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Safety around the Plasmodium Vivax induced blood stage malaria model

Odedra, Anand (2020) Safety around the Plasmodium Vivax induced blood stage malaria model, Thesis (Doctoral), Liverpool School of Tropical Medicine.

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Experimental malaria infection studies entailing the infection of healthy volunteers using the induced blood stage malaria (IBSM) model where blood stage Plasmodium vivax parasites are injected intravenously provide valuable information on parasite biology and the development of drugs and vaccines. A single serious adverse event could threaten the ongoing use of this and other experimental malaria infection models.
This thesis aimed to explore the safety of the P. vivax IBSM model, centring around an exploratory study using apheresis as a method to extract and concentrate all stages of P. vivax parasites from healthy volunteers infected with blood stage P. vivax. The absence of a method to culture P. vivax has hampered many aspects of P. vivax research. Apheresis harvested asexual parasites may be used to produce human malaria parasite banks, and gametocytes for cryopreservation as well as for mosquito feeding and subsequent attainment of sporozoites. The safety evaluation involved; a review of safety aspects across all malaria experimental infection models, a systematic review of the safety and efficacy of apheresis in the treatment of malaria and other infectious diseases, an assessment of the safety of apheresis for the harvesting of P. vivax parasites and analysis of post treatment transaminase elevations encountered in prior P. vivax IBSM.
No safety concerns were identified during the review of malaria VIS or the use of apheresis in the treatment of infectious diseases that were concerning enough to interfere with the plan for the exploratory study. Publications identified in the systematic review were case reports, case series, and cohort studies, thus publication bias was considered to be high. Apheresis may be a potentially useful adjunct to chemotherapy in the treatment of patients hospitalised for babesia, and prior to chemotherapy in loiasis with microfilarial count >8000/mL. The data did not support the use of apheresis in critical pertussis infection or for patients with severe P. falciparum malaria. No serious safety concerns were encountered in the four subjects involved in the exploratory study. Apheresis achieved a modest level of parasite enrichment compared to whole blood sampling (4.9-fold and 1.45-fold per mL of sample for asexual parasites and gametocytes respectively) but was insufficient to meet the objectives for the collection of parasites for downstream research. Therefore apheresis should not be used as a method for harvesting P. vivax parasites. Post treatment transaminase elevations are transient, asymptomatic and appear to be more common in P. vivax IBSM than in natural infection. Evidence indicates that parasite clearance burden, haemolysis and systemic inflammation post anti-malarial treatment may be drivers for the observed transaminase elevations. However, the mechanisms underlying these abnormalities remain unclear and require further investigation.

Item Type: Thesis (Doctoral)
Subjects: QX Parasitology > Protozoa > QX 135 Plasmodia
QX Parasitology > QX 20 Research (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Depositing User: Lynn Roberts-Maloney
Date Deposited: 16 Sep 2020 09:42
Last Modified: 16 Dec 2020 02:02


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