Malaria treatment (Current WHO recommendations & guidelines) Presentation by Dr Maryse Dugué RBM Partnership Secretariat, Malaria Medicines & Supplies Services Copenhagen – 31 January 2006 7.3

Malaria distribution and reported case of resistance or treatment failure

First demonstration project in Thailand Treatment efficacy at Thai-Burmese border Thailand has been known for two decades as the country, where one antimalarial treatment after another has become ineffective following around 10 years of use. Thus, by the mid-1990s, the efficacy of mefloquine 25 mg/kg in western Thailand was as low as 75% (parasitological cure rate in 42 day tests). The combination of quinine and tetracycline (QT) has maintained its efficacy relatively well, but is considered far from satisfactory because of the long duration of the regimen (7 days), which leads to poor adherence. Following a number of clinical trials, it was decided to introduce a combination of artesunate 4mg/kg/day x 3 with mefloquine 25mg/kg in the most multi-drug resistant areas in the west of the country from 1996. This regimen has maintained a 42 day parasitological cure rate of around 95% since it was introduced. This is a truly remarkable achievement, and must be related to the artesunate, which is short-acting and to which no true resistance has been detected so far, somehow protecting the long-acting mefloquine, which has a long terminal half-life and is very vulnerable to the development of resistance.

Adoption of ACT as first-line treatment in 2000 Countries with falciparum malaria Few countries deployed ACTs in selected provinces/districts

ACT as first-line malaria treatment in 2006 Countries with falciparum malaria Countries which adopted ACT as 1st-line treatment

56 countries have adopted ACTs Updated 15 Jan. 2006 Continent Countries Drug Line AFRICA Burundi, Cameroon, Côte d'Ivoire, DRC, Eq.Guinea, Gabon, Ghana, Guinea, Liberia, Madagascar, Senegal, ST&P, Sierra Leone, Sudan (S), Zanzibar AS + AQ 1st Angola, Benin, Burkina Faso, Comoros, Ethiopia, Gambia, Guinea Bissau, Kenya Mali, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Togo, Zambia AL Côte d'Ivoire, Gabon, Mozambique, Sudan (N), ST&P, Zanzibar 2nd Mozambique, Sudan (N), South Africa (Mpumalanga) AS + SP ASIA Cambodia, Thailand AS + MQ Bangladesh, Bhutan, Laos, Myanmar Indonesia Afghanistan, India (5 Provinces), Iran, Tajikistan, Yemen Viet Nam DP Papua New Guinea Philippines, Iran SOUTH AMERICA Ecuador, Peru Bolivia, Peru, Venezuela Brazil, Guyana, Suriname AQ=amodiaquine; AL=artemether/lumefantrine; AS=artesunate; DP=dihydroartemisinin/piperaquine; MQ=mefloquine; SP=sulfadoxine/pyrimethamine

26 countries are deploying ACTs Updated 15 Jan. 2006 Continent Countries Drug Line AFRICA Burundi, Cameroon, Côte d'Ivoire, DRC, Eq.Guinea, Gabon, Ghana, Guinea, Liberia, Madagascar, Senegal, ST&P, Sierra Leone, Sudan (S), Zanzibar AS + AQ 1st Angola, Benin, Burkina Faso, Comoros, Ethiopia, Gambia, Guinea Bissau, Kenya Mali, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Togo, Zambia AL Côte d'Ivoire, Gabon, Mozambique, Sudan (N), ST&P, Zanzibar 2nd Mozambique, Sudan (N), South Africa (Mpumalanga) AS + SP ASIA Cambodia, Thailand AS + MQ Bangladesh, Bhutan, Laos, Myanmar Indonesia Afghanistan, India (5 Provinces), Iran, Tajikistan, Yemen Viet Nam DP Papua New Guinea Philippines, Iran SOUTH AMERICA Ecuador, Peru Bolivia, Peru, Venezuela Brazil, Guyana, Suriname 29% deploying 60% deploying 71% deploying AQ=amodiaquine; AL=artemether/lumefantrine; AS=artesunate; DP=dihydroartemisinin/piperaquine; MQ=mefloquine; SP=sulfadoxine/pyrimethamine

Malaria diagnosis Parasitological confirmation (microscopy or RDT) before treatment Exceptions: children under 5 years of age, from areas of high transmission where treatment is based on clinical diagnosis suspected severe malaria where parasitological confirmation is not immediately possible

Changing antimalarial treatment policy Treatment failure of >10% (as assessed through monitoring of therapeutic efficacy at 28 days) New treatment – an average cure rate of > 95% as assessed in clinical trials

Treatment of uncomplicated falciparum malaria Artemisinin-based combination therapies (ACT) are the treatments recommended for all cases of uncomplicated falciparum malaria including: in infants, in people living with HIV/AIDS for home-based management of malaria pregnant women in the 2nd and 3rd trimesters Exception: 1st trimester of pregnancy

Treatment of uncomplicated falciparum malaria The following ACTs are presently recommended: artemether-lumefantrine artesunate + amodiaquine artesunate + mefloquine artesunate + sulfadoxine-pyrimethamine Efficacy of ACTs depend on the efficacy of the partner medicine The artemisinin derivatives (oral formulations) and partner medicines of ACTs are not recommended as monotherapy

Treatment of uncomplicated falciparum malaria Second-line treatment: alternative ACT quinine + tetracycline or doxycycline or clindamycin

Treatment of severe falciparum malaria Any of the following antimalarial medicines are recommended Artesunate i.v. or i.m artemether i.m. quinine (i.v. infusion or i.m. injection). Full course of ACT or quinine + clindamycin or doxycycline when patient can tolerate oral treatment

How to contact us… Malaria Medicines & Supply Services (MMSS) Roll Back Malaria Partnership Secretariat Website: http://rbm.who.int/mmss/ Dr Maryse Dugue Manager Tel: +41 (0)22 791 4439 E-mail: duguem@who.int