Parasitol Res
DOI 10.1007/s00436-015-4898-9
REVIEW
Insecticide resistance and its molecular basis in urban insect pests
Muhammad Nadir Naqqash 1 & Ayhan Gökçe 1 & Allah Bakhsh 2 & Muhammad Salim 1
Received: 25 November 2015 / Accepted: 28 December 2015
# Springer-Verlag Berlin Heidelberg 2016
Abstract Insecticide resistance is one of the most important
evolutionary phenomena for researchers. Overuse of
chemicals has induced resistance in insect pests that ultimately
has led to the collapse of disease control programs in many
countries. The erroneous and inappropriate management of
insect vectors has resulted in dissemination of many vector-
borne diseases like dengue, malaria, diarrhea, leishmaniasis,
and many others. In most cases, the emergence of new dis-
eases and the revival of old ones can be related with ecological
changes that have favored rapid growth of vector densities.
Understanding molecular mechanisms in resistant strains can
assist in the development of management programs to control
the development and spread of resistant insect populations.
The dominant, recessive, and co-dominant forms of genes
encoding resistance can be investigated, and furthermore, re-
sistance development can be addressed either by the release of
susceptible strains or timely insecticide rotation. The present
review discusses the resistance level in all important insect
vectors of human diseases; the molecular basis of evolvement
of resistance has also been discussed.
Keywords Chemical control . Vector-borne diseases .
Genetics . Mutation
* Muhammad Nadir Naqqash
muhammadnadir.naqqash@mail.nigde.edu.tr
1
Department of Plant Production & Technologies, Ayhan Şahenk
Faculty of Agricultural Sciences and Technologies, Niğde
University, Niğde, Turkey
2
Department of Agricultural Genetic Engineering, Ayhan Şahenk
Faculty of Agricultural Sciences and Technologies, Niğde
University, Niğde, Turkey
Introduction
Among the evolutionary phenomena, insecticide resistance
has wider applications and is of great economic importance.
However, this phenomenon received the attention of re-
searchers when resistance was reported in insect vectors of
human diseases viz., houseflies (Musca domestica) in 1946
(Metcalf 1989).
The resistance ratio in insect vector populations depends on
the volume and frequency of applications of insecticides used
for their management. Additionally, the inherent capabilities
of insect species also play a significant role in resistance de-
velopment. Evolutionary theories have also included ongoing
arguments relevant to the significance of single-gene and
polygenic alterations during adaptation (Georghiou 1972).
When a newer insecticide is introduced in a new ecosystem
for the insect pest management, population consists of suscep-
tible phenotypes (Macnair 1991). Many hereditary as well as
ecological factors regulate the resistant phenotype in a popu-
lation. Within the same population, different factors like size,
age, general physiological condition, etc. can be observed.
Among continuous phenotypic distribution, genetic variations
among individuals of same population are usually polygenic.
Consequently, the exposed concentration of the insecticide
selecting in this distribution selection will significantly affect
these polygenic variants. After consecutive generations, the
alterations in the resistance level of the population would be
polygenic (McKenzie 1985; Roush and McKenzie 1987;
Macnair 1991). Therefore, prime factors influencing the de-
velopment of resistance include length of life cycle of the
insect pest, reproductive potential, and environmental stress
(Macnair 1991).
Many of the infectious diseases that threaten public health
are transmitted by insect vectors, e.g., mosquitoes, houseflies,
sandflies, cockroaches, tsetse fly, blowflies, human louse, and

many others (Hemingway and Ranson 2000; Naqqash et al.
2014). Over-reliance on chemicals to control these insect spe-
cies has led to resistance in them. Insecticide resistance, in-
deed, to all classes of insecticides is posing a hindrance in
management of approximately all important invertebrate pests
of agricultural and public health (Cui et al. 2006; Benelli
2015). Currently, the foremost importance in resistance re-
search is being given to the molecular mechanisms of insecti-
cidal resistance and resistance management accordingly, with
a view to manage the dispersal of resistant insect vectors’
populations on a larger area. Hemingway and Ranson (2000)
reported insecticide resistance in insect vectors, but there was
limited focus on all the important human disease-transmitting
vectors. Additionally, a scientific update is the need of the
hour keeping in view changing situation of insecticide resis-
tance in urban insect pests. In this view, the resistance level
and the mutations involved in this mechanism have been
discussed.
Resistance in urban insect pests
Resistance in housefly
The housefly is a very important pest of urban vicinity, live-
stock, and poultry. It transmits a variety of microbes, e.g.,
protozoans, bacteria, viruses, etc. (Malik et al. 2007). These
pathogens are transmitted via mouthparts, feces, excess mouth
saliva, and also their body surface (Kobayashi et al. 1999). It
disseminates disease-causing pathogens when it comes in con-
tact with people and/or animals (Malik et al. 2007) (Table 1).
M. domestica has developed resistance against almost all
available insecticide groups; therefore, this phenomenon has
Table 1 Diseases transmitted by different insect vectors of human diseases
Disease(s)/damage
Typhoid, cholera, dysentery, salmonella, anthrax, tuberculosis, etc.
Chikungunya, yellow fever, dengue fever, dengue hemorrhagic fever, etc.
Malaria, filarial worms, etc.
West Nile virus, filariasis, Japanese encephalitis, St. Louis encephalitis,
and avian malaria
Leishmaniasis, phlebovirus, vesiculovirus, Toscana virus, Sicilian
virus, sandfly fever, Naples virus, and orbivirus
Human onchocerciasis (or river blindness), mansonellosis, avian
leucocytozoonosis, bovine onchocerciasis, and arboviruses
Sleeping sickness
Human myiasis and allergy
Bubonic plague, dysentery, boils and abscesses, diarrhea, typhoid, etc.
Typhus fever, trench fever, and relapsing fever
Plague, murine typhus, and epidemic typhus
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gained worldwide the attention of researchers (Akiner and
Caglar 2006). Many insecticides belonging to organophos-
phate, carbamates, pyrethroids, and new chemical classes
have been used for the control of M. domestica worldwide.
Among the vectors of human, M. domestica is the first insect
in which resistance was reported against organochlorides
(DDT) (Metcalf 1989), and with the passage of time, it devel-
oped resistance not only against organophosphates, e.g.,
DDVP ranging between 45.4 and 62.5 (Acevedo et al.
2009), and carbamates, e.g., propoxur >290-fold resistance
(Liu and Yue 2000), but also to all other groups of insecticides
in many areas of the world (Shi et al. 2011).
Development of resistance in the house flies to pyrethroids
(permethrin, lambda-cyhalothrin, beta-cypermethrin, etc.)
was reported in a number of regions of the world. It is specu-
lated that resistance to pyrethroids like permethrin may en-
hance to 18,400-fold (Shono et al. 2002). Resistance can en-
hance to 430-fold against some new chemistry insecticides
like fipronil both in laboratory-selected and field populations
(Scott et al. 2000; Acevedo et al. 2009; Kristensen et al. 2004).
Moreover, resistance to some insect growth regulators (IGRs)
(primarily pyriproxyfen, novaluron, triflumuron) up to 1000-
fold has been also reported in a number of countries of the
world (Kristensen and Jespersen 2003) (Table 2).
Molecular basis of resistance in housefly
M. domestica completes its development within 10–12 days,
so a shorter life cycle (Khan et al. 2012) contributes to a
quicker response to selection pressure (Roush and McKenzie
1987). It has been established that the major resistance mech-
anisms involve either mutation leading to target site insensi-
tivity or modification in the metabolic resistance process
Vector Family
Housefly (Musca domestica) Muscidae
Aedes spp. (mosquito) Culicidae
Anopheles spp. (mosquito) Culicidae
Culex spp. (mosquito) Culicidae
Sandflies (Phlebotomus spp.) Culicidae
Black flies (Simulium spp.) Simuliidae
Tsetse fly (Glossina spp.) Glossinidae
Blowflies (Lucilia spp., Chrysomya spp.) Calliphoridae
Cockroaches Blattidae
Human louse (Pediculus humanus capitis, Pediculidae
P. humanus humanus, and Pthirus pubis)
Human flea (primarily Pulex irritans) Pulicidae
Parasitol Res

Table 2 Maximum resistance

level reported in different insect Name of insect pest Insecticide class Level of resistance
vectors of human diseases against
different insecticide classes Housefly (Musca domestica) Organochlorines Resistant but level not known
Organophosphates 62.5×
Carbamates >290×
Pyrethroids >18,400×
New chemistry 140×
insecticides
IGRs 1000×
Mosquito spp.
Aedes spp. Organochlorines >30×
Organophosphates 192.7×
Carbamates <5×
Pyrethroids 337.5×
New chemistry Low level of resistance
insecticides
Anopheles spp. Organochlorines 19.5×
Organophosphates 75×
Carbamates Resistant but resistance level not known
Pyrethroids Resistant but resistance level not known
Culex spp. Organochlorines Resistant but resistance level not known
Organophosphates 80×
Carbamates 2.93×
Pyrethroids 959×
Sandflies (Phlebotomus spp.) Organochlorines Resistant but resistance level not known
Organophosphates Resistant but resistance level not known
Carbamates Resistant but resistance level not known
Pyrethroids 34×
Black flies (Simulium bonaerense) Organochlorines 59.2×
Organophosphates Moderate level of resistance
Carbamates Not yet reported
Pyrethroids 90.0×
Tsetse fly (Glossina palpalis palpalis) Organochlorines 4.0×
Organophosphates Not yet reported
Carbamates Not yet reported
Pyrethroids 2.6×
Blowfly (Lucilia cuprina) Organophosphates A mild level of resistance
Cockroach (Blattella germanica) Organophosphates 28.80×
Carbamates 62.50×
Pyrethroids 468.00×
Phenyl pyrazoles 10.0×
Neonicotinoids 3.8×
Oxadiazines 5.3×
Human louse Organochlorines 8.5×
Organophosphates 4.9×
Avermectins (abamectin) 2.5×
Cat flea Organophosphates 190×
Carbamates 28×
Pyrethroids 12×

being carried out by enzymes. Basically, three major groups of monooxygenases, and carboxylesterases, are found to be in-
detoxifying enzymes, i.e., glutathione-S-transferases (GSTs), volved in resistance development in insects (Peiris and

Hemingway 1993). Among these three, monooxygenase-
mediated resistance is the most common and efficient tool
by which insects become resistant to insecticides as proven
in the cases of various insect species and insecticides (Scott
1999).
Target site insensitivity to organochlorines and pyrethroids
(sodium channels insensitivity) was firstly reported in
M. domestica as earlier as 1976 (Farnham and Sawicki
1976). Furthermore, leucine to phenylalanine was the first
point mutation in the sodium channel sequence of
M. domestica (Williamson et al. 1993) while DDT-
dehydrochlorinase being the first DDT-detoxifying enzyme
(glutathione S-transferase in nature) (Clark and Shamaan
1984). Selection of mutant A302S in Rdl (GABA-gated
chloride channel) allele is also found to be associated with
cyclodiene resistance (Gao et al. 2007) (Fig. 1).
Target site insensitivity to organophosphate and carbamate
insecticides, i.e., alteration in acetylcholinesterase (AChE),
has been argued as the main source of resistance in numerous
arthropod species. Five point mutations in the AChE gene
viz., Val → Leu, Gly → Ala, Gly → Val, Phe → Tyr, and
Gly → Ala (either singly or in combination) contribute to the
insecticide resistance to different levels in M. domestica
(Walsh et al. 2001). One or more enzymes from GST group
have often been associated with the resistance development to
organophosphates (OPs) in M. domestica (Wei et al. 2001)
(Fig. 2). Gene known as BCYP6D1^ is a member of cyto-
chrome P450 which plays a role in metabolic resistance to
pyrethroids. Overexpression of this gene confers pyrethroid
resistance (Liu and Scott 1998; Kasai and Scott 2000), while
some has provided evidence that carboxylesterase plays a sig-
nificant role in pyrethroid resistance (Zhang et al. 2007). The
suggested mechanisms in IGRs’ (diflubenzuron) resistance
in housefly larvae include the combined effect of reduced
cuticular penetration and metabolic resistance as well as
rapid excretion of diflubenzuron (Pimprikar and Georghiou
1979). Resistance to pyriproxyfen is due to the metabolic de-
toxification by mono-oxygenases in M. domestica (Zhang
et al. 1997). Resistance to fipronil or other related insecticide
is related with elevated detoxification or target site resistance
mechanism activated due to cross-resistance to γ-HCH or
other organochlorides (Kristensen et al. 2004) (Table 3).
Fig. 1 Graphic representation of the locations of mutations in the sodium
channel of organochloride/pyrethroid-resistant insect pests (red color
depicting the polymorphs in sodium channel) adapted from
Hemingway and Ranson et al. (2000) after modifications
Parasitol Res
Fig. 2 Depiction of mutations in the active sites of acetylcholinesterase
in carbamate/organophosphate-resistant insect pests. Reproduced with
permission from Walsh et al. (2001). © The Biochemical Society
Resistance in mosquitoes
Nearly 3000 mosquito species are existing in the world,
and more than 100 species transmit human diseases (Liu
1990; Murugan et al. 2015). Adult females belonging to
genera (Anopheles, Aedes, Culex, and Mansonia) com-
monly need blood meal either from human or animals
and thus play a role in transmission of infectious dis-
eases as bridge, secondary, or principal vectors.
Important infectious diseases spread by mosquitoes in-
clude malaria, lymphatic filariases (filarial worms, i.e.,
wuchereria, brugia), arboviral encephalitides, dengue,
yellow fever, encephalitis, and many others (Liu 1990;
Service 1993) (Table 1). Among these diseases transmit-
ted by mosquitoes, malaria and dengue are the most
important infectious diseases and around 390 million
people are affected by dengue per year (Bhatt et al.
2013) while nearly 216 million people are affected an-
nually due to malaria (WHO 2011).
Dengue is transmitted by Aedes spp. that are most im-
portant medical pests for people living in subtropical areas
of the world. DDT was the first insecticide used for mos-
quito management during World War II. Mosquitoes be-
came resistant against DDT shortly after its introduction
(Brown 1986). Since 1947, around 100 mosquito species
including more than 50 Anopheles spp. have become resis-
tant to one or more insecticides (WHO 1992). Aedes
aegypti has developed resistant to DDT in about every
region of the world wherever this species is present. OP
resistance is evident in the Caribbean region and its neigh-
boring countries. Pyrethroid resistance is reported in Asian
countries and also in Caribe (WHO 1992; WHO 2003).
Resistance level in Aedes spp. (Ae. aegypti) is reported
as >330-fold to pyrethroids like deltamethrin (Chadwick
et al. 1977), up to 200-fold to OPs (temephos), and
>30-fold against organochlorines (DDT) (Rodríguez et al.
Parasitol Res

Table 3 Genes/mutation involved in insecticide resistance in insect vectors of human diseases

Name of insect pest Insecticide class Mutation/gene involved

Housefly (Musca domestica) Organochlorines Leucine to phenylalanine point mutation

Organophosphates Five mutations viz., Val-180 → Leu, Gly-262 → Ala,
Gly-262 → Val, Phe- → 327 → Tyr, and Gly-365 → Ala
Carbamates Same as for organophosphates
Pyrethroids CYP6D1 gene
Mosquito spp.
Aedes spp. Organochlorines 164 (A/G), 194 (C/T), and 227 (A/G)
Organophosphates CYP9 and CYP6 genes
Carbamates Same as for organophosphates
Pyrethroids Same as for organochlorines
Anopheles spp. Organochlorines CYP4C27, CYP4H15, CYP6Z1, CYP6Z2, and CYP12F1 genes
Organophosphates Mutant G119S
Carbamates Mutant G119S
Pyrethroids A→T or T→C point mutations
Culex spp. Organophosphates Eight alleles viz., Al, B1, B6, B7, A2–B2, A4–B4, A5–B5, and A8–B8
Carbamates Same as above
Pyrethroids CYP6F1 gene along with L1014F mutation
Sandflies (Phlebotomus spp.) All insecticides Genetic basis for resistance not yet explored
Black flies (Simulium bonaerense) All insecticides Genetic basis for resistance not yet explored
Tsetse fly (Glossina palpalis palpalis) All insecticides Genetic basis for resistance not yet explored
Blowfly (Lucilia cuprina) Organophosphates Point mutations in Rop-1/E3
Cockroach (Blattella germanica) Organochlorines Alanine → serine point mutation
Organophosphates Not yet reported
Carbamates Not yet reported
Pyrethroids Four point mutations viz., E434→K434,
C764→R764, D58→G58, and P1880→L1888
Phenyl pyrazoles Alanine–serine (A302S) mutation
Human louse Organophosphates and carbamates AP-AChE
Pyrethroids T929I and L932F mutations
Cat flea All insecticides Genetic basis for resistance not yet explored

2002). Lower level of resistance is also reported against
carbamates like propoxur, i.e., <5-fold (Mazzarri and
Georghiou 1995), but a moderate resistance to a fewer
new chemistry insecticides like imidacloprid and spinosad
among the new chemistry insecticides is also reported
(Paul et al. 2006).
Resistance in Anopheles spp. could enhance up to 19.5-fold
to organochlorines (DDT (Diabate et al. 2002). Similarly, re-
sistance to OPs (temephos) around 75-fold resistance is also
reported while a lower level of resistance to carbamates
(propoxur) is reported (Cui et al. 2006). About 69 % of pop-
ulation has become resistant to even higher dose of pyre-
throids, i.e., permethrin with the passage of time (Ranson
et al. 2009).
Resistance level can be increased, in Culex spp., to 7–80-
fold against OPs (chlorpyrifos), 46-fold in case of carbamates
(propoxur), and 959-fold against pyrethroids (deltamethrin
and cyfluthrin) (Kim et al. 2007) (Table 2).
Molecular basis of resistance in mosquitoes
Molecular study of sodium channel genes revealed that three
polymorphs viz., 164 (A/G), 194 (C/T), and 227 (A/G) were
associated in producing sodium channel insensitivity to DDT
and pyrethroids (Brengues et al. 2003). Significant enhance-
ment of MFOs is reported in pyrethroid resistant of Ae.
aegypti. Gene amplification and/or increased transcription
resulting in elevated esterase activity (Enayati et al. 2003)
along with increased activity of non-specific esterases may
play a role in OP (fenitrothion) resistance in Ae. aegypti.
According to literature, presently, there is no alteration in the
enzyme AChE; however, esterases play a significant role in
pyrethroid resistance (Pethuan et al. 2007). Families of cyto-
chrome P450, glutathione transferases, and carboxy/
cholinesterase contain 235 members in Ae. aegypti. Around
37 CYP9 genes are present in the Ae. aegypti genome in
addition to CYP6, alpha esterase families, and Epsilon GSTs

(Macoris et al. 2003). The role of P-glycoproteins in produc-
ing resistance against IGRs, e.g., diflubenzuron in Ae. aegypti,
is well proven by literature (Porretta et al. 2008).
Members of the glutathione S-transferase enzymes’
family are associated with detoxification of the insecti-
cides, i.e., playing a role in detoxification of DDT in the
Anopheles gambiae. Two quantitative trait loci (QTLs)
have a significant effect on the susceptibility to DDT in
An. gambiae. The first locus, i.e., rtd1 which is located on
chromosome no. 3, has a recessive impact on resistance,
while the second locus (rtd2) present on chromosome 2L
(near the marker H325) has a dominant effect (Ranson
et al. 2000). Recently, five genes have been identified in
An. gambiae on P450 loci viz., CYP4C27, CYP4H15,
CYP6Z1, CYP6Z2, and CYP12F1 that confer significantly
higher DDT resistance (Chiu et al. 2008). Genetic studies
to find the molecular basis of carbamate and OP resistance
in An. gambiae have revealed that mutation in G119S of
AChE (ace-1R) plays a role in carbamate and OP resis-
tance (Djogbénou et al. 2007). Pyrethroid resistance can
be due to polyfactorial partly recessive expression in na-
ture (Vatandoost et al. 1998). Protein-level studies regard-
ing pyrethroid resistance have also revealed that the resis-
tant alleles possess A→T or T→C substitution giving rise
to Leu-Phe and Leu-Ser substitutions (Etang et al. 2006),
while some suggest two majors and one minor QTLs for
pyrethroid resistance in An. gambiae (Ranson et al. 2004).
In Culex pipiens, two different types of acetylcholin-
esterases (AChEs) viz., AChE1 and AChE2 with sub-
strate specificity and inhibitor sensitivity have been dis-
covered up to now. Three loci play a role in OP resis-
tance in C. pipiens. Global presence of some resistance
conferring alleles could only be described as originating
from a single origin by mutation followed by extensive
migration. OP resistance in C. pipiens has been found
to be associated with eight different types of alleles viz.,
Al, B1, B6, B7, A2–B2, A4–B4, A5–B5, and A8–B8
(Qiao et al. 1999). Different resistance alleles are capa-
ble of accumulation and competing within populations
after their selection by point mutation (Chevillon et al.
1999). Resistance against organophosphorus and carba-
mate insecticides in C. pipiens is due to surplus produc-
tion of nonspecific esterases, i.e., Estβ11 and Estα21/
β21. These esterases are capable of inducing multiple
resistance in C. pipiens against organophosphorus and
carbamate insecticides. A new esterase named Estα8/
β8 is also found associated with resistance in
C. pipiens (Qiao et al. 1999). A gene named CYP6F1
is overexpressed in the pyrethroid-resistant strains
(Gong et al. 2005). Genetic studies regarding pyrethroid
resistance have depicted that L1014F mutation frequen-
cy is the key mutation inducing resistance to deltameth-
rin (Chen et al. 2010) (Table 3).
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Resistance in sandflies
A complex of diseases, with significant clinical and epidemi-
ological diversity, is associated to leishmaniasis (common
name Kala-azar). Leishmaniasis, a vector-borne disease, is
endemic in 88 countries (including 72 developing and 13 least
developed countries) (Desjeux 1996). Around 30 sandfly spe-
cies (belonging to genera Phlebotomus) are proven vectors of
many important diseases (Desjeux 2004). In addition to
Leishmaniasis, Phlebotomus spp. also transmit many other
bacteria and viruses which cause different disease outbreaks
in human beings. These viruses include phlebovirus, the
vesiculovirus, Toscana virus, Sicilian virus, sandfly fever,
Naples virus, and the orbivirus (Depaquit et al. 2010)
(Table 1).
There are only a fewer reports of resistance in Phlebotomus
spp. Most of them are from India especially against DDT
(Hemingway and Ranson 2000). According to literature, re-
sistance level against pyrethroids (deltamethrin) is nearly 34-
fold (Amalraj et al. 1999). Recently, resistance in
Phlebotomus spp. against OPs (malathion) and carbamate
(propoxur) from area other than India, i.e., Sudan, is also
reported (Hassan et al. 2012) (Table 2).
Molecular basis of resistance in sandflies
High activity of AChE works in association with elevated
levels for EST and GST to play an important role in inducing
resistance against OPs and carbamates. However, the genes/
mutation involved in resistance development in sandflies is
still to be discovered, primarily due to fewer reports on resis-
tance in sandflies (Hassan et al. 2012) (Table 3).
Resistance in black flies
Around 2000 species of black flies (family: Simuliidae) are
found in the world. They transmit important diseases like river
blindness, mansonellosis, avian leucocytozoonosis, bovine
onchocerciasis, and a variety of arboviruses leading to signif-
icant human anguish and economic damage (Adler and
McCreadie 1997; Adler et al. 2010) (Table 1).
Higher level of resistance is reported in Simulium spp. (es-
pecially Simulium bonaerense) against organochlorines (59.2-
fold) and pyrethroids (up to 90.0-fold) (Montagna et al. 1999)
and a moderate level of resistance against OPs (Hemingway
et al. 1991) (Table 2).
Molecular basis of resistance in black flies
Resistance to pyrethroids and DDT is partially due to activity
of mono-oxygenases and higher esterase activity along addi-
tional role of non-metabolic resistance mechanism, i.e., target
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site insensitivity (Montagna et al. 2003; Montagna et al. 2012)
(Table 3).
Resistance in tsetse flies
Limited number of species of tsetse flies (Diptera:
Glossinidae) represents their lower diversity. The Glossina
spp. are of great medical and economic importance due to
their role in transmission of African trypanosomes,
Trypanosoma sp. (Kinetoplastida: Trypanosomatidae)
(Table 1). The principle trypanosome vectors include four
species, i.e., Glossina fuscipes fuscipes, Glossina morsitans,
Glossina pallidipes, and Glossina palpalis (Krafsur 2009).
A mild tolerance maximum 4.0-fold and 2.6-fold is report-
ed in only pregnant females of G. palpalis palpalis against
organochlorines (DDT, dieldrin, and endosulfan) and pyre-
throids (tetramethrin), respectively (Riordan 1987) (Table 2).
However, no molecular basis of insecticide resistance has
been described till now in any of the species of tsetse flies
(Table 3).
Resistance in blowflies
A number of species are included in blowflies. They are im-
portant pests of man, animals, and also birds. Important spe-
cies of medical and veterinary importance include Chrysomya
albiceps, Chrysomya chloropyga, Cochliomyia macellaria,
Cochliomyia horninivorax, Chrysomya putoria, Chrysomya
rufifacies, Lucilia sericata, Lucilia cuprina, etc. Myiasis is
the infestation of live human and vertebrate animals with dip-
terous larvae, which feed on the hosts’ living tissue, liquid
body substances, or ingested food and then pupate
(Erzinclioglu 1987) (Table 1).
Only a mild resistance to diazinon and malathion (OPs) is
till reported in L. cuprina (Arnold and Whitten 1976;
McKenzie and O’farrell 1993) (Table 2).
Molecular basis of resistance in blowflies
The point mutations in Rop-1/E3 point have played a role in
evolution of OP resistance in L. cuprina. Mutation in
carboxylesterases not only decreases its carboxylesterase ac-
tivity but also confers OP resistance with hydrolase activity
(Parker et al. 1991; Chen et al. 2001). OP-resistant allele of the
gene that encodes E3 varies from OP-susceptible allele, at
five-amino acid replacement locations. Gly137 → Asp substi-
tution orients the water molecule in a suitable position for
hydrolysis of the intermediate products produced by enzymes
(Newcomb et al. 1997; Claudianos et al. 1999). The molecular
basis of resistance for the rest of insecticides is not yet discov-
ered (Table 3).
Resistance in cockroaches
Human dwellings are associated with 30 out of 4000 discov-
ered species of cockroaches. Cockroaches are responsible for
transmitting microorganisms like pathogenic bacteria, virus,
and fungi. Some examples of common bacterial diseases of
human beings transmitted by cockroaches are bubonic plague,
dysentery, boils and abscesses, diarrhea, typhoid, etc. (Naeem
et al. 2014) (Table 1).
Resistance level of cockroaches has increased to higher
levels even in field populations. Resistance level in cock-
roaches (German cockroach) reported till now is about
62.50× against the carbamates (propoxur), up to 28.80×
against OPs (chlorpyrifos), up to 468.00× against pyrethroids
(beta-cyfluthrin, deltamethrin), and 10.0× against phenyl
pyrazole (fipronil). However, moderate level of resistance is
found in cockroaches against neonicotinoids, i.e.,
imidacloprid (0.8–3.8×) and the oxadiazines like indoxacarb
(1.4–5.3×) (Chai and Lee 2010) (Table 2).
Molecular basis of resistance in cockroaches
In the organochlorine-resistant strains, the mutation has oc-
curred which has led to an amino acid change of alanine res-
idue to serine (Kaku and Matsumura 1994). Exploring the
molecular basis for pyrethroid resistance, it will become clear
that four point mutations from glutamic acid to lysine
(E434→K434), from cysteine to arginine (C764→R764),
from aspartic acid to glycine (D58→G58), and from proline
to leucine (P1880→L1888) are involved in producing pyre-
throid resistance in cockroaches. The four mutations coexist
with the previously identified knockdown resistance (kdr) mu-
tation in IIS6 (brought change in protein leucine to phenylal-
anine) (Liu et al. 2000). Overexpression of CYP4G19 is also
involved in inducing pyrethroid resistance in cockroaches
(German cockroach) (Pridgeon et al. 2003). Increased levels
of GST activity confer broad-spectrum resistance to a range of
OPs and carbamates (Hemingway et al. 1993). Fipronil is
metabolically detoxified in German cockroaches, possibly
through sulfone formation by microsomal oxidases (Valles
et al. 1997). Enhanced metabolism by cytochrome P450s
and target site insensitivity caused by the alanine–serine
(A302S) mutation confer resistance to new chemistry insecti-
cides like fipronil (Gondhalekar and Scharf 2012) (Table 3).
Resistance in human louse
There are three major lice species viz., Pediculus humanus
capitis (head louse), Pediculus humanus humanus (body
louse), and Pthirus pubis (crab louse) which infest human
beings. Head lice are ectoparasites that feed exclusively on
human blood several times per day. Typhus fever, trench fever,

and relapsing fever are usually transmitted by body lice (Ko
and Elston 2004) (Table 1).
Resistance against DDT (organochlorides), pyrethroids
like permethrin (8.5-fold) (body louse), and 2.5-fold against
avermectins (abamectin) in both body louse and head louse
are reported till now (Yoon et al. 2004). A mild level of mal-
athion (OP) resistance, i.e., 3.7-fold, is also reported (Gao
et al. 2006) (Table 2).
Molecular basis of resistance in human louse
GST-based mechanism is found to be involved in producing
DDT resistance, with no cross-resistance to pyrethroids. The
increased malathion resistance can be attributed to enhanced
carboxylesterase and esterase activity in the human louse (Gao
et al. 2006). Among the two cDNA sequences encoded with
Drosophila Ace-orthologous and Ace-paralogous acetylcho-
linesterase precursors (AO- and AP-AChE precursors, respec-
tively), the AP-AChE isoform confers resistance in human
louse against OPs and carbamates (Lee et al. 2007). Nerve
insensitivity and higher monooxygenase activity confer pyre-
throid resistance in human louse (Gao et al. 2003).
Exploration of molecular basis for pyrethroid resistance has
revealed two point mutations, T929I and L932F in kdr, i.e.,
sodium channel insensitivity (Gao et al. 2003; Lee et al. 2007)
(Table 3).
Resistance in fleas
Plague, caused by infection with Yersinia pestis, is transmitted
by Human flea with the biggest share of species, Pulex
irritans. Murine typhus and epidemic typhus are also known
diseases (Bitam et al. 2010) (Table 1).
Resistance reported in fleas includes malathion (OP) resis-
tance up to 190-fold, bendiocarb (carbamate) with resistance
level of 28-fold, and permethrin (pyrethroid) resistance level
enhanced up to 12-fold in cat flea but not in other species yet
(Lemke et al. 1989; Moyses 1995; El-Gazzar et al. 1986)
(Table 2).
Molecular basis of resistance in fleas
Target site insensitivity due to detoxification of OP by GST
conjugation occurs in resistant fleas along with cytochrome
P450, i.e., mixed function oxidase activity (Bossard 1997).
However, the genes/mutation involved in resistance is not
yet discovered in any flea species (Table 3).
Conclusions
The resurgence of endemic vector-borne diseases that have
been relatively under control is mainly owing to most
Parasitol Res
important ecological phenomenon, i.e., insecticide resistance.
So, understanding the molecular basis of insecticide resistance
and explaining the resistance mechanism have acquired prior-
ities among entomologists. The ultimate goal of genome se-
quencing information in insect pests is development of tools
for determining the role and pathways of detoxification by
detoxification proteins. An ongoing challenge is the imple-
mentation of this basic knowledge of molecular basis of in-
secticide resistance in eco-friendly sustainable integrated pest
management programs. The ultimate result of every chemical
pesticide either being used currently or it is in development
process or yet to be considered will eventually result in resis-
tance in target insect pests’ populations and that such resis-
tance will at least, in some cases, involve metabolic enzyme
systems. So, there is an urgent need of considering the types of
genes viz., dominant, recessive, or co-dominant involved in
the resistance and then implementing genetic control or re-
lease of susceptible strains or other such tactics for ease in
insecticide resistance management.
References
Acevedo GR, Zapater M, Toloza AC (2009) Insecticide resistance of
house fly, Musca domestica (L.) from Argentina. Parasitol Res
105:489–493
Adler PH, McCreadie JW (1997) Insect life: the hidden ecology of black
flies: sibling species and ecological scale. Am Entomol 43:153–162
Adler PH, Cheke RA, Post RJ (2010) Evolution, epidemiology, and pop-
ulation genetics of black flies (Diptera: Simuliidae). Infect Genet
Evol 10:846–865
Akiner MM, Caglar SS (2006) The status and seasonal changes of organ-
ophosphate and pyrethroid resistance in Turkish populations of the
house fly, Musca domestica L. (Diptera: Muscidae). J Vector Ecol
31:58–64
Amalraj DD, Sivagnaname N, Srinivasan R (1999) Susceptibility of
Phlebotomus argentipes and P. papatasi (Diptera: Psychodidae) to
insecticides. J Commun Dis 31:177–180
Arnold JTA, Whitten MJ (1976) The genetic basis for organophosphorus
resistance in the Australian sheep blowfly, Lucilia cuprina
(Wiedemann) (Diptera, Calliphoridae). Bull Entomol Res 66:561–
568
Benelli G (2015) Research in mosquito control: current challenges for a
brighter future. Parasitol Res 114:2801–2805
Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL et al
(2013) The global distribution and burden of dengue. Nature 496:
504–07
Bitam I, Dittmar K, Parola P, Whiting MF, Raoult D (2010) Fleas and
flea-borne diseases. Int J Infect Dis 14:667–676
Bossard RL (1997) Evaluation and use of bioassays for surveying insec-
ticide susceptibility of cat fleas, Ctenocephalides fells felis
(Bouch6). In: relation to resistance, Ph.D. dissertation. Kansas
State University, Manhattan
Brengues C, Hawkes NJ, Chandre F, McCarroll L, Duchon S, Guillet P
et al (2003) Pyrethroid and DDT cross‐resistance in Aedes aegypti is
correlated with novel mutations in the voltage‐gated sodium channel
gene. Med Vet Entomol 17:87–94
Parasitol Res
Brown AWA (1986) Insecticide resistance in mosquitoes: a pragmatic
review. J Am Mosq Control Assoc 2:123–40
Chadwick PR, Invest JF, Bowron MJ (1977) An example of cross-
resistance to pyrethroids in DDT resistant Aedes aegypti. Pestic
Sci 8:618–624
Chai RY, Lee CY (2010) Insecticide resistance profiles and synergism in
field populations of the German cockroach (Dictyoptera:
Blattellidae) from Singapore. J Econ Entomol 103:460–471
Chen Z, Newcomb R, Forbes E, McKenzie J, Batterham P (2001) The
acetylcholinesterase gene and organophosphorus resistance in the
Australian sheep blowfly, Lucilia cuprina. Insect Biochem Mol
Biol 31:805–816
Chen L, Zhong D, Zhang D, Shi L, Zhou G, Gong M et al (2010)
Molecular ecology of pyrethroid knockdown resistance in Culex
pipiens pallens mosquitoes. PLoS One 5(7):e11681
Chevillon C, Raymond M, Guillemaud T, Lenormand T, Pasteur N
(1999) Population genetics of insecticide resistance in the mosquito
Culex pipiens. Biol J Linnean Soc 68:147–157
Chiu TL, Wen Z, Rupasinghe SG, Schuler M (2008) Comparative mo-
lecular modeling of Anopheles gambiae CYP6Z1, a mosquito P450
capable of metabolizing DDT. Proc Natl Acad Sci 105:8855–8860
Clark AG, Shamaan NA (1984) Evidence that DDT-dehydrochlorinase
from the house fly is a glutathione S-transferase. Pest Biochem
Physiol 22:249–261
Claudianos C, Russell RJ, Oakeshott JG (1999) The same amino acid
substitution in orthologous esterases confers organophosphate resis-
tance on the house fly and a blowfly. Insect Biochem Mol Biol 29:
675–686
Cui F, Raymond M, Qiao C-L (2006) Insecticide resistance in vector
mosquitoes in China. Pest Manag Sci 62:1013–1022
Depaquit J, Grandadam M, Fouque F, Andry PE, Peyrefitte C (2010)
Arthropod-borne viruses transmitted by Phlebotomine sandflies in
Europe: a review. Euro Surveill 15:19507
Desjeux P (1996) Leishmaniasis: public health aspects and control. Clin
Derm 14:417–423
Desjeux P (2004) Leishmaniasis: current situation and new perspectives.
Comp Immunol Microbiol Infect Dis 27:305–318
Diabate A, Baldet T, Chandre F, Akoobeto M, Guiguemde TR, Darriet F
et al (2002) The role of agricultural use of insecticides in resistance
to pyrethroids in Anopheles gambiae sl in Burkina Faso. Am J Trop
Med Hyg 67:617–622
Djogbénou L, Weill M, Hougard JM, Raymond M, Akogbeto M,
Chandre F (2007) Characterization of insensitive acetylcholinester-
ase (ace-1R) in Anopheles gambiae (Diptera: Culicidae): resistance
levels and dominance. J Med Entomol 44:805–810
El-Gazzar LM, Milio J, Koehler PG, Patterson RS (1986) Insecticide
resistance in the cat flea (Siphonaptera: Pulicidae). J Econ
Entomol 79:132–134
Enayati AA, Vatandoost H, Ladonni H, Townson H, Hemingway J
(2003) Molecular evidence for a kdr‐like pyrethroid resistance
mechanism in the malaria vector mosquito Anopheles stephensi.
Med Vet Entomol 17:138–144
Erzinclioglu YZ (1987) The larvae of some blowflies of medical and
veterinary importance. Med Vet Entomol 1:121–125
Etang J, Fondjo E, Chandre F, Morlais I, Brengues C, Nwane P et al
(2006) First report of knockdown mutations in the malaria vector
Anopheles gambiae from Cameroon. Am J Trop Med Hyg 74:795–
797
Farnham AW, Sawicki RM (1976) Development of resistance to pyre-
throids in insects resistant to other insecticides. Pestic Sci 7:278–282
Gao J-R, Yoon KS, Lee SH, Takano-Lee M, Edman JD, Meinking TL et
al (2003) Increased frequency of the T929I and L932F mutations
associated with knockdown resistance in permethrin-resistant pop-
ulations of the human head louse, Pediculus capitis, from California,
Florida, and Texas. Pestic Biochem Physiol 77:115–124
Gao J-R, Yoon KS, Frisbie RK, Coles GC, Clark JM (2006) Esterase-
mediated malathion resistance in the human head louse, Pediculus
capitis (Anoplura: Pediculidae). Pestic Biochem Physiol 85:28–37
Gao JR, Kozaki T, Leichter CA, Rinkevich FD, Shono T, Scott JG (2007)
The A302S mutation in Rdl that confers resistance to cyclodienes
and limited cross-resistance to fipronil is undetectable in field pop-
ulations of house flies from the USA. Pest Biochem Physiol 88(1):
66–70
Georghiou GP (1972) The evolution of resistance to pesticides. Annu Rev
Ecol Syst 133–168
Gondhalekar AD, Scharf ME (2012) Mechanisms underlying fipronil
resistance in a multiresistant field strain of the German cockroach
(Blattodea: Blattellidae). J Med Entomol 49:122–131
Gong M-Q, Gu Y, Hu X-B, Sun Y, Ma L, Li X-L et al (2005) Cloning and
overexpression of CYP6F1, a cytochrome P450 gene, from
deltamethrin-resistant Culex pipiens pallens. Acta Bioch Bioph Sin
37:317–326
Hassan MM, Widaa SO, Osman OM, Numiary MSM, Ibrahim MA,
Abushama HM (2012) Insecticide resistance in the sand fly,
Phlebotomus papatasi from Khartoum State, Sudan. Parasit
Vectors 5:46
Hemingway J, Ranson H (2000) Insecticide resistance in insect vectors of
human disease. Annu Rev Entomol 45:371–391
Hemingway J, Callaghan A, Kurtak DC (1991) Biochemical characteri-
zation of chlorphoxim resistance in adults and larvae of the
Simulium damnosum complex (Diptera: Simulidae). Bull Entomol
Res 81:401–6
Hemingway J, Small GJ, Monro AG (1993) Possible mechanisms of
organophosphorus and carbamate insecticide resistance in German
cockroaches (Dictyoptera: Blattelidae) from different geographical
areas. J Econ Entomol 86:1623–1630
Kaku K, Matsumura F (1994) Identification of the site of mutation within
the M2 region of the GABA receptor of the cyclodiene-resistant
German cockroach. Comp Biochem Physiol C Pharmacol Toxicol
Endocrinol 108:367–376
Kasai S, Scott J (2000) Overexpression of cytochrome P450 CYP6D1 is
associated with monooxygenase-mediated pyrethroid resistance in
house flies from Georgia. Pest Biochem Physiol 68:34–41
Khan HAA, Shad SA, Akram W (2012) Effect of livestock manures on
the fitness of house fly, Musca domestica L. (Diptera: Muscidae).
Parasitol Res 111:1165–1171
Kim NJ, Chang KS, Lee WJ, Ahn YJ (2007) Monitoring of insecticide
resistance in field-collected populations of Culex pipiens pallens
(Diptera: Culicidae). J Asia Pac Entomol 10:257–261
Ko CJ, Elston DM (2004) Pediculosis. J Am Acad Dermatol 50:1–12
Kobayashi M, Sasaki T, Saito N, Tamura K, Suzuki H, Watanabe H, Agui
N (1999) Houseflies are not simple mechanical vectors of
enterohemorragic Escherichia coli O157:H7. Am J Trop Med Hyg
61:625–629
Krafsur ES (2009) Tsetse flies: genetics, evolution, and role as vectors.
Infect Genet Evol 9:124–141
Kristensen M, Jespersen JB (2003) Larvicide resistance in Musca
domestica (Diptera: Muscidae) populations in Denmark and estab-
lishment of resistant laboratory strains. J Econ Entomol 96:1300–
1306
Kristensen M, Jespersen JB, Knorr M (2004) Cross‐resistance potential of
fipronil in Musca domestica. Pest Manag Sci 60:894–900
Lee SW, Kasai S, Komagata O, Kobayashi M, Agui N, Kono Y et al
(2007) Molecular characterization of two acetylcholinesterase
cDNAs in Pediculus human lice. J Med Entomol 44:72–79
Lemke LA, Koehler PG, Patterson RS (1989) Susceptibility of the cat flea
(Siphonaptera: Pulicidae) to pyrethroids. J Econ Entomol 82:839–
841
Liu W-D (1990) The evolution of insecticides resistance of mosquitoes in
China (in Chinese). Chin J Vec Biol Contr 1:41–44

Liu N, Scott JG (1998) Increased transcription of CYP6D1 causes cyto-
chrome P450-mediated insecticide resistance in house fly. Insect
Biochem Mol Biol 28:531–535
Liu N, Yue X (2000) Insecticide resistance and cross-resistance in the
house fly (Diptera: Muscidae). J Econ Entomol 93:1269–1275
Liu Z, Valles SM, Dong K (2000) Novel point mutations in the German
cockroach para sodium channel gene are associated with knock-
down resistance (kdr) to pyrethroid insecticides. Insect Biochem
Mol Biol 30:991–997
Macnair MR (1991) Genetica 84:213–219
Macoris MDLG, Andrighetti MTM, Takaku L, Glasser CM, Garbeloto
VC, Bracco JE (2003) Resistance of Aedes aegypti from the state of
São Paulo, Brazil, to organophosphates insecticides. Mem I
Oswaldo Cruz 98:703–708
Malik A, Singh N, Satya S (2007) House fly (Musca domestica): a review
of control strategies for a challenging pest. J Environ Sci Health Part
B 42:453–469
Mazzarri MB, Georghiou GP (1995) Characterization of resistance to
organophosphate, carbamate, and pyrethroid insecticides in field
populations of Aedes aegypti from Venezuela. J Am Mosq Control
Assoc 11:315–322
McKenzie JA (1985) In Resistance in nematodes to anthelmintic drugs
(Anderson, N. and Wailer, P.J.. eds). CSIRO. Australian Wool
Corporation, pp. 89–95.
McKenzie JA, O’farrell K (1993) Modification of developmental insta-
bility and fitness: malathion-resistance in the Australian sheep blow-
fly, Lucilia cuprina. Genetica 89:67–76
Metcalf RL (1989) Insect resistance to insecticides. Pestic Sci 26:333–
358
Montagna CM, Anguiano OL, Gauna LE, Pechen de D’Angelo AM
(1999) Resistance to pyrethroids and DDT in a field-mixed popula-
tion of Argentinean black flies (Diptera: Simuliidae). J Econ
Entomol 92:1243–1245
Montagna CM, Anguiano OL, Gauna LE, Pechen DD, Angelo AM
(2003) Mechanisms of resistance to DDT and pyrethroids in
Patagonian populations of Simulium blackflies. Med Vet Entomol
17:95–101
Montagna CM, Gauna LE, D’Angelo APD, Anguiano OL (2012)
Evolution of insecticide resistance in non-target black flies
(Diptera: Simuliidae) from Argentina. Mem Inst Oswaldo Cruz
107:458–465
Moyses EW (1995) Measurement of insecticide resistance in the adult cat
flea. In: Meola RW (ed) Proceedings of the Third International
Symposium on Ectoparasites of Pets, 2-4 April, College Station.
Texas A&M University, College Station TX, TX, pp 21–34
Murugan K, Vadivalagan C, Karthika P, Panneerselvam C, Paulpandi M,
Subramaniam J et al (2015) DNA barcoding and molecular evolu-
tion of mosquito vectors of medical and veterinary importance.
Parasitol Res 11:1–15
Naeem A, Jaleel W, Saeed Q, Zaka SM, Saeed S, Naqqash MN et al.
(2014) Life style of people and surveillance of management related
to cockroaches in Southern Punjab, Pakistan. Turk J Agri Nat Sci
1:227–233
Naqqash MN, Saeed Q, Saeed S, Jaleel W, Zaka SM, Faheem M et al
(2014) A cross sectional survey of community awareness about
typhoid and its major vector cockroach in southern Punjab,
Pakistan. Middle-East J Sci Res 21:602–608
Newcomb RD, Campbell PM, Ollis DL, Cheah E, Russell RJ, Oakeshott
JG (1997) A single amino acid substitution converts a
carboxylesterase to an organophosphorus hydrolase and confers in-
secticide resistance on a blowfly. Proc Natl Acad Sci 94:7464–7468
Parker AG, Russell RJ, Delves AC, Oakeshott JG (1991) Biochemistry
and physiology of esterases in organophosphate-susceptible and-re-
sistant strains of the Australian sheep blowfly, Lucilia cuprina.
Pestic Biochem Physiol 41:305–318
Parasitol Res
Paul A, Harrington LC, Scott JG (2006) Evaluation of novel insecticides
for control of dengue vector Aedes aegypti (Diptera: Culicidae). J
Med Entomol 43:55–60
Peiris HTR, Hemingway J (1993) Characterisation and inheritance of
elevated esterases in organophosphorus and carbamate insecticide
resistant Culex quinquefasciatus (Diptera: Culicidae) from Sri
Lanka. Bull Entomol Res 83:127–132
Pethuan S, Jirakanjanakit N, Saengtharatip S, Chareonviriyaphap T,
Kaewpa D, Rongnoparut P (2007) Biochemical studies of insecti-
cide resistance in Aedes aegypti (Stegomyia) and Aedes albopictus
(Stegomyia) (Diptera: Culicidae) in Thailand. Trop Biomed 24:7–15
Pimprikar GD, Georghiou GP (1979) Mechanisms of resistance to
diflubenzuron in the house fly, Musca domestica (L.). Pest
Biochem Physiol 12:10–22
Porretta D, Gargani M, Bellini R, Medici A, Punelli F, Urbanelli S (2008)
Defence mechanisms against insecticides temephos and
diflubenzuron in the mosquito Aedes caspius: the P‐glycoprotein
efflux pumps. Med Vet Entomol 22:48–54
Pridgeon JW, Zhang L, Liu N (2003) Overexpression of CYP4G19 as-
sociated with a pyrethroid-resistant strain of the German cockroach,
Blattella germanica (L.). Gene 314:157–163
Qiao CL, Sun ZQ, Liu JE (1999) New esterase enzymes involved in
organophosphate resistance in Culex pipiens (Diptera: Culicidae)
from Guang Zhou, China. J Med Entomol 36:666–670
Ranson H, Jensen B, Wang X, Prapanthadara L, Hemingway J, Collins
FH (2000) Genetic mapping of two loci affecting DDT resistance in
the malaria vector Anopheles gambiae. Insect Mol Biol 9:499–507
Ranson H, Paton MG, Jensen B, McCarroll L, Vaughan A, Hogan JR et al
(2004) Genetic mapping of genes conferring permethrin resistance in
the malaria vector, Anopheles gambiae. Insect Mol Biol 13:379–386
Ranson H, Abdallah H, Badolo A, Guelbeogo WM, Kerah-Hinzoumbé
C, Yangalbé-Kalnoné E et al (2009) Insecticide resistance in
Anopheles gambiae: data from the first year of a multi-country study
highlight the extent of the problem. Malar J 8:299
Riordan EK (1987) Insecticide tolerance of pregnant females of Glossina
palpalis palpalis (Robineau-Desvoidy) (Diptera: Glossinidae). Bull
Entomol Res 77:213–226
Rodríguez MM, Bisset J, Ruiz M, Soca A (2002) Cross-resistance to
pyrethroid and organophosphorus insecticides induced by selection
with temephos in Aedes aegypti (Diptera: Culicidae) from Cuba. J
Med Entomol 39:882–888
Roush RT, McKenzie JA (1987) Annu Rev Entomol 32:361–380
Scott JG (1999) Cytochromes P450 and insecticide resistance. Insect
Biochem Mol Biol 29:757–777
Scott JG, Alefantis TG, Kaufman PE, Rutz DA (2000) Insecticide resis-
tance in house flies from caged-layer poultry facilities. Pest Manag
Sci 147–153
Service MW (1993) Mosquitoes (Culicidae). In: Lane RP, Crosskey RW
(eds) Medical insects and arachnids. Chapman & Hall, London, pp
120–240
Shi J, Lan Z, Zhang XG (2011) Characterisation of spinosad 1 resistance
in the housefly Musca domestica (Diptera: Muscidae). Pest Manag
Sci 67:335–340
Shono T, Kasai S, Kamiya E, Kono Y, Scott JG (2002) Genetics and
mechanisms of permethrin resistance in the YPER strain of house
fly. Pestic Biochem Physiol 73:27–36
Valles SM, Koehler PG, Brenner RJ (1997) Antagonism of fipronil tox-
icity by piperonyl butoxide and S, S, S-tributyl phosphorotrithioate
in the German cockroach (Dictyoptera: Blattellidae). J Econ
Entomol 90:1254–1258
Vatandoost H, McCaffery HR, Townson H (1998) An electrophysiolog-
ical investigation of target site insensitivity in permethrin-resistant
and susceptible strain of Anopheles stephensi. Iran J Publ Health 27:
29–38
Walsh S, Dolden T, Moores G, Kristensen M, Lewis T, Devonshire AL,
Williamson M (2001) Identification and characterization of
Parasitol Res
mutations in housefly (Musca domestica) acetylcholinesterase in-
volved in insecticide resistance. Biochem J 359:175–181
Wei SH, Clark AG, Syvanen M (2001) Identification and cloning of a key
insecticide-metabolizing glutathione S-transferase (MdGST-6A)
from a hyper insecticide-resistant strain of the housefly Musca
domestica. Insect Biochem mol Biol 31:1145–1153
WHO (2011) World Malaria Report 2011. World Health Organization,
Geneva
WHO-World Health Organization 2003. Dengue (online, access in 03/06/
2003). Available at http://www.who.int/inf-fs/en/fact117.html
WHO-World Health Organization, Expert Committee on Vector Biology
and Control (1992). Vector resistance to pesticides, 818 report, un-
published document, WHO technical report series, pp. 63
Williamson MS, Denholm I, Bell CA, Devonshire AL (1993)
Knockdown resistance (kdr) to DDT and pyrethroid insecticides
maps to a sodium channel gene locus in the housefly (Musca
domestica). Mol Gen Genet MGG 240:17–22
Yoon KS, Gao J-R, Lee SH, Coles GC, Meinking TL, Taplin D et al
(2004) Resistance and cross-resistance to insecticides in human head
lice from Florida and California. Pestic Biochem Physiol 80:192–
201
Zhang L, Harada K, Shono T (1997) Genetic analysis of pyriproxyfen
resistance in the housefly, Musca domestica L. Appl Entomol Zool
32:217–226
Zhang L, Gao X, Liang P (2007) Beta-cypermethrin resistance associated
with high carboxylesterase activities in a strain of house fly, Musca
domestica (Diptera: Muscidae). Pest Biochem Physiol 89:65–72