1 Global Malaria Programme Update from the Global Malaria Programme Update from the Global Malaria Programme Silvia Schwarte Diagnosis, Treatment and Vaccines Global Malaria Programme Interagency Pharmaceutical Coordination Group Meeting June 2015 UNICEF SD, Copenhagen, Denmark

Outline  Global Technical Strategy  WHO Guidelines for the Treatment of Malaria: 3 rd Edition  Primaquine - Transmission blocking: Single low-dose primaquine in P. falciparum malaria - Relapse prevention: Primaquine in P. vivax / P. ovale malaria (G6PD status!) - Evidence Review Group meeting on G6PD point of care tests  Antimalarial medicines - Sourcing of quality-assured products - SMC SPAQ supply shortage  Vaccine RTS,S/AS01

Since 2000, substantial progress achieved Malaria case incidence has been reduced by 30% globally Malaria mortality rates have decreased by 47% worldwide ~50 for person at risk ~25 for person at risk ~ per persons at risk ~9 000 per person at risk Incidence rate Mortality rate

44 Global Technical Strategy Calls for an acceleration of efforts and a shift on strategic priorities Ambitious goals calling for an acceleration of efforts Strategic framework increasing focus on elimination and surveillance Reduce malaria mortality rates vs ≥40%≥75%≥90% Reduce malaria case incidence vs ≥40%≥75%≥90% Eliminate malaria from countries ≥ 10 countries ≥ 20 countries ≥ 35 countries Prevent re- establishment in all malaria-free countries Pre- vented 3 key pillars 2 supporting elements 1.Ensure universal access to malaria prevention, diagnosis and treatment 2.Accelerate efforts towards elimination and attainment of malaria-free status 3.Transform malaria surveillance into a core intervention 1.Harnessing innovation and expanding research 2.Strengthening the enabling environment

55 WHO Guidelines for the Treatment of Malaria 3 rd Edition released on World Malaria Day

66 WHO Guidelines for the Treatment of Malaria What's new? (1) Prevention  IPTp-SP: Intermittent preventive treatment in pregnancy with at least three doses of sulfadoxine-pyrimethamine (SP)  IPTi: Intermittent preventive treatment in infants with SP together with DPT vaccination  SMC: Seasonal malaria chemoprevention with SP + AQ in areas with highly seasonal transmission Primaquine (PQ)  P. falciparum (Pf): Single low dose of PQ to reduce the trans- missibility of Pf infections  P.vivax (Pv) / P. ovale (Po): Recommendations for treating G6PD deficient patients with weekly PQ dose to prevent relapse in Pv or Po malaria under medical supervision DPT – diphtheria, pertussis, tetanus G6PD – Glucose-6-phosphate dehydrogenase

77 WHO Guidelines for the Treatment of Malaria What's new? (2) Uncomplicated Pf malaria  Revised dose recommendation for dihydroartemisinin + piperaquine in young children (< 25kg body weight)  Close monitoring of people with Pf hyperparasitemia presenting with uncomplicated malaria Severe malaria  Revised dose recommendation for parenteral artesunate (AS) in young children (< 20kg body weight)  Recommendation for pre-referral rectal AS limited to children <6 years of age Medicines' formulation  Recommended use of fixed-dose combinations and paedi- atric solid formulations

88 Single-dose primaquine as gametocytocide in P. falciparum malaria Single dose of primaquine at 0.25mg base/kg:  is effective in transmission blocking  is unlikely to cause serious toxicity in subjects with any of the G6PD variants In low transmission areas, a single 0.25 mg base/kg primaquine dose should be given to all patients with parasitologically-confirmed P. falciparum malaria on the first day of treatment in addition to an ACT, except for pregnant women, breastfeeding women in the first six months and children less than six months of age due to insufficient data on the safety of its use in these categories. G6PD testing is not required.

99 Primaquine to prevent relapse in P. vivax or P. ovale malaria  The G6PD status of patients should be used to guide the administration of primaquine for relapse prevention  Where status is unknown and G6PD testing is unavailable, the decision to prescribe primaquine must be based on an assessment of the risks and benefits of treating versus not treating  To prevent future relapse, treat people with P. vivax or P. ovale malaria (excluding people with G6PD deficiency, pregnant, infants aged <6months, women breast- feeding infants < 6 months of age) with a 14-day course ( mg/kg daily) of primaquine in all transmission settings.  In people with moderate G6PD deficiency, consider relapse prevention with primaquine 0.75 mg base/kg once a week for 8 weeks under close medical supervision.  In women who are pregnant or breastfeeding, consider weekly chemo- prophylaxis with chloroquine until delivery and breastfeeding is com- plete, then treat with 14 days of primaquine to prevent future relapse.

10 Recommendations on G6PD testing to promote safe use of primaquine anti-relapse therapy  WHO recommends that G6PD status is ascertained before administering daily primaquine ther­apy for 14 days to prevent relapses in patients with confirmed acute P.vivax or P. ovale infection.  The introduction of point-of-care G6PD tests should proceed, with appropriate investment in quality assurance and quality control including training, supervision, behaviour change communications and close monitoring of the feasibility, acceptability and ease of use of these tests. Lessons learnt from initial small scale deployment should guide decisions to expand deployment of G6PD diagnostic services across the health care system.  If G6PD status is unknown, then G6PD qualitative point-of-care tests can be deployed to identify G6PD non-deficient patients prior to prima­quine administration. Such tests should be >95% sensitive compared to spectro- photometry or equivalent quantitative tests, stable at temperatures expected in tropical settings (30–40°C) and have a negative predictive value of >95% at G6PD enzyme activity levels <30% of normal.  The specific indications and contraindications for primaquine radical cure in males and females with G6PD deficiency should follow the recommendations given in the WHO Guidelines for the Treatment of Malaria (3 rd edition, 2015).

AL: artemether/lumefantrine; AS: artesunate; AQ: amodiaquine; MQ: mefloquine; SP: sulfadoxine/pyrimethamine WHO-prequalified medicines Last updated 8 June 2015 – no changes since November 2014  Fixed-dose combinations - AL, 20mg/120mg: Ajanta, Cipla, Ipca, Macleods, Mylan, Novartis, Strides - AL, 20mg/120mg, dispersibles: Ajanta, Novartis - AL, 40mg/240mg: Mylan - ASAQ: Ajanta, Cipla, Guilin, Ipca, Sanofi - ASMQ: DNDi/Cipla  Co-Blisters (Co-B) - AS + AQ: Cipla, Guilin, Ipca, Strides - AS + SP: Guilin  Injectables - AS powder for injection (30mg, 60mg, 120mg): Guilin Full list of WHO- prequalifed medicines available at:  Eurartesim (DHA-PPQ) (Uncomplicated Pf malaria) – EMA approval  Rectal AS (Pre-referral treatment of severe malaria in children < 6 years)  PQ (Pf transmission blocking and Pv/Po relapse prevention)  SP (Intermittent Preventive Treatment in pregnancy and during infancy)  SP+AQ (Seasonal Malaria Chemo- prevention)

12 PQ and SP sourcing for procurement (last updated 8 June 2015) LIST OF MALARIA PHARMACEUTICAL PRODUCTS classified according to the Global Fund Quality Assurance Policy (Version 76 reviewed, April 2015)

13 Seasonal Malaria Chemoprevention (SMC) Medicine shortage: sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) IEC – Information, education and communication  Single-source supplier for quality-assured co-blistered SP+AQ: WHO PQ: SP+AQ (500/ 25 mg mg), GF ERP: SP+AQ (250/12.5 mg + 75 mg)  Target area: Highly seasonal malaria transmission across the Sahel sub-region  Target population: A complete SP+AQ treatment course should be given to children aged 3 and 59 months, at monthly intervals beginning at the start of the transmission season, up to a maximum of four doses during the malaria transmission season.  Prioritization: WHO strongly encourages prioritization of communities that have implemented SMC in the years 2013 and 2014 for continuation in  Interim measure: Procurement and distribution of separate blisters / loose tablets; training, IEC materials, etc.  Impact monitoring!

14 4 th set of results on RTS,S/AS01 released Effect of booster dose and longer-term follow up to an average of four years per child from vaccination  Efficacy is short-lived – booster dose required.  Clinical malaria: Overall efficacy with booster dose in 6-12 weeks and 5-17 months old children at 26% and 36%, respectively, over full duration of trial.  Severe malaria: Without booster dose, no protection in both age groups, as cases averted in the first 18 months were shifted to older age groups as efficacy wanes. With booster: Overall efficacy in 5-17 months old children at 32%.  European Medicines Agency is currently reviewing under Article 58 – only in case of a "positive scientific opinion" WHO will convene the Strategic Advisory Group of Experts (SAGE) on Immunization and the Malaria Policy Advisory Committee (MPAC) to assess a potential policy recommendation. RTS,S/AS01 would be evaluated as a possible addition to – not a replacement for – existing prevention, diagnostic and treatment measures. 

15 Global Malaria Programme Thank you

16 Global Malaria Programme Backup slides

17 ACT deliveries ( ) by combination

18 ACT deliveries ( ) Fixed-dose combinations versus co-blisters

19 ACT versus RDT delivery / sales trends ( )