A Trial of Antimalarial Drugs Used in Pregnancy in Tanzania

Inclusion Criteria:

A pregnant woman who has either a positive blood smear for P.falciparum with at least 1000 asexual parasites/uL in an asymptomatic woman

or any of the following symptoms within 2 days prior to consultation:

• history of fever;
• headache,
• vomiting,
• chills/rigors,
• and/or any of the following signs: temperature >37.50C and <39.50C, Hb>5 and <9 g/dl together with P.falciparum parasitaemia at any density

and (in both cases) the following:

1. Has no exclusion criterion (see below);
2. Is 14-34 weeks pregnant on the day of attending the ANC clinic or OPD;
3. Has a viable foetus, defined by presence of foetal heartbeat by sonicaid or pinnard (foetal heartbeat is not heard until 14 weeks);
4. Is able to take study drugs by the oral route;
5. Is able to attend stipulated days for follow up clinic and provide specimens;
6. Gives informed written or witnessed verbal consent to participate by herself, and also through her parent/guardian if aged <15 years (in conformity to Tanzania Law).

Exclusion Criteria:

1. Severe and complicated forms of malaria (as defined by WHO, 1996);
2. Pregnancy in the first trimester;
3. A mixed plasmodial infection;
4. Complicated pregnancy, e.g. signs/symptoms of toxaemia of pregnancy;
5. 23 or more abortions or stillbirths;
6. Presence of concomitant disease masking assessment of the response to treatment ;
7. An intake of drugs contraindicated in pregnancy, e.g. tetracycline, cotrimoxazole or a macrolide antibiotic;
8. An intake of drugs with effective antimalarial activity within the last 2 weeks.
9. Significantly abnormal baseline haematology (except anaemia) or clinical chemistry parameters, e.g. laboratory evidence of renal impairment (serum creatinine >2 mg/dl) or of hepatitis (alanine aminotransferase [ALT] >5 times upper limit of normal);
10. Previous participation in the study: Women having a second episode of malaria after completing the 28-day follow up will have details recorded and offered quinine but not be re-enrolled.
11. Multiple gestation pregnancies, eg twins
12. Mother aged 38 years or above