Anti-Malarial Strategies Among Vulnerable Populations: exploring bed net underutilization among internally displaced persons and novel adjunctive therapies for cerebral malaria

• Author / Creator

  Brooks, Hannah M

• Background: Despite declining incidence globally, malaria morbidity and mortality remain elevated among internally displaced persons (IDPs) and children under five, particularly in sub-Saharan Africa. Malaria prevention and treatment efforts in the Democratic Republic of the Congo (DRC) are hindered by armed conflict, which has resulted in the forced displacement of an estimated 1.5 million individuals. Among children under five, cerebral malaria (CM) represents a severe manifestation that may result in death or developmental disability. This thesis has two major focuses: 1) to describe the burden of malaria and reasons for the underutilization of bed nets, a key intervention in malaria control efforts, among IDPs in Eastern DRC; and 2) to test recently licensed pharmaceuticals as putative neuroprotective agents in an in vitro model of CM. Methods: 1) A cross-sectional survey was conducted in Lushebere IDP camp in Eastern DRC to describe the burden of malaria in the population. A second cross-sectional survey was conducted in Birambizo IDP camp in Eastern DRC, supplemented with qualitative descriptions by IDP camp residents, neighbouring villagers, and health workers from the camp, to describe reasons for use and disuse of bed nets among IDPs. 2) An in vitro model of the blood brain barrier (BBB) was created using endothelial and astrocyte cells in a transwell system to test select pharmacological agents in their ability to prevent BBB breakdown, measured as a function of changes in transendothelial electrical resistance (TEER). Three challenges were independently used to compromise endothelial monolayer integrity: tumour necrosis factor (TNF), vascular endothelial growth factor (VEGF) and Plasmodium falciparum infected red blood cells (Pf-IRBCs). Pharmacological agents are recently licensed and were tested at physiologically plausible concentrations. Results: The proportion of IDP camp residents who tested positively for malaria via rapid diagnostic test was high, particularly among children under five (61% of febrile children under 5 in Lushebere, and 58% of children under 5 in Birambizo). Despite free bed net distribution campaigns throughout both camps, bed net ownership and use was low (36% in Lushebere and 29% in Birambizo). Focus group discussions revealed several pragmatic barriers to bed net use within the camp setting and competing needs for ii nutrition which often drove individuals to sell or exchange their nets in order to feed their families. In our in vitro studies of CM, three pharmacologic agents were successful in rescuing BBB break down induced by either TNF, VEGF, or Pf-IRBCs: fingolimod, sunitinib, and pazopanib. If successful in future in vivo studies and human clinical trials, these recently licensed agents may be repurposed for use as adjunctive therapies in CM. Conclusions: These studies highlight the burden of malaria among two key vulnerable populations: IDPs and children under five. Our findings call attention to the need for new and improved malaria control and treatment efforts within these populations. Current malaria vector control and cerebral malaria adjunctive therapies are incompletely effective for IDPs in regions of sub-Saharan Africa and children under five, respectively. Global efforts to further reduce malaria associated morbidity and mortality should not forget vulnerable and often hard-to-reach populations, and efforts should be tailored to meet the individual needs of these large populations if progress is to be made.

• Subjects / Keywords

  • Global Health
  • Malaria
  • Public Health

• Graduation date

  Fall 2017

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3JD4Q33Z

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.