Aaby, Peter

Bennett, J.

Knudsen, K.

Samb, B.

Seck, A.M.C.

Simondon, François

Whittle, H.

Horizon / Pleins textes

I - SW-STD I 
L - E-fiT 
- SN-HT 
0.80 ' I I I ,  
i 2  1'8 i4 $0 3k i 2  i 8  i 4  EO 66 72 78 
Age in months 
Figure: Survival curves for boys (from ags 10 months) who had 
recsived EZ-HI at 5 months, SW-HI at 5 months, or SW-STD 
measles vaccine at 10 months 
Children born between February, 1987, and January, 1989, and followea 
until February, 1994. Comparison made with 10 months of age wnen 
children in control group received SW-STD measles vaccine. 
From data in the thesis and using a different cut-off of -2. 
z-scores Garenne concludes that EZ-HT measles vaccine is 
de!ererious for boys, the difference being especially striking 
for wasting (weight-for-height). It should be noted that with 
a prevalence of 6.3% and 2.0% for EZ-HT and SW-STD 
boys, respectively (table), wasting was uncommon in bo& 
groups, being acrually lower than expeczed (2.5%) in the 
The most re!evant crireria for malnutrition may be 
debatable. However, monaliry is the critical issue. We have 
followed the trial cohort until the annual c e m x  in February, 
1994. As shown in che figure, there was no difference in 
morraliry beween boys who had received EZ-HT, SW-HT, 
or SW-STD. In the subgroup of children participating in the 
nutritional survey, there was sipiiïcantly lower survival for 
EZ-HT girls than in recipients of standard vaccine 
(mor1ah-y ratio [MR] 2-53 [95% CI 1-13-5-71]). Akhoug!! 
SW-STD groups. 
Deaths/number of chlldren 
Female Male 
€2-HT SW-STD E.HT SW-STD ' Number 19/251 8/269 10/238 12:251 
High-titre measles vaccines for boys UR (EL'SW) 2.95 (1.13-3.71) 0.88 10.39-2.00) 
WelgM-forage 
<-3 z.score 3414 0/6 1/13 3/15 
high-titre measles vaccines in Niakhar, Senegal. Tne Endings -3 to -2 z-score 6/54 1/50 3/63 4/42 
of the trial were reponed'.' and in detail more recently.' >-2z-score 10/181 7/213 6/162 5/194 
SIR-Garenne (July 25, p 261) analyses data from a rial of 
246 (1.06-5.72) 042 (0.37-1.84) Briefly, 1579 children bom between February, 1987, and 
January, 1989, were randomised to receive Edmonston- He1gM-fo-W 
Zagreb high-titre (EZ-HT), Schwarz high-titre (SW-HT), or 
placebo at 3 months of age. Recipients of placebo were 
months. 
MR 
6/34 0/21 2/27 
3/55 5/70 
10/162 3/lÏ8 >-2Fscore 
Welght-forhelght 
<=-3 z-score 
offered Schwan standard (SW-STD) measles vaccine at 10 UR (EZISW) 2.40 (1.01-549) 0.82 (0.35-1.91) 
- 0/1 0/2 In autumn, 1990, when we suspected that EZ-HT measles 
vaccine could be associated with reduced survival,:*4 we -3 :o -2 z-score 1/8 0/4 2/13 
conducted a follow-up study and a nuuitionai survey of all &2(i:;yi) 18/240 2.57 (1.14-5.81) 8/265 8/223 0.77 (0.34-1.701 1 Participants still residing in the study  are^. Weight, height, 
and arm-circumference were measured in 1261 of 1323 
eligible children who were seen a t  home. At the time, the 
elsewhere' there were significantly more EZ-HT girls than 
fe3IakS in the standard group who had 2-scores of -3 O r  
lower for weight-for-age (14249 zts 6i269; p=@O45) and 
height-for-age (34251 vs 21/269; p=O.O33), but no (2-scores) in November4ecamber. 1990 for recipients of 
W r - c ?  +èr the boys. EZ-HT and SW-STD measles vacci*. - 
- 0 / 2  
~ - ~ ~ ~ m f e r e n c J  
1/3 
1/6 1/11 3/12 3/10 i 11.1-12.5 
2.54 (1.12-3.75) 0.84 (0.38-147) I UR (EZ/SW) 
252 ch~ldren wno had received SW-HT ~/accine not included. 
Table: Mortaiity (1990-94) in relation to nutritional status 1 
children were aged 2 2 4 5  months. As is being reported >i26 17/240 7/258 7/222 9/2411 h" y-j 
ar" CO5 
EZ-HT girls were more malnourished, the difference in 
mortaiin- was not explained by differences in nutritional 
Siams, and the AAR remained unchanged when adjusment 
was made for nutritional status (table). For boys, there was 
no indication of increased risk for recipients of EZ-HT 
compared with standard vaccine (MR 0.88 [0*39-2*00]). 
Hence, in contrast to Garenne and colleagues' earlier 
conclusion,' there is no indicauon that high-urre vaccine was 
dzlererious for boys from (a) the complete set of nutritional 
cata  (rable),' (b) the currently available follow-up data on 
mortality from the trial (fi,we), (c) routine use of EZ-HT in 
Senegal following the nial (unpublished data), or (d) other 
t;ials.'.j 
.Although unesplained, the conclusion remains that EZ- 
HT and Schwarz-HT vaccines are only associated with 
rzauced survival among female recipients compared with 
siris receiving standard vaccine, and this difference is not 
explained by nutritional status. Most importantly, there is no 
increase in mortality for female recipients of EZ-HT ' 
compared with unvaccinated We caution readers to 
wi-irhhold jud,ment about the findings in these studies until 
I 
i 
complete data sets are available for scrutiny. 
\Te thank the Espanded Progamme on Immunization, % 
of ti-ie European Community, Bruelles (TS3'-CT9 1-0001) for financial 
i 
? ' Organization. the Task Force for Child Survival and Development, 
.Adanta. L'SA: and Science and Technology for Development Programme 
support. i 
i 
i 
3 Peter Aaby, Kim Knudsen, Francois Simondon, Badara Samb, i 
Hilton Whittie, Awa Marie Col/ Seck, John Bennett 
Danish Eaidemiology Science Centre. Statens Serumlnstitut. 2300 CoDenhagen S. 
DenmarK: UR Maladies InTeCrleuses et Parasitaries, ORSTOM, Dakar, Senegal: 
h!RC LaDoratories. Banjul, the Gambia: Univerité Cheikn Anta DIOP. Dakar. Senegal: 
ani  Task Force for Child Survival and Develo 
1 
~ 
Garenne M. Leroy O, Beau Jp, Sene I. Child mortality after hi, Wh-tine 
mrasies vaccines: prospective study in Senegal. Lancer 199 1; 338: 
903-OÏ. 
Aaby P. Samb B, Simondon F, et al. Child morraliq after high-nue 
messies racclnes in Senegal: the complete data set. Laizczr 1991; 338: 
151s. 
3 .laby P, Samb By Simondon F, et al. Ses specific monaliF after high 
titre measles vaccines in rural Senegal. Bull Wúrld Health Organ 
(in press). 
Aaby P, Knudsen IC, Whirrle H, et al. Long-term survival after 
Edmonston-Zagreb measles vaccination: increased female mortalir).. 
J" Pcdiarr 1093: 122: 90448. 
Holt EA, Moulton LH, Sibem GE;, Halsey NA. Differential mortaiin. 
by me3sles vaccine titre and ses. 
2 
4 
5 
Infecr Dis 1993; 168: 1087-96. 
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High-titre measles vaccines for boys

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