Measles in the United Kingdom - The “Wakefield Factor”

Measles in the United Kingdom

The “Wakefield Factor”

By

F. Edward Yazbak MD, FAAP

 

Dr. Andrew Wakefield has been persecuted and vilified ever since he published an article in Lancet in February 1998 and answered questions about MMR vaccination at a press conference in London.

Of all the insults and accusations leveled against Dr. Wakefield, the most painful must have been that because of his research, children in the United Kingdom and elsewhere were more likely to come down with measles and die.

Dr Wakefield’s recommendation for single measles vaccine in preference to MMR was made after his extensive review of the quality of safety data in relation to measles-containing vaccines and the revelation, by a senior member of the UK Department of Health, about the licensing of knowingly unsafe MMR vaccines by the UK authorities.[1] His position on the relative paucity of good safety data for MMR compared with the single measles vaccine has since been endorsed by the Cochrane Collaboration.[2] It is important to note that at the time of The Lancet publication and beyond, Dr Wakefield strongly endorsed the use of single measles vaccine. Despite false allegations to the contrary by The Lancet editor, Dr Richard Horton[3], single vaccines were available in the UK when Dr Wakefield made this recommendation.

In order to protect the MMR vaccine programs the option of single vaccines was later removed from parents wishing to vaccinate their children, but concerned, quite reasonably, over the safety of MMR.

In the UK, the government withdrew the importation license for single vaccines a few months after Dr Wakefield’s 1998 press conference. Well worth noting is the fact that Merck ceased supplying the single measles, mumps and rubella vaccines in the United States over ten years later, in October 2009[4].

Because of inconsistent testing results and non-availability of pre-1998 data, it is near impossible to define a trend or to draw conclusions regarding confirmed measles cases; yet the relatively few confirmed cases of measles in the UK received an inordinate amount of publicity that always included extensive blame of Dr. Wakefield, particularly as his GMC hearing approached.

While this was happening in England, multiple measles outbreaks were being reported worldwide, sometimes in highly vaccinated populations.

Official statistics from the United Kingdom Health Protection Agency show that:

• The number of reported measles cases kept dropping after1998 and only exceeded the 1998 figures ten years later, when there were outbreaks worldwide

• There were strikingly far fewer reported measles cases in the UK in the 10 years that followed Wakefield’s paper than in the 10 years that preceded its publication
  

The reporting of measles cases in the United Kingdom was not affected by Dr. Andrew Wakefield’s research.
 

Measles in the United Kingdom

The role of the Health Protection Agency (HPA)[5] is “to provide an integrated approach to protecting UK public health through the provision of support and advice to the NHS … The Centre for Infections at Colindale is the base for communicable disease surveillance and specialist microbiology …”

According to the HPA, “After clean water, vaccination is the most effective public health intervention in the world for saving lives and promoting good health.”[6]

The HPA lists in a single master table[7], the annual totals from 1982 to 2009 for England and Wales, of all “Statutory Notifications of Infectious Diseases (NOIDs)”.

Selected measles information for the years 1988-2007 from that particular HPA Master Table is listed in the following table.

Table I - HPA: Measles Reported Cases – England and Wales											Totals
10 Years     Pre-Wakefield	1988	1989	1990	1991	1992	1993	1994	1995	1996	1997	Last 5	All
	86,001	26,222	13,302	9,680	10,268	9,612	16,375	7,447	5,614	3,962	43,010	188,483
10 Years    Post-Wakefield	1998	1999	2000	2001	2002	2003	2004	2005	2006	2007	First  5	All
	3,728	2,438	2,378	2,250	3,187	2,488	2,356	2,089	3,705	3,670	13,981	28,289

The MMR vaccine was licensed and the MMR vaccination program was launched in the United Kingdom in 1988.

There were 188,483 reported measles cases in the ten years preceding the Wakefield paper compared to 28,289 cases in the following ten years, an 85% decrease.

Although increasing uptake of the MMR vaccine could account for much of the early decline, the fact that there were 43,010 reported measles cases in the five years preceding the publication compared to 13,981 cases in the following 5 years, a decrease of 67%, suggests that there was no “Wakefield Factor”, at least insofar as an impact on reported measles cases is concerned. 

If one postulated that the UK MMR vaccination rates near-reached targeted levels 3 years after the launch of the vaccination program and compared the 7-year periods before and after the Wakefield paper, the following would also be obvious: There were only 18,825 measles notifications in the 7 years following the publication of the paper in early 1998 compared to 62,950 measles notifications in the previous 7 years.

The fact that the number of notified measles cases decreased from 1998 to 1999 to 2000 to 2001, the 4 years immediately after the Wakefield publication and press conference, when maximal impact should have been noted clearly speaks for itself.

The same holds true when calculated as cases per 100,000 of population.

Dr. Elizabeth Miller, Head of the Immunization Department at the Health Protection Agency, Center for infections, and a member of the WHO Global Advisory Committee on Vaccine Safety, was never a fan of Dr. Wakefield. A staunch defender of the MMR vaccination program and the author / co-author of eight publications on MMR vaccination and autism between 2002 and 2005, she never once revealed in her many addresses that reported measles cases had decreased after The Lancet paper.

Neither did Sir Liam Donaldson, the Chief Medical Officer nor Professor David Salisbury, Director of Immunization at the UK Department of Health.

The World Health Organization (WHO) lists infectious diseases reported by all nations.

The following table lists that data[8] for the ten years before and after the Wakefield paper as reported by the UK Health Authorities, possibly the HPA.

Table II - WHO: Measles Reported Cases – UK and Northern Ireland											Totals
10 Years     Pre-Wakefield	1988	1989	1990	1991	1992	1993	1994	1995	1996	1997	Last 5	All
	88,259	30,160	28,228	11,727	12,317	12,018	23,525	9,017	6,866	4,844	56,270	226,961
10 Years    Post-Wakefield	1998	1999	2000	2001	2002	2003	2004	2005	2006	2007	First  5	All
	74	-	104	73	314	460	189	79	764	1022	565	3,079

An attempt at explaining the above somewhat inconsistent numbers will follow. The fact remains that the reported cases of measles in the United Kingdom and Northern Ireland did not increase and actually decreased in the years immediately following the 1998 publication by Wakefield et al in The Lancet. 

This is further supported by Jick and Hagberg of the Boston University School of Medicine Collaborative Drug Surveillance Program[9] who identified all children in the UK General Practice Research Database diagnosed with measles from 1990 to 2008 and recently reported (June 2010) that “…Since 1996, the incidence of measles has fallen …”

Reported cases of measles[10] decreased 15 to 44% in England and Wales between 1998 and 2007. They also decreased from year to year during 5 of the 6 years that followed the Wakefield paper in spite of the frenzied publicity.

Trying to make sense of the number and percentage of confirmed measles cases in the UK since 1998 is a challenge. As evident in the following table, the number and percentage of confirmed cases spiked in 2002 and again in 2006-2007.

Table III - HPA: Measles Reported and Confirmed Cases – England and Wales
	1998	1999	2000	2001	2002	2003	2004	2005	2006	2007	Total
Reported	3,728	2,438	2,378	2,250	3,187	2,488	2,356	2,089	3,705	3,670	28,289
Confirmed	56	92	100	70	319	437	188	78	740	990	3,070
% Confirmed	1.5	3.8	4.2	3.1	10.0	17.6	8.0	3.7	20.0	27.0	10.9

A comparison of the data for the 2002 and 2007 spikes illustrates the difficulty to draw conclusions. While reported cases rose from 3,187 to 3,670, an increase of 15%, confirmed cases jumped disproportionately from 319 to 990, an increase of 210%.

Looking at the 2002 spike and comparing 2001 with 2002, reported cases increased by 42% from 2,250 to 3,187 while confirmed cases increased by 355% from 70 to 319. 

Comparing the first quarters of both years was also helpful.

There were 741 notified measles cases and 569 (72%) tested. Only 3 had a positive saliva test, a yield of 0.5% from weeks 1 to 13 of 2001.[11]

During the same weeks of 2002,[12] there were 1,199 notified cases and 1,386 (116%) tested cases. The following explanation was provided by the Public Health Laboratory Services (PHLS) for this strange situation: “due to the increase in confirmedmeasles in this quarter many oral fluid tests were submitted early for detection of IgM antibody for suspected cases, some of which were not subsequently notified, thus more samples were submitted than notified in this period.”

[No lucid comment on the above statement is possible.]

In any case, of the 1,386 tested cases, 91 or 6.6% were positive, a yield 13 times greater than in the first quarter of 2001. Because 9 cases had recently been vaccinated, PHLS recorded the confirmed saliva-tested cases as 82. Unlike in Q1 of 2001, PHLS then added 44 “other lab confirmed cases” to push the number of confirmed cases to 126 for the quarter. 

In spite of all the changes and lack in conformity, there were fewer confirmed cases of measles[13] in England and Wales in 2005 than in 1999. Also noteworthy is the fact that the percentages of confirmed cases remained low during the four years that immediately followed the publication of the Wakefield study.  

The fact that there were only 2,089 notified cases and 78 confirmed measles cases in 2005, while the same diagnostic modalities as in 2002-2004 were in use, strongly suggests that seven years after the Lancet publication, the so-called Wakefield Factor was still not much of a factor.  

A careful look at the first quarter of 2005[14] may help shed some light on the issue of case confirmation in the United Kingdom by saliva testing. In week 1 to 13, 2005 there were 591 reported cases of measles of which 575 (97.3%) were tested. In only 20 (3.5%) the saliva test was positive.

The same was true for rubella: Of 299 cases of clinical rubella reported by physicians during the quarter, 220 had a saliva test performed and only 2 (0.9%) of the 220 tests were positive. 

The results for mumps testing were much different. During the same quarter, 5,945 cases of mumps were reported, 3,356 or 56.5% were tested and 1,381 (41%) were positive by the saliva test.

Clearly, the validity of measles, rubella and even mumps reporting is suspect.

A similar picture was also evident in the second and third quarters of 2005.[15] [16]

Oral fluid testing (saliva) for measles, mumps and rubella began in the UK in 1995.[17] It is worth noting that until 1998, the health authorities continued to provide counts of reported and not of confirmed measles cases to the World Health Organization. (See WHO table above). 

It is important to point out that the increases in reported and confirmed cases of measles during 2006 and 2007 were part of the global increase in measles activity still going on and will be discussed in the next section.

Considering measles-related deaths in the UK and according to information provided by HPA[18] and updated April 13, 2010: “In 2006 there was one measles death in a 13 years old male who had an underlying lung condition and was taking immunosuppressive drugs. Another death in 2008 was also due to acute measles in unvaccinated child with congenital immunodeficiency whose condition did not require treatment with immunoglobulin.  Prior to 2006, the last death from acute measles was in 1992. All other measles deaths, since 1992, shown above are in older individuals and were caused by the late effects of measles. These infections were acquired during the 1980s or earlier, when epidemics of measles occurred.”

Measles outbreaks worldwide

Measles outbreaks have been occurring worldwide since 2006 even in highly vaccinated countries.

In Saudi Arabia[19], where infants routinely receive a monovalent measles vaccine at age 9 months and two MMR vaccines, at age 1 and again at age 4-6 years and where vaccination rates with measles-containing vaccines have consistently been between 95 and 98% during the last 6 years, there were 4,648 cases of measles in 2007 compared to 373 cases in 2005, 807 in 2006, 157 in 2008 and 82 in 2009.

So in 2007, in spite of the superior vaccination rates in Saudi Arabia, there were 4,648 reported cases of measles in an estimated population of 27.6 million. In the same year, there were 3,670 reported cases of measles, of which 990 were confirmed, in the United Kingdom, estimated population 61 million.[20] 

In Switzerland, the MMR vaccine has been licensed and used since 1985 when a catch-up vaccination was also recommended for teenagers aged 12 - 15 years. A second dose of MMR was recommended in 1996. Vaccination coverage for at least one dose by age 2 remained stable at around 82% during the decade of the nineties. It increased to around 87% in 2005 - 2007. For eight-year olds, the MMR vaccination rate was 90% while for adolescents, it was at 94%. Full vaccination with two doses of MMR reached 71 to 76% in Switzerland.

There were on average 50 notified cases of measles a year in Switzerland (population 7.5 million) from 1999 to 2006 except for 2003, when there was an outbreak of 612 cases.

From November 2006 to September 2009, Switzerland experienced a full scale epidemic with 4415 reported measles cases. The incidence rates of 15 per 100,000 in 2007 and 29 per 100,000 in 2008 were reportedly the highest in Europe.[21]

Switzerland and Saudi Arabia use serum and not saliva testing to confirm measles cases. 

Measles outbreaks are still going on worldwide regardless of vaccination rates as evidenced by a CDC Update to Travelers dated September 9, 2010[22] stating: “Measles remains a common disease in many parts of the world. An estimated 10 million cases and 164,000 deaths from measles occur worldwide each year… Measles outbreaks are common in many areas including Europe …”

In England, any report of a small cluster of measles was an opportunity to blame Dr. Wakefield and his research, particularly as the much advertised GMC hearings got underway. [23] [24] [25]

Even a single confirmed case of measles in an unvaccinated or under-vaccinated English child always signaled an avalanche of blame by many who should have remembered that it was not Andrew Wakefield who banned the importation of the single vaccines in 1999

Meanwhile, Autism Spectrum Disorders have increased in Great Britain at an alarming rate. As described in an article on March 2, 2006, there were 3,484 schoolchildren with autism in Scotland in 2005, compared to only 820 in 1998, a four-fold increase.[26]

More recently, (June 2009), Professor Baron-Cohen et al[27] estimated the prevalence of autism-spectrum conditions in the UK to be 157 per 10 000.
 

Conclusions

For the last 12 years, Andrew Wakefield has been abused and attacked for having dared say that research was needed to rule out an MMR vaccine-autism connection in a small subset of genetically predisposed children. His suggestion to have single vaccines available until such research was done was also harshly and consistently criticized.  

Wakefield accusers have never mentioned the fact that the UK Department of Health stopped the importation of the monovalent measles, mumps and rubella vaccines in order to force parents to accept the MMR, giving those who were concerned about its safety and unwilling to go the triple-vaccine route, difficult choices: To buy the single vaccines at private clinics in England, to take a train ride to France to get them a little cheaper or … to do nothing.

The most painful insult hurled against Dr. Wakefield must have been the allegation that his research caused measles epidemics and killed children.

The unrelenting press coverage, the explosion in the number of autism cases in the UK and the reports by some parents that their children regressed after MMR vaccination were in all likelihood more responsible for the drop in MMR vaccination rates than an article in The Lancet and a statement at a press conference in 1998. 

Another important but rarely mentioned factor, was that young parents who saw how shabbily families who had children with MMR-related regression and GI disorders were treated by the authorities, how their legal aid was curtailed and how thousands went  uncompensated, decided to forgo the vaccination altogether rather than take a chance.   

However, whatever the reasons for the drop in vaccination rates in England, it appears that when measles outbreaks occurred in the United Kingdom in the last twelve years they also occurred in Europe and elsewhere in the world, often in well vaccinated populations.   

The evidence presented here is clear: According to official UK Government reports, the number of notified measles cases decreased from 1998 to 1999 to 2000 to 2001 and there were fewer cases of the disease during the ten years that followed the Wakefield paper than in the previous ten years.

It is impossible to draw reasonable conclusions concerning the number of confirmed measles cases in the United Kingdom during the last twelve years. What seems clear is that increases coincided with worldwide measles activities or sudden changes in diagnostic techniques and classification.  

According to HPA statistics, there was no “Wakefield Factor”.

It is time to stop blaming Andrew Wakefield and start putting the blame where it belongs.

References:


Acknowledgement: The assistance of a distinguished Israeli vaccine researcher who prefers not to be named is greatly appreciated. 

Conflict of Interest: I am a proud and grateful supporter of Dr. Andrew Wakefield

F. Edward Yazbak MD, FAAP
Falmouth, Massachusetts