39

Original Article

Pedimune in Recurrent Respiratory Infection and Diarrhoea- The Indian Experience-The PRIDE Study Kamlesh Patel and Rajiv Rana

Merck Ltd., Mumbai

ABSTRACT

Objective. To evaluate the efficacy and tolerability of bovine colostrum in preventing recurrent episodes of upper respiratory tract infections and diarrhoea in children

Methods. 605 children (1-8 yrs) having recurrent episodes of upper respiratory tract infections or diarrhea received Bovine Colostrum (Pedimune | for 12 weeks. Total no of episodes of recurrent infections, hospitalization rate, overall well being and adverse events were assessed at every 4 weeks.

Results. Episodes of URTI and diarrhoea reduced significantly by 91.19 % and 86.60% at the end of therapy respectively. High to average improvement in overall well-being in 96 % of the patients were found by pediatrician while overall well-being stated by the patient/care taker was very good to good in 90.56 % of the patients.

Conclusion. Bovine colostrum was highly effective in the prophylactic treatment of recurrent URTIs and diarrhea in reducing nnt only the episodes but also the hospitalization due to them. [Indian J Pediatr 2006; 73 (7) : 585-591] E-mail : rajiv.rana@merck.co.in

Key words : Bovine colostrum; Respiratory infection; Diarrhoea

Respiratory diseases are a major cause of morbidity and mor ta l i ty in deve lop ing countries. Data sugges t that chi ldren could suffer f rom 7 to 8 u p p e r r e s p i r a t o r y infections per year until they are 5 years of age, when their i m m u n e s ta tus reaches adu l t level . ~ Acute u p p e r respiratory tract infection (URTI) is a common disease in young children and contributes to approximately 20% of mor ta l i ty in chi ldren younge r than 5 years of age. It represents the most frequent problem in general pediatric practice and are responsib le for more than a th i rd of school absence. 2

Diarrhea on the other hand is a major killer disease in children under five and recurrent diarrhea affects nearly 20% of the population, thus an important public health problem. 3-6

The use of b o v i n e c o l o s t r u m as p r o p h y l a x i s or t reatment for infectious disease relates to the historical concept of " immune milk" being capable of transferring passive immunity. Bovine colostrum contains not only detectable levels of immunoglobul ins far much higher (several hundred fold) than ordinary bovine milk 7, 8 but

Correspondence and Reprint requests : Dr. Rajiv Rana, Merck Ltd., Shiv Sagar Estate, 'A', Annie Besant Road, Worli, Mumbai-18.

also conta ins a ser ies of p h y s i o l o g i c a l l y b ioac t ive constituents such as growth promoting factors that act as media to r s of infantile g rowth and d e v e l o p m e n t 9~1 in addition to a series of antimicrobial fractions including lactoferrin : lactoperoxidase and lysozymes. 12q*

Local p ro t ec t i on in the f o r m of i m m u n o - supplementation with bovine antibodies has been shown to be an effective means of providing local protection to the GI t ract aga ins t d isease . 1~ C o l o s t r u m f rom nonimmunized cows contains antibodies against many enteric pa thogens and bovine immunog lobu l in in the fo rm of specific an t i body has also been shown to be effective against various enteric diseases. ~5~7

Regular consumpt ion of bovine colostrum has been reported as a protective role for infantile gastrointestinal i m m u n i t y due to its direct effect on s t imula t ion and development of infantile gut-associated lymphoid tissues which are responsible mainly for enhancing the infantile gut immunity. ~a2~ The studies 2~-24 in infants indicate the poss ib le t h e r a p e u t i c role of o ra l ly inges t ed b o v i n e c o l o s t r u m aga ins t m a n y bac te r i a l and v i ra l gastrointestinal infectious diseases.

In childhood, evaluation of immune system functions is necessary if these recurrent infections especially acute respiratory tract infection have an unexpectedly severe course. Bovine co los t rum increases sa l ivary IgA that

Indian Journal of Pediatrics, Volume 73--July, 2006 585

40

Kamlesh Patel and Rajiv Rana

primari ly protects against respiratory tract infections. 2s Bovine colostrum contains high levels of oligosaccharides, which help prevent bacteria from attaching to the mucous membranes, which line the gut and the throat. 26 Clinical evidence suggests that bovine colost rum may prevent upper respiratory tract infection (URTI). ~7

To date, local clinical tr ial da ta on use of bov ine colostrum in recurrent infection in India is lacking. The present s tudy was therefore conducted to evaluate the efficacy and tolerability of bovine colostrum in preventing recurrent episodes of upper respiratory tract infections and diarrhea in children.

MATERIALS AND METHODS

Patient Popula t ion

In this open, mul t i -cent r ic , n o n - c o m p a r a t i v e , pos t - marke t ing s tudy, a total of 605 chi ldren of either sex between i to 8 years of age were enrolled after obtaining in fo rmed wri t ten consent f rom parents , gua rd ian or caretaker of the child. The study was conducted involving 133 pediatricians across the country. Children having recurrent episodes of upper respiratory tract infections (def ined as >6 ep i sodes of u p p e r r e s p i r a t o r y t rac t infections during the period 6 months prior to enrollment in the study) or having recurrent episodes of diarrhea (def ined as >6 ep i sodes of d i a r rhea not r e q u i r i n g hospi ta l iza t ion or >2 episodes of d iar rhea requ i r ing hosp i ta l i za t ion du r ing the per iod 6 mon ths pr ior to enrol lment in the study) were inc luded in the study. Children, having any abnormali t ies of the respi ra tory tract, those having >3 episodes of lower respiratory tract and infections requir ing hospi ta l izat ion in the past 6 m o n t h s or those ch i ld ren r ece iv ing co r t i cos te ro ids ( sys temic or topical) , i m m u n o m o d u l a t o r s or w h e n p a r e n t / g u a r d i a n did not give informed consent, were exc luded . All ch i ld ren r ece ived Bovine C o l o s t r u m ( P e d i m u n e | Mfg. by Merck Ind ia Ltd.) 3 gm (one teaspoonful) with a glass of water once daily for a period of 12 weeks. The selection and recruitment of patients in the trial commenced f rom I October 05 and s tudy was completed by March 06.

A s s e s s m e n t Parameters

Primary outcome measure was reduction in the number of episodes of upper respiratory tract infections occurring dur ing the s tudy per iod (time f rom enrol lment to 12 weeks of bovine colostrum therapy) as compared to the 6 months prior to enrollment in the study.

Seconda ry o u t c o m e m e a s u r e s we re r educ t ion in n u m b e r of ep i sodes of d i a r rhea and f r e q u e n c y of hospitalization required for RTI & diarrhea during study period as compared to 6 months prior to enrollment.

An overall well-being of patients and tolerability was evaluated by the patient / parent / guardian/caretaker on

a 5-poin t r a n k i n g scale of "1=Very Good, 2=Good , 3=Average, 4=Poor & 5=Very Poor". Physician evaluated global assessment of the patient's condition after 12 weeks of bovine colostrum therapy on a 5-point ranking scale of "1=High improvement, 2--Average improvement, 3=Poor improvement , 4=No improvement and 5--Worsening' . Fol low-up was done every 4 weeks for a per iod of 12 weeks and total no of episodes of recurrent infections; hospi ta l iza t ion rate, overal l wel l -be ing and adver se events were assessed at every 4 weeks.

Statistical A n a l y s i s

The quantitative data is expressed as mean and standard deviation, whereas incidence is expressed as proportions. Ranking or categorical data was analyzed using Kruskall- Wallis test, Mann-Whi tney 'U ' test & Chi-Square test. Quan t i t a t i ve data is a n a l y z e d us ing the A N O V A & s tudents t-test. For all tests, a ' p ' va lue of <0.05 was considered significant at 95% C.I.

RESULTS

Of the 605 patients enrolled, 551 patients (341 males & 210 females) completed the study. 50 patients were lost to fotlow-up, 2 patients withdrew due to poor acceptability, i patient needed bronchodilator therapy for severe lower respiratory tract infection & was withdrawn, Whereas 1 patient developed macular skin rash and was withdrawn. The results of 551 patients who completed the study were ana lyzed . Table 1 shows the d e m o g r a p h y and the baseline data of the patients enrolled in the study. Large number of children were between 2-4 & 4-6 years of age (38.29% & 29.04% respectively) as compared to <2 & > 6 yrs of age (15.43% & 17.24% respectively) (Fig. 1).

TABLE 1. Demography of the Patients Enrolled in the Study

Parameter Mean S.D. Range

Age (yr) 3.79 1.97 i yr - 12 yrs Height (cm) 92.03 17.59 19.00 - 152.00 Weight (Kg) 13.29 4.43 5.00 - 35.00

No. of Episodes in past 6 months URTI 5.94 3.83 0 - 20 Hospitalization for RTI 0.33 0.95 0 - 10 Diarrhea 1.08 2.03 0 - 12 Hospitalization for 0.18 0.75 0 - 10

Diarrhea Other Infections 0.20 0.58 0 - 4

As shown in table 2, the number of episodes [Mean _+ S.D.] of URTIs occu r r ing 6 m o n t h s p r io r to b o v i n e co los t rum the r apy was 5.94 _+_ 3.88 which dec reased significantly to 1.60 + 1.74, 0.99 + 1.20 and 0.52 _+_ 0.91 at the end of 4 wks, 8 wks and 12 wks of bovine colostrum therapy respectively (p<0.05). The reduction in the mean number of episodes of URTI was similar in the children of

586 Indian Journal of Pediatrics, Volume 73--~July, 2006

41

P e d i m u n e in Recurrent Respiratory Infect ion and Diarrhoea

< 2 years > 6 years [n=85]

[n=9~ - N ~ f 1543% 17.2~/o ~ ,

[n=160] |Niiii~.i~i:i:] r X,_ [n=2111 29.04% ~ ~ , - - ' " 38.29%

Fig. 1. Age distribution of the patients enrolled in the study [n=551]

all age g roups (p>0.05). As shown in the table, after bovine colos t rum therapy,

the pe rcen t age r e d u c t i o n in the n u m b e r of ep i sodes of URTI f rom basel ine was, 73.01%, 83.25 % and 91.19 % at 4,8, and 12 weeks respect ively.

The mean n u m b e r of ep isodes of d ia r rhea occurr ing 6 months pr ior to bovine colos t rum the rapy was 1.08 _+ 2.03. This decreased signif icant ly to 0.33 -+ 0.84, 0.18 _+ 0.66 and 0.14 _+ 0.61 at t he e n d of 4, a n d 12 w e e k s of b o v i n e co los t rum the r apy respect ive ly (p<0.05).

S h o w n in Table 3 is the p e r c e n t a g e r e d u c t i o n f rom baseline, in the n u m b e r of pat ients r epor t ing ep isodes of URTI a n d d i a r r h o e a at 4, 8 a n d 12 w e e k s af te r b o v i n e c o l o s t r u m t h e r a p y . A s i g n i f i c a n t r e d u c t i o n of 20.5%, 35.6% a n d 64.5% w a s o b s e r v e d at 4, 8 a n d 12 w e e k s of therapy, respect ively, in the n u m b e r of pat ients r epor t ing episodes of URTI. A significant reduct ion of 35.6%, 64.3% a n d 71.3% was a lso o b s e r v e d at 4, 8 a n d 12 w e e k s of therapy, respect ively, in the n u m b e r of pat ients repor t ing e p i s o d e s of d i a r r h o e a . F i g 2 s h o w s the p e r c e n t a g e r e d u c t i o n in the n u m b e r of e p i s o d e s of URTI in the different age groups . After bovine co los t rum therapy, the

percentage reduc t ion in the n u m b e r of ep i sodes of URTI f rom base l ine was 73.01%, 83.25 % a n d 91.19 % at 4, 8, a n d 12 w e e k s r e s p e c t i v e l y . T h e r e w a s a s i g n i f i c a n t reduct ion in the number of episodes of URTI in all the age g r o u p s at the va r i ous obse rva t ion in tervals . The va lue s s h o w n in Fig 2 indicate that at 12 weeks , the decrease in p e r c e n t a g e of p a t i e n t s r e p o r t i n g U R T I e p i s o d e s is s igni f icant ly less in age g r o u p < 2yr as c o m p a r e d to the other three age groups. The decrease is s imilar in the other 3 age groups. As shown in Fig 3 a m o n g the age g roups of

7 ~ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I ~ \

5 i , . .

Baseline 4 Weeks 8 W~eeks 12 Weeks

< 2 years [n=85] ~11 - - 2 to < 4 years [n=211]

4 to < 6 years [n=160] - , - > 6years [n=9S] ..... ~ .... Total [n=551]

Fig. 2. No [Mean _+ S.D.] of episodes of URTI in the patients during the study period [n=551]

0-

< 2 years 2 to < 4 years 4 to < 6 years > 6 years Total (n=551) In=85] [n=211] (n=160] (n=95)

10- ~ 20-

30- .~ 40-

50- 60-

~ 70 80

Fig.

50.91

67.05 66.67 64.86 64.56

3. Percent change in no. of patients reporting symptoms of URTI from baseline after 12 weeks of Pedimune therapy [n=551]

TABLE 2. Primary & Secondary Assessment Parameters at Baseline and Change at 4, 8 and 12 Weeks of Bovine Colostrum Therapy [n=551]

Parameter Baseline Mean (%) change from baseline 'p' value Mean (SD) 4 wks. 8 wks. 12 wks.

URTI episodes 5.94 (3.88) 4.33 (73.01) 4.94 (83.25) 5.41 (91.19) <0.001 Hospitalization for RTI 0.33 (0.95) 0.26 (77.74) 0.30 (90.87) 0.31 (94.22) <0.05 Diarrhea episodes 1.08 (2.03) 0.75 (69.56) 0.89 (82.87) 0.93 (86.60) <0.05 Hospitalization for diarrhea 0.18 (0.75) 0.13 (75.95) 0.16 (89.05) 0.17 (92 32) <0.05

TABLE 3. Number of Patients Reporting Episodes of URTI and Diarrhea at Baseline and at 4, 8 & 12 Weeks of Bovine Colostrum Therapy [n=551]

Parameter Baseline % reduction from baseline 'p' value No. (%) 4 w ~ . 8 w ~ . 1 2 w ~ .

URTI episodes 443 (80.40) 20.54 35.67 64.56 <0.01 Hospitalization for RTI 91 (16.52) 74.73 90.11 90.11 <0.001 Diarrhea episodes 157 (28.49) 35.67 64.33 71.34 <0.05 Hospitalization for diarrhea 39 (07.08) 66.67 84.62 84.62 <0.01

Indian Journal of Pediatrics, Volume 73--July, 2006 587

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K a m l e s h Patel and Raj iv R a n a

<2 yrs , 2-4 yr , 4-6 y r a n d 6-8 yr , p e r c e n t a g e change in pa t ien t s r e p o r t i n g s y m p t o m s of URTI was s ign i f ican t ly r e d u c e d up to 50.91%, 67.05 %, 66.67 % & 64.86 % at the end of bovine co los t rum the r apy respect ively.

F r o m F i g 4 i t is a l so e v i d e n t t h a t t he n u m b e r of e p i s o d e s of d i a r r h o e a w a s h i g h e r in t he age g r o u p b e t w e e n 2-<4 yr, as c o m p a r e d to the o ther age g roups . P e r c e n t a g e r e d u c t i o n in n u m b e r of p a t i e n t s r e p o r t i n g ep isodes of d ia r rhoea was s ignif icant ly less in age g roup 4-6 y r s c o m p a r e d to the o the r th ree age g r o u p s w h e n compar i son was done a m o n g the four age groups to f ind o u t m a x i m u m p e r c e n t a g e r e d u c t i o n in n u m b e r of d ia r rhoea episodes.

As shown in Fig 5 a m o n g the age g roups of <2 yr, 2-4 yr , 4-6 y r a n d 6-8 yr , p e r c e n t a g e c h a n g e in no of p t s hav ing d ia r rhea was s ignif icant ly r educed up to 77.14 %, 76.47%, 55.88% & 70.0% at the end of bov ine co los t rum the r apy respect ively.

F e w e r p a t i e n t s r e q u i r e d h o s p i t a l i z a t i o n d u e to diarrhea. The mean number of episodes of hospi ta l iza t ion o c c u r r i n g 6 m o n t h s p r i o r w a s 0.18 + 0.75 d e c r e a s e d s ignif icant ly to 0.04 _+ 0.29, 0.02 _+ 0.17 and 0.01 + 0.12 at the end of 4 wk, 8 w k and 12wk respect ively after t ak ing bovine co los t rum the r apy (p<0.05). N u m b e r of ep isodes of h o s p i t a l i z a t i o n d u e to d i a r r h e a w a s s i g n i f i c a n t l y r e d u c e d (p<0.05) b y 75.95 %, 89. 05 % a n d 92.32 % at 4 w e e k s , 8 w e e k s a n d 12 w e e k s of b o v i n e c o l o s t r u m

2.00 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.80 ' m,

1.60 1.40 1.20 q 1.00 0.80

{

0.60 0.40 0.20 0,00 -i

< 2 years [n=85] 2 to < 4 years [n=211] 4 to < 6 years [n=160]

, , " * -- >6years[n=95] ~':. ". ---~* - Total [n=551]

"~-x% ,.

Baseline 4 Weeks 8 Weeks 12 Weeks

Fig. 4. No . [Mean _+ S.D.] of e p i s o d e s of diarrhea in the pat ients during the s tudy period [n=551]

t h e r a p y r e s p e c t i v e l y c o m p a r e d to b a s e l i n e data . Tota l i n c i d e n c e of a d v e r s e e v e n t s w a s f o u n d to be 2.97 % s h o w n in table 4. Al l of t h e m were m i l d to m o d e r a t e in nature. One pat ient was w i t h d r a w n from the s tudy due to skin rash.

< 2 y e a r s 2 t o < 4 y e a r s 4 t o < 6 v e a r s > 6 y e a r s T o t a l ( n = 5 5 1 )

[n=85] [n=211] (n=160] (n=95) 0

10 e~ 20 "~ 30 d = 40

50 60 t~

70 80 90

100

77.14 76.47

55.88

70.00 71.34

Fig. 5. % change in no. of pts. having diarrhea from baseline after 12 wks of Pedimune therapy [n=551]

96% of the p e d i a t r i c i a n r e p o r t e d a h i g h to a v e r a g e i m p r o v e m e n t in the ove ra l l w e l l - b e i n g of the p a t i e n t s r ece iv ing b o v i n e c o l o s t r u m (Fig. 6). Overa l l w e l l - b e i n g s ta ted b y the pa t i en t or p a r e n t or g u a r d i a n or ca re t ake r

N o

Improvement Worsening Poor _.___ 1~% " - j / - 0.00%

hnprovement " - - - - - ~ 2.45% 1.. :. i i ! .~-.~:,~

u . . , . . . . , , . . ,

~!i!iiiiiiiii:iiii" "-,

/ / i 'iii i i::iii iii:;r "., ' ~ ' , i : : : : : ' : : : : : ' :Y High

Average "-' "' ~" :- 51.23% Improvement Improvement 44.96%

Fig. 6. Overall well-being assessed by the physicians after 12 weeks of Pedimune therapy on a 5-point ranking scale [n=551]

TABLE 4. Adverse Events Reported b y the Patients Dur ing the Study Period [n=605].

Event No. of patients & Severity

Mild Moderate Severe Total Outcome

Cough 01 00 00 01 Skin Rash 00 01 00 01 Stomatitis 01 00 00 01 Abdominal Pain 01 01 01 03 Nausea 01 01 00 02 Sneezing 01 00 00 01 Diarrhea 01 02 00 03 GI Upset 00 02 00 02 Vomiting 00 01 00 01 Bad taste 00 01 00 01 Wheeze attack 00 01 O0 01 Constipation 00 01 00 01 Total 06 11 01 18

Resolved Pt. withdrawn from study Resolved Resolved Resolved

Resolved Persisted in 1 pt. Resolved 1 pt. Discontinued Single episode, causality not established Resolved, Therapy continued Total Incidence = 2.97 %

588 Indian Journal of Pediatrics, Volume 73~July, 2006

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Pedimune in Recurrent Respiratory Infection and Diarrhoea

Poor - Average_ 1.20% ~ V e r y Poor

, ~ Ii::ili.:.:.-, rVe~yCooa . . . . . . . . . . - ~ ~ 35.14% ,, - . . . . . - . . . : \ ~

. . . . . i : i : : : i : : : i : i . i i~ '

Y Cood _ j - ~ i : ', ..... .-.i ' .=,iY

55.42% " . . . . . . '- ' . . . . ~

Fig. 6a. Overa l l w e l l - b e i n g a s s e s s e d b y the pa t i en t s af ter 12 w e e k s of P e d i m u n e t h e r a p y on a 5 -po in t r a n k i n g scale [n=551]

was very good to good in 90.56 % of the patient receiving bovine colostrum (Fig. 6a).

DISCUSSION

Children with a history of recurrent infections present a diagnostic challenge to their pediatricians because of the expectations of the parents for an explanation regarding the increase in the f requency of infections. 2s A wide spec t rum of diseases influences the respi ra tory tract directly or indirectly, by causing recurrent infections. The immune system is not at its full maturity at birth and may not be totally developed until school going age. The most common serological abnormali ty repor ted in children with recurrent infections is partial IgA deficiency or IgG subclass deficiency. Humoral immunodeficiency diseases such as transient hypogammaglobulinemia of infancy arid IgG subclass deficiency are also a common problem that increases susceptibility to recurrent infections. 2s Most children with recurrent respiratory infections do not have an immunodeficiency, however they often have deficient antibodies. 29 IgA a n d / o r IgG subclass deficient children may be asymptomatic, may be associated with recurrent infections, allergic disorders, au to immune disorders, malignancies or recurrent sinopulmonary infections. 3~ In humans the protective antibody in the intestinal lumen has always been assumed to be secretory IgA. 33

Lack of Indian experience and looking into above facts, we used bov ine colost ra l concent ra te con ta in ing i m m u n o g l o b u l i n d ry p o w d e r bov ine co los t rum for chi ldren (1-8 yr) having recurrent episodes of upper resp i ra tory tract infections. The choice for 3 months du ra t ion was based on the au thor ' s knowledge of frequency of URTI.

In the present study the number of episodes of URTI reduced significantly by 91.19 % at the end of 12 weeks of bov ine co los t rum the rapy . The n u m b e r of pa t ien ts reporting URTI episodes was also significantly reduced by 67.05% at the end of 12 weeks of bovine colostrum therapy. Another noteworthy finding of the present study was 86.60% reduction in number of episodes of diarrhea

and 92.00% reduction in hospitalization due to diarrhea after 12 weeks of bovine colostrum therapy, across the all age groups.

Out of the 605 pat ients , only 54 were not able to complete the study as many of them were lost to follow up. 2 patients discontinued treatment, out of which one discontinued due to skin rash and the other discontinued due to poor acceptabil i ty of taste. Total incidence of adverse effect was found to be 2.97%, and was mild to modera t e in na ture and reso lved after appropr i a t e therapy. No treatment discontinuation was reported.

After 12 weeks of bov ine co los t rum the rapy , pediatrician reported high to average improvement in an overall well-being in 96% of the patients while an overall well-being stated by the patient or parent or guardian or care taker was ve ry good to good in 90.56 % of the patients. Overal l Pedimune | was very well tolerated in almost all the patients across all the age groups.

Bogstedt et a134 demonstrated sufficient prophylactic act iv i ty of a dai ly dose of 500 mg bov ine immunoglobulins against rotavirus diarrhea. Similarly, 200 - 400 mg lozenges of bovine colostrum was found to be effect ive by Sherif Se t a135 in i m p r o v e m e n t and modula t ion of humora l and cell medica ted immune indices during the feeding (2 weeks) and post-feeding (2 weeks) pe r iod in h u m a n volunteers . Also, a direct positive correlation between the daily colost:rum dose and titers of measured immuni ty indices are found. Many s tudies 21-z4 sugges t the possible t he rapeu t i c and prophylact ic role of oral bovine colost rum in infants against m a n y bacter ia l and viral infect ions of gastrointestinal tract and upper respiratory tract. The dosage of bovine oral immunoglobulins needed to obtain therapeutic efficacy is still to be determined and the ideal durat ion of treatment with bovine colostrum in an "at risk" population is not known. In previous studies, dried bovine colostrum is studied in doses between 200 mg to 40 gm daily orally for 10 days to 3 months.

Similarly, Brinkworth and colleagues had reported in their study, a 48% significant reduction in the number of subjects reporting symptoms of URTI in the bovine co los t rum t rea tment arm as compa red to the w h e y protein treatment arm ~7. The reduction in the number of episodes of URTIs in the present study is consistent with an earlier observation by Brinkworth GD et al, however, there were certain important differences in the duration and dosage of the bovine colostrum in the studies.

Shafiqul A et al2Z found antirotavirus immunoglobins of bovine colostral origin effective in the management of ch i ld ren aged 4 to 24 mon ths wi th acute ro tav i rus diarrhea. Another study 33 also reported 100 % protection against symptomatic rotavirus infection with the efficacy of bovine colostrum in rotavirus diarrhea in children aged 3 to 15 months. The present study has also demonstrated significant reduction in number of episodes of diarrhea, no of pa t ien ts suf fe r ing f rom d ia r rhea and also hospitalization due to it.

Indian Journal of Pediatrics, Volume 73--July, 2006 589

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Kamlesh Patel and Rajiv Rana

The defense of mucosal surfaces against pathogenic microorganisms is provided by a variety of mechanisms, a m o n g which the p r e d o m i n a n t role of IgA is well- established? 6 IgA antibodies are the major mediators of resistance to viral infection of the respiratory mucosa. 37 The quantity of secretory IgA in the nasopharynx appears to be age-dependent: it is lowest in young children and increases thereafter gradually with age. 38 Previous studies have shown that there is a direct relationship between salivary IgA levels and resistance to URT127, as such that higher salivary IgA levels reduce the incidence of URTI and vice versa. Mero et al "-s repor ted that sal ivary IgA concentration increases after 2 weeks of bovine colostrum supplementation. Colostral induced increase in IgA may be a probable mechanism for building respiratory tract i m m u n i t y and thus decrease in episodes of URTI as reported in the present study.

Regular consumpt ion of bovine colostrum has been reported as a protective role for infantile gastrointestinal i m m u n i t y due to its direct effect on p r o m o t i n g and development of infantile gut-associated lymphoid tissues wh ich are r e spons ib l e m a i n l y for p r o n o u n c i n g the infantile gut immunityY Colostrum from nonimmunized cows contains antibodies against many enteric pathogens and bov ine i m m u n o g l o b u l i n in the fo rm of specif ic an t ibody has also been shown to be effective against var ious enteric diseases, ls-~7 Thus, immunoglobul ins in Pedimune and its competitive inhibition of the binding of luminal toxins could be a plausible mechanism of reduced episodes of diarrhea seen with bovine colostrum therapy.

The present study has some limitations. It is unblinded o b s e r v a t i o n a l s t u d y and there is fu r the r need for r a n d o m i z e d control t r i a l There m a y be a p rob lem of recall bias with parents, as the outcome variables were decreased in ARI and diarrhea. Due to short follow up period, incidence of ARI may vary with seasonal changes, which may effect the end results of the study as outcomes were compared with preceding 6 months baseline data of the patients.

The results of the present study clearly demonstrated that bovine colostrum protects children against recurrent upper respiratory tract infection and diarrhea. Pedimune | (bovine colostrum) provides a simple way of preventing episodes of recurrent upper respiratory tract infection and diarrhea in susceptible children and thus may be useful in preventing recurrent infections in immunocompromised children or adults.

CONCLUSION

In conclusion, bovine colostrum was highly effective in the p r o p h y l a c t i c t r e a t m e n t of r ecu r r en t URTIs and diarrhea in reducing not only the episodes but also the hospitalization due to them. These results suggest that clinical appl ica t ion of bov ine co los t rum migh t soon provide a therapeut ic option for a condit ion affecting

millions of children worldwide. Al though the present f indings are based on self- reported symptoms , hence considered only of pre l iminary nature. Future studies shou ld a t t e m p t to con f i rm these f ind ings a n d simultaneously measure markers of immune function in order to identify the possible correlation by which this supplement elicits this effect.

Acknowledgement

The authors acknowledge with thanks the following pe&atricians who have contributed in the above study.

Roy Bikash (Agartala); Dasgupta Alekhya (Agartala); Chakraborty Satyaji (Agartala); Chakraborty Milan (Agartala); Bhatia Rakesh (Agra); Prasad Piyush (Agra); Sunder Shyam (Agra); Taneja Vinita K (Agra); Kurian Sosamma (Alleppee); Ghosh Ashim Kumar (Asansol); Jagadish (Bangalore); Nagesh A (Bangalore); Nagabhushana S (Bangalore); Prakash K (Bangalore); Balakrishnan C M (Bangalore); Kasi SG (Bangalore) Baklani Shubha (Bangalore); Jagadishan S (Bangalore); Deka P (Bongaigaon); Gupta CN (Burdwan); Islam Aminul (Burdwan); Bhadra Atanu (Burdwan); Clement K A (Cochin); Namachivayam V (Cuddalore); S. Chattaraj (Durgapur); Subhasish Chakrabarti (Durgapur); Khankakar A M (Guwahati); Das Brajendra (Guwahati); Patangia Kalpana (Guwahati); Kayal Raj K (Guwahati); Kalita Dibakar (Guwahati); Jahi Nirmal Kumar (Guwahati); Das A (Guwahati); Bhuyan Deepsikha (Guwahati); Khankakar AM (Guwahati); Kumar Vijay G (Hanamkonda); Murah Mohan C (Hyderabad); Toshniwal Shyam Sunder (Hyderabad); Chakravarthy V (Hyderabad); Mehta Amit (Hyderabad); Veeraiah R (Hyderabad); Chintawar U (Hyderabad); Veerapaneni Vishnun Rao (Hyderabad); Rao Vljaya Mohan '(Hyderabad); Sudhir M V (Hyderabad); Kedia Pawan (Kanpur); Shukla Ashwani Kumar (Kanpur); Chitranshi Sheila (Kanpur); Tandon Vishnu Kumar (Kanpur); Agrawal Vineet (Kanpur); Shah RK (Kanpur); Dhanavel N (Kattumannarkoil); George Abraham T (Kochi); Quader Manzur (Kolkata); Nihar Ranjan Kayal (Kolkata); P.K. Bhattacharjee (Kolkata); S.P.Singh (Kolkatta); Naniwadekar Narendra (Kolhapur); Balachandar D (Kottayam); T. Rajagopal (Madurai); R. Durai Raj (Madurai); Prabakar Navamani (Madurai); Prasad S R Vara (Malkajgiri); Rau ATK (Mangalore); Suresh Babu PS (Mangalore); Philip Saji (Mannar); Chauhan PPS (Meerut); Agarwal Sudhanshu (Meerut); Kmnar Nalini (Meerut); Sridhar Ganapathy (Mumbai); Suresh Shah (Mumbai); Vishwas Khajanchi (Mumbai); Mohan Joshi (Mumbai); Sunil Shah (Mumbai); Pramod Bagul (Mumbai); Kumar Girish (Muzaffarnagar); Tyagi Mukesh (Muzaffarnagar); Thiraviam Mohan (Nagercoil); K. Thanappan (Nagercoil); Gandhi Vinod (Nagpur); S. Raju (Palayamkottai); M. Nambiyappan (Palayamkottai); Ravichandar A (Pondicherry); Gondhalekar Medha (Ratnagiri); Murali M V (Secunderabad); Rao Seshagiri K (Secunderabad); Vijay Shekhar Janapareddy (Secunderabad); Charoo Bashir A (Srinagar); Farooq Arshad (Srinagar); Ahmad Nisar (Srinagar); Chowdhary Javed (Srinagar); Ahmad Qazi Iqbal (Srinagar); Syed Tariqq (Srinagar); Khurshid S (Srinagar); Sufi G M (Srinagar); Singh Daljit (Srinagar) ; Singh Gavinderjit (Srinagar); Menon Ajitha S (Thnssur); Skariah Jose (Thrissur); Damodaran K S (Thrissur); Antony Thomas (Trichur); Senthil Kumar T (Trichy); Jesudasan Ramola (Trichy); Antony Clement D (Trichy); Palaniraj P K (Trichy); Shaft Mohammed (Trivandrum); Elizabeth K E (Trivandrum); S Sobha Kumar (Trivandrum);

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