Evaluation of immune responses to an oral typhoid vaccine, Ty21a, in children from 2 to 5 years of age in Bangladesh.
Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years. We studied immune responses to a liquid formulation of Ty21a in children 2-5 years of age. Since children in developing countries are in general hypo responsive to oral vaccines, the study was designed to determine if anti-helminthic treatment prior to vaccination, improves responses. In a pilot study in 20 children aged 4-5 years, the immune responses in plasma and in antibody in lymphocyte secretions (ALS) to the enteric coated capsule formulation of Ty21a was found to be comparable to a liquid formulation (P>0.05). Based on this, children (n=252) aged ≥ 2-<3 years and ≥3-<5 years were randomized to receive a liquid formulation of Ty21a with and without previous anti-helminthic treatment. The vaccine was well tolerated with only a few mild adverse events recorded in <1% of the children. De-worming did not improve immune responses and both age groups developed 32-71% IgA, IgG, and IgM responses in plasma and 63-86% IgA responses in ALS and stool specimens to a membrane preparation (MP) of Ty21a. An early MP specific proliferative T cell response was also seen. We recommend that safety and efficacy studies with a liquid formulation of the vaccine are carried out in children under five, including those less than two years of age to determine if Ty21a is protective in these age groups and applicable as a public health tool for controlling typhoid fever in high prevalence areas of typhoid fever including Bangladesh.
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Taufiqur R
TR
Bhuiyan
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Feroza K
FK
Choudhury
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Farhana
F
Khanam
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Amit
A
Saha
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Md Abu
MA
Sayeed
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Umme
U
Salma
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Anna
A
Lundgren
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
David A
DA
Sack
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Ann-Mari
AM
Svennerholm
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh. Electronic address: fqadri@icddrb.org.
Firdausi
F
Qadri
D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage; D000871:Anthelmintics / Q000008:administration & dosage; D000907:Antibodies, Bacterial; D001459:Bangladesh; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000031:analogs & derivatives; D010865:Pilot Projects; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage* / Q000276:immunology*
D000871:Anthelmintics; D000907:Antibodies, Bacterial; D011135:Polysaccharides, Bacterial; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; D008795:Metronidazole; D015766:Albendazole; C016724:secnidazole
Antibodies; Children; Mucosal; Oral; T cells; Typhoid vaccine