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Letters to the Editor

Indian Pediatrics 1998; 35:686-688

Reply


We thank Dr. Jacob John for his comments and suggestions which are well taken. We have tried to re-analyse our data based on his suggestions.

On analysis of the infants based on the preimmunization titer, it was found that the infants having pre-immunization titer
0.15 mcg/ml (n = 33) had lesser degree of rise in the titer following immunization with Hib as compared with their other counterpart, i.e., those with preimmunization titer < 0.15 mcg/ml (n = 70). However, this difference was not statistically significant (Table 1).

When tabulated for the age at first dose in weeks against the basal anti PRP titers, there was no trend towards an increasing titer with increasing age at first dose
(Table II). Therefore the higher titers are more likely to have come from the mothers. The percentage of children with a basal level
0.15 mcg/ml in this study is consistent with published international data(1).

As suggested we did regroup the infants according ,to the interval between doses. Only one child had been vaccinated at exactly 4 weeks interval between three doses and no infant had an interval of 8 weeks between doses. Due to this fact, such analysis was not feasible. Although we agree with the thought of doing such an analysis, we may need to plan this out in a larger study.

We would also like to point out that apart from dosage interval, there are many other factors that influence Hib immune responses. For example, for Hib oligosaccharide-CRM 197 conjugate vaccine (HbOC) (HibTITER), a direct relationship has been noted between the magnitude of the immune response and increasing age, up to approximately 13 months of age, following a single 10 mcg dose of HbOC(I,2). There is also a direct relationship between increasing age and percentage of children with titers greater than 1 mcg/ml following one dose' of HbOC(2). Avidity (i.e., binding power), which is a measure of the func- tional capacity of antibody response, is also an important factor. HbOC stimulates anti- bodies with high avidity, suggesting that lower levels than l,mcg/ml are potent functionally(3). In addition, for primary series Hib vaccination, protective antibody levels have been noted with inter-dose intervals as one month between doses(4).
 

V.B. Sovani,
Medical Director,
Wyeth Lederle Limited, Mumbai,
India.
 




TABLE I

Comparative Change in GMT for Infants with Pre-Titer0.15 mcg/ml and 0.15 mcg/ml.

Titres (log 10 values)

Group (Pre 0.15 mcg/ml) Pre Post Change
N 33 33 33
Mean -0.3164 0.5926 0.9090"
SD 0.4141 0.9180 1.0847
P (paired-t)
Geometric mean 0.483

3.914

 
Group (Pre 0.15 mcg/ml) 
N 70 70

70

Mean -1.1841 0.6954

1.8795**

SD 0.1712 0.9649

0.9660

P (paired-t)    

< 0.001

Geometric Mean 0.065

4.959

 
Analysis of Covariance Results Post Means adjusted for common Pre-mean
Pre < 0.15 mcg/ml      
Mean -0.7503 0.688  
Geometric mean 0.178  4.875  
Pre < 0.15 mcg/ml      
Mean  -0.7503  0.600  
Geometric 0.178 3.981  
Difference   NS  
P     0.81  

NS-Not significant.




TABLE II

Age Specific GMT in Children With
Basal Levels;? 0.15 mcg/ml.

No. of Infants at various pre titer intervals (mcg/ml).

Age >0.15 0.40 0.65 ≥0.90 ≥ 1.15 ≥1.40 Total Pre-titer
(Weeks) <0.40 <0.65 <0.90 < 1.15 < 1.40     GM
6 4 1 2 1     8 0.425
7 4 1 2 1   1 9 0.521
8     1     1 2 1.521
9   2     1   3 1.729
10 6     1   1 8 0.534
11 1           1 0.434
12 1           1 0.300
16 1           1 0.190
Total 17 4 5 3 1 3 33 0.220


 

References

1. Madore DV, Johnson CL, Phipps DC, Pennridge Pediatric Associates, Popejay LA, Eby R, et al. Safety and immuologic response to Haemophilus influenzae type b Oligosaccharide- CRM 197 Conjugate Vaccine in 1-to-6 months old infants. Pediatrics 1990; 85: 331-337.

2. Madore DV, Phipps DC, Eby R. Immune response of young children vaccinated with Haemophilus influenzae type b conjugate vaccines. Contr Microbiol Immunol 1989; 10: 125-150.

3. Schlesinger Y, Granoff DM, The Vaccine Study Group. Avidity and bactericidal activity of antibody elicited by different Haemophilus Influenzae type b conjugate vaccines. JAMA 1992; 267: 1489-1494.

4. Goldblatt D, Fairley CK, Cartwright K, Miller E. Interchangeability of conjugated Haemophilus influenzae type b vaccines during primary immunization of infants. BMJ 1996; 312: 817-818.
 

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