How to protect yourself against malaria

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1 World Health Organization 17 September, 2008 How to protect yourself against malaria Mine Action Technology Workshop 2008 co-hosted by the United Nations Mine Action Service (UNMAS) and the Geneva International Centre for Humanitarian Demining Presented by Dr Andrea Bosman Global Malaria Programme Geneva, 10 September 2008 THE BURDEN OF MALARIA: EVERY DAY MALARIA KILLS IN NUMBERS EQUIVALENT TO "9/11" TRAGEDY OF THE NEW YORK TWIN TOWERS 2 1

If malaria burden was proportional to country surface areas Dorling D Worldmapper. PLoS Med 4 (1), 2007 3 Global malaria burden 4 species of malaria parasites infect people Plasmodium falciparum, P.

2 If malaria burden was proportional to country surface areas Dorling D Worldmapper. PLoS Med 4 (1), Global malaria burden 4 species of malaria parasites infect people Plasmodium falciparum, P. vivax, P. malariae, P. ovale 247 million malaria patients per year Nearly 1 million deaths due to malaria per year 90% of deaths and 60% of cases occur in Africa south of the Sahara 109 malaria endemic countries/territories 15 countries with no P.falciparum transmission, only P.vivax 7 countries with recently no more locally transmitted cases 4 2

3 The Global Malaria Picture Resurgence in Central Asia & Eastern Europe Poor access to health care in the Amazonas Childhood dealths in sub- Saharan Africa MDR falciparum malaria Vast burden of morbidity & economic loss Evolution of global malaria distribution Sweden and parts of North America freed from malaria Mid 19th century countries freed from malaria Tunisia, Maldives and UAE freed from malaria EMRO INTERCOUNTRY MEETING, 1-4 June

4 Lower malaria vectorial capacity in temperate and sub-tropical areas mid 19 th century 7 8 4

Cured Cured Non- Infected Infected Disease Severe Death Vector control Intermittent Preventive Therapy

5 The life cycle of the malaria parasite, Plasmodium Sporozoites Hepatic phase Sexual phase Invading ring stage Asexual Erythrocytic cycle Trophozoite Gametocytes Effective interventions are available Resolved Cured Cured Non- Infected Infected Disease Severe Death Vector control Intermittent Preventive Therapy in pregnancy Chemoprophylaxis Early Diagnosis Appropriate Treatment Referral Hospital-based management 5

drug formulations Current WHO recommendations for risk areas in malaria endemic countries Green Blue Yellow Orange Red no prevention needed

6 Need for new tools and technologies Resolved Cured Cured Non- Infected Infected Disease Severe Death ITN: new long lasting Insecticides: Safer & longer residual effect Intermittent Rx: safer drugs in pregnancy Vaccines New combination therapies Better rapid diagnostic tests Better drug formulations Current WHO recommendations for risk areas in malaria endemic countries Green Blue Yellow Orange Red no prevention needed type I prevention (anti-mosquito) type II prevention (CQ) type III prevention (CQ+P) type IV prevention (M, D or A-P) Plus mosquito bite prevention 6

7 Personal protection Insecticide treated mosquito nets & curtains Now insecticides are incorporated into the synthesis of the netting material itself - LLNs Can you see any problem? 7

8 Chemoprophylaxis for areas with high falciparum transmission or high resistance WHO Recommended regimens Mefloquine 5mg/kg weekly Doxycycline 1.5 mg/kg daily Atovaquone proguanil * kg: One pediatric tab daily kg: Two pediatric tabs daily kg: Three paediatric tabs daily - > 40 kg: One adult tablet daily * start 1 day before departure and continue for 7 days after return Additional regimen Primaquine off-label use 30 mg base daily has protective efficacy above 85% against P.falciparum and primary infections with P.vivax Needs G6PD screening JAMA 2007; 297: Similar protective efficacy and effective against all Plasmodium species 15 Current WHO recommendations when to start & when to stop taking chemoprophylaxis regimen atovaquoneproguanil Chemoprophylaxis preferably 2-3 weeks before departure start 1 week before arrival day before arrival 1 week upon return stop 4 weeks upon return exceptionally 4 weeks upon return When interrupted daily chloroquine proguanil doxycycline weekly chloroquine mefloquine International Travel and Health (WHO, 2008) 8

9 current guidelines & WHO recommendations long-term travellers atovaquone-proguanil chloroquine doxycycline proguanil mefloquine long term use > 6 months In European countries use of limited duration (5 weeks, 3 months, 6 months, "many months", 1 year), in USA unlimited duration risks low, except retinal toxicity at cumulative dose of 100 g (3-5 yrs) limited data > 12 months use, but reassuring risks low no increased risks if tolerated in the short term, no accumulation In sum: "Anything tolerated in the short term can most probably also be taken long-term" Adherence -- Tolerability High risk group: pregnant women In areas with low or unstable transmission Acquired Immunity = Low Clinical Illness Severe Disease All pregnancies at risk Up to 60% fetal loss and 10% maternal deaths 50% maternal mortality with severe disease Risk to Mother Risk to Fetus 18 9

10 current guidelines & WHO recommendations chemoprophylaxis use in special groups Chemoprophylaxis 1st trimester pregnancy 2nd & 3rd trimester pregnancy breast feeding young children atovaquoneproguanil <11 kg chloroquine doxycycline < 8 yrs mefloquine?? < 5 kg proguanil = safe = not recommended for lack of data = contra-indicated International Travel and Health (WHO, 2008) Chemoprophylaxis during pregnancy and breastfeeding period Areas with P.vivax or CQ sensitive P.falciparum - Chloroquine weekly chemoprophylaxis Areas with P.vivax and P.falciparum and emerging CQ resistance - Chloroquine + proguanil daily chemoprophylaxis Areas with high P.falciparum transmission or high levels of resistance Mefloquine weekly chemoprophylaxis (limited safety information in first trimester) 20 10

11 The clinical presentation of malaria Fever (uncomplicate d malaria) Foundations of the Case Management Strategy Cumulative Probability of a fatal outcome ANTIMALARIAL TREATMENT t (hours) The earlier the treatment, the lower the probability of fatal outcome Severe malaria 11

12 Plasmodium falciparum Malaria mortality Plasmoodium vivax Malaria Rapid Diagnostic Tests (RDTs) contact for specific questions: 12

Rapidly increasing range of malaria RDT products ~50 manufacturers with named products known to WHO >50 million tests procured in 2007 Most endemic countries have no / weak regulations Manufacturer

13 Rapidly increasing range of malaria RDT products ~50 manufacturers with named products known to WHO >50 million tests procured in 2007 Most endemic countries have no / weak regulations Manufacturer Access Bio ACON laboratories Alldiag Ameritek Amgenix Binax r-biopharm Bio-Quant Inc. Biotech Trading Partners Cellabs Brittney Bio-Analytics C.A. Core Diagnostics Cortez CTK Diamed AG Fortress Diagnostics Genelabs GlobaleMed Guangzhou Wondfo Human Gmbh Inbios International Immunodiagnostics J Mitra KAT Medical Makro Medical Merlin Labs Omega Diagnostics Orchid Biomedical Systems Premier Medical Corporation R&R Marketing SDHO Span Diagnostics Standard Diagnostics Syntillent Tashima Trinity Biotech Unimed Vision Biotech Zephyr Biomedical Systems Product Carestart Malaria Malaria Rapid Test Device Palutop dbest Malaria Rapid Test OnSight Malaria NOW-ICT MalaQuick (~NOW-ICT) One Step malaria Rapid Test Malaria Pf-only Rapid Test Rapimal Immu-Sure Malaria Malaria Test Core Malaria Malaria P.f. RapiCard InstaTest CTK Onsite OptiMal Malaria Test Assure Malaria Smart Check Malaria One Step Malaria Hexagon Malaria Malaria Test Card Advantage Malaria KatQuick MakroMAL Malaria Pf test Visitect malaria Paracheck First Response Malaria Antigen Test ICT Malaria ParaHIT SD Bioline Malaria ADI Malaria Uni-Gold Malaria FirstSign / Paraview Malaria Malaria Pf Falcivax Vulnerabilities of RDTs in the field Cautions: Detect antigen, not parasites. (-) May reflect recent, not current, parasitaemia. Degraded by excessive heat. Limited shelf life. Accuracy is dependent on technique used. 13

Field trials eg. Variation in results in published trials e.g. ICT Malaria, OptiMAL : Sensitivity >90% in multiple trials, but.

6 Huong et al 2002 80.8 Stow et al 1999 74-90 W ongsrichanalai 1999 89 Gaye et al 1998 86.

microscopy) 'O ptim AL' 80% Hernandez et al 2001 88.5 Jelinek et al. 1999 70.

3 Rubio et al 2001 All had poor sensitivity below 100 parasites per microlitre.

14 Field trials eg. Variation in results in published trials e.g. ICT Malaria, OptiMAL : Sensitivity >90% in multiple trials, but... Sensitivity (% ) for P. falciparum (vs. microscopy) ICT M alaria Pf, Pf/Pv Iqbal et al Huong et al Stow et al W ongsrichanalai Gaye et al M ason et al Rubio et al Leke 1999 Sensitivity (% ) for P. falciparum (vs. microscopy) 'O ptim AL' 80% Hernandez et al Jelinek et al M ankhambo et al Ricci et al Huong et al M ason et al Rubio et al 2001 All had poor sensitivity below 100 parasites per microlitre. Malaria diagnosis Quality-assured confirmation of diagnosis with microscopy before treatment Exception: Patients with suspected severe malaria when blood slide examination is not immediately possible 28 14

Treatment of uncomplicated falciparum malaria Artemisinin-based combination therapies (ACT) are treatments of choice for all cases of uncomplicated falciparum malaria including: infants, people

15 Treatment of uncomplicated falciparum malaria Artemisinin-based combination therapies (ACT) are treatments of choice for all cases of uncomplicated falciparum malaria including: infants, people living with HIV/AIDS for home-based management of malaria pregnant women in the 2 nd and 3 rd trimesters Exception: 1 st trimester of pregnancy* * use ACTs only if no alternative effective antimalarials 29 Treatment of uncomplicated falciparum malaria The following ACTs are recommended by WHO: artemether-lumefantrine artesunate + amodiaquine in artesunate + mefloquine artesunate + sulfadoxine-pyrimethamine 95% cure rates in most studies 1 st -line treatment based on therapeutic efficacy studies in the country Response to treatment of travellers depends on the origin of infection 30 15

16 Anti-relapse therapy in vivax malaria To achieve radical cure, relapses must be prevented by giving primaquine. In low-transmission areas the benefits of deploying primaquine are considered to exceed the risks. Primaquine in 0.25 mg/kg daily doses (adult daily dose of 15 mg) should be given for 14 days - no evidence that shorter courses are effective. P. vivax infections acquired in Indonesia and Oceania require higher dose of primaquine for radical cure, i.e mg/kg per day for 14 days 31 Key points to remember 1. No protective malaria "immunity" even after living many years without clinical attacks in endemic areas be aware of the risk 2. Travel to endemic areas with insecticide-treated mosquito nets, preferably long-lasting 3. Start appropriate chemophrophylaxis as for short-term travellers, and continue for all the duration of exposure 4. Evaluate possibilities for access to early malaria diagnosis and prompt treatment at destination 5. Procure highly effective artemisinin-based combination therapy for stand-by emergency treatment of uncomplicated malaria 6. If febrile, report exposure to malaria risk to the treating clinician 32 16

17 Acknowledgements David Bell, WHO Western Pacific Region Kamini Mendis, WHO Global Malaria Programme Aafje Rietveld, WHO Global Malaria Programme Contact to ask more specific malaria questions: Many thanks for your kind attention 33 17

Antimalarials in the WHO Essential Drugs List for Children Reviewer No.1

Antimalarials in the WHO Essential Drugs List for Children Reviewer No.1 Part I: Evaluation of the current list Proposed grouping from the March 2007 meeting 6.5.3 Antimalarial medicines 6.5.3.1 For curative