potential adverse effects are perceived as the problem, while the present problem of preventing deadly diseases is ignored.