Clinical efficacy of chloroquine in young children with uncomplicated falciparum malaria – a community-based study in rural Burkina Faso
We report on a 14-day study on the efficacy of chloroquine for treating uncomplicated falciparum malaria in young children of a malaria holoendemic area in rural Burkina Faso. In this community-based study, the overall treatment failure rate was 12/120 (10%), with no differences between villages. This supports the evidence for a still sufficient efficacy of chloroquine in north-western Burkina Faso.
Chloroquine has been the mainstay for malaria control in sub-Saharan Africa (SSA), but the emergence of chloroquine-resistant Plasmodium falciparum has put into question the efficacy of this well-known drug (Trape 2001). In fact, increasing resistance has already convinced several SSA countries to replace chloroquine as first line drug for treatment and prophylaxis (Nuwaha 2001). It has been suggested to change to a new first-line drug when the prevalence of RIII parasitological resistance has reached the range of 14–31%, or when the mean duration of clinical response decreases to <14 days (Sudre et al. 1992;Bloland et al. 1993). We report data on the efficacy of chloroquine treatment in young children of a rural area of Burkina Faso with high P. falciparum transmission intensity.
The study was nested into an ongoing cohort study on the long-term effects of insecticide-treated mosquito nets (ITN) in young children from six villages of Nouna Health District in north-western Burkina Faso. These villages belong to the research zone of the Centre de Recherche en Santé de Nouna (CRSN), consisting of Nouna town and 41 of the surrounding villages. They were purposely selected to represent the rural study population in its sociocultural, demographic and geographical diversity. The Nouna area is a dry orchard savanna, populated mainly by subsistence farmers of different ethnic groups.
Cohort children were visited daily by village-based field staff for temperature measurement and recording of relevant data during illness episodes. In case of fever, blood films were taken and the films were examined by two experienced microscopists of the Nouna Health Research Centre. Malaria is holoendemic but highly seasonal in the area (Müller et al. 2001). Approval for the study was granted by the Ethical Committee of the Heidelberg University Medical School and the Ministry of Health in Burkina Faso.
Cohort children were consecutively enrolled from July until October 2001 if they fulfilled the following inclusion criteria: age ≥6 months, falciparum malaria (≥37.5 °C axillary temperature + ≥5.000 P. falciparum parasites per microlitre in the absence of another obvious fever cause), absence of antimalarial treatment during past 2 weeks, informed oral consent. All study children received fully supervised treatment with 25 mg/kg bodyweight of chloroquine (drugs taken from the essential drug stock of Nouna Health District) over 3 days. Enrolled children were followed clinically over a 14-day period, and a systematic blood slide was taken on days 7–10. For the evaluation of treatment outcome, we used a modified definition of the WHO protocol for assessment of therapeutic efficacy of antimalarial drugs in areas with intense transmission (WHO 1996). We defined early treatment failure (ETF) as development of severe malaria on days 1–3 or axillary temperature≥ 37.5 °C on day 3 in the presence of parasitaemia on days 7–10, and late treatment failure (LTF) as development of severe malaria and/or axillary temperature ≥37.5 °C on days 4–14 in the presence of parasitaemia on days 7–10 without previously meeting the criteria of ETF.
A total of 120 children were recruited and there was no loss to follow-up. The mean age was 10.4 months (range 6–15), and the male/female ratio was 0.71. Mean temperature on day 0 was 38.7 (range 37.5–40.7), and mean P. falciparum density was 38 400 (range 5500–287 000).
On days 7–10, 32/120 (27%, 95% confidence interval 19–35%) children were still parasitaemic (mean P. falciparum density 3620, range 50–23 000). The overall treatment failure rate was 12 of 120 (10%, 95% confidence interval 5–15%), with six of 120 (5%) being ETF and six of 120 (5%) being LTF. None of the children developed severe malaria, and there were no differences in parasitological and clinical failure rates between villages (Table 1).
Table 1. Parasitological and clinical failure rates of chloroquine treatment in young children with uncomplicated falciparum malaria (fever + ≥5000 parasites/μl) in six villages of ruralBurkina Faso, July–October 2001
|Total||32/120 (27%)||12/120 (10%)|
After standard treatment with chloroquine, we found a parasitological failure rate of 27% and a clinical failure rate of 10% in children aged 6–15 months. This significant discrepancy supports the evidence for a rapid development of immunity in young children exposed to intense malaria transmission (WHO 1996).
The first cases of in vitro and in vivo chloroquine resistance in Burkina Faso were seen in 1983 and 1988, respectively, and reported clinical failure rates after use of chloroquine for treatment of uncomplicated malaria in children were around 5% in the early 1990s (Guigemdéet al. 1994). Our finding of a low chloroquine clinical failure rate in a representative group of young children from rural Burkina Faso provides further evidence for chloroquine remaining sufficiently effective after many years of resistance occurence in parts of West Africa (Guigemdéet al. 1994; Brasseur et al. 1999; Plowe et al. 2001).
The study was funded by the Deutsche Forschungsgemeinschaft (SFB 544, Control of Tropical Infectious Diseases).
Dr Bocar Kouyaté, Centre de Recherche en Santé de Nouna, BP34, Nouna, Burkina Faso. E-mail: firstname.lastname@example.org
Dr Olaf Müller, Department of Tropical Hygiene and Public Health, Ruprecht-Karls-University, INF 324, 69120 Heidelberg, Germany. E-mail: email@example.com (corresponding author).
Dr Corneille Traoré, Centre de Recherche en Santé de Nouna, BP34, Nouna, Burkina Faso. E-mail: firstname.lastname@example.org