The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447].
BACKGROUND
Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects "spill-over", altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life.


OBJECTIVE
To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood.


METHODS
The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 x 2(x2) factorial design. Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed.


CONCLUSIONS
This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy.
Elliott
Alison M
AM
Uganda Virus Research Institute, Entebbe, Uganda. alison.tom@infocom.co.ug
Kizza
Moses
M
Quigley
Maria A
MA
Ndibazza
Juliet
J
Nampijja
Margaret
M
Muhangi
Lawrence
L
Morison
Linda
L
Namujju
Proscovia B
PB
Muwanga
Moses
M
Kabatereine
Narcis
N
Whitworth
James A G
JA
D015766:Albendazole / Q000627:therapeutic use; D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006373:Helminthiasis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D006376:Helminths / Q000276:immunology*; D006801:Humans; D007114:Immunization; D015994:Incidence; D008297:Male; D011223:Praziquantel / Q000627:therapeutic use; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D012107:Research Design; D014454:Uganda
D000977:Antiparasitic Agents; D011223:Praziquantel; D015766:Albendazole