BackgroundIn Southeast Asia, Plasmodium knowlesi, a parasite of long-tailed macaques (Macaca fascicularis), is an important cause of human malaria. Plasmodium cynomolgi also commonly infects these monkeys, but only one naturally acquired symptomatic human case has been reported previously.MethodsMalariometric studies involving 5422 subjects (aged 6 months to 65 years) were conducted in 23 villages in Pailin and Battambang, western Cambodia. Parasite detection and genotyping was conducted on blood samples, using high-volume quantitative PCR (uPCR).ResultsAsymptomatic malaria parasite infections were detected in 1361 of 14732 samples (9.2%). Asymptomatic infections with nonhuman primate malaria parasites were found in 21 individuals living close to forested areas; P. cynomolgi was found in 11, P. knowlesi was found in 8, and P. vivax and P. cynomolgi were both found in 2. Only 2 subjects were female, and 14 were men aged 20–40 years. Geometric mean parasite densities were 3604 parasites/mL in P. cynomolgi infections and 52488 parasites/mL in P. knowlesi infections. All P. cynomolgi isolates had wild-type dihydrofolate reductase genes, in contrast to the very high prevalence of mutations in the human malaria parasites. Asymptomatic reappearance of P. cynomolgi occurred in 2 subjects 3 months after the first infection.ConclusionsAsymptomatic naturally acquired P. cynomolgi and P. knowlesi infections can both occur in humans.Clinical Trials RegistrationNCT01872702.

Background: Uncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines. Early in the pandemic the monoclonal antibody cocktail, casirivimab/imdevimab, proved highly effective in clinical trials but because of weak or absent in vitro activity against the SARS-CoV-2 Omicron BA.1 subvariant, it is no longer recommended. Methods: In a multicenter open label, randomized, controlled adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days), casirivimab/imdevimab (600mg/600mg), and no study drug. The primary outcome was the viral clearance rate in the modified intention-to-treat population derived from daily log10 viral densities (days 0-7) in standardized duplicate oropharyngeal swab eluates. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). Results: Acceleration in mean estimated SARS-CoV-2 viral clearance, compared with the contemporaneous no study drug arm (n=64), was 42% (95%CI 18 to 73%) for remdesivir (n=67). Acceleration with casirivimab/imdevimab was 58% (95%CI: 10 to 120) in Delta (n=13), and 20% (95%CI: 3 to 43) in Omicron variant (n=61) infections compared with contemporaneous no study drug arm (n=84). In a post hoc subgroup analysis viral clearance was accelerated by 8% in BA.1 (95%CI: -21 to 59) and 23% (95%CI: 3 to 49) in BA.2 and BA.5 Omicron subvariants. Conclusions: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Despite substantially reduced in vitro activities, casirivimab/imdevimab retains in vivo antiviral activity against COVID-19 infections caused by currently prevalent Omicron subvariants.

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