TRANSACTIONSOFTHEROYALSOCIETYOFTROPICALMEDICINEANDHYGIENE(2000)94,327

Emergence of chloroquine-resistant vivax malaria in south Bihar (India)

Ranjan Kumar Singh District Hospital, DaZtongunj, South Bihar, India

Keywords: malaria, Plasmodium virxzx, drug resistance, chlor- equine, India

Introduction Daltonganj in south Bihar is a region in India where

both falciparum and vivax malaria have posed serious health problems. Chloroquine plays a crucial role in the treatment of malaria because of its high efficacy and low cost. However, in south Bihar, treatment failure with chloroquine is being faced continuously in cases of Plasmodium vivax infection. To date there has been no documented report of the chloroquine resistance ofvivax malaria in this region although cases of vivax malaria resistant to chloroquine have been reported from other areas of India and elsewhere. The present work was conducted to assess the current status of the standard regimen of chloroquine in the treatment of P. vivax infection in south Bihar (India).

Methods The study was conducted on patients attending Dis-

trict Hospital Daltonganj located in south Bihar. The study was approved by the Ethics Committee of the District Hospital, and the patients gave their consent to take part. Seventy-five patients [aged 14-70 years, mean (SD), 28 (14) years; male:female ratio, 2.4: l] with vivax malaria were studied in August 1998-June 1999 for chloroquine resistance. Chloroquine was given at a total dose of 1500 mg over 3 days: day 0 (600 mg), at 6 h (300 mg), 24 h (300 mg) and 48 h (300 mg). Thereafter primaquine (15 mg/day) was given for 14 days. Chlor- oquine was given in the form of Resochin tablets [Bayer (India) Ltd] containing 250 mg of chloroquine phos- phate (150 mg of chloroquine base). Primaquine was used in the form of Quinaprim tablets [PC1 Gujarat (India)] (each tablet containing 15 mg base of prima- quine). Chloroquine was given under supervision after admitting the patient for 3 days. Vomiting was looked for for 1 h after each administration of the drug. The drug was well tolerated; vomiting was not observed in any case. Peripheral blood smears for l? tivux (asexual stages) were made on days 2,7, 14,21 and 28 after start of the treatment, as thick and thin films, and stained with Giemsa stain. Parasite counts were based on the number of asexual parasites per 200 white blood cells: multi- plying the number of parasites by 40 gave a rough estimate of parasite count/&. Blood films were consid- ered negative ifno parasite was found in 200 fields under oil-immersion in thick and thin blood films.

Chloroquine responsiveness was defined as the ab- sence of l? vivax parasitaemia during the 28 days of follow-up. Failure to clear parasitaemia within 7 days or reappearance of parasitaemia within 28 days was treated as chloroquine failure or unresponsiveness with the standard regimen of chloroquine.

Address for correspondence: Dr Ranjan Kumar Singh, Near Vishal Bajrangbali Mandir, Mainpura, G.P.O. Patna -800 001, Bihar, India; phone +91 612 266030, fax +91 612 229009.

Results The l? vivax parasite count of the 75 studied patients

before treatment ranged from 40 to 2400/&L [mean (SD), 892 (7 16)/l&]. Splenomegaly was observed in 22 (29.3%) patients.

Of the 75 cases of vivax malaria only 58 (77.3%) were found to be sensitive to chloroquine. Of the 17 cases of chloroquine failure, 5 (6.7%) failed to clear parasites within 7 days and 12 (16%) showed reappearance of parasitaemia within 7-28 days of follow-up.

Comments At one time chloroquine resistance was a feature only

of falciparum malaria and vivax malaria was thought to be fully responsive to chloroquine. In recent years, resistance of vivax malaria to chloroouine has been observed in different parts of the world, including Myanmar ( MAFUAR-THAN et al., 1995), Indonesia (LONGWORTH, 1995) and Bombav (GARG et al.. l995), although resistance to chloroquine was not obl served in a study conducted at Baroda (India) (DUDANI et al., 1998). In our study, resistance of vivax malaria to chloroquine has been found. Persistence of parasitaemia within 7 days was found in 5 cases (6.7%) while recrudescence of parasitaemia within the 28 days of follow-up was seen in 12 cases (16%). Use of primaquine along with chloroquine could potentially mask chloro- quine failure but this view was found unlikely (IBOAR- EESUWAN et al., 1999). Chloroquine resistance rather than chloroquine failure needs to be confirmed by determination of chloroquine level in the blood.

Chloroquine, which is the first-line drug in the treat- ment of vivax and uncomplicated falciparum malaria because of cost and effectiveness, is losing its efficacy. The mechanism of drug resistance has been defined for antifolates but remains incompletely understood for the quinolines (LONGWORTH, 1995). Improper administra- tion of chloroquine might be a contributory factor to the development of chloroquine-resistant vivax malaria in someregions(CoJ,,LlN~ &JEFFERY, 1996).

Acknowledgement I am grateful to the laboratory technicians of Distict Hospital

Daltonganj for their co-operation in the work.

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Received 27 September 1999; revised 7 December 1999; accepted for publication 20 December 1999