Researchers Find Malarial Parasites Resistant to Last-line Drug

Even as India attempts to eradicate malaria by 2030, researchers have reported malarial parasites resistant to drugs.

(Photo: iStock)

Terming it as “alarming”, Indian researchers have for the first time reported cases of malarial parasites resistant to artemisinin- a top last line anti-malarial drug.

The cases of partial artemisinin resistance were identified in 20 patients in the eastern Indian state of West Bengal and documented in two separate studies that analysed data from a total of 362 patients over a three-year period.

The work was carried out by researchers Somenath Roy (Vidyasagar University, Midnapore), Sabyasachi Das (Lincoln University College, Selangor, Malaysia) Amiya K. Hati (Calcutta School of Tropical Medicine, Kolkata), and Bhaskar Saha (National Centre for Cell Science, Pune).

A delay in the clearance of malaria parasites from the bloodstream following treatment with an artemisinin-based combination therapy (ACT) is referred to as artemisinin resistance. WHO currently recommends five different ACTs.

In ACTs, artemisinin compounds reduce the number of parasites during the first 3 days of treatment (reduction of parasite biomass), while the role of the partner drug is to eliminate the remaining parasites (cure).

Artemisinin-based combination therapies (ACTs) are recommended by WHO as the first-and second-line treatment for uncomplicated P. falciparum malaria as well as for chloroquine-resistant P. vivax malaria.

The findings assume significance as South Asia sits in the middle of the malaria corridor that cuts from Southeast Asia to Africa.

As per the World Malaria Report, India contributes 89 percent of the total malaria incidence in southeast Asia region. India is also charting a course to eliminate malaria by 2030.

Why is this a Cause of Concern?

In the studies, the patients were found to be resistant to the recommended combination drug therapy of artesunate-sulfadoxine-pyrimethamine (ASSP) and continued to show presence of malarial parasites (P. falciparum) with persistence of fever even after three days of taking the drugs.

“This is a sign of early treatment failure which leads to partial artemisinin resistance,” said study author Somenath Roy, professor of human physiology at the Vidyasagar University.

As a result of this resistance, the artemisinin compound is less effective in clearing all parasites within a three-day period among patients who are infected with partial artemisinin-resistant strains of malaria, the researchers said.

The team then used an alternative strategy to successfully treated the drug-resistant patients. They administered the drug combo of artemether-lumefantrine .

This approach worked because of the high efficiency of lumefantrine and because the dose of artemisinin was higher (six doses than three)

Further, the studies also shed light on late treatment failure which means that the parasites reappeared in the blood stream seven to 42 days after treatment with ASSP. This was because sulfadoxine-pyrimethamine could not wipe out the parasites.

The novelty of the studies, according to Roy, lies in the genetic evidence to resistance. The team identified previously unseen mutations in the kelch13 gene.

“In this study, we identified G625R as a potential novel mutation that, along with R539T, is associated with artemisinin resistance. Other mutations in kelch13 have previously been reported, but how this newly identified mutation affects artemisinin resistance and the outcome of infection remains to be elucidated,” the authors note in the study.

Although artemether–lumefantrine is recommended in northeastern India, artesunate–sulfadoxine–pyrimethamine is still the first-line medicine in the rest of India.

What Does this Mean for India?

“Our findings with regard to early treatment failure related to artemisinin resistance and late treatment failure due to partner-drug resistance emphasise the need for increased surveillance of drug resistance in order to manage the spread of resistant parasites,” the study concludes.

India is targeting malaria elimination by 2030 in sync with the Global Technical Strategy (GTS) for Malaria 2016-2030 of World Health Organisation.

According to a 2015 WHO ‘Status report on artemisinin and ACT resistance’, artemisinin resistance probably emerged in 2001 and is confirmed in Cambodia, Laos, Myanmar, Thailand and Vietnam.

According to government data, malaria is mainly concentrated in the states of Orissa, Chattisgarh, Jharkhand, Meghalaya, Mizoram and Tripura because of the inaccessible terrain (many areas get cut off post monsoon) and presence of efficient vectors that transmit malaria.

However, the World Malaria Report 2018, shows that in the year 2017, reported malaria cases declined by 24 percent as compared with 2016. This is equivalent to three million fewer cases in that period.

India has a vision of a malaria-free country by 2027 and eradication by 2030 according to the National Strategic Plan (NSP) for malaria elimination (2017-2022).

Neighbour Sri Lanka has achieved malaria elimination by deploying malaria mobile clinics besides strengthening surveillance system.