Malaria

Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the malaria parasites multiply in the liver, and then infect red blood cells.

Symptoms of malaria include fever, headache, and vomiting, and usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs. In many parts of the world, the parasites have developed resistance to a number of malaria medicines.

Key interventions to control malaria include: prompt and effective treatment with artemisinin-based combination therapies; use of insecticidal nets by people at risk; and indoor residual spraying with insecticide to control the vector mosquitoes.

The importance of malaria research in Viet Nam

Malaria remains a public health challenge in Viet Nam despite a substantial reduction in the incidence of disease over the last 20 years. In 2016 there were only 10,446 cases reported to the National Malaria Control Programme (Annual Report NMCP 2016) and 03 deaths attributed to malaria. Viet Nam was one of the first countries to deploy artemisinin derivatives in its fight against malaria over 20 years ago. Since 2005, Viet Nam has used dihydroartemisinin-piperaquine (DHA-PPQ) as the first-line treatment for falciparum malaria. The spread of artemisinin resistance in Plasmodium falciparum and the subsequent loss of partner antimalarial drugs in the Greater Mekong subregion (GMS)

represent one of the greatest threats to the control and elimination of malaria. Artemisinin resistance is associated with mutations in the Pfkelch gene; initially multiple independent kelch mutations were observed, but gradually the single dominant artemisinin-resistant P. falciparum C580Y mutant lineage which has arisen in Western Cambodia, is becoming the dominant resistant malaria parasites, and subsequently acquiring resistance to piperaquine. We now find that this Pf kelch C580Y lineage which had reached the south of Vietnam by 2011. In 2016 in Binh Phuoc the Pf Pailin lineage had outcompeted all other parasites, and now accounted for nearly all P. falciparum isolated (94%; 85/90), and it had acquired piperaquine resistance evidenced by amplification in the Pf plasmepsin II,III gene. This multi-drug resistant Pf Pailin lineage is responsible for an alarming rise in dihydroartemisinin-piperaquine treatment failure in this area with recrudescence rates now exceeding 50%.

These findings present policymakers in Vietnam with a dilemma, because the current recommended second-line regimen combines quinine with doxycycline which not well tolerated and so adherence to the required seven day regimen is poor. Although the combination DP and mefloquine (Triple ACT) has high efficacy on artemisinin resistant P. falciparum it has not approved and needed to be monitored for side-effects. Newer antimalarials such as cipargamin (KAE 609), KAF 156, and artefenomel (OZ 439) are in phase II of development and will likely not reach the market until 2020.

The prevention of relapse in P.vivax infections, ongoing studies would answer whether the short course regimen of primaquine is as effective as the 14 day regimen and how to manage patient with G6PD deficiency. The long acting 8-aminoquinoline (Tafenoquine) would be a promising candidate for radical cure for vivax patients worldwide.

Our malaria researchers

  • Prof Tran Tinh Hien, MD, PhD
  • Nguyen Thanh Thuy Nhien, PhD
  • Ngo Viet Thanh, MD
  • Nhu Thi Hoa, MD, MSc
  • Nguyen Hoang Chau, MD
  • Do Hung Son, MD, MSc
  • Nguyen Thi Kim Tuyen, MSc
  • Nguyen Tam Uyen, MSc
  • Nguyen Thanh Tong, MSc
  • Nguyen Thi Tuong Vy, MSc
  • Pham Nguyen Huong Thu, BSc

What we’re doing to improve outcomes for malaria patients

Our research studies are to define and develop new antimalaria drugs: Despite the Malaria Control Program, Viet Nam still adheres to the dihydroartemisinin-piperaquine combination because there is no alternative anti-malarial drug which is as good, as available, or as affordable as the current one. We initiate research to find out new antimalarial drugs such as new combinations (triple ACT): DP+M, Coartem+ amodiaquine, KAF156+ lumefantrine …KEA 609 OZ 439 or to re-enforce the armory to fight against malaria.

As well as clinical studies, our malaria researcher conduct many activities focused on improving patient outcomes, including:

  • Genetics surveillance of resistant P. falciparum
  • Ex-vivo and in vitro drug susceptibility testing
  • Molecular markers of antimalarial drugs resistance
  • Parasite and host interaction
  • Public engagement

Our malaria research locations

Our studies have been conducted in several provinces of Viet Nam including Binh Phuoc (Phuoc Long, Bu Gia Map), Gia Lai (Krongpa, Iato),  Ninh Thuan (Phuoc Thang Bac Ai) …

Binh Phuoc is a mountainous province in the western region of the Southeast of Viet Nam. It is surrounded by Lam Dong and Dong Nai provinces on the east, Tay Ninh Province and Cambodia on the west, Binh Duong province on the south, Dak-Lak and Cambodia on the north. Binh Phuoc province has 8 districts.

The area of Binh Phuoc is a plateau in the north and northeast and is mountainous and hilly the west and South West. It is located on in a specific region with tropical and cross-equatorial monsoon climate. There are 2 distinct seasons: the rainy season and dry season. The average temperature is high and stable from 25.80 C to 26.20 C.

With a total natural area of 6,855.99 km2 which is covered by forests, Binh Phuoc province plays a very important role in protecting the ecological environment of the Southeast region and regulating the flow of rivers.

Our malaria research collaborations/partnerships

Important milestones in our malaria research

  • 2010: Invivo susceptibility of artesunate in treatment of adult with P. falciparum malaria in Binh Phuoc Province, Vietnam in collaboration with WHO
  • 2011: Tracking Resistance to Artemisinin (TRAC): collaboration with Mahidol University and Worldwide Antimalarial Resistance Network (WWARN) funded by DFID UK
  • 2014: Collaboration with Novartis, GSK, MMV to assess the KAE609, KAF156, Tafenoquine in several clinical trials in Vietnam

Key malaria publications

  1. Imwong M, Hien TT, Thuy-Nhien NT, Dondorp AM, White NJ. Lancet Infect Dis. 2017 Oct;17(10):1022-1023. Spread of a single multidrug resistant malaria parasite lineage (PfPailin) to Vietnam. doi: 10.1016/S1473-3099(17)30524-8. .
  2. Thuy-Nhien, N., Tuyen NK, Tong NT, Vy T, Thanh NV, Van HT, Huong-Thu P, Quang HH, Boni MF, Dolecek C, Farrar J, Thwaites GE, Miotto O, White NJ, Hien TT. (2017). K13-Propeller Mutations in Plasmodium falciparum Populations in Malaria Endemic Regions of Vietnam from 2009 to 2016. Antimicrob Agents Chemother. doi:1128/AAC.01578-16
  3. Thanh NV, Thuy-Nhien N, Tuyen NT, Tong NT, Nha-Ca NT, Dong LT, Quang HH, Farrar J, Thwaites G, White NJ, Wolbers M, Hien TT. (2017). Rapid decline in the susceptibility of Plasmodium falciparum to dihydroartemisinin-piperaquine in the south of Vietnam. Malar J, 16(1), 27. doi:1186/s12936-017-1680-8
  4. Nguyen TN, Thu PN, Hung NT, Son DH, Tien NT, Van Dung N, Quang HH, Seidlein LV, Cheah PY, Dondorp AM, Day NP, White NJ, Hien TT. (2017). Community perceptions of targeted anti-malarial mass drug administrations in two provinces in Vietnam: a quantitative surveyMalar J, 16(1), 17. doi:1186/s12936-016-1662-2
  5. Hien, T. T., White, N. J., Thuy-Nhien, N. T., Hoa, N. T., Thuan, P. D., Tarning, J., Nosten, Magnusson B. ,  Jain JK.,  Hamed, K. (2017). Estimation of the In Vivo MIC of Cipargamin in Uncomplicated Plasmodium falciparum Malaria. Antimicrob Agents Chemother, 61(2). doi:10.1128/AAC.01940-16
  6. Thuan PD, Ca NT, Van Toi P, Nhien NT, Thanh NV, Anh ND, Phu NH, Thai CQ, Thai le H, Hoa NT, Dong le T, Loi MA, Son do H, Khanh TT, Dolecek C, Nhan HT, Wolbers M, Thwaites G, Farrar J, White NJ, Hien TT . (2016). A Randomized Comparison of Chloroquine versus Dihydroartemisinin-Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam. Am J Trop Med Hyg, 94(4), 879-885. doi:4269/mtmh.15-0740
  7. Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, Suangkanarat P, Jeeyapant A, Vihokhern B, Wongsaen K, Van Hue D, Dong le T, Nguyen TU, Lubell Y, von Seidlein L, Dhorda M, Promnarate C, Snounou G, Malleret B, Rénia L, Keereecharoen L, Singhasivanon P, Sirithiranont P, Chalk J, Nguon C, Hien TT, Day N, White NJ, Dondorp A, Nosten F. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malaria J. 2015 Sep 30;14:381.
  8. Son DH, Thuy-Nhien N, von Seidlein L, Le Phuc-Nhi T, Phu NT, Tuyen NTK, Tran NH, Van Dung N, Van Quan B, Day NPJ, Dondorp AM, White NJ, Thwaites GE, Hien TT. The prevalence, incidence and prevention of Plasmodium falciparum infections in forest rangers in Bu Gia Map National Park, Binh Phuoc province, Vietnam: a pilot study. Malar J. 2017 Nov 6;16(1):444. doi: 10.1186/s12936-017-2091-6.