Baseline study of the Effectiveness of Chloroquine and Sulphadoxine/ Pyrimethamine against uncomplicated Plasmodium falciparum malaria in Swaziland, Mozambique and South Africa.

 

The resistance of Plasmodium falciparum to antimalarial drugs is a serious impediment to the control of malaria.1,2   In vitro and in vivo studies3-8 have shown the existence of chloroquine resistance in two malarial areas of South Africa, namely northern KwaZulu Natal (KZN) and Mpumalanga Province and this prompted a decision to replace chloroquine with sulfadoxine-pyrimethamine (SP) as the first-line therapy of uncomplicated malaria in South Africa despite there being no drug sensitivity data for the Northern Province. Subsequent in vivo studies have demonstrated acceptable therapeutic success with SP in Mpumalanga9 but indications of reduced therapeutic efficacy in patients referred to a hospital in KZN (Freese et al, in press). 

     
 

If we are to effectively manage malaria in the South-East African Region and make informed policy decisions on the introduction of combination therapy, we need to know how effective these first-line drugs are at clearing parasites in the host.

 
     
 


In order to facilitate the formulation of an effective regional drug policy and to provide a database for decisions on the implementation of combination therapy, it is essential that the in vivo response to monotherapy in all three countries be investigated at the appropriately chosen sentinel sites.  This investigation will be performed at operational level and as far as possible follow control programme treatment and follow-up procedures to ensure that it can be sustainably repeated on a regular basis.  Should baseline parasitological failure of SP monotherapy exceed 30%, an alternative artesunate combination therapy (eg co-arthemether) will be implemented in that province.

Once combination antimalarial therapy is introduced, an in vivo study will be conducted according to this modified WHO protocol to evaluate the efficacy of artesunate plus SP at the time of introduction, and biannually thereafter. 

Background

Resistance to chloroquine occurs in virtually every country in which transmission of P. falciparum occurs,1,2 chloroquine resistance being first reported in Africa in 197910,11 and arriving in South Africa in the mid 1980s.3-5,12-14  However no formal in vivo susceptibility studies have been carried out using accepted WHO techniques in Northern Province, Swaziland or Mozambique.  The effects of partial immunity on the clinical effectiveness of chloroquine in Mozambique and Swaziland have also not been determined.  Similarly a primary level SP in vivo study has only been conducted in Mpumalanga Province at introduction9. If we are to effectively manage malaria in the South-East African Region and make informed policy decisions on the introduction of combination therapy, we need to know how effective these first-line drugs are at clearing parasites in the host.

Objectives

   To define the sensitivity in vivo to first-line therapy for P. falciparum at sentinel sites in malarial areas of Mozambique, Swaziland and the three South African Provinces affected by malaria, namely KwaZulu Natal, Mpumalanga and Northern Province, towards ensuring effective drug management

   To develop the capacity of southern African malaria control programmes to sustain sentinel sites for future evaluations of drug sensitivity.

   To determine the species composition of the Plasmodium populations in the three countries.

Timetable

In KwaZulu and Mpumalanga the baseline in vivo study commenced in January 2000 to optimise recruitment and will proceed until the required number of patients has been recruited at each site.  The baseline in vivo study for Northern Province (South Africa), Maputo province (Mozambique) and Lowveld Region (Swaziland) are due to commence in January 2001 and will proceed until the required number of patients has been recruited at each site. 

References

 
[SEACAT] [Introduction] [Exec Summary] [ Study Design] [Participants] [Links]