Therapeutic Efficacy of Anti-Malarial Drugs in Ethiopia: Trends and Policy Implications

1. Therapeutic Efficacy of Anti-Malarial Drugs in Ethiopia: Trends and Policy Implications Meeting on Discussion Towards the Development of an Inter-Regional Network for Monitoring Anti-Malarial Drug Efficacy in the Horn of Africa, 23 � 25 March 2004, Cairo, Egypt Ambachew M. Yohannes, NPO/WHO

2. Background Information 75% of the land malarious & 47.6 million people (68%) at risk, Dominant parasite species: P. falciparum (60 - 70%) & P. vivax (30 - 40%) & A. arabiensis is the main vector, Transmission is Seasonal & unstable � epidemic prone All age groups are at risk & no protective immunity, In 2003 malaria was the first cause of OPD consultations, admission & hospital deaths, In 2003 Malaria epidemics affected 211 (46%) 2524 villages and 2.2 million cases recorded (June-December) Malaria prevention and control (CM, IRS, ITNs &EM) Major Problems in Malaria Control Low Health Service Coverage (61%) Resource limitation � manpower, budget Poor malaria epidemics surveillance, preparedness and response, Lack of coordinated operational studies esp. on dugs & insecticides,

3. Therapeutic Efficacy of Anti-Malarial Drugs- Chloroquine 1950s Chloroquine first introduced during the launch of the Malaria Eradication Service, 1974 Ethiopian strains less sensitive to chloroquine (CQ) but fully respond to normal regimen (Dennis et al), 1986 First report on emergence of CQ resistant P. falciparum (Teklehaimanot, A.) 1997 Nationwide therapeutic efficacy study on chloroquine (WHO protocol 1996) in 14 sites showed high treatment failure rates: 73.7% (0-100) in children under five years of age 63.7% (12.5-88.2) in subjects aged 5 and above, 2003 Therapeutic efficacy study on chloroquine for the treatment of vivax malaria conducted in 2002 � no conclusive results reported yet.

4. Therapeutic Efficacy of Anti-Malarial Drugs: Amodiaquine & Sulfadoxine-Pyrimethamine Therapeutic efficacy of Amodiaquine for the treatment of falciparum malaria evaluated in 1998, Mean treatment failure rate of 21% (6 � 67%) reported, Possible cause due to cross resistance with chloroquine, Therapeutic efficacy of SP conducted from 1997 � 1998 Results from 7 sites showed SP treatment failure rate of 5% (0 � 10%), Study conducted 13 years after introduction the drug in 1985.

5. Malaria Treatment Policy (1998 to Present) July 1998: National Anti-malarial Drug Policy Workshop conducted, Data collected from therapeutic efficacy studies reviewed, (WHO protocol, 14 days follow-up), Recommendations P. falciparum ----------- Sulfadoxine-Pyrimethamine (SP) P. vivax ------------------- Chloroquine (CQ) Second-line --------------- Quinine Clinical malaria ------- CQ + SP SCM------------------------ Quinine

6.  Trends in the Efficacy of Sulfadoxine-Pyrimethamine Nationwide representative study not conducted in the period 1998 � 2002, Results from Isolated studies showed different levels of resistance to SP, Treatment failure of <5% in Tigray Region (1999/2000), (WHO 1996, 14 days) Treatment failure rate of 18% in Zuwai in 1998 Institute of Pathobiology, (extended test, 28 days) Treatment failure rate of 30% in Zuwai in 2000 Institute of Pathobiology, (WHO 1996, 14 days) Treatment failure of >80% in Central Ethiopia (2000)Ethiopian Nutrition & Health Research Institute, (low txn. Accra Meeting & consultations with WHO-HQ) Consumer and service provider complaints on Sulfadoxine-Pyrimethamine increasing, Nation wide study conducted on SP efficacy (in 14 sites, October 03 � January 04) Preliminary results show treatment failure rate of 32.7% (13.6 � 58.8) final results pending verification.

7. Trends in the Burden of Malaria Increase over the past three years, OPD Consultations Admissions In-patient deaths Large scale malaria epidemics in 2003 (retrospective surveys results). Major climatic changes Poor coverage & targeting of vector control interventions, Decline in the efficacy of the first line drug, SP Limited use of gametocytocidal (primaquine) drugs during epidemics & the inefficiency of SP on P. falciparum gametocytes � High gametocyte carriage?

8. The Malaria Burden � Yearly Out-patients

9. The Malaria Burden � Yearly Admissions

10. The Malaria Burden � Yearly Deaths

11. Actions Strengthen Malaria Prevention & Control Activities, Vector control through better targeting, coverage and timing of interventions. Surveillance, preparedness & response capabilities at all levels. malaria diagnosis & treatment services at all levels Timely & correct diagnosis of cases, Treatment with safe, effective & affordable drugs - Which drug (s)?

12. Options (1) Treatment of uncomplicated falciparum malaria Artemether-Lumefantrine (highly recommended) Artesunate + Amodiaquine (unlikely) Artesunate + Sulfadoxine-Pyrimethamine (unlikely) Artesunate + Mefloquine (needs investigation) Non ACT option: SP + Amodiaquine (unlikely) Treatment of vivax malaria Chloroquine Primaquine (radical cure)

13. Options (2) Falciparum malaria during pregnancy P. falciparum � Quinine, Artesunate (registration?), Drug for IPT - ? Sever and complicated malaria Quinine IM Artemether in peripheral areas & epidemics (registration?) Chemoprophylaxis Mefloquine (registration?)

14.  The Way Forward Revise the malaria treatment policy based on available evidences, Data validation and finalization of report on SP efficacy study � April 2004, National Workshop on anti-malarial treatment policy � June 2004, Hasten process to include Artemether-Lumefantrine in to the national drug list Safety & efficacy evaluation on CoArtem completed in four sites, Application for registration submitted to the Drug Administration & Control Authority, DACA), Resource mobilization GFATM 2nd round fund secured, GAFTM 4th round proposal prepared with special focus on ACTs and RDTs, Preparations for Implementation Guidelines will be revised based on the workshop recommendations, Training of trainers on the storage & use of ACTs & RDTs will be conducted, Ensure supply of RDTs for peripheral areas with no laboratory facility and for rapid investigation of malaria epidemics.