Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial.
BACKGROUND
Despite WHO recommendations to offer pregnant women treatment with praziquantel, many nations continue to withhold treatment, awaiting data from controlled trials addressing safety and efficacy. The objectives of this study were to assess whether treatment of pregnant women with schistosomiasis at 12-16 weeks gestation leads to improved maternal and newborn outcomes and to collect maternal and newborn safety data.


METHODS
This phase 2, randomised, double-blind, placebo-controlled trial was done in 72 baranguays (villages) serviced by six municipal health centres in a schistosomiasis endemic region of northeastern Leyte, Philippines. Pregnant women (at 12-16 weeks gestation) who were otherwise healthy but infected with Schistosoma japonicum were enrolled and randomly assigned (1:1) to receive either over-encapsulated praziquantel (total dose 60 mg/kg given as two split doses) or placebo. Participants, investigators, midwives, and laboratory staff were all masked to treatment. The primary outcome was birthweight. Safety data were collected including immediate reactogenicity, post-dosing toxicology ascertained 24 h after study drug administration, and maternal and newborn serious adverse events. Analysis followed the intention-to-treat principle. Analyses were done using hierarchical generalised linear models to adjust for identified confounders and account for potential clustering of observations within villages and municipalities. This trial is registered with ClinicalTrials.gov, number NCT00486863.


RESULTS
Between Aug 13, 2007, and Dec 3, 2012, 370 pregnant women were enrolled and randomly assigned to each treatment group (184 to the placebo group, 186 to the praziquantel group). Most women had low-intensity infections (n=334, 90%). Treatment with praziquantel did not have a significant effect on birthweight (2·85 kg in both groups, β=-0·002 [95% CI -0·088 to 0·083]; p=0·962). Treatment was well tolerated with reactogenicity rates similar to those seen in non-pregnant participants (severe reactions occurred in five patients in the praziquantel group and two in the placebo group, and included headache, fever, and malaise). There were no significant differences in key safety outcomes including abortion, fetal death in utero, and congenital anomalies.


CONCLUSIONS
Results from this study provide important data from a controlled trial in support of the expansion of treatment policies to include pregnant women as recommended by WHO.


BACKGROUND
National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050).
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines.
Remigio M
RM
Olveda
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines.
Luz P
LP
Acosta
Department of Epidemiology, Research Institute of Tropical Medicine, Manila, Philippines.
Veronica
V
Tallo
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines.
Palmera I
PI
Baltazar
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines; Remedios Trinidad Romualdez Hospital, Tacloban City, Leyte, Philippines.
Jenny Lind S
JL
Lesiguez
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines; Remedios Trinidad Romualdez Hospital, Tacloban City, Leyte, Philippines.
Georgette G
GG
Estanislao
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines; Remedios Trinidad Romualdez Hospital, Tacloban City, Leyte, Philippines.
Edna B
EB
Ayaso
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines; Remedios Trinidad Romualdez Hospital, Tacloban City, Leyte, Philippines.
Donna Bella S
DB
Monterde
Department of Immunology, Research Institute of Tropical Medicine, Manila, Philippines.
Antonio
A
Ida
EMMES Corporation, Rockville, MD, USA.
Nora
N
Watson
Center for International Health Research, Rhode Island Hospital, Providence, RI, USA; Department of Pediatrics, Alpert Medical School of Brown University and Hasbro Children's Hospital, Providence, RI, USA.
Emily A
EA
McDonald
Center for International Health Research, Rhode Island Hospital, Providence, RI, USA; Department of Pediatrics, Alpert Medical School of Brown University and Hasbro Children's Hospital, Providence, RI, USA.
Hannah W
HW
Wu
Center for International Health Research, Rhode Island Hospital, Providence, RI, USA; Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University and Rhode Island Hospital, Providence, RI, USA.
Jonathan D
JD
Kurtis
Center for International Health Research, Rhode Island Hospital, Providence, RI, USA; Department of Pediatrics, Alpert Medical School of Brown University and Hasbro Children's Hospital, Providence, RI, USA. Electronic address: Jennifer_Friedman@Brown.edu.
Jennifer F
JF
Friedman
D000328:Adult; D000871:Anthelmintics / Q000008:administration & dosage* / Q000009:adverse effects*; D001724:Birth Weight / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D010679:Philippines; D011223:Praziquantel / Q000008:administration & dosage* / Q000009:adverse effects*; D011247:Pregnancy; D012552:Schistosomiasis / Q000188:drug therapy*; D055815:Young Adult
D000871:Anthelmintics; D011223:Praziquantel