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Mobile migrant populations in GMS pose a challenge to monitoring drug efficacy

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Results from the Mekong Therapeutic Efficacy Monitoring Network show increasing pockets of artemisinin resistance in the Greater Mekong Subregion. The challenge, now, is to develop innovative approaches to monitor drug resistance in highly mobile local migrant populations.

Mobile migrants might be at high risk of contracting malaria due to their occupations, working, for instance, in areas just cleared of forests.

Mobile migrants might be at high risk of contracting malaria due to their occupations, working, for instance, in areas just cleared of forests.

Malaria in mobile and migrant populations in the Greater Mekong Subregion (GMS) is a challenge for the containment and elimination of artemisinin resistance, including monitoring the effectiveness of anti-malaria drugs, as the discovery of mutations that neutralise artemisinin leads to efforts to chart their independent spread in different parts of the region.

“Parasite resistance to anti-malarial drugs is changing faster than was predicted and it is now known that artemisinin resistance has occurred not just at the Thailand-Cambodia border, but at multiple new areas throughout the region,” said Dr. Walter Kazadi, coordinator of the WHO Emergency Response to Artemisinin resistance (ERAR) regional hub.

With global and regional concern about the fast-evolving drug resistance situation, a Mekong Therapeutic Efficacy Monitoring Network (Mekong TES Network) was formed with the participation of member states and partners. The results of the therapeutic efficacy studies (TES) since 2008 have identified nine areas in the GMS with suspected resistance to artemisinin and three with confirmed resistance. The areas with confirmed resistance are Tak, at the Thailand-Myanmar border; Pailin at Cambodia-Thailand border and Champasak at Lao PDR-Thailand-Cambodia border.

“Therapeutic efficacy studies (TES) play an important role in supporting GMS countries develop and implement quality surveillance of antimalarial drug efficacy. The challenge is to develop innovative approaches to monitor drug resistance in local migrant populations when usual TES cannot be carried out due to their high mobility,” added Dr. Kazadi when addressing the start of two back-to-back workshops organized in Hanoi, Viet Nam, between 20 to 23 May 2014 by the ERAR regional hub in collaboration with the WHO Regional Offices for South-East Asia and the Western Pacific and the Global Malaria Programme in WHO headquarters.

The workshops were co-hosted by the National Institute of Malariology, Parasitology and Entomology of the Ministry of Health, Viet Nam with the WHO country office in Hanoi, Viet Nam.

The first workshop, with the Mekong TES Network, was to review and plan therapeutic efficacy studies to monitor antimalarial drug resistance in the GMS. The second focused on improving access to malaria control services for mobile and migrant populations in the GMS.

Intense mobility in the GMS is expected to increase in 2015 as the ASEAN Economic Community (AEC) ushers in a region with a single market and production base characterized by free flow of goods, services and labour – both skilled and unskilled. Poor young adults, who cannot earn enough to support their families in their places of origin are moving across ASEAN common borders to find employment in neighbouring countries. They are at high risk of contracting malaria due to their occupations, working, for instance, in mines and forested areas.

“Development projects in the GMS influence the malaria situation,” said Dr. Deyer Gopinath, the Malaria and Border Health Technical Officer in the ERAR regional hub. “The influx of foreign workers into one area can change the malaria parasite species ratio and can introduce drug resistant parasites. Further, without access to health services, migrant workers tend to self-medicate and exposure to unregulated substandard antimalarials and monotherapies exacerbate further the problem of artemisinin resistance,” added Dr. Gopinath.

Participants in the workshop on mobile and migrant populations in the GMS agreed to proactively seek innovative approaches to malaria prevention and treatment in these populations, including work site interventions with labour organisers, employers and the private sector. The workshop also agreed to engage other sectors, like mining and forestry, for effective control of malaria among migrant workers to reduce the risk of emergence and spread of arteminisin resistance.

“Engaging the private sector is crucial in providing diagnosis and quality treatment to mobile populations that are often located in remote areas and are difficult to target and access for surveillance,” said Dr Bouasy Hongvanthong, Director of the Centre for Malaria Parasitology and Entomology of Lao PDR.

The Mekong TES Network first met in Phuket in September 2007 where they agreed to a standardised protocol for conducting therapeutic efficacy studies. It also planned to consolidate laboratory networking across the GMS to assess and standardise molecular techniques differentiating recrudescence from reinfection, genotyping and use of molecular markers for resistance.

Participants at the TES workshop discussed the difficulty in monitoring artemisinin resistance in border areas particularly when trying to understand where the infection originally came from. They expressed concern that results found in one country influence that country’s drug policy, but in fact, the infection may have been acquired in another country. But this has also been a problem with in-country mobility of seasonal migrant workers moving across their own country, for instance, forest workers acquiring malaria infection in northwestern Cambodia then returning sick to their home province in the south.

The possible spread or independent emergence of artemisinin resistance out of the GMS region was also discussed. Participants pointed out that it would likely first occur in India, before reaching the African region. This underscored the importance of collaboration between the GMS TES network and Bangladesh, Bhutan, India, Nepal, Sri Lanka (BBINS) Malaria Drug resistance network.

“Meeting organisers invited representatives of the Indian National Institute of Malaria Research to discuss the malaria situation in India, control strategies, treatment policies and share results of their artemisinin resistance tracking studies,” said Dr Maria Dorina Bustos, Malaria Technical Officer, in WHO Thailand.

Though India is not part of the GMS TES network it, however, shares a long border with Myanmar and has a high malaria burden.

“An understanding of the malaria situation in the GMS countries benefits India and helps them to better plan malaria control activities and the tracking of artemisinin resistance, and vice versa,” added Dr. Bustos.

Topmost in the TES workshop discussions were mutations in the malaria parasite that underlie its resistance to artemisinin, which have been pinpointed for the first time. Researchers have identified mutations in the PF3D7_1343700 kelch propeller domain (K-13 propeller) of the parasite in an artemisinin-resistant parasite line, and investigated the prevalence of these mutations in patients with malaria, from samples collected between 2001 and 2012 across various provinces in Cambodia.

The researchers, in their investigations, found that in the provinces where artemisinin resistance is known to exist, the frequency of K-13 propeller mutations increased significantly over time. Conversely, this increase was not observed in provinces where there is no evidence of artemisinin resistance. Furthermore, patients who carried parasites with K-13 propeller mutations took significantly longer to clear the infection (with Day 3 positivity rate in more than 10% of cases) than patients carrying parasites without these mutations.

By testing for these genetic variants, public-health officials now plan to map malaria strains that are resistant to artemisinin derivatives in the GMS, with the hope of stemming their spread to Bangladesh, India and elsewhere.

Participants agreed that the recent identification of a marker for artemisinin resistance (mutations in K-13 gene) has led to a new working definition for both suspected and confirmed artemisinin resistance which can affect the way decisions are made about changes to drug policy. TES samples from the GMS countries are now undergoing K-13 assays in two reference laboratories in the region.

“In order to make decisions on drug policy change, we can now use TES results as well as the confirmatory results of molecular techniques. Our understanding is that the findings of K13 mutations and their correlation to clinical artemisinin resistance is evolving. For this reason, for the moment, TES results still remain the cornerstone of artemisinin resistance monitoring,” said Dr. Bustos.

 

 

 

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Written by malariacontainment

September 9, 2010 at 11:53 pm

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