BackgroundDue to the widespread resistance of Plasmodium falciparum to chloroquine drug, artemisinin-based combination therapy (ACT) has been recommended as the first-line treatment. This study aims to evaluate the extent of chloroquine resistance in P. falciparum infection after the introduction of ACT. This study was carried out based on the mutation analysis in P. falciparum chloroquine resistant transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes. Identification of these molecular markers plays a significant role in monitoring and assessment of drug resistance as well as in designing an effective antimalarial drug policy in India.MethodsSixty blood samples were collected from patients infected with P. falciparum from JIPMER, Puducherry and MKCG Medical College, Odisha. Polymerase chain reaction-restriction fragment length polymorphism was performed, targeting the point mutation of K76T in pfcrt and N86Y in pfmdr1 gene. The PCR products were sequenced, genotyped and further analysed for amino acid changes in these codons.ResultsThe frequency of pfcrt mutation at 76th position was dominant for mutant T allele with 56.7% and wild type K, 43.3%. Majority of pfmdr1 86 allele were wild type, with N (90%) and mutant, Y (10%). Additionally, we found three haplotypes for CQ resistance, SVMNT, CVIET and CVIKT in association with the pfcrt gene. However, a poorly studied SNP in pfmdr1 gene (Y184F) associated with CQ resistance showed high frequency (70%) in P. falciparum isolates.ConclusionsThe point mutation K76T of pfcrt is high in P. falciparum suggesting a sustained high CQ resistance even after five years of the introduction of ACTs for antimalarial therapy. The present study suggests a strong association of CQ resistance with pfcrt T76, but not with the pfmdr1 Y86 mutation. However, sequence analysis showed that Y184F mutation on pfmdr1 gene was found to be associated with high resistance. Also, a new pfcrt haplotype ‘CVIKT’ associated with CQ resistance was found to be present in Indian strains of P. falciparum. The data obtained from this study helps in continuous monitoring of drug resistance in malaria and also suggests the need for careful usage of CQ in Plasmodium vivax malarial treatment.

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Aim To study the clinical profile and outcomes in children with multisystem inflammatory syndrome in children (MIS‐C). Methods Children aged 1 month to 15 years presenting with MIS‐C (May 2020 to November 2021) were enrolled. Clinical, laboratory, echocardiography parameters and outcomes were analysed. Results Eighty‐one children (median age 60 months (24–100)) were enrolled. Median duration of fever was 5 days (3–7). Twenty‐nine (35.8%) had shock (severe MIS‐C) including 23 (28.3%) requiring inotropes (median duration = 25 h (7.5–33)). Ten required mechanical ventilation, 12 had acute kidney injury and 1 child died. Left ventricular (LV) dysfunction was seen in 38 (46.9%), 16 (19.7%) had coronary artery abnormalities (CAA) and 13 (20%) had macrophage activation syndrome. Sixty‐one (75.3%) were SARS CoV‐2 positive (10 by RT‐PCR and 51 by serology). Sixty‐eight (83.9%) received immunomodulators. Younger age was significantly associated with CAA (P value = 0.05). Older age, LV dysfunction, SARS CoV‐2 positivity, low platelet count and elevated serum ferritin were significantly associated with severe MIS‐C (univariate analysis). Younger age was an independent predictor of CAA (P = 0.05); older age (P = 0.043) and low platelet count (P = 0.032) were independent predictors of severe MIS‐C (multivariate logistic regression analysis). Conclusion Our patients had diverse clinical manifestations with a good outcome. Younger age was significantly associated with CAA. Older age, LV dysfunction, low platelet count and elevated serum ferritin were significantly associated with severe MIS‐C. Younger age is an independent predictor of CAA. Older age and low platelet count are independent predictors of severe MIS‐C.

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