title: Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections.
  
  
  METHODS
  In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda. With a computer-generated random number sequence in blocks of 100, we assigned patients to 440 mg albendazole and 40 mg/kg praziquantel (n=628), 440 mg albendazole and a praziquantel-matching placebo (n=625), 40 mg/kg praziquantel and an albendazole-matching placebo (n=626), or an albendazole-matching placebo and praziquantel-matching placebo (n=628). All participants and hospital staff were masked to allocation. Primary outcomes were immune response at age 1 year to BCG, tetanus, and measles immunisation; incidence of infectious diseases during infancy; and vertical HIV transmission. Analysis was by intention-to-treat. This trial is registered, number ISRCTN32849447.
  
  
  RESULTS
  Data were available at delivery for 2356 women, with 2345 livebirths; 2115 (90%) of liveborn infants remained in follow-up at 1 year of age. Neither albendazole nor praziquantel treatments affected infant response to BCG, tetanus, or measles immunisation. However, in infants of mothers with hookworm infection, albendazole treatment reduced interleukin-5 (geometric mean ratio 0·50, 95% CI 0·30-0·81, interaction p=0·02) and interleukin-13 (0·52, 0·34-0·82, 0·0005) response to tetanus toxoid. The rate per 100 person-years of malaria was 40·9 (95% CI 38·3-43·7), of diarrhoea was 134·1 (129·2-139·2), and of pneumonia was 22·3 (20·4-24·4). We noted no effect on infectious disease incidence for albendazole treatment (malaria [hazard ratio 0·95, 95% CI 0·79-1.14], diarrhoea [1·06, 0·96-1·16], pneumonia [1·11, 0·90-1·38]) or praziquantel treatment (malaria [1·00, 0·84-1·20], diarrhoea [1·07, 0·98-1·18], pneumonia [1·00, 0·80-1·24]). In HIV-exposed infants, 39 (18%) were infected at 6 weeks; vertical transmission was not associated with albendazole (odds ratio 0·70, 95% CI 0·35-1·42) or praziquantel (0·60, 0·29-1·23) treatment.
  
  
  CONCLUSIONS
  These results do not accord with the recently advocated policy of routine antenatal anthelmintic treatment, and the value of such a policy may need to be reviewed.
  
  
  BACKGROUND
  Wellcome Trust.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK. emily.webb@lshtm.ac.uk
authors.forename: Emily L
authors.initials: EL
authors.lastname: Webb
authors.forename: Patrice A
authors.initials: PA
authors.lastname: Mawa
authors.forename: Juliet
authors.initials: J
authors.lastname: Ndibazza
authors.forename: Dennison
authors.initials: D
authors.lastname: Kizito
authors.forename: Alice
authors.initials: A
authors.lastname: Namatovu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kyosiimire-Lugemwa
authors.forename: Bridget
authors.initials: B
authors.lastname: Nanteza
authors.forename: Margaret
authors.initials: M
authors.lastname: Nampijja
authors.forename: Lawrence
authors.initials: L
authors.lastname: Muhangi
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Woodburn
authors.forename: Hellen
authors.initials: H
authors.lastname: Akurut
authors.forename: Harriet
authors.initials: H
authors.lastname: Mpairwe
authors.forename: Miriam
authors.initials: M
authors.lastname: Akello
authors.forename: Nancy
authors.initials: N
authors.lastname: Lyadda
authors.forename: Joseph
authors.initials: J
authors.lastname: Bukusuba
authors.forename: Macklyn
authors.initials: M
authors.lastname: Kihembo
authors.forename: Moses
authors.initials: M
authors.lastname: Kizza
authors.forename: Robert
authors.initials: R
authors.lastname: Kizindo
authors.forename: Juliet
authors.initials: J
authors.lastname: Nabulime
authors.forename: Christine
authors.initials: C
authors.lastname: Ameke
authors.forename: Proscovia B
authors.initials: PB
authors.lastname: Namujju
authors.forename: Robert
authors.initials: R
authors.lastname: Tweyongyere
authors.forename: Moses
authors.initials: M
authors.lastname: Muwanga
authors.forename: James A G
authors.initials: JA
authors.lastname: Whitworth
authors.forename: Alison M
authors.initials: AM
authors.lastname: Elliott
mesh_terms: D000328:Adult; D015766:Albendazole / Q000008:administration & dosage / Q000009:adverse effects; D000871:Anthelmintics / Q000008:administration & dosage* / Q000009:adverse effects; D003141:Communicable Diseases / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D011223:Praziquantel / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000871:Anthelmintics; D011223:Praziquantel; D015766:Albendazole