Malaria border area

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  • 1. MALARIA DIAGNOSIS ANDTREATMENT IN BORDER AREAS: WHAT SHOULD WE PAY ATTENTION TO? Asep Purnama TC Hillers Hospital, Maumere, NTT
  • 2. STRATEGIES Prevention Vector control, Long Lasting Insecticide Net, Repellent etc Accurate diagnosis Prompt treatment with ACT Partnership Increase Coverage of ServiceErna Tresnaningsih, Direktur Pemberantasan Penyakit Bersumber Binatang, Depkes RISeminar Nasional Manajemen Malaria Terkini, Manhattan Hotel-Jakarta, 14 Juni 2008
  • 3. MALARIA DIAGNOSIS PROBLEMS
  • 4. Clinical responses to malaria infection vary widely
  • 5. CLINICAL MALARIA, BLOOD SAMPLE TAKEN & POSITIVE DIAGNOSIS IN INDONESIA 3,500,000 3,000,000 2,500,000 2,000,000 1,500,000 1,000,000 500,000 0 8 00 01 02 03 04 05 06 07 0 20 20 20 20 20 20 20 20 ar M n- Ja Not all Malaria cases are diagnosed by microscopist or RDT Slide positive malaria cases don’t decrease significantly
  • 6. M ALARIA KLINIS DAN PE E M RIKSAAN SE DIAAN DARAH M ALARIA DI JAWA BALI TAHUN 2000-20041600000 Klinis Pem SD 147570414000001200000 12105301000000 998791800000 756833600000 480048400000200000 0 2000 2001 2002 2003 2004 MALARIA KLINIS DAN PEMERIKSAAN SEDIAAN DARAH MALARIA DI LUAR JAWA BALI TAHUN 2000-2004 1974882 2000000 1702508 1732557 1686176 Kl i ni s Pem SD 1800000 1522831 1600000 1400000 1200000 1000000 404714 389477 337583 348366 479441 800000 600000 400000 200000 0 2000 2001 2002 2003 2004
  • 7. S ED I A A N D A R A H M A L A R I A P OS I T I F D A N M A L A R I A P f D A N M I X D I J A WA B A L I TA H U N 2 0 0 0 - 2 0 0 4 120000 SD Positif Pf + mix 100000 80000 60000 40000 20000 0 2000 2001 2002 2003 2004 SED I A A N D A R A H M A LA R I A PO SI T I F D A N M A LA R I A Pf D A N M I X D I LU A R JA W A B A LI T A HU N 2 0 0 0 - 2 0 0 4 SD Posit if Pf + mix200000 181315 155796 148478150000 140769 13209510000050000 0 2000 2001 2002 2003 2004
  • 8. MALARIA DIAGNOSIS What should we pay attention to? Prompt and accurate diagnosis is critical to the effective management of malaria Based on microscopic diagnosis/RDT Capacity building Equipment (microscope, RDT) Cost Quality Control
  • 9. Survey of General Practitioner’sKnowledge, Attitude and Practice on Malariain Sikka District, East Nusa Tenggara 2008 Jane Hidayat, Asep Purnama
  • 10. MALARIA TREATMENT PROBLEMS
  • 11. P. falsiparum : chloroquine resistance Countries with at least one study indicating chloroquine total failure rate > 20% Countries with at least one study indicating chloroquine total failure rate > 10% No recent data available
  • 12. P. falsiparum:Sulfadoxin-pyrimethamine resistance Countries with at least one study indicating sulfadoxine-pyrimethamine total failure rate > 20% Countries with at least one study indicating sulfadoxine-pyrimethamine total failure rate > 10% Sulfadoxine-pyrimethamine total failure rate < 10% No failure reported No recent data available
  • 13. P. vivaxprophylactic or treatment failure P. vivax prophylactic or treatment failure
  • 14. Anti Malaria Drug Resistance In Indonesia,RESISTANCE OF PLASMODIUM TO MALARIA DRUGS IN INDONESIA 1978 - 2003
  • 15. SAFE & EFFECTIVE DRUGS
  • 16. COMPLIANCE
  • 17. COST
  • 18. MALARIA TREATMENT What should we pay attention to? Artemisinin based Combination Treatment Radical treatment is essential Outcome focus on clinical cure, parasitological clearance, and blocking transmission Monitoring therapeutic efficacy of antimalarial drugs based on clinical and parasitological responses (in- vivo 28 days)
  • 19. 74 countries have adopted ACTs Updated 1 Oct 2007Continent Countries Drug Line Burundi, Cameroon, Congo, Côte dIvoire, Democratic Republic of Congo, Eq. AS + AQ 1st Guinea, Gabon, Ghana, Guinea, Liberia, Madagascar, Eritrea, Mali, Mauritania, Senegal, Sao Tomé & Principe (ST&P), Sierra Leone, Sudan (S), AFRICA Tchad, Zanzibar Angola, Benin, Botswana, Burkina Faso, Central African Republic, Comoros, AL 1st Ethiopia, Gambia, Guinea Bissau, Kenya, Malawi, Mozambique, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Togo, Zambia, Zimbabwe Côte dIvoire, Djibouti, Gabon, Sudan (N), ST&P, Zanzibar AL 2nd Djibouti, Somalia, Sudan (N) AS + SP 1st Cambodia, Malaysia, Myanmar, Thailand AS + 1st MQ Bangladesh, Bhutan, Laos, Philippines, Solomon Islands, Sri Lanka, Vanuatu AL 1st ASIA Indonesia AS + AQ 1st Afghanistan, India, Iran, Pakistan, Saudi Arabia, Tajikistan, Yemen AS + SP 1st Viet Nam, China DP 1st Papua New Guinea AS + SP 2nd Iran, Saudi Arabia, AL 2nd SOUTH Ecuador, Peru AS + SP 1st AMERICA Bolivia, Colombia, Peru, Venezuela AS + 1st MQ Brazil, Colombia, Guyana, Suriname AL 1st
  • 20. INDONESIA’S TREATMENT POLICYUncomplicated Pf Complicated Pf ATS3+AQ3+PQ  QN parenteral-oral7+Dx7/Clin7 DHP3+PQ  Artemether im-AQ3+ATS3 QN7+DX7/Clin7+PQ  Artesunate iv-AQ3+ATS3Uncomplicated Pv Prophylaxis ATS3+AQ3+PQ14  Doxycycline DHP3+PQ14 Outbreak containment (MFS) QN7+PQ14  AQ3+ATS3+PQ1
  • 21.  Since 2004 Artesunate-amodiaquine as the first line ACT for P.falciparum malaria (based on the African study Adjuik M et al, Lancet 2002). Efficacy of Artesunate-amodiaquine varied between study sites 78-96% (Gasem H et al, 2004 ; Tjitra E et al, 2004; and Sutanto I et al, 2004; Setyoningrum E et al, 2005; Hasugian et al, CID 2006 ). Utility of Artesunate-amodiaquine reported low (<50%) due to poor compliance and adherent events because of need to take large number of pills (personal communication)
  • 22. ASSESMENT OF CHLOROQUINE AND ARTESUNATE- AMODIAQUINE COMBINATION EFFICACY FOR THETREATMENT OF UNCOMPLICATED FALCIPARUM MALARIA IN BELU DISTRICT, EAST NUSA TENGGARA Asep Purnama et al, IJIM 2006:38;327-31
  • 23. RESULTS Due to an increase in the chloroquine treatment failure rate to 47,62%, recruitment was terminated prematurely A total of 95 of the originally recruited 203 patients were enrolled in the study Artesunate-amodiaquine showed superior 28-day cure rate Chloroquine versus artesunate-amodiaquine was 22/42 [52,38%] versus 49/53 [92,45%]; p<0,01 However , efficacy of As+Aq was <95%, below than WHO standard
  • 24. ARTESUNATE - AMODIAQUINE VERSUS CHLOROQUINE FOR THE TREATMENT OF VIVAX MALARIA IN MAUMERE, EAST NUSA TENGGARA National Institute of Health Research and Development, MOH, Jakarta
  • 25. RESULTS A prospective comparative clinical trial of efficacy, safety and tolerability of As+Aq versus chloroquine for treatment of uncomplicated vivax malaria with a 28-day follow up Of a total 105 enrolled patients there were 100 patients could be analysed The efficacies of As+Aq and Chloroquine were 88% and 40,8% on day 28 by ITT and 93,2% and 47,2% by PP, respectively However , efficacy of As+Aq was <95%, below than WHO standard
  • 26. NEED ALTERNATIVE ACTsATS3+AQ3 QN7+Dx7/Clind Efficacy <95% (Papua 70-87%)  Efficacy ? AR: nausea and vomiting  AR: dizziness, tinnitus Compliance? (no of pills)  Poor compliance Cost and accessibility?
  • 27. IMPROVING ACTCOMPLIANCE CURE RATE  Effective: rapid Tolerate: tasteless Safe: risk groups (infancy broad spectrum  Practice : all species and pregnancy) adverse events single dose only Simple: fixed-dose regimen all age groups single daily dose/ single dose only
  • 28. CLINICAL TRIALS ON ACTs (ATS+PD)3 (ART+NTQ)1 VS Parentral ATM vs QN ATS3+AQ3 VS (DHA+PPQ)3 (ART+PPQ)2 (ATS+PD)3 vs ((ATM+LMF)3CQ3 vs (CQ3+SP1) vs AQ3 IV ART vs QN (ATS+PD)3 vs (ART+NTQ)1 VS ((CQ)3 (ATM+LMF)3 VS (DHA+PPQ)3 (ATS+PD)3 vs (DHA+PP)Q3 ((ATM+LMF)3 ATS3+AQ3 VS (DHA+PPQ)3
  • 29. EFFICACY COMBO VS FIXED REGIMEN N=352Artesunate+amodiaquine (ATS3+AQ3) vs Artemisinin+piperaquine (ART+PPQ)2 Pf: 93.8% vs 96.5% Pv:96.5% vs 100% (Tjitra E et al, 2005) 47 3.56 35 2.54 23 1.52 11 0.50 0 Day 0 Day 1 Day 2 Day 3 Day 7 Day 14 Day 21 Day 28 Day 0 Day 1 Day 2 Day 3 Day 7 Day 14 Day 21 Day 28 ATS3+AQ3 ART2+PPQ2 ATS3+AQ3 ART2+PPQ2
  • 30. Artemisinin/naphtoquine P. vivax, P. falciparum, P.mix phase III trial A Phase III randomized, open label, non-inferiority trialof artemisinin plus naphtoquine (ARCO) versus dihydroartemisininplus piperaquine in adult uncomplicated malaria patients: A Multi- centre study in Indonesia
  • 31. Artemisinin/naphtoquine phase III trial Study outline 401 patients randomized Study duration: April 2007 – August 2008 Treatment : single dose, F/U to 42 days Multicentre: 2 sites, 4 hospital :
  • 32. Artemisinin/naphtoquine phase III trial Conclusions The trial demonstrated non inferiority treatment study Arco vs Duocotecxin  P. vivax 98,7% vs 97,3%  P. falciparum 98,7% vs 97,1% Both new fixed-dose ACTs are confirmed very effective, safe and tolerate for treatment of any malaria in adults, and meet with the recent WHO recommendation for replacing ineffective drugs
  • 33. ARTEMISININ FOR SEVERE MALARIAARTEMETHER QUININE DIHYDROCHLORIDE FCT= 35.5 hours  FCT= 37.4 hours PCT= 38.9 hours  PCT= 41.8 hours Regain consciousness=  Regain consciousness = 32 hours 62.8 hours CFR cerebral mal =  CFR cerebral mal = 71.4% 37.5%  Overall CFR= 23% Overall CFR= 13% Tjitra E et al, MJI, 1996
  • 34. SEAQUAMAT TRIAL Study design: Open label, multi centre, randomised, comparison of artesunate and quinine in severe falciparum malaria Study sites: 2003-2005  Bangladesh  Indonesia (Timika Hospital, Timika)  India  Myanmar Target sample size: 2,000 patients 1400 enrolled as at February 2005 Coordination: Wellcome Unit, Bangkok
  • 35. RESULTS (SEAQUAMAT Group, Lancet, 2005) Trial stopped early (n=1461) by Safety Monitoring committee because clear benefit with artesunate Overall reduction in mortality with artesunate 34.7% (95%CI 19-48%) p=0.0002  mortality quinine: 164/731 (22%)  mortality artesunate: 107/730 (15%) Indonesian national policy change before the results published Australian policy change 2006
  • 36. THE IMPORTANCE OF COOPERATION BETWEEN NEIGHBOURING COUNTRIES  Many health problems are cross border (malaria, rabies, filaria, DHF etc)  Limited resource: mutual cooperation important  Potential for inefficiency if countries work alone  Sharing expertise and facilities  Cooperation on research projects  Share results of individual research  Cooperation to develop guidelines or policy
  • 37. MASS BLOOD SURVEY-YASPEM Target 45.454 [3 kecamatan] Blood sample taken 37.974 83,48 % Results F 351 0,9 % V 517 1,4 % Mix 71 0,2 % Total 939 2,5 %
  • 38. DROP OUT Adverse event 18 [1,9%] Hospitalized 6 [0,6%] Loss of follow up 8 [0,8%] Reject to take medicine 12 [1,3%]
  • 39. SOME EXAMPLES OF POOR PRACTICE• Giving SP to patients with fever even though blood smear negative• Treating uncomplicated malaria with parenteral quinine or arthemeter im• Treating complicated malaria with chloroquine or ACT• Giving SP for P vivax malaria• Giving Primaquine 15 mg for 14 days for P falciparum malaria• Giving all available forms of treatment to the one patient
  • 40. SOME EXAMPLES OF POOR PRACTICE (contd)• Using RDT to evaluate response to treatment• Giving transfusion to malaria patients with mild anaemia• Using steroids to treat cerebral malaria• Inadequate fluid for complicated malaria• Postponing haemodialysis for complicated malaria with acute renal failure• Unawareness of hypoglycemia in complicated malaria• Not giving ACT for 3 days• Giving inadequate doses of artesunate or arthemeter