dc.description.abstract |
Epstein–Barr virus (EBV) is an oncogenic virus that has been implicated in the etiology
of endemic Burkitt’s lymphoma (eBL). Infection with EBV early in life and repeated
Plasmodium falciparum malaria exposures have been linked to the etiology of eBL.
Previous study reported that 35% of children in Kisumu were infected before 6 months
of age. However, the underlying mechanism that predisposes infants to EBV infection
before 6 months of age and the role of P. falciparum malaria in EBV transmission is a
significant gap in the etiology of eBL. The objective of this study was to determine the
effect of P. falciparum malaria infection on EBV reactivation during pregnancy, and
subsequent EBV shedding in breast milk postpartum among pregnant women. The study
enrolled 175 HIV negative pregnant women attending the antenatal clinic and followed
them prospectively from antenatal to delivery through to postpartum. Data on
demographic, obstetrics and socioeconomic status were collected. Blood and breast milk
samples were collected at various visits. Malaria diagnosis and EBV load were measured
by quantitative polymerase chain reaction assay (Q-PCR). EBV serology was measured
using ELISA. DNAse I based assay was used to assess whether there was encapsidated
virus in breast-milk. EBV DNA positive breast-milk supernatant was exposed to 106
cells/ml Peripheral Blood Mononuclear Cells (PBMC) and observed for evidence of
transformation. Results show that pregnant women who had malaria during pregnancy
were more likely to have a detectable EBV DNA than pregnant women who had no
evidence of malaria during pregnancy (64% vs. 36%, p=0.01). EBV load, as quantified
using area under the longitudinal observation curve (AUC), was significantly higher in
women with P. falciparum malaria than in women without malaria (p =0.01). Increase in
EBV load correlated with that of malaria load (p <0.0001). Independent of malaria
infection, EBV load was significantly higher at third trimester (p =0.04) than first and
second trimester of pregnancy. EBV DNA and EBV load in breast-milk was
significantly higher at 6 weeks and decreased sequentially in subsequent visits (p <
.0001). Virus in breast milk supernatant was found to be DNAse I resistant in 24/40
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(60%) of samples, and showed evidence of lymphocyte transformation. Being infected
with P. falciparum infection at delivery was significantly associated with increased EBV
shedding in early breast milk (p = 0.02), whereas, levels of EBV load in maternal blood
at delivery was positively correlated with that of EBV load at 6 weeks postpartum (p =
0.002). The findings suggest that malaria during pregnancy causes EBV reactivation
leading to high EBV load in maternal circulation, which subsequently increases
shedding of infectious EBV in breast milk, a possible conduit of EBV transmission in
infants at an early age. This study recommends sustained long-term efforts in malaria
control programs such as, use of insecticide treated bed nets, intermittent preventive
therapy, and indoor vector control, with a view to reducing EBV reactivation during
pregnancy and subsequent EBV shedding in breast milk, consequently stemming eBL. |
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