Insecticide resistance and management

By Matowo J, KCMUCo
 Overview

•  Main classes of insecticides for public health

•  Insecticide resistance

•  Mechanisms of insecticide resistance

•  Management of Insecticide Resistance

 Insecticides used in public health
•  There are four major insecticide classes based on their chemical nature
are used for malaria vector control.
– Organochlorines
– Organophosphates
– Carbamates
– Pyrethroids

•  These insecticides have different modes of action which determine their

mechanisms of resistance
•  Other class of insecticides include biopesticides such as bacteria
Ø  Most common are Bacillus thuringiensis israelensis (Bti) and Bacillus
sphaericus)
-Produce proteins that are toxic to mosquito and black flies larvae.
 Insecticides used in public health  
Insecticide formulations are adapted to requirements of various
application methods, storage and delivery systems

•  Water-dispersible powder (WDP)

Ø  Dry powder mixed with surface-active agent that allows insecticide to
dissolve in water, as suspension

•  Emulsifiable concentrate (EC)

Ø  Consists of solvent + emulsifying agent in which the insecticide is
dissolved. When mixed with water-forms milky emulsion of finely
suspended particles

•  Suspension (or flowable) concentrate

Ø  Consists of particles of insecticide with wetting agent and some water.
 Insecticides used in public health
•  Pyrethroids are the only class of insecticides approved for use
with ITNs/LLNs due their rapid knock-down effect and with no
adverse effects on human

• Challenges:
Ø Development of behavioural resistance such as
exophily, whereby mosquitoes avoid internal
walls treated with insecticide

Ø Development of pyrethroid resistance

-  Pyrethroid resistance has become widespread in major malaria

vectors, threatening sustainability of both ITNs and IRS scaling-up
programmes
 Insecticide resistance
Definition:
Ø Developed ability in a strain of insects to tolerate doses of insecticides which
prove lethal to the majority of individuals in a normal population of the same
species
• There are two broad mechanisms of insecticide resistance, the target-site
insensitivity and insecticide detoxification.
• Target-site insensitivity due to modification of a neural target sites are of 3
types:
Ø  ↓sensitivity to DDT and pyrethroids (kdr mutation).
Ø  ↓sensitivity to carbamates and organophosphates (Ace-1 mutation).
Ø  ↓ sensitivity to cyclodienes such as dieldrin (Mutation in GABA receptors)
 kdr  and  Ace-­‐1  muta(ons  
kdr  (knockdown  resistance)  muta2on  
•  Due  to  muta(ons  in  the  gene  encoding  the  voltage-­‐gated  sodium  channel  
•  Occurs  in  the  domain  II  S6  transmembrane  segment  of  the  sodium  channel  protein,  important  for  channel  ac(va(on      
 
 
 
 
 
 
•  Induces  a  change  of  one  of  the  amino    acids  on  the  target  site  for  DDT  and  all  pyrethroids  
 
Ø     Point  muta(on  in  gene                                                                Amino  acid  change  
                   Wildtype:  GGAAATTTAGTCGTAAGT    
                   West  Afr:  GGAAATTTTGTCGTAAGT(L1014F)-­‐Leucine  to  phenyalalnine  (kdr-­‐W)  
                     East  Afr:    GGAAATTCAGTCGTAAGT(L1014S)-­‐Leucine  to  serine  (kdr-­‐E)  
 
Ace-­‐1  muta2on  
Single   point   muta(on   in   the   Ace-­‐1   gene   encoding   acetylcholinesterase,   the   target   binding   site   of   Organophosphates   and  
Carbamates  
Ø  Subs(tu(on   of   a   Glycine   (GGC)   into   a   Serine   (AGC)   at   posi(on   119   of   the   encoded   protein   (i.e.   G119S   /Glycine   to  
serine  muta(on)  
 Insecticide detoxification
•  Three enzyme classes involved in insecticide detoxification:
Ø  Cytochrome P450s–Confer resistance to Pyrethroids, DDT,
Organophosphates

Ø  Non-specific esterases- Eleveted levels implicated in, Carbamates,

Organophosphates,and Pyrethroids resistance

Ø  Glutathione-S-transferases (GST) –Implicated in DDT resistance

•  Resistant insects may produce large amounts of enzymes, such

as esterases which either break down the insecticide molecule
or bind to it so tightly that it cannot function (a process known
as sequestration).
 Cross-­‐resistance  
•  Cross-­‐resistance  occurs  when  resistance  to  one  insec(cide  confers  
resistance  to  another  insec(cide,  even  where  the  insect  has  not  
been  exposed  to  the  laRer  product.  
•  May  be  to  other  insec(cides  within  the  same  class  or  to  insec(cides  
in  other  classes-­‐  depending  on  mechanism.    
Ø E.g.  DDT  &  pyrethroid  insec9cides  are  chemically  unrelated  but  both  
act  on  the  same  target  site  

 
Cross resistance patterns of different classes of insecticides

Circle size reflects the relative impact of the mechanism on resistance

Source: IRAC, 2010: 72pp
 Insec2cide  resistance  
•  Mul2ple  resistance  is  a  common  phenomenon  and  occurs  when  
several  different  resistance  mechanisms  are  present  
simultaneously  in  resistant  insects  
Ø  The  different  resistance  mechanisms  may  combine  to  provide  
resistance  to  mul9ple  classes  of  products    
 
•  Mul(ple  resistance  has  been  documented  in  malaria  vectors  in  
several  parts  of  Africa  including  Ivory  Coast,  Burkina  Faso,  
Cameroon  
 
 Management of insecticide resistance
•  Insecticide resistance management is aimed at:
Ø  Preventing onset of resistance
Ø  Prolonging as long as possible the effective life of existing
insecticides (Few alternative insecticides in public health coming on-
stream)

•  Requires a reliable system for vector surveillance and

resistance monitoring with an ultimate knowledge of the
genetical, biochemical and physiological basis of the
resistance mechanisms in each instance
 Strategies and tacticts for managing IR
IR management can be undertaken using insecticides based approaches in conjunction with other
non insecticidal vector control approaches (Integrated Vector and Pest Management)
Insecticides based approaches could take several forms:
•  Mixtures:
Ø  Application of two mixed compounds so individuals are exposed simultaneously to each
compound

• Rotations:
Ø  Based on the rotation over time of two or preferably ore insecticide classes with different
modes of
•  Mosaics:

Ø  Adjacent areas are treated simultaneously with different insecticides

• Use of Synergists e.g. Piperonyl butoxide (PBO) to enhance the effect of
several classes of insecticides including pyrethroids