DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20161909

Per protocol analysis of therapeutic efficacy of chloroquine for the treatment of Plasmodium vivax malaria in children

Leeha Singh, Surbhi Rathi, Santosh Kondekar, Alpana Kondekar, Swapnaja Dongare

Abstract


Background:High incidence of chloroquine-resistant vivax malaria has led to increasing case fatality and incidence of complicated malaria with Plasmodium vivax contributing to morbidity and mortality. Current guidelines recommend the use of chloroquine along with tissue schizontcides like primaquine for the treatment of          Plasmodium vivax malaria. There were reports of increasing resistance to chloroquine in Plasmodium vivax species especially from Asia during the period when this study was taken up.   

Methods: Present study is a one arm, 28 day follow up, hospital based prospective observational study including 150 children aged 1 to 12 years with smear positive isolated Plasmodium vivax infections. Chloroquine was administered at the standard dose of 25 mg base/kg body weight over three days. Recurrence of parasitaemia and clinical conditions of patients were assessed on days 1, 2, 3, 7, 14, and 28 during the 28-day follow-up period.

Results:All 150 children included in the study, completed their 28 day follow up. Mean age for enrolment was 5.96±2.38 years. The mean parasite index (%) on enrolment was 1.22±0.46. Based on the per protocol analysis, chloroquine efficacy (adequate clinical and parasitological response) was 92.7%. Treatment was well tolerated. Early treatment failure was seen in 2.7% of study population, late clinical failure in 2% and late parasitological failure in 2.7% of study population, suggesting that response to chloroquine was good in the study population.

Conclusions:In the present study the chloroquine therapy showed high therapeutic efficacy (92.7%) in the treatment of uncomplicated vivax malaria. It was also well tolerated and equally safe when used in therapeutic doses. Regular monitoring of the pattern of resistance to chloroquine is needed in vivax malaria endemic areas of the country and measures are taken rapidly and effectively to control spread of resistance.  


Keywords


Plasmodium vivax, Chloroquine resistance, Therapeutic efficacy, Treatment failure

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References


Joshi H, Prajapati SK, Verma A, Kang’a S, Carlton JM. Plasmodium vivax in India. Trends Parasitol. 2008;24(5):228-35.

Pukrittayakamee S, Chantra A, Simpson JA, Vanijanonta S, Clemens R, Looareesuwan S, et al. Therapeutic responses to different antimalarial drugs in vivax malaria. Antimicrob Agents Chemother. 2000;44(6):1680-5.

Manju K, Radha G, Kumari M, Ghildiyal R. Clinical profile of Plasmodium vivax malaria in children and study of severity parameters in relation to mortality: a tertiary care centre perspective in Mumbai, India. Malar Res Treat. 2014;2014:765657.

Price RN, Seidlein L, Valecha N, Nosten F, Baird JK, White NJ. Global extent of chloroquine-resistant Plasmodium vivax: a systematic review and meta-analysis. Lancet Infect Dis. 2014;14(10):982-91.

Indrayan A, Satyanarayana L. Basic philosophy of statistical tests, confidence intervals and sample size determination. Indian Pediatr. 2000;37(7):739-51.

World Health Organization, WHO guidelines for the treatment of malaria. Geneva, World Health Organisation;2010.

World Health Organization. Monitoring Antimalarial Drug Resistance, Report of a WHO consultaion. WHO/CDS/CSR/EPH/2002. Geneva, World Health Organisation;2002.

Douglas NM, Anstey NM, Buffet PA, Poespoprodjo JR, Yeo TW, White NJ, et al. The anaemia of Plasmodium vivax malaria. Malar J. 2012;11:135.

Rodríguez MAJ, Sánchez E, Vargas M, Piccolo C, Colina R, Arria M. Anemia and thrombocytopenia in children with Plasmodium vivax malaria. J Trop Pediatr. 2006;52(1):49-51.

Congpuong K, Bangchang NK, Thimasarn K, Tasanor U, Wernsdorfer WH. Sensitivity of Plasmodium vivax to chloroquine in Sa Kaeo Province, Thailand. Acta Trop. 2002;83(2):117-21.

Tasanor O, Ruengweerayut R, Sirichaisinthop J, Congpuong K, Wernsdorfer WH, Bangchang NK. Clinical-parasitological response and in-vitro sensitivity of Plasmodium vivax to chloroquine and quinine on the western border of Thailand. Trans R Soc Trop Med Hyg. 2006;100(5):410-8.

Baird JK. Neglect of Plasmodium vivax malaria. Trends Parasitol. 2007;23(11):533-9.

Barnadas C, Ratsimbasoa A, Tichit M, Bouchier C, Jahevitra M, Picot S, et al. Plasmodium vivax resistance to chloroquine in Madagascar: clinical efficacy and polymorphisms in pvmdr1 and pvcrt-o genes. Antimicrob Agents Chemother. 2008;52(12):4233-40.

Teka H, Petros B, Yamuah L, Tesfaye G, Elhassan I, Muchohi S, et al. Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit, Ethiopia. Malar J. 2008;7:220.

Yohannes AM, Teklehaimanot A, Bergqvist Y, Ringwald P. Confirmed vivax resistance to chloroquine and effectiveness of artemether-lumefantrine for the treatment of vivax malaria in Ethiopia. Am J Trop Med Hyg. 2011;84(1):137-40.

Hwang J, Alemayehu BH, Reithinger R, Tekleyohannes SG, Takele T, Birhanu SG, et al. In vivo efficacy of artemether-lumefantrine and chloroquine against Plasmodium vivax: a randomized open label trial in central Ethiopia. PLoS One. 2013;8(5):e63433.

Assefa M, Eshetu T, Biruksew A. Therapeutic efficacy of chloroquine for the treatment of Plasmodium vivax malaria among outpatients at Hossana health care centre, southern Ethiopia. Malar J. BioMed Central. 2015;14(1):458.

Gonsalves LA, Cravo P, Ferreira MU. Emerging Plasmodium vivax resistance to chloroquine in South America: an overview. Mem Inst Oswaldo Cruz. 2014;109(5):534-9.

Salem OA, Lemine MYO, Deida JM, Lemrabott MA, Ouldabdallahi M, Ba MD, et al. Efficacy of chloroquine for the treatment of Plasmodium vivax in the Saharan zone in Mauritania. Malar J. 2015;14(1):39.

Government of India. Ministry of Health and Family welfare, NVBDCP, National Drug Policy on Malaria. Delhi; 2010.

Dua VK, Kar PK, Sharma VP. Chloroquine resistant Plasmodium vivax malaria in India. Trop Med Int Health. 1996;1(6):816-9.

Mohan K, Maithani MM. Congenital malaria due to chloroquine-resistant Plasmodium vivax: a case report. J Trop Pediatr. 2010;56(6):454-5.

Kshirsagar NA, Gogtay NJ, Rajgor D, Dalvi SS, Wakde M. An unusual case of multidrug-resistant Plasmodium vivax malaria in Mumbai (Bombay), India. Ann Trop Med Parasitol. 2000;94(2):189-90.

Zaki SA. Chloroquine resistant vivax malaria in an infant: a report from India. J Vector Borne Dis. 2009;46(1):83.

Singh RK. Emergence of chloroquine-resistant vivax malaria in south Bihar (India). Trans R Soc Trop Med Hyg. 2016;94(3):327.

Shah I. Chloroquine resistant vivax malaria in an infant: A report from India. J Vector Borne Dis. 2008;46(2):168-9.

Garg M, Gopinathan N, Bodhe P, Kshirsagar NA. Vivax malaria resistant to chloroquine: case reports from Bombay. Trans R Soc Trop Med Hyg. 1995;89(6):656-7.

Srivastava HC, Yadav RS, Joshi H, Valecha N, Mallick PK, Prajapati SK, et al. Therapeutic responses of Plasmodium vivax and P. falciparum to chloroquine, in an area of western India where P. vivax predominates. Ann Trop Med Parasitol. 2008;102(6):471-80.

Ganguly S, Saha P, Guha SK, Das S, Bera DK, Biswas A, et al. In vivo therapeutic efficacy of chloroquine alone or in combination with primaquine against vivax malaria in Kolkata, West Bengal, India, and polymorphism in PVMDR1 and PVCRT-o genes. Antimicrob Agents Chemother. 2013;57(3):1246-51.

Shalini S, Chaudhuri S, Sutton PL, Mishra N, Srivastava N, David JK, et al. Chloroquine efficacy studies confirm drug susceptibility of Plasmodium vivax in Chennai, India. Malar J. 2014;13(1):129.