SMRU : Shoklo Malaria Research Unit
Status:SMRU was established in 1986 in Shoklo. It is a field station of the faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, and is part of the Mahidol-Oxford Research Unit (MORU) supported by the Wellcome Trust (UK).
Read more about Health research activities in the region (brochure)
Location:The S.M.R.U is now based in Mae Sot and the activities extend to the populations living along the Thai-Myanmar border.
Beneficiaries:Population living along the border, including refugees and other migrants.
- 1. To treat and care for patients with malaria.
- 2. To define the epidemiology, entomology, and clinical features of malaria in this area of low (unstable) transmission, and to determine the best methods of prevention and treatment.
- 3. To advise the Thai Medical Institutions and the Non Governmental Organisations involved in the treatment and the control of malaria in the South East Asia region.
Project Objectives:The projects are designed to be of direct benefit to the local community, and also to provide information useful to other populations living in malaria endemic areas elsewhere in the world through publications in mainstream international scientific journals.
- I Malaria in Pregnancy and Infancy
- II Malaria treatment studies
- III Entomology
- IV HIV/Aids awareness and prevention of vertical transmission
- V Nutrition and Anaemia
- VI Laboratory studies
- VII Control of malaria and detection of epidemics along the border
Projects:Current projects include: optimising the treatment of multi drug resistant malaria, investigating new antimalarial drugs, ante-natal care, epidemiological and malariometric surveys, studies on entomology and genetics of drug resistance, studies on vitamin B1 deficiency and studies on the neurological development of young infants. SMRU also collaborate in a campaign of Education on HIV/AIDS.
Staff:More than 200 local staff (Nurses, Midwives, Medics, Lab-technicians, Data entry clerks, Administrator, Accounting officer, Home-visitors, Drivers, Cleaners) and 7 expatriates 5 Doctors, 1 laboratory scientist, 1 Laboratory technician).
Funding Bodies:The Wellcome Trust of Great Britain, through the Wellcome-Mahidol University-Oxford Tropical Medicine Research Programme. In the past 14 years the SMRU has secured funding from various sources such as research grants, the pharmaceutical industry, the World Health Organisation, the European Union, VIHPAL (French Gvt). In 2000 SMRU (via Oxford University) was awarded a grant from the Bill and Melinda Gates Foundation to extend the control of malaria to the entire Tak Province in collaboration with the Thai Ministry of Health.
Long-Term Plans:To continue to provide malaria clinics and conduct community based research to elucidate the best methods of malaria control, against a backdrop of ever increasing drug resistance. Recently, the Unit has initiated a programme of AIDS awareness. Although the situation seems under control in the refugee populations, there is a great concern that further disruptions or population movements could lead to devastating epidemics and spread of resistant malaria to neighbouring populations. The recently funded Tak Malaria Initiative provides an opportunity to strengthen the results obtained in the refugee population and extend it to all surrounding areas.
Refugees:There are more than 100,000 Karen, Mon, Karenni ethnic minority living in a string of refugee camps along the Thai-Burmese border. This area is endemic for malaria transmission which results in symptomatic infection in all age groups. In Shoklo camp the attack rate was 3 episodes per person per year for the potentially fatal P.falciparum parasite (which accounts for approximately 70% of infections). P.vivax accounts for 20% of cases, the remaining being mixed PF/PV. The most important medical problem confronting the refugee community is the increasing anti-malarial drug resistance. The main consequence of the deterioration of treatment efficacy is anaemia. Children are particularly susceptible to malaria induced anaemia. In 1992 mortality from malaria accounted for 15% of all deaths in the camps. Between 1995 and 2000 the burden of malaria has fallen dramatically in the refugee camps has a result of the strategy designed at SMRU and used by all medical NGOs.
The migrants:In recent years the population influx from Myanmar has increased dramatically for both economic and political reasons. People from all ethnic groups (Shan, Karenni, Karen, Mon and Burman) are travelling back and forth across the border in search of work. It is thought that this population of migrant workers totals more than one million people in Thailand. Unlike refugees, they are highly mobile, and the majority does not have access to basic health care. Collectively, they harbour the majority of Thailand's malaria cases. This population of migrant workers, especially those living in the border areas, constitutes a major challenge to the control of malaria in the region and is now probably the major factor contributing to the spread of resistant strains of malaria. As they have done before, these strains will spread to the host population, the entire region, and later to other parts of the world. Given the paucity of new drugs against malaria this apparently local problem takes on a global dimension. Untreatable malaria infections would be a major threat to anyone living in or travelling to endemic areas. The "border population" can be seen as a mosaic of various communities linked by cultural and/or geographical similarities: Thai nationals (the majority is ethnic Karen), refugees and migrant workers from Myanmar. This complicates the task of the Thai Malaria Control programme because of language barriers, cultural differences and access difficulties. As a result, many individuals remain out of reach of the otherwise highly efficient malaria control efforts. SMRU has initiated novel approach for an effective malaria control programme in the populations living along the Thai-Myanmar border, through existing and new medical facilities, based on extensive experience with the displaced populations living in camps in this area.
This malaria research and control project differs from nearly all others in that it proposes to evaluate and deploy a strategy based on evidence acquired in the region, rather than on principles developed elsewhere or empirically. Since 1986 an operational research programme, initiated in response to the alarming rise in antimalarial drug resistance, has guided the malaria control programs of the various NGOs provided health services to the displaced populations in refugee camps along the Thai Myanmar border. This programme was (and still is) part of the Wellcome-Mahidol University-Oxford Tropical Medicine Research Programme based in the Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. It has focused on the epidemiology, the treatment and the prevention of falciparum malaria in the populations living in camps along the border. The main achievements of this programme and the deployment by all medical NGOs of the strategy elaborated were:
- The very significant reduction (over 90%) in the incidence of P.falciparum infections in the camps.
- The reduction in morbidity and mortality due to malaria and in particular the maternal mortality.
- The halt to the hitherto rapid increase in drug-resistance.
Shoklo Malaria Research Unit (SMRU)The SMRU is attached to the Hospital of Tropical Medicine, Mahidol University, Bangkok which provides scientific, administrative and logistical support. There is an office in Mae Sod which provides the logistical support and has two laboratories. In Maela there are hospital, laboratory, obstetric unit, outpatients department, ante and post-natal clinic, computing area and staff accommodation. Advanced training has been provided over the years so that today, highly competent Karen staff are operating the Unit. In Maela camp, three clinics, an office and staff housing have been built in 1995-6. Maela has become the centre for SMRU operations in the camps. Mae Sot base, the vehicles and Maela Unit are linked by radio. One hour drive to the south of Mae Sot SMRU has opened 2 clinics for migrant workers: Mawker Tai and Muruchai. These 2 clinics serve a population of 15-20,000. The importance of malaria, the size and stability of the population, the ability to follow the patient's progress and the excellent co-operation of the community make the site an ideal place to study malaria. Since 1986 over 10,000 people have been enrolled in more than 18 studies with excellent compliance (over 90% patients attending follow up assessments).
I) Malaria in Pregnancy & infancy
Malaria in PregnancyObjective: To quantify the effects of malaria, anaemia, antimalarial drug treatment, and thiamine depletion during gestation on the outcome of pregnancy.
Pregnant women in SE Asia have a high risk of getting severe malaria, hence a large part of the Unit's work is devoted to intensive ante natal care. The Ante Natal Clinics (ANCs) are now established in five different camps and in the clinics for migrants as well as in 3 district health centres and offer weekly screening for malaria and anaemia to ensure early treatment. As a result of this intensive programme, the maternal mortality due to malaria has been eliminated in the Karen refugee camps. Facilities for safe child birth are also provided. The ANCs are attended by 80-90% of pregnant women in the camps. On the research side, the Unit is looking at the treatment of malaria in pregnancy and the impact of the disease on the neonate and its subsequent development. All women attending the ANCs with malaria enter treatment studies if they give a written and verbal consent. Data can be collected on deliveries and the health of the new-born and during the first year of life. Studies include: The search for the optimum treatment for malaria (falciparum and vivax) and new methods of prevention. The effects of early and late pregnancy exposure to malaria and antimalarials on the subsequent development of the child and the natural history of malaria. The assessment of the thiamine status of pregnant and lactating woAmen to detect vitamin B1 deficiency and prevent it.
Malaria in infancyObjective: To measure malaria morbidity during the first two years of life; to describe clinical features of the infection in this risk group; to assess the efficacy of antimalarial treatment in this target population.
The children born to mothers attending the ANCs are prospectively followed for two years, with a monthly routine visit and a weekly home visiting to detect any illness. Previous studies have shown that P. vivax malaria is higher in this age group than in older children and adults. The incidence of falciparum malaria is lower than in older patients, but young children have a higher risk of developing a severe infection. This population is therefore followed closely and all children with malaria are admitted in chemotherapic studies after parental consent. Clinical features of falciparum malaria and malaria induced anaemia are monitored.
II) Chemotherapeutic TrialsObjective: To define the optimum treatment schedules in different patient groups; to identify those patients at increased risk of recrudescent infections, developing better methods of predicting treatment failure and monitoring emerging drug resistance.
Currently SMRU is conducting a series of large community based studies into the best therapies available for the treatment of primary uncomplicated malaria, hyperparasitaemic malaria and multiple failures. These studies are focusing on the use of the artemisinin derivatives alone or in combination A with other compounds. The standard regimen now in use along the border, and developed at the SMRU is a combination of high dose mefloquine and 3 days of artesunate. The current cure rate of this combination is >95% at 63 days. Recrudescences are treated with longer courses of artesunate (7 days) alone or in combination with tetracycline in non pregnant adults. We have studied prospectively >1000 patients with multiple exposures to an artemisinin derivative to look for evidence of toxicity but none was found. The Qinghaosu drugs are one for our last options. In combination with mefloquine they have translated into a dramatic reduction in the incidence of malaria in the camps, and halted the progression of resistance.
III) Epidemiology and EntomologyObjective: To provide a comprehensive description of the epidemiology and entomology of malaria.
Malaria cases are recorded weekly in Maela. In other refugee camps the data generated by the clinics and by the laboratories are centralised in Mae Sot and entered on to computer data bases. All patients treated for malaria in the SMRU clinics have medical records and data are computerised. This provides valuable information to monitor the malaria situation and detect emerging epidemics and also helps to establish decision algorithms applicable to South East Asia. The entomology studies determine the major malaria vectors, their man-biting habits, breeding sites, susceptibility to insecticides and repellents, and thus facilitate appropriate vector control and protection measures. These studies (together with the ANCs and the cohort of infants) provide a comprehensive descriptioAn of the malaria epidemiology and entomology in the area.
IV) Nutrition and AnaemiaObjective: To highlight the importance of nutrition in the morbidity and mortality of the community.
In 1989 SMRU identified thiamine deficiency as an important cause of infant mortality in this population. Several investigations have been carried out to document the relationship between vitamin B1 depletion in the mothers, and the sudden infant death. After recognition of the problem and systematic vitamin supplementation, the infant mortality has dropped from 250 per 1000 in 1988 to 40 per 1000 today. Recently the SMRU has completed a prospective detailed study of the causes and effects of anaemia and thiamine deficiency in pregnancy. This investigation showed that the Karen women are deficient in vitamin B1 after delivery even though they receive a supplement of food and B1 while lactating.
V) Immunology and other laboratory workObjective: To study the possible mechanisms involved in the effects of malaria during pregnancy on the baby. To characterise the in vitro resistance of P. falciparum to the main antimalarial drugs and to develop a method using PCR to differentiate between new infections and recrudescences.
Through detailed studies of the immune response to malaria infection, at the peripheral and placental levels and with studies on the placenta tissue, we are getting a better understanding of the deleterious effects of malaria in pregnancy. Parasites isolated from infectAed placenta are characterised using PCR and their cyto-adherence and rosetting properties studied. Most of the laboratory work is done at the Mae Sot base. The in vitro sensitivity work is done in collaboration with the department of immunology at AFRIMS (Bangkok) and the Pasteur Institute in Paris. Pattern of resistance are studied and monitored over time for all major antimalarial drug including the artemisinin derivatives. The results so far have confirmed that the strains of P. falciparum encountered in this area are the most resistant in the world. The PCR protocol has been developed in collaboration with Oxford University and paired specimen (in patients who are treated and present with a new parasitaemic episode during the follow-up) are compared using 3 genetic markers: MSP1, MSP2 and GLURP. More laboratory based work using strains from Shoklo and Maela is underway in the UK and in USA to look at their genetic structure.
To date the Shoklo Malaria Research Unit has....
- Provided the first detailed description of the effects of malaria in pregnancy in South East Asia.
- Developed a system of antenatal care that has eliminated maternal malaria related mortality.
- Established the safety of the artemisinin derivatives in pregnancy.
- Identified vitamin B1 deficiency in infant as the main cause of death in the first year of life.
- Defined the development of mefloquine drug resistance in this area and produced extensive information (in over 5000 patients) on its adverse effects and on predictors of treatment response.
- Assessed the benefit of high dose halofantrine and discovered its cardio toxicity.
- Treated over 10 000 patients with artemisinin derivatives (the largest single centre study in the world). Conducted the first studies to look at a possible cumulative toxicity of this family of drugs in humans.
- Documented for the first time the impact of artesunate on transmission of malaria and on the spread of resistance and pioneered the use of artemisinin based combination therapy.
- Evaluated the US manufactured malaria vaccine SPf66 in the most detailed and carefully conducted trial with this vaccine.
- Documented for the first time the effects of P. vivax in pregnancy.
- Became the reference for malaria control programs supported by international NGO working along the border.
- Initiated the first Family Planing and HIV awareness programme in the Karen camps, as well as the mother-to-child transmission prevention programme.
- Established collaborations with scientific institutions in USA, Europe and Australia.
- Published over 100 papers in international journals and presented results in several international scientific meetings.