• Newborn congenital anomalies. [ Time Frame: Delivery, within 2-6 days of delivery, and 28 days of life. ] [ Designated as safety issue: Yes ]
• Pre-eclampsia. [ Time Frame: 22 weeks and 32 weeks. ] [ Designated as safety issue: Yes ]
• Parasitological response to treatment. [ Time Frame: Measured at 22 weeks gestation. ] [ Designated as safety issue: Yes ]
• Newborn hemoglobin and iron status. [ Time Frame: At 2-6 days of life. ] [ Designated as safety issue: Yes ]
• Praziquantel (PZQ) toxicology. [ Time Frame: Just before the dose at 12-16 weeks gestation (baseline) and 24 hours after the second part of the split dose and before discharge from the hospital. ] [ Designated as safety issue: No ]
• Pharmacokinetics. [ Time Frame: 4.5 and 8 hours after the first praziquantel dose (subjects assigned to an even study number) or 6 and 10 hours after the first praziquantel dose (subjects assigned to an odd study number). ] [ Designated as safety issue: No ]
• Maternal weight gain. [ Time Frame: From 12-16 weeks to 32 weeks. ] [ Designated as safety issue: Yes ]
• Extra-placental mechanisms mediating improved outcomes in the praziquantel group. These factors will relate to both birthweight and iron status of the newborn. [ Time Frame: 32 weeks. ] [ Designated as safety issue: Yes ]
• Maternal hemoglobin and iron status, assessment of anemia of inflammation. [ Time Frame: Hemoglobin and iron status will be measured at 14 (+/- 2) weeks and 32 weeks. ] [ Designated as safety issue: No ]

• Efficacy: presence or absence of low birth weight as defined by a birth weight less than 2.5kg. [ Time Frame: Within 24 hours of delivery. ] [ Designated as safety issue: Yes ]
• Maternal hemoglobin and iron status, assessment of anemia of inflammation. [ Time Frame: Measured at 13 weeks and 32 weeks gestation, change over baseline ] [ Designated as safety issue: Yes ]
• Maternal change in nutritional status. [ Time Frame: From 12-16 weeks to 32 weeks. ] [ Designated as safety issue: Yes ]
• Newborn hemoglobin and iron status. [ Time Frame: At delivery. ] [ Designated as safety issue: Yes ]
• Parasitological response to treatment. [ Time Frame: Measured at 22 weeks gestation. ] [ Designated as safety issue: No ]
• PZQ safety/toxicology for mother, fetus, and newborn. [ Time Frame: 12-16 weeks gestation (baseline) and 24-48 hours after the dose and before discharge from the hospital. ] [ Designated as safety issue: Yes ]
• Newborn congenital anomalies [ Time Frame: Delivery, within 2-6 days of delivery, and 28 days of life. ] [ Designated as safety issue: Yes ]
• Pre-eclampsia [ Time Frame: 22 weeks and 32 weeks ] [ Designated as safety issue: Yes ]
• Extra-placental mechanisms mediating adverse birth outcomes. [ Time Frame: Within 24 hours of delivery. ] [ Designated as safety issue: Yes ]
• Placental mechanisms mediating adverse birth outcomes. [ Time Frame: Within 24 hours of delivery. ] [ Designated as safety issue: Yes ]
• Identifying extra-placental mechanisms mediating adverse birth outcomes [ Time Frame: Delivery ] [ Designated as safety issue: Yes ]

The purpose of the study is to understand whether the drug praziquantel (PZQ) is safe for the mother and developing baby when the mother has schistosomiasis (a type of worm) infection, and whether the drug may improve the mother's and baby's health. The usual practice is to wait until after a mother has finished breast feeding before giving the medicine. Five hundred infected pregnant women, ages 18 and over, in endemic villages in Leyte, The Philippines will participate. Study volunteers 12-16 weeks pregnant will be given PZQ or a pill without any medicine (placebo) and stay in the hospital overnight. Small blood samples will be collected before and after the medication is taken. Three stool and urine samples will be taken during a total of 7 study visits. An ultrasound image (picture or outline of the unborn baby) will be performed. When the baby is born, a small blood sample will be taken. Mother and baby will be followed for up to 8 months before the baby is born and 1 month after.

This double-blind, placebo-controlled study will investigate praziquantel (PZQ) for the treatment of Schistosomiasis japonicum in pregnant women living in endemic villages of Leyte, The Philippines. The study will enroll 500 pregnant women, ages 18 and over, infected with S. japonicum. The primary study objective is to quantify the efficacy of PZQ treatment for S. japonicum at 12-16 weeks gestation on newborn birth weight among live births. This will be assessed by measuring birth weight within 96 hours of delivery to 10 grams. The first secondary objective is to assess treatment efficacy with respect to maternal and newborn nutritional status and maternal parasitologic response to treatment. This will be assessed by evaluating: maternal iron status (ferritin and serum transferrin receptor) and hemoglobin at 32 weeks gestation; change in maternal nutritional status from first trimester to 32 week visit; newborn iron stores as assessed by cord blood ferritin and hemoglobin; and parasitologic response to treatment reported as percent reduction in egg counts from the mean S. japonicum eggs per gram of stool at screening to the mean S. japonicum eggs per gram of stool at 22 weeks gestation. "Successful" treatment will be defined as a 90% or greater reduction in egg counts from pre-treatment to 22 weeks gestation. The second secondary objective is to collect preliminary safety and toxicity data on use of PZQ among pregnant women and their newborns. This will be assessed by evaluating: incidence of maternal convulsion after PZQ dosing; toxicity to maternal bone marrow, kidney, and liver as measured by laboratory parameters collected just before, and 24-48 hours after dose; immediate toxicity to the fetus as assessed by abortion (fetal demise before 20 weeks gestation); and long-term toxicity to the fetus as assessed by rates of pre-maturity measured by modified Dubowitz exam at delivery, low-birth weight, stillbirth as defined by fetal demise after 20 weeks gestation, congenital anomalies as determined by physical exam performed by a pediatrician at 28 days of life; and pharmacokinetics of PZQ during pregnancy as assessed by 2 blood draws (4.5 and 8 hours after the first dose or 6 and 10 hours after the first dose). The third secondary objective is to identify extra-placental mechanisms mediating the hypothesized beneficial effect of PZQ on birth outcomes. The hypothesized mechanisms include: improved maternal iron bio-availability for transfer to the developing fetus and improved maternal nutritional status as assessed by anthropometric measures of body size. The fourth secondary objective is to identify extra-placental mechanisms mediating the hypothesized beneficial effect of PZQ on birth outcomes. The hypothesized mechanisms include: decreased concentrations of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 and increased concentrations of IL-10 compared in placental blood from S. japonicum infected, PZQ treated mothers compared to untreated mothers; decreased secretion of TNF-alpha, IFN-gamma, and IL-6 and more IL-10 secretion from placental explants from S. japonicum infected, PZQ treated women when stimulated with soluble parasite egg antigen compared to placental explants from S. japonicum infected, PZQ untreated mothers; and lower level of apoptosis in cultured trophoblasts exposed to peripheral serum as measured by cytokeratin 18 neo-epitope staining among S. japonicum infected, PZQ treated mothers versus untreated mothers. Participants will be involved in study related procedures for 9 months (8 months pre-natally and 1 month post-natally) for mother and infant.

• Drug: Placebo
• Drug: Praziquantel

• Experimental: Praziquantel at 12-16 weeks gestation.
• Placebo Comparator: Placebo at 12-16 weeks gestation.

Inclusion Criteria:

For screening:

• Female, age 18 or over.
• Present to a study midwife with suspected pregnancy.
• Live in a study village.

For the main study:

• Infected with S. japonicum.
• Pregnancy as determined by urine pregnancy test.
• Age 18 or older.
• Participant is otherwise healthy as determined by history, physical exam, ultrasound and laboratory assessment.
• Pregnancy between 12-16 weeks gestation.
• Ability to provide informed consent to participate.

Exclusion Criteria:

• Presence of significant disease/illness that is either acute or chronic. This will be defined by history, physical examination, ultrasound and laboratory assessment. In particular:

  1. History of seizures or other neurologic disorder, chronic medical problem determined by history or physical examination, e.g. active hepatitis, tuberculosis, heart disease.
  2. Grade 3 or higher laboratory abnormality of blood urea nitrogen (BUN), Creatinine, bilirubin, white blood cell count, or platelet count will warrant exclusion. Grade 2 or higher abnormality of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) will warrant exclusion. For hemoglobin, women with severe anemia defined as hemoglobin less than 7.0 g/dl will be excluded.
  3. Women with myoma on ultrasound that are sub-mucosal or women with myoma that are in any location and greater than 5 cm in size.
  4. Women with congenital anomalies of the reproductive tract that would be expected to cause decreased fetal weight or greatly increase the risk of prematurity such as duplicate uterus, uterine septum.
  5. For less clear cases, the researchers will define significant illness as one that significantly alters a woman's ability to perform activities of daily living, causes symptoms at least two days per week, or necessitates regular use of medication. In the case of acute medical conditions such as urinary tract infection, pneumonia, febrile illness, enrollment may be postponed until the illness is successfully treated (not currently on any medication for the illness) or the illness itself resolves if this occurs before 16 weeks gestation.
• Presence of cysts in the eye suggestive of neurocysticercosis.
• Regular use of a medication for a chronic medical condition.
• History of severe allergic reaction (anaphylaxis, facial swelling, or difficulty breathing) or seizure with praziquantel administration.
• Fetus has congenital anomaly determined by 12-16 week ultrasound or is determined to be nonviable (e.g. blighted ovum).
• Twin or higher order pregnancy.
• Woman has been enrolled into this study for a previous pregnancy.
• Inability to comprehend study procedures and provide informed consent due to limited cognitive abilities or other, or refuses to provide informed consent.