Act In Current Scenario

Act In Current Scenario

Write About Act In The Current Scenario And Why Recommended By Who.
Answer:

Act In Current Scenario

ACT is artemisinin-based combination therapy.

ACT regimens for oral treatment of uncomplicated falciparum malaria that are already in use in India or are WHO approved or have completed clinical trials are:

• Artesunate – sulfadoxine + pyrimethamine WHO approved: This ACT has been adopted as the first line drug for uncomplicated falciparum malaria under the ‘National antimalaria drug policy’ of India, and has replaced chloroquine throughout the country. This does not imply that it is the most effective/best ACT because it is not effective against multidrug-resistant strains which are nonresponsive to pyrimethamine. However, treatment failures with artesunate–pyrimethamine. ACT is mostly restricted to Northeast areas bordering Myanmar; while in the rest of India so far this ACT appears to be working satisfactorily with >96% success rate. National Vector Born Diseases Control Programme continues to use artesunate – sulfadoxine + pyrimethamine ACT as the first line therapy, including that during the 2nd and 3rd trimesters of pregnancy. This ACT appears to produce fewer side effects than artesunate/mefloquine. Private clinics, however, are using other ACTs. Most other malaria-endemic countries have found artesunate – sulfadoxine + pyrimethamine ACT to be inferior.
  Regimen: Artesunate 100 mg BD (4 mg/kg/day) for 3 days + sulfadoxine 1500 mg (25 mg/kg) and pyrimeth- amine 75 mg (1.25 mg/kg) single dose.
• Artesunate – mefloquine WHO approved: This is the standard and most extensively used ACT in Thailand. Myanmar and other Southeast Asian countries as well as South America and Africa. It was found highly effective and well tolerated in uncomplicated falciparum malaria. However, many areas in the Far East already have mefloquine-resistant Plasmodium falciparum, but by combining with artesunate further spread of mefloquine resistance was checked. Nevertheless, some of them have switched over to alternative ACTs. ln India artesunate–mefloquine ACT has been used to a limited extent. A kit with separate artesunate and mefloquine tablets is available and an FDC formulation has been approved.
  Regimen: Artesunate 100 mg BD (4 mg/kg/day) for 3 days + mefloquine 750 mg (15 mg/kg) on the 2nd day and 500 mg (10 mg/kg) on the 3rd day (total 25 mg/kg).
• Artemether ­ lumefantrine (1: 6) WHO approved: Lumefantrine is used only in combination with artemether, and FDC tablets. The two components protect each other from plasmodial resistance. As such, no clinically relevant resistance has developed so far. Clinical efficacy is high achieving a 95–99% cure rate, which is comparable to artesunate – mefloquine. Artemether–lumefantrine is active even in multidrug-resistant Plasmodium falciparum areas including mefloquine resistant. It has been extensively employed in Southeast Asia and Africa. In India, it is frequently used by private doctors. While artemether quickly reduces parasite biomass and resolves symptoms, lumefantrine prevents recrudescence. The gametocyte population is reduced, checking transmission. Artemether–lumefantrine must be administered with fatt food or milk, which markedly enhances lumefantrine (and to some extent artemether)
  absorption, and ensures adequate blood levels. Failure to take it with fat-rich food limits absorption.
  Regimen: Artemether (80 mg BD) + lumefantrine (480 mg BD) for 3 days.
• Arterolane – piperaquine: Arterolane is a novel orally active synthetic trioxolane congener of artemisinin that has been developed in India and recently marketed in combination with piperaquine. Arterolane acts rapidly at all stages of asexual schizogony of malarial parasites including multidrug-resistant Plasmodium falciparum but has no effect on the hepatic stages. It accumulates in the food vacuole of the parasite and thus differs from artemisinins which do not accumulate at this site. It also has a moderate gametocidal activity similar to that of artemether-lumefantrine. Arterolane—piperaquine FDC has undergone multicentric clinical trials in India, Bangladesh, and Thailand. In uncomplicated falciparum malaria, this act has produced a ≥ 95% cure rate with fever and parasitemia clearance time of 24 to 48 hours.
  Regimen: Arterolane (as maleate) 150 mg + piperaquine, 750 mg daily for 3 days.
• Dihydroartemisinin – piperaquine (1:8) WHO approved: Piperaquine has been formulated with dihydroartemisinin in a dose ratio of 8: l and is extensively evaluated in multidrug-resistant plasmodium falciparum areas of Cambodia, Thailand, Vietnam, etc. with high success rate. In clinical trials, the efficacy of the Dihydroartemisinin– piperaquine fixed-dose combination has been found comparable to artemether–lumefantrine or to artemether–Mefloquine. The safety profile of dihydroartemisinin–piperaquine is good and it is well tolerated even by children. Dihydroartemisinin – piperaquine FDC has completed clinical trials in India producing > 98% response rate in uncomplicated falciparum malaria and is likely to be approved soon.
  Regimen: Dihydroartemisinin 120 mg (2 mg/kg) + piperaquine 960 mg (16 mg/kg) daily for 3 days.
• Artesunate – amodiaquine WHO approved: Amodiaquine has long been used parallel to chloroquine. While amodiaquine itself has a short t1/2 due to rapid metabolism, its metabolite, an equally potent antimalarial has a long t1/2 of 10-18 days. Because of the close structural resemblance of amodiaquine to chloroquine, it was apprehended that amodiaquine may not be an effective antimalarial in areas with chloroquine-resistant Plasmodium falciparum. However, trials in Africa showed that amodiaquine produced a satisfactory response in such areas. The addition of artesunate further improved the cure rate. Trials were conducted in Africa with Artesunate – Amodiaquine co-formulated as FDC tablets, which produced high cure rates, and now this ACT has become the first-line therapy of uncomplicated falciparum malaria in many African countries. A recent trial in India also yielded ~ 97% cure for falciparum malaria. This ACT has been approved in India as FDC tablets in 3 strengths for different age groups.
  Regimen: Artesunate 200 mg (4 mg/kg) + amodiaquine 600 mg (10 mg/kg) per day for 3 days. Artesunate 25 mg/50 mg/100 mg +Amodiaquine 67.5 mg/135 mg/270 mg fixed dose combination tablets have been approved in India.
• Artesunate – pyronaridine (1:3): Clinical efficacy of artesunate – pyronaridine FDC (dose ratio l:3) has been tested in falciparum malaria in China, Thailand, and Africa with >95% success and no recrudescence in 28 days. Multidrug-resistant Plasmodium falciparum and Plasmodium vivex also respond. Clinical trials have been completed in India with a > 95% cure rate, and Ariesunate-pyronaridine is well tolerated. This ACT has not yet been approved for use in India.
  Regimen: Artesunate 100-200 mg (2-4 mg/kg) + pyronaridine 300-600 mg (6-12 mg/kg) per day for 3 days All the above-mentioned drugs should be administered orally

ACT Recommended By WHO

• Noting that the use of antimalarial drugs singly has failed to curtail the prevalence of malaria globally particularly due to emergence of chloroquine-resistant, followed by multidrug-resistant P. falciparum, the WHO has recommended that all cases of acute uncomplicated falciparum malaria should be treated only by combining one of the artemisinin compounds with another effective erythrocytic schizontocide.
• In choosing the companion drug, the most important consideration is its elimination t1/2, because effective concentrations in the blood must be maintained for at least 3 to 4 asexual cycles of the parasite, i.e. 6–8 days, to exhaust the parasite burden. Therefore, short t1/2 drugs have to be given for 7 days while longer-acting drugs can be given for l to 3 days. However, long t1/2 drugs allow subinhibitory concentrations to persist in the blood facilitating the selection of resistant mutants. Combining a short t1/2 drug with a long t1/2 drug in the conventional 3-day regimen runs the risk of de facto monotherapy after the short t1/2 drug is eliminated. This risk is minimized by choosing a short t1/2 drug that reduces the parasite load rapidly and drastically.
• Artemisinin compounds filing this requirement, as they rapidly kill > 95% plasmodia. They leave only a small biomass of the parasites to be eliminated by the long t1/2 drug, reducing the chances of selecting resistant mutants.

Advantages Of ACT Over Other Antimalarials

• Rapid clinical and parasitological cure.
• High cure rates (>95%) and low recrudescence rate.
• Absence of parasite resistance