The Eijkman-Oxford Clinical Research Unit (EOCRU) opened in 2008 within the Eijkman Institute of Molecular Biology (EIMB), situated on the large Salembacampus of the Faculty of Medicine University of Indonesia (FMUI) and CiptoMangunkusumo Hospital in Central Jakarta. EOCRU and its Indonesian hosts and partners collaboratively develop a research agenda of interest and relevance to Indonesian providers and their patients. Through more broadly relevant and high-impact clinical research endeavors, EOCRU deliberately cultivates technical capacities and people within Indonesia with the aim of fostering further independent clinical research. The direct access to patients suffering tropical and neglected infectious diseases allows the collaborative efforts to deliver tangibly better health outcomes for them. Previous or ongoing research include adjunctive dexamethasone therapy for TB meningitis patients living with HIV, hypnozoitocidal therapies for radical cure of Plasmodium vivax malaria, experimental live sporozoite vaccines against malaria, diagnostics for G6PD deficiency and CYP2D6 pharmacogenetics in connection with that therapy, mechanisms of primaquine hemolytic toxicity in G6PD-deficient patients, and assessment of automated malaria diagnostic instruments. Additionally, this unit investigates the impact of population mobility on malaria importation risks by applying big data cellphone-based geospatial analysis, quantifying burdens of morbidity and mortality of infectious and non-infectious diseases in relation to geography, socio-demography, and poverty in Indonesia.
Deeper Understanding and Better Health Outcomes
EOCRU has long focused on trials assessing the treatment of vivax malaria. Millions of cases of malaria occur in Indonesia each year, with about half of those caused by Plasmodium vivax. This species places dormant forms that awaken in people in the months following infection to cause repeated attacks of malaria. Arresting acute vivax malaria and preventing recurrent attacks requires treatment with two classes of drugs, one aimed at each. Assessing the safety and efficacy of the many possible combinations of such therapies ensures access to those treatments.
The therapeutics for Plasmodium vivax malaria includes two problems of human genetics: 1) hemolytic toxicity of the drug called primaquine in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; and 2) impaired metabolism of primaquine by natural polymorphism of cytochrome P-450 type 2D6 (CYP2D6). Primaquine is the only currently available drug effective against the dormant liver stages of P. vivax. Research at EOCRU takes aim at both of these issues in terms of diagnostics and understanding molecular mechanisms of these problems in order to ensure patients with vivax malaria are safely and effectively treated every time.
In 2017, EOCRU and FMUI jointly created the Universities of Indonesia and Oxford Clinical Research Laboratory (IOCRL) within the FMUI Department of Parasitology, with the aim of expanding its clinical research activities. New areas of interest include central nervous system infections, tuberculosis, HIV and antimicrobial resistance. TB meningitis, the most serious form of tuberculosisin patients living with HIV,is common in Indonesia. Aclinical trial of adjunctive dexamethasone therapy has been undertaken by EOCRU and its partners in striving to improve the quality of life and survival of these patients. The global rise in drug-resistant infections, a consequence of antimicrobial usage and abuse, is one of the greatest public health challenges worldwide. In Indonesia, high-quality data on the burden and associated morbidity, mortality and economic cost of antimicrobial resistance are lacking. EOCRU aims to systematically study antibiotic access and usage, vital for developing biomedical and social interventions to curb drug-resistant infections.
Where We Work
EOCRU operates within two historic institutions in the center of Jakarta: the Eijkman Institute of Molecular Biology (EIMB), and the Faculty of Medicine University of Indonesia (FMUI). We also work with partners at the University of North Sumatra at Medan, Hasanuddin University at Makassar, Udayana University at Bali, the National Malaria Control Programme, and the Health Directorate of the Indonesian Army at Jakarta. We work within two hospitals in Jakarta, CiptoMangunkusumo Hospital and PersahabatanHospital – each a teaching hospital affiliated with FMUI. We also work at remote hospitals, clinics, and villages at study sites on Sumatra, Java, Bali, Alor, and Sumba islands. EOCRU also collaborates regionally, with research activities in Cambodia, Nepal, and Pakistan, as well as routinely collaborating with the World Health Organization (WHO) in Geneva, Delhi (SEARO), Manila (WPRO), and Cairo (EMRO) on research and policy consultations. EOCRU engages and organizes capacity strengthening in malaria diagnostics and surveillance services to 10 regional laboratories and 34 provinces in Indonesia with Global Fund and NMCP resource support.
- Developed the clinical and laboratory evidence demonstrating the crucial importance of CYP2D6 polymorphisms to therapeutic success of primaquine against dormant liver stages of P. vivax.
- Executed two clinical trials of primaquine therapy in Indonesian soldiers representing the first demonstrations of safety and efficacy against relapsing malaria when combined with modern blood schizontocidal drugs (2013, 2015).
- Played a leadership role in the creation of WHO’s Global Technical Strategy for Malaria Control and Elimination (2015) and its Technical Brief for the Control and Elimination of Plasmodium vivax (2015).
- Hosted the Fifth International Conference for Plasmodium vivax Malaria Research at Bali in May 2015
- Played a leadership role in the formulation of WHO policy and recommendations regarding the problem of primaquine toxicity in G6PD-deficient patients, serving on that Evidence Review Group (2014).
- Described a laboratory model for the highly diverse G6PD deficiency phenomenon using normal red blood cells treated with copper as a crucially important aid in assessing diagnostic devices or technologies (2014).
- Hospital-based studies lead to demonstration of Plasmodium vivax malaria as pernicious and often fatal and positing of a hypothesis of the infection being primarily of erythropoietic tissues rather than vascular sinuses (2013).
- First geospatial high-resolution (1 km2) mapping of Plasmodium falciparum and P. vivax in Indonesia (2011, 2012).
- First spatial distribution maps of all 20 Anopheles malaria vectors across Indonesian archipelago (2012), along with comprehensive cataloguing of the bionomics of each species and that evidence.
Baird JK. Telling the human story of Asia’s invisible malaria burden. Lancet 2017; 389: 781-782.
Ding XC, Ade MP, Baird JK, et al. Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: target product profiles. PLoSNegl Trop Dis 2017; 11:e0005516.
Satyagraha AW, Sadhewa A, Elvira R, et al. Assessment of point-of-care diagnostics for G6PDdeficiency in malaria endemic rural eastern Indonesia. PLoSNegl Trop Dis 2016; 10: e0004457.
Nelwan EJ, Ekawati LL, Tjahjono B, et al. Randomized trial of primaquinehypnozoitocidal efficacy when administered with artemisinincombinedblood schizontocides for radical cure of Plasmodium vivax in Indonesia. BMCMedicine 2015; 13: 294.
Baird JK, Valecha N, Duparc S, White NJ, Price RN. Diagnosis and treatment of Plasmodium vivax malaria. Am J Trop Med Hyg 2016; 95(6 Suppl): 35-51.
Baird JK. 2015. Point-of-care G6PD diagnostics for Plasmodium vivax malaria is a clinical and public health urgency. BMC Medicine 13: 296.
Kheng S, Muth S, Taylor WR, et al. Tolerability and safety of weekly primaquine against relapse of Plasmodium vivax in Cambodians with glucose-6-phosphate dehydrogenase deficiency. BMC Medicine 2015; 13: 167.
Nguyen TD, Olliaro P, Dondorp AM, Baird JK, Lam HM, Farrar J, Thwaites GE, White NJ, Boni MF. Optimum population-level use of artemisinin-combined therapies: a modelling study. Lancet Global Health 2015; 3: e758-766.
Battle KE, Guerra CA, Golding N, et al. Global database of matched Plasmodium falciparum and P. vivax incidence and prevalence records from 1985-2013. Sci Data 2015; 2: 150012.
Baird JK. Evidence and implications of mortality associated with acute Plasmodium vivax malaria. Clinical Microbiol Rev 2013; 26: 36-57.
Gething PW, Elyazar IRF, Moyes CL, Smith DL, Battle KE, Guerra CA, Patil AP, Tatem AJ, Howes RE, Myers MF, George DB, Horby P, Wertheim HFL, Price RN, Müeller I, Baird JK, Hay SI. 2012. A long neglected world malaria map: Plasmodium vivax endemicity in 2010. PLoSNeglTropDis. 6:9.
Elyazar IRF, Gething PW, Patil AP, Rogayah H, Sariwati E, Palupi NW, Tarmizi SN, Kusriastuti R, Baird JK, Hay SI. 2012. Plasmodium vivax malaria endemicity in Indonesia in 2010. PLoS ONE. 7:5.
Elyazar IRF, Gething PW, Patil AP, Royagah H, Kusriastuti R, Wismarini DM, Tarmizi SN, Baird JK and Hay SI. 2011. Plasmodium falciparum malaria endemicity in Indonesia in 2010. PloS ONE. 6:6.
Elyazar IRF, Sinka ME, Gething PW, Tarmisi SN, Surya A, Kusriastuti R, Winarno, Baird JK, Hay SI, Bangs MJ. 2013. The distribution and bionomics of Anopheles malaria vector mosquitoes in Indonesia. Adv Parasitol. 83: 171-264.
Elyazar IRF, Hay SI, Baird JK. 2011. Malaria distribution, prevalence, drug resistance and control in Indonesia. AdvParasitol. 74: 41-175.