Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients

Shofiqur Rahman, Kyoko Moriguchi, Khaing Win Htun, Koki Taniguchi, Faustino C. Icatlo, Takao Tsuji, Yoshikatsu Kodama, Sa Van Nguyen, Kouji Umeda, Htun Naing Oo, Yi Yi Myint, Than Htut, Swe Swe Myint, Kyaw Thura, Hlaing Myat Thu, Ni Nengah Dwi Fatmawati, Keiji Oguma

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Abstract

This study aims to evaluate the effect of hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) among pediatric patients receiving standard supportive treatment for rotavirus-associated diarrhea mostly with an enteric non-cholera co-pathogen in a hospital setting. Two natural HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274 were used as mixed immunizing antigens in poultry hens to generate anti-HRV IgY (Rotamix IgY). The Rotamix IgY was used in laboratory and clinical studies against control or placebo IgY. The control or placebo IgY was prepared using tissue culture medium from mock-infected MA104 cell line as antigen for poultry immunization. In vitro, Rotamix IgY exhibited multi-serotypic cross neutralization activities along with synergistic effects against major global serotypes G1, G2, G3, G4 and other human or animal rotavirus strains when compared with mono-specific IgY. Suckling mice (ICR strain) pre-treated orally once with Rotamix IgY and then challenged with rotavirus 3. h later showed a significant dose-dependent reduction in frequency (. p<. 0.05) and duration (. p<. 0.05) of diarrhea compared to placebo IgY-treated mice. Out of 114 children aged between 3 and 14 months and with diarrhea upon admission in a Myanmar hospital, 54 dehydrated and rotavirus-positive children were randomized into Rotamix IgY group and placebo IgY group. Of these, only 52 children had complete data with . n=. 26 children per study group. Ninety-two percent of patients in each of these groups were positive for co-infecting enteric non-cholera pathogen and all patients received standard supportive therapy for diarrhea. The patients were monitored for volume and duration of oral rehydration fluid (ORF) and intravenous fluid (IVF) intake, daily stool frequency and overall duration of diarrhea, and frequency and duration of rotavirus shedding. Compared to placebo IgY group, the Rotamix IgY group had statistically significant reduction in mean ORF intake (. p=. 0.004), mean duration of intravenous fluid administration (. p=. 0.03), mean duration of diarrhea from day of admission (. p<. 0.01) and mean duration of rotavirus clearance from stool from day of admission (. p=. 0.05). Overall, our novel approach using oral Rotamix IgY for rotavirus-infected children mostly with non-cholera enteric pathogen co-infection appears to be a promising, safe and effective adjunct to management of acute diarrhea in pediatric patients.

Original languageEnglish
Pages (from-to)4661-4669
Number of pages9
JournalVaccine
Volume30
Issue number31
DOIs
Publication statusPublished - 29-06-2012

Fingerprint

immunoglobulin Y
Rotavirus
placebos
clinical trials
Diarrhea
diarrhea
Randomized Controlled Trials
Placebos
Pediatrics
therapeutics
duration
Therapeutics
oral rehydration
Fluid Therapy
IgY
Poultry
pathogens
poultry
Myanmar
antigens

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Rahman, Shofiqur ; Moriguchi, Kyoko ; Htun, Khaing Win ; Taniguchi, Koki ; Icatlo, Faustino C. ; Tsuji, Takao ; Kodama, Yoshikatsu ; Van Nguyen, Sa ; Umeda, Kouji ; Oo, Htun Naing ; Myint, Yi Yi ; Htut, Than ; Myint, Swe Swe ; Thura, Kyaw ; Thu, Hlaing Myat ; Fatmawati, Ni Nengah Dwi ; Oguma, Keiji. / Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients. In: Vaccine. 2012 ; Vol. 30, No. 31. pp. 4661-4669.
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abstract = "This study aims to evaluate the effect of hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) among pediatric patients receiving standard supportive treatment for rotavirus-associated diarrhea mostly with an enteric non-cholera co-pathogen in a hospital setting. Two natural HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274 were used as mixed immunizing antigens in poultry hens to generate anti-HRV IgY (Rotamix IgY). The Rotamix IgY was used in laboratory and clinical studies against control or placebo IgY. The control or placebo IgY was prepared using tissue culture medium from mock-infected MA104 cell line as antigen for poultry immunization. In vitro, Rotamix IgY exhibited multi-serotypic cross neutralization activities along with synergistic effects against major global serotypes G1, G2, G3, G4 and other human or animal rotavirus strains when compared with mono-specific IgY. Suckling mice (ICR strain) pre-treated orally once with Rotamix IgY and then challenged with rotavirus 3. h later showed a significant dose-dependent reduction in frequency (. p<. 0.05) and duration (. p<. 0.05) of diarrhea compared to placebo IgY-treated mice. Out of 114 children aged between 3 and 14 months and with diarrhea upon admission in a Myanmar hospital, 54 dehydrated and rotavirus-positive children were randomized into Rotamix IgY group and placebo IgY group. Of these, only 52 children had complete data with . n=. 26 children per study group. Ninety-two percent of patients in each of these groups were positive for co-infecting enteric non-cholera pathogen and all patients received standard supportive therapy for diarrhea. The patients were monitored for volume and duration of oral rehydration fluid (ORF) and intravenous fluid (IVF) intake, daily stool frequency and overall duration of diarrhea, and frequency and duration of rotavirus shedding. Compared to placebo IgY group, the Rotamix IgY group had statistically significant reduction in mean ORF intake (. p=. 0.004), mean duration of intravenous fluid administration (. p=. 0.03), mean duration of diarrhea from day of admission (. p<. 0.01) and mean duration of rotavirus clearance from stool from day of admission (. p=. 0.05). Overall, our novel approach using oral Rotamix IgY for rotavirus-infected children mostly with non-cholera enteric pathogen co-infection appears to be a promising, safe and effective adjunct to management of acute diarrhea in pediatric patients.",
author = "Shofiqur Rahman and Kyoko Moriguchi and Htun, {Khaing Win} and Koki Taniguchi and Icatlo, {Faustino C.} and Takao Tsuji and Yoshikatsu Kodama and {Van Nguyen}, Sa and Kouji Umeda and Oo, {Htun Naing} and Myint, {Yi Yi} and Than Htut and Myint, {Swe Swe} and Kyaw Thura and Thu, {Hlaing Myat} and Fatmawati, {Ni Nengah Dwi} and Keiji Oguma",
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Rahman, S, Moriguchi, K, Htun, KW, Taniguchi, K, Icatlo, FC, Tsuji, T, Kodama, Y, Van Nguyen, S, Umeda, K, Oo, HN, Myint, YY, Htut, T, Myint, SS, Thura, K, Thu, HM, Fatmawati, NND & Oguma, K 2012, 'Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients', Vaccine, vol. 30, no. 31, pp. 4661-4669. https://doi.org/10.1016/j.vaccine.2012.04.091

Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients. / Rahman, Shofiqur; Moriguchi, Kyoko; Htun, Khaing Win; Taniguchi, Koki; Icatlo, Faustino C.; Tsuji, Takao; Kodama, Yoshikatsu; Van Nguyen, Sa; Umeda, Kouji; Oo, Htun Naing; Myint, Yi Yi; Htut, Than; Myint, Swe Swe; Thura, Kyaw; Thu, Hlaing Myat; Fatmawati, Ni Nengah Dwi; Oguma, Keiji.

In: Vaccine, Vol. 30, No. 31, 29.06.2012, p. 4661-4669.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized placebo-controlled clinical trial of immunoglobulin Y as adjunct to standard supportive therapy for rotavirus-associated diarrhea among pediatric patients

AU - Rahman, Shofiqur

AU - Moriguchi, Kyoko

AU - Htun, Khaing Win

AU - Taniguchi, Koki

AU - Icatlo, Faustino C.

AU - Tsuji, Takao

AU - Kodama, Yoshikatsu

AU - Van Nguyen, Sa

AU - Umeda, Kouji

AU - Oo, Htun Naing

AU - Myint, Yi Yi

AU - Htut, Than

AU - Myint, Swe Swe

AU - Thura, Kyaw

AU - Thu, Hlaing Myat

AU - Fatmawati, Ni Nengah Dwi

AU - Oguma, Keiji

PY - 2012/6/29

Y1 - 2012/6/29

N2 - This study aims to evaluate the effect of hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) among pediatric patients receiving standard supportive treatment for rotavirus-associated diarrhea mostly with an enteric non-cholera co-pathogen in a hospital setting. Two natural HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274 were used as mixed immunizing antigens in poultry hens to generate anti-HRV IgY (Rotamix IgY). The Rotamix IgY was used in laboratory and clinical studies against control or placebo IgY. The control or placebo IgY was prepared using tissue culture medium from mock-infected MA104 cell line as antigen for poultry immunization. In vitro, Rotamix IgY exhibited multi-serotypic cross neutralization activities along with synergistic effects against major global serotypes G1, G2, G3, G4 and other human or animal rotavirus strains when compared with mono-specific IgY. Suckling mice (ICR strain) pre-treated orally once with Rotamix IgY and then challenged with rotavirus 3. h later showed a significant dose-dependent reduction in frequency (. p<. 0.05) and duration (. p<. 0.05) of diarrhea compared to placebo IgY-treated mice. Out of 114 children aged between 3 and 14 months and with diarrhea upon admission in a Myanmar hospital, 54 dehydrated and rotavirus-positive children were randomized into Rotamix IgY group and placebo IgY group. Of these, only 52 children had complete data with . n=. 26 children per study group. Ninety-two percent of patients in each of these groups were positive for co-infecting enteric non-cholera pathogen and all patients received standard supportive therapy for diarrhea. The patients were monitored for volume and duration of oral rehydration fluid (ORF) and intravenous fluid (IVF) intake, daily stool frequency and overall duration of diarrhea, and frequency and duration of rotavirus shedding. Compared to placebo IgY group, the Rotamix IgY group had statistically significant reduction in mean ORF intake (. p=. 0.004), mean duration of intravenous fluid administration (. p=. 0.03), mean duration of diarrhea from day of admission (. p<. 0.01) and mean duration of rotavirus clearance from stool from day of admission (. p=. 0.05). Overall, our novel approach using oral Rotamix IgY for rotavirus-infected children mostly with non-cholera enteric pathogen co-infection appears to be a promising, safe and effective adjunct to management of acute diarrhea in pediatric patients.

AB - This study aims to evaluate the effect of hyperimmune immunoglobulin Y (IgY) against human rotavirus (HRV) among pediatric patients receiving standard supportive treatment for rotavirus-associated diarrhea mostly with an enteric non-cholera co-pathogen in a hospital setting. Two natural HRV reassortant clinical strains ATCC VR 2273 and ATCC VR 2274 were used as mixed immunizing antigens in poultry hens to generate anti-HRV IgY (Rotamix IgY). The Rotamix IgY was used in laboratory and clinical studies against control or placebo IgY. The control or placebo IgY was prepared using tissue culture medium from mock-infected MA104 cell line as antigen for poultry immunization. In vitro, Rotamix IgY exhibited multi-serotypic cross neutralization activities along with synergistic effects against major global serotypes G1, G2, G3, G4 and other human or animal rotavirus strains when compared with mono-specific IgY. Suckling mice (ICR strain) pre-treated orally once with Rotamix IgY and then challenged with rotavirus 3. h later showed a significant dose-dependent reduction in frequency (. p<. 0.05) and duration (. p<. 0.05) of diarrhea compared to placebo IgY-treated mice. Out of 114 children aged between 3 and 14 months and with diarrhea upon admission in a Myanmar hospital, 54 dehydrated and rotavirus-positive children were randomized into Rotamix IgY group and placebo IgY group. Of these, only 52 children had complete data with . n=. 26 children per study group. Ninety-two percent of patients in each of these groups were positive for co-infecting enteric non-cholera pathogen and all patients received standard supportive therapy for diarrhea. The patients were monitored for volume and duration of oral rehydration fluid (ORF) and intravenous fluid (IVF) intake, daily stool frequency and overall duration of diarrhea, and frequency and duration of rotavirus shedding. Compared to placebo IgY group, the Rotamix IgY group had statistically significant reduction in mean ORF intake (. p=. 0.004), mean duration of intravenous fluid administration (. p=. 0.03), mean duration of diarrhea from day of admission (. p<. 0.01) and mean duration of rotavirus clearance from stool from day of admission (. p=. 0.05). Overall, our novel approach using oral Rotamix IgY for rotavirus-infected children mostly with non-cholera enteric pathogen co-infection appears to be a promising, safe and effective adjunct to management of acute diarrhea in pediatric patients.

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