Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring: results of a randomised, placebo-controlled trial

TY - JOUR

T1 - Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on immune responses to schistosome antigens among the offspring

T2 - results of a randomised, placebo-controlled trial

AU - Tweyongyere, Robert

AU - Mawa, Patrice A.

AU - Kihembo, Macklyn

AU - Jones, Frances M.

AU - Webb, Emily L.

AU - Cose, Stephen

AU - Dunne, David W.

AU - Vennervald, Birgitte J

AU - Elliott, Alison M.

PY - 2011/8/2

Y1 - 2011/8/2

N2 - Background: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown.Methods: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy.Results: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel.Conclusions: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated.Trial registration: ISRCTN: ISRCTN32849447.

AB - Background: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown.Methods: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy.Results: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel.Conclusions: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated.Trial registration: ISRCTN: ISRCTN32849447.

KW - Animals

KW - Antibodies, Protozoan

KW - Antigens, Protozoan

KW - Antiprotozoal Agents

KW - Cytokines

KW - Female

KW - Humans

KW - Immunity, Maternally-Acquired

KW - Infant

KW - Infant, Newborn

KW - Leukocytes, Mononuclear

KW - Placebos

KW - Praziquantel

KW - Pregnancy

KW - Pregnancy Complications, Parasitic

KW - Schistosoma mansoni

KW - Schistosomiasis mansoni

KW - Treatment Outcome

KW - Uganda

U2 - 10.1186/1471-2334-11-234

DO - 10.1186/1471-2334-11-234

M3 - Journal article

C2 - 21888656

SN - 1471-2334

VL - 11

JO - B M C Infectious Diseases

JF - B M C Infectious Diseases

IS - 234

ER -