Prospective Study of Infant Dengue
Prospective Study of Infant Dengue
Dengue is a common disease and a major health concern in the Philippines. Dengue is caused by
 a virus transmitted from the bite of an infected mosquito. The purpose of this study is to
 understand why some infants remain well or have a mild illness, and why other infants become
 very sick from this virus. Studies have shown that the mother's immune response to dengue can
 play a role in the infant's immune response and affect whether or not the infant becomes
 sick. This study will enroll up to 10,000 healthy infants 6-14 weeks old and their mothers in
 San Pablo City. At the first study visit, information about the mother and birth will be
 collected and blood samples will be taken from the mother and infant. The infant will have
 blood drawn at all 3 study visits. The infants will be followed until the age of 16 months.
 The information obtained from this study may help in the development and future testing of a
 safe and effective dengue vaccine.
This is a prospective natural history study to define the levels of maternally-acquired
 neutralizing antibody (Ab) and other correlates of immunity that may protect against the
 development of dengue hemorrhagic fever in infants. Approximately 10,000 mother-infant pairs
 will be enrolled to achieve a continuous study cohort of approximately 4,000 children less
 than 16 months of age. Children leave the study when they reach 16 months of age and are
 replaced by new participants at 6-14 weeks of age. The investigators will recruit study
 participants among 3rd trimester pregnant women receiving pre-natal care and women with
 newborns receiving post-natal care in San Pablo City. The first aim of this study is to
 define levels of serotype-specific neutralizing Abs associated with protective immunity
 against symptomatic dengue virus (DV). Neutralizing Ab titers in blood samples collected from
 Filipino infants before DV infection, and predicted neutralizing Ab titers at the time of
 illness, will be correlated with disease severity rankings and peak viremia levels.
 Neutralizing Ab titers at which infants developed symptomatic dengue will be determined. The
 second aim will be to delineate risk factors contributing to the pathogenesis of dengue
 hemorrhagic fever (DHF) in infants. From pre-illness blood samples, the association of Ab
 neutralizing capacity or enhancement of infection with DHF will be measured while controlling
 for other potential covariates. The covariates will include measures representing viral load
 and infant host immune responses. The third aim will be to strengthen the capacity for
 diagnosis and research on dengue in the Philippines. A collaborative and international
 consortium has been formed to advance dengue research in the Philippines. The research will
 generate vital data for the effective testing of dengue vaccines and future public health
 vaccination campaigns throughout the region. This study will enroll up to 10,000 healthy
 infants 6-14 weeks old and their mothers in San Pablo City. The infants will be followed
 until the age of 16 months. Mothers and infants will enter the study when the infant is
 between the ages of 6-14 weeks. At the 1st study visit, data on the mother and the birth will
 be collected and blood samples will be collected from the mother and infant. The infant will
 have blood drawn at all 3 study visits. The 2nd study visit will take place when the infant
 is between the ages of 4-6 months. At this time, data on infant health will be obtained. In
 all infants, an anticoagulated blood sample will be collected for plasma and PBMC isolation.
 At age 15-16 months, 250 infants per year will be selected to return for a 3rd study visit.
 The 250 infants will be randomly selected from those without prior symptomatic dengue and
 whose study visits 2 and 3 span a significant portion of the peak DV transmission season
 (June-October). Data on infant health will be obtained and an anticoagulated blood sample for
 plasma will be collected. Surveillance for DV infections will occur year round and throughout
 the entire period of an infant's study participation (ages 6 weeks-16 months). Study
 personnel will screen infants in the study who present with acute febrile illnesses. Those
 infants will have history and clinical data abstracted, and an acute illness blood sample
 (serum) taken for dengue diagnostic testing. A convalescent blood sample (serum) will also be
 taken 10-14 days later. The primary outcome measured will be the identification of DV
 infection and the classification of disease severity. The secondary outcome measured will be
 the estimation of peak viremia levels.
Inclusion Criteria:

 1. Infants born to mother residing in San Pablo Health District

 2. Planned residence in San Pablo Health District for at least 1 year

 3. Age 6-14 weeks*

 4. Informed consent

 5. General good health * Except on study initiation, when over the first 5 months of Year
 1 (est. Feb-June 2006), infants between the ages of 6-24 weeks will be allowed to
 enter the study.

 Exclusion Criteria:

 1. Infant born with congenital medical disorder

 2. Mother known to be HIV seropositive