RESEARCH VACCINE TURNED DEADLY TO THIRD WORLD BABIES -----W. Cooley-Prost
worth@igc.apc.org 

FACT SHEET

*1987  Major studies of high dose EZ measles vaccine started in Haiti, Senegal,
Mexico,1 Guinea Bissau.  EZ vaccine in normal doses had been used in Europe since
1970s and by UNICEF since 1988, but high dose EZ was made specifically for
studies in the Third World.  Researchers hoped that very high doses -- 10 to 500
times normal -- would overwhelm the maternal antibodies that normally prevent a
young infant's immune system from responding to measles vaccine.

*October 1989  WHO recommended high dose EZ for 6-month-old babies in Third World
countries, changing a long-standing policy of delaying measles vaccine until at
least 9 months.  In the U.S., the usual age for measles vaccine is 15 months. CDC
announced a contract with Kaiser for the Los Angeles study, and filed an
Investigational New Drug application with FDA.

*April 1990  The director of an African study site alerted WHO and CDC to
possible mortality increase in babies given high dose EZ. Mortality data from the
Senegal and Guinea Bissau sites were borderline then, but by that fall were
statistically significant.  Still, the problem was reportedly ignored, dismissed
or contradicted by CDC and WHO researchers for many months.

*June 1990  Los Angeles trial began enrolling inner-city minority infants as
young as 6 months.  Funded by CDC and NIH, about 1,500 black and Hispanic babies
were enrolled.

*February 1991  The mortality data were deemed inconclusive at a vaccine
committee meeting, and studies continued.  The investigator who identified the
mortality problem decided the only ethical alternative was to publish his
findings whether the other researchers agreed or not.

*April-May 1991  Haiti study mortality data was collected by Johns Hopkins
researchers, but according to subsequent independent analysis, they located only
63% of the high dose EZ babies.

*October 1991  Lancet published the African mortality data.  WHO's vaccine
committee asked all study sites to submit their mortality data for independent
analysis, and scheduled a June 1992 meeting to address the results. Enrollment
was halted in Los Angeles, and followup studies began there in 1992.

*June 1992  Independent analysis confirmed increased mortality in high dose EZ
babies, especially girls.  The mortality pattern suggested lasting
immunosuppression.  Analysis conducted by the London School of Hygiene and
Tropical Health found "consistent evidence of increased mortality risk..."

*August 1993  NIH's Office of Protection from Research Risks visited CDC during
an investigation of the Los Angeles study and a complaint about failure to inform
parents of the vaccine's experimental status, risk of adverse reactions, and
possible long term problems.

*June 1996  CDC director Satcher explained that Los Angeles parents weren't
informed of EZ vaccine's experimental status because of "a little mistake." (Los
Angeles Times, June 17, 1996)


1  The Mexico study enrolled about 1,400 babies, but excluded those with
malnutrition, any immune disorder, a history of measles or measles vaccination,
or recent oral polio vaccine.  Thus, this population was not comparable to either
the other study populations or usual Third World populations.  Mortality followup
was done in spring 1992, but no data on infants in the Mexico or Los Angeles
studies were submitted for WHO's independent analysis.  The CDC measles expert
who led both studies, currently in Thailand overseeing a project related to AIDS
vaccine, did write the independent analyst that mortality was not increased in
either study. worth@igc.apc.org

FACT SHEET: SELECTED REFERENCES

Note:	Fact Sheet information is drawn from a wide range of sources, including:
published medical literature, mainstream press, and materials from WHO, CDC, FDA,
NIH, PAHO and other agencies; government project and funding databases; documents
obtained under the Freedom of Information Act; regulatory, clinical and bioethics
documents; unpublished reports; correspondence; and numerous interviews between
1994 and 1996 in seven states and three foreign countries. Persons interviewed
include principal investigators and other research workers involved in the EZ
studies; other physicians, research professionals and study site personnel; U.S.
government officials, senior compliance officers, attorneys and agency staff;
foreign government officials, including Ministers of Health, Social Affairs and
Foreign Affairs; university faculty members; vaccine experts; journalists; and
nonprofit organization staff.  Citations selected from over 150 references are
provided below.


1987  Major studies of high dose EZ measles vaccine...

*  Haiti--  Job JS, Halsey NA, et al. Successful immunization of infants at 6
months of age with high dose Edmonston-Zagreb measles vaccine.  Pediatr Infect
Dis J 1991; 10(4):303-311. *  Senegal-- Garenne M, Leroy O, et al. Efficacy,
safety and immunogenicity of two high-titre measles vaccines: Final Report,
ORSTOM, Dakar, June 1991.  Also Garenne M, Leroy O, et al. High-titer measles
virus vaccines: protection evaluation. In Measles and Poliomyelitis, ed. by E.
Kurstak, Springer-Verlag 1993: 119-131.  * Mexico-- Markowitz LE, Sepulveda J, et
al. Immunization of six- month-old infants with different doses of
Edmonston-Zagreb and Schwarz measles vaccines. N Eng J Med 1990; 322:580-587.  
*  Guinea Bissua-- Aaby P, Jensen TG, et al. Trial of high-dose Edmonston-Zagreb
measles vaccine in Guinea-Bissau: protective efficacy. Lancet 1988; i:809-811,
and 811-814 (antibody response and side effects).  * Standard titer EZ vaccine:  
Ikic D, Jazbasic M, et al. Attenuation and characterization of Edmonston-Zagreb 
measles virus. Ann Immunol Hung 1972; 16:175-181.

October 1989  WHO recommended high dose EZ...  Expanded Programme on
Immunisation. Safety and efficacy of high titre measles vaccine at 6 months of
age. Weekly Epidemiol Rec 1990; 65:5-12.

* Los Angeles study: Kaiser/CDC contract #200-89-0736 (9-30-89).

* Office of Protection from Research Risks, National Institutes of Health.
Evaluation of human subject protections in research conducted by the Centers for
Disease Control and the Agency for Toxic Substances and Disease Registry, Sept.
25, 1995.

January & April 1990  The directors of two African study sites alerted WHO...
Garenne M, Leroy O, et al. Child mortality after high-titre measles vaccines:
prospective study in Senegal. Lancet, Oct. 12, 1991; 338:903-907, 920.  * Fine P,
xxxxxxxxxxxx  * Also interviews 1/95 - 7/96 (Arlington VA, Boston, Geneva,
Paris).

June 1990  Los Angeles trial began enrolling... CDC press materials, June 1996.
Office of Protection from Research Risks, National Institutes of Health.
Evaluation of human subject protections in research conducted by the Centers for
Disease Control and the Agency for Toxic Substances and Disease Registry, Sept.
25, 1995.

February 1991  The mortality data were deemed inconclusive... Expanded Programme
on Immunisation. Safety and efficacy of high titre measles vaccine at 6 months of
age. Weekly Epidemiol Rec 1991; 66:249-251, and 1992; 67:357-360.   * Also
interviews 1/95 - 4/96 (Arlington VA, Boston, Paris, Washington DC).
worth@igc.apc.org

April-May 1991  Haiti study mortality data collected... Holt EA, Moulton LH, et
al. Differential mortality by measles vaccine titer and sex. J Infect Dis 1993;
168:1087-1096.  Also Dowell SF, Davis HL, et al. The utility of verbal autopsies
for identifying HIV-1-related deaths in Haitian children. AIDS 1993; 7:1255-1259.
Also London School of Hygiene & Tropical Medicine, mortality analysis presented
in Atlanta GA, June 1992.

October 1991  Lancet published...   Garenne M, Leroy O, et al. Child mortality
after high-titre measles vaccines: prospective study in Senegal. Lancet, Oct. 12,
1991; 338:903-907, 920.  Aaby P, et al. Child mortality after high-titre measles
vaccine in the Senegal: the complete data set. Lancet 1991; 338:1518 and Garenne
M, et al, 1519.

June 1992  Independent analysis confirmed...  London School of Hygiene & Tropical
Medicine, mortality analysis presented in Atlanta GA, June 1992.  * High-titre
measles vaccine dropped. Lancet, July 25, 1992; 340:232.  * Haiti-- Holt EA,
Moulton LH, et al. Differential mortality by measles vaccine titer and sex. J
Infect Dis 1993; 168(5): 1087-1096.  * Halsey NA. Increased mortality after high
titer measles vaccine: too much of a good thing. Pediatr Infect Dis J 1993;
12-462- 465.

August 1993  NIH's OPRR visited CDC...  Office of Protection from Research Risks,
National Institutes of Health. Evaluation of human subject protections in
research conducted by the Centers for Disease Control and the Agency for Toxic
Substances and Disease Registry, Sept. 25, 1995.

June 1996  CDC director Satcher explained... Cimons M. CDC says it erred in
measles study; Agency failed to tell parents that one of two vaccines used on
infants in L.A. during epidemic was experimental, officials say. Los Angeles
Times, June 17, 1996.  Also CDC and Kaiser press materials, June-August 1996.
cities / states:

Arlington VA (Michel, Barbara), Vienna VA (NVIC 1995, 1996) Atlanta GA
(Rosenthal, CDC) Baltimore MD (Halsey et al), Bethesda (OPRR, OAR, NIH);
Rockville (FDA, FOI offices) Boston MA (Maria Madison) Los Angeles CA (Michael
Marcy) Miami FL (Kathi Maternowska) New York NY (Michelle Karshan, Ron Howell)
Washington DC (Maurice Hilleman, USAID, PAHO)


cities / countries:

Geneva, Suisse (Clements) Paris, France (Michel) Port-au-Prince, Haiti (Boulos,
many others)

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