Intrahost modeling of artemisinin resistance in Plasmodium falciparum

Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia. Resistance is characterized by prolonged in vivo parasite clearance times (PCTs) following artesunate treatment. The biological basis is unclear. The hypothesis that delayed parasite clearance results from a stage-specific reduction in artemisinin sensitivity of the circulating young asexual parasite ring stages was examined. A mathematical model was developed, describing the intrahost parasite stage-specific pharmacokinetic-pharmacodynamic relationships. Model parameters were estimated using detailed pharmacokinetic and parasite clearance data from 39 patients with uncomplicated falciparum malaria treated with artesunate from Pailin (western Cambodia) where artemisinin resistance was evident and 40 patients from Wang Pha (northwestern Thailand) where efficacy was preserved. The mathematical model reproduced the observed parasite clearance for each patient with an accurate goodness of fit (rmsd: 0.03-0.67 in log(10) scale). The parameter sets that provided the best fits with the observed in vivo data consist of a highly conserved concentration-effect relationship for the trophozoite and schizont parasite stages, but a variable relationship for the ring stages. The model-derived assessment suggests that the efficacy of artesunate on ring stage parasites is reduced significantly in Pailin. This result supports the hypothesis that artemisinin resistance mainly reflects reduced ring-stage susceptibility and predicts that doubling the frequency of dosing will accelerate clearance of artemisinin-resistant parasites.     

Assessing the cost-effectiveness of COVID-19 vaccines in a low incidence and low mortality setting: the case of Thailand at start of the pandemic

Objective

This study aimed to assess the cost-effectiveness of COVID-19 vaccines, preferred COVID-19 vaccine profiles, and the preferred vaccination strategies in Thailand.

Methods

An age-structured transmission dynamic model was developed based on key local data to evaluate economic consequences, including cost and health outcome in terms of life-years (LYs) saved. We considered COVID-19 vaccines with different profiles and different vaccination strategies such as vaccinating elderly age groups (over 65s) or high-incidence groups, i.e. adults between 20 and 39 years old who have contributed to more than 60% of total COVID-19 cases in the country thus far. Analyses employed a societal perspective in a 1-year time horizon using a cost-effectiveness threshold of 160,000 THB per LY saved. Deterministic and probabilistic sensitivity analyses were performed to identify and characterize uncertainty in the model.

Results

COVID-19 vaccines that block infection combined with social distancing were cost-saving regardless of the target population compared to social distancing alone (with no vaccination). For vaccines that block infection, the preferred (cost-effective) strategy was to vaccinate the high incidence group. Meanwhile, COVID-19 vaccines that reduces severity (including hospitalization and mortality) were cost-effective when the elderly were vaccinated, while vaccinating the high-incidence group was not cost-effective with this vaccine type. Regardless of vaccine type, higher vaccination coverage, higher efficacy, and longer protection duration were always preferred. More so, vaccination with social distancing measures was always preferred to strategies without social distancing. Quarantine-related costs were a major cost component affecting the cost-effectiveness of COVID-19 vaccines.

Conclusion

COVID-19 vaccines are good value for money even in a relatively low-incidence and low-mortality setting such as Thailand, if the appropriate groups are vaccinated. The preferred vaccination strategies depend on the type of vaccine efficacy. Social distancing measures should accompany a vaccination strategy.