IN May 2015, in a bid to accelerate malaria eradication worldwide by 2030 and shift gears from its earlier strategy of malaria control, the World Health Organization (WHO) adopted its Global Technical Strategy for Malaria 2016-2030. Even as the gains from malaria control needed to be consolidated, it was becoming clear that antimalarials, artemisinin combination therapy (ACT) in particular, and vector control products could become ineffective within a few years’ time.
Aligning its strategy with WHO’s new vision, India too reformulated its national malaria control programme towards elimination. In February 2016, India launched its National Framework for Malaria Elimination 2016-2030. The government proposes to attain the status of “zero indigenous cases” by 2027, maintain it up to 2030, and get the WHO certification of malaria-free India by 2030.
In this direction India has made significant progress according to the figures of the Union Ministry of Health and Family Welfare. The number of cases has declined by 84 per cent, from 11,69,261 in 2015 to 1,86,532 in 2020, and deaths have decreased by 76 per cent, from 384 in 2015 to 93 in 2020 (Table 1). According to the Ministry, from 2012, India has sustained an annual parasite incidence (API) of less than 1 new infection per 1,000 population at the national level though tens of districts still have an API greater than 1. The number of districts with an API ≥ 1 dropped to 32 in 2020 from 154 in 2015 (Fig. 1). In 2020, the national API was 0.14 per 1,000 population. But as it approaches the last phase in the next eight years to eliminate the disease, the task could become daunting.
Malaria, transmitted by the infective bite of the female Anopheles mosquito, is caused by different species of the parasite Plasmodium: P. falciparum, P. vivax, P. malariae, and P. ovale. P. vivax and P. falciparum are more common in India. If not treated immediately, P. falciparum can lead to serious complications, cerebral malaria being the most serious, and death. P. vivax infection, on the other hand, can remain latent and cause recurrences of the disease.
Although there was an overall decline (~85 per cent) in the number of P. falciparum cases between 2015 and 2020 (Table 1), P. falciparum remains the dominant cause of the disease in India and accounted for 7,74,627 cases (~66 per cent) in 2015 and 1,17,567 cases (~63 per cent) in 2020. However, it should be noted that P. vivax contributes a significant fraction, almost equal in some years, to the caseload. In 2019, more than half the total number of cases was due to P. vivax (Table 1).
The above statistics are official figures of the government as recorded by the surveillance system put in place by the Union and State Health Ministries and do not include cases and deaths it missed. The surveillance network can miss cases because private health care settings do not automatically share data; because of non-reporting, misdiagnoses, undetected asymptomatic infections; and because the network does not reach areas that have no or poor access to the national health care system.
As per the World Malaria Report 2021, WHO’s estimates of malaria cases and deaths for India in 2020 are about 4.2 million and 7,341 (Fig. 2). India accounted for 83 per cent of the estimated malaria cases and 82 per cent of the estimated malaria deaths in the WHO South-East Asia region. Thus, there is nearly a 23-fold and 79-fold mismatch in the number of malaria cases and deaths respectively between official figures and WHO estimates. Enormous by any standards, this is indicative of a very poor surveillance system.
The figure shows WHO’s estimates of malaria cases and deaths for India.
While there is a sustained decline in the overall malaria burden, both as per official statistics and WHO estimates, besides the big challenge of getting the numbers correct, the vast sociocultural, demographic, economic, and ethnic diversity in the country presents an enormous challenge to the country’s healthcare system. Besides, there is also a high degree of heterogeneity in the epidemiology of the disease across the country, which poses multiple challenges of its own.
In a paper published in late May in The Lancet, the malaria researchers Manju Rahi and Amit Sharma of the Division of Epidemiology and Communicable Diseases of the Indian Council of Medical Research (ICMR) comprehensively addressed the multiple issues involved in the approach to eradication in India and discussed in detail the challenges that lie ahead in meeting the 2030 deadline. They suggested initiatives the country can take, which, according to them, can prove to be game changers.
“India’s road to malaria elimination plan is riddled with many roadblocks.”Manju Rahi & Amit SharmaThe Lancet
“India’s road to malaria elimination plan is riddled with many roadblocks,” write Rahi and Sharma. “Major challenges,” they say, “include insufficient surveillance, slow and aggregated data reporting especially in exigent situations like cross-border areas and vulnerable high-risk groups.” The duo dwelt upon the key issues, such as surveillance, P. vivax malaria, diagnostics, drug resistance, and vector control, under separate heads and suggested possible solutions for each.
The major hurdle in malaria eradication is the extremely weak surveillance of active and passive cases in the country, note Rahi and Sharma. According to the World Malaria Report 2018, India’s surveillance system was able to capture only about 8 per cent of the actual burden. One of the chief reasons for this, the authors say, is because the private sector and other non-governmental actors who provide healthcare services are not included in the surveillance system.
A municipal worker spraying insecticide on the tracks of a railway station in New Delhi in October 2021 when vector-borne diseases were on the rise in the capital. | Photo Credit: MOORTHY R.V.
The role of the private sector is important in any disease surveillance programme; the National Sample Survey (NSS) records that the private health care sector provides ~75 per cent of outpatient care and ~62 per cent of inpatient care. A 2017 study noted that 65 per cent of communities sought malaria healthcare providers in the private sector. Besides, even within the government sector, healthcare in settings other than the public health programme, such as public sector undertakings, the railways, and the services, gets left out. Then there is also the semi-government sector, medical colleges, hospitals in industries and the corporate sector, and missionary hospitals which do not always report cases despite malaria being made notifiable in 31 States and Union Territories of India, point out Rahi and Sharma.
“The multiple healthcare partners … [including] doctors practising at home, traditional/faith healers, informal volunteers, untrained providers and gypsies … that address burden of malaria add complexity to the control and elimination efforts,” the Rahi-Sharma paper notes. “There is also no cross-communication between the different partners and … in [the] absence of one digital single platform makes efficient data reporting and data utilization nearly impossible.”
“The current surveillance system,” the authors write, “continues to be aggregated, paper-based and restricted to a limited number of public healthcare facilities. The need of the hour is to modernise the existing sluggish surveillance and data reporting systems into a near real-time digital data collection with platforms like [malaria] dashboards where data could be uploaded.” They point out that a platform like Nikshay, the Web-based patient management system that has been introduced for TB (set for elimination by 2025), can be adopted for reporting, registering, and monitoring malaria patients by both the public and the private sector, and these various datasets can be pooled into the national surveillance system. Likewise, a mobile app–based platform for data collection can also be considered.
“The surveillance system in India is an underperforming system leading to delays in detection of outbreaks and hotspots, delays in data visualisation, and thus delayed analysis and decision making.”Manju Rahi & Amit SharmaThe Lancet
“The surveillance system in India is an underperforming system leading to delays in detection of outbreaks and hotspots, delays in data visualisation, and thus delayed analysis and decision making,” the paper says. According to the authors, the current data aggregation system also results in a loss of granularity below the district level. Further, besides the symptomatic malaria cases that the rapid diagnostic test (RDT) or microscopy detect, there is a substantial burden of asymptomatic or subclinical (below the threshold of detection by routine diagnostics) cases, they point out.
Many regions in the country, the authors say, persistently report a high incidence of malaria despite deployment of effective control measures. One of the reasons, they say, could be the presence of asymptomatic and submicroscopic infections. According to studies, highly malaria endemic regions have as high as 70–80 per cent asymptomatic infections and 30–45 per cent subpatent, or below-threshold, infections, which are transmissive but are missed by the surveillance system. The authors, therefore, recommend the use of more sensitive molecular tools in the national programme at least at the district level (tertiary care level).
A worker of the Municipal Corporation of Delhi carrying out fumigation work in a colony in West Delhi in October 2021. | Photo Credit: Shiv Kumar Pushpakar
Another crucial gap in the surveillance system is insufficient capture of vulnerable groups such as forest dwellers, antenatal women, indigenous/urban slum populations, migrants, and mobile populations. According to the authors, about 7 per cent of the population living in forested areas disproportionately contributes to about 21 per cent of malaria cases and to about 53 per cent of deaths. An analysis by the ICMR’s epidemiology division showed that malaria incidence was fourfold higher in 2000 in forested areas than in non-forested areas and three times higher in 2019. P. falciparum malaria is the predominant one in forest regions, and drug/insecticide resistance are major threats, the paper notes.
The authors have also highlighted the additional risk of malaria to pregnant women (especially in the case of the first pregnancy) living in endemic areas, particularly those belonging to the poor socio-economic strata, because of altered immune status, susceptibility to severe P. falciparum malaria, and placental malaria. Rahi and Sharma advocate strengthening surveillance by integrating intermittent screening and treatment with routine antenatal care. “Following mothers post-delivery for administering of radical cure for P. vivax malaria is also important, but [is] largely neglected under the national programme,” says the paper.
Tracking cross-border malaria, which is important to check importation (through movement of people) from a neighbouring country, is another complex but critical and largely neglected component in the surveillance system, according to the duo. However, many of India’s neighbours are nearing elimination of the disease, and therefore, monitoring of international borders is especially important from their perspective. So, say the authors, joint epidemiological and entomological surveillance and sharing of near real-time data across neighbouring countries assume importance. “However, this is not being actively pursued currently at India’s international border areas,” the paper notes. “Some efforts were made in the past by WHO to ramp up monitoring at [the] Indo-Bhutan border but concrete steps could not be taken as yet.”
A health worker carrying out fogging operations in the flood-affected Morigaon district of Assam on May 23. | Photo Credit: RITU RAJ KONWAR
The high P. vivax malaria burden in absolute numbers in the country and the fact that it has not not been adequately dealt with are the next important stumbling blocks in the eradication efforts. India reported 67,444 P. vivax cases (36 per cent of total malaria cases) in 2020. First, as the paper notes, the malaria P. vivax causes is difficult to resolve compared with the malaria other species cause. Further, P. vivax has the tendency to develop hypnozoites (dormant forms in the life cycles of parasitic protozoa that are associated with latency and relapse in infections caused by P. vivax and P. ovale). The recommended radical treatment to clear hypnozoites is a 14-day regime of primaquine (PQ). However, there is poor PQ compliance by patients, and there is no mechanism to administer the treatment directly to ensure compliance. Further, since PQ is contraindicated in pregnant and lactating women, they are at a greater risk of relapses.
Host factors, such as G6PD (glucose-6-phosphate dehydrogenase) deficiency and other genetic factors, which are common among populations in malaria endemic areas, affect PQ metabolism and complicate its efficacy. The prevalence of G6PD deficiency is reported to range from 0.8 per cent to 6.3 per cent with a national level prevalence of 1.9 per cent. Rahi and Sharma point out that there is inadequate testing for G6PD deficiency and, likewise, inadequate mapping of the prevalence of the other predisposing genetic factors in Indian populations. There is also insufficient data on the burden of asymptomatic P. vivax and relapses.
Further, G6PD deficiency, according to the authors, is more prevalent in tribal areas than in non-tribal regions. Besides inadequate diagnostic facilities (for both malaria and G6PD testing), these tribal communities run a greater risk of relapses and/or reinfections of P. vivax because of lack of timely treatment or incomplete radical PQ treatment.
The authors, therefore, are of the view that P. vivax will be more difficult to eliminate than P. falciparum. To solve the problem of poor compliance, the duo has suggested the introduction of tafenoquine to clear hypnozoites with the companion G6PD point-of-care diagnostic after due regulatory approvals. “Tafenoquine is a robust alternative to PQ as a hypnozoiticidal drug and India must consider it in due course of time, though there are certain limitations to the use of the drug,” says the paper.
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Limited access to diagnostic tools and lack of sensitive methods is another important issue that Rahi and Sharma address in their paper. Currently, diagnostic tools for detection are mostly available only through the national programme, and these include mainly RDT kits and light microscopy. These are largely facility-based or are provided by healthcare workers at the premises. While private practitioners may be able to purchase these diagnostic tools, they are not available for communities or the general public to purchase and use the way blood sugar–testing kits, pregnancy kits, and pulse oximeters are. This limited access leads to delays in case identification and treatment and contributes indirectly to malaria transmission. The authors suggest that, after certain training in dispensing the tests and reporting the positive cases to the health authorities, RDTs should be made accessible to private practitioners, communities, drug stores, and pharmacies in India as has been done in some other South Asian countries.
But, more importantly, these RDTs are able to detect only patent infections (where the malaria parasite can be clinically demonstrated). These kits miss low-density infections and sometimes misdiagnose submicroscopic and mixed parasite infections. Further, the RDTs mostly use the P. falciparum antigen histidine rich protein 2 (HRP2) as the preferred target because of its abundant production by the parasite in red blood cells and their thermal stability. RDTs are thus unable to detect the parasite P. falciparum with deletions of HRP2 and HRP3 genes. A study conducted across 16 sites in eight malaria endemic States showed 0-8 prevalence of these deletions. Similarly, the burden of the disease due to species other than P. falciparum and P. vivax largely remains unknown because the tools currently used miss these. States in the north-eastern region (NER) have reported cases of mixed parasite infections and mono infections of P. malariae and P. ovale.
All these limitations in diagnostics, the authors say, are serious challenges in the national programme. They, therefore, make a case for adopting at the district level molecular tools (such as polymerase chain reaction, loop-mediated isothermal amplification, and other platforms) that can detect subpatent infections, non-P. falciparum/P. vivax species, mixed infections, peripheral parasitemia, placental malaria, and even gametocytes (precursor cells of the parasite in the host blood).
Artemisinin-based antimalarials constitute the front-line treatment for malaria. However, there is increasing evidence of many of the ACT drugs losing their efficacy. According to the authors, in the Greater Mekong Subregion (Cambodia, Laos, Myanmar, Thailand, and Vietnam), out of the six ACTs in use, more than two have failed in four countries. Following reports of resistance of the parasite to sulfadoxine-pyrimethamine (SP) in the NER, India switched from the artesunate-sulfadoxine pyrimethamine (ASSP), the predominant ACT that was being used in the country, to artemether lumefantrine (AL) in 2013 in the region. But recent studies indicate that resistance towards SP is emerging in other parts of the country as well. “The longevity of the ACT ASSP in India is doubtful due to resistance mutation accumulation,” argue Rahi and Sharma.
Resistance to artemisinin is associated with mutations in a malaria parasite protein called Kelch 13 (K13). The authors, therefore, stress the need for generating data on the K13 mutations in P. falciparum. According to them, nearly 50 K13 mutations have been identified in South Asia of which nine have been validated in India. But the others require corresponding clinical data on treatment failure. Besides, the role of 14 other mutations found in India, including four new ones, needs to be studied. Periodic monitoring of clinical efficacy and continuing therapeutic efficacy studies, combined with molecular epidemiology, are needed to keep track of emerging drug resistance and help the country to quickly switch over to an effective ACT.
“Though much needed, data on insecticide resistance, frequency, intensity and mechanism of resistance are not routinely generated by the national programme.”Manju Rahi & Amit SharmaThe Lancet
The authors have also drawn attention to the felt need for better vector control products for diverse entomological requirements. The mainstay of vector control against malaria is insecticide-treated nets, including long-lasting insecticide-treated nets (LLINs), and indoor residual sprays (IRS). While the malarial parasite develops drug resistance, the vector (mosquito) that transmits the infection develops insecticide resistance. DDT, malathion, and synthetic pyrethroids are predominantly used for IRS and deltamethrin and alpha-cypermethrin are used for impregnated bed nets. “Though much needed, data on insecticide resistance, frequency, intensity and mechanism of resistance are not routinely generated by the national programme,” the paper notes. “Also,” the authors add, “there is a lack of data on intensity assays which, as per WHO’s recommendation, should be taken into account for decision making on when to switch over to other effective insecticides.”
In the eagerness to phase out DDT, synthetic pyrethroids are thoughtlessly being used both in IRS and LLINs in some malaria endemic areas of India, the authors point out. “Cross-resistance within the same class of insecticides is a common occurrence. Therefore, where deltamethrin resistance has occurred, resistance to other synthetic pyrethroids is not far [behind],” the paper notes. “Though insecticide resistance management strategies are recommended, these are not actively pursued or planned despite evidence of emergence of insecticide resistance.”
Also, as in the case of diagnostic kits, access to even insecticide-treated nets in India is through the Health Ministry’s national malaria programme. This limitation creates a deficit in the ready availability of bed nets (including LLINs) for households with more members, visitors, and inaccessible populations, as well as during emergencies, such as floods, the paper points out. To strengthen vector control, the authors have recommended commercial availability of insecticidal bed nets and LLINs.
The mainstay of vector control is insecticide-treated nets. A fever ward at the Institute of Child Health and Hospital for Children, Chennai, in November 2021. (Photo used for representational purposes.) | Photo Credit: JOTHI RAMALINGAM B.
They have also suggested exploration of novel vector control tools such as using the antiparasitic drug ivermectin in cattle and humans to serve as endectocides for the malaria vector. Endectocides are veterinary parasiticides, and the idea is that when mosquitoes feed on the blood of treated cattle/humans it reduces the possibility of their survival irrespective of their biting pattern or host preferences. Also, cattle treated with these products faecally excrete residues that are toxic to dung-inhabiting insects, including mosquitoes.
Rahi and Sharma have suggested that India should consider testing and evaluating ivermectin as an endectocide in cattle first because Anopheles culcifacies, the primary malaria vector that is responsible for about 70 per cent of malaria transmission in the country, is zoophilic (feeds on the blood of humans and animals). “We have delineated the steps for its evaluation in Indian settings beginning from assessing the susceptibility of Indian vectors to ivermectin, followed by finding the lethal dose, preclinical studies and finally cattle and human trials recently,” they write. India is already administering ivermectin as part of mass drug therapy to prevent lymphatic filariasis. Therefore, expanding its use as an endectocide should be feasible, they note.
Last, but not the least, Rahi and Sharma point out that although there are many agencies working in the field of malaria, there is need for more communication, coordination, and cooperation among them at the local or central level for malaria control. “Enhancing synergy amongst various stakeholders would also catalyze the malaria elimination plans,” the paper emphasises.
