Progressi sui Millennium Developmental Goal: MALARIA SERGIO SPINACI Global Malaria Programme Organizzazione Mondiale de

1. Progressi sui Millennium Developmental Goal: MALARIA SERGIO SPINACI Global Malaria Programme Organizzazione Mondiale della Sanità, Ginevra

2. La malaria è uno dei quattro grandi flagelli dell’Africa • (gli altri sono la fame, la tubercolosi e l’HIV)

3. Global strategic objectives Ecco la serie dei progetti internazionali per controllarla, dal 1998 a oggi. I progetti sono progressivamente meno ottimistici (meno miracolistici) • RBM Partnership (1998): halve the burden of malaria by 2010 • Abuja coverage targets (2000): by 2005, achieve a 60% coverage of all at-risk populations with suitable curative and preventive measures • Millennium Development Goals (2000): by 2015, • MDG 4: Reduce child mortality • MDG 5: Improve maternal health • MDG 6: Combat HIV/AIDS, malaria and other diseases; particularly, halt and begin to reverse the incidence of malaria and other major diseases • World Health Assembly Resolution (2005): by 2010, at least 80% of at-risk populations benefit from major preventive and curative interventions

4. Associations between malaria & the MDGs La malaria in realtà non è implicata in uno solo degli MDG, quello che la menziona formalmente, cioè lo MDG6; ma è implicata nella maggioranza dei traguardi da raggiungere: 6 MDG su 8 • MDG 1: Eradicate extreme poverty and hunger • Malaria keeps poor people poor, costing Africa an estimated US$ 12 billion/yr in lost GDP & consuming up to 25% of household income and up to 40% of government health spending. • MDG 2: Achieve universal primary education • Malaria is a leading cause of illness and absenteeism in children and teachers in malarious areas, impairs attendance and learning and can cause lasting neurological damage in children. • MDG 4: Reduce child mortality • Malaria is a leading cause of child mortality in Africa, accounting for nearly one death in five among African children under five. Every day, an estimated 3000 children and infants die of malaria– representing approximately 82% of all malaria deaths. • It is estimated that the indirect effects of malaria - which are mostly overlooked in estimates of malaria-related morbidity and mortality - result in up to 200,000 infant deaths per year in Africa alone. • MDG 5: Improve maternal health • Approximately 50 million women become pregnant in malaria-endemic countries each year. • Malaria during pregnancy is a major cause of severe maternal anemia and puts women at increased risk of dying from the complications of severe malaria, and of experiencing spontaneous abortion, premature delivery or stillbirth. • MDG 6: Combat HIV/AIDS, malaria and other diseases • MDG 8: Global partnership for development • GMP is part of the RBM partnership and especially involved in the partnership working groups GMP is working in strengthening Health Services delivery by supporting countries to strengthen their monitoring, supervision and supply chain management practices.

5. Malaria imposes a staggering worldwide burden • Death toll • Incidence • Health impacts • Economic impacts • High None • Level of malaria burden • At least 1 million deaths annually; one child every 30 seconds • 350 to 500 million cases worldwide • Debilitating fevers, low birth weights, anemia, epilepsy—and death • Reduced current productivity resulting from days and often weeks of missed work, reduced foreign direct investment and tourism • Constraints on future growth resulting from reduced investments in human capital (missed schooling, higher fertility rates) Source: World Malaria Report 2005, expert interviews Ecco i numeri e le sedi di maggiore impatto. L’Africa è il regno di Plasmodium falciparum

6. Current global estimates of population at risk by WHO Region L’Africa è anche il continente dove l’endemia di malaria è infinitamente più alta che altrove: qui la malaria è oloendemica o iperepidemica Approximately 0.95 billion at risk (Source: WHO regional offices, Kicewski, 2007)

7. Reproduction rate of malaria varies by endemicity 2000 - >3000 new cases For every 1 infected case, there will be... 100 - 2000 new cases 2.5 – 100 new cases >2.5 new cases # of infectious bites per yr (EÌR) <0.25 0.25 - 10 11 - 140 >140 Dove la malaria è oloendemica o iperepidemica ogni persona infetta dà luogo ad altre 2000-3000 infezioni • (R0) # new • infections • per infected • person • 4.000 • 3.000 • 2.000 • 1.000 • 0 • Hypoendemic • Mesoendemic • Hyperendemic • Holoendemic L’azzeramento della malaria richiederebbe un R0 (cioè un numero di nuove infezioni per ogni persona infetta) <1; e in Africa ne siamo lontanissimi Source: Smith DL, et al (2007); Prospects for Eradication and Elimination of Malaria, DFID, 2007

8. Sub-Saharan Africa bears a disproportionate share of the malaria burden • Africans suffer from the majority of worldwide malaria deaths (90% or at least 900,000) and malaria cases (60% or at least 300 million) • Majority of cases/deaths • Countries in Africa with the heaviest burdens are forced to expend significant resources on malaria: • 40% of health expenditure • 20-45% of hospital admissions • 50% of outpatient visits • High proportion of health expenditures • Unfavorable entomology & climate • Africa is home to the most deadly form of the parasite (Plasmodium falciparum) and has the climate and vector (mosquito species) most conducive to its proliferation • Many sub-Saharan African governments lack the funds and/or infrastructure to single-handedly mount large-scale anti-malaria campaigns • Lack of domestic capacity Source: World Malaria Report 2005, expert interviews L’Africa è dunque, come abbiamo visto, non solo il Continente che più soffre per questa malattia, ma anche, con ogni evidenza, quello che più difficilmente se ne potrà liberare

9. Ecco il ciclo vitale del parassita malarico, tra il vettore infetto, che immette nell’uomo lo sporozoite, l’uomo nel cui fegato lo sporozoite svolge il suo ciclo trasformandosi in merozoite e alla fine in gametocita, che viene succhiato dal vettore infettante, all’interno dei cui organismo i gametociti si uniscono per dar luogo a uno zigote, da cui derivano gli sporozoiti, che il vettore infettante trasmetterà ad altri umani. Host Parasite Infecting vector Infected vector Source: http://encarta.msn.com/media_461541582/Life_Cycle_of_the_Malaria_Parasite.htmlAccessed on 31 March 2008

10. Elements of malaria control strategies Human Drugs and diagnosis at health centre and community level Universal LLIN coverage STOP STOP Parasite Infected vector Infecting vector STOP Universal LLIN coverage/ IRS Ecco come l’associazione della protezione mediante zanzariera impregnata LLINs e della pronta ed efficace terapia terapia con antimalarici IRS può bloccare il ciclo del parassita tra vettore infetto, uomo, e vettore infettante. Zanzariera impregnata e antimalarici rappresentano gli strumenti essenziali e possibili per contenere e ridurre la mortalità e la trasmissione della malaria

11. Case management: recommendations • Malaria diagnosis: Parasitological confirmation (microscopy or RDT) before treatment except in U-5s, in areas of high transmission • Malaria treatment: ACTs are recommended for all cases of uncomplicated falciparum malaria, • artemether-lumefantrine; artesunate + amodiaquine; artesunate + mefloquine; and artesunate + sulfadoxine-pyrimethamine Second-line treatment: • an effective alternative ACT to the 1st line or • quinine + tetracycline or doxycycline or clindamycin • Community / home management of malaria: Effective treatment with ACT should be made available at all levels of service delivery up to the community including through the private sector • Intermittent preventive treatment in pregnant wWomen: IPTp w/ith SP is a strategy for malaria control in pregnant women in sub-Saharan African in countries with stable malaria transmission

12. Malaria vector control: IRS & ITNs/LLINS • ITNs: Free or highly subsidized LLINs should be provided to the entire population, initially targeting high risk groups • IRS: Can be used in all epidemiological settings, and is mostly indicated: • to control 1). malaria outbreaks, 2). emerging drug resistance, 3). malaria in complex emergencies, and 4). to decrease malaria transmission in stable areas • to interrupt transmission with the objective of eliminating malaria (where feasible) • LLINs & IRS can be deployedin combination as complementary measures to enhance extended insecticide coverage • Insecticide resistance monitoring in sentinel sites must be an integral part of effective vector control.

13. Ma la sfida principale è quella dell’emergenza di nuove resistenze • Monitoring therapeutic efficacy must be an integral component of effective case management. • Consequences of anti-malarial drug resistance: • Increased morbidity and mortality (including anaemia, low birth weight) • Increased gametocyte carriage • switch to effective drug combinations in situations of low to moderate endemicity has always resulted in a dramatic decrease in transmission • Economic impact • increases cost to health services (to both provider and patient) because of returning treatment failures • Greater frequency and severity of epidemics • Modification of malaria distribution • A chaotic informal private sector (including with sub-standard and counterfeit medicines)

14. Ecco la geografia della resistenza alla clorochina, farmaco a bassisimo costo, difficilmente sostituibile 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

15. Ecco la strategia per rallentare o inibire la progressione delle resistenze • Change antimalarial treatment policies when treatment failure is >10% (as assessed through monitoring of therapeutic efficacy at 28 days) • Change to a treatment which has an average cure rate ≥ 95% as assessed in clinical trials "…Prompt and accurate diagnosis of malaria is the key to effective disease management and to the reduction of unnecessary use of antimalarial medicines."

16. Storia dell’insorgenza di resistenze agli antimalarici La comparsa delle resistenze è sempre più rapida: dal momento in cui è stato usato la prima volta il chinino alla prima resistenza segnalata sono passati 300 anni; la clorochina ci ha messo 20 anni, la meflochina ce ne ha messi 5, il proguanil, la sulfadoxina-pirimatamina, l’atovaquone non ci ha messo nemmeno un anno. 1910 1632 Quinine First case ofresistance X Introduced X 1934 Chloroquine 1957 X 1948 1949 Proguanil X Sulfadoxine-Pyrimethamine 1967 1967 Reports of in vitro resistance. Example: Resistance of P. falciparum field isolates (French Guiana /Senegal) to in-vitro ArtemetherLancet (Dec 2005) X 1977 1982 Mefloquine X 1996 1996 Atovaquone X ? 1972 (herbal) Artemisinin Source: Talisuna et al, Clinical Microbiology Reviews (2004)

17. Progress on malaria control goals(in particular towards MDGs)

18. Ma quanto occorrerà perché almeno gli strumenti oggi disponibili possano essere distribuiti o comunque utilizzati da tutte le persone in bisogno? • In particolare, quanto siamo distanti da un’utilizzazione sufficientemente diffusa delle zanzariere impregnate e degli antimalarici per tutti i bambini sotto i 5 anni, la classe di età più esposta alla morte per malaria?

19. Goal 6: Combat HIV/AIDS, malaria and other diseases Target 8: Have halted by 2015 and begun to reverse the incidence of malaria and other major diseases Malaria-control efforts are paying off, but additional effort is needed • Indicator 22: Children under 5 sleeping under insecticide-treated bednets & with fever who are treated w/ appropriate anti-malarial drugs % of children sleeping under ITNs in selected African countries: Base year (around 2000) and Latest year (2005) Come si vede, la copertura è molto cresciuta, in tutti o quasi tutti gli stati africani, nel 2005 rispetto al 2000; ma siamo egualmente molto lontani da una copertura soddisfacente Source: Demographic and health surveys and Multi-indicator household surveys.

20. Recent impact: Rwanda & Ethiopia Ethiopia2003-2007, 7 in-patient facilities In-patient malaria and non-malaria cases in children <5 years old Rwanda, 2001-2007, 19 health facilities In-patient malaria and non-malaria cases in children <5 years old. LLINs, ACTs Sep-Oct 2006 LLINs, ACTs ACTs Eppure le facilitazioni economiche (in particolare la distribuzione gratuita o a prezzo molto conveniente di zanzariere impregnate e la distribuzione di antimalarici scontati) riducono oggettivamente e significativamente, dove vengono introdotte, l’impatto della malaria

21. Conclusioni

22. Challenges • Implementation • Countries need continued clear guidance & support on how to implement global policies and use funds effectively • Integration of malaria control into health systems, particularly at district level • Focus on the integration of malaria with EPI for commodity distribution and malaria programme supervision • Resource mobilization • Strategies for human resource training and retention to be put in place • Effective mobilization for technical assistance to countries • Malaria impacts 6 of the MDGs • More resources need to be put towards M&E to ensure that resources are being effectively targeted.

23. Malaria control getting to the MDGs • Comprehensive packages need to be put in place: malaria control objectives cannot be achieved without focusing on both prevention, treatment, diagnosis and monitoring & evaluation. • Increased scale-up will also demand greater vigilance and monitoring to prevent resistance and loss of tools • Frontloading and increased scale-up in 2008-2010 will demand greatly increased resources – both human & financial • However rapid scale up in 2008-2010 could save at least 3.5 million lives and avert about 672 million cases • Research and development are needed both in the near term (particularly operational and new and improved tools to replace those lost to resistance) and with a view to long-term development of new tools (e.g. vaccines)