SMRU PROGRAMMES

I) Malaria in Pregnancy & infancy

Malaria in Pregnancy

Objective: 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 infancy

Objective: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 Trials

Objective: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 Entomology

ObjectiveTo 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 Anaemia

Objective: 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 work

Objective: 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.