Viral haemorrhagic fevers in pregnancy with a focus on lassa fever

The viral haemorrhagic fevers (VHFs) are thought to be major causes of morbidity and mortality in pregnant women. However, there remains a paucity of evidence in pregnancy, due in part to the exclusion of pregnant women from clinical trials. The recent occurrence of large VHF outbreaks, coupled with the increased vulnerability of Sub-Saharan Africa to VHF epidemics, particularly in areas reporting high poverty and high maternal mortality increases the importance of improving our understanding of VHFs in pregnancy. The thesis sets out to generate evidence to inform disease control and clinical trial design and implementation by investigating the epidemiology of the VHFs in pregnancy and exploring issues around trial implementation. It consists of three results chapters. Chapter 2 is an epidemiological evidence synthesis of the priority VHFs in pregnancy. It identifies research gaps and facilitates selection of one of the VHFs for in-depth study. Chapter 3 sets the stage for the next two results chapters. Chapter 4 investigates three gaps in the epidemiology of Lassa fever in pregnancy. Specifically, prevalence, incidence, and risk factors for Lassa fever, and begins work on the kinetics of Lassa antibodies in pregnancy by presenting evidence regarding transplacental transfer of Lassa antibodies. Chapter 5 explores issues around trial implementation by generating qualitative evidence specific to participation, recruitment, and retention of pregnant women in Lassa fever clinical trials. The thesis presents new data on the epidemiology of the VHFs in pregnancy, particularly Lassa fever, which facilitates estimation of disease burden and, as such inform policy for disease control and drug and vaccine development. It describes trial design and implementation issues that arise with respect to the inclusion of pregnant women in clinical trials and suggests relevant actors and subject areas for effective trial implementation.