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INSECTICIDE RESISTANCE IN MOSQUITOES
Mosquito-borne disease control is best achieved with insecticides
...
The phenomenon is striking; since often a thousand-fold higher insecticide
dosage is required to kill a resistant mosquito population, compared with a ‘normal’ one
...

Insecticide resistance is currently a major problem in several mosquito species, such as the major
malaria vector Anopheles gambiae
...
Insecticide formulations for use in mosquito control are particularly limited, as
insecticide companies may not be very interested in registering new active ingredients for public health
products, as the market is very small (e
...
compared with agriculture) and the registration procedure
demanding
...
Thus management of the available insecticides requires very careful
consideration, to prevent or delay resistance development
...
When
insecticides are applied on insects, the active principle reaches the target sites as follow;
APPLICATION OF INSECTICIDE CONTAINING ACTIVE INGREDIENTS
PENETRATES INTEGUMENT OF INSECT
REACHING TARGET SITES
BINDING ACTIVE SITES
THRESHOLD CONCENTRATION CAUSE THE DEATH OF INSECT
1
...
It reaches the site of action,
3
...
When they have attained threshold concentrations they cause the insect's death
...
Minal (MPhil), 2016

Insecticide Resistance: A Global Threat to Public Health
According to WHO (1957) resistance has been defined as “the developed ability in a strain of insects
to tolerate doses of toxicant which would prove lethal to majority of individuals in a normal population
of the same species”
...
More than 40
years of intensive organic synthetic insecticide use to control arthropod pests and disease vectors have
resulted in pesticide resistance among over 450 species
...
The number of insecticide-resistant arthropods of public health importance has
been observed to rise from 2 in 1946 to 150 in 1980 and 198 in 1990
...




The situation in Burkina Faso is emblematic with Anopheles gambiae populations showing high
levels of resistance to most of the existing synthetic insecticides
...
culicifacies, An
...
fluviatilis, An
...
dirus and An
...
In addition to these, An
...

philippinensis, An
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jeyporiensis have also been reported as secondary malaria
vectors
...
culicifaciess
...
, the major vector in most parts of the country, has been observed to
develop with widespread resistance to DDT, dieldrin/HCH, and also to Malathion in several
districts
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stephensi, An
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philppinensis
...
stephensi and An
...
Larvae of both the species showed
some evidence of resistance to chlorpyriphos followed by fenthion
...




It is important to note that not only mosquitoes, but also the other public health important insects
such as fleas, ticks, cockroaches, bedbugs, sand flies, and houseflies evolved insecticide resistance,
due to their permanent exposure
...
Minal (MPhil), 2016

Causes of Resistance Development


The resistance usually occurs due to insecticide detoxification by mutant enzymes (isozymes)
engendered by resistant gene alleles, but some resistance may also be conferred by the reduced
toxicant uptake
...

Insecticide Resistance Action Committee (IRAC)

In 1984, the Insecticide Resistance Action Committee (IRAC) was formed in order to provide a
coordinated private-sector response to prevent or at least delay the development of resistance
...

Over the past several decades, the induction of modern synthetic insecticides in the vector control
programme has led to the selection pressure on insect populations
...

At the moment, it has been reported that there is a widespread resistance to all classes of existing
insecticides among many insect pests of agricultural and public health importance, making their control
more arduous than ever before
...
The resistant insects may possess
overproduction of detoxification enzymes that break-down the toxic insecticides into nontoxic compounds,

(iii)

Behavioral resistance occurs when the resistant insects avoid the insecticide treated
surface area by changing their customary behavior
...
Arabiensis
mosquito has changed its resting behavior from endophilic (resting indoor) nature to
exophilic (resting outdoor) in order to avoid the contact or exposure to indoor residual spray
in africa
...
Minal (MPhil), 2016

(iv)

Penetration resistance occurs when the cuticle (outer layer of insects) absorb the
insecticides molecules much more slowly than the susceptible insects
...
(1996) (42),
but its significance has not been well established
...
It is
a large class of structurally very diverse, synthetic analogues of natural pyrethrins from the
plant of Chrysanthemum spp
...
The insecticide resistance mechanism of pyrethroid is
known as knockdown resistance (kdr) resulting from mutations in the voltage-gated sodium
channel (the target-site for DDT and pyrethroids)
...


a
...
gambiae
...
A)
...
The regulatory element termed the Barbie
Box al oxidase and esterase resistance genes
(Fig
...

c
...
An
amplicon is a piece of DNA or RNA that is the
source of replication process, which produce one or more copies of a genetic fragment
...

It has been estimated that nearly more than 100 copies of this amplicon may be present
within a single species of mosquito (Fig
...
Minal (MPhil), 2016

Three Principal Types of Resistance Mechanisms
Three types of résistance mechanisms are clearly illustrated in the Figure
...
Resistance may happen at each step of this
pathway:
(i)

The integument/ outer-layer (cuticle) of an insect may

be altered into a lesser permeable, thus reducing the entry
rate/amount of insecticide;
(ii)

New or more abundant metabolic enzymes may be

selected, which break down the insecticide active
ingredients more efficiently and make it ineffective; and
(iii)

Alter the target sites - as a result insecticide molecules are no longer able to bind with action
sites
...
However, it is important to note that a reduction in the rate of
cuticular penetration fosters both types of mechanisms in a more synergistic way
...




The continuous application of insecticides with similar mode of action, results in the selection of
the resistant individuals and hence resistance gradually increases among insect population which
eliminates the susceptible ones
...




Mosquito control has focused on the use of insecticides (initially organochlorines, followed by
organophosphates and carbamates) through indoor residual spraying
...




The use of ITNs for both individual and collective protection against malaria has shown potential
in reducing childhood malaria morbidity by 50% and global mortality by 20–30% in the Gambia,
Ghana, and Kenya
...


Course work by Savy P
...
Even the frequent exposure to lower concentrations
of pyrethroids, the risk of toxicity is remote
...




To date, only four classes of synthetic insecticides such as organochlorines (now banned in many
countries), organophosphates, carbamates and pyrethroids are available to control adult mosquitoes
...
Consequently there is much less target-site diversity among the
public health important insect vectors than the pests of agriculture
...
Indeed, the quality vector control programmes must ensure the quality assurance
in terms of minimizing the unnecessary insecticide selection pressure in non-endemic areas, which
may considerably reduce the avoidable operational costs too
...
Résistance may develop rapidly in
some populations and slowly in some others
...
Resistance
evolved most rapidly to higher levels toward the pyrethroid permethrin and most slowly toward the
toxin complex of Bacillus thuringiensis subsp
...




Several biotic and non-biotic factors have contributed to the evolution of insecticides, factors such
as rapid reproduction of insects, migration, existence of susceptible populations, host range, the
effective dosage of insecticides, the period and number of applications of insecticides
...




In addition, the degree of resistance in insect vector populations is largely dependent both on the
volume and frequency of insecticide applications and the inherent nature of the insect species
involved
...


Course work by Savy P
...
However, it has been estimated that nearly 90% of all insecticides
worldwide are used for agricultural purposes
...




However, Lines (1988) and Georghiou (1990) have reviewed the correlation between
agrochemicals and insecticide resistance in mosquito vectors
...




The cross-resistance among different classes of insecticides could substantially impair the usage of
existing insecticides due to alterations of target sites or detoxification process
...




The mechanism of detoxification is also commonly known as metabolic resistance, which primarily
involves three major groups of enzymes such as Esterases (ESTs), Glutathione-Stransferases
(GSTs), and Mixed Function Oxidases (MFOs)
...
The oxidase-based DDT-pyrethroid cross-resistance has been reported in
Guatemalan An
...
gambiae, between organophosphates and pyrethroids
crossresistance conferred by esterases in An
...
Albimanus
...
It is mainly due to the wide-spread and sequential application of different
classes of insecticides to control several species of Anopheles
...




In most of the cases, not only does resistance render the selecting compound much less effective
but it also often confers cross-resistance to other chemically inter-related compounds
...




The medically important insects successfully adapt to most of insecticides by becoming
physiologically or behaviourally resistant to them and this creates immense practical problems
...
Minal (MPhil), 2016



Additionally, previous selection with insecticides can confer resistance to new materials through
cross-resistance and can have serious impacts on control by reducing the effectiveness of many new
insecticides
...
However, if the likelihood of resistance development to novel insecticides can be
predicted before they are used; it should be possible to establish an effective resistance management
program
...
Indeed
resistance to insecticides by insects is considered as a recent evolutionary adaptation to
environmental changes, occurring in less than one century in response to sequential applications of
chemical insecticides like organochlorines (OCs), organophosphates (OPs), carbamates and
pyrethroids, and even biological insecticides
...




In addition, data on insecticide use for vector control are extremely important to design appropriate
pesticide management systems on judicious use, resistance management, and reduction of risks to
human health and the environment
...
It includes the lack of pesticide registration guidelines, gaps in pesticide
procurement practices, and a lack of expertise of vector control decision makers
...


INSECTICIDE RESISTANCE MANAGEMENT (IRM)


Indeed, there is always a considerable risk of resistance evolution, especially when the insecticides
are indiscriminately misused or over-used
...




Since the majority of the insect pest/vector populations are usually larger in size and have the
potential for rapid proliferation in terms of shorter life-span with huge number of progeny
...


Course work by Savy P
...

Indeed, no single prescription can be offered to forestall resistance under any conditions
...




Management by moderation should be the basic approach and should be supplemented to the
maximum possibly by integrated pest management measures
...




The World Health Organization (WHO) strongly recommends the simultaneous use of different
vector control tools and this has formulated the basis for Integrated Vector Management (IVM)
strategies
...




The main objective of the IVM approach is to contribute to the achievement of the global targets
set for vector-borne disease control, by making vector control more efficient, cost effective,
ecologically sound and sustainable with the available tools and resources
...
In addition, the rotation of chemically
different classes of insecticides has been tested and the use of novel insecticides alone or in a mosaic
with existing insecticides has also been proposed
...




However, currently, to address the insecticide resistance by means of biological control agents like
the entomopathogenic fungi such as Metarhiziumanisopliae and Beauveriabassiana have also been
advocated
...

gambiae mosquitoes
...




Howard et al
...
gambiae mosquitoes
were more highly susceptible to fungal infection than the insecticide susceptible strain of An
...
It provides an opportunity to kill insecticide resistant mosquitoes more quickly than the
susceptible ones
...




Furthermore, the entomopathogenic fungal infection may quickly and easily eliminate the
insecticide-resistance genes from the wild population and it leaves the susceptible mosquitoes to

Course work by Savy P
...
This could lead to an effective resistance management without further application
of insecticides
...



IRM is used to describe practices aimed at reducing the potential for insect pests to become resistant
to a pesticide
...
The first three
factors are indigenous to the population and beyond control
...




Today, resistance management in the context of integrated pest management has evolved as the
favored approach to prevent, delay, or reduce the impact of insecticide resistance
...

darlingi
...
This alternative intervention has
removed the selection pressure and reduced the frequency of resistance
...




It clearly suggests that the resistance genes can be eliminated from the vector population by
removing the selection pressure
...

INSECTICIDE RESISTANCE MONITORING AND SURVEILLANCE



Resistance monitoring and evaluation are critical elements of vector control programme and their
impacts are essential to understand the progress, challenges and success of disease control
...




Knowledge of vector/pest susceptibility to pesticides, changing trends of resistance and their
operational implications are the basic requirements to guide pesticide use in vector-borne disease
and pest control programmes
...




If, resistance is once established in a vector population, there is a genuine threat of the resurgence
of vector borne diseases that had been presumed to be under control and by the time such resistance
is detected, it is often far too late
...


Course work by Savy P
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REFERENCES:

1
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nature
...
html
2
...
, & Sabesan, S
...
Insecticide resistance in insect vectors of disease
with special reference to mosquitoes: a potential threat to global public health
...

3
...
, Ng, L
...
, Lam-Phua, S
...
, Tang, C
...
, Itokawa, K
...
& Tomita,
T
...
First detection of a putative knockdown resistance gene in major mosquito
vector, Aedes albopictus
...

4
...
nature
...
10643

Course work by Savy P

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