EFFECTIVENESS OF QUININE MONOTHERAPY FOR THE TREATMENT OF PLASMODIUM FALCIPARUM INFECTION IN PREGNANT WOMEN IN LAMBARE ´ NE ´ , GABON AYO ˆ LA A. ADEGNIKA,* LUTZ PH. BREITLING, SELIDJI T. AGNANDJI, SANDERS K. CHAI, DANIELA SCHÜTTE, SUNNY OYAKHIROME, NORBERT G. SCHWARZ, MARTIN P. GROBUSCH, MICHEL A. MISSINOU, MICHAEL RAMHARTER, SAADOU ISSIFOU, AND PETER G. KREMSNER Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon; Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Tübingen, Germany; Department of Internal Medicine I, Division of Infectious Diseases, Medical University of Vienna, Vienna, Austria Abstract. Pregnant women participating in a longitudinal immuno-epidemiologic survey in Lambaréné, Gabon, and presenting with Plasmodium falciparum parasitemia at monthly blood smear examinations were offered treatment with oral 7-day quinine monotherapy according to national health guidelines. A total of 50 pregnant women were offered 7-day oral quinine sulfate 10 mg/kg thrice daily. Clinical examinations and laboratory tests were performed on Days 28 and 56 to assess the effectiveness of this standard regimen. By Day 28, the effectiveness of the 7-day quinine regimen was 60% (95% confidence interval: 46–72%). We conclude that a 7-day course of quinine has a poor effectiveness and that alternative treatment regimens for malaria in pregnant women should be assessed. INTRODUCTION Plasmodium falciparum malaria is one of the leading causes of death in tropical countries, taking the highest burden in tropical Africa. It is estimated that 90% of the worldwide falciparum malaria occur in sub-Saharan Africa. 1 Pregnant women and newborns are at an elevated risk for P. falciparum infection associated morbidity and mortality. Symptomatic or asymptomatic P. falciparum infection during pregnancy leads to an increased risk for maternal anemia. This is, in conjunction with placental P. falciparum infection, one major predictor for poor birth outcome due to low birth weight and prematurity. 2,3 Intermittent preventive treatment, treatment of anemia, and insecticide-treated nets are possible effective control strategies. In the absence of an efficient implementation of the above-mentioned malaria control measures in many Af- rican countries, chemotherapeutic treatment of falciparum malaria remains the only viable option against pregnancy- associated malaria for the majority of affected people. To date, there is a limited choice of approved treatments for chloroquine-resistant P. falciparum malaria in pregnancy in most African countries. In Gabon and many other sub- Saharan African countries, quinine remains the first-line therapy for pregnant women, either administered intrave- nously in hospitalized patients or orally as a 7-day regimen. Sulfadoxine-pyrimethamine is privileged for intermittent pre- ventive treatment during pregnancy in most malaria endemic areas, however its actual use during pregnancy might in fact be more common. 1,4–7 Although quinine monotherapy shows high efficacy in the setting of clinical trials, it also has consid- erable disadvantages foremost due to its poor tolerability (i.e., cinchonism) and the prolonged treatment course. 8 However, whether high efficacy observed under artificial circumstances such as clinical trials translates similarly into real life remains doubtful. The aim of this clinical trial was to assess the actual usefulness of quinine monotherapy when prescribed under routine health care facilities in sub-Saharan Africa. MATERIALS AND METHODS The study took place at the Medical Research Unit of the Albert Schweitzer Hospital in the semi-urban setting of Lam- baréné, Gabon, from June 2003 to February 2004. The city is characterized by hyperendemic and perennial malaria trans- mission with an entomological inoculation rate of approxi- mately 50 infective bites/person per year. 9,10 The predomi- nant species is Plasmodium falciparum, which has been shown to be highly resistant to chloroquine but sensitive to quinine in vitro and in vivo. 11–13 Two mother-child health care centers that are part of the governmental hospital (Gen- eral Hospital) and the nongovernmental hospital (Albert Schweitzer Hospital) serve the local population. Pregnant women living in Lambaréné and attending one of the above-mentioned mother-child health care centers in Lambaréné were invited to participate in an immuno- epidemiologic study on the impact of parasitic infections in pregnancy. As part of this study, patients were invited for monthly follow-up visits assessing clinical status and parasi- tological laboratory diagnostics for malaria, filariasis, and schistosomiasis throughout pregnancy. This study was designed as an uncontrolled effectiveness study assessing the parasitological cure rate of quinine mono- therapy. Women diagnosed with microscopically confirmed P. falciparum monoinfection were considered eligible for this study if the following inclusion criteria were met: 1) absence of signs of severe malaria, 2) ability to tolerate oral therapy, 3) no antimalarial drug intake in the preceding two weeks, and 4) written informed consent. A study physician examined all patients at enrollment and subsequent follow-up visits assessing vital signs, blood pres- sure, tympanic temperature, and blood count. A thick blood smear was also done, and each blood film was read by two laboratory technicians following the standard quality con- trolled procedure. 14 Patients who met all entry criteria were assigned to a 7-day weight-adjusted treatment course of thrice-daily quinine sul- * Address correspondence to Ayôla A. Adegnika, Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon. E-mail: aadegnika@yahoo.com Am. J. Trop. Med. Hyg., 73(2), 2005, pp. 263–266 Copyright © 2005 by The American Society of Tropical Medicine and Hygiene 263