PERSPECTIVE

Malaria Elimination in India: Bridging the Gap Between Control and

Elimination
SHRIKANT NEMA1, PAWAN GHANGHORIA2 AND PRAVEEN KUMAR BHARTI1
From 1Division of Vector Borne Diseases, ICMR-National Institute of Research in Tribal Health; and 2Department of Pediatrics,
Netaji Subhash Chandra Bose Medical College; Jabalpur, Madhya Pradesh, India.
Correspondence to: Dr. Praveen Kumar Bharti, Scientist ‘E’, Division of Vector Borne Diseases, ICMR-National Institute of
Research in Tribal Health (NIRTH), DHR, Ministry of Health and Family Welfare, Government of India, Nagpur Road, PO - Garha,
Jabalpur 482 003, Madhya Pradesh, India. saprapbs@yahoo.co.in.

India observed a significant reduction in malaria cases in the previous year, reaffirming our trust and efficiency of the existing tools to
achieve malaria elimination. On 25 April, 2019, countries around the world marked World Malaria Day under the theme “Zero malaria
starts with me”. This provides an opportunity to rejoice the success and re-evaluate ongoing challenges in the fight against this
preventable and treatable parasitic disease. We highlight the potential gaps in the malaria elimination program, and underscore potential
solutions and strategies to implement, improve and intensify the success of the national goal of malaria elimination by 2030.
Keyword: Diagnosis, Epidemiology, Vector-borne disease.

I
ndia has a long history of success and struggles organization (WHO) has developed the Global technical
with malaria control. The unsuccessful endeavor to strategy for malaria under the National framework for
eliminate malaria, and increasing morbidity and malaria elimination in India 2016-2030 to eliminate
mortality bring back the elimination agenda in the malaria (zero indigenous cases) throughout the entire
health care priorities [1]. In 1976, there was a massive country by 2030, and maintain malaria-free status and
resurgence of malaria cases and Plasmodium falciparum prevent its re-introduction. Therefore, we need to put all
resistance to chloroquine and vector resistance to our efforts to achieve the desired success this time.
insecticides were reported [1]. As a consequence, the
DISEASES BURDEN AND SURVEILLANCE
modified plan of operations was launched in 1977 with a
three-pronged strategy: early diagnosis with prompt In 2018, an estimated 228 million cases of malaria
treatment, vector control, and Information Education occurred worldwide, compared to 251 million cases in
Communication (IEC)/Behavior Change Communication 2010 [3]. In India, a population of 126 million was at risk
(BCC), resulting in the decline of malaria incidence again of malaria with an estimate of 6 million cases in 2018 [3],
in 1984. Subsequently, Enhanced Malaria Control while 0.43 million confirmed cases of malaria were
Project in 1997 and Intensified Malaria Control Project in reported by NVBDCP in 2018 [4]; although,
2005 were launched to combat malaria in high discrepancies between various sources have been noted
transmission areas of the country. New tools for malaria [5]. In India, malaria is highly endemic in rural and tribal
prevention and control were introduced by National areas of Madhya Pradesh, Maharashtra, Odisha,
Vector Borne Disease Control Program (NVBDCP) i.e., Rajasthan, Gujarat, Jharkhand, Chhattisgarh, Andhra
monovalent rapid diagnostic tests (RDT) for P. Pradesh, West Bengal, and Karnataka. Further, districts
falciparum detection in 2005; Artemisinin-based with 30% or more tribal population comprising about 8%
combination therapy (ACT) in 2006; Long-lasting of the country’s population contributed to 46% of total
insecticide-treated nets (LLINs) in 2009; antigen malaria cases, 70% P. falciparum cases and 47% malarial
detecting bivalent RDTs for detection of both P. deaths in the country [6]. However, India has shown a
falciparum and P. vivax in 2013; and newer insecticides 71% reduction in 2019 as compared to 2015 and this
and larvicides in 2014-15. However, these strategies reduction was achieved by strengthening the surveillance
failed to build on its expected level of achievements. measures, improving diagnosis and treatment, and
India moved towards global commitment for malaria intensive vector control measures using existing tools.
elimination and endorsed a plan to eliminate malaria For example, Odisha contributed 37.4% of total malaria
throughout the region by 2030 [2]. World health cases in 2015 which reduced to 12% in 2019 using the

INDIAN PEDIATRICS 613 VOLUME 57__JULY 15, 2020

NEMA, ET AL. MALARIA ELIMINATION IN INDIA

Durgama Anchalare Malaria Nirakaran (DAMaN) initia- hospital and healthcare facilities are inaccessible. They
tive and compre-hensive case management of malaria. To provide diagnosis using RDT, and treatment, as well as
sustain the achieved reduction and moving forward to the advise them about the importance of preventive
elimination, we have to strengthen all the strategies using measures. Strengthening the qualitative and quantitative
existing tools and by developing new tools. capacity of the ASHA may prove an asset in malaria
elimination as children under the age of 5 are more
CHALLENGES AND SOLUTIONS vulnerable in the community for developing severe
Strengthening Malaria Diagnosis malaria. Tribal people are mostly dependent on
traditional healers and unlicensed medical practitioners
Accurate diagnosis is the key to success in the elimination (UMP), which delays the correct diagnosis, and improper
goal. Among the five Plasmodium species, P. falciparum treatment may lead to severe malaria, as well as further
and P. vivax cause the majority of cases and other species transmission in the community [10]. Therefore, the
are rare, but the diagnosis is complicated by the varied stakeholders may think about providing training to
distribution of both mono-infection and mixed infections unlicensed medical practitioners on national guidelines
[7]. Microscopy has always been the gold standard method for malaria diagnosis and treatment to overcome this
but it requires highly skilled microscopist with genuine issue. An integrated community case management
knowledge of different stages of Plasmodium species with strategy along with ASHA/UMP may be needed to fight
capability to read low-density parasitemia - fulfilling such against malaria in the community.
a requirement in rural India is a daunting task, as a
consequence, more than a quarter of malaria cases are Malaria in Children
missed by microscopy [8]. RDTs are used where Children aged below 5 years are the most vulnerable
microscopy is not feasible. P. falciparum histidine-rich group and accounted for 67% of global malaria deaths in
protein 2 (PfHRP2) antigen targeting P. falciparum is used 2018 [3], and complicated malaria is more common in
in more than 90% of the malaria RDTs [9]. However, children than adults. The clinical symptoms (fever,
deletions of the Pfhrp2 gene in the parasite, fluctuation in vomiting, cough, difficulty in breathing and inability to eat
the expression level of Plasmodium Lactic Dehydrogenase and drink) of malaria in children may be mistaken for a
(pLDH), and prozone phenomena are the major problems viral syndrome or acute gastroenteritis. P. falciparum
leading to inaccurate diagnosis of plasmodium species. seems to be notorious for severe malaria but vivax is also
Therefore, other potential biomarkers such as heme- presenting as severe malaria in children [11]. In high
detoxification protein, apical merozoites surface protein transmission areas, young children are at high risk of
Pf34, Glutamate dehydrogenase, and hypnozoites-based severe vivax-associated anemia, where the relapses
serological marker should be validated to strengthen the phenomenon is frequent [12]. Children need portable,
RDT tool. Molecular methods such as Polymerase chain easy to take medicine adapted to their weight and age.
reaction (PCR) are feasible for the diagnosis of malaria Therefore, careful consideration should be given to the
(particularly low-density infection). However, these formulations of child-friendly antimalarials because
methods like conventional PCR, nested PCR, qPCR, children absorb and metabolize medicines differently
multiplex PCR, and Loop-mediated isothermal ampli- [13]. Although the medicines for malaria ventures (MMV)
fication (LAMP) are less frequently used techniques due to has taken the initiative for discovering and developing
longer time required, need for advanced equipment, new medicines [13]. The improper and inadequate drug
expensive reagents and experienced personnel, and and doses in the long term may create problems of drug
difficultly in organizing in most field conditions. A resistance resulting in high morbidity and mortality in
hemozoin-based magneto-optical detection device children as deaths in infants and children <14 years of age
(Gazelle) may prove an alternative to RDT for accurate accounted for 20.6% in India [14].
diagnosis in the field. These new markers/tools can make
an impact on elimination efforts by addressing the problem Pregnant Women: A Vulnerable Group
of missed diagnosis. Pregnant women are more susceptible to malaria,
The Frontline Staff although the prevalence during pregnancy was
substantially lower in areas of high transmission [15].
Accredited Social Health Activists (ASHA) and During placental malaria, P. falciparum-infected
community health workers are the key players and erythrocytes sequester in the placenta, causing health
leading contributors to the malaria elimination program problems for both the mother and fetus, increasing risk
as they are primary healthcare providers in the malaria for congenital malaria [16]. Therefore, in the malaria-
endemics rural and tribal areas where government endemic areas, pregnant women should be screened for

INDIAN PEDIATRICS 614 VOLUME 57__JULY 15, 2020

NEMA, ET AL. MALARIA ELIMINATION IN INDIA

malaria if they have malaria-like symptoms or even in the ACT has made a thrilling effect on malaria treatment in
cases of anemia, which not only helps malaria elimination many countries. At present, these drugs are successful;
but also delivering a healthy baby. however, there are already hints that resistance to
artemisinin has emerged [22]. Other factors that may
Migration Malaria and Surveillance Strategy
contribute to drug resistance are the mutation in
Migration malaria is also an important affair as it serves resistance markers, counterfeit or substandard treat-
as a reservoir and seeds local outbreaks. Moreover, ments, improper doses, and artemisinin monotherapy. To
migrant workers who either take temporary shelter or avoid artemisinin resistance, triple artemisinin-based
coming from malaria-endemic areas could impede combination therapies such as artemether–lumefantrine
surveillance. Therefore, imported/migratory cases should plus amodiaquine are already in pipeline for the treatment
be tracked by using surveillance networks, similar to of uncomplicated P. falciparum malaria [23]. In the case
GeoSentinel, EuroTravNet and TropNetEurop. Malaria of P. vivax, a 14-day course of primaquine (gametocidal
elimination requires a strong surveillance mechanism that drug) is recommended in all transmission settings to
can reliably and rapidly detect the disease using the ‘1-3- overcome the issue of relapse but poor drug compliance
7’ strategy [17] and the ‘1-2-5’ strategy [18] during the is a major challenge.
elimination phase to overcome the problem. Additionally,
However, the single dose regimen of tafenoquine may
mobile surveillance tools may be efficient in real-time
be helpful to improve the adherence issues associated
information sharing such as Solutions for Community
with primaquine regimens. Clinicians must document the
Health-workers (SOCH) and Integrated Health
G6PD status because primaquine and tafenoquine both
Information Platform (IHIP) to prevent them from
may induce hemolytic anemia in patients with a glucose-
spreading disease and outbreak situations [19].
6-phosphate dehydrogenase deficiency (G6PD). Never-
Therefore, the utilization of such networks may have
theless, novel P. vivax anti-relapse medicines that targets
importance in the malaria elimination program in India.
hypnozoites are greatly needed. Implementation of
Asymptomatic/ Afebrile Malaria: A Reservoir Directly-observed therapy (DOT) reduces the anti-
malarial resistance development, reappearance rate of the
Afebrile cases do not show presentable routine symptoms
parasite, and may subsequently decrease P. vivax
but may become a source of parasitic transmission under
transmission [24]. This ultimate goal of developing new
a favorable setting. Asymptomatic malaria (the presence
antimalarial drugs and modifying existing ones will take
of sexual or asexual parasites and/or absence of clinical
us one step closer to the elimination goal.
symptoms) poses a serious challenge worldwide [20].
Naturally acquired immunity and partial immunity with Plasmodium vivax: Roadblock in the Success
past exposure and age are the probable factors to
In India, P. vivax contributed 53.4% of the infections in
asymptomatic malaria in the malaria-endemic areas that
2019. It is often termed benign malaria but substantial
plays a significant role in transmission and malaria
increases in morbidity and mortality, especially in infants
severity in children 2 to 5 years of age [21]. Therefore,
due to weak immunity is considered alarming.
proper attention is warranted in children; else they may
Pathophysiology of P. vivax such as a low-density blood-
act as a key reservoir of malaria infection.
stage infection, hypnozoites, transmission facilitated by
Antimalarial Drug Treatment and Resistance the early production of infective stages, mature
gametocytes and more genetically diverse P. vivax
Schizonticidal and gametocidal drugs have been used to
populations have limited understanding. Vivax Duffy-
treat and prevent malaria for centuries. Chloroquine was
negative phenotype and Fy glycoprotein (FYA) need
first developed in the 1930s; but in 1973, chloroquine-
proper understanding in the Indian context to fight
resistance (CQR) was initially pointed out in Assam,
against P. vivax malaria [25].
India. The rise in CQR (Pfcrt gene, a molecular marker to
track the CQR) contributed to a worldwide increase in The risk of P. vivax parasitaemia is high in co-
malaria-related mortality. To combat resistant strains, endemic regions (where both P. falciparum and P. vivax
several alternative synthetic antimalarial drugs are equally prevalent) after treatment for P falciparum
(sulfadoxine-pyrimethamine and mefloquine) were infection. This is probably due to fast acting and rapid
deployed to treat and prevent malaria. Sulfadoxine- parasite clearance property of artemisinin-based therapy
pyrimethamine (SP) is utilized as the second line of against the treatment of falciparum malaria, in the area
therapy after chloroquine-resistant in India. However, the where short periodicity of P. vivax relapse cases occurred.
mutation at the dhps and dhfr genes make it ineffective Therefore, complete radical cure may be assured to
against the P. falciparum malaria. The introduction of prevent recurrent parasitaemia, reduce ongoing

INDIAN PEDIATRICS 615 VOLUME 57__JULY 15, 2020

NEMA, ET AL. MALARIA ELIMINATION IN INDIA

transmission to ensure malaria elimination success [26]. CONCLUSION

Vector Control and Insecticide Resistance Healthcare communities have undertook serious efforts
to reduce malaria cases in India, but it is still threatening
National Malaria Program has distributed about 50
millions in India. This time the elimination efforts would
million Long Lasting Insecticidal nets (LLINs) to
require targeted approaches and strategies starting from
communities during 2016-2018 in India [4] as an
the village level to the national level. At the same time, we
intervention tool for malaria control and prevention to
need to take care of all the possible gaps such as human
cover the 126 million populations that were under risk
resources, robust surveillance, and hotspot targeted
[3]. Among children under 5 years of age, LLINs provide
interventions by proper utilization of existing as well as
up to 55% protective efficacy in preventing malaria
new tools. All the laboratory-confirmed positive cases
attributed to mortality [27]. Operational success can only
should be advised to stay under mosquito net until
be achieved when universal coverage is attained and is at
parasite clearance to avoid community transmission.
least 80% [28]. The major drawbacks of LLINs include
Universal and continuous availability of drugs,
personal discomfort and feelings of suffocation when
diagnostic and essential malaria commodities are to be
humidity and indoor temperature are high. Therefore,
ensured for effective management of community malaria.
child-friendly nets using color combinations and cartoon-
If the lessons learned from elimination efforts are
based print may increase the use of LLIN. Thus, Zero
properly utilized, the malaria elimination goal mayvery
vector durable lining (ZVDL) is designed to cover
well be achieved on time.
interior wall surfaces, utilizing slow-release technology
that has the advantages of both LLINs and IRS, i.e. long- Contributors: All authors have contributed, drafted and
lasting residual use and no insecticide dusting [29]. approved the manuscript.
Funding: None; Competing interests: None stated.
Vaccines: The Last Piece of the Puzzle
REFERENCES
There is no commercially available malaria vaccine
currently. However, efforts to make an effective malaria 1. Sharma VP. Re-emergence of malaria in India. Ind J Med
vaccine are underway for the last three decades. Phase 3 Res. 1996;103:26-45.
trial of RTS, S/AS01 (Mosquirix) (at month 0, 1, and 2) in 2. Guerin PJ, Dhorda M, Ganguly NK, Sibley CH. Malaria
children aged 5-17 months showed vaccine efficacy of control in India: A national perspective in a regional and
28.3% against severe malaria in children [30]. PfSPZ global fight to eliminate malaria. J Vector Borne Dis. 2019;
based genetically attenuated vaccines which halt the 56:41-5.
3. World Health Organization. World Malaria Report 2019.
development in the early liver stages were found to offer
Available from: https://www.who.int/publications-detail/
protection to 55% recepients [31]. Limited understanding world-malaria-report--2019. Accessed December 7, 2019.
of how immunity develops against malaria poses a great 4. National Vector Borne Disease Control Programme
challenge to researchers in designing effective vaccines. (NVBDCP). Malaria. Available from: https://nvbdcp.gov.
Recent advances in the generation of recombinant in/index1.php?lang=1&level=1&sublinkid=5784&lid=
proteins, DNA and RNA based approaches may be useful 3689. Accessed October 8, 2019.
in vaccine development [32]. 5. Dhingra N, Jha P, Sharma VP, Cohen AA, Jotkar RM,
Rodriguez PS, et al., Million Death Study Collaborators.
Inter-sectoral Coordination Adult and child malaria mortality in India: A nationally re-
presentative mortality survey. Lancet. 2010;376:1768-74.
Several government organizations, such as the ICMR
6. Sharma RK, Thakor HG, Saha KB, Sonal GS, Dhariwal AC,
through Malaria Elimination Research Alliance-India and Singh N. Malaria situation in India with special reference to
NVBDCP are moving forward to fill the gaps with tribal areas. Indian J Med Res. 2015;141:537-41.
research and innovative strategies. India Health Fund and 7. Nema S, Verma AK, Bharti PK. Strengthening diagnosis is
several non-governmental organi-zations such as TATA key to eliminating malaria in India. Lancet Infect Dis.
Trust and Godrej have also taken an initiative to work on 2019;19:1277-8.
parasite control, vector control, technology-integration, 8. Okell LC, Ghani AC, Lyons E, Drakeley CJ.
and awareness and behavioral change. Moreover, the Submicroscopic infection in Plasmodium falciparum-
success story of neighboring countries like Sri Lanka and endemic populations: a systematic review and meta-
analysis. J Infect Dis. 2009;200:1509-17.
China echoes the importance of public-private
9. Ahmad A, Verma AK, Krishna S, Sharma A, Singh N,
partnerships to accelerate malaria elimination efforts. Bharti PK. Plasmodium falciparum glutamate dehydro-
ICMR and Sun Pharma Ltd have partnered for malaria genase is genetically conserved across eight malaria
elimination activities in Mandla district of Madhya endemic states of India: Exploring new avenues of malaria
Pradesh [19]. elimination. PloS One. 2019;14:e0218210.

INDIAN PEDIATRICS 616 VOLUME 57__JULY 15, 2020

NEMA, ET AL. MALARIA ELIMINATION IN INDIA

10. Singh MP, Chand SK, Saha KB, Singh N, Dhiman RC, Yewhalaw D, Pillai DR. Asymptomatic malaria in the
Sabin LL. Unlicensed medical practitioners in tribal clinical and public health context. Expert Rev Anti-infect
dominated rural areas of central India: Bottleneck in Ther. 2019;17:997-1010.
malaria elimination. Malaria J. 2020;19:18. 22. Das S, Saha B, Hati AK, Roy S. Evidence of artemisinin-
11. Singh J, Purohit B, Desai A, Savardekar L, Shanbag P, resistant Plasmodium falciparum malaria in eastern India.
Kshirsagar N. Clinical manifestations, treatment, and New Engl J Med. 2018;379:1962-4.
outcome of hospitalized patients with Plasmodium vivax 23. van der Pluijm RW, Tripura R, Hoglund RM, Phyo AP,
malaria in two Indian states: a retrospective study. Malar Lek D, Ul Islam A, et al. Triple artemisinin-based
Res Treat. 2013;2013:341862. combination therapies versus artemisinin-based
12 Douglas NM, Anstey NM, Buffet PA, Poespoprodjo JR, combination therapies for uncomplicated Plasmodium
Yeo TW, White NJ, Price RN. The anaemia of Plasmodium falciparum malaria: a multicentre, open-label, randomised
vivax malaria. Malaria J. 2012;11:135. clinical trial. Lancet. 2020 395:1345-60.
13. Medicines for Malaria Venture. Children and malaria: 24. Takeuchi R, Lawpoolsri S, Imwong M, Kobayashi J,
treating and protecting the most vulnerable. Available Kaewkungwal J, Pukrittayakamee S, et al. Directly-
from:https://www.mmv.org/newsroom/publications/ observed therapy (DOT) for the radical 14-day primaquine
children-and-malaria-treating-and-protecting-most- treatment of Plasmodium vivax malaria on the Thai-
vulnerable. Accessed December 8, 2019. Myanmar border. Malaria J. 2010;9:308.
14. Kumar A, Valecha N, Jain T, Dash AP. Burden of malaria 25. Gai PP, Van Loon W, Siegert K, Wedam J, Kulkarni SS,
in India: Retrospective and prospective view. Am J Trop Rasalkar R, et al. Duffy antigen receptor for chemokines
Med Hyg. 2007;77(6_Suppl): 69-78. gene polymorphisms and malaria in Mangaluru, India.
15. Kitojo C, Gutman JR, Chacky F, Kigadye E, Mkude S, Malaria J. 2019;18:328.
Mandike R, et al. Estimating malaria burden among 26. Commons RJ, Simpson JA, Thriemer K, Hossain MS,
pregnant women using data from antenatal care centres in Douglas NM, Humphreys GS, et al. Risk of Plasmodium
Tanzania: a population-based study. Lancet Glob Hlth. vivax parasitaemia after Plasmodium falciparum infection:
2019;7:e1695-705. a systematic review and meta-analysis. Lancet Infect Dis.
16. Pereira MA, Clausen TM, Pehrson C, Mao Y, Resende M, 2019;19:91-101.
Daugaard M, et al. Placental sequestration of Plasmodium 27. Eisele TP, Larsen D, Steketee RW. Protective efficacy of
falciparum malaria parasites is mediated by the interaction interventions for preventing malaria mortality in children
between VAR2CSA and chondroitin sulfate A on in Plasmodium falciparum endemic areas. Int J Epidemiol.
syndecan-1. PLoS Pathog. 2016;12:e1005831. 2010;39(suppl_1):i88-101.
17. Zhou SS, Zhang SS, Zhang L, Rietveld AE, Ramsay AR, 28. Walldorf JA, Cohee LM, Coalson JE, Bauleni A,
Zachariah R, et al. China’s 1-3-7 surveillance and response Nkanaunena K, Kapito-Tembo A, et al. School-age
strategy for malaria elimination: Is case reporting, children are a reservoir of malaria infection in Malawi.
investigation and foci response happening according to PloS One. 2015;10: e0134061.
plan? Infect Dis Poverty. 2015;4:55. 29. Mishra AK, Bharti PK, Kareemi TI, Chand SK, Tidgam
18. Sitohang V, Sariwati E, Fajariyani SB, Hwang D, Kurnia AS, Sharma RK, et al. Field evaluation of zero vector
B, Hapsari RK, et al. Malaria elimination in Indonesia: durable lining to assess its efficacy against malaria vectors
Halfway there. Lancet Global Hlth. 2018;6: e604-6. and malaria transmission in tribal areas of the Balaghat
19. Lal AA, Rajvanshi H, Jayswar H, Das A, Bharti PK. district of central India. Trans Royal Soc Trop Med Hyg.
Malaria elimination: Using past and present experience to 2019;113:623-31.
make malaria-free India by 2030. J Vector Borne Dis. 30. Lancet T. Vaccines: A step change in malaria prevention?
2019; 56:60-5. Lancet. 2015;385:1591-3.
20. Hassanpour G, Mohebali M, Zeraati H, Raeisi A, 31. Ghosh SK, Rahi M. Malaria elimination in India—the way
Keshavarz H. Asymptomatic malaria and its challenges in forward. J Vector Borne Dis. 2019;56:32-40.
the malaria elimination program in Iran: A systematic 32. Doolan DL, Hoffman SL. DNA-based vaccines against
review. J Arthropod Borne Dis. 2017;11:172-4. malaria: status and promise of the multi-stage malaria DNA
21. Cheaveau J, Mogollon DC, Mohon MA, Golassa L, vaccine operation. Int J Parasitol. 2001;31:753-62.

INDIAN PEDIATRICS 617 VOLUME 57__JULY 15, 2020