Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial

Abstract

SummaryBackgroundDespite 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 the study were to 1) assess whether treatment of pregnant women with schistosomiasis at 12–16 weeks gestation leads to improved maternal and newborn outcomes and 2) collect maternal and newborn safety data.MethodsWomen who were otherwise healthy and infected with S. japonicum (N=370) were enrolled and randomized 1:1 to receive either over-encapsulated praziquantel (60 mg/kg in split dose) or placebo. The following efficacy outcomes were ascertained: maternal hemoglobin, iron status, and gestational weight gain, birth weight (primary outcome), newborn hemoglobin and iron status. Safety data were collected including immediate reactogenicity, post dosing toxicology ascertained 24 hours after study agent administration, and maternal and newborn serious adverse events.FindingsMost women harbored low intensity infections (90.9%). Treatment with praziquantel did not have a significant impact on birth weight (2.85 kg in both groups, Beta −0.002, [0.88, 0.083]) or the incidence of low birth weight (OR 1.319 [0.729, 2.387]. Lack of treatment success may be due to the lack of difference in measures of maternal inflammation at 32 weeks gestation. Treatment with praziquantel resulted in a higher likelihood of treatment success (OR 5.815, [3.52, 9.61], P < 0.0001). Treatment was well tolerated with reactogenicity rates similar to that observed in non-pregnant subjects. There were no significant differences in key safety outcomes including abortion, fetal death in utero and congenital anomalies.InterpretationResults 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.FundingThe trial was funded by the United States National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050).

Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

“…It has been used in preventive chemotherapy programmes in many endemic countries, in some continuously since more than 15 years [25, 110, 111]. However, it is not until recently that preschool-aged children and pregnant women were included into the recommended target population for preventive chemotherapy [112, 113]. Both these groups are now recommended to be treated with praziquantel when needed; still there are existing gaps due to drug shortage and lack of a pediatric praziquantel formulation [112].…”

Endotoxin at the Maternal–Fetal Interface in a Resource-Constrained Setting: Risk Factors and Associated Birth Outcomes

“…Of note, treatment did not impact birth weight, risk for LBW, or small for gestational age (SGA). 18 All women in this cohort delivered vaginally.…”

“…Characteristics and enrollment strategies of this study population have been described elsewhere. 18 All women were positive for schistosomiasis and were randomized to praziquantel treatment to resolve infection, or placebo at 14 ± 2 weeks gestation. Of note, treatment did not impact birth weight, risk for LBW, or small for gestational age (SGA).…”

Mechanistic Pathways From Early Gestation Through Infancy and Neurodevelopment

“…Details of the trial are described elsewhere. 7 Briefly, 370 pregnant women were recruited in their villages or municipal health centers by trained midwives. To be eligible to participate, women had to be infected with Schistosoma japonicum; be otherwise healthy as determined by history, physical examination, and laboratory studies; and have a viable, singleton gestation.…”

“…At 32 weeks' gestation, maternal complete blood count was captured as well as iron status by using a multiplex bead-based platform (Bio-Rad, Hercules, CA) as described previously. 7 Iron status was determined by quantifying serum Transferrin Receptor (sTfR), a receptor predominantly expressed by red blood cells when they are iron thirsty, and ferritin, indicative of stored iron. The sTfR: log 10 (ferritin) ratio (sTfR-F index) at 32 weeks' gestation was used as the primary measure of maternal iron status, as it is thought to be more robust in the setting of inflammation and has been validated against a gold standard of bone marrow iron in a setting with high rates of infection and inflammation.…”