the challenges of malaria elimination/eradication · 2014-11-26 · eradication programme in sri...
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MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
The challenges of malaria
elimination/eradication
Umberto D’Alessandro
Medical Research Council
London School of Hygiene and Tropical Medicine
(Institute of Tropical Medicine, Antwerp)
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
October
2007
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
The three components of the global strategy
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Gates and malaria eradication
• Davos 2013 • Malaria Can Be Eradicated
• Tools for eradication not available yet
• Funding for new drugs and vaccines
• ASTMH 2014-keynote speech • Malaria eradication in my lifetime
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Zanzibar - hospitalizations and malaria deaths 1999-2008
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
The Gambia - slide positivity rates 2003-2009
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Farafenni demographic surveillance, 1989 – 2008
<5yrs mortality from 159/1000 live births in 1990 to 45/1000 lb in 2008
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Non-thyphoid Salmonella and malaria (Mackenzie et al, 2010)
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Crude mortality rates before and after the eradication programme in Sri Lanka (Molineaux 1985)
0
5
10
15
20
25
30
35
40
-10 10 30 50 70
Cru
de
mo
rta
lity
ra
te (1
/10
00
)
Spleen index 1938-1941
Decrease of overall mortality
was related to the level of malaria
endemicity before the campaign
r²= 0,938
1930-1945
1946-1960
Malaria control vs. malaria elimination
GOAL
Reduction of the malaria burden to a level that it is no longer a major public health problem
Interruption of local mosquito-borne malaria transmission in a defined geographical area
Area of Operations
Malaria endemic areas: Universal coverage of prevention and treatment (SUFI)
Foci identified through epidemiological intelligence
Surveillance
May not be the best but is sufficient
Must be rapid and highly efficient
CONTROL ELIMINATION
Adapted from WHO, 2007
Elimination: A Paradigm Shift for Surveillance
For elimination purposes, a malaria case is a person in whom, regardless of the presence or absence of clinical symptoms, malaria parasites have been confirmed by quality-controlled laboratory diagnosis.
Clinical Cases Infections
Interventions during elimination programs are based on the concept of a malaria focus, assuming that transmission is focalized and no longer homogeneous across the country.
Universal Coverage Targeting Foci
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Final parasite prevalence after 15 years of sustained intervention (Griffin et al, PLoS
Medicine, 2010)
EIR 3 43 46 81 586 675
Elimination achievable with current methods only in areas with extremely low transmission
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
The hidden reservoir of malaria infection
Modified from Breman, AJTMH 2001
Clinical cases
Patent infections
Sub-patent infections
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Hollow: microscopy Filled: PCR
Diamonds:Asia Triangles: LA Squares: Africa
Lindblade et al, 2013
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Lin et al,
Trends in
Parasitology,
2014
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Submicroscopic gametocytaemia and mosquito infectivity threshold
Lin et al,
Trends in
Parasitology,
2014
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Higher carriage than suspected
• Blood volume for PCR assay about 5μl
• Detection threshold about 1,000 parasites/ml
• Use of ≥200μl of blood increases sensitivity (Imwong et al, 2014)
• Are these carriers important in maintaining transmission?
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Asymptomatic malaria infections
• About half infections undetected by microscopy
• Difference is greatest in low transmission settings
• Many asymptomatic infections can persist for significant periods of time;
• P. falciparum gametocytes positively associated with no symptoms and low asexual parasite densities;
• Mosquitoes infected with gametocyte densities as low as 5 gametocytes/μl
• Children with undetectable gametocytaemia by molecular methods could still transmit to mosquitoes;
• Gametocyte carriers may be more attractive to mosquitoes than both uninfected individuals and individuals with only asexual parasites.
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Extreme heterogeneity- school survey (Takem et al, 2011)
Heterogeneity
•Apparent geographically homogeneous area with similar villages
•Major differences in the prevalence of malaria
•Genetic factors
•Haemoglobin abnormalities
•Immune responsiveness
•Environmental factors
•Vector breeding and survival
•Exposure to vector mosquitoes
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Bed net and indoor residual spraying coverage, malaria
prevalence by study sites (Mwesigwa et al, submitted)
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Heterogeneity of risk and transmission
• Kilifi, Kenya (Mwangi et al, 2008)
– 21% of the children categorized as ‘more susceptible’ and experienced 55% of total clinical malaria episodes (contributed only 23% of the person-time of follow-up)
• Smith et al, 2005: Heterogeneous biting or heterogeneous susceptibility to infection are important and pervasive factors determining the prevalence of infection: 20% of people receive 80% of all infections
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Questions
• Who are the people initiating/maintaining transmission?
• How can we identify them?
• If identified, can we stop transmission by treatment and/or vaccination?
• When these interventions should be implemented and for how long?
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Two broad different approaches
Active case detection (ACD)
• Reactive – Screening people around a
passively detected clinical case
– No studies on impact on transmission
• Proactive – Screening of high risk
populations
– Low sensitivity of diagnostic tests
Presumptive treatment
• Mass drug administration (MDA) – Whole population
– Targeted to high risk groups
• IPT/SMC
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Combined impact of MDA and vector control (Okell et al, 2010)
1,000 people
10,000 people
500,000 people
MDA 2 rounds I year
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
MDA (1 yearly round for 2 years) plus RTS,S/AS01
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
2011 2016 2021 2026
PC
R p
rev
ale
nce
in
2-1
0 y
ea
r o
lds
Year
A)
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
2011 2016 2021 2026
PC
R p
rev
ale
nce
in
2-1
0 y
ea
r o
lds
Year
B)
Control - LLIN plus IRS
MDA Only
Vaccine only
MDA plus vaccine
VE=30% VE=50%
MRC Unit, The Gambia Leading scientific research to save lives and improve health across the developing world
Conclusions
• Eradicating P. falciparum malaria may be much harder than anticipated
• P. vivax malaria would be even harder
• Most if not all new interventions, e.g. MDA, require a huge investment of the health services and involvement of the local populations
• Different approaches poorly defined and evaluated
• Factors affecting effectiveness not well understood but human/social factors are extremely important - Risk of embarking in large interventions without the required information
• Social scientists should be involved in any attempt of elimination from the very beginning
Thank you for your attention