Jpn. J. Infect. Dis., 68, 321–323, 2015

Short Communication

Impact of Artemisinin-Based Combination Therapy on Falciparum Malaria in Urban Kolkata: A Clinic-Based Report Pabitra Saha1, Swagata Ganguly1*, Soma Dutta1, Pratip K. Kundu1, Dilip K. Bera1, Nandita Basu2, and Ardhendu K. Maji1 1Deparment

of Microbiology, Calcutta School of Tropical Medicine, Kolkata; and 2Calcutta School of Tropical Medicine, Kolkata, India.

SUMMARY: In India, artemisinin-based combination therapy (ACT; specifically artesunate + sulfadoxine-pyrimethamine) has been implemented for uncomplicated falciparum malaria since 2010. But for vivax malaria drug policy remained unchanged i.e., chloroqine and primaquine. We observed the impact of this intervention in urban Kolkata by analyzing data from the Malaria Clinic from 2001 to 2013. In Kolkata, we observed that Plasmodium vivax was perennial, whereas P. falciparum infection was seasonal. Before ACT implementation, the proportion of P. falciparum was as high as 50z and it steadily decreased during 4 successive years post intervention. No change was observed in the number of P. vivax cases. ACT may be an effective measure in reducing falciparum malaria cases. Artemisininderivative combination therapies should be explored in vivax malaria to reduce the overall burden of malaria. intervention period because ACT was introduced in 2010. The majority of patients were from a nearby locality belonging to a lower socio-economic status. Most of the patients were originally residents of Jharkhand, Bihar, and were mainly migratory workers to Kolkata with frequent visits to their domicile states. Consent was not obtained for each case detection and treatment administered for malaria as these are routine health system activities for clinical care and conducted according to NVBDCP guidelines. All individuals who attended our clinic were examined clinically and blood was collected from a finger prick (thick and thin smears) for malarial parasite detection and species identification following Giemsa staining. Laboratory-confirmed P. falciparum, P. vivax, and mixed infections were treated according to the agespecific dosage guidelines of the National Drug Policy. Prior to ACT implementation, malaria cases were treated with CQ (25 mg/kg divided over 3 days) and primaquine (PQ) (0.25 mg/kg body weight daily for 14 days after estimating their glucose 6 phosphate dehydrogenase levels for vivax malaria and a single dose of 0.75 mg/kg body weight on day 2 for falciparum malaria). In 2010, AS + SP replaced CQ for the treatment of uncomplicated P. falciparum cases with 4 mg/kg body weight of artesunate for 3 days, 25 mg/kg body weight of sulfadoxine on day 1, 1.25 mg/kg body weight of pyrimethamine on day 1 and a single dose of PQ at 0.75 mg/kg body weight on day 2. All patients with falciparum malaria were advised to report to the clinic weekly for 6 weeks of follow-up. We summarized the pre- and post-intervention malaria cases by tabulating standard yearly epidemiological indicators. We also assessed the seasonal variation in the incidence of each species. Prior to ACT implementation, the average slide positivity rate was 35.94z, ranging from 29.91z– 43.03z (Table 1). This rate declined over the 4 succes-

A total of 207 million diagnosed cases of malaria and 627,000 deaths globally were reported in 2012 (http:// www.who.int/malaria/publications/world _ malaria _ report_2013/en/). Approximately one-third of the world's population at risk for malaria lives in India, where Plasmodium falciparum accounts for about 50z of the total malaria cases (1). Since 2005, the National Vector Borne Disease Control Programme (NVBDCP) of India has introduced new interventions and undertaken several policy changes to improve malaria control (2). Artemisinin-based combination therapy (ACT), a combination of artesunate + sulfadoxine-pyrimethamine (AS + SP), was introduced in 2010 as a first-line agent to treat uncomplicated falciparum cases, but chloroquine (CQ) remains the drug of choice for vivax malaria. The introduction of ACT in different countries was associated with a decline in the incidence of falciparum malaria in successive years (3–5). Such data from India are scarce (6). The present report focuses on the impact of ACT on the total number of falciparum malaria cases in urban Kolkata, India. The present study was a clinic-based study from the Malaria Clinic of the Protozoology Unit of Calcutta School of Tropical Medicine located in the central part of Kolkata. Symptomatic patients from surrounding wards of the Kolkata Municipal Corporation attend this clinic for malaria diagnosis and treatment. This study retrospectively analyzed the data maintained in the Malaria Clinic of the host Institute. The period from 2001–2009 was considered our baseline, and the period from 2010–2013 was considered the post Received June 27, 2014. Accepted October 27, 2014. J-STAGE Advance Publication February 13, 2015. DOI: 10.7883/yoken.JJID.2014.284 *Corresponding author: Mailing address: Department of Microbiology, Calcutta School of Tropical Medicine 108, C. R. Avenue, Kolkata 700 073, India. Tel: 91 9830822130, E-mail: swagatamedicine@gmail.com 321

Table 1. Incidence of malaria as detected and treated in the Malaria Clinic, Calcutta School of Tropical Medicine from 2001 to 2013 Parasite species Yr 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

BSE 14,341 12,922 11,926 13,248 17,355 16,571 12,769 22,875 24,491 23,669 16,127 15,235 11,627

Pv

Pf

Mixed

3,319 3,405 3,244 4,142 4,254 3,797 2,811 5,243 5,619 5,892 3,593 3,178 2,763

2,362 1,486 973 1,386 1,105 1,549 1,005 4,577 4,783 2,224 865 646 417

8 2 7 1 0 3 3 22 44 14 13 10 4

Total positive

SPR

SFR

Pf z

Pv z

SVR

5,689 4,893 4,224 5,529 5,359 5,349 3,819 9,842 10,446 8,130 4,471 3,834 3,184

39.67 37.87 35.42 41.73 30.88 32.28 29.91 43.03 42.65 34.35 27.72 25.17 27.38

16.47 11.50 8.16 10.46 6.37 9.35 7.87 20.01 19.53 9.40 5.36 4.24 3.59

41.66 30.41 23.20 25.09 20.62 29.01 26.39 46.73 46.21 27.53 19.64 17.11 13.22

58.34 69.59 76.80 74.91 79.38 70.99 73.61 53.27 53.79 72.47 80.36 82.89 86.78

23.14 26.35 27.20 31.27 24.51 22.91 22.01 22.92 22.94 24.89 22.28 20.86 23.76

BSE = Blood slides examined. Slide positivity rate (SPR) = Total positive × 100/Total slides examined. Slide falciparum rate (SFR) = Total positive P. falciparum × 100/Slides examined. Slide vivax rate (SVR) = Total positive P. vivax × 100/Slides examined. Pf percentage (Pf z) = Total positive for P. falciparum × 100/Total positive for MP. Pv percentage (Pv z) = Total positive for P. vivax × 100/Total positive for MP.

ACT in mixed or misdiagnosed infections (10). On the contrary, we observed that P. vivax burden remained almost constant in both the pre- and post-intervention periods, which might be due to the unchanged drug policy and a high rate of recurrent infection following treatment with CQ + PQ (9). In urban Kolkata, microscopy is used as diagnostic tool for malaria, which minimizes the chance of misdiagnosis. In rural settins, malaria diagnosis is mainly based on rapid diagnostic test, leading to chances of misdiagnoses resulting in falciparum cases receiving CQ. A similar problem was addressed by Douglas et al, 2010 (10). Though we have not registered any cases of CQ-resistant P. vivax in our setting (11), any ACT that is effective against both malarial species will be convenient in treating all malaria cases irrespective of species identification. We also assessed the seasonal changes in P. falciparum burden in the same study areas from 2006 by analyzing data from the 5 years prior to ACT implementation. Every year, P. falciparum cases declined beginning in the dry season (April), disappeared in May–June, increased during the monsoon season (July), and attained peak levels in the post-monsoon period (November–December), with a gradual decline after that. On the contrary, P. vivax cases persisted throughout the year; they increased beginning in the dry season (March), attained a plateau in the monsoon season (May–September), gradually decreased in winter, and maintained a constant level in the rest of the year. Interestingly, the 2 different peaks of P. vivax and P. falciparum never coincided with one another in any year from 2006–2013 (Fig. 1). This pattern of seasonal distribution was different from that reported in Delhi (12). It was also a hospital-based study, showing that P. falciparum occurred throughout the year and started increasing in July with a peak in September, then gradually declined. P. vivax appeared in June, peaked in August-September, and then showed a steady decline

sive years of the post-intervention period (34.35z, 27.72z, 25.17z, and 27.38z, respectively) with an average of 29.43z. The percentage of P. falciparum cases ranged from 20.62z–46.73z reaching almost 50z in 2009 and declining steadily after the intervention (Table 1). The actual decrease in falciparum malaria cases in the post-intervention period can be better depicted by the slide falciparum rate (SFR) (Table 1). During 2001–2009, SFR ranged from 6.37z–20.01z, with an average of 13.12z. After ACT implementation, the SFR decreased to 6.23z ranging from 3.59z– 9.40z. The number of vivax malaria cases remained almost constant throughout (Table 1). Before ACT implementation patients with falciparum infection attended our clinic with repeated episodes of malaria that were due to recrudescence (7), thus increasing P. falciparum cases and acting as source of transmission. In our previous study (8), we showed that the combination of AS + SP was highly effective against falciparum malaria in urban Kolkata with a therapeutic efficacy rate of 100z. The efficacy of this combination is unknown against P. vivax malaria, as it has never been implemented. CQ and PQ are still in use for vivax malaria. A high rate of recurrent P. vivax infection has been reported during the 1-year post-treatment period with CQ alone (26.7z) and CQ + PQ for 14 days (16.5z) (9). In Kolkata, 2 interventions, namely insecticide treated net and indoor residual spray, were not found to be implemented. Since other parameters have remained unchanged, the reduction in P. falciparum cases was probably due to the drug policy change. Similar observations have also been reported from West Bengal during the post-ACT implementation period (http://www.nvbdcp.gov.in/Doc/mal_situation_ Apr2015.pdf) and other malaria-endemic countries (3–5). Several workers reported a decrease in P. vivax cases whose treatment remained unchanged (CQ + PQ) in areas receiving ACT for P. falciparum only (6). This decline was probably due to improved treatment with 322

ACT Effect on Falciparum Malaria in Urban Kolkata

Fig. 1. Monthly rainfall and seasonal distribution of P. falciparum and P. vivax cases as recorded in the Malaria Clinic, Calcutta School of Tropical Medicine from 2006–2013.

in the October–November timeframe, disappearing in winter. Our study had certain limitations. Because this was a clinic-based report, our findings may not be a true reflection of the entire population. ACT implementation in urban Kolkata had a significant effect on total falciparum malaria cases during the 4 years after the intervention. Even so, a substantial falciparum malaria burden still persists and needs adequate attention. Since ACT is highly effective in treating falciparum malaria, a study of the effectiveness of ACT for treatment of vivax malaria is recommended.

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Acknowledgments We are grateful to the Director, Calcutta School of Tropical Medicine, for her kind permission to publish the data. Foremost, we would like to thank Asish Bhowmick and Ritick Paul of the Malaria Clinic without whose assistance we could not complete the study. We acknowledge Sujay Gupta, data entry operator of our Unit for his assistance in compiling the data. Lastly we highly appreciate the support rendered by Dr. G. C. Debnath, Director, Regional Meteorological Department, Alipore, Kolkata and Debdut Ghosh Thakur, Presidency University, Kolkata for assistance with the meteorological data.

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Conflict of interest None to declare.

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Impact of Artemisinin-Based Combination Therapy on Falciparum Malaria in Urban Kolkata: A Clinic-Based Report.

In India, artemisinin-based combination therapy (ACT; specifically artesunate + sulfadoxine-pyrimethamine) has been implemented for uncomplicated falc...
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