Evaluate Azithromycin Plus Chloroquine And Sulfadoxine Plus Pyrimethamine Combinations For Intermittent Preventive Treatment Of Falciparum Malaria Infection In Pregnant Women In Africa

• Occurrence at birth of a LBW live neonate [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of severe maternal anemia (Hb <8 g/dL) [ Time Frame: at 36-38 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of anemia (Hb <11 g/dL) [ Time Frame: at 36-38 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of placental parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of placental malaria as determined by histology [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Number of episodes of STIs per subject including T. pallidum, N. gonorrhoeae, C. trachomatis, during the study period (diagnosis based on clinical presentation and/or on laboratory test results between Weeks 36-38). [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence at birth of a neonates with congenital abnormalities [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of a perinatal or neonatal death [ Time Frame: Day 28 after delivery ] [ Designated as safety issue: No ]
• Birth weight of the live-borne neonate (singleton); [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Number of episodes of symptomatic malaria per subject anytime from first IPTp dose administration to delivery [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of a subject requiring additional treatment for symptomatic malaria during the study period following the first dose (diagnosed based on clinical presentation and/or lab test results) [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of peripheral parasitemia [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of peripheral parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of cord blood parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of STIs including T. pallidum, N. gonorrhoeae, C. trachomatis during the study period following first dose (diagnosed based on clinical presentation prior to Week 36-38 and/or lab test results between Week 36-38 of gestation) [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of a positive result for C. trachomatis infection (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of a positive result for N. gonorrhoeae infection (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of a positive result for T. pallidum test (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of a T. vaginalis infection (diagnosed based on lab result); [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of bacterial vaginosis (diagnosed based on lab result); [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of ophthalmia neonatorum (diagnosed based on lab test results) in the neonate; [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of bacterial infections including pneumonia and other lower respiratory tract infections anytime from first IPTp dose administration to delivery; [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of pre-eclampsia from Week 20 to delivery; [ Time Frame: Wk 20 to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of nasopharyngeal swabs positive for macrolide resistant and penicillin resistant Streptococcus pneumoniae. This test will be done in about 600 subjects each from the AZCQ and SP arms from two or more sites. [ Time Frame: baseline, Day 28 (window Day 28 - Day 42) post delivery, and about 6 mos following last IPTp course ] [ Designated as safety issue: No ]

• Occurrence at birth of a LBW live neonate [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of severe maternal anemia (Hb <8 g/dL) [ Time Frame: at 36-38 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of anemia (Hb <11 g/dL) [ Time Frame: at 36-38 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of placental parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of placental malaria as determined by histology [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Number of episodes of STIs per subject including T. pallidum, N. gonorrhoeae, C. trachomatis, during the study period (diagnosis based on clinical presentation and/or on laboratory test results between Weeks 36-38). [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence at birth of a neonates with congenital abnormalities [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of a perinatal or neonatal death [ Time Frame: Day 28 after delivery ] [ Designated as safety issue: No ]
• Birth weight of the live-borne neonate (singleton); [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Number of episodes of symptomatic malaria per subject anytime from first IPTp dose administration to delivery [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of a subject requiring additional treatment for symptomatic malaria during the study period following the first dose (diagnosed based on clinical presentation and/or lab test results) [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of peripheral parasitemia [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of peripheral parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of cord blood parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of STIs including T. pallidum, N. gonorrhoeae, C. trachomatis during the study period following first dose (diagnosed based on clinical presentation prior to Week 36-38 and/or lab test results between Week 36-38 of gestation) [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of a positive result for C. trachomatis infection (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of a positive result for N. gonorrhoeae infection (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of a positive result for T. pallidum test (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of a T. vaginalis infection (diagnosed based on lab result); [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of bacterial vaginosis (diagnosed based on lab result); [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
• Occurrence of ophthalmia neonatorum (diagnosed based on lab test results) in the neonate; [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of bacterial infections including pneumonia and other lower respiratory tract infections anytime from first IPTp dose administration to delivery; [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of pre-eclampsia from Week 20 to delivery; [ Time Frame: Wk 20 to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
• Occurrence of nasopharyngeal swabs positive for macrolide resistant and penicillin resistant Streptococcus pneumoniae. This test will be done in about 600 subjects each from the AZCQ and SP arms from two or more sites. [ Time Frame: baseline, Day 28 (window Day 28 - Day 42) post delivery, and about 6 mos following last IPTp course ] [ Designated as safety issue: No ]

The primary objective is to establish superiority of AZCQ over SP in protective efficacy for IPTp as measured by the proportion of subjects with sub-optimal pregnancy outcome.

• Drug: Azithromycin plus chloroquine
  combination tablet of 250mg azithromycin/155 chloroquine, Once daily PO for three days per treatment. There are total 3 treatments at 4-8 weeks intervals. The first treatment course will be administered during the second trimester (14-26 weeks of gestation as confirmed by ultrasound). The last treatment course should be given to subjects prior to or during 36 weeks of gestation.
• Drug: sulfadoxine-pyrimethamine
  Fansidar tablet (500 mg sulfadoxine /25 mg pyrimethamine), once daily, PO, single dose per treatment. There are total 3 treatments at 4-8 weeks intervals. The first treatment course will be administered during the second trimester (14-26 weeks of gestation as confirmed by ultrasound). The last treatment course should be given to subjects prior to or during 36 weeks of gestation.
  Other Name: Fansidar

• Experimental: AZCQ
  Azithromycin/chloroquine
  Intervention: Drug: Azithromycin plus chloroquine
• Active Comparator: SP
  sulfadoxine-pyrimethamine (Fansidar)
  Intervention: Drug: sulfadoxine-pyrimethamine

Inclusion Criteria:

• Pregnant women (all gravidae) with ≥14 and ≤26 weeks of gestational age (by ultrasound).
• Evidence of a personally signed and dated informed consent/assent document. Assent will be obtained from subjects <18 years of age.
• Subjects who are willing to and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Subjects who are available for follow up at delivery and on 28 days post delivery.

Exclusion Criteria:

• Age <16 years old or >35 years old.
• Multiple gestations as per the ultrasound at screening.
• Clinical symptoms of malaria.
• Hemoglobin < 8 g/dL (at enrollment).
• Any condition requiring hospitalization at enrollment.
• History of convulsions, hypertension, diabetes or any other chronic illness that may adversely affect fetal growth and viability.
• Inability to tolerate oral treatment in tablet form.
• Known allergy to the study drugs (azithromycin, chloroquine, and sulfadoxine-pyrimethamine) or to any macrolides or sulphonamides.
• Requirement to use medication during the study that might interfere with the evaluation of the study drug eg, trimethoprim-sulfamethoxazole use in subjects positive for HIV infection.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
• Evidence of current obstetric complications that may adversely impact the pregnancy and/or fetal outcomes, including presence of congenital anomalies, placenta previa or abruption.
• Known severe Sickle Cell (SS) disease or Sickle Hemoglobin C (SC) anemia.
• Known family history of prolonged QT Syndrome, serious ventricular arrhythmia, or sudden cardiac death.