Defining and Defeating the Intolerable Burden of Malaria Joel G. Breman, MD, DTPH Fogarty...
-
Upload
ashlie-hodges -
Category
Documents
-
view
217 -
download
1
Transcript of Defining and Defeating the Intolerable Burden of Malaria Joel G. Breman, MD, DTPH Fogarty...
Defining and Defeating the Intolerable Defining and Defeating the Intolerable Burden of MalariaBurden of Malaria
Joel G. Breman, MD, DTPHJoel G. Breman, MD, DTPH
Fogarty International CenterFogarty International Center
U.S. National Institutes of HealthU.S. National Institutes of Health
BioVisionAlexandria 2008BioVisionAlexandria 2008
New Life Sciences: From Promises to PracticeNew Life Sciences: From Promises to Practice
Alexandria, EgyptAlexandria, Egypt
April 14, 2008April 14, 2008
Our Goal Malaria Free Mothers and Malaria Free Mothers and
ChildrenChildren
and all others
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
Interventions
Progress
Research
Transmission of Transmission of PlasmodiumPlasmodium from from Mosquito to Human…to MosquitoMosquito to Human…to Mosquito
White and Breman, 2008 (after Hoffman), Harrison’s Principles of Internal Medicine
P. falciparum
P. vivax
P. ovale
P. malariae
P. knowlsei
Defining Malaria and its ConquestDefining Malaria and its Conquest
ManifestationsBurden
Goals
Interventions
Progress
Research
Manifestations of the Malaria BurdenManifestations of the Malaria Burden
Infected Mosquito
Infected Human
Chronic effects
Anemia
Neurologic
Cognitive
Developmental
Impaired growth and development
Malnutrition
Acute febrile illness
Severe illness
Anemia
Hypoglycemia
Cerebral malaria
DeathRespiratory distress
Pregnancy
Fetus
MaternalAcute illness
Anemia
Low birth weight
Abortion, stillbirth
Infant and fetal mortality
Long-termsequelae
Hypovolemia
Long-termsequelaeBreman, Alilio, Mills, 2004, Am J Trop Med Hyg
Overlap of Cerebral Malaria, Anemia, Respiratory Distress in Children
Marsh et al, 1995, NEJM
Respiratory Distress
Severe Malarial Anemia
Hypoglycemia
Cerebral Malaria
22/177(12%)
3/7(43%)
2/126(2%)
1/14(7%)
1/4(25%)
2/2(100%)
1/1(100%)
3/7(43%)
3/4(75%)
1/2(50%)
2/23(9%)
Ranque et al 2008, Ped Inf Dis J( ) = number of patients
31/58(53%)
KenyaMali
% = CFR
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
BurdenGoals
Interventions
Progress
Research
Global Malaria and Endemicity, Global Malaria and Endemicity, 20032003
Global Distribution of Malaria Global Distribution of Malaria Anopheline VectorsAnopheline Vectors
Kizewski et al., 2004, Am J Trop Med Hyg
Plasmodium falciparum in 2005
Clinical CasesRegionRegion Population Population
at riskat risk (million)(million)
Cases (%)Cases (%)
((million)million)
AfricaAfrica 521521 365 (215 - 374) 365 (215 - 374) (57%)(57%)
South East South East AsiaAsia
1,3141,314 119 (66 - 224) 119 (66 - 224) (34%)(34%)
Western Western PacificPacific
142142 15 (9 - 26) (4%)15 (9 - 26) (4%)
Eastern Med.Eastern Med. 176176 12 (5 - 25) (4%)12 (5 - 25) (4%)
AmericasAmericas 5555 4 (2 - 8) (1%)4 (2 - 8) (1%)
EuropeEurope 44 1 (0 - 1) (<1%)1 (0 - 1) (<1%)
Total 2,211 515 (298 – 659) (100%)
Snow et al, 2005, Nature
Leading Causes of Disability-Leading Causes of Disability-Adjusted Life Years (DALYs) Adjusted Life Years (DALYs)
in Sub-Saharan African in Sub-Saharan African Region, 2001Region, 2001
Total DALYsTotal DALYs %%
1.1. HIV/AIDSHIV/AIDS 17.817.8
2.2. MalariaMalaria 10.310.3
3.3. Lower respiratory infections Lower respiratory infections 8.4 8.4
4.4. Perinatal conditionsPerinatal conditions 6.3 6.3
5.5. Diarrheal diseasesDiarrheal diseases 6.1 6.1
6.6. MeaslesMeasles 4.6 4.6
7.7. TuberculosisTuberculosis 2.4 2.4
8.8. Whooping coughWhooping cough 1.9 1.9
9.9. Road traffic accidentsRoad traffic accidents 1.8 1.8
10.10. Protein-energy malnutritionProtein-energy malnutrition 1.6 1.6
TotalTotal 61.261.2
Source: Mathers, et al., 2006, Global Burden of Disease and Risk Factors
Burden of Malaria on Health Burden of Malaria on Health Systems in Sub-Saharan Africa, Systems in Sub-Saharan Africa,
1999-20041999-2004
Source: WHO 2005
OUTPATIENTS
FEVER
HISTORY
ADMISSIONS
HOSPITAL
DEATHS
Number of malaria deathsCause of malaria-related death
Severe anemia 190,000-974,000
Hypoglycemia 153,000-267,000
Low birth weight 62,000-363,000
Cerebral malaria 110,000
Respiratory distress 110,000
Total deaths from malaria 625,000-1,824,000
Deaths from Malaria: Children Deaths from Malaria: Children Under FiveUnder Five
and Total, Africa 2001and Total, Africa 2001
962,000-2,806,000
● Under fives
● Total, all ages
Sources Breman, Alilio and Mills, 2004, Am J Trop Med Hyg; Murphy and Breman, 2001, Am J Trop Med Hyg
Population at Risk of Population at Risk of P. vivax P. vivax and and Clinical Cases Per Year (in millions)Clinical Cases Per Year (in millions)
Price et al, 2007, Am J Trop Med Hyg
Population at Population at risk (millions)risk (millions)
Infections/year Infections/year (millions)(millions)
South East AsiaSouth East Asia 1,3471,347 90-24890-248
Western PacificWestern Pacific 8989 20-7720-77
East East MediterraneanMediterranean
211211 11-3411-34
AmericasAmericas 7878 10-2810-28
EuropeEurope 2020 1-41-4
AfricaAfrica 5050 ——
Central AsiaCentral Asia — — ——
TotalTotal 2,5962,596 132-391132-391
Countries With Widespread Transmission, 2006
Breman and Holloway, 2007, Am J Trop Med Hyg
PopulatioPopulatio
n n (millions)(millions)
Cases Cases ConfirmeConfirme
dd
Cases Cases EstimatEstimat
eded
AfghanistaAfghanistann
31.631.6 83,00083,000 1,500,01,500,00000
DjiboutiDjibouti 0.60.6 2,0002,000 60,00060,000
PakistanPakistan 164.7164.7 24,00024,000 1,600,01,600,00000
SomaliaSomalia 8.88.8 16,00016,000 1,300,01,300,00000
SudanSudan 40.240.2 589,000589,000
5,000,05,000,00000
YemenYemen 19.819.8 55,00055,000 900,000900,000
TotalTotal 265.2265.2 569,000569,000 10,360,10,360,000000
Surveys of Surveys of P. falciparumP. falciparum, Eastern , Eastern Mediterranean Mediterranean
Regional Office (EMRO), 1985-2007Regional Office (EMRO), 1985-2007
Malaria in Eastern Mediterranean Region, WHO:
Countries Having Interrupted or Limited Transmission
Breman and Holloway, 2007, Am J Trop Med Hyg
CountryCountry CasesCases CountryCountry CasesCases
BahrainBahrain 7070 MoroccoMorocco 8383
EgyptEgypt 2929 OmanOman 443443
IranIran 15,909 15,909 (13,127)(13,127)
PalestinePalestine 22
IraqIraq 2424 QatorQator 198198
JordanJordan 116 (2)116 (2) Saudi Saudi ArabiaArabia
1,278 (26)1,278 (26)
KuwaitKuwait 235235 SyriaSyria 3434
LebanonLebanon 4242 TunisiaTunisia 3636
LibyaLibya 1010 United United Arab Arab RepublicRepublic
1,6631,663
TotalTotal 20,142 20,142 (13,432)(13,432)
( ) local transmission
Community Surveys of Community Surveys of P. falciparumP. falciparum Prevalence Conducted between 1985 Prevalence Conducted between 1985
and 2007 in AFROand 2007 in AFRO
Guerra et al, 2008, PLoS Med MARA/ARMA (http://www.mara.org.za)
Community Surveys of Community Surveys of P. falciparumP. falciparum Prevalence Conducted between 1985 and Prevalence Conducted between 1985 and
2007 2007 in AMRO and SEARO-WPROin AMRO and SEARO-WPRO
Guerra et al, 2008, PLoS Med
Malaria Cases and Death in South East Asia Region Malaria Cases and Death in South East Asia Region of WHO, 2004of WHO, 2004
Malaria Cases = 2,525,715
DEMOCRATIC PEOPLE’S REPUBLIC OF KOREA
0.5%
Malaria Deaths = 3,768Malaria Danger in Central Asia and Malaria Danger in Central Asia and Kazakhstan
Breman and Holloway, 2007Am J Trop Med Hyg
Cases of Malaria in the European Cases of Malaria in the European Region , 2005Region , 2005
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
GoalsInterventions
Progress
Research
To Halve the Burden of Malaria by 2010Abuja Malaria Summit, April 2000, revised 2007
RBM strategy
Prompt access to effective treatment
Insecticide-treated nets (ITNs)
Prevention and Prevention and control in pregnant control in pregnant womenwomen
Epidemics
Abuja target (by 2005), RBM (2007)
80% patients using correct/affordable treatment w/in 24 hrs
80% of children <5 years and pregnant women having ITNs
80% of pregnant women using 80% of pregnant women using intermittent preventive intermittent preventive treatmenttreatment
60% detected w/in 2 weeks of 60% detected w/in 2 weeks of onsetonset
60% responded to w/in 2 weeks60% responded to w/in 2 weeks
Roll Back Malaria’s Goals, Strategies, Roll Back Malaria’s Goals, Strategies, and Targetsand Targets
RBM, WHO, 2008
Major Manifestations of MalariaMajor Manifestations of Malaria
Cerebral malaria
Anemia
Martin WeberLennart Nielson (Karolinska Instituteg), Hedvig Perlmann (Stockholm University)
George Grau Roll Back Malaria Info Sheet
Rick Steketee National Human Genome Research Institute
Low birthweight
ConditionCondition ManifestationsManifestations Required EquipmentRequired Equipment ManagementManagementaa
ComaComa
Unable to respond to stimuliUnable to respond to stimuli Blantyre coma scaleBlantyre coma scale Parenteral therapyParenteral therapy
ConvulsionsConvulsions Convulsions (grand and Convulsions (grand and
petit mal)petit mal)
ObservationObservation Anticonvulsants, Anticonvulsants, protection from injuryprotection from injury
Renal failureRenal failure Urine output in 24h Urine output in 24h
Serum creatinineSerum creatinine
Biochemical analysisBiochemical analysis
Urine collectionsUrine collections
Rehydration (no Rehydration (no overhydration)overhydration)
Hemofiltration if Hemofiltration if neededneeded
Other Other
SepsisSepsis
Febrile, hypotensive, shock Febrile, hypotensive, shock (after malaria treatment)(after malaria treatment)
Blood culture, complete Blood culture, complete blood countblood count
Antibiotics, supportive Antibiotics, supportive carecare
Rehydration, Rehydration,
Low birth weightLow birth weight <2500 gm<2500 gm Scale (calibrated)Scale (calibrated) Resuscitation, breast, Resuscitation, breast, warmthwarmth
Selected Severe Patient Management Clinical Malaria Conditions Selected Severe Patient Management Clinical Malaria Conditions Requiring Diagnosis and ReportingRequiring Diagnosis and Reporting
Breman and Holloway, 2007, Am J Trop Med Hyg
*
*
*
ConditionCondition ManifestationsManifestations Required EquipmentRequired Equipment ManagementManagementaa
HematologicHematologic
Anemia Anemia Hematocrit<15%Hematocrit<15%
Hemoglobin <50 g/dL Hemoglobin <50 g/dL
Hematocrit equipmentHematocrit equipment
HemoglobinometerHemoglobinometer
Blood transfusionBlood transfusion
BiochemicalBiochemical
HypoglycemiaHypoglycemia
AcidosisAcidosis
Plasma glucosePlasma glucose
Arterial pH Arterial pH Plasma bicarbonatePlasma bicarbonate
Analytic equipmentAnalytic equipment
GlucosometerGlucosometer
Blood gas analysisBlood gas analysis
Glucose infusionGlucose infusion
Correct hypovolemiaCorrect hypovolemia
HemofiltrationHemofiltration
Parasitologic:Parasitologic:
HyperparasitemiaHyperparasitemia
>100,000 parasites/ml>100,000 parasites/ml Microscopy (or Rapid Microscopy (or Rapid Diagnostic Test)Diagnostic Test)
Microscope, slides, Microscope, slides, reagents reagents
Parenteral treatment Parenteral treatment with artemisinins, with artemisinins, quinine or quinidinequinine or quinidine
Selected Severe Clinical Malaria Conditions Requiring Diagnosis, Selected Severe Clinical Malaria Conditions Requiring Diagnosis, Assessment and Reporting (2)Assessment and Reporting (2)
a in addition to antimalarial drugs; referral to a secondary or temporary care facility for patients requiring parenteraltherapy and intensive supportive care.b consider exchange transfusion for parasitemia >10%* essential measurement
Breman and Holloway, 2007, Am J Trop Med Hyg
*
*
*
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
InterventionsProgress
Research
Environmental and Behavioral
Modification
Genetic modification
of vectorsFuture Interventions
Vaccines (preerythrocytic,
blood stage, transmission-
blocking)
Protection (insecticide-impregnated
materials)
Control of the Malaria Burden
Current Interventions
Drugs (treatment, prevention)
Insecticides (house
spraying, larvicides)
0 5 10 15 20 25 30
Intermittent preventive treatment
Insecticide-treated bed nets
Insecticide residual spraying
Intermittent preventive treatment/
pregnancy (SP)
Cost-effectiveness ratio ($ per DALY averted)
Cost-Effectiveness of Interventions Cost-Effectiveness of Interventions Against Malaria in Sub-Saharan AfricaAgainst Malaria in Sub-Saharan Africa
Laxminarayan et al (DCPP authors), 2006, in Jamison et al, Disease Control Priorities in Developing Countries, 2nd ed.
Artemisinin comb.therapy
(resistance)
Malaria: Prevention and Malaria: Prevention and TreatmentTreatment
Treatment with a new group of Treatment with a new group of antimalarials – the artemisinin antimalarials – the artemisinin compounds, in combination with compounds, in combination with lumefantrine, amodiaquine, sulfadoxine–lumefantrine, amodiaquine, sulfadoxine–pyrimethamine, or otherspyrimethamine, or others
O
O
O O
O
Spread of chloroquine resistanceArtemesia annua
The Process for the Microbial Production of The Process for the Microbial Production of Artemisinin Artemisinin
Hale et al, 2007, Am J Trop Med Hyg
WHO/Tropical Diseases Research/Crump
Verband Forschender Arzneimittelhersteller e.V.
Insecticide Treated Materials WorkInsecticide Treated Materials Work
Sleep Inside the NetSleep Inside the Net
AnophelesAnopheles Mosquito, Larva Mosquito, Larva Breeding SitesBreeding Sites
Insecticides recommended by the World Health Insecticides recommended by the World Health Organization Organization
for Indoor Residual Sprayingfor Indoor Residual Spraying
Sadasivaiah et al, 2007, Am J Trop Med Hyg
Insecticide Class
Recommendeddosage of activeingredient (g/m2)
Duration of effective action (months)
DDTFenitrothionMalathionPirimiphos-methylPropoxurBendiocarbAlpha-cypermethrinCyfluthrinDeltamethrinEtofenprox Lambda-cyhalothrinBifenthrin
OrganochlorineOrganophosphateOrganophosphateOrganophosphateCarbamateCarbamatePyrethroidPyrethroidPyrethroidPyrethroidPyrethroidPyrethroid
1-2221-21-20.1-0.40.02-0.030.02-0.050.02-0.0250.1-0.30.02-0.030.025-0.05
>63-62-32-33-62-64-63-63-63-63-63-6
*DDT, dichlorodiphenyltrichloroethane
Photo: W
orld Health O
rganization
Cost/house/6 months
DDT
Deltamethrin
Malathion
Lambda-cyhalothrin
Bendiocarb
Fenitrothion
Propoxur
Cost/ratio
$1.6/1.0
1.6/1.0
8.2/5.1
8.6/5.4
13.8/8.6
14.8/9.3
18.8/11.8
WHO, 2004, Sadasavaiah, Tozan, Breman, 2007
Insecticides Used for Malaria Vector Control, 1995-Insecticides Used for Malaria Vector Control, 1995-2006 2006
Vector Surveillance Capacity in Sub-Saharan Africa, Vector Surveillance Capacity in Sub-Saharan Africa, 2006 2006
Entomological Capacity, 2006
no capacity
basic for control or research
basic/advanced for control, advanced in research
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
1995
1996
1997
1998
1999
2000
2001
200220
0
320
0420
05
thousands of kg
tho
usa
nd
s o
f kg
DDT
OP
C
PY
Flamboyant Trees on the Grounds of the Flamboyant Trees on the Grounds of the Lamumba Health Clinic in Kisumu, Lamumba Health Clinic in Kisumu,
KenyaKenya
Omlin et al, 2007, Am J Trop Med
Malaria Diagnostics: Microscopy and Malaria Diagnostics: Microscopy and Rapid Diagnostic TestingRapid Diagnostic Testing
Blood Smears
RDT
Source: UNICEF, 2007
Global Fund: HIV/AIDS, Global Fund: HIV/AIDS, Tuberculosis, and Malaria Tuberculosis, and Malaria per-capita funding levelsper-capita funding levels
Countries with Countries with President’s Malaria Initiative and President’s Malaria Initiative and
World Bank Booster FundingWorld Bank Booster Funding
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
Interventions
ProgressResearch
Rwanda: Malaria ProgressRwanda: Malaria Progress
Vital Statistics
Population: 9.3 million
Women 15-45 yrs: 2.7 million
Children <5 yrs: 4.0 million
Infant mortality: 152 (2005)
Malaria
Risk: 4.8 million
Cases: 1.4 million (2005)
Deaths <5yrs: 510 (2006)
IndicatorIndicator 2000(%)2000(%) 2005 (%)2005 (%) 2007 (%)2007 (%)
Pregnant womenPregnant women
sleeping under ITNsleeping under ITN —— 1717 6060
received IPT (received IPT (≥2 doses)≥2 doses) —— 00 6565
Children with fever (%)Children with fever (%)
receiving anti-malaria drugsreceiving anti-malaria drugs 1313 1212 ——
receiving drugs <24 hoursreceiving drugs <24 hours —— 33 ——
sleeping under ITNsleeping under ITN 55 1313 6060Roll Back Malaria
Ethiopia: Malaria ProgressEthiopia: Malaria ProgressVital Statistics
Population: 77.3 million
< 5 mortality: 123
Malaria
Risk: 52.5 million
Cases (est): 12 million (2006) (reported): 3.7 million
Child Deaths : 94,400
IndicatorIndicator 2005 (%)2005 (%) 2006 (%)2006 (%)
% Households with % Households with ≥1 ITN≥1 ITN 33 9191
Children < 5 yrs sleeping under ITN previous nightChildren < 5 yrs sleeping under ITN previous night 22 8787
Pregnant women sleeping under ITN Pregnant women sleeping under ITN
previous nightprevious night
11 ——
Roll Back Malaria
Zambia: Malaria ProgressZambia: Malaria ProgressVital Statistics
Population: 11.7 million
Malaria
Cases: 2.1 million (2005)
IndicatorIndicator 2002 2002 (%)(%)
2004 2004 (%)(%)
2006 2006 (%)(%)
% Households % Households with with ≥1 ITN≥1 ITN
1414 2727 4444
Children < 5 yrs Children < 5 yrs sleeping under sleeping under ITNITN
1616 —— 2727
Pregnant women Pregnant women sleeping under sleeping under ITN ITN
88 1212 2424
Roll Back Malaria
Results from Zanzibar Results from Zanzibar Island, TanzaniaIsland, Tanzania
Population: 1,116,001 (2006)
Outpatient Malaria Cases (Confirmed and non-confirmed)
per 1000 of the population
Results from ZanzibarResults from ZanzibarProportion of malaria Proportion of malaria
confirmed casesconfirmed cases
Ali, et al 2007, EARN Meeting
Defining Malaria and its ConquestDefining Malaria and its Conquest
Manifestations
Burden
Goals
Interventions
Progress
Research
Research Needs: Disease Burden that Can or Cannot be Averted with Existing Interventions
Not Avertable
Disease Burden:
Avertable
Already averted
coverage
Biomedical research to identify new and improved interventions
Increase effectiveness or reduce costs of existing interventions
Broader implementation of cost-effective interventions; identify obstacles to expansion of coverage
Research and Development Categories and Results for Implementation
New basic understanding• Fundamental research • Basic epidemiology, risk factors, modeling
New and improved tools • Drugs• Vaccines • Diagnostics• Devices• Vector control • Environmental modification• Behavioral, social, and economic change
Research and Development Categories and Results for Implementation
New and improved intervention methods • Treatment algorithms and guidelines • Intervention packaging • Priority setting via costing and cost-effectiveness studies • Delivery: health systems and health services • New and improved policy instruments
Malaria Research Needs: Major Malaria Research Needs: Major Gaps and Controversies Requiring Gaps and Controversies Requiring
AttentionAttention Multiple pathologiesMultiple pathologies
– AnemiaAnemia– Low birthweightLow birthweight– MalnutritionMalnutrition– HIVHIV– EnteritisEnteritis– Sepsis Sepsis – NeurocognitiveNeurocognitive– Neglected diseasesNeglected diseases
Host factorsHost factors– Immunity and Immunity and
vaccinesvaccines– Genetic susceptibilityGenetic susceptibility
PlasmodiumPlasmodium– falciparumfalciparum– vivaxvivax– Antigenic diversityAntigenic diversity– Drug resistanceDrug resistance
AnophelesAnopheles– Transmission dynamicsTransmission dynamics– Human Correlation of Human Correlation of
Entomologic Entomologic Inoculation Rate with Inoculation Rate with clinical manifestationsclinical manifestations
Special conditionsSpecial conditions– EpidemicsEpidemics– UrbanizationUrbanization– MigrationMigration
Fetal Growth Velocity and Impact of Fetal Growth Velocity and Impact of Intermittent Preventive Treatment for Intermittent Preventive Treatment for
Malaria of MothersMalaria of Mothers
Rogerson et al, 2007
Overlapping Burden of Neglected Diseases Overlapping Burden of Neglected Diseases and Malariaand Malaria
(leprosy, lymphatic filariasis, onchocerciasis, (leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, schistosomiasis,
soil-transmitted helminths and trachoma)soil-transmitted helminths and trachoma)
Neglected Tropical Diseases, 2007
Malaria Transmission to Human and Malaria Transmission to Human and MosquitoMosquito
Vaccine TargetsVaccine Targets
White and Breman, 2007 (adapted from Hoffman), Harrison’s Principles of Internal Medicine
October 17, 2007
Thank youThank you