An artesunate-containing antimalarial treatment regimen did not suppress cytomegalovirus viremia

Abstract

Background Additional drugs are needed for the treatment of cytomegalovirus (CMV) infection. Artesunate is an antimalarial drug that has activity against CMV in vitro and in a rodent model. Only a small number of case reports are available describing the clinical effects of artesunate on CMV infection, and these yielded inconsistent results. Objective To evaluate the effect of artesunate on CMV infection, using blood samples collected from children who participated in malaria treatment trials. Study design Quantitative CMV DNA PCR was performed on dried blood spots collected from 494 Ugandan children, who were randomized either to artesunate plus amodiaquine or sulfadoxine-pyrimethamine plus amodiaquine for acute malaria infection. Poisson regression was used to compare treatment regimens with respect to the change in the frequency and quantity of CMV detected that occurred before and after treatment. Results CMV was detected in 11.4% of children immediately prior to treatment and 10.7% 3 days later (p=0.70). The average quantity of CMV was 0.30 log10 copies per million cells higher on day 3 than at treatment initiation (95% CI 0.01 to 0.58, p=0.041). There was no measurable difference in either the frequency or quantity of CMV detected in blood between children randomized to the two treatment arms. Conclusions A standard 3-day artesunate-containing antimalarial regimen had no detectable effect on CMV viremia in children with malaria. Longer treatment courses and/or higher doses of artesunate than those routinely used for malaria may be required for effective treatment of CMV infection.

The Use of Antimalarial Drugs against Viral Infection

“…One of these combinations, AS plus amodiaquine (AQ), was tested against HCMV in a clinical study conducted on 494 Ugandan children treated for acute malaria either with the ACT or with sulfadoxine-pyrimethamine plus AQ. No measurable difference was observed in either the HCMV detection frequency or load in the blood of children in the two groups [49].…”

Review of cytomegalovirus coinfection in HIV-infected individuals in Africa

“…A modestly reduced cervical CMV shedding was observed. Finally, the effect of artesunate on CMV was investigated in Uganda, as some case reports had described activity against CMV. Yet a 3‐day artesunate containing antimalarial regimen had no detectable effect on CMV viremia in children with malaria.…”

Effect of artemether-lumefantrine (Coartem) on cytomegalovirus urine viral load during and following treatment for malaria in children

“…al did not observe a difference in their 3-day follow up study in which dried blood spots were used to evaluate viremia in patients receiving artemisinin combination therapy (ACTs) for malaria (17). Since viremia is likely uncommon in the normal host and typically at low levels, (only 11% of participants in that study were found to have low level viremia) changes in viral loads during artemisinin therapy may have been difficult to detect (25).…”

“…While there is compelling in vitro data that these compounds are highly effective against CMV, in vivo data supporting the use of artemisinin derivatives is scattered and consists largely of case reports and one observational clinical study (15, 16). A trial of Ugandan children receiving either artesunate plus amodiaquine or sulfadoxine-pyrimethamine plus amodiaquine showed no difference in CMV viral loads measured from dried blood spots at day one or day three following therapy (17). …”