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Table of Contents
REVIEW ARTICLE
Year : 2019  |  Volume : 56  |  Issue : 1  |  Page : 41-45

Malaria control in India: A national perspective in a regional and global fight to eliminate malaria


1 WorldWide Antimalarial Resistance Network; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
2 Institute of Liver & Biliary Sciences, New Delhi; Translational Health Science & Technology Institute (THSTI), Faridabad, India
3 WorldWide Antimalarial Resistance Network; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Genome Sciences, University of Washington, Seattle, WA, USA

Date of Submission09-Mar-2019
Date of Web Publication7-May-2019

Correspondence Address:
Prof. P J Guerin
WorldWide Antimalarial Resistance Network (WWARN), Centre for Tropical Medicine and Global Health, University of Oxford, Nuffield Department of Clinical Medicine Research Building, Old Road Campus, Roosevelt Drive, Headington, Oxford OX3 7FZ
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-9062.257773

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  Abstract 


Since the declaration of the vision of malaria eradication in 2007, the overall burden of malaria has been reduced substantially in many countries in the endemic world. This progress has, however, recently slowed worldwide and even an increase of morbidity and mortality has been observed in some regions. That reality has led to reflection on the strategy for malaria elimination, noting that focusing only on low transmission sites has competed with the efforts in countries that still have foci with high malaria burdens. This opinion piece outlines the collaboration of the ICMR-National Institute of Malaria Research (ICMR–NIMR) and other partner Institutions in India with the WorldWide Antimalarial Resistance Network (WWARN), one part of a global effort to manage the spread of Plasmodium falciparum parasites associated with antimalarial resistance.

Keywords: India; malaria; malnutrition; network; resistance


How to cite this article:
Guerin P J, Dhorda M, Ganguly N K, Sibley C H. Malaria control in India: A national perspective in a regional and global fight to eliminate malaria. J Vector Borne Dis 2019;56:41-5

How to cite this URL:
Guerin P J, Dhorda M, Ganguly N K, Sibley C H. Malaria control in India: A national perspective in a regional and global fight to eliminate malaria. J Vector Borne Dis [serial online] 2019 [cited 2019 Aug 22];56:41-5. Available from: http://www.jvbd.org/text.asp?2019/56/1/41/257773




  Introduction Top


Since the declaration of the vision of malaria eradication in 2007, the overall burden of malaria has been reduced substantially in many countries in the endemic world. This progress has, however, recently slowed worldwide and even an increase of morbidity and mortality has been observed in some regions[1]. That reality has led to reflection on the strategy for malaria elimination, noting that focusing only on low transmission sites has competed with the efforts in countries that still have foci with high malaria burdens[2],[3].

India has the largest population at risk from malaria in a single country, with citizens living in extremely varied geographic and ecological areas[4]. Moreover, malaria manifests itself in a variety of forms such as tribal malaria, desert malaria, urban malaria and these require different approaches in management or elimination[5],[6]. In addition, the diversity of the vectors and behaviour varies enormously within the country, further complicating strategies to control the disease. The growing urban development, laying of rail tracks and building activities also adds to the problem of vector control, increasing the risk of transmission in places that were previously malaria-free[7],[8]. As a result of all these factors, the malaria burden has been historically among the highest and most complex in the world.

However, among the high burden countries, India stands out as it has continued to reduce malaria incidence even as overall progress has levelled off. By 2017, malaria cases had been reduced by 24% in the country as a whole compared to the case burden in 20162,9. In 2015, India increased investment and scaled-up malaria control efforts nationally and committed malaria elimination by 2030.

Currently, areas of high malaria burden are concentrated in the East and Northeast of the country; six states contribute 75% of the reported cases [Figure 1]. An innovative collaborative project of the state and local malaria programmes, the ICMR-National Institute of Malaria Research (ICMR-NIMR) and the Medicines for Malaria Venture (MMV) has been focused on approaches to standardize and improve malaria diagnosis and treatment in some of these remaining foci. An interim report demonstrates that these changes have already had a significant impact on key indicators[10], and a broader consortium has just been launched to respond appropriately to this interim data[11].
Figure 1: Map of transmission intensity from Indian National Malaria Elimination Framework (reproduced with permission of ICMR-NIMR).

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However, countries that have been certified free of locally transmitted malaria still face the challenge of importation of malaria from neighbouring, or even distant regions where malaria is endemic[12],[13]. India has particular challenges. It shares a long border with Myanmar where Plasmodium falciparum parasites with reduced susceptibility to artemisinins are becoming predominant[14],[15],[16],[17]. International human movements from the rest of SE Asia can also lead to the importation of artemisinin resistant falciparum parasites[18]. There is a recent report of patients carrying artemisinin resistant parasites into India from Southeast Asia[19],[20]. Although some concerns about the strength of the evidence have been raised[21], such events may compromise the efficacy of the artemisinin combination therapies (ACTs) that are the foundation of efficacious malaria treatment in India and worldwide[18]. Malnutrition in children is highly prevalent in some parts of India and often common in the poorest regions where transmission of malaria is the highest. This co-morbidity raises specific issues of suboptimal dosage of antimalarials associated to poor bioavailability of the drug, which over the time, could facilitate selection of resistant parasites.

Furthermore, emphasis on elimination often focuses only on P. falciparum, but in Asia, P. vivax is a major part of the malaria burden (37% in India)[1]. The prolonged period during which some individuals carry P. vivax allows them to carry infections far from their geographic source and long after the time of their initial infection. Thus, elimination of malaria must include radical cure of P. vivax infections.

These internal and external challenges dictate that India’s plans have included attention to regional and worldwide elimination activities. India’s active participation in both the WHO/SEARO and, since 2015, in the Asia Pacific Malaria Elimination Network (APMEN) have provided a solid foundation for regional collaborations. In addition, Indian scientists have been a part of the planning and activities of the WorldWide Antimalarial Resistance Network (WWARN) since its inception in 2009. WWARN is a collaborative platform generating innovative resources and reliable evidence to inform the malaria community on the factors affecting the efficacy of antimalarial medicines and is part of the Infectious Diseases Data Observatory (IDDO). The Indian Council of Medical Research (ICMR) and the National Institute of Malaria Research have been the key members of the WWARN Board (Prof. Nirmal Kumar Ganguly— Former Director General of ICMR); Scientific Advisory Committee (Dr Neena Valecha—Former Director of NIMR); and its independent Data Access Committee (Dr Anupkumar R. Anvikar—Scientist ‘F’ of NIMR) who advise on decisions on access to malaria datasets in the WWARN repository.

Furthermore, NIMR has participated in WWARN efforts by sharing data from a number of studies conducted by the Institute which were used subsequently for conducting individual patient data (IPD) meta-analyses[22],[23],[24],[25]. To date, these data sets have been used in 9 IPD meta-analyses, 4 that are currently in progress and 5 that have already been published[14],[26],[27],[28],[29]. These meta-analyses have contributed to a better definition of the impact of chloroquine dose and primaquine for the treatment of P. vivax[29]. In collaboration with data contributed by colleagues from Africa, Asia and South America, the Indian data have also contributed to enhanced understanding of the efficacy of ACTs in these disparate locations. In particular, large harmonised datasets have tracked the extent of poor response to artemisinins[14], examined the role of ACTs on parasite transmission[28] and provided the statistical power to identify vulnerable subgroups of patients, who are at increased risk of clinical failure after treatment with particular ACTs[26],[27].

Along with NIMR, WWARN is a member of the Tracking Resistance to Artemisinins Collaboration (TRAC) led by the Mahidol-Oxford Tropical Medicine Research Unit. The initial TRAC studies first confirmed the presence of artemisinin-resistant parasites in Myanmar and other countries in the Greater Mekong Sub-region outside of Cambodia. These were followed by the TRAC2 trials focused on identifying effective and safe triple artemisinin-based combination treatments for infections with multi-drug resistant parasites. As for the TRAC studies, WWARN has also provided quality assurance and specimen management support to surveys being conducted by the St. John’s Research Institute in Bengaluru to assess the prevalence of genetic markers of drug resistance in remote forested areas of southern Odisha. Some of the highest malaria burden sites in India are in Odisha, and may make this region especially vulnerable to artemisinin resistance spreading over the border from Myanmar. All the available data on the prevalence of validated molecular markers associated with antimalarial resistance published in literature can be downloaded from the WWARN surveyors (https:// www.wwarn.org/tracking-resistance). These interactive maps visualise the dynamic and spatial distribution of parasite resistance to antimalarials used in the region. The maps also illustrate that there are some gaps of up-to-date information on the distribution of those markers in India; filling these gaps could improve knowledge easily accessible to stakeholders to guide their surveillance efforts.

The spatial and clinical heterogeneity of both P. falciparum and P. vivax in the Indian subcontinent engenders similar challenges to those encountered by global WWARN collaborations. In response, WWARN has developed and adapted tools to probe new questions that now need to be solved by the malaria community (https://www.wwarn.org/tools-resources). How can the effect of artemisinin on clearance of parasites be measured most reproducibly?[30],[31] How can laboratory-based assays be used to establish the response of parasites to drug challenge in the laboratory?[32] What is the most effective way to treat the relapses that often follow initial P. vivax infections?[33] What is the relationship of the drug concentration in patient blood to parasite clearance and drug efficacy?[34],[35],[36].

The interim report of the NIMR collaborative programme designed to optimize treatment efficacy in the high burden regions of the Central and Northeastern regions of India[10] certainly applies many such tools, and illustrates both the successes and remaining challenges that India now faces. The recognition that far better control of clinical malaria in high transmission sites must be addressed in parallel with efforts to eliminate importation of symptomatic and asymptomatic patients when transmission is low has sharpened the challenges for the malaria community[2],[3]. WWARN looks forward to continued productive collaboration with the NIMR both within India and in regional and global studies to address the issues facing the global malaria community.


  Acknowledgements Top


WWARN is supported by grants from the Bill & Melinda Gates Foundation and the ExxonMobil Foundation. The funders had no input on the manuscript. No authors have a conflict of interest with publication.



 
  References Top

1.
World Malaria Report 2018. Geneva, Switzerland: World Health Organization 2018 [updated Nov 19, 2018. 1-210]. Available from: http://apps.who.int/iris/bitstream/handle/10665/275867/9789241565653-eng.pdf.  Back to cited text no. 1
    
2.
RBM-WHO partnership to end malaria: High burden to high impact–A targetted malaria response. Geneva: World Health Organization 2018. Available from: https://apps.who.int/iris/bitstream/handle/10665/275868/WHO-CDS-GMP-2018.25-eng.pdf?ua=1 (Accessed on February 16, 2019).  Back to cited text no. 2
    
3.
MESA. Innovate for collective impact to end malaria 2019 [cited February 16, 2019]. Describes the one day meeting. Available from: https://malariaworld.org/blog/new-mesa-critical-global-gathering-innovate-collective-impact-end-malaria.  Back to cited text no. 3
    
4.
Wangdi K, Gatton ML, Kelly GC, Banwell C, Dev V, Clements ACA. Malaria elimination in India and regional implications. Lancet Infect Dis 2016; 16(10): e214-e24.  Back to cited text no. 4
    
5.
Wilson ML, Krogstad DJ, Arinaitwe E, Arevalo-Herrera M, Chery L, Ferreira MU, et al. Urban malaria: Understanding its epidemiology, ecology, and transmission across seven diverse ICEMR network sites. Am J Trop Med Hyg 2015; 93 (Suppl 3): 110-23.  Back to cited text no. 5
    
6.
Raveendran S, Rakesh PS, Dev S, Prasannakumar P, Vijaykumar N. Investigation of an outbreak of malaria in a non-endemic coastal area, Kerala, Southern India. Int J Commun Med Public Health 2016; 3(12): 3581-3.  Back to cited text no. 6
    
7.
Cator LJ, Thomas S, Paaijmans KP, Ravishankaran S, Justin JA, Mathai MT, et al. Characterizing microclimate in urban malaria transmission settings: A case study from Chennai, India. Malar J 2013; 12: 84.  Back to cited text no. 7
    
8.
Dayanand KK, Punnath K, Chandrashekar V, Achur RN, Kakkilaya SB, Ghosh SK, et al. Malaria prevalence in Mangaluru city area in the southwestern coastal region of India. Malar J 2017; 16(1): 492.  Back to cited text no. 8
    
9.
APLMA. India leading LMICs in R&D investment to tackle malaria: Asia Pacific Leaders Malaria Alliance 2018. Available from: http://www.aplma.org/blog/114/india-leading-lmics-in-r-amp-d-investment-to-tackle-malaria.html (Accessed on February 15, 2019).  Back to cited text no. 9
    
10.
Pradhan S, Pradhan MM, Dutta A, Shah NK, Joshi PL, Pradhan K, et al. Improved access to early diagnosis and complete treatment of malaria in Odisha, India. PLoS One 2019; 14(1): e0208943.  Back to cited text no. 10
    
11.
Indian Council of Medical Research-National Institute of Malaria Research. Available from: http://nimr.org.in/ [Accessed on February 16, 2019).  Back to cited text no. 11
    
12.
Bagcchi S. Sri Lanka declared malaria free. BMJ 2016; 354: i5000.  Back to cited text no. 12
    
13.
Galappaththy GNL, Fernando SD, Abeyasinghe RR. Imported malaria: A possible threat to the elimination of malaria from Sri Lanka? Trop Med Int Health 2013; 18(6): 761-8.  Back to cited text no. 13
    
14.
Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2014; 371(5): 411-23.  Back to cited text no. 14
    
15.
Imwong M, Hien TT, Thuy-Nhien NT, Dondorp AM, White NJ. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. Lancet Infect Dis 2017; 17(10):1022-3.  Back to cited text no. 15
    
16.
Tun KM, Imwong M, Lwin KM, Win AA, Hlaing TM, Hlaing T, et al. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: A cross-sectional survey of the K13 molecular marker. Lancet Infect Dis 2015; 15(4): 415-21.  Back to cited text no. 16
    
17.
Rosenthal PJ. Artemisinin resistance in eastern India. Clin Infect Dis 2018. doi: 10.1093/cid/ciy1043.  Back to cited text no. 17
    
18.
Mishra N, Bharti RS, Mallick P, Singh OP, Srivastava B, Rana R, et al. Emerging polymorphisms in falciparum Kelch 13 gene in northeastern region of India. Malar J 2016; 15(1): 583.  Back to cited text no. 18
    
19.
Das S, Saha B, Hati AK, Roy S. Evidence of artemisinin-resistant Plasmodium falciparum malaria in eastern India. N Engl J Med 2018; 379(20): 1962-4.  Back to cited text no. 19
    
20.
Das S, Manna S, Saha B, Hati AK, Roy S. Novel pfkelch13 gene polymorphism associates with artemisinin resistance in eastern India. Clin Infect Dis 2018. doi: 10.1093/cid/ciy1038.  Back to cited text no. 20
    
21.
Rasmussen C, Valecha N, Ringwald P. Lack of convincing evidence of artemisinin resistance in India. Clin Infect Dis 2019. doi: 10.1093/cid/ciz166.  Back to cited text no. 21
    
22.
Valecha N, Joshi H, Eapen A, Ravindran J, Kumar A, Prajapati SK, et al. Therapeutic efficacy of chloroquine in Plasmodium vivax from areas with different epidemiological patterns in India and their Pvdhfr gene mutation pattern. Trans R Soc Trop Med Hyg 2006; 100(9): 831-7.  Back to cited text no. 22
    
23.
Valecha N, Srivastava P, Mohanty SS, Mittra P, Sharma SK, Tyagi PK, et al. Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India. Malar J 2009; 8:107.  Back to cited text no. 23
    
24.
Valecha N, Joshi H, Mallick PK, Sharma SK, Kumar A, Tyagi PK, et al. Low efficacy of chloroquine: Time to switch over to artemisinin-based combination therapy for falciparum malaria in India. Acta Trop 2009; 111(1): 21-8.  Back to cited text no. 24
    
25.
Mishra N, Singh JP, Srivastava B, Arora U, Shah NK, Ghosh SK, et al. Monitoring antimalarial drug resistance in India via sentinel sites: Outcomes and risk factors for treatment failure, 2009–2010. Bull World Health Organ 2012; 90(12): 895–904.  Back to cited text no. 25
    
26.
WorldWide Antimalarial Resistance Network (WWARN) DP Study Group. The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin-piperaquine: A pooled analysis of individual patient data. PLoS Med 2013; 10(12): e1001564.  Back to cited text no. 26
    
27.
WWARN Artesunate-Amodiaquine SG. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data. BMC Med 2015; 13(1): 66.  Back to cited text no. 27
    
28.
WWARN GSG. Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: A systematic review and metaanalysis of individual patient data. BMC Med 2016; 14(1): 79.  Back to cited text no. 28
    
29.
Commons RJ, Simpson JA, Thriemer K, Humphreys GS, Abreha T, Alemu SG, et al. The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: A World Wide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis. Lancet Infect Dis 2018; 18(9): 1025-34.  Back to cited text no. 29
    
30.
Dahal P, Simpson JA, Dorsey G, Guerin PJ, Price RN, Stepniewska K. Statistical methods to derive efficacy estimates of anti-malarials for uncomplicated Plasmodium falciparum malaria: Pitfalls and challenges. Malar J 2017; 16(1): 430.  Back to cited text no. 30
    
31.
Flegg JA, Guerin PJ, White NJ, Stepniewska K. Standardizing the measurement of parasite clearance in falciparum malaria: The parasite clearance estimator. Malar J 2011; 10: 339.  Back to cited text no. 31
    
32.
Woodrow CJ, Dahlstrom S, Cooksey R, Flegg JA, Le Nagard H, Mentre F, et al. High-throughput analysis of antimalarial susceptibility data by the World Wide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool. Antimicrob Agents Chemother 2013; 57(7): 3121-30.  Back to cited text no. 32
    
33.
Commons RJ, Simpson JA, Thriemer K, Hossain MS, Douglas NM, Humphreys GS, et al. Risk of Plasmodium vivax parasitaemia after Plasmodium falciparum infection: A systematic review and meta-analysis. Lancet Infect Dis 2019; 19(1): 91–101.  Back to cited text no. 33
    
34.
Hoglund RM, Workman L, Edstein MD, Thanh NX, Quang NN, Zongo I, et al. Population pharmacokinetic properties of piperaquine in falciparum malaria: An individual participant data meta-analysis. PLoS Med 2017; 14(1): e1002212.  Back to cited text no. 34
    
35.
Kloprogge F, McGready R, Hanpithakpong W, Blessborn D, Day NPJ, White NJ, et al. Lumefantrine and desbutyl-lumefantrine population pharmacokinetic-pharmacodynamic relationships in pregnant women with uncomplicated Plasmodium falciparum malaria on the Thailand-Myanmar border. Antimicrob Agents Chemother 2015; 59(10): 6375-84.  Back to cited text no. 35
    
36.
Kloprogge F, Workman L, Borrmann S, Tekete M, Lefevre G, Hamed K, et al. Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis. PLoS Med 2018; 15(6): e1002579.  Back to cited text no. 36
    


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