Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure
Neelima Mishra1, Bina Srivastava1, Ram Suresh Bharti1, Roma Rana1, Kamlesh Kaitholia1, Anupkumar R Anvikar1, Manoj Kumar Das2, Susanta K Ghosh3, Rajendra M Bhatt4, Prajesh K Tyagi5, Vas Dev6, Sobhan Phookan6, Suman Lata Wattal7, Gagan Singh Sonal7, Akshay Chand Dhariwal7, Neena Valecha1
1 ECR Division, National Institute of Malaria Research, New Delhi, India
2 National Institute of Malaria Research (Field Unit), Ranchi, Jharkhand, India
3 National Institute of Malaria Research (Field Unit), Bengaluru, Karnataka, India
4 National Institute of Malaria Research (Field Unit), Raipur, Chhattisgarh, India
5 National Institute of Malaria Research (Field Unit), Rourkela, Odisha, India
6 National Institute of Malaria Research (Field Unit), Guwahati, Assam, India
7 National Vector Borne Disease Control Programme, Delhi, India
Scientist 'G' and Director, National Institute of Malaria Research, (ICMR), Sector 8, Dwarka, New Delhi-110 077
Source of Support: None, Conflict of Interest: None
Background & objectives: To combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. Since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. Potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas.
Methods: A total of 1864 patients with acute uncomplicated malaria were enrolled in therapeutic efficacy studies of artesunate plus sulphadoxine-pyrimethamine (AS+SP) for Plasmodium falciparum; those infected with P. vivax were given chloroquine (CQ). Polymerase chain reaction (PCR) was used to distinguish post-treatment reinfection from treatment failures. Isolates of P. falciparum were also analysed for dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) gene mutations.
Results: Overall, 1687 (91.7%) patients completed the follow-up. In most of the falciparum patients the parasitaemia was cleared within 24 h of treatment, except 12 patients who remained parasite positive after 72 h. Presence of dhfr and dhps quintuple mutation was observed predominantly in treatment failure samples. A daily dose of artesunate of < 3 mg/kg of body weight, age of <5 yr, and fever at enrolment were associated with an increased risk of treatment failure. The AS+SP in P. falciparum was effective in > 95% cases in all the sentinel sites except in Northeastern region (NE). Chloroquine remained 100% efficacious in case of P. vivax infections.
Interpretation & conclusion: Till 2012, India's national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.