Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data

Abstract

Background: As a result of widespread chloroquine and sulphadoxine-pyrimethamine (SP) resistance, 90% of sub-Saharan African countries had adopted policies of artemisinin-based combination therapy (ACT) for treatment of uncomplicated malaria by 2007. In Malawi, cessation of chloroquine use was followed by the re-emergence of chloroquine-susceptible malaria. It was expected that introduction of ACT would lead to a return in chloroquine susceptibility throughout Africa, but this has not yet widely occurred. This observation suggests that there is continuing use of ineffective anti-malarials in Africa and that persistent chloroquine-resistant malaria is due to ongoing drug pressure despite national policy changes.

Methods: To estimate drug use on a national level, 2006-2007 Demographic Health Survey and Multiple Indicator Cluster Survey data from 21 African countries were analysed. Resistance data were compiled by systematic review of the published literature on the prevalence of the Plasmodium falciparum chloroquine resistance transporter polymorphism at codon 76, which causes chloroquine resistance.

Results: Chloroquine was the most common anti-malarial used according to surveys from 14 of 21 countries analysed, predominantly in West Africa. SP was most commonly reported in two of 21 countries. Among eight countries with longitudinal molecular resistance data, the four countries where the highest proportion of children treated for fever received chloroquine (Uganda, Burkina Faso, Guinea Bissau, and Mali) also showed no significant declines in the prevalence of chloroquine-resistant infections. The three countries with low or decreasing chloroquine use among children who reported fever treatment (Malawi, Kenya, and Tanzania) had statistically significant declines in the prevalence of chloroquine resistance.

Conclusions: This study demonstrates that in 2006-2007, chloroquine and SP continued to be used at high rates in many African countries. In countries reporting sustained chloroquine use, chloroquine-resistant malaria persists. In contrast, a low level of estimated chloroquine use is associated with a declining prevalence of chloroquine resistance.

Figure 1

Anti-malarial use in Africa for the treatment of fever or convulsions. Map of African malaria endemic countries showing the proportion of children under age 5 with fever or convulsions within the last 2 weeks that reported the use of anti-malarials.

Figure 2

Drug use data from 21 DHS and MICS household surveys, 2006--2007. a MICS 2006. b MICS 2007. c DHS 2006. d DHS 2007. † >15% reporting quinine use. ‡ >15% reporting amodiaquine use. *Year of official policy change could not be confirmed.

Figure 3

Longitudinal chloroquine use and chloroquine resistance trends. Bars indicate the proportion of children who had fever or convulsions in the preceding two weeks who reported chloroquine use. Observed (dots) and predicted prevalence using regression modelling (trendlines) of pfcrt 76T are displayed with the coefficient for time in years with p-value (b) for the country regression model in the upper right hand corner of each graph.