Epidemiology of malaria and chloroquine resistance in Mizoram, northeastern India, a malaria-endemic region bordering Myanmar

Abstract

Background: Mizoram, a northeastern state in India, shares international borders with Myanmar and Bangladesh and is considered to be one of the key routes through which drug-resistant parasites of Southeast Asia enter mainland India. Despite its strategic location and importance, malaria epidemiology and molecular status of chloroquine resistance had not been well documented, and since chloroquine (CQ), as the first-line treatment in Plasmodium falciparum infection was discontinued since 2008, it was expected that CQ-sensitive haplotype would be more abundant. Methods: Malaria epidemiology data for the period 2010 to 2018 was collected from the office of State Vector Disease Control Programme. Plasmodium falciparum-positive blood samples were collected from government district hospitals, community health centres, primary health centres, sub-centres, and diagnostic centres from six malariaprone districts. The samples were processed and analysed using genes-P. falciparum chloroquine-resistant transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) via sequencing of PCR amplicon from 2015 to 2017. Results: Malaria occurred throughout the year and P. falciparum accounted for > 89% of total malaria cases. During 2010-2018, the highest number of malaria incidence was recorded in Lawngtlai (36% of total malaria cases; average API 2010-2018 of 34.8) while Champhai remained consistently low (0.4%; average API 2010-2018 of 0.04). Males of ≥ 15 years old contributed maximum (35.7%) among gender and age malarial distribution recorded during 2014-2018. Death due to malaria gradually decreased over the years. A higher abundance of mutated pfcrt (58.5% of the total sample analysed) and a lower prevalence of mutated pfmdr1 (48.7%) were observed. All mutations identified for pfcrt belong to the Southeast Asian CVIET haplotype. Only a single point mutation was observed at 86 (N → Y) position in pfmdr1 (48.7%). The key N86Y mutation in pfmdr1 that had been shown to modulate CQR was found in 67.1% of the samples positive for the CVIET haplotype. Conclusions: This is the first report that details malaria epidemiology and also the molecular status of CQ-resistance in P. falciparum population of the region. The efforts of the State Vector Borne Disease Control Programme have proved to be quite effective in controlling the malaria burden in the state. Despite the discontinuation of CQ for a decade, local P. falciparum is observed with decreased CQ-sensitive haplotype. It is believed that the present findings will form a basis for further studies on genetic diversity in P. falciparum, which could confer better understanding of the complexity of the disease in Southeast Asia.

Effect of climate change and deforestation on vector borne diseases in the North-Eastern Indian state of Mizoram bordering Myanmar

“…Plasmodium falciparum is responsible for the majority of the cases, and accounts for >90% of the malaria cases [22]. Based on the cumulative cases from 2008-2018, and population density, 1.1% of the total population is estimated to be affected by malaria on an average per year, and is the second most malarious state in NE India after Meghalaya [24].…”

“…Mizoram, located between latitude 21°58′N -24°35′N and longitude 92°15′E -93°29′E is a NE state that lies within the Indo-Myanmar region, and one of the four biodiversity hotspots in India [22]. Mizoram's altitude ranges from 500-2157m, and the tropical humid climate of Mizoram is characterized by short and dry winter (part of November to February, 11-24 °C), and long summer (March to September, 18-33 °C) [22]. The monsoon season starts in May and extends till September, and June to August account for ~80% of rainfall.…”

Socio-economic and Household Determinants of Malaria in Adults Aged 45 and Above: Analysis of Longitudinal Ageing Survey in India (2017-2018)

“…[19]. On the other hand, Mizoram is considered to be one of the highly malaria endemic states in India [20,21]. One explanation for the unexpected numbers could be the study site where the survey was undertaken.…”

“…In sub-Saharan Africa, many adults who harbour the parasites rarely show clinical symptoms [22]. At Mamit, the average annual parasite index (API) from 2010 to 2018 was 34.4 (34 cases / 1000), one of the highest in the country [20]. During 2014 to 2015, there was a big spike in malaria cases in Mizoram, and in Mamit district, nearly 50% of the total population (8766 cases out of 17731) were affected in 2015 [20].…”

Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India

“…445,000 deaths and an estimated 216 million confirmed malaria cases—including an increase of about 5 million cases over and above what was recorded in 2015-were reported in 2016 1 . Malaria transmission in India potentially occurs through either P. falciparum or P. vivax infection 2 , 3 . In India, 844,558 malaria cases were reported in 2017, of which 529,530 cases were P. falciparum positive 4 .…”