MALARIA: New Trends MALARIA: New Trends in Treatment/Vaccinationin Treatment/Vaccination

Presenter – Dr Victor OrduPresenter – Dr Victor Ordu

Malaria (it. “bad air”) is a disease caused by Malaria (it. “bad air”) is a disease caused by infection with parasites of the genus infection with parasites of the genus Plasmodium.Plasmodium.First described by HippocratesFirst described by HippocratesP. falciparum, P. malariae, P. ovale and P. vivax P. falciparum, P. malariae, P. ovale and P. vivax cause disease in humans.cause disease in humans.Falciparum malaria accounts for majority of Falciparum malaria accounts for majority of complications and deaths.complications and deaths.It is transmitted from person-to-person by female It is transmitted from person-to-person by female anopheline mosquitoes during blood mealsanopheline mosquitoes during blood meals

Distribution Distribution A disease of the A disease of the tropics tropics

500 million 500 million cases annuallycases annually

1 million deaths 1 million deaths every year – every year – 90% of these in 90% of these in Sub-Saharan Sub-Saharan Africa (SSA)Africa (SSA)

Most deaths are Most deaths are among children among children aged 1 – 59 aged 1 – 59 monthsmonths

Transmission Transmission occurs in 2 occurs in 2 forms – forms – endemic and endemic and epidemic epidemic

Endemic – Endemic – young children young children and pregnant and pregnant women are women are worst hitworst hit

Epidemic – Epidemic – population population usually non-usually non-immune & all immune & all age groups age groups affected affected

First successful efforts by the ancient First successful efforts by the ancient Romans – drainage of marshlandsRomans – drainage of marshlandsCinchona bark used by Peruvians in the Cinchona bark used by Peruvians in the 1600s1600sDiscovery of malaria agent by Alphonse Discovery of malaria agent by Alphonse Laveran in 1879Laveran in 1879Malaria transmission elucidated by Malaria transmission elucidated by Ronald Ross (1897)Ronald Ross (1897)DDT discovered by Paul Muller in 1942; DDT discovered by Paul Muller in 1942; first used in Italy in 1944first used in Italy in 1944

Malaria ControlMalaria Control

Failure of malaria eradication efforts of the 1950s-60sFailure of malaria eradication efforts of the 1950s-60s gave way to an era of maintenance of malaria-free gave way to an era of maintenance of malaria-free zonezoneControl in N. Africa largely successful b/c of Control in N. Africa largely successful b/c of predominance of P.vivax infections. Surveillance predominance of P.vivax infections. Surveillance efforts continue in these countriesefforts continue in these countriesIn SSA resilience of main vector (In SSA resilience of main vector (A. gambiae)A. gambiae), dearth , dearth of resources & complacency led to failure.of resources & complacency led to failure.In SSA, data shows rise in malaria related deaths in In SSA, data shows rise in malaria related deaths in the 1990s due to drug resistance, breakdown of the 1990s due to drug resistance, breakdown of control programmes, climate & environmental change, control programmes, climate & environmental change, exposure of non-immune popns and HIV/AIDS exposure of non-immune popns and HIV/AIDS

Rolling Malaria BackRolling Malaria Back

WHO initiated Roll Back Malaria campaign WHO initiated Roll Back Malaria campaign in 1998 to coordinate a global effort at in 1998 to coordinate a global effort at reducing malaria-related morbidity and reducing malaria-related morbidity and mortality.mortality.African Heads-of-State pledge to fight African Heads-of-State pledge to fight malaria at Abuja Summit in 2000.malaria at Abuja Summit in 2000.Private sector involvement Private sector involvement Global Fund to Fight AIDS, Tuberculosis & Global Fund to Fight AIDS, Tuberculosis & MalariaMalaria

New Strategies and New Strategies and TechnologiesTechnologies

Insecticide-Treated Nets (ITNs)Insecticide-Treated Nets (ITNs)

Intermittent Preventive Treatment (IPT)Intermittent Preventive Treatment (IPT)

Artemisinin-based Combination Therapy (ACTs)Artemisinin-based Combination Therapy (ACTs)

Home-based management of fever (HBMF)Home-based management of fever (HBMF)

Malaria Early Warning Systems (MEWS)Malaria Early Warning Systems (MEWS)

Vaccine developmentVaccine development

Malaria GenomicsMalaria Genomics

Insecticide-Treated Nets (ITNs)Insecticide-Treated Nets (ITNs)Introduced in the mid 1980sIntroduced in the mid 1980s

Pyrethroids in use – deltamethrin, labda-cyalothrinPyrethroids in use – deltamethrin, labda-cyalothrin

Probably the most effective preventive measure in Probably the most effective preventive measure in useuse

15% U5s slept under nets; 2% under ITNs 15% U5s slept under nets; 2% under ITNs

(AMR, 2003)(AMR, 2003)

Evidence of some studies show:Evidence of some studies show: Reduced U5 mortality by 20%Reduced U5 mortality by 20% Reduced Clinical falciparum dx by 50%Reduced Clinical falciparum dx by 50% Reduced maternal morbidityReduced maternal morbidity

Problems of cost; need for relaxation of taxes Problems of cost; need for relaxation of taxes and tariffs and tariffs Progress – Long Lasting Insecticide treated Nets Progress – Long Lasting Insecticide treated Nets (LLINS) can last for 4 – 5 years & resist washing (LLINS) can last for 4 – 5 years & resist washing reduce exposure and environmental reduce exposure and environmental contaminationcontamination

Intermittent Preventive Intermittent Preventive Treatment (IPT)Treatment (IPT)

2 single-dose administrations of antimalarials at 2 single-dose administrations of antimalarials at therapeutic doses during the routine antenatal therapeutic doses during the routine antenatal visitsvisitsSulfadoxine-pyrimethamine (SP) is drug of Sulfadoxine-pyrimethamine (SP) is drug of choice (in areas where there is no resistance)choice (in areas where there is no resistance)Studies so far indicate a decreased proportion of Studies so far indicate a decreased proportion of women with anaemia and placental infection at women with anaemia and placental infection at deliverydeliveryComplemented by ITNs & effective case Complemented by ITNs & effective case managementmanagement

Artemisinin-based Combination Artemisinin-based Combination Therapy (ACTs)Therapy (ACTs)

Monotherapies are failing!Monotherapies are failing!Many countries have changed drug policies in Many countries have changed drug policies in favour of combination therapies especially where favour of combination therapies especially where CQ resistance ehas been documentedCQ resistance ehas been documentedACTs are currently recommended (WHO 2004) ACTs are currently recommended (WHO 2004) due to:due to: Documented efficacyDocumented efficacy Likely delay in devt of resistant strains Likely delay in devt of resistant strains

Costly and hence require donor inputsCostly and hence require donor inputs CQ – USD 0.13CQ – USD 0.13 SP – USD 0.14SP – USD 0.14 ACTs – USD 1-3ACTs – USD 1-3

(for adult outpatient treatments)(for adult outpatient treatments)

Favoured combinationsFavoured combinations Atrmether-lumefantrine (Coartem)Atrmether-lumefantrine (Coartem) Artesunate-amodiaquineArtesunate-amodiaquine Artesunate-SPArtesunate-SP

Non artemisinin based combination are also Non artemisinin based combination are also acceptable e.g. amodiaquine- SP, acceptable e.g. amodiaquine- SP,

Malaria Early Warning Systems Malaria Early Warning Systems (MEWS)(MEWS)

Used to predict and improve response to Used to predict and improve response to malaria epidemicsmalaria epidemicsLargely employed in the SADC bloc and the Largely employed in the SADC bloc and the northern fringe of the malaria zonenorthern fringe of the malaria zoneInvolves monitoring vulnerability and Involves monitoring vulnerability and transmission risk factors such as:transmission risk factors such as: Seasonal climate forecastsSeasonal climate forecasts Rainfall estimatesRainfall estimates Population movementsPopulation movements Entomological indicesEntomological indices

MEWS often require high degree of MEWS often require high degree of technical expertise and inter-sectoral technical expertise and inter-sectoral collaborationcollaboration

Very helpful in the event of complex Very helpful in the event of complex emergencies such as natural distasters or emergencies such as natural distasters or civil strife which account for 30% of civil strife which account for 30% of malaria deaths (malaria is No.1 killer in malaria deaths (malaria is No.1 killer in complex emergencies in SSA)complex emergencies in SSA)

Malaria GenomicsMalaria Genomics

Recent advancesRecent advances Human genome elucidatedHuman genome elucidated Genomes of Genomes of A. gambiaeA. gambiae and and P. falciparumP. falciparum

(Oct 2002)(Oct 2002) P. yoelliP. yoelli – rodent malaria. Provides a model – rodent malaria. Provides a model

for studiesfor studies

Possible usesPossible uses Study of mechanisms of drug/insecticide Study of mechanisms of drug/insecticide

resistanceresistance Development of vaccinesDevelopment of vaccines Elucidation of mechanisms of immune Elucidation of mechanisms of immune

evasionevasion Genetic engineering of vectorsGenetic engineering of vectors Discovery of drug targetsDiscovery of drug targets

Malaria Vaccine ResearchMalaria Vaccine Research

Ideal vaccine – multispecies, multistrainIdeal vaccine – multispecies, multistrain4 general vaccine candidates undergoing 4 general vaccine candidates undergoing R&DR&D Pre-erythrocytic (Sporozoite & liver stage) – Pre-erythrocytic (Sporozoite & liver stage) –

e.g. CS, LSAse.g. CS, LSAs Asexual blood stage – e.g. MSPs, AMA-1Asexual blood stage – e.g. MSPs, AMA-1 Transmission-blocking – Pfs 25 & 28, Pvs 25Transmission-blocking – Pfs 25 & 28, Pvs 25 Anti-disease – Anti-GPI Anti-disease – Anti-GPI

Still undergoing clinical trialsStill undergoing clinical trials

Thank youThank you