This thesis presents the development of quantitative imaging tools to study parasite migration. Since migration is crucial for malaria parasites to continue their life cycle, factors influencing... Show moreThis thesis presents the development of quantitative imaging tools to study parasite migration. Since migration is crucial for malaria parasites to continue their life cycle, factors influencing their migration capability may also impact the efficacy of malaria vaccine candidates. Here, imaging of parasite migration was used to gain insights that can support the development of antiparasitic vaccines. SMOOT (Sporozoite Motility Orienting and Organizing Tool) was developed and established as a quantitative software analysis tool for tracking the migration of malaria sporozoites in vitro and in human skin explant. This tool provides a readout with high kinematic detail, enabling the quantitative characterization of novel factors influencing the migration capability of malaria sporozoites. Subsequently, the study of sporozoite migration was expanded beyond in vitro and ex vivo models. A hybrid tracer labeling approach for malaria sporozoites was developed and used to reveal the in vivo dissemination of malaria sporozoites in a murine model. This multimodal imaging approach was also applied to investigate human skin invasion by helminth larvae. This thesis concludes with a review of the broader potential for imaging technology to advance the development of new diagnostic methods, therapeutic interventions and vaccines for combating parasitic infections. Show less
Alabi, A.; Hussain, M.; Hoogerwerf, M.A.; Mengome, C.N.; Egesa, M.; Driciru, E.; ... ; Agnandji, S.T. 2021
BackgroundHookworm is a major contributor to worldwide disease burden with over 230 million people infected. It has been identified as one of the Neglected Tropical Diseases that can be controlled... Show moreBackgroundHookworm is a major contributor to worldwide disease burden with over 230 million people infected. It has been identified as one of the Neglected Tropical Diseases that can be controlled and even eliminated through mass drug administration and other effective interventions. Mathematical models have shown that hookworm can only be eliminated via a vaccine. Controlled Hookworm Human Infection (CHHI) models can facilitate rapid development of vaccines and drugs.MethodsAs a first step towards the establishment of CHHI in Africa, we held a stakeholders meeting in Lamberene, Gabon from 10 to 11 November 2019.ResultsDiscussions revolved around the roles of the different regulatory institutions concerned; the need to strengthen existing regulatory capacity and the role of legislation; creating Gabon-specific ethical guidelines to govern Controlled Human Infection (CHI) studies; development of a study protocol; consideration of cultural and social peculiarities; the need for regular joint review meetings between interested parties throughout the process of protocol implementation; and participant compensation. Moreover, operational considerations concerning the introduction of CHHI in Gabon include the use of the local strain of hookworm for the challenge infections, capacity building for the local production of challenge material, and the establishment of adequate quality assurance procedures.ConclusionThe workshop addressed several of the anticipated hurdles to the successful implementation of CHHI in Gabon. It is our aim that this report will stimulate interest in the implementation of this model in the sub-Saharan African setting. Show less
Hookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune... Show moreHookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune regulatory effects, hookworms likely impact the bacterial microbiota. However, microbiota studies struggle to deconvolute the effect of hookworms from confounders such as coinfections and malnutrition. We thus used an experimental human hookworm infection model to explore temporal changes in the gut microbiota before and during hookworm infection. Volunteers were dermally exposed to cumulative dosages of 50, 100 or 150 L3 Necator americanus larvae. Fecal samples were collected for microbiota profiling through 16S rRNA gene amplicon sequencing at weeks zero, four, eight, fourteen and twenty. During the acute infection phase (trial week zero to eight) no changes in bacterial diversity were detected. During the established infection phase (trial week eight to twenty), bacterial richness (Chao1, p = .0174) increased significantly over all volunteers. No relation was found between larval dosage and diversity, stability or relative abundance of individual bacterial taxa. GI symptoms were associated with an unstable microbiota during the first eight weeks and rapid recovery at week twenty. Barnesiella, amongst other taxa, was more abundant in volunteers with more GI symptoms throughout the study. In conclusion, this study showed that clinical GI symptoms following N. americanus infection are associated with temporary microbiota instability and relative abundance of specific bacterial taxa. These results suggest a possible role of hookworm-induced enteritis on microbiota stability. Show less
