Abstract
SUMMARY
The study on therapeutic efficacy of chloroquine was carried out in a tribal dominated block of Kalahandi district of Orissa, India. It revealed 94% treatment failure with standard dose of chloroquine in the treatment of uncomplicated P. falciparum malaria cases. The study warrants the change to alternate antimalarials in this region.
Introduction
The anti-malarial drug, chloroquine (CQ) has always played an important role in malaria control. However, since early the 1960s the sensitivity of the parasite to CQ, the most widely used drug, has been on the decline. The resistance of Plasmodium falciparum to CQ began in two epicenters, namely, Columbia (South America) and Thailand (South East Asia). 1 In the Indian states, the first report came from Assam in 1973. 2 The increasing anti-malarial drug-resistance is now an important concern and has become a serious global challenge because, as anti-malarials loose their effectiveness, morbidity and mortality from malaria will inevitably continue to rise.
Orissa contributes more than 43% of all cases of P. falciparum malaria and 50% of all malaria-attributable deaths in India. 3 P. falciparum accounts for 80%–90% of all malaria cases. Sketchy reports are available on the status of the existence and extent of the CQ resistance. The present study was undertaken in order to ascertain the efficacy of CQ in the treatment of uncomplicated P. falciparum malaria.
Patients and methods
The study was conducted in the M. Rampur block of the Kalahandi district of Orissa. The district has a high malaria transmission with an average slide positivity rate (SPR) of 10.3 and annual parasitic index of 17.3 noted during 2002–2006. The epidemiological data on malaria in the M. Rampur Block indicates an increase of malaria in the area. The SPR increased by 6.6% and the P. falciparum rate went gone up from 72.7% to 85% during 2002–2004. 4 The SPR of more than 5% is indicative of high transmission, and the annual blood examination rate of more than 10 indicates the needs for proper surveillance in the area.
The therapeutic efficacy of CQ study was conducted as per the World Health Organization (WHO) guidelines. 5 The institutional ethical committee has approved the study protocol. The fever cases were selected randomly from the villages. We followed the inclusion and exclusion criteria and the eligible cases were enrolled in the study. After obtaining the informed and written consent, the clinical examination was done with the recording of axillary temperature and body weight. Finger prick blood was collected for thick and thin films. The parasite count was done against 200 white blood counts in thick smears. A CQ tablet with a 150 mg base (as per the WHO recommendations) was administered to each patient under the supervision of the medical team. They were advised not to take any other drugs during the study period without informing the investigators. The study subjects were followed up with blood smears for a parasite count and a clinical examination on days 2, 3, 7, 14, 21 and 28 of the initiation of treatment. The cases of treatment failure without complications were treated with an alternative drug, sulfadoxine-pyrimethamine (SP), and cases with complications were transferred to the Government health facility.
Results
A total of 124 fever cases were screened for malaria parasites, of which, 64 (51.6%) were P. falciparum mono infection, two (1.6%) had P. vivax mono infection, 29 (23.4%) had mixed infection of both and 29 (23.4%) did not have malaria parasite. Out of 64 P. falciparum cases, 53 met the criteria for inclusion, which included 28 male and 25 female patients. The mean age of the cases was 21.3 years. Three cases (5.6%) dropped out for varied reasons. Thus, a total of 50 (94.3%) subjects are followed for all 28 days of the study period.
The study revealed only three (6.0%) adequate clinical and parasitological responses. Eight patients (16%) showed early treatment failure – one of whom developed danger signs on the second day and had repeated vomiting, lethargy and was unable to sit or stand up – and seven patients (14.0%) had parasitaemia on day 2 (i.e. more than that recorded on day 0). Late clinical failure was marked in one case (2%) that developed fever on day 28 and had a body temperature of more than 37.5°C. A total of 38 (76%) had late parasitological failure. Of these, 30 (79.0%) had parasitaemia on day 7, one (2.6) on day 14, five (13.1%) on day 21 and two (5.3%) on day 28. Thus, around 94.0% of the patients in the study suffered treatment failure with CQ.
Discussion
CQ has been the mainstay of the treatment of uncomplicated P. falciparum malaria and has been used in the National Malaria Eradication Programme since 1960. It is used in the modified plan operation at multiple levels of the health system in the presumptive treatment of malaria. The propagation of a resistance strain depends on the widespread use of the drug to which resistance has been developed. This may be an important factor in restraining competition from drug-susceptible strains of the parasite. 6 The resistance of CQ has been a stumbling block in the effective control of malaria. The other known methods of controlling malaria without the use of an effective drug treatment, however well done, can never achieve effective results. Drug treatment is still the mainstay for the elimination of the infective focus and parasite carriers. Therefore, the ideal drug should have maximum cure rate when the recommended dose is used. Otherwise, the future strategy for malaria control must include early diagnosis and prompt treatment.
This study has unveiled a high prevalence of CQ resistance in this tribal block of Kalahandi district, Orissa. Never before, has such a high percentage of CQ resistance been reported from Orissa. The first CQ resistance in Orissa was detected in Gumagarh PHC of Phulbani district in 1978 and then in Keonjhargarh town of Keonjhar district in 1979, afterwards it was reported from Koraput, Malkangiri and Sundargarh districts. 7–8 But the SP combination therapy was found to be effective in the areas which had CQ resistance. 9 A recent study from the Phulbani districts, reported 65% treatment failure rate with CQ. 10 The present study has revealed a 94% treatment failure rate when using the standard dose of CQ in uncomplicated malaria cases. This situation highlighted the threat to the control of malaria in the State. There must, therefore, be changes made to the alternate anti-malarial drug. The authority implementing the control programme must be made aware of this situation and must withdraw CQ from this area and introduce a second-line drug immediately. However, more studies should be undertaken to identify and delineate such pockets of CQ resistance in the state.
Footnotes
Acknowledgements
This work was funded by the Enhanced Malaria Control Project, Government of Orissa, Bhubaneswar, India. We are grateful to Mr K Dhal, Mr H K Nayak, Mr R C Parida and Mr R N Nayak, the district health officials of the Kalahandi district and the medical officer, the technician and the health workers of M. Rampur primary health centre who assisted throughout the study. We are also grateful to the patients who participated in the study. Dr B V Babu is gratefully acknowledged for his help during drafting of the manuscript.