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

Abstract

BackgroundAs 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.MethodsTo 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.ResultsChloroquine 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.ConclusionsThis 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.

High prevalence of Plasmodium falciparum pfcrt K76T mutation in children with sickle cell disease at a tertiary hospital in north-western Tanzania

“…SCD patients seem to be a special group that maintains sub patent level of mutant parasites that are not static and probably continues to be transmitted to other individuals. This group should be considered while studying the re-emergence of pfcrt wild type parasites especially in countries showing slower progress as reported by Frosch et al (2011). Unpublished data (A. Kheir, unpubl) have revealed that parasites continue to change in patients during the dry season in Sudan when there is no transmission and are capable of being transmitted to other patients at the beginning of next transmission season.…”

“…In some countries there is clear re-emergence of wild type strains coupled with CQ sensitivity (Kublin et al, 2003;Lauffer et al, 2006;Ginsburg et al, 2006;Frosch et al, 2011;Kamugisha et al, 2012;Mohamed et al, 2013;Malmberg et al, 2013). In other countries the level of CQ resistance is going down very slowly or is fixed (Frosch et al, 2011). Reasons for the difference in these countries are not clear but continued use of CQ for other purposes or combined treatment regimens for malaria have been proposed (Frosch et al, 2011).…”

“…After discontinuation of CQ use, several studies in African countries have reported different prevalence of pfcrt K76T mutation. In some countries there is clear re-emergence of wild type strains coupled with CQ sensitivity (Kublin et al, 2003;Lauffer et al, 2006;Ginsburg et al, 2006;Frosch et al, 2011;Kamugisha et al, 2012;Mohamed et al, 2013;Malmberg et al, 2013). In other countries the level of CQ resistance is going down very slowly or is fixed (Frosch et al, 2011).…”

“…In other countries the level of CQ resistance is going down very slowly or is fixed (Frosch et al, 2011). Reasons for the difference in these countries are not clear but continued use of CQ for other purposes or combined treatment regimens for malaria have been proposed (Frosch et al, 2011).…”

Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems

“…Endemic countries should embrace an empirical analysis of these risk factors, starting with historical data for the temporal and spatial emergence of resistance to chloroquine and sulfadoxine-pyrimethamine, to examine the mapped rates of spread of drug resistance alleles in populations exposed to diverse treatments and malaria transmission intensities. [64][65][66] Assembling these data will be difficult, but not impossible. Africa is witnessing a renaissance of malaria transmission-intensity mapping, and data for drug-use patterns are expanding.…”