Impact of delayed introduction of sulphadoxine-pyrimethamine and artemether-lumefantrine on malaria epidemiology in KwaZulu-Natal, South Africa.

Abstract

Background The years 1985 to 1988 and 1997 to 2001, were periods of high morbidity and mortality due to malaria in KwaZulu-Natal, South Africa. One reason for the increased burden of disease was the emergence of drug resistant Plasmodium falciparum. The parasite was resistant initially to chloroquine and then to sulphadoxine-pyramethamine, the medication of choice for the treatment and prevention of malaria in different periods of time. The changing epidemiology of malaria in Mrica was exacerbated by policy makers not making timely and rational change to the failing malaria drug regimens to newer and effective ones. Purpose ofthe study This study was conducted to determine the impact of delayed introduction of sulphadoxine-pyramethamine (Fansidar®) and artemether-lumefantrine (Coartem®) as a first-line drugs for malaria in KwaZulu-Natal from 1985 to 1988 and 1997 to 2001 respectivel y, Study Design Observational, Analytic, Ecological Method The incidence of malaria in KwaZulu-Natal was compared during different phases of the period when chloroquine was the first line treatment. The baseline phase (1982 to 1984) was taken when chloroquine correctly should have been used and this was compared with the delayed phase (1985 to 1988), when it should have been replaced by of sulphadoxinepyramethamine. During the second period sulphadoxine-pyramethamine was the first line treatment of malaria, the baseline phase (1993 to 1996) when it correctly should have been used was compared to the delayed phase (1997 to 2001) of introduction of the alternate treatment of malaria with artemether-Iumefantrine. Ethical approval for this study was obtained from the Biomedical Research Ethics Committee, of the University of KwaZulu-Natal. Statistical Methods The relative association of malaria infection during the chloroquine baseline and change phases and the sulphadoxine-pyrametharnine baseline and change phases were compared with statistical significance at 0.05. Results The risk of malaria infection was 4.5 times (Incidence Risk Ratio = 4.5; 95% Confidence Interval: 4.1 to 5.0; P < 0.0001) higher in chloroquine change phase relative to the baseline phase. During the sulphadoxine-pyrametharnine period, the malaria risk was 3.5 times greater (Incidence Risk Ratio = 3.50; 95% Confidence Interval: 3.40- 3.60; p < 0.0001) in the change phase. In the chloroquine period, the malaria mortality risk was 9.1 times higher (95% Confidence Interval: 2.1 to 38.5; p=0.0003) and the case fatality rate was increased 1.3 times more (95% Confidence Interval: 1.0 to 1.7; p< 0.001) in the change period. The risk of death during the sulphadoxine-pyramethamine change phase was 4.8 times (95% Confidence Interval: 3.3 to 7.0; p<O.OOl) and case fatality rate of2 times (95% Confidence Interval: 1.5 to 2.7; p <0.001) relative to the baseline phase. Conclusions The dramatic change in the malaria epidemiology in Africa in recent times was exacerbated by delay in replacing first line failing antimalarial drugs. The establishment of sentinel sites for assessing drug resistance or failure and the application of World Health Organisation standards in drug resistance studies will go a long way to achieving the Roll Back Malaria target by 2010.