In the last decade, India has seen a steep decline in malaria morbidity and mortality22. In most parts of the country, malaria prevalence and incidence have been consistently declining22. However, Mizoram is one of the few malaria-endemic pockets where the decrease in malaria prevalence has been relatively low and has even increased in the last two years, despite the COVID-19 pandemic. As per National Framework for Malaria Elimination (NFME), Mizoram falls under category 3 (intensified control phase); these are States/Union Territories having API > 123. Malaria control in Mizoram is critical for India’s malaria elimination efforts, as its western and eastern districts share porous international borders with Bangladesh and Myanmar, countries that are endemic to malaria.
Mamit, Lunglei, and Lawngtlai, the western districts of Mizoram, share international borders with Chittangong Hill Tract (CHT) of Bangladesh; the CHT comprises Rangamati, Bandarban and Khagrachhari districts. Of the 64 districts in Bangladesh, malaria is endemic in 13, and 19 million people are at risk24. In Bangladesh, from 2008 (84,690 cases) to 2020 (6,130 cases), malaria incidence has steeply declined by ~ 93%25. The remaining malaria cases are from the 13 of the 64 districts, and of these 13 districts, 3 (Rangamati, Bandarban and Khagrachhari) in the Chittagong Hill Tracts (CHT) contribute to ~ 90% of the malaria cases26. GIS analysis of public health sub-centre-wise malaria data of Mizoram from 2015-21 shows malaria is highly endemic in the western districts, and as we move towards the east, the malaria prevalence decreases steeply. It is best illustrated by the steep decrease in malaria cases as we move from Mamit district (> 10,000 cases) in the west, traversing the central districts of Kolasib/Aizawl and/or Serchhip to Champhai district (< 200) in the east. The high endemicity of malaria in the CHT and Western districts of Mizoram could be attributed to the favorable meteorological parameters-temperature, humidity, and rainfall. Studies predict malaria transmission is bounded by the thermal optimum of 17°C and 34°C 27–29. In addition, the relatively plain terrain of this region would also be conducive for breeding of vectors. As we move towards the East, the temperature and RH drops, and the altitude from the mean sea level increases, resulting in less favorable breeding conditions for mosquitoes and malaria transmission. Similar to Aizawl, Mizoram30, in CHT, the minimum temperature, RH and rainfall have shown a consistent upward trend in the last 4 decades, thus favoring mosquito breeding and malaria transmission. Multiple global climate models show an overall net increase in populations at risk and climate suitability for malaria31. The trend analysis shows there is a gradual shift in average maximum temperature towards less than 34°C, minimum temperature towards 18°C and reduction in diurnal temperature, thus favoring malaria transmission in the CHT and Western districts of Mizoram. Unless malaria transmission is stringently controlled in CHT and western districts of Mizoram, the effect of climate change could result in a more conducive ecological niche favoring malaria transmission in the central and eastern parts of Mizoram.
After a gradual decline in malaria prevalence from 2015-18, Mizoram has seen an uptick of cases from 2019 onwards, especially in its western districts. This trend is worrisome, especially with escalating malaria and the recent emergence of K13 independent ART resistance in the CHT of Bangladesh 10. Molecular screening of Pfkelch13 in NE carried out in 2014-15 has identified non-synonymous mutations (K189T and A578S) in Lunglei district, Mizoram32. ACT efficacy studies carried out in Lunglei district from 2011–2013 showed no correlation between K13 propeller mutation (A578S) and treatment failures33. In the last decade, studies have reported delayed clearance phenotypes from parasites in Central (Chhattisgarh), South-West (Goa), and NE (Assam, Arunachal Pradesh, and Tripura) India, independent of K13 gene polymorphisms34,35. Decreased ART sensitivity across India and CHT and the recent increase in malaria cases in Mizoram’s international borders necessitates the need for continuous surveillance of the parasite phenotypes, especially in Mizoram’s western districts. Unlike molecular surveillance, which can be carried out in filter paper spots, assessing ART resistance through ring-stage survival assays (RSA) will be challenging as it will involve the collection and quick transport of blood samples from these arduous terrains to a malaria culture facility. Effective malaria control in the Indo-Bangladesh border districts would require coordinated efforts by both countries. Unless malaria is effectively controlled in CHT, the porous Indo-Bangladesh borders will allow the movement of parasites and vectors to Mizoram’s western districts and vice versa.
The eastern districts of Mizoram share international borders with the Chin State of Myanmar. In addition to the geographical proximity, Mizoram shares deep cultural and religious ties with Myanmar, and the people are bonded by similar customs, traditions, and beliefs9. In these porous borders, people from Mizoram and Myanmar continue to move in both directions, leading to the free movement of parasites in either direction, complicating malaria control. Historically, South East Asia (SEA) has been a hotspot for the generation of acquired resistance to pyrimethamine, chloroquine, sulphadoxine, quinine, mefloquine, and most worryingly, artemisinins7. The first instance of drug resistance to chloroquine and SP in India has been from the NE region; these drug-resistant parasites are suspected to have entered the NE from SEA through the porous international borders36. In a state-wise study carried out across Mizoram from 2015-17, all the mutations identified in the pfcrt gene conferring chloroquine resistance belonged to the South-East Asian CVIET haplotype, suggesting an evolutionary link between the parasites in Mizoram and SEA7. In the Chin state of Myanmar that borders Mizoram, the K13 propeller mutations have been very low, and previous studies have not reported any decrease in ART sensitivity in this region37,38. However, in Homalin from the Sagaing region of Myanmar, 25 Km from Manipur (India), ~ 47% of the parasites carried propeller mutations37. Mizoram shares domestic borders with Manipur State in the north37. Unlike the western districts bordering Bangladesh, the elevated altitude and climatic variables are less conducive to mosquito breeding and malaria transmission in the Mizoram-Myanmar border. The current absence of ART-resistant parasites does not preclude the future entry of drug-resistant parasites through Mizoram-Myanmar’s porous international borders. GIS-based analysis shows the emergence of malaria (> 10 API) in 47 sub-centres in 2021 and out of these, the highest API (> 100 API) is recorded in two sub-centres of Champhai district, bordering Myanmar. These clusters have to be monitored to assess for the emergence of drug-resistant parasites.
In these high transmission malaria settings, it is also pertinent to track the status of Pv drug resistance. Pv parasites resistant to chloroquine have emerged in most Pv endemic countries39. Literature on Pv drug resistance is sparse in NE, and there are no reports on the status of Pv drug resistance in Mizoram. In India’s urban settings, Pv predominates40, and GIS analysis shows Pv cases to be concentrated in the urban districts of Aizawl East, Aizawl West, and Kolasib. Therapeutic efficacy studies, as assessed by response to treatment on day 2841, have to be carried out in Lungtian, Lungpher, Sangau, and Vawmbuk subcentres in Lawngtlai, where Pv predominates.
In addition to parasite surveillance within these international borders, it is imperative to continuously assess the vector population. A district-wise mosquito survey carried out from late 2000 to early 2010 shows a high density of Anopheles minimus in Western Mizoram and South Tripura, bordering Bangladesh (RMRC Dibrugarh, Unpublished data). Vector epidemiology and vector-parasite relationship can change spatio-temporally42,43, and is critical to devise vector-control strategies based on the existing malaria vectors.
In Mizoram, ~ 54% of the rural households are engaged in shifting cultivation, also known as Jhum cultivation, which involves slashing and burning of selected forest area, followed by a short period of growing mixed crops, harvesting, following, and subsequently, the site will be abandoned44,45. Jhum cultivation continuously exposes the farmers to malaria vectors as they stay and sleep in the forests. By opening up the forests, Jhum cultivation leads to associated streams, creating favorable breeding grounds for An. minimus 46. In recent years, the jhum cycle has reduced from 10–20 years to 2–3 years, and encroachment of virgin forested areas has led to new perennial malaria transmission zones47. Malaria control should include strategies to continuously track, test, and treat farmers involved in Jhum cultivation.
As our analysis shows, 5 of the 8 districts in Mizoram are high malaria transmission settings, and continuous exposure to Plasmodium in these endemic areas may result in low-density infections and/or asymptomatic carriers. The low-density infections from asymptomatic carriers can lead to malaria transmission48,49. For effective malaria control, strategies should include mass screening of the community with molecular tools. Continuous molecular surveillance and prompt treatment will greatly help lessen the malaria burden and break the transmission cycle in these high transmission settings.
Overall, an integrated management approach involving regional cooperation, molecular surveillance in sentinel sites, laboratory investigation of ART resistance using RSA, community level screening for detection of asymptomatic carriers, appropriate vector control strategies tailor-made for existing vectors, developing skilled manpower and infrastructure for molecular studies of malaria are required to effectively control malaria in this region.