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

Abstract

BACKGROUND Artemisinins, commonly used to treat malaria, have shown activity against cytomegalovirus (CMV) in vitro, in an animal model, and in case reports; however, the in vivo anti-CMV activity has not been well investigated. OBJECTIVES To evaluate whether artemisinins affect CMV shedding among subjects co-infected with CMV and malaria. STUDY DESIGN A prospective observational study of children in Mali (6 mo-10 yr) presenting with fever. Urine samples were collected at day 0, 3, and 14 from children treated with artemether-lumefantrine (Coartem®) for malaria and those who had other illnesses not treated with Coartem. CMV DNA was quantified using a real-time PCR. Resulting urine viral loads were compared between the groups at three time points. RESULTS 164 malaria cases and 143 non-malaria comparisons were enrolled. Eighty-one (49%) cases and 88 (62%) comparisons shed CMV at day 0. Day 0 and day 3 viral loads were similar, but at day 14 the median viral load of cases was lower than that of comparisons (360 versus 720 copies/mL or 2.56 versus 2.86 log10), p=0.059. A stratified analysis of day 0 high viral shedders (defined as >1000 copies/mL) showed significantly lower median viral load at day 14 among cases (490 copies/mL, 2.69 log10) versus comparisons (1200 copies/mL, 3.08 log10), p=0.045. CONCLUSION A high rate of urinary CMV shedding was found in a malaria-endemic area. Among high virus shedders artemether-lumefantrine decreased urine viral load, but the effect was not observed when analysis of both high and low shedders was performed. These results support additional studies of artemisinin dosing and duration in CMV infection.

Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization

“…The serum IgG avidity index for CMV was determined at enrollment to assess for recent or past prior infection. Eight of 15 (53%) patients were CMV-seropositive (n=15; index range, 0.55 to 0.82), a prevalence consistent with the lower end of that reported in the general population (20, 21). Of 38 plasma samples that were collected at baseline and during participation in the study, low level viremia was detected by US17 real-time PCR in 3 samples at baseline (Table 2) and only in one follow-up sample.…”

“…The measurable range of the assay is 1.0E+02 to 1.0E+08 copies/mL and the limit of detection is 1.0E+02 copies/mL. This assay has been used extensively in our laboratory to detect CMV DNA and measure CMV loads in different body fluids (21). Beta-actin real-time PCR was used to assess efficiency of DNA extraction from FFPE tissues (Applied Biosystems/ThermoFisher Scientific, Foster City, CA).…”

The Use of Antimalarial Drugs against Viral Infection

“…One of the commercial versions of this combination, Coartem ® , was used in a prospective observational study in Mali in children (6 months-10 years) coinfected with HCMV and malaria. Viral load in the urine decreased but only in high virus shedders [64]. The artemether-lumefantrine combination was also used in patients infected with EBOV, showing reduced efficacy in reducing the risk of death compared to that of AS-AQ, as already described in the "Artesunate" paragraph [58].…”

“…Herpesviridae HCMV Artesunate [12,13,[46][47][48] Artesunate-amodiaquine [49] Arthemeter-lumefantrine [64] HHV6 Artesunate [52] Polyomaviridae JCPyV Artesunate [54,55] Mefloquine [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][122][123][124][125][126] Mefloquine and mirtazapine [86,87,127,128] Mefloquine, mirtazapine and a third drug [118,119] Mefloquine and risperidone [75] Mefloquine, risperidone and cytarabine [120] Mefloquine and cidofovir [121] Mefloquine and PML standard of care [129] Filoviridae EBOV Artesunate-amodiaquine [58,60] Nevertheless, some drugs have already been used in several clinical trials, as summarized in Table 1. Most of them regard the use of antimalarial drugs against HIV infection, but some of them failed, and...…”

Ganciclovir‐Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature

“…Artesunate inhibits the expression of immediate early viral proteins necessary for DNA replication and prevents the proinflammatory downregulation of host cell–surface proteins in CMV‐infected cells . In vitro studies suggest that artesunate has a synergistic effect when used in combination with GCV and has at least an additive effect with FOS and CDV A 2016 prospective trial of malaria in children from Mali further supported the anti‐CMV activity of oral artemisinins …”