Malaria-attributable morbidity and mortality in different States and Union Territories (UTs) of India during 2014–2017*.
India is ecologically vast and has close to a billion-population living at risk of malaria. Given the evidence-based present-day intervention tools and large-scale implementation, India has recorded declining trends in disease transmission from 2 million cases in 2001 to close to a million cases in 2017 and embarked upon malaria elimination in keeping with the Global Technical Strategy by 2030. India is malaria endemic, but transmission intensities varied across its landscape with just few States of the east, central and northeast contributing bulk (80%) of total positive cases. Plasmodium falciparum and P. vivax are the predominant infections of which there has been steady increase in proportions of the former for constituting >60% of total cases what was 50:50 in 2001, a phenomenon attributed to emerging drug resistance. With the rolling out of the available intervention tools, malaria elimination is foreseeable yet there are multiple challenges which must be addressed to overcome the constraints. We strongly advocate continued disease surveillance and monitoring, universal coverage and intensification of core-interventions for prevention and treatment prioritizing high-risk States, strengthening cross-border collaborations for information sharing and coordinated activities, and above all sustained allocation of resources, creating the enabling environment to end malaria transmission.
- malaria elimination
- Plasmodium falciparum
- mosquito vectors
- insecticide resistance
- Southeast Asia
The advent of new intervention tools including Noble prize-winning discovery of Artemisinin by Tu Youyou for treatment of malaria combined with large-scale implementation of insecticide-treated netting materials for vector containment has once again renewed the optimism of malaria elimination globally. Malaria map is shrinking with more than 35 countries certified to be malaria free, and another 21 countries that are likely to reach zero indigenous transmission (categorized as E-2020) are set to be declared malaria free by 2020 [1, 2]. Many more countries are moving forward from control to elimination. The Global Technical Strategy for Malaria 2016–2030 envisages: (i) to reduce global malaria mortality rates and case incidence by at least 90% compared to 2015 levels, (ii) to make at least 35 countries malaria free that reported cases in 2015 and (iii) preventing re-establishment in countries with no indigenous transmission . Among member countries of the Southeast Asia Region of WHO (SEAR), Maldives and Sri Lanka have already been certified malaria free in 2015 and 2016, respectively, and Bhutan is targeting elimination in the foreseeable future. In the past decade, India has registered drastic decrease in cases and have formulated National Framework for Malaria Elimination (2016–2030) in close alignment with the Global Technical Strategy for Malaria, Roll Back Malaria Action (RBM), Investment to defeat Malaria (AIM) and the Asia Pacific Leaders Malaria Alliance (APLMA) for shared experiences and coordinated action to eliminate malaria (zero indigenous cases) throughout the country by 2030 . The said task is set to be accomplished in phased manner with the following objectives: (i) eliminate malaria in all 26 low-to-moderate transmission States/Union Territories (UTs) by 2022, (ii) reduce the case incidence to <1 per 1000 population by 2024 in all States/UTs, (iii) interrupt indigenous transmission throughout the country by 2027 and (iv) prevent re-establishment of local transmission and maintain malaria-free status by 2030 and beyond.
India is historically endemic for both
2. Malaria transmission in India: current distribution and parasite formula
Malaria transmission is heterogenous across Indian landscape for its diverse ecology and multiplicity of disease vectors . Malaria is a serious public health concern and almost all 36 States/UTs are consistently contributing cases, but transmission intensities varied ranging from low-to-moderate (Table 1). Among these, north-eastern, eastern and central Indian States consistently contributed 80% of the total disease burden having concentration of cases (API > 10) associated with large forest cover, ethnic tribes, poverty and high rainfall (Figure 1). These included States of Odisha (formerly Orissa) and Jharkhand (eastern India), Chhattisgarh and Madhya Pradesh (central India) and Meghalaya and Tripura (northeast India), which together contributed >65% of
|Total malaria cases||Deaths||Total malaria cases||Deaths||Total malaria cases||Deaths||Total malaria cases||Deaths|
|10||Jammu & Kashmir||291||21||0||216||8||0||242||11||0||226||0||0|
|32||D & N Haveli||669||90||1||418||46||0||375||30||0||297||16||0|
|33||Daman & Diu||56||4||0||84||18||0||48||7||0||37||4||0|
|All India total||1,102,205||722,546||562||1,169,261||778,821||384||1,090,724||716,213||331||840,838||533,481||103|
The reported cases and deaths; however, are far from acccurate for disease surveillance that can be best described as fragmented and there is no system in place to capture data from private and public sectors alike, least the asymptomatic cases ; WHO estimates are much higher to the tune of >10 million cases and deaths manifold . Nevertheless, the presented data showed disease transmisison trends in relation to existing interventions, and monitoring and evaluation in practice.
3. Multiple disease vectors and insecticide resistance
India holds the distinction in malaria epidemiological research for Noble prize-winning discovery that malaria is transmitted by mosquitoes by Sir Ronald Ross on the day of August 20, 1897, and for monumental work on faunistic surveys dating back to 1930s . Of the 58 anopheline species recorded in India , six major vector taxa are implicated in malaria transmission, including
|Sibling species prevalent in India (total identified)||Diagnostic cytotaxonomic/molecular tools||Breeding habitats||Feeding behavior (peak biting activity)||Resting habitats||Sporozoite infectivity (%)||Insecticide susceptibility status||Distribution range|
|A,B,C,D and E (5)||Fixed paracentric inversions, PCR based sequencing of 28S-D3 domain; ITS2-PCR-RFLP; rDNA ITS2||Rain water collections, riverine pools, rice fields, seepage water, streams, borrow pits, irrigation channels||Predominantly zoophilic except ‘E’ (A and B: 22:00–23:00; C and D: 18:00–21:00; no data for E)||Human-dwellings indoors and cattle sheds||Incriminated (0.3–20)||Resistant to DDT, malathion and pyrethroids||Throughout rural India|
|S, T, U and Form ‘V’ (4)||Fixed paracentric inversions; PCR based sequencing of rDNA ITS2; 28S rDNA-D3||Seepage water foothill streams, irrigation channels, river ecology, shallow wells||Sibling species ‘S’—highly anthropophilic (20:00–24:00); ‘T’—zoophilic||S—human dwellings indoors; T—cattle sheds||Incriminated||Highly susceptible to all residual insecticides||Throughout India except north-eastern States|
|rDNA ITS2; 28S rDNA-D3||Perennial foothill seepage water streams||Highly anthropophilic (01:00—04:00)||Human-dwellings indoors||Incriminated (3.0)||Highly susceptible to all residual insecticides||North-eastern of Arunachala Pradesh, Assam, Meghalaya, Manipur, Mizoram, Nagaland, Tripura, and Eastern State of Odisha|
|Karyotypic studies, polytene chromosome analysis, gene-enzyme variation, DNA probes, rDNA ITS2; SCAR-PCR||Jungle water pools, Elephant foot-prints||Highly anthropophilic (21:00—24:00)||Exophilic||Incriminated (1.9)||Highly susceptible to all residual insecticides||North-eastern of Arunachala Pradesh, Assam, Meghalaya, Manipur, Mizoram, Nagaland, Tripura|
|Mitochondrial DNA cytochrome oxidase 1 and cytochrome-b; rDNA ITS2; 28S rDNA-D3||Brackish water including swamps, salt water lagoons, creeks as well as fresh water||Predominantly zoophilic except indoor resting populations (21:00—04:00)||Both indoors and outdoors||Incriminated||Highly susceptible to all residual insecticides||Andaman & Nicobar Islands|
|Not applicable||Domestic containers, building construction sites, overhead water storage tanks, underground cement tanks, desert coolers||Predominantly anthropophilic (22:00—24:00)||Endophilic||Incriminated||Resistant to DDT and Malathion||Urban metropolitan cities of India|
Besides these dominant vectors, member species of
4. Drug-resistant malaria
Of the two prevalent malaria parasite species, the rising proportions of
Plasmodium vivaxmalaria: the neglected parasite
The Southeast Asian countries contribute most of the vivax cases (58%) in the World of which India is the largest contributor . Historically, much of the control efforts continue to be focused on control of falciparum malaria due to its associated severity and critical illness; the vivax malaria remained a neglected parasite . Paradoxically, control of falciparum malaria is rather measurable in relation to interventions due to development of gametocytaemia 9–10 days post primary infection; instead the formation of gametocytes in vivax malaria is concurrent within few days of initial infection even before the patient seeks treatment permitting uninterrupted transmission. This biological characteristic of vivax malaria along with intrinsic ability of formation of latent hibernating ‘hypnozoites’ has made control efforts a difficult proposition. Nevertheless, the control of vivax malaria is gaining eminence in the context of malaria elimination across the continents .
The magnitude of vivax malaria is huge but grossly underestimated throughout India and continues to be neglected . The transmission and distribution of vivax malaria varied across Indian States/UTs, but large concentrations of cases are occurring in urban metropolitan cities . Although it remains highly susceptible to CQ therapy [62, 63, 64, 65, 66], its elimination is one difficult issue owing to latent stage ‘hypnozoites’ in the liver causing relapses amounting to extended morbidity over months/years. The only available anti-relapse drug ‘primaquine (PQ)’ does not guarantee radical cure much due to extended therapy over days coupled with poor compliance resulting in repeated episodes [67, 68, 69]. In addition, the administration of PQ is associated with several issues including contraindication in special groups, that is, infants, pregnant or lactating mothers, and inborn glucose-6-phosphate dehydrogenase (G6PD) deficiency syndromes due to associated hemolytic anemia; these population groups are excluded from primaquine therapy. There exists no diagnostics for detection of G6PD at point-of-care in the present surveillance system except few laboratories procedure for which it is time consuming and impractical in field conditions where the problem exists. Further, given the available technologies, the detection of latent hypnozoites and sub-patent parasitemia is presently not built in the disease surveillance.
The primary attack of vivax malaria is invariably associated with acute paroxysm presenting classical symptoms but treatable and rarely fatal [70, 71, 72]; although few sporadic cases of CQ-resistant cases have been reported in India and several other countries . There is acute need of alternative 8-aminoquinolines, which are safe and universally applicable for radical cure across all population groups preventing relapses. As of today, we stand ill equipped to tackle this stubborn parasite calling for renewed attack both on parasite and disease vectors in reducing parasite reservoir which is likely to persist for long.
6. Asymptomatic malaria
India is historically endemic for malaria with record of devastating epidemics in the pre-DDT era and varied population groups have been subject to repeated attacks of malarial bouts, resulting in acquired immunity and consequent build-up of asymptomatic sub-patent parasitemia in the endemic communities, serving as infectious reservoir for continued transmission. In India, the surveillance program is aimed at taking blood-smears from those who are either febrile (active surveillance) or presenting themselves (passive surveillance) for malaria diagnosis or treatment. There is no built-in mechanism to detect asymptomatic cases or even low-density/sub-patent parasitemia in the endemic communities. These infections may go undetected with conventional diagnostic techniques leaving them untreated, except for mass-blood surveys/mass-drug administrations that are conducted only to contain epidemics. Asymptomatic malaria is more abundant than assumed and have been reported in different endemic States of India; however, the extent and distribution vary corresponding to transmission intensities [74, 75, 76, 77]. Asymptomatic parasitemia is often associated with gametocyte carriage and may persist infectious throughout the year to mosquito vectors. These gametocytes are unable to cause clinical symptoms of malaria, rather ensure the uninterrupted transmission of malaria in the presence of efficient vectors. Asymptomatic cases remain undetected and not accounted for disease incidence amounting to gross underestimates.
Asymptomatic malaria in India remains entrenched in low-socioeconomic groupings living in forest-fringe communities, particularly along inter-border areas (both inter-province and international borders), which are largely inaccessible (marred with insurgent activities), wherein healthcare infrastructure is meager or even non-existent. Such areas are ‘hot-spots’ for explosive disease outbreaks due to mixing/importation of drug-resistant strains associated with illegal migration more so in the northeast (the gateway to India) that shares wide international border with Myanmar, a member country of GMS (an epicenter of multi-drug resistant malaria) and other WHO SEAR countries. Asymptomatic malaria has been documented for both
7. Cross-border malaria
India shares vast international border with Nepal, Bhutan and China to the North, Myanmar to the East, Bangladesh to the South and Pakistan to the West. Among these, borders with Myanmar and Bangladesh are of immediate concern for their high endemicity and common disease vectors and ecology in the adjoining vicinity on either side of the border [79, 80]. These border areas are porous for cross-migration and have high forest cover inhabited by indigenous tribes living in impoverished conditions. These communities have poor access to healthcare services and are at high-risk to disease outbreaks attributed to drug-resistant strains originating from the GMS countries. These populations are largely marginalized and just as reluctant to seek treatment amounting to unattended parasite reservoirs. Border with Myanmar in particular is believed to be the corridor for entry of drug-resistant strains to northeast India for onward spread. The detection of artemisinin-resistant malaria in closer proximity to Indian border is seen as threat for making its way to India and beyond, similar to the path that was followed by CQ-resistant malaria [48, 49]. Cross-border malaria transmission from neighboring endemic countries can be daunting task and has regional implications jeopardizing the elimination efforts [81, 82]. For example, most cases reported in Bhutan (a country that is heading for malaria elimination), are imported from adjoining districts of Assam seeking treatment on other side of the border. Labor migration across borders engaged in developmental projects is unstoppable for want of livelihood and there exists every possibility of re-entry of malaria given the similar vectors and ecology. It is important to characterize the imported malaria strains enabling interventions well in place and time to prevent re-establishment of local transmission in declared malaria-free territories . Inter-country coordinated efforts are deemed essential to maintain vigil and strengthening border-posts (entry/exit doors) with capacity to detect and treat malaria in the migrant/itinerant labor force at the earliest available opportunity. In keeping the same mandate, India has joined hands with the Asia Pacific Malaria Elimination Network (APMEN) countries for shared experiences and coordinated action to achieve malaria elimination by 2030 . Mitigating cross-border malaria should be accorded priority in context of malaria elimination.
8. Strengthening health systems
India has a well-structured vector-borne disease control program in place providing logistics support along with guidance and monitoring/evaluation services to malaria endemic States/UTs [4, 7]. Utilizing the evidence-based intervention tools and large-scale implementation, India has registered notable decline in cases and malaria-attributable deaths in the preceding few years (Figures 2 and 3). Among these, roll-out of ACT for treatment of every single case of
9. The way forward
In India, some States (Sikkim and Himachal Pradesh) and UTs (Lakshadweep, Daman & Diu and Puducherry) are already reporting <100 cases, while others recorded substantial decrease (>50%) in cases over past few years, for example, Assam and Karnataka (Table 1). Given the reducing transmission levels, malaria elimination at sub-national level is seemingly achievable. However, the emergence of artemisinin-resistant malaria and possible spread, coupled with multiple insecticide resistance in disease vectors (Table 2), could reverse the gains for which disease surveillance, monitoring and evaluation should be the corner-stone activity.
We are thankful to Professor S. Manguin (Montpellier, France) for inviting us to contribute this article for this compilation, and the Directorate of National Vector Borne Disease Control Programme, Directorate of Health Services, Government of India for grant of permission to data access.
|ACT||artemisinin-based combination therapy|
|AIM||action and investment to defeat malaria|
|API||annual parasite incidence|
|APLMA||Asia Pacific Leaders Malaria Alliance|
|APMEN||Asia-Pacific Malaria Elimination Network|
|ASHA||Accredited Social Health Activist|
|AS + SP||artesunate + sulfadoxine-pyrimethamine|
|GMS||Greater Mekong Subregion|
|IDSP||Integrated Disease Surveillance Project|
|IRS||indoor residual spray|
|ITN||insecticide treated nets|
|ITS-2||internal transcribed spacer-2|
|LLIN||long-lasting insecticidal nets|
|NHM||National Health Mission|
|NVBDCP||National Vector Borne Disease Control Programme|
|PCR||polymerase chain reaction|
|Pfk 13||Plasmodium falciparum kelch 13|
|RBM||roll back malaria|
|RDT||rapid diagnostic test|
|SCAR||Sequence Characterized Amplified Region|
|SEAR||WHO Southeast Asia Region|
|WHO||World Health Organization|