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Journal of Applied Pharmaceutical Science 01 (08); 2011: 235-238 Over prescribing and resistance to chloroquine
Gandhi AM, Patel PP, Desai CK, Desai MK and Dikshit RK
ABSTRACT
Malaria is a major health concern in the developing world including India. Overdiagnosis and overprescribing of malaria may lead to increase morbidity, mortality and o antimalarial drugs and hence increase the economical burden to Gandhi AM, Desai CK, Desai MK
health care system. The pres ent study was carried out to determine the actual cases of malaria and extent of chloroquine resistance at Civil Hospital Ahmedabad, a tertiary care teaching hospital in Gujarat, India. After Institutional Ethics Committee approval, adult patients of either gender, presenting with a his tory of fever at the Out Patient Department (OPD), diagnosed to nd prescribed chloroquine were included in the study. Peripheral thick blood smear test and OptiMAL-rapid diagnostic test (RDT) were carried out. RDT was Patel PP
performed in these patients on day 0 before the start of chloroquine treatment and after completion of the 3 day chloroquine treatment. They were again subjected to RDT on day 4. The positive cases on RDTo n day 4 were considered as resistant to chloroquine. During the study period of 12 months, out of the 250 clinically suspected cases of malaria who were prescribed chloroquine, 80 (31%) cases (35 cases of P. vivax and the 45 of P. falciparum ) were positive for malaria (by the peripheral smear and the Rapid Diagnostic Test (RDT) OptiMAL test). Thirty out of the 35 ca ses of P. vivax malaria, responded to the three- day chloroquine Dikshit RK
treatment. Out of the 45 case s of P. falciparum malaria, 30 responded to chloroquine while 15 patients (35%) continued to be OptiMAL positive on 4th day and required change of treatment. B.J. Medical college, Ahmedabad , It suggests that an early diagnosis, definitive treatment and avoiding overprescribing could delay drug resistance and reduce the morbidity and mortality due the disease. Keywords: Malaria, chloroquine, overprescribing, resistance.
INTRODUCTION
ment in malaria depends on the right diagnosis, selection of the right drug and its efficacy, correctne ss of the advice given to the patient and compliance of the patient Chloroquine (CQ) is the first drug of choice for among the available antimalarial drugs 2(National dr ug policy on malaria, 2008) and widely used as self-medication for ria despite the existence of parasite resistance to the drug (Picot et al, 1997). Resistance to antimal arial drugs is on the rise and has become a major factor in deciding gs. For instance, as per estimates in the past decade, 50% of the strains of P.falciparum are resi stant to chloroquine (Garg, 1999) and resistant strains of P. vivax are also increasing in different parts of India (Kochar, 2007). A presumptive approach alone may result in overdiagnosis of mala ria. Empirical treatment based on this approach may also result in For Correspondence
Dr Anuradha M Gandhi
g use with a consequent increased risk of morbidity, mortality, resistance to antimalarial drug s and increased cost of therapy (Plowe, 2003). It thus becomes imperative to detect the extent of presumptive diagnosis of malaria study was therefore conducted at Civil Hospital, Ahmedabad, a tertiary care teaching hospital in Gujarat, India, with an objective Journal of Applied Pharmaceutical Science 01 (08); 2011: 235-238 to determine the actual cases of malaria out of such clinically
diagnosed cases and to determine the extent of chloroquine
resistance in this population.
METHODS

The study protocol was approved by the Institutional Ethics Committee (IEC) of Civil Hospital, Ahmedabad (CHA). Adult patients of either gender, above the age of 18 years and presenting with a history of fever at the Out Patient Department (OPD) were screened for the study. All those patients who are clinically diagnosed to be suffering from malaria and prescribed chloroquine were included in the study. Patients who had taken prior treatment for malaria and those with a history of vomiting Table 1: Chloroquine sensitivity in patients suffering from malaria.
were excluded from the study. Pregnant and lactating women, Type of malaria ►
P. vivax malaria
P. falciparum malaria
patients with a history of hypersensitivity to antimalarial drugs and those suffering from major illnesses like hypertension or severe diabetes mellitus were also excluded from the study (OptiMAL –IT kit was supplied by Doctor & Company, Ahmedabad : Morepan Laboratories, New Delhi, Manufractured by DiaMed AG Diagnostics and Medical Products, Switzerland). DISCUSSION
Patients were informed about the aims and methods of the Outcome of treatment of malaria depends on the efficacy study and a written consent was obtained. Detailed history, clinical of the drug, right diagnosis, the treatment given and compliance of examination and treatment given were recorded in a case record patient while presumptive use of antimalarial drugs may increase form (CRF). Peripheral thick blood smear test and OptiMAL-rapid parasite resistance. Confirming the clinical diagnosis with diagnostic test (RDT) were carried out for malaria in all patients microscopy or Rapid Diagnostic Tests (RDTs) may prevent that were included in the study. RDT was performed in these overuse of antimalarial drugs and decrease the risk of drug- patients on day 0 before the start of chloroquine treatment. The cases that showed positive microscopic examination In the present study, 250 patients of fever were prescribed and +ve RDT for malaria on day 0 were considered as true/actual chloroquine on the basis of a presumptive clinical diagnosis. cases of malaria either P. vivax or P. falciparum. These patients However, only 80 cases were positive either for P. vivax or were advised to return on day 4 after the completion of the 3 day P.falciparum malaria on microscopy and RDT (OptiMAL) while chloroquine treatment. They were again subjected to RDT on day 170 cases (67.86%) showed a negative peripheral smear and 4. The positive cases on RDT on day 4 were considered as resistant We further observed that out of 80 cases detected to be positive for malaria by peripheral smear and RDT (OptiMAL) tests, 35 (44 %) were of P.vivax and 45 (56% ) were of P. During the study period, 250 cases of fever and clinically falciparum malaria. Chloroquine was effective in 30 cases (86%) suspected cases of malaria, who were prescribed chloroquine were of P. vivax & 30 cases (67%) of P. falciparum origin. Resistance studied. Out of these, 80 (31%) patients showed a positive was therefore observed in 5 patients (14%) and 15 cases of (33%) peripheral smear as well as positive RDT (OptiMAL test) for either P.vivax and P.falciparum of malaria respectively. There is P. vivax or P. falciparum malaria. Two false positive and one false therefore an evidence based of treatment on presumptive diagnosis negative cases were reported (cases where peripheral smear was alone, which may contribute to antimalarial drug resistance. positive for malaria parasites and RDT was negative were Treatment based on presumptive clinical diagnosis alone considered as false negative and vice versa). Therefore it was is an accepted approach for management of most cases of malaria observed that 170 (68%) cases of fever presumptively diagnosed in areas with high rates of transmission e.g. in rural and remote with malaria, were not actually suffering from this infection yet areas of the healthcare system where laboratory facilities for they were prescribed chloroquine. (Figure 1). Out of the 80 definitive diagnosis may not be available. Patients in endemic areas positive malaria cases, 35 cases were suffering from P. vivax are familiar with the symptoms and they frequently self-diagnose malaria (44%) and the remaining 45 patients were suffering from malaria and practice self medication with chloroquine and other P. falciparum (56%) (Table 1) Out of 35 cases of P. vivax malaria, antimalarial drugs. These drugs are easily available from 30 patients responded to chloroquine treatment while 5 patients pharmacies in India. Treatment based on presumptive clinical (14%) were still positive on RDT after three days chloroquine diagnosis alone may result in unnecessary and irrational drug use. treatment. They required alternate antimalarial drugs and were In addition, overdiagnosis and overprescribing of malaria may lead referred to the medicine consultant. Thirty out of 45 confirmed to increase morbidity, mortality and increases risk of resistance to Journal of Applied Pharmaceutical Science 01 (08); 2011: 235-238 antimalarial drugs and an increased economical burden to health investigated by microscopy or RDT and presumptive treatment care system of the country. Thus, the clinical diagnosis would benefit from laboratory confirmation by microscopy/Rapid Hence, We conclude that early diagnosis, treatment and reduction in overprescribing based on presumptive symptoms Therapeutic efficacy and / or parasitological resistance alone may delay the progress of drug resistance and reduce in may be measured by in vivo test. (Plowe, 2003) However, standard overall morbidity and mortality due to malaria. Rapid diagnostic in vivo tests are expensive and time-consuming while in vitro tests can be useful in monitoring and management of malaria. This methods for measuring drug resistance are not practical and have a may reduce the unnecessary use of antimalarial drugs and also limited scope. All available tests either do not give quick results to reduce risk of complications of P. falciparum malaria particularly influence the therapeutic decisions or nor do they give results that are not interpretable in terms of individual patient treatment (ICMR, 2002) . Alternatively, non-microscopic methods, rapid ACKNOWLEDGEMENT
We are thankful to Department of Medicine and Department of Microbiology for helping us in diagnosis and dehydrogenase (pLDH) have the capacity to detect and distinguish enrolling patients. We are also thankful to Government of Gujarat infections caused by P. falciparum and P. vivax species (Ferro et (India) for giving us funds for our study. OptiMAL is the first RDT, approved on June 13, 2007 by REFERENCES
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