Breanna Barger-Kamate1, Michael Forman2, Cheik Oumar Sangare3, Aboubecrin Sedhigh A Haidara3, Hamma Maiga3, Dhananjay Vaidya4, Abdoulaye Djimde3, Ravit Arav-Boger5. 1. Johns Hopkins University, Department of Pediatrics, Division of Pediatric Emergency Medicine, Baltimore, MD, USA. 2. Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, MD, USA. 3. Malaria Research and Training Center, Bamako, Mali. 4. Johns Hopkins University, Department of Medicine, Baltimore, MD, USA. 5. Johns Hopkins University, Department of Pediatrics, Division of Pediatric Infectious Disease, Baltimore, MD, USA. Electronic address: boger@jhmi.edu.
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 month-10 year) 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 vs 720 copies/mL or 2.56 vs 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) vs 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.
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 month-10 year) 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 vs 720 copies/mL or 2.56 vs 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) vs 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.
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