Artesunate Resistance - An Emerging Threat

Drug resistant malaria represents a challenging health problem in developing countries like India. The failure of drug artemisinin, which is the cornerstone of malaria therapy will rapidly compromise the treatment and prognosis of malaria. Resistance should be suspected if inspite of full treatment with Artesunate Combination Therapy and with no history of vomiting or diarrhoea, there is no clinical or parasitological response in the patient after 72 hours. The emergence of partial artemisinin resistant parasites were previously reported from West Bengal in the form of resistance to drugs. Presence of mutations in molecular markers was reported from different parts of India (Uttar Pradesh,Andhra Pradesh,Odisha and Jharkhand). We report four cases of complicated malaria in Eastern India between January 2020 and July 2021, with apparent treatment failure with artemisinin drugs. Case1 A 45 old male known diabetic and hypertensive presenting with fever with loose stools since 5 days and seizures since 1 day. Case 2 A 59 year old male patient, known diabetic admitted with fever,black stools and decreased urination for 10 days. Case 3 A 35 year old male patient admitted with fever, headache, vomiting and hematuria for 5 days. Case 4 A 25 year old pregnant female admitted with complaints of bleeding per vaginum since 10 days with fever and vomiting for 6 days. In all cases malaria was confirmed with rapid card test and peripheral smears showed ring forms of plasmodium falciparum.Parasite levels were estimated to be between 30% to 45% in all cases.The patients were treated with injectable artesunate and once they tolerated oral medication they were started on oral artesunate combination therapy. After 4 days repeat peripheral smears showed persistence of parasites. Organ dysfunction did not subside. Hence Injectable Quinine and clindamycin was started in all cases. On day 7 all obtained microscopic parasite clearance. Cases 2 and 4 attained complete recovery,but the other two cases developed multiorgan dysfunction followed by septic shock and succumbed on 11th and 14th day of admission respectively. We could not confirm artemisinin resistance in any of these cases due to lack of availability of gene testing in our area. This report emphasizes the need for increased surveillance to identify artemisinin resistance in India. It will aid the treating physician for more selective use of drug-combinations which are less likely to foster resistance.