Influence of intermittent preventive treatment on transplacental transfer of anti-measles immunoglobulin-g antibodies in mother-infant pairs from Ahero sub-county hospital in Kisumu county, western Kenya

Abstract

Measles still remains one of the leading causes of vaccine preventable deaths globally with 140,000 deaths in 2019. These deaths occur despite the existence of a safe and effective measles vaccine. In Kenya, annual measles incidence ranges from 2-65 cases per million persons with about 76% of these being reported in unvaccinated infants aged less than a year. Primary protection against measles during infancy is mediated by maternally derived antibodies prior to vaccination with the levels in infants correlating with maternal antibody levels. The efficiency of transfer of measles specific antibodies is dependent on a number of factors including malaria infection. World Health Organization recommends malaria chemoprophylactic treatment in pregnant women in malaria endemic areas like western Kenya which may improve or suppress the vertical transfer of antibodies against other infectious diseases like measles. This study investigated the levels and vertical transfer of anti-measles Immunoglobulin-G to infant in expectant women taking either Dihydroartemisinin Piperaquine(DP) or Sulphadoxine Pyrimethamine (SP) for malaria Intermittent Preventive Treatment in pregnancy (IPTp). Specifically, this study compared the levels of anti-measles antibodies in mother-infant pairs undertaking IPTp-SP; compared the levels of anti-measles antibodies in mother-infant pairs undertaking IPTp-DP; compared the levels of anti-measles antibodies in mother-infant pairs between the IPTp-DP and SP treated participants, and finally investigated the influence of confounding variables (placental malaria, maternal age, hyper/po-gammaglobulinemia, parity and gestational age)- on the vertical transfer of anti-measles antibodies in women attending Ahero Sub-County Hospital in Kisumu County, Western Kenya. Using convenient sampling, samples from 132 mothers and 66 infants’ samples were included in this retrospective-prospective study design. The levels of antibodies against measles; EBV and malaria antibodies (internal positive controls) in maternal venous, cord (neonatal), and infants blood samples at one and six weeks were quantified using Luminex technology. Total IgG levels were determined in maternal venous blood by Enzyme-linked Immunosorbent Assay (ELISA). Wilcoxon paired test was used to compare the median levels of antibodies in mother-infant pairs to measles, EBV and malaria within the DP and SP treated groups. Using Wilcoxon paired test, the levels of MV (measles), EBV and malaria antibody levels were comparable between the mother-infant pairs in the SP treatment arm (P= 0.47, 0.97, 0.16, 0.47 and 0.73 for MV, AMA1, MSP1, EBNA1 and ZEBRA respectively). The levels were also comparable for the mother-infant pairs treated with DP (P= 0.71, 0.66, 0.96, 0.94, 0.71 for MV, AMA1, MSP1, EBNA1 and ZEBRA, respectively). Mann-Whitney U test comparing median antibody levels between the DP and SP treated mothers and their respective infants only showed a significant difference at enrollment (baseline) for MV and EBNA1 (P= 0.0057 and 0.0035, respectively). Anti-MV, AMA1, MSP1, ZEBRA and EBNA1 were however comparable at birth and among the infants. Spearman correlation analysis showed a positive correlation between maternal and neonatal antibody levels. Multivariate linear regression analysis showed no influence of the confounding variables investigated on transplacental transfer of antibodies. These findings suggest that malaria chemoprophylaxis with either DP or SP does not affect the levels and subsequent transfer of MV as well as EBV and malaria specific antibodies. This study also demonstrates that more than 20% of the infants by six weeks postpartum are highly susceptible to measles infection thereby pointing to the need for a booster dose of measles vaccine in women of child bearing age before conception to increase the duration of protection in infants before vaccination. In addition, this data confirms the safety of IPTP- DP/SP which makes them suitable for use in malaria endemic settings after considering their efficacy in malaria management.