The concept of combination therapy is based on the synergistic or additive potential of two or more drugs, to improve therapeutic efficacy and also delay the development of resistance to the individual components of the combination. Anti-malarial combination therapy is the simultaneous administration of two or more blood schizonticidal anti-malarial drugs. The two drugs can either be co-formulated or co-administered. The two drugs have independent modes of action and different biochemical targets in the parasite.
Artemisinin-based combinations (ACT)
Various Artemisinin compounds, in different formulations, are used in combination with other anti-malarial drugs include artisunate, artemether and di-hydroartemisinin. The Artemisinin-based combination therapy (ACT) improves the therapeutic efficacy and delays the development of drug resistant parasites in areas of low to moderate malaria transmission.
The National Malaria Control Program recommends the use of following two Artemisinin-based combination therapies in Pakistan:
1. Artesunate plus Sulfadoxine-Pyrimethamine (SP) for confirmed falciparum malaria (both uncomplicated and severe)
2. Artemether-lumefantrine for mixed infections as well as treatment failure with the first line anti-malarial drugs.
Advantages:
· The duration of Artemisinin treatment is reduced due to combination with partner drugs that have longer half-time.
· The combination enhances the efficacy and reduces the likelihood of resistance development of partner drug.
· The combination therapy rapidly reduces (substantially) the parasite biomass, and improves the clinical condition.
· The combination therapy is effective against multi-drug resistant plasmodium falciparum.
· The combination therapy reduces the gametocyte carriage thus affect transmission.
Potential Challenges:
· Availability of raw material can become a problem because the plant (from which it is extracted) takes at least two years lead-time for cultivation.
· Difficulty of administering multiple doses in the situations of complex emergencies and malaria epidemics.
· Non-fixed dose combinations may affect compliance, particularly at household level.
· Effort, time and cost of the program to implement the change in treatment policy
· Comparatively higher cost per patient treated (>2 US $/person)
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