Where are we with Malaria in Africa? P.Olliaro WHO/TDR (Geneva, CH) U. Oxford (UK) Firenze 19Dec2012
1. Malaria receding focally Elimination (?) Consequences: Risks Syndromic approach to case-management of FEVER Tools 2. Resistance? 3. Co-morbidities & other conditions SUMMARY
WHO data & guidelines
Changes in malaria burden 2000-2010 (*10^6) 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 N cases (Africa) 175 179 183 188 190 191 189 187 182 179 174 N cases (World) 223 225 226 233 235 237 231 229 225 222 216 N deaths (Africa) 0.682 0.705 0.726 0.74 0.748 0.74 0.727 0.701 0.654 0.63 0.596 N deaths 15% (World) 0.755 0.771 0.789 0.801 0.81 0.801 0.782 0.756 0.711 0.691 0.655 10% % variation since 2000 5% 0% -5% 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 N cases (Africa) N cases (World) N deaths (Africa) N deaths (World) -10% -15% From WHO World Malaria Report 2011
Cases 217M Numbers matter Deaths 655,000 0.3% lethality Africa 81% Africa 91% 200M cases (10B parasites/individual) = 2^18 parasites in the world 1M hyperparasitaemic (10^12 parasites/individual) = 10^18
West Africa East Africa Southern Africa WHO World Malaria Report 2011
Uninfected susceptible Infected & ill (mild) Severely ill Dead infection progression fatal complications Prevent infection: Nets, Spraying, Repellents (Vaccine) Prevent transmission: Drugs [gametocytes in humans; cycle in mosquitoes] (Vaccine) Infected not ill Prevent disease: Prophylaxis, IPT Prevent complications: Early case management Oral Rx Pre-referral (Rectal) Rx Prevent fatal outcome: Parenteral Rx [antimalarials & supportive] Infection cleared
Malaria moving the goalposts Changing Patterns Prevalence receding in some areas in SSA (but not all) Interventions: Change in treatment policy: {Dx (RDT) + Rx (ACT)} Availability of RDT & ACT Availability of LLIN IRS IPT [> low-dose (0.25mg/kg) primaquine + ACT](*) Mechanisms (GFATM, etc.) Elimination possible in some settings (*) Artemisinin resistance in SE Asia New Targets Elimination requires drugs acting upon gametocytes (reduce transmission) liver stages (vivax) Changing epidemiology + difficult differential Dx require drugs for syndromic approach to fever Threat of resistance requires Intensified monitoring alternative to current artemisinin-based drugs = NOVELTY
Malaria & Bacterial Infections (2006) World vs. South-Saharan Africa (Buchanan et al, PLoS One 2010) World malaria ~250M episodes person-year World bacterial infections ~450M episodes person-year ~121M =>5yo 80% SSA 100M ~291M <5yo 33% SSA 96M ~125M <5yo 97% SSA 118M ~156M <5yo 24% SSA 37M SSA: 88% 218M malaria episodes person-year SSA: 30% 133M bacterial episodes person-year
"Fevers" {malaria + bacterial} (2006) World Tot: ~693M SSA Tot: ~351M (51%) (data from Buchanan et al, PLoS One 2010)
Is it malaria? (SSA, 2006) FEVERS (bacterial, viral, parasitic, ) 351M "fevers" 133M non-malaria (38%) 218M malaria (62%) Clinically suspected? Parasitologically confirmed? Anti-malaria treatments Presumptive Rx on clinical grounds Over-treatment Previous recommendation but still practice (new recommendation: Dx + ACT) Consequence: wastage, costs, toxicity, (resistance?) Morbidity & mortality due to other causes (not diagnosed and not treated) Failure to access care Under-treatment Consequence: avoidable morbidity, mortality to malaria
Uninfected susceptible Infected & ill (mild) Severely ill Dead infection progression fatal complications Probability in Low transmission* Probability in Medium/High Transmission* <5 adults <5 30% 73% 18% 70% 13% 60% adults 3% 45% * Data from Delphi survey: Yobel et al, PLoS one, 2011
Delphi survey estimates children adults Lubell Y, Staedke SG, Greenwood BM, Kamya MR, et al. (2011) Likely Health Outcomes for Untreated Acute Febrile Illness in the Tropics in Decision and Economic Models; A Delphi Survey. PLoS ONE 6(2): e17439. doi:10.1371/journal.pone.0017439 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017439
The big five 1. Streptococcus pneumoniae 2. Staphylococcus aureus 3. Non-typhoidal salmonellae 4. Escherichia coli 5. Salmonella typhi (from White NJ) Numbers & Weights E. coli, S.aureus bacteraemia: 1 bacterium per ml of blood = 20% mortality P.falciparum parasitaemia in a nonimmune: 5 x 10 8 parasites per ml of blood = 20% mortality A 500,000,000 fold difference
Where we would like to be Fever Parasitologically confirmed malaria Anti-malaria treatments
Mlomp, district of Oussouye, Basse Casamance, Sénégal
What proportion of fevers is malaria? from ~50% "MAFF" to ~20% Brasseur Harrogate, et al, MalJ 30Mar09 2011
Witnessing immunity wane Same age of malaria All ages have & non-malaria same risk Brasseur et al, MalJ 2011
Mlomp 2000-2011 QUESTION TEST? RESULT DECISION test +ve trust the test: treat 6,893 6,893 37% maybe: test trust the test: don't treat 18,859 test -ve 1,844 54% 11,966 Is it malaria? 63% don't trust the test: treat fever 35,169 definitely yes: treat, no test 10,122 6,466 18% definetely not: no test 9,844 28% Prior probability = 72% 85% 67% treated Vs. Harrogate, 37% confirmed 30Mar09 Brasseur et al, ASTMH 2012
Antimalarial treatments in Mlomp 2000-2011 Staggered implementation of microscopy + ASAQ starts Pilot phase-in: children, rainy season only 2000 RDT + ASAQ national policy 2006 RDTs provided to health centres 2007 RDT + ASAQ Provided for free 2010 Brasseur et al, ASTMH 2012
THE THREAT OF ARTEMISININ RESISTANCE
Low transmission areas = catalysts for the development of antimalarial drug resistance 30% of malaria in hypo & meso-endemic areas of SEARO National falciparum prevalence (NfP) cartogram for 2002 Hay et al, LID04
Malaria + Co-morbidities: disease-disease interactions - HIV, helminths (STNs, schistosomiasis, onchocerciasis) Concomitant treatments: drug-drug interactions - ARVs drug-disease interactions antimalarials/schistosomiasis; deworming/malaria Pregnancy: Complications, risks Embryotox
The battle wages on Paolo Uccello, Battaglia di S.Romano, Galleria degli Uffizi
Gentile da Fabriano, Adorazione dei Magi, Galleria degli Uffizi Buon Natale