Improving the Impact of Malaria Prevention Activities
Submitting InstitutionsUniversity of Liverpool,
Liverpool School of Tropical Medicine
Unit of AssessmentClinical Medicine
Summary Impact TypePolitical
Research Subject Area(s)
Biological Sciences: Genetics
Agricultural and Veterinary Sciences: Crop and Pasture Production
Medical and Health Sciences: Medical Microbiology
Summary of the impact
Malaria kills around 650,000 children a year but can be prevented by
killing the mosquito vectors. As mosquitoes become resistant to
insecticides the prevention measures can become ineffective. Research at
the Liverpool School of Tropical Medicine (LSTM) led by Professor
Hemingway FRS has been instrumental in the development of current World
Health Organisation (WHO) guidelines to manage resistance, and has led to
improved resistance diagnostics and novel monitoring software to integrate
entomological and human health outcomes. LSTM's research led to the
creation of the Innovative Vector Control Consortium (IVCC) which was
established as an independent Product Development Partnership (PDP) in
2008. New, longer lasting formulations of insecticides developed by IVCC
are now in operational use, and several novel public health insecticides
are under development.
This case study encompasses the outputs from five academic staff; Janet
Hemingway, (2001-) Director of LSTM, Hilary Ranson (2001-) Professor of
Medical Entomology, Martin Donnelly, (2001-) Professor of Evolutionary
Genetics, Mark Paine (2006 -) Senior Lecturer, and Charles Wondji (2005-)
Research Fellow, leveraging several hundred millions of pounds of research
income since 2001.
Scale up of insecticide based interventions to target the mosquito
vectors that transmit malaria have resulted in a 33% reduction in malaria
cases over the last decade in Africa. However, malaria prevention is
currently reliant on a very small number of insecticides with only the
pyrethroids approved for insecticide treated bednets. Malaria mosquitoes
are rapidly developing resistance to these insecticides. There is a
critical lack of alternative vector control technologies, and a further
impediment to effective malaria control is often the absence of accurate
timely information on which to base disease prevention measures, which can
result in wasted resources and increased disease burden. New vector
control tools, decision support systems and new insecticides are urgently
needed to save lives in Africa. If current tools fail due to resistance,
the gains in malaria prevention could be quickly eroded.
Understanding the mechanisms and spread of insecticide resistance.
LSTM leads the malaria control community in understanding the causes and
consequences of the evolution of insecticide resistance in malaria
vectors. Research into the molecular basis of insecticide resistance has
resulted in new resistance monitoring tools and new approaches to measure
the speed of spread of resistance . LSTM has characterised a newly
emerging resistance mechanism that confers cross resistance to multiple
insecticide classes , and alerted the community to the presence of a
population of malaria vectors in Cote d'Ivoire that has now developed
resistance to all available insecticides . The molecular tools
developed are now being used in insecticide development to identify new,
resistance-breaking chemistries. LSTM has the largest collection of
characterised insecticide resistant and susceptible mosquito colonies in
the world, maintained by the Liverpool Insect Testing Establishment (LITE;
facility is being used by a range of commercial partners as part of the
insecticide development pipeline.
Programmatic monitoring and evaluation
LSTM has conducted evidence based monitoring and evaluation strategies for
insecticide resistance in multiple countries including defining the types
of insecticide resistance that have a major impact on the ability to
prevent disease transmission. As an example, research into the mechanisms
of resistance in Equatorial Guinea has guided and improved international
policy on resistance management . LSTM led a Tropical Disease Research
(TDR) network on insecticide resistance in malaria vectors in four
countries, establishing protocols for longitudinal resistance monitoring
and data evaluation and has worked with the Presidents Malaria Initiative
(PMI), and National Malaria Control Programmes to introduce entomological
monitoring and evaluation into routine control activities [5, 6]. The EU
funded FP7 AvecNet project is working with IVCC and in country partners,
setting new standards in quality assurance for evaluation of new
insecticides in field trials.
Underpinning Research leading to product development.
a) LSTM's research on the insect detoxification systems has led to the
development of simple, cost-effective and user friendly kits for
monitoring insecticide residues on insecticide-treated materials.
Pyrethroid Quantification Kits were initially aimed at pyrethroid
insecticides used on bednets but the insecticide quantification kits (IQKTM)
now also encompasses diagnostics kits to monitor DDT and Carbamates used
in indoor residual spraying (IRS) .
b) New insecticide based products to overcome the rapid selection of
pyrethroid resistance in African malaria vectors are under development by
IVCC and commercial partners. The LSTM led AvecNet consortium is
evaluating these products in the field, including undertaking the first
clinical trial of a new dual action bednet.
c) Strategic and day to day operational decisions within disease control
programmes have to be based on quality information. The Disease Data
Management (DDMS) was established to assist in the operational running,
monitoring and evaluation of a malaria control/elimination programme.
Development of a software platform that could be configured for any
environment was completed in 2011 .
References to the research
2. Mitchell SN, Stevenson B, Muller P, Wilding CS,
Egyir Lawson A, Field SG, Hemingway J, Paine JI, Ranson
H, Donnelly MJ. Identification
and validation of a gene causing cross-resistance between insecticide
classes in Anopheles gambiae from Ghana. (2012) Proceedings of
National Academy of Sciences, 109:6417-52. Citations: 20 Impact Factor:
Selected Research Awards
2005-2013. Bill & Melinda Gates Foundation. `Innovative
Vector Control Consortium (IVCC)'. $50,744,497. Janet Hemingway
2010-2016. Bill & Melinda Gates Foundation. `IVCC
Product Development Partnership', $50m Janet Hemingway. (PI)
2011-2016. European Commission (FP7). 'African Vector Control: New Tools
(AvecNet)'. €11,999,989. Hilary Ranson. (PI)
Details of the impact
The WHO estimates that insecticide resistance in African malaria vectors,
if left unchecked, could potentially result in an additional 120,000
childhood deaths, rising to 250,000 as current vector control tools are
scaled up . LSTM's research is working to prevent this
eventuality. Its approach to resistance analysis has contributed to the
greater understanding of insecticide resistance, and has led to proactive
decisions being made on insecticide use to avoid control relapses by
malaria control programmes in Bioko, Zambia, Mozambique Uganda and
Zanzibar. Global Malaria Programme at the World Health Organization has
stated "As part of the global malaria community, LSTM has made significant
contribution through their research efforts to the prevention and control
measures in addressing the problem of insecticide resistance in the WHO
African Region" leading to the 25% reduction in malaria mortality rates
since 2000 and by 33% in the WHO African Region .
LSTM technical input was sought for the WHO Global Plan for Insecticide
Resistance Management in Malaria Vectors 2012 (GPIRM)  and the
recommendations for action in the GPIRM are substantially based on the
research output of LSTM in identifying resistance mechanisms and means to
track resistance in the field, and in helping countries to generate an
evidence base for resistance management strategies. LSTM managed the only
large-scale public health insecticide resistance management programme with
a 7-year trial in Mexico, sponsored by industry which demonstrated that
Indoor Residual Spraying (IRS) in either an annual rotation system or a
village scale mosaic maintained control and extended the useful life of
LSTM worked directly with National Malaria Control Programmes in Malawi,
Bioko, South Africa, Swaziland, Mozambique and Zambia between 2001 and
present day advising on the optimal resistance management strategies.
Changes in insecticide use in malaria control have occurred in each of
these countries as a direct result. LSTM also supported entomological
monitoring and evaluation in a further six African countries (Zanzibar,
Liberia, Uganda, DRC, Ethiopia, Ghana, Mozambique and Zambia), through
technical assistance to the PMI and, again, several of these countries,
including Zanzibar and Uganda, have changed the class of insecticide used
in as a direct result. The Co-Chair of the Roll Back Malaria Vector
Control Working Group, has highlighted the increased urgency for routine
monitoring of resistance and acknowledged LSTM's leading position in
driving this forward, in working with country programmes, conducting
evidence based monitoring and evaluation and insecticide selection .
Impact of product development partnership:
a. Kits for monitoring insecticide residues on insecticide treated
materials. Sub-standard spraying, loss of insecticidal activity in
the field and even fake bednets are all major problems facing malaria
control programmes. The diagnostic insecticide quantification systems
developed by LSTM are undergoing trials by AVIMA Pty (SA) for commercial
production in Africa, under the brand name "Assure" . They cost
<$1, are easy to use and have a unique ability to provide a rapid
assessment of spray team performance, so that any problems can be
rectified promptly, whether by re-spraying, retraining or improved
supervision. The IQK TM have undergone fields trials in Bioko
Island (Dec 2010), Vanuatu (Nov 2010) and Ethiopia (Aug 2013). Based on
the success of the Bioko trial, approximately 2000 prototype kits were
ordered for the subsequent spray rounds in 2011.
b. New insecticides. The first longer lasting insecticide
formulations (Actellic, Syngenta) became commercially available in 2012
and a second set was launched in 2013 (K-Othrine, BayerCropScience). These
new formulations increase the residual performance of the insecticide.
IVCC and AvecNet funded and managed all of the efficacy trials, both in
the Laboratory (LITE) and in the African field trials sites. The new
formulations make the insecticide more effective on traditional muds used
in house building in rural African communities, and reduces IRS programme
costs by increasing the required interval between applications (e.g
Syngenta's original formulation, Actellic EC, was effective for two to
three months, whereas the new Actellic CS formulation lasts for 4 - 6
months). Actellic CS is now being used in Ghana and Zambia. K-Othrine,
Bayer's long lasting formulation of Deltamethrin, is now being used in
Equatorial Guinea. Syngenta's Actellic CS country registrations are
accessible for Ghana, Equatorial Guinea . The IVCC annual
report includes further information on industry investment in research and
c. New software for assessing malaria control programmes. The DDMS
software enables managers in countries to monitor interventions and
evaluate impact in ways they have not been able to do before. They operate
in both resource-poor and resource-rich environments and can be tailored
to operate as a single database to an integrated system, combining data
from several resources, producing maps, reports and alerts for disease
outbreaks. DDMS is being implemented in Ethiopia, Mozambique and Zambia. A
Spanish version of the software was produced by LSTM in 2012 and is being
used by the Bioko Island Malaria Control Programme, Equatorial Guinea.
This highly successful programme has reduced transmission of malaria in
Bioko by more than 80% .
Sources to corroborate the impact
Each source listed below provides evidence for the corresponding numbered
claim made in section 4 (details of the impact).
- Global Plan for Insecticide Resistance Management in Malaria Vectors
- Contact: Vector Control Unit, Global Malaria Programme at the WHO. To
corroborate LSTM's significant contribution to the prevention and
control measures in addressing the problem of insecticide resistance in
the WHO African Region leading to reduction in malaria mortality in the
WHO African Region.
- Contact: Co-Chair of Roll Back Malaria Vector Control Working Group.
To corroborate LSTM's global influence and impact on resistance
management strategies used in control programmes.
- Contact: Director for Avima Pty, the company licensing the IQK in
Africa. To corroborate Quantification Kits are in commercial production.
- Syngenta's Actellic CS country registrations can be provided on
request (Ghana, Equatorial Guinea.)
- IVCC annual report 12/13, http://www.ivcc.com/documents/IVCCAnnualreport2011-12.pdf
- Contact: Senior Officer at Medical Care Development International, who
is the PI in the Bioko Island Control Project, confirming DDMS has had a
major impact reducing transmission of malaria.