Drug studies

Studies evaluating the efficacy of antimalarials showed there was over-the counter use of antimalarial drugs, together with empirical diagnosis and treatment of fever with antimalarials. The repeated intake/administration of these drugs was attributed to their low therapeutic efficacy, use of sub-therapeutic doses, or erroneous primary diagnosis.

The proportion of clinical failures was unacceptably high in some countries of the Region such as Sudan. On the other hand, Jezan region, Southwestern Saudi Arabia, a highly endemic malaria region, recorded high cure rates for the antimalarial drug chloroquine. These studies also reported that Sulfadoxine-pyrimethamine proved to be a safe and efficacious alternative to chloroquine for management of resistant cases.

The relatively high prevalence of drug resistance reported from a study conducted in Sudan was mainly attributed to the spread of resistance strains from neighboring African countries as well as displaced populations from the Southern Sudan.

Regarding Chloroquine efficacy, research conducted revealed that both early and late treatment failure were significantly higher in children than in adults. Moreover, children had a significantly higher parasite count compared to adults. This could reflect lower immunity in children. It also indicates that drug efficacy studies should consider children as a subgroup with higher risk of therapeutic failure. The lack of response to chloroquine was also significantly correlated with high body temperature on initial presentation.

The most important recommendations of these studies were:

• Developing sentinel posts for monitoring drug resistance as initial step for a nation-wide plan for malaria control in the different countries.

• Revision of the current malaria treatment policies in some EMR countries such as Sudan that consider chloroquine as the first line drug for treatment of uncomplicated P. falciparum malaria.

• Improvement of diagnostic services and health education regarding the rational use of antimalarials.

Two projects investigated the impact of treating gametocyte carriers during the dry season on malaria prevalence during the next transmission season in areas of seasonal transmission in Sudan. The first study conducted during 2001-2002 tested a schizontocidal drug (chloroquine) and a gametocytocidal drug (primaquine). The second study conducted during 2003-2004 tested two combinations: artesunate/SP versus artesunate/SP/+ primaquine. The two studies reported a prevalence of 18.5-40% prevalence of subpatent prasitaemia during the dry seasons of these areas; they also reported a significant reduction in the prevalence of malaria in the next transmission season.  

A randomized clinical trial was carried out in 2 neighboring villages in Eastern Sudan, Daraweesh and Kajara during 2002-2004, in order to asses the efficacy of 2 combinations of anti-malarial drugs:  chloroquine (CQ) plus sulfadoxine/pyrimethamine (SP) and CQ plus Dihydroartemisinin (DHA).

The adequate clinical response and parasite clearance was found to be 64% and 69.6% in the CQ/SP and CQ/DHA treatment groups, respectively. The corresponding rate of treatment failure in both groups was mainly due to parasite resistance type RI, with low parasitemia and mild, vague or no symptoms. The recrudescence was proved by genotyping and the prevalence of gametocytemia after treatment was significantly lower in the CQ/DHA group (p=0.02).

This study revealed a lower than expected efficacy of both SP and DHA in parasite clearance in this area, a fact that will have consequences on the control programs in the long term. 

Studies on the use and quality of antimalrial drugs in Yemen reported common patterns of irrational use of antimalarial drugs during 2001-2002. They also provided baseline information necessary for designing future interventions to promote the rational use of drugs in the country. Several problems of substandard products within the drug distribution chain were identified. These included high and low failures in ingredient content for chloroquine tablets (CQT) and chloroquine syrup (CQS), some dissolution failure for CQT and high sulphadoxine/pyrimethamine tablets (SPT) dissolution failures, mainly attributed to pyrimethamine at most collection points. These findings have serious implications not only on the reduced therapeutic effectiveness of antimalarial drugs but also on the development of drug resistance.  

A study carried out in Yemen during 2003-2004 reported a high rate of treatment failure to chloroquine (60.7%). Children younger than 10 years of age were at 9 folds increased risk for treatment failure. Therefore, chloroquine is no more acceptable as the first line antimalarial drug in Yemen.

Validation of pfcrt-T76 as a molecular marker for chloroquine resistance showed that this marker is of high sensitivity (100%) but low specificity (4.5%), hence cannot be used as a valid diagnostic test for chloroquine resistance. Therefore, the genotype failure index was calculated and recommended as a better indicator for prediction of clinical in vivo treatment failure in this area.  

A currently ongoing study (2004-2005) aimed at evaluating the efficacy of chloroquine in the management of vivax malaria in South and South-East of Islamic Republic of Iran.

Another randomized control trial of eight-week primaquine using single weekly doses versus conventional primaquine administration is currently evaluated for vivax malaria in Pakistan.