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MALARIA
VECTOR CONTROLE
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Acknowledgements
This project was financially supported by the Bill
& Melinda Gates Foundation. Special thanks go to
Dr Kathryn Aultman, Senior Programme Officer,
Infectious Diseases, for her continued support
throughout the project’s implementation.
This report was prepared by the following WHO
staff members: Magaran Bagayoko, Lucien Manga,
Stephanie Guillaneux, Nkuni José and Anne
Damnon.
With the contribution of the following national
project officers: Etienne Fondjo (Cameroon),
Evan Mathenge (Kenya), Simon Rakotondrazafy
(Madagascar), Sitan Traore (Mali), Abdoulaye Diop
(Senegal), Bilali Kabula (Tanzania) and Samira
Sibindy, (Mozambique).
Special thanks go also to WHO National
Professional Officers in the seven countries
concerned: Alexis Tougordi (Cameroon), Sambou
Bacary (Senegal), Ritha Njau (Tanzania), Luciano
Tuseo (Madagascar), Cheick Oumar Coulibaly
(Mali), Eva De Carvalho (Mozambique), Kalu
Akpa (Kenya).
We are grateful to the members of the African
Network for Vector Resistance (ANVR),
particularly the following institutions, for their
support:
Executive Summary
There was a significant
increase in the amounts of
insecticides used for malaria
control in Africa following both the
expansion of indoor insecticide residual house
spraying (IRS) and the distribution of long-lasting
insecticidal nets (LLINs). This massive use of public
health insecticides stems directly from an increased
selective pressure on insecticide resistance of malaria
vector mosquitoes. This will, in turn, contribute
to accelerating the development and spread of
resistance of malaria vectors and potentially
jeopardize the long-term benefit of existing and
newly developed insecticides
The project contributed to filling the gaps in skills,
expertise, infrastructure and working procedures
and strengthened the entomological skills of
national malaria control programmes and local
research institutions in the participating countries.
Seven national reference entomology laboratories
were renovated and fully equipped; more than
300 national technicians were trained in basic
entomology and vector control in the seven
participating countries; 20 graduate students in
four countries were sponsored through the project
to complete their BSc, MSc, and PhD courses. In
addition, the project supported the establishment
of functional sentinel sites for vector surveillance
within the countries. Insectaries equipped with
vector sampling and rearing facilities were built to
facilitate and intensify vector resistance monitoring
activities. One of the most important outcomes in
the area of insecticide resistance monitoring was the
development of a regional database comprising over
1909 bioassay results covering 364 different sites in
30 countries
Abbreviations
ANVR African Network on Vector Resistance
CDC Centers for Disease Control and Prevention
CREC Centre de Recherche entomologique de Cotonou
DDT dichloro-diphenyl-trichloroethane
DFID Department for International Development
DHIS District Health Information System
ELISA Enzyme-linked Immunosorbent Assay
FORTH Foundation for Research and Technology of Heraklion
GFATM Global Funds to fight Aids, Tuberculosis and Malaria
GPIRM Global Plan for Insecticide Resistance Monitoring
GPS Global Positioning System
IDSR Integrated Disease Surveillance and Response
IMBB Institute for Molecular Biology and Biotechnology
INSP Institut National de Santé publique
IPR Institut Pierre Richet
IRbase Insecticide Resistance database
IRD Institut de Recherche pour le Développement
IRS Indoor Residual Spraying
IVCC Innovative Vector Control Consortium
IVM Integrated Vector Management
KEMRI Kenya Medical Research Institute
LBMA Laboratory of Applied Molecular Biology
1 Project Rationale, Goal and
Objectives
The project was prepared in
2007 on the basis that there
was a rapid increase in the
amounts of insecticides used
for malaria control in Africa This
was due to the expansion of both Indoor Residual
House Spraying (IRS) and distribution of long lasting insecticidal nets. One of the consequences
of this massive scale up of vector control
interventions was an increased selective pressure
for resistance of malaria vector mosquitoes. There
were fears that this would, in turn, contribute to
accelerated development and spread of resistance
of malaria vectors and potentially jeopardize
the long-term benefit of existing and newly developed insecticides.
It was therefore critical to set the basis for
judicious use of insecticide products so as to
ensure optimal and long-term benefit and returns
to the investments made towards developing new
insecticide products. The project strategy was
based on five key elements:
1. basic vector surveillance capacities of
national malaria control programmes;
2. existence of a local research institute
or laboratory with at least advanced
capacity in vector surveillance;
development of the entomological skills of
national malaria control programmes;
The project was formally launched in February
2008 and implemented over a four-year period in
the following seven selected countries: Cameroon,
Kenya, Madagascar, Mali, Mozambique, Senegal
and Tanzania. It ended in December 2011.
2 Technical Report
All the above milestones were
reached during the first three years
of implementation. The summary
of achievements in Activity 1 is set
forth below and shows that all the
milestones were attained:
Countries’ baseline situation in terms
of vector surveillance capacity was
established at an inception meeting
held in Yaoundé, Cameroon, in 2008.
The needs of national malaria control
programmes (NMCP) and national
reference units (NRU) in terms of
staffing, training, equipment and
supplies were assessed.
The assessment revealed that
challenges hampering appropriate
selection and application of available
vector control measures included:
weak infrastructural, technical and
institutional capacities of national
vector control services and weak
collaboration between vector control
centres and networks of excellence
and national malaria control
programmes, leading to suboptimal
use of entomological information
for decision-making. The assessment
also showed that the critical role
of local research institutes in the
implementation of control programmes
was not formally recognized, clearly
defined and endorsed by the ministry
of health and its partners.
Establish countryspecific databases
The following two milestones were set for this
major activity:
(a) Train NRUs and NMCPs in
management of the database.
(b) Generate country-specific resistance
reports.
In 2010 a hands-on training was provided for
15 scientists from the project countries on the
concept and methodology of development of
malaria entomological profiles. These were drilled
on the practical guidelines and the state-of-the
art methodology on how to fill the data collection
proforma, use the database and analyze the data
to build the profile documents that were validated
and approved locally for decision making
Activity 2: Harmonize procedures
and protocols
The following two milestones were set for this
activity:
(a) Organize two standardization
workshops.
(b) Disseminate new and standardized
protocols.
The trial edition of “Standard Operating
Procedures (SOPs) for vector surveillance in the
context of integrated disease surveillance (IDSR)
and integrated vector management (IVM)” was
produced, translated into French and Portuguese
and adapted by countries to their national
contexts.
3 Monitoring, Evaluation, and
Dissemination
The monitoring and
evaluation milestones were
the following:
(a) Undertake mid-term project evaluation.
(b) Undertake final project evaluation.
1. Mid-term project
evaluation
In accordance with the project implementation
framework, a mid-term evaluation was conducted
at the end of the second project fiscal year. In
order to achieve this activity, two consultants were
recruited to simultaneously review the project in
the project countries as follows:
(a) Dr Nabie Bayoh (KEMRI) for
Madagascar, and the three Anglophone
countries: Kenya, Mozambique and
Tanzania.
(b) Dr Patrick Bitsindou (MoH, Congo) for
Francophone countries: Cameroon, Mali
and Senegal.
The following objectives were set for the midterm review:
2. Final project
evaluation
The final evaluation meeting was organised
in Yaoundé, Cameroon, in February 2012.
The meeting brought together all the project
implementation stakeholders including the
national project officers, representatives of
National Malaria Control Programmes, scientists
from National References Units (NRUs) in
the seven project countries, the project steering
committee member, representatives of the Bill
and Melinda Gates Foundation as well as WHO
vector control staff at both global and regional
levels
(a) To assess the status of implementation
of the major activities of the project at
all levels.
(b) To validate the level of attainment of
project objectives and targets.
© To share countries’ experiences in
the project management including
challenges, opportunities as well as
issues pertaining to the sustainability of
achievements.
(d) To examine and agree on suitable
project exit strategies and propose a
sustainability plan based on the project
achievements and lessons learnt.
Enabling factors
(a) Effective implementation of the project
was facilitated by the renewed interest
in vector control in pursuance of the
malaria elimination goal set by endemic
countries and their partners.
(b) Availability, in the Region, of a number
of institutions able to undertake capacity
building and make sophisticated
laboratory analysis.
© Availability of well-qualified trainers in
each project country (only few requests
for external expertise were made by
project countries).
(d) Willingness of other reputable
institutions to collaborate in or
contribute to the development of
a Global Interactive Database on
insecticide resistance (IRbase): IMBB
(Crete University), IVCC (Liverpool
School), Vector Base, Anobase (Notre
Dame University).
(e) Momentum gained by ANVR in the
Region.
(f ) Synergy between this project and other
malaria control activities supported by
other partners especially GFATM, PMI,
World Bank booster programme.
Constraints and Challenges
Operational problems encountered during the
project’s implementation included:
(a) Delay in the procurement of some
project equipment including resistance
monitoring test kits in some countries.
(b) Delay in the disbursement of funds
allocated at country level (lengthy local
disbursement procedures and slow flow
of funds in some countries).
© Interruption of the contract of some
project officers.
(d) Weakness of reporting from national
project officers (inadequate information
flow at all levels).
(e) Lack of vector control focal person/
entomologist in some NMCPs.
Proposed Exit Strategies
and Sustainability
During the project’s final evaluation meeting,
there was a brainstorming and discussion session
on how to sustain the gains of the project and
continue with its activities in the context of the
national malaria control programme.
Conclusion
The capacity building approach piloted in this
project shows that it is possible to harness existing
local resources to expand the expertise base of
control programmes, if research institutions are
given an opportunity to contribute to programme
implementation. This project also revealed that
by having better information, countries will be
sufficiently able to support their programmes
by improving the efficiency and effectiveness
of delivering vector control interventions. The
business model of this project will serve as a
springboard for the deployment of the Global Plan for Insecticide Resistance Monitoring
(GPIRM) in the African Region through the
African Network of Vector Resistance.
Recommendations
(a) Use the achievements of this project to
advocate for entomological surveillance
and insecticide resistance monitoring.
(b) Develop and disseminate, to countries,
a comprehensive and well-packaged
project document.
© Share the project final reports and
products with potential donors (DFID
and PMI) through ANVR.
(d) Explore the possibilities of funding and
fund-raising at country level.
(e) Formalize and maintain collaboration
between NMCP and national research
institutes.
(f ) Foster country ownership to maintain
and strengthen the capacity built
through this project as well as continuity
in in-service training.
(g) Insecticide resistance monitoring and
management should be part of the
NMCP’s routine activities as opposed to
only operational research.
(h) Replicate the capacity building approach
experimented in this project in other
malaria-endemic countries in the
African Region.
4 Financial Report
The Global Health Division
Programme of the Bill &
Melinda Gate Foundation
(also referred to herein as
“the Foundation”) gave the
World Health Organization
(WHO) a project support
grant in a total amount of
US$ 4 943 750.00 for the
period from 10 October 2007
to 10 October 2011.
The use of funds of this grant was restricted to
filling the gap between product development
and effective delivery for African countries by
consolidating and strengthening the medical
entomology, vector control structure and technical
resources within each country as described in the
foregoing narrative report.
Constraints
The preparation of this financial report was
hampered by the two GSM transitions that
occurred during the grant life (transition of
WHO headquarters, beginning 2008, and
transition of WHO African Region, beginning
2011). GSM transition of the African Region
occurred during the reporting period. All
information related to 2011 expenditures
were reflected properly in GSM. In contrast,
information related to activities/expenditures
effected before GSM went live were in the old
ROAFI system and needed to be tracked:
Conclusion and recommendation
The review showed that all the planned activities
were successfully implemented. More than 95%
of the overall grant funds were used as planned.
This performance reflects collaboration among the project’s implementing partners at all levels
(the national malaria control programme and the
national reference unit for vector control).
A final certified financial report will be
submitted by GMG in May 2012 as per the
grant agreement. It is important to note that
any discrepancies in expenditure by budget item
between this financial report prepared by the
project team and the Final Certified Financial
report which will be provided by WHO GMG/
ACT should be due to the fact that expenditures
were not recorded in GSM in the same way
1 Atlas of insecticide resistance
in malaria vectors of the WHO
African Region
1 Atlas of insecticide resistance
in malaria vectors of the WHO
African Region
1. Introduction
In the African Region, there
is a renewed interest in
vector control and in the
use of insecticide treated
nets and indoor residual
spraying.
The repeated application of insecticides for
malaria vector control is now happening on an
unprecedented scale. This has saved a lot of
lives: it is estimated that in the last ten years,
vector control interventions have prevented more
than 700,000 deaths due to malaria, 90% of
these in Africa. However, it has also caused the
appearance and spread of insecticide resistance.
In each of the major vector species, a variety of
resistance genes have been reported, and some
are already widespread throughout the Region.
Control failure associated with insecticide
resistance has already been seen in South Africa,
and insecticide choice is constrained by resistance
in operations in many places, including Ethiopia,
and parts of Eastern, Central and Southern
Africa
2. ANVR framework
All NMCP are de facto members of ANVR,
and the network is coordinated by the WHO
Regional Office for Africa. The following
scientific institutions are founding members of
the network:
♦ Centre Muraz, Bobo Dioulasso, Burkina Faso.
♦ Centre de Recherche Entomologique de
Cotonou (CREC), Benin.
♦ Institut Pierre Richet (IPR), Bouaké, Côte
d’Ivoire.
♦ Institut de Recherche pour le Développement
(IRD), Montpellier France.
3. Methodology
Resistance data were collected and collated by
the ANVR sub-regional network coordinating lambdacyhalothrin, Bendiocarb,
Fenitrothion and Malathion) and per vector
species. Much fewer tests have been carried
out with An. funestus because this species
is far more difficult to collect and to breed
than species of the An. gambiae complex.
Tested mosquitoes have been identified
morphologically, and when possible, species,
and resistance mechanisms have been
identified using molecular markers. The kdr
mutation responsible for pyrethroid and
DDT cross-resistance has been detected
using specific primers (Martinez-Torres
et al., 1998; Lynd et al., 2005). Modified
acethylcholinesterase (AchE), a major
mechanism for organophosphate and
carbamate resistance, has been identified
using both biochemical (Hemingway et al.,
1998) and molecular assays (Weill et al.,
2004).
4. Results
4.1 Survey locations
In total, 1909 tests over 30 countries
covering 364 different sites have been
reported through (Map 1). This result
shows an increase in the number of surveys conducted, countries covered as well as
sentinel sites compared to the previous Atlas. The
evolution of vector resistance status is provided
below. For detailed information by country,
readers should refer to the corresponding map(s)
displayed by major vector species and insecticide.
4.2 Distribution of malaria
vectors in the African Region
A regional data base on the geographical
distribution of vectors belonging to the
Anopheles gambiae complex has been developed
in the previous Atlas. Three main vector species
(An. gambiae s.s. An. arabiensis, and An. melas)
belonging to this complex have quite different
distribution patterns. Anopheles gambiae s.s.,
globally the most important vector, is widely
distributed in low lands throughout inter-tropical
Africa. Commonly associated with An. funestus,
this species is responsible for intense transmission
either seasonal or perennial depending on local
climatic conditions and opportunities for larval
breeding. In some areas, two other important
vectors of local importance can also be found
(Anopheles nili and Anopheles moucheti),
especially in Central Africa.
Anopheles arabiensis has a wide distribution but
is found predominantly in fringes and highlands:
Southern and Eastern Africa, highlands, Sahelian
areas of Western and Central Africa. In these
areas, it is commonly associated with Anopheles
funestus and, to a lower extent, to Anopheles
gambiae s.s.
4.3 Resistance of Anopheles
gambiae complex to DDT and
pyrethroids
In the majority of surveyed localities in West,
Central, and Eastern Africa, An. gambiae has
been found resistant to DDT (Map 3). Pyrethroid
resistance is also widespread, especially in West
Africa (Map 4 to 6). Occurrence of Deltamethrin
and Lambdacyhalothrin resistance is apparently
lower than that of Permethrin. However, this
difference is likely due to the relative “strength”
of the discriminative concentrations used than a
lower resistance to these specific insecticides.
In West Africa, the presence of the kdr mutation
is clearly associated with cross-resistance between
DDT and all public health pyrethroids. Kdr is
widely distributed and allelic frequencies of the
gene in several areas are very high, commonly
higher than 80 % (Map 7)
4.4 Resistance to carbamates and
organophosphate (OP)
Resistance to carbamate (carbosulfan) was already
detected in Côte d’Ivoire earlier (Chandre et al.,
2003) and is now wide spreading (Bendiocarb)
across West Africa (Map 8). Resistance to OP
(Fenitrothion) was observed in very few localities
(Map 9). The mechanism involved is a modified
acethylcholinesterase (AchE). A molecular
diagnostic test has been recently developed.
4.5 Resistance of Anopheles
gambiae s.s.
Resistance of Anopheles gambiae s.s. to the
different commonly used insecticides is shown in
Map 11 to 16. In West Africa An. gambiae s.s.
is the predominant species of An. gambiae s.l.
Therefore the resistance distribution pattern in the
complex and An. gambiae s.s. is quite similar.
4.6 Resistance of Anopheles
arabiensis
Insecticide resistance has been found much less
frequent in An. arabiensis than in An. gambiae s.s.
(Maps 17 to 22). In several countries of Southern
Africa, this species is fully susceptible to DDT and
pyrethroids. However, DDT resistance has been
reported in South Africa. There is also evidence
of DDT resistance in Eritrea and Ethiopia and of
cross resistance between DDT and pyrethroids in
An. arabiensis from northern Cameroon.
4.7 Resistance of Anopheles
funestus s.l.
Only few data on susceptibility of An. funestus
s.l. have been collected through ANVR. Except
in Ghana, Nigeria and Kenya where a possible
resistance to lambdacyhalothrin has been detected
that needs to be confirmed, full susceptibility to
DDT and pyrethroids has been found in all tested
localities (Map 23 to 28). However, these data do
not include tests carried out in South Africa and
Mozambique where resistance to Deltamethrin
has been found that has got important
operational consequences. On the basis of the
usually dramatic impact that residual spraying and
ITNs have got on An. funestus s.l. populations
throughout Africa (published data and grey
literature), it is reasonable to assume that outside
Southern Africa, this species is mostly susceptible
to insecticides, including DDT and Pyrethroids.
However, more detailed information on resistance
status of this species is needed.
5. Overall situation
analysis, potential impact of
insecticide resistance, and
selection of interventions
Although there are important gaps in the
resistance mapping, some general conclusions can
be already drawn and practical recommendations
made. Detailed analysis country by country
should be made by readers themselves on the
basis of maps presented in this document.
5.1 Resistance in major vectors
♦ An. gambiae s.s. DDT and Pyrethroid
resistance are already widespread throughout
Western and Central Africa. According to
other sources of information, it is also present
in several parts of Eastern Africa. Carbamate
resistance has been detected in West Africa
involving a major resistance mechanism
that has been found already spread over
several countries
6. Recommendations
To countries
♦ To initiate and/or strengthen insecticide
resistance monitoring as a component of the
national malaria control plans. The necessary
resources (human and financial) should be
made available, eventually obtained from
funding partners.
♦ To fill gaps in the current knowledge of
resistance in malaria vectors (distribution,
mechanisms involved) and to start testing
susceptibility to insecticides other than
DDT and pyrethroids (carbamates,
organophosphates).
♦ To share and disseminate information on
insecticide resistance. The present Atlas
offers opportunity for rapid dissemination of
information. It will easily be updated.
♦ To select vector control interventions and
insecticides taking into account, among other
important factors, the resistance status of local
vector populations.
♦ To ensure continuous resistance monitoring.
♦ To adopt insecticide resistance management as
part of national policies for vector control.
be that personal protection provided by ITNs
will be maintained despite resistance while
the community protection expected from high
coverage of this intervention might be reduced
because of resistance. As far as residual spraying
is concerned, an impact of resistance should a
priori be expected unless absence of such impact
has been shown. Only insecticides to which local
vectors are susceptible should be selected for
residual indoor spraying. Resistance management
policies should be progressively adopted by all
residual spraying programs to prolong the use-life
of existing insecticides. The arsenal of insecticides
that are currently available for residual spraying is
already very limited.
5.5 Choice of malaria vector
control interventions
ITNs. In most lowlands of Africa with intense
transmission, an interruption or a dramatic
reduction of transmission through residual
spraying or ITNs interventions would be
technically difficult to achieve because of intensity
of transmission, widespread insecticide resistance
or the absence of operational vector control
services. It would also be financially difficult to
sustain. On the contrary, a significant reduction
in malaria incidence can be achieved through
personal protection of vulnerable groups by mass
distribution of ITNs, including in areas where
vectors are resistant to pyrethroids. ITNs are
effective also in low transmission areas (unstable
malaria). However, to benefit from the full
potential of this intervention, programs should
target the highest possible coverage in order to Filling the gap between product development and effective delivery | 47
To funding partners
♦ To ensure resistance assessment and
monitoring is included in requests for funding
related to malaria vector control and is
adequately funded.
♦ To support the adoption of insecticide
resistance management policies.
To WHO
♦ To further build capacity for resistance
monitoring at country level and coordinate
resistance monitoring activities in the African
region, in the framework of ANVR.
♦ To develop regional guidelines for insecticide
resistance management and promote adoption
and implementation of resistance management
tactics.
♦ To update and complete the present
document, collecting and incorporating data
obtained at country level as well as published
information.
♦ On request of national programs, to
review country by country the situation of
insecticide resistance and to provide technical
advice on the selection of insecticides and
implementation of locally adapted vector
control strategies.
♦ To further stimulate research on the
operational impact of insecticide resistance on
the efficacy of vector control interventions.
♦ In view of the situation of insecticide
resistance in malaria vectors, to further
promote the adoption of integrated vector
management principles, with the objective to
further reduce reliance on single insecticide
and intervention.
To WHO and Industry
♦ To promote the search for new insecticides
alternative to DDT and pyrethroids.
The surveys were repeatedly carried out in the
same locations in most countries. In total data
were collected in 364 localities with geographic
coordinates across the continent as shown on the
map.