Yesterday, I saw the nurse practitioner at my doctor's office, and she was very concerned about the blurred vision. She told me to stop the artemisinin and get an eye exam right away, since artemisinin can cause permanent damage to the eye sight. I wasn't aware of this.

Should I be concerned? I thought that blurred vision was just a typical side effect of the meds/treatment.

I tried searching but was unsuccessful.

Thanks.

Fatal neurotoxicity of arteether and artemether.

Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS, Heiffer MH, Schuster BG.

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, District of Columbia.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteether-induced brain injury in Macaca mulatta. I. The precerebellar nuclei: the lateral reticular nuclei, paramedian reticular nuclei, and perihypoglossal nuclei.

Petras JM, Young GD, Bauman RA, Kyle DE, Gettayacamin M, Webster HK, Corcoran KD, Peggins JO, Vane MA, Brewer TG.

Division of Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.

Malaria poses a threat across several continents: Eurasia (Asia and parts of Eastern Europe), Africa, Central and South America. Bradley (1991) estimates human exposure at 2,073,000,000 with infection rates at 270,000,000, illnesses at 110,000,000, and deaths at 1,000,000. Significant mortality rates are attributed to infection by the parasite Plasmodium falciparum, with an estimated 90% among African children. A worldwide effort is ongoing to chemically and pharmacologically characterize a class of artemisinin compounds that might be promising antimalarial drugs. The U.S. Army is studying the efficacy and toxicity of several artemisinin semi-synthetic compounds: arteether, artemether, artelinic acid, and artesunate. The World Health Organization and the U.S. Army selected arteether for drug development and possible use in the emergency therapy of acute, severe malaria. Male Rhesus monkeys (Macaca mulatta) were administered different daily doses of arteether, or the vehicle alone (sesame oil), for a period of either 14 days, or 7 days. Neuropathological lesions were found in 14-day arteether treated monkeys in the precerebellar nuclei of the medulla oblongata, namely: (1) the lateral reticular nuclei (subnuclei magnocellularis, parvicellularis, and subtrigeminalis), (2) the paramedian reticular nuclei (subnuclei accessorius, dorsalis, and ventralis), and the perihypoglossal nuclei (n. intercalatus of Staderini, n. of Roller, n. prepositus hypoglossi). The data demonstrate that the simina meduallry precerebellar nuclei have a high degree of vulnerability when arteether is given for 14 days at dose levels between 8mg/kg per day and 24 mg/kg per day. The neurological consequences of this treatment regimen could profoundly impair posture, gait, and autonomic regulation, while eye movement disorders might also be anticipated.

1: Med Trop (Mars). 1998;58(3 Suppl):61-2.

Treatment of severe malaria with artemisinin derivatives. A systematic review of randomised controlled trials.

McIntosh HM, Olliaro P.

Liverpool School of Tropical Medicine, United Kingdom.

This systematic review of randomised or pseudorandomised trials aimed at summarising the effectiveness and safety of artemisinin drugs for treating severe falciparum malaria in adults and children. Survival was better with artemisinin drugs in 1.265 patients compared with 1.183 treated with quinine (OR: 0.68; 95% CI: 0.55-0.84). However, the difference is barely significant when only studies with adequate concealment of allocation at enrolment are included in the analysis (OR: 0.77; 95% CI: 0.61-0.98). In 1784 patients with cerebral malaria, mortality was also lower with artemisinin drugs overall (OR: 0.70; 95% CI: 0.55-0.90), but not significantly better than quinine in studies reporting adequate concealment of allocation. No difference in neurological sequelae has been demonstrated. Artemisinin drugs clear parasites from the blood faster than quinine. Adverse effects are similarly common with artemisinin drugs and quinine, although reporting varies between trials. There is no evidence from this review that any one artemisinin derivative is better than the others, but comparative studies are few, small and heterogeneous.

Thanks for the research summaries and comments.

I am seeing an eye doctor in 10 days and will let you know what he says (though he will probably tell me that I am on so many medications that he can't tell what's causing the blurred vision.)