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Killing Plasmodium Parasites in the Mosquito: Target Identification and Feasibility Testing for a Novel Malaria Control Strategy
Killing Plasmodium Parasites in the Mosquito: Target Identification and Feasibility Testing for a Novel Malaria Control Strategy
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260311091458.5
- ISBN
- 9798280711013
- DDC
- 614.432
- 서명/저자
- Killing <em>Plasmodium</em> Parasites in the Mosquito: Target Identification and Feasibility Testing for a Novel Malaria Control Strategy / Alexandra Sterling Probst
- 발행사항
- [Sl] : Harvard University, 2025
- 형태사항
- 1 electronic resource (202 pages)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisors: Catteruccia, Flaminia; Wirth, Dyann Committee members: Mazitschek, Ralph; Neafsey, Daniel; Idris, Azza; Goldberg, Daniel.
- 학위논문주기
- - Ph.D. : Harvard University, 2025.
- 초록/해제
- 요약Malaria is a devastating disease that affects hundreds of millions of people worldwide, leading to nearly 600,000 deaths in 2023. Plasmodium falciparum parasites are the causative agent of over 90% of malaria cases and are transmitted to people by the bite of an infectious Anopheles female mosquito. Vector control strategies that target these mosquitoes have been instrumental to control efforts, and the extensive rollout of insecticide treated bed nets has contributed to substantial reductions in malaria prevalence and mortality since the turn of the century. However, high levels of insecticide resistance have emerged in anophelines, and to-date, insecticide-resistant mosquitoes have been identified in over 80% of malaria endemic countries. This widespread resistance jeopardizes the efficacy of current vector control tools and has contributed to the recent plateau in malaria cases worldwide. New interventions are thus urgently needed.In this dissertation, I describe our efforts to develop a novel transmission blocking strategy that circumvents insecticide resistance by targeting parasites directly with antimalarial compounds during their development in the mosquito. In Chapter 1, I review the current state of malaria control and promising new tools, with an emphasis on vector control. I introduce the concept of mosquito-targeted antiplasmodials and outline key features for their successful implementation. In Chapter 2, I identify suitable targets for this strategy by performing an in vivo screen of antiplasmodial compounds in mosquitoes, optimize key inhibitors for improved uptake and activity, and assess their resistance propensity and transmissibility. In Chapter 3, I test the feasibility of incorporating hit compounds in bed net-like materials, determine their antiplasmodial activity in insecticide-resistant mosquitoes, and assess their activity across sporogonic development. Finally, in Chapter 4 I discuss implications of this work and directions for further development of this strategy. Altogether, this dissertation significantly expands our understanding of mosquito-targeted antiplasmodials and demonstrates their potential for malaria control in the context of widespread insecticide resistance.
- 언어주기
- English
- 일반주제명
- Parasitology
- 일반주제명
- Public health
- 일반주제명
- Pathology
- 키워드
- Anopheles
- 키워드
- Malaria
- 기타저자
- Harvard University Biological Sciences in Public Health
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr|nu||||||||
■020 ▼a9798280711013
■040 ▼aMiAaPQD▼beng▼cMiAaPQD▼erda
■082 ▼a614.432
■1001 ▼aProbst, Alexandra Sterling▼eauthor.▼0(orcid)0000-0001-8389-8159
■24510▼aKilling emPlasmodium/em Parasites in the Mosquito: Target Identification and Feasibility Testing for a Novel Malaria Control Strategy ▼cAlexandra Sterling Probst
■260 ▼a[Sl]▼bHarvard University▼c2025
■264 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a1 electronic resource (202 pages)
■336 ▼atext▼btxt▼2rdacontent
■337 ▼acomputer▼bc▼2rdamedia
■338 ▼aonline resource▼bcr▼2rdacarrier
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisors: Catteruccia, Flaminia; Wirth, Dyann Committee members: Mazitschek, Ralph; Neafsey, Daniel; Idris, Azza; Goldberg, Daniel.
■5021 ▼bPh.D.▼cHarvard University▼d2025.
■520 ▼aMalaria is a devastating disease that affects hundreds of millions of people worldwide, leading to nearly 600,000 deaths in 2023. Plasmodium falciparum parasites are the causative agent of over 90% of malaria cases and are transmitted to people by the bite of an infectious Anopheles female mosquito. Vector control strategies that target these mosquitoes have been instrumental to control efforts, and the extensive rollout of insecticide treated bed nets has contributed to substantial reductions in malaria prevalence and mortality since the turn of the century. However, high levels of insecticide resistance have emerged in anophelines, and to-date, insecticide-resistant mosquitoes have been identified in over 80% of malaria endemic countries. This widespread resistance jeopardizes the efficacy of current vector control tools and has contributed to the recent plateau in malaria cases worldwide. New interventions are thus urgently needed.In this dissertation, I describe our efforts to develop a novel transmission blocking strategy that circumvents insecticide resistance by targeting parasites directly with antimalarial compounds during their development in the mosquito. In Chapter 1, I review the current state of malaria control and promising new tools, with an emphasis on vector control. I introduce the concept of mosquito-targeted antiplasmodials and outline key features for their successful implementation. In Chapter 2, I identify suitable targets for this strategy by performing an in vivo screen of antiplasmodial compounds in mosquitoes, optimize key inhibitors for improved uptake and activity, and assess their resistance propensity and transmissibility. In Chapter 3, I test the feasibility of incorporating hit compounds in bed net-like materials, determine their antiplasmodial activity in insecticide-resistant mosquitoes, and assess their activity across sporogonic development. Finally, in Chapter 4 I discuss implications of this work and directions for further development of this strategy. Altogether, this dissertation significantly expands our understanding of mosquito-targeted antiplasmodials and demonstrates their potential for malaria control in the context of widespread insecticide resistance.
■546 ▼aEnglish
■590 ▼aSchool code: 0084
■650 4▼aParasitology
■650 4▼aPublic health
■650 4▼aPathology
■653 ▼aAnopheles
■653 ▼aMalaria
■653 ▼aPlasmodium falciparum
■653 ▼aVector control strategies
■7102 ▼aHarvard University▼bBiological Sciences in Public Health.▼edegree granting institution.
■7201 ▼aCatteruccia, Flaminia▼edegree supervisor.
■7201 ▼aWirth, Dyann▼edegree supervisor.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357472▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
