Treatment of Pediculosis Capitis - A Critical Appraisal of The Current Literature

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Am J Clin Dermatol (2014) 15:401412

DOI 10.1007/s40257-014-0094-4

REVIEW ARTICLE

Treatment of Pediculosis Capitis: A Critical Appraisal


of the Current Literature
Hermann Feldmeier

Published online: 16 September 2014


Springer International Publishing Switzerland 2014

Abstract Pediculosis capitis is the most common ectoparasitic disease in children in industrialized countries and
extremely common in resource-poor communities of the
developing world. The extensive use of pediculicides with a
neurotoxic mode of action has led to the development and
spread of resistant head lice populations all over the world.
This triggered the development of compounds with other
modes of action. The current literature on treatment approaches of head lice infestation was searched, and published
randomized controlled trials were critically analyzed. The
following compounds/family of compounds were identified:
spinosad, a novel compound with a new neurotoxic mode of
action, isopropyl myristate, 1,2-octanediol, ivermectin,
plant-based products, and dimeticones. The efficacy and
safety of these compounds are reviewed and recommendations for the treatment of pediculosis capitis in individuals as
well as the interruption of ongoing epidemics are provided.

Key Points
A broad spectrum of compounds is used to treat
pediculosis capitis
Randomized controlled trials performed in the
previous 15 years have rarely fulfilled the
requirement defined by expert groups
Based on the existing evidence, dimeticones are
recommended as first-line treatment

H. Feldmeier (&)
Institute of Microbiology and Hygiene,
Charite University Medicine, Campus Benjamin Franklin,
Hindenburgdamm 27, 12203 Berlin, Germany
e-mail: [email protected]

1 Introduction
Pediculosis capitis is a ubiquitous parasitic skin disease
associated with intense pruritus of the scalp. It causes
considerable distress to affected children and their families
and absorbs important resources from public health institutions [1, 2]. Whereas in industrialized countries head lice
infestation mainly occurs in children aged 314 years, in
resource-poor communities of developing countries it frequently affects children and adults alike [3].
The prevalence of pediculosis capitis varies greatly from
country to country. In Europe, prevalence varied from 1 to
20 % in studies performed during the last two decades [4].
In developing countries, prevalences up to 40 % have been
observed in children [5]. Furthermore, there are striking
differences in prevalence within a country. A recent study
from Norway, for instance, showed that the prevalence of
head lice infestation was almost twice as high in school
children in major cities in the south and the west of the
country as compared with rural towns [2].
Even if the point prevalence in children is low, the
ectoparasite may circulate extensively in the population. In
Norway, 36.4 % of all households surveyed had previously
experienced pediculosis capitis, although the prevalence in
school children was \1 % [2]. A similar observation had
been made in Germany [1].
The number of children per household, crowding, the
custom of sharing beds and other attitudes, the type and
frequency of social contacts, and access to healthcare all
contribute to the prevalence of head lice infestation in a
population [3].
There are hints that the prevalence of pediculosis capitis
has increased globally over the last decade [6]. Whether the
increase is mainly the result of massive use of pediculicides
with a neurotoxic mode of action in the pastwith the

402

subsequent emergence and spread of resistant head lice


populationsor whether socio-economic and cultural factors also played a role remains to be elucidated [711].
1.1 Parasitological and Epidemiological Background
and Treatment Rationales
The head louse is an obligate parasite that spends its
entire life on its human host. Head lice feed exclusively
on blood, and humans are the only known hosts. Typically, head lice are transmitted to a new host only when
there is head-to-head contact [4]. More than 99 % of
viable eggs attached to the hair hatch after 79 days and
only less than 0.1 % hatch after 10 days [12]. The
hatching rate depends, among other factors, on the
external temperature [12]. Because many pediculocides
do not affect eggs at all or are only partially ovicidal, a
second treatment is necessary and given 710 days after
the first treatment [12].
In industrialized countries, pediculosis capitis occurs in
small epidemics in the child population of educational
institutions such as kindergartens and primary schools.
Because children in the respective age groups have tight
social bonds and protective immunity does not develop,
head lice can easily spread and infest a considerable proportion of the child population. Usually, several members
of the same household are infested [2].
The most characteristic symptom of pediculosis capitis
is pruritus of the scalp, which begins 14 weeks after the
initial infestation. Because the pruritus is an immunemediated process, subsequent infestations usually result in
rapid itching. The itching induces scratching, which in turn
favors secondary bacterial infection, sometimes leading to
impetigo and pyoderma. Swelling of the local lymph nodes
and fever is rare in developed countries but can be common
in resource-poor communities [3]. Generalized prurigo-like
allergic dermatitis due to antigens from lice has also been
reported [12].
An unknown portion of infested individuals develop
pruritus of the scalp and, therefore, can be diagnosed by a
symptom-based approach. Why some individuals do not
develop pruritus is not known. If individuals without pruritus remain untreated, they will continue to spread head
lice in the family, the play group, or the institution. The
presence of overlooked carriers explains why epidemics
are difficult to extinguish and re-infestation is common
[13].
The diagnosis of pediculosis capitis is time consuming
and laborious, particularly when the number of lice present
is small (which is usually the case in children in affluent
communities). If only visual inspection is used, the
majority of cases with an active infestation, e.g., those who
can spread the infestation, are overlooked [14].

H. Feldmeier

In many societies, head lice infestation in children


causes mental strain and distress in patients and in caregivers. Commonly, popular media portray head lice as an
affliction of the unclean and uncouth. Television in the
USA often depicts pediculosis as a disgrace invited by
lapsed personal hygiene. Hence, the presentation of
pediculosis capitis in the media perpetuates shame and
stigmatization [15]. Lay media also convey myths about
treating head lice by household remedies such as mayonnaise and vinegar [15].
Head lice and body lice are closely linked subspecies
and are morphologically and genetically very similar [16,
17]. A genetic analysis did not find any differences
between the two subspecies [18]. This makes it plausible
that both subspecies have the same vector capacity for
pathogens. In fact, there is clear evidence that P. humanus
capitis can transmit R. prowazekii (the agent of louse-born
epidemic typhus) and Bartonella quintana (the agent of
trench fever, endocarditis, bacillary angiomatosis, and
other disease manifestations) [19]. In a study in rural
Ethiopia, B. quintana was detected in 7 % of head lice and
in 18 % of body lice [20]. This indicates that pathogens for
which transmission by Pediculus humanus corporis is
proved, may also be transmitted by P. humanus capitis
[21]. However, whether this is of clinical importance in
Western countries remains to be determined.
Taken together, there are many reasons to treat pediculosis capitis in a rational and effective manner. This
review attempts to provide readers with the necessary
information.

2 Methods
The review critically summarizes treatment approaches
that have emerged in recent years. PubMed was searched
from January 2000 to July 2014 using the keywords head
lice, pediculus humanus capitis, head lice infestation, pediculosis capitis, treatment, and prevention. An additional search was made through Google
Scholar. Only randomized controlled trials (RCTs) published in peer reviewed journals were analyzed. Open
clinical trials and RCTs published as abstracts only or only
accessible on the website of the sponsor were not used for
this review.
In 2012, international guidelines were developed with
the aim to standardize research protocols and to improve
consistency in RCTs of pediculocides [12]. However, even
studies performed after 2012 only partially or not at all
complied with this guideline [12]. In 2014, the guideline
was further specified including detailed recommendations
for the design of RCTs investigating pediculocides [22].
Recent advances in the ex-vivo development of adult head

Treatment of Pediculosis Capitis

403

lice and eggs make it possible to assess the efficacy of new


compounds in vitro in a standardized manner [23, 24].
However, this technique cannot replace clinical studies.
The overall validity of the publications was judged in a
semi-quantitative manner based on methodological rigor,
adequateness of statistical analysis, and generalizability of
study population and outcome measures. The overall
validity was categorized semiquantitatively: GGGOOO
(G = very low, OGG = low, OOG = moderate-high,
OOO = very high).

3 Results
Basically, two different approaches are used to eliminate
head lice: topical application of and oral treatment with a
pediculicide. The only drug currently used for oral treatment is ivermectin. Topically applied compounds can be
divided into pediculicides with neurotoxic mode of action
(permethrin, phenothrin, malathion, carbaril, spinosad),
pediculicides with physical mode of action (dimeticones,
isopropyl myristate, 1,2-octanediol), and herbal remediesusually a mixture of different essential oilsfor
which the mode of action is not known or has not been
investigated thoroughly. Physical methods such as the
application of hot air have not been evaluated sufficiently.
3.1 Pediculocides with a Neurotoxic Mode of Action
The extensive use of pediculicides with a neurotoxic mode
of action such as pyrethroids and organophosphates has led
to the development and spread of resistant head lice

populations on all continents [25]. Resistance has increased


in frequency and geographic extent in recent years [711].
Double and cross-resistance are frequent [2628]. Not
surprisingly, recent clinical trials in Great Britain showed
an unacceptable low efficacy of permethrin, the pyrethroid
most widely used [2931]. The efficacy decreased from
97 % in the mid-1990s to 13 % in 2013 [32, 33]. Similarly,
the efficacy of phenothrin decreased from 75 to 13 %
between 2005 and 2008 [3436]. In practice, this means
that a clinician cannot anticipate whether a product containing a pyrethroid or an organophosphate will be effective or not.
Almost by definition, neurotoxic pediculocides have no
ovicidal activity provided the embryo has not developed a
nervous system. Other concerns of these pediculicides are
transcutaneous resorption [37], the development of hypersensitivity [13], severe neurological complications after
accidental ingestion [38], and increased risk for the
development of childhood leukemia [39]. By consequence,
studies in which pyrethroids and organophosphates were
used are not reviewed here.
Recently, a novel pediculocide with a neurotoxic mode
of action was developed. Spinosad, a mixture of two
spinosins (tetracyclic macrolides that bind to the nicotinic
acetylcholine and the c-aminobutyric acid receptors of
neurons), has been introduced to the American market [40].
The results of two RCTs performed in the USA showed an
efficacy in the order of 85 %. However, the overall validity
of the studies was low (Table 1).
The tolerability and safety of spinosad are not sufficiently documented.

Table 1 RCTs performed with spinosad, a novel compound with a neurotoxic mode of action
Study
performed
in (year)

Number of
participants

Intensity
of
infestation

Comparison

Outcome

Overall
validity
of
study
results

Comment

Reference

USA;
children,
adolescents,
adults
(20072008)

1.038a

Not
known

Spinosad 0.9 %
creme rinse vs.
permethrin
1 % creme
rinse

Proportion of primary
participants head lice
free 14 days after last
treatmentb:

OGG

All household members of


the index participant with
head lice infestation were
admitted to the studyd

[40]

Spinosad *85/*87 %
Permethrin *45/*43 %c

GGGOOO (G = very low, OGG = low, OOG = moderate-high, OOO = very high)
a

Two RCTs were performed with three arms in each RCT; results presented here concern primary participants in the spinosad-without-combing
and the permethrin-without-combing groups

Defined as the youngest person in the household with three or more live lice present at admission

Data only represented geographically


This minimizes the risk of re-infestation

RCTs randomized controlled trials

404

3.2 Plant-Based Pediculicides


A multitude of herbal pediculocides has been developed in
the last two decades. However, evidence for their efficacy
is still sparse. Heukelbach et al. [41] evaluated six herbal
pediculocides popular in Australia in vitro and compared
the efficacy against lice with that of 1 % permethrin. With
one exception, all products had a low efficacy. In a comprehensive review, the authors concluded that there is a
substantial lack of evidence concerning the efficacy and
safety of plant-based pediculocides [42]. Hitherto, the
mechanisms of action of plant-based pediculocides were
not investigated thoroughly.
Four products have been assessed in RCTs. With the
exception of one study, the validity was low (Table 2). Brand
names are provided to identify the product in question.
3.3 Ivermectin
Ivermectin is a broad-spectrum parasiticide with widespread use since 1987. Initially, it was applied against
intestinal and skin-dwelling nematodes, later against various species of insects and sarcoptes mites. Ivermectin
targets glutamate-gated chloride channels, found only in
invertebrates, and c-aminobutyric acid-gated ion channels.
These mechanisms cause muscular paralysis in the target
parasites. Oral ivermectin is restricted to children aged
[5 years and weighing [15 kg.
Four RCTs investigated the efficacy of ivermectin,
either as a topical application or as an oral treatment
(Table 3). The efficacy of a single topical treatment was
74 % and that of oral treatment varied from 78 to 97 %.
The validity of the studies varied considerably. In vitro
experiments suggest that the topical application of ivermectin effectively kills permethrin-resistant head lice [43].
In a study in a slum in Brazil (where exposure risk and
incidence were extremely high), a single treatment with
ivermectin of all children living in a household and free of
head lice at admission significantly delayed re-infestation
(Table 3).
3.4 Isopropyl Myristate and 1,2-Octanediol
A new approach is based on compounds that dissolute/
disrupt the wax layer that covers the cuticle of the louse
exoskeleton. In vitro assays have shown that isopropyl
myristate diluted in cyclomethicone extracts hydrocarbons
from the cuticular wax [44]. This should lead to uncontrollable water loss through the cuticle and, consequently,
the parasites death.
Two RCTs have been performed with isopropyl myristate with an efficacy of 5282 % [30, 45]. The overall
validity of the studies was low (Table 4).

H. Feldmeier

In one RCT, 1,2-octanediol was investigated. The efficacy of 1,2-octanediol mousse applied for 8 h was 77 %
compared with 60 % for 1,2-octanediol lotion applied for
2 h [46] (Table 4). A study intended to show a protective
effect of the regularly spraying of hair with 1,2-octanediol
showed a statistically significant advantage compared with
placebo spray [47].
Products containing isopropyl myristate or 1,2-octanediol seem to be safe [30, 45, 46].
3.5 Dimeticones
Dimeticones are linear poly-dimethyl-siloxanes of varying
chain length. Dimeticones belong to the group of synthetic silicone oils. The chain length and the solvent
determine the viscosity of the substance and other physico-chemical characteristics. Dimeticones licensed for the
treatment of pediculosis capitis vary with regard to viscosity, surface-spreading propensity, concentration, and
the addition of other compounds that may also have a
pediculicidal effect [48]. Almost a dozen products are on
the market of which only very few have been investigated
in RCTs. To enable readers to identify a particular dimeticone, brand names of the different pediculicidal
products are provided below.
Dimeticones are clear, colorless, odorless, and hydrophobic. Dimeticones of low surface tension can perfectly
coat microscopic surfaces [49]. If applied on a louse, they
coat the cuticle of the insect, enter into the spiracles (tiny
tracheae-like tubes leading into the louse body and bringing oxygen to internal organs), and displace the air needed
for breathing [49].
Two studies have shown that dimeticones have a pure
physical mode of action [50, 51]. Richling and Bockeler
demonstrated that a two-phase dimeticone containing a
total of 92 % dimeticones (NYDA) entered the tracheal system, displaced air, and blocked oxygen supply
within less than 1 min. This resulted in immediate death
of the parasite. Burgess demonstrated that a 4 % dimeticone diluted in cyclomethicone (Hedrin) killed
head lice by disruption of water management, subsequent osmotic stress, and probable rupture of the gut.
This caused death of the parasite with a delay of several
hours [50].
Two dimeticones have been investigated in appropriate
clinical trials. Hedrin, a 4 % dimeticone dissolved in
cyclomethicone, showed an efficacy between 70 and 92 %
in studies performed in Great Britain and Turkey (Table 5).
The efficacy seemed to be higher when the intensity of
infestation was low. NYDA, a mixture of two dimeticones with different physico-chemical properties, showed
an efficacy of 97 % in a population with a high intensity of
infestation [52] (Table 5).

216

143

100

123

78 Children,
13 adults

Australia; children
(2008)

Israel; children (not


provided)

Great Britain; children,


adults (2008)

Australia; children
(2009)

Great Britain; children,


adults 2008

Not
known

Not
known

Light to
heavy

Not
known

Not
known

Intensity
of
infestation

Soya oil shampoof vs. permethrin


lotion 1 %

Mixture of tea tree oil and


lavenderd vs.
pyrethrin ? piperonyl butoxide
pressurized aerosol mousse vs.
suffocation producte

Mixture of coconut, anise, ylang


ylang oil spray vs. permethrin
0.5 % alcohol lotion

Mixture of coconut, anise, ylang


ylang oil spray vs. permethrin
0.5 % ? malathion 0.25 %
spray

Mixture of eucalyptol, sodium


lauroyl sacronisate,
cocamidopropyl betaine,
cocamide diethanolaminea vs.
malathion 1 % foam

Comparison

Permethrin 37 %

Soya oil 74 %

Proportion of head lice-free


individuals:

Pyrethrin 33 %
Suffocation product 100 %

Herbal product 98 %

Proportion of head lice-free


individuals:

Permethrin 44 %

Herbal oil 83 %

Proportion of head lice-free


individuals:

Permethrin ? malathion *92 %c

Proportion of head lice-free


individuals according to schools:
Herbal oil *92 %c

Malathion 43 %

MOOV shampoo 68 %

Proportion of head lice-free


individuals:

Outcome

10 % tea tree oil ? 1 % lavender oil (Neutralice Lotion)


Benzyl alcohol, mineral oil, polysorbate 80, sorbitan monooleate, carbopol 934, triethanole (Neutralice Advance)
Mosquito Lauseshampoo

No precise figures given; the authors stated there were no significant differences in efficacy between the two treatments

This reduces the risk of re-infestation

MOOV head lice shampoo; the product was applied three times during a period of 14 days

RCTs randomized controlled trials

GGGOOO (G = very low, OGG = low, OOG = moderate-high, OOO = very high)

Number of
participants

Study performed
in (year)

Table 2 RCTs performed with plant-based pediculocides

OGG

OGG

OGG

GGG

OOG

Overall
validity
of study
results

Herbal pediculocide and


suffocation product were
applied three times within
14 days, but pyrethrin only
twice; siblings of participants
were also treatedb
Ineligible household members
were also treatedb

Ineligible household members of


participants were also treatedb

Sparse data, high withdrawal rate,


and flaws in study design make
conclusions impossible

Siblings of participants were also


treatedb

Comment

[29]

[63]

[31]

[62]

[61]

Reference

Treatment of Pediculosis Capitis


405

812

78

765

80

132

France, Great Britain, Ireland,


Israel; children, adolescents,
adults (2004)

USA; children, adolescents,


adults (not reported)

USA; children, adolescents,


adults (2010)

Egypt; children (not reported)

Brazil; children (2007)

Oral ivermectin 1 9 400 lg/kg


vs. no intervention

Oral ivermectin (single dose)


1 9 400 lg/kg vs. 0.5 %
malathion lotion

Light to heavyd

All individuals
lice free at
admissione

0.5 % ivermectin lotion (single


application) vs. vehicle
placebo

0.15, 0.25, 0.5 % ivermectin


lotion (single application) vs.
vehicle placebo

Proportion of head lice-free


individuals:

Oral ivermectina vs. malathion


0.5 alcohol lotionb

OOO

GGG

OO

OGG

OOO

Overall
validity
of study
results

This study aimed at showing the


protective effect of a single oral
treatment with ivermectin in
children living in an area of
extremely high transmission

Sparse data and flaws in study


design make conclusions
impossible

2 RCTs reported in one


publication; household members
of the index participant were also
treatedc

Phase II study with single topical


application of ivermectin

Inclusion of all household


members of the index participant
in the studyc

Comment

[67]

[66]

[65]

[56]

[64]

Reference

Defined as the youngest household members with three or more viable lice

C50 % only light infestation

This minimizes the risk of re-infestation

RCTs randomized controlled trials

b
Eligibility criterion was previously failed treatment in either the index case or a household member despite topical application of a pyrethroid- or malathion-based insecticide 26 weeks
prior to admission

Control 14 days

Ivermectin 24 days

Length of lice-free period in


treated and control children:

Malathion 88 %

Oral ivermectin 78 %

Proportion of head lice-free


individuals:

Ivermectin 74 %
Vehicle placebo 18 %

Proportion of head lice-free


index patientse in the
intention-to-treat
population:

0.5 % ivermectin 74 %
Placebo vehicle 9 %

0.25 % ivermectin 50 %

0.15 % ivermectin 56 %

Proportion of head lice-free


individuals:

Malathion 90 %

Ivermectin 97 %

Outcome

Comparison

Not known

Mild to
moderated

Not known

Intensity of
infestation

GGGOOO (G = very low, OGG = low, OOG = moderate-high, OOO = very high)
a
Two doses of 400 lg/kg bodyweight 8 days apart

Number of
participants

Study performed in (year)

Table 3 RCTs performed with ivermectin

406
H. Feldmeier

141 children,
27 adults

60

520

63

Great Britain;
children and adults
20052006

Canada, USA;
children and adults
(2004)

Great Britain;
children and adults
(2006)

Great Britain;
children (2012)

Light to
heavy

Not known

Not known

Light to
heavy

Intensity of
infestation

1 % 1,2-Octanediol spray vs.


placebo spray

5 % 1,2-Octanediol (in 20 %
alcohol) lotion vs. malathion
0.5 % aqueous solution

Isopropyl myristate 50 % in
cyclomethicone vs. pyrethrum
0.33 % ? piperonyl butoxide
4 % shampoo

Isopropyl myristate 50 % in
cyclomethicone vs. permethrin
1 % creme rinse

Comparison

Placebo spraya

1,2-Octanediol spraya

Malathion 48 %
Time until re-infestation
occurredc:

1,2-Octanediol 88 %b

Proportion of lice-free
individuals:

Pyrethrum *20 %a

Isopropyl myristate *52 %

Proportion of lice-free
individualsa:

Permethrin 19 %

Isopropyl myristate 82 %

Proportion of lice-free
individualsa:

Outcome

OGG

Study intended to show a


protective effect by regular
application of octanediol spray
after elimination of a current
infestation

Prevention of re-infestation of
participants through treatment of
ineligible household members

Two phase II trials; sparse data;


inappropriate data analysis

GGG

OOO

2 RCTs analyzed in one


publication; prevention of reinfestation of participants
through treatment of ineligible
household members

Comment

OGG

Overall
validity
of study
results

Data only displayed graphically in a KaplanMeier-plot; the authors stated per protocol analysis showed only trends but no statistical significance

When applied 8 h/overnight; when applied 22.5 h, the efficacy of octanediol was 71 %

Data only reported graphically

RCTs randomized controlled trials

GGGOOO (G = very low, OGG = low, OOG = moderate-high, OOO = very high)

Number of
participants

Study performed in
(year)

Table 4 RCTs performed with isopropyl myristate or octanediol

[47]

[46]

[45]

[30]

Reference

Treatment of Pediculosis Capitis


407

214
Children
and 39
adults

73

145

72

90

Great Britain; children,


adolescents, adults
(not reported)

Great Britain; children


and adults (not
reported)

Brazil; children (2007)

Turkey; children,
adolescents, adults
(2008)

Great Britain; children,


adults (2012)

Not
known

Low to
heavyc

High to
very
high

Low to
moderate

Low to
moderate

Intensity
of
infestation

Dimeticone 4 % liquid gel (Hedrin


Once liquid gel) vs. permethrin
1 % creme rinse

Dimeticone 4 % in a volatile
silicone vehicle lotiona
(Hedrin) vs. dimeticone 4 %
lotion ? 2 % nerolidol

Two-phase dimeticone 92 %
(NYDA) lotiona vs. permethrin
1 % aqueous solution

Dimeticone 4 % in a volatile
silicone vehicle lotiona
(Hedrin) vs. malathion 0.5 %
aqueous solution

Dimeticone 4 % in a volatile
silicone vehicle lotiona
(Hedrin) vs. phenothrin 0.5 %
aqueous solution

Comparison

C75 % of participants had a light infestation

This minimizes the risk of re-infestation

Solvent = cyclomethicone D5

RCTs randomized controlled trials

GGGOOO (G = very low, OGG = low, OOG = moderate-high, OOO = very high)

Number of
participants

Study performed in
(year)

Table 5 RCTs performed with dimeticones

Permethrin 16 %

Dimeticone 77 %

Prevention of re-infestation of participants


through treatment of ineligible
household membersb

OOG

Proportion of lice-free
individuals:

Ineligible household members of study


participants were also treatedb

Exposure to re-infestation was minimized


by temporarily absence of participants
from their households

Other infested household members were


also treatedb

Comment

Dry combing for assessment of efficacy


was performed five times within 14 days

OGG

OOG

OGG

OOG

Overall
validity of
study results

Dimeticone 92 %
Dimeticone ? nerolidol
86 %

Proportion of lice-free
individuals:

Permethrin 67 %

Dimeticone 97 %

Proportion of lice-free
participants:

Malathion 30 %

Dimeticone 70 %

Proportion of lice-free
participants:

Phenothrin 75 %

Dimeticone 70 %

Proportion of lice-free
participants:

Outcome

[32]

[69]

[52]

[68]

[34]

Reference

408
H. Feldmeier

Treatment of Pediculosis Capitis

Recently, the ovicidal activity of various dimeticones


has been assessed in vitro [53]. The efficacy to kill
developing lice embryos essentially depended on the
physico-chemical properties of the dimeticone applied.
Whereas a 92 % two-phase dimeticone (NYDA) showed
an efficacy of 100 %, a 4 % dimeticone diluted in cyclomethicone (Hedrin) was not effective at all.
Dimeticones have been globally used as anti-foaming
agents in children and adults for many years. They are
biochemically inert and are considered non-toxic [49, 54].
Because of their mode of action, the development of
resistant head lice is very unlikely [49].
3.6 Miscellaneous Interventions
Head lice eggs remain firmly attached to the hair after
successful elimination of adults by topical or oral treatment
and are difficult to remove. Visible eggs are a cosmetic
issue that may cause shame and stigmatization [15]. How
to get rid of eggs and egg shells is, therefore, an important
issue. Previous investigations have shown that vinegar,
acetone, bleach, all-purpose degreases, and petrolatum
were not effective in eliminating eggs [55]. The authors
demonstrated that ordinary hair conditioner facilitates the
removal of nits in vitro. Ordinary conditioner had a similar
effect as products specifically marketed for egg removal
[55].
The simplest way to solve the cosmetic problem is to
selectively cut those hairs to which eggs are attached.
Obviously, this is not possible if thousands of hairs are
affected.

4 Discussion
The development of resistance and the global spread of
multi-resistant head lice populations have prompted the
development of new treatment approaches, such as the
topical application of essential oils from plants, dimeticones, and ivermectin. These compounds have different
modes of action and different safety profiles. The critical
analysis of the published articles showed several characteristics that may bias the interpretation of the results and
that impede general conclusions.
First, efficacy of the compound in question was determined after different intervals, the time frame varying from
8 to 23 days after the last treatment. This is important,
because the probability of re-infestation rises with an
increasing observation time (see below).
Second, in many studies, the presence of head lice was
defined as the outcome measure, irrespective of the
developmental stage of the parasites recovered. If developmental stages are not differentiated, one cannot

409

distinguish between persistence of head lice initially present or hatched from eggs after treatment and re-infestation
caused by re-exposure, e.g., through non-treated household
members. If re-infestation is likely, the study will underestimate the true efficacy of the treatment.
Third, in some studies household members of the
patient were also treated. Because head lice easily move
from head to headeven several times in a night, if
children sleep togetherre-infestation is expected to
occur as soon as study participants resume their day-today activities. Re-exposure to the original or other sources
of infestation and subsequent re-infestation will result in
an underestimate of actual product efficacy [56]. Vice
versa, it can be assumed that in studies in which household members were treated, re-infestation was minimized
or did not occur at all and, thereby, the proportion of head
lice-free participants was higher than in studies with the
same product in which re-infestation in the households
was not prevented.
Fourth, patients admitted differed widely in intensity of
infestation, i.e., the number of head lice present varied
from a few to several hundreds. Becauseas in other
parasitic diseasesthe efficacy of a drug depends on the
number of parasites present, studies that predominantly
included patients with a low intensity of infection will
overestimate the cure rate.
Fifth, the most sensitive method to assess the efficacy of
a drug is to perform wet combing. However, wet combing
is an effective therapeutic approach by itself [14]. Hence, if
wet combing is performed several times during follow-up,
the true efficacy of a treatment cannot be determined, as the
investigator cannot differentiate to which extent cure was
due to the application of the drug or to the removal of
persisting head lice by assessment combing. Therefore, the
guidelines for clinical trials with pediculocides clearly state
that assessment should be performed by dry combing (a
technique that is less sensitive than wet combing and that
does not cause harm to head lice), and that the combing
should be stopped as soon as lice are found to reduce the
therapeutic effect of the dry combing.
How the outcome of a trial can be manipulated by an
increased number of assessment combings is shown by a
RCT performed in Germany. A newly developed dimeticone (Dimet 20) was compared with a compound
already on the market (Hedrin) [57]. In the Dimet 20
group, the hair of the participants was combed five times
during the follow-up, whereas in the participants of the
Hedrin group, combing was performed only once [57].
This resulted in a cure-rate of 100 % in the Dimet 20
group.
Sixth, investigators used different methods to assess the
efficacy of the intervention. Because the sensitivity of
visual inspection and of wet combing differs by a factor of

410

H. Feldmeier

35, visual inspection is used for the assessment of efficacy. This will overestimate the proportion of head licefree individuals at the end of the study [14].
Taken together, the published RCTs rarely fulfilled the
prerequisites defined by expert groups [12, 22] and varied
considerably with regard to study design, outcome, statistical analysis, and presentation of results. Our findings
corroborate a previous systematic review highlighting that
RCTs on the treatment of head lice infestation are frequently biased [33]. Such biases make the comparison
between studies difficult or impossible. The following
conclusions are justified.

4.5 Dimeticones

4.1 Pyrethroids and Organophosphates

5 Conclusions

Taking into account the low efficacy of and the spread of


resistance to pyrethroids and organophosphates and the
potential health hazards associated with their use, these
groups of pediculocides can no longer be recommended.
Based on a series of studies performed in the UK during the
last 20 years, Burgess et al. [32] stated that a review of
the licensing of these preparations is overdue and concluded that permethrin should be withdrawn from the
market.

Based on the epidemiological and parasitological characteristics outlined above, treatment of head lice infestation
should encompass the following principles. The application
of these principles makes cure very likely and guarantees
the interruption of an ongoing epidemic:

4.2 Plant-Based Pediculocides


The evidence of plant-based products in the treatment of
head lice infestation is still sparse, and the tolerability and
safety are not sufficiently investigated. The precise mechanism of action is not known.
4.3 Isopropyl Myristate and Octanediol
Evidence of isopropyl myristate and octanediol in head
lice infestation is scarce, and the tolerability and safety
are not sufficiently documented. Whether the proposed
mechanism of action actually takes place in vivo is not
known.
4.4 Ivermectin
Ivermectin 0.5 % lotion is a prescription-only drug
approved for the topical treatment of head lice infestation
in patients aged 6 months or older [58]. Its efficacy is in the
order of 75 %. Oral ivermectin is a prescription-only drug
and is currently not licensed for the treatment of pediculosis capitis in any country [59]. The efficacy appears to be
higher than of the topical application. Ivermectin is considered to be a third-line treatment for head lice infestation
in the USA because of high costs and limited clinical
experience [58].

The efficacy of dimeticones has been proved in appropriately designed studies on three continents. Dimeticones are
non-toxic and can be used in all age groups. The efficacy of
dimeticones varies according to the physico-chemical
property of the compound. Dimeticones with optimal
physico-chemical characteristics also kill lice embryos
independent of their developmental stage. The application
of dimeticones does not engender the risk of the development of resistant head lice populations.

Apply active contact tracing to identify other infested


individuals in the household, play group, kindergarten,
and school, and prevent re-infestation of the patient.
Use wet combing, because only this technique has a
sufficiently high sensitivity to detect few head lice.
Recommend a non-toxic drug with an efficacy [90 %
against nymph, adults, and eggs; apply the second
treatment 79 days after the first one.
Synchronize treatment; i.e., all infested individuals
have to be treated at the same time. The importance of
synchronized treatment for the interruption of transmissionand hence the prevention of re-infestation
has been demonstrated in school-based control programs as well as by mathematical modeling [2, 60].

Acknowledgments The excellent secretarial assistance by U. Kolander is gratefully acknowledged.


Conflict of interest Dr. Feldmeier reports receiving consulting and
lecture fees from Pohl-Boskamp. No other potential conflict of
interest relevant to this article is reported.

References
1. Jahnke C, Bauer E, Feldmeier H. Pediculosis capitis im Kindesalter: epidemiologische und sozialmedizinische Erkenntnisse
einer Reihenuntersuchung von Schulanfangern. Gesundheitswesen. 2008;70(11):66773.
2. Rukke BA, Birkemoe T, Soleng A, Heggen-Lindstedt H, Ottesen
P. Head lice prevalence among households in Norway; importance of spatial variables and individual and household characteristics. Parasitology. 2011;138:1296304.

Treatment of Pediculosis Capitis


3. Feldmeier H, Heukelbach J. Epidermal parasitic skin diseases: a
neglected category of poverty-associated plagues. Bull World
Health Org. 2009;87(2):1529.
4. Feldmeier H. Pediculosis capitis: new insights into epidemiology,
diagnosis and treatment. Eur J Clin Microbiol Infect Dis.
2012;31:210510.
5. Lesshafft H, Baier A, Guerra H, Terashima A, Feldmeier H.
Prevalence and risk factors associated with pediculosis capitis in
an impoverished urban community in Lima, Peru. J Global Infect
Dis. 2013;5(4):13842.
6. Falagas ME, Matthaiou DK, Rafailidis PI, Panos G, Pappas G.
Worldwide prevalence of head lice. Emerg Infect Dis.
2008;14(9):14934.
7. Vassena CV, MougabureCueto GA, Alzogaray RA, Zerba EN,
Picollo MI. Prevalence and levels of permethrin resistance in
Pediculus humanus capitis De Geer (Anoplura: Pediculidae) from
Buenos Aires, Argentina. J Med Entomol. 2003;40:44750.
8. Kasai S, Ishii N, Natsuaki M, Fukutomi H, Komagata O, Kobayashi M, Tomita T. Prevalence of kdr-like mutations associated
with pyrethroid resistance in human head louse populations in
Japan. J Med Entomol. 2009;46(1):7782.
9. Durand R, Millard B, Bouges-Michel C, Bruel C, Bouvresse S,
Izri A. Detection of pyrethroid resistance gene in head lice in
schoolchildren from Bobigny, France. J Med Entomol.
2007;44:7967.
10. Kristensen M, Knorr M, Rasmussen AM, Jespersen JB. Survey of
permethrin and malathion resistance in human head lice populations from Denmark. J Med Entomol. 2006;43:5338.
11. Yoon KS, Gao JR, Lee SH, Clark JM, Brown L, Taplin D. Permethrin resistant human head lice, Pediculus capitis, and their
treatment. Arch Dermatol. 2003;139:9941000.
12. Barker SC, Burgess IF, Terri L, Meinking TL, Mumcuoglu KY.
International guidelines for clinical trials with pediculocides. Int J
Dermatol. 2012;51:8538.
13. Feldmeier H, Jahnke C. Pediculosis capitis: epidemiologie,
diagnose und therapie. Padiatrische Praxis. 2010;76:35970.
14. Jahnke C, Bauer E, Hengge U, Feldmeier H. Accuracy of diagnosis of pediculosis capitis: visual inspection versus wet combing. Arch Dermatol. 2009;145:30913.
15. Pickett MM, Muszynski MA, Norton S. Of Lice and Men. JAMA
Dermatol. 2014;150(3):250.
16. Veracx A, Raoult D. Biology and genetics of human head and
body lice. Trends Parasitol. 2012;28:56371.
17. Parola P, Fournier PE, Raoult D. Bartonella quintana, lice, and
molecular tools. J Med Entomol. 2006;43:787.
18. Light JE, Allen JM, Long LM, Carter TE, Barrow L, Suren G,
Raoult D, Reed DL. Geographic distributions and origins of
human head lice (Pediculus humanus captitis) based on mitochondrial data. J Parasitol. 2008;94(6):127581.
19. Boutellis A, Medlannikov O, Bilcha KD, Ali J, Campelo D,
Barker SC, Raoult D. Borrelia recurrentis in head lice, Ethiopia.
Emerg Infect Dis. 2013;19:7968.
20. Angelakis E, Diatta G, Abdissa A, Trape JF, Mediannikov O,
Richet H, Raoult D. Altitude-dependent Bartonella quintana
genotype C in head lice, Ethiopia. Emerg Infect Dis.
2011;17(12):23579.
21. Feldmeier H. Lice as vectors of pathogenic microorganisms. In:
Heukelbach J, editor. Management and control of head lice
infestation. Bremen: UNIMED; 2010. p. 1325.
22. Do-Pham G, Le Cleach L, Giraudeau B, Maruani A, Chosidow O,
Ravaud P. Designing randomized-controlled trials to improve
head louse treatment: systematic review using a vignette-based
method. J Investig Dermatol. 2014;134:62834.
23. Sonnberg S, Oliveira FA, de Melo ILA, de Melo Soares MM,
Becher H, Heukelbach J. Ex vivo development of eggs from head
lice (Pediculus humanus capitis). Open Dermatol J. 2010;4:829.

411
24. Strycharz JP, Lao AR, Alves A, Clark JM. Ovicidal respone of
NYDA formulations on the human head louse (Anoplura: PEdiculidae) using a hair tuft bioassay. Lanham: Entomological
Society of America; 2012.
25. Elston
DM.
Drug-resistant
lice.
Arch
Dermatol.
2003;139:10614.
26. Picollo MI, Vassena CV, Mougabure Cueto GA, Vernetti M,
Zerba E. Resistance to insecticides and effect of synergesis on
permethrin toxicity in Pediculus capitis (Anoplura: Pediculidae)
from Buenos Aires. J Med Entomol. 2000;37:7215.
27. Bailey AM, Provic P. Persistent head lice following multiple
treatments: evidence for insecticide resistance in Pediculus
humanus capitis. Australas J Dermatol. 2000;41:2504.
28. Hunter JA, Barker SC. Susceptibility of head lice (Pediculus
humanus capitis) to pediculicides in Australia. Parasitol Res.
2003;90:4768.
29. Burgess IF, Kay K, Burgess NA, Brunton ER. Soya oil-based
shampoo superior to 0.5 % permethrin lotion for head louse
infestation. Med Devices Evid Res. 2011;4(4):3542.
30. Burgess IF, Lee PN, Brown CM. Randomised, controlled, parallel
group clinical trials to evaluate the efficacy of isopropyl myristate/cyclomethicone solution against head lice. Pharm J.
2008;280:3715.
31. Burgess IF, Brunton ER, Burgess NA. Clinical trial showing
superiority of a coconut and anise spray over permethrin 0.43 %
lotion for head louse infestation, ISRCTN96469780. Eur J Pediatr. 2010;169:5562.
32. Burgess IF, Brunton ER, Burgess NA. Single application of 4 %
dimeticone liquid gel versus two applications of 1 % permethrin
creme rinse for treatment of head louse infestation: a randomised
controlled trial. BMC Dermatol. 2013;13:5. doi:10.1186/14715945-13-5.
33. van der Stichele RHV, Dezeure EM, Bogaert MG. Systematic
review of clinical efficacy of topical treatments for head lice.
BMJ. 1998;311:6048.
34. Burgess IF, Brown CM, Lee PN. Treatment of head louse
infestation with 4 % dimeticone lotion: randomised controlled
equivalence trial. BMJ. 2005;330:14236.
35. Plastow L, Luthra M, Powell R, Wright J, Russel D, Marshall
MN. Head lice infestation: bug busting vs. traditional treatment.
J Clin Nurs. 2001;10:77583.
36. Willems S, Lapeere H, Haedens N, Pasteels I, Naeyaert JM, De
Maeseneer J. The importance of socio-economic status and
individual characteristics on the prevalence of head lice in
schoolchildren. Eur J Dermatol. 2005;15(5):38792.
37. Tomalik-Scharte D, Lazar A, Meins J, Bastian B, Ihrig M,
Wachall B, Jetter A, Tantcheva-Poor I, Mahrle G, Fuhr U. Dermal absorption of permethrin following topical administration.
Eur J Clin Pharmacol. 2005;61(56):399404.
38. Anonymous Topische Therapie bei Kopflausen. Der Arzneimittelbrief. 2009;43:8186.
39. Menegaux F, Baruchel A, Bertrand Y, Lescoeur B, Leverger G,
Nelken B, Sommelet D, Hemon D, Clavel C. Household exposure
to pesticides and risk of childhood leukaemia. Occup Environ
Med. 2006;63(2):1314.
40. Stough D, Shellabarger S, Quiring J, Gabrielsen AA Jr. Efficacy
and safety of spinosad and permethrin creme rinses for Pediculosis capitis (head lice). Pediatrics. 2009;124(3):38995.
41. Heukelbach J, Canyon DV, Heukelbach-Oliveira F, Muller R,
Spear RC. In vitro efficacy of over-the-counter botanical pediculicides against the head louse Pediculus humanus var capitis
based on a stringent standard for mortality assessment. Med Vet
Entomol. 2008;22:26274.
42. Heukelbach J, Canyon DV, Speare R. The effect of natural products on head lice: in vitro tests and clinical evidence. J Pediatr
Infect Dis. 2007;2:6776.

412
43. Strycharz JP, Yoon KS, Clark JM. A new ivermectin formulation
topically kills permethrin-resistant human head lice (Anoplura:
Pediculidae). J Med Entomol. 2008;45(1):7581.
44. Barnett E, Palma KG, Clayton B, Ballard T. Effectiveness of
isopropyl myristate cylcomethicone of removing cuticular
hydrocarbons from human head lice. BMC Dermatol.
2012;12:15. doi:10.1186/1471-5945-12-15.
45. Kaul N, Palma KG, Silagy SS, Goodman JJ, Toole J. North
American efficacy and safety of a novel pediculicide rinse, isopropyl myristate 50 % (Resultz). J Cutan Med Surg.
2007;11(5):1617.
46. Burgess IF, Lee PN, Kay K, Jones R, Brunton ER. 1,2-Octanediol, a novel surfactant, for treating headlouse infestation: identification of activity, formulation, and randomised, controlled
trials. PLoS One. 2012;7(4):e35419.
47. Burgess IF, Brunton ER, French R, Burgess NA. Prevention of
head louse infestation: a randomised, double-blind, cross-over
study of a novel concept product, 1 % 1,2-octanediol spray versus
placebo. BMJ Open. 2014;4(5):e004634.
48. Feldmeier H. Pediculosis capitis: Eine Herausforderung fur das
Apothekerteam. PTA-Forum. 2013;11:226.
49. Heukelbach J, Oliveira FA, Richter J, Haussinger D. Dimeticonebased pediculicides: a physical approach to eradicate head lice.
Open Dermatol J. 2010;4:7781.
50. Burgess IF. The mode of action of dimeticone 4 % lotion against
head lice, Pediculus capitis. BMC Pharmacol. 2009;9:3. doi:10.
1186/1471-2210-9-3.
51. Richling I, Bockeler W. Lethal effects of treatment with a special
dimeticone formula on head lice and house crickets (Orthoptera,
Ensifera: Acheta domestica and Anoplura, Phthiraptera: Pediculus humanus). Arzneim-Forsch/Drug Res. 2008;58:24854.
52. Heukelbach J, Pilger D, Oliveira F, Khakban A, Ariza L, Feldmeier H. A highly efficacious pediculocide based on dimeticone:
randomized observer blinded comparative trial. BMC Infect Dis.
2008;8:115. doi:10.1186/1471-2334-8-115.
53. Heukelbach J, Sonnberg S, Becher H, Melo I, Speare R, Oliveira
FA. Ovicidal efficacy of high concentration dimeticone: a new
era of head lice treatment. J Am Acad Dermatol.
2011;64(4):e612.
54. Nair B. Final report on the safety assessment of stearoxy
dimethicone, dimethicone, methicone, amino bispropyl dimethicone, aminopropyl dimethicone, amodimethicone, amodimethicone hydroxystearate, behenoxy dimethicone, C24-28 alkyl
methicone, C30-45 alkyl methicone, C30-45 alkyl dimethicone,
cetearyl methicone, cetyl dimethicone, dimethoxysilyl ethylenediaminopropyl dimethicone, hexyl methicone, hydroxypropyldimethicone, stearamidopropyl dimethicone, stearyl dimethicone,
stearyl methicone, and vinyldimethicone. Int J Toxicol.
2003;22:1135.
55. Lapeere H, Brochez L, Verhaeghe E, Vander-Stichele RH,
Remon JP, Lambert J, Leybaert L. Efficacy of products to remove
eggs of Pediculosis humanus capitis (Phthiraptera: Pediculidae)
from the human hair. J Med Entomol. 2014;51(2):4007.

H. Feldmeier
56. Meinking TL, Mertz-Rivera K, Villar ME, Bell M. Assessment of
the safety and efficacy of three concentrations of topical ivermectin lotion as a treatment for head lice infestation. Int J Dermatol. 2013;52:10612.
57. Dornseiff M, Schwartz T. Randomisierte, Untersucher-verblindete
kontrollierte, multizentrische Therapiestudie mit Dodecanol plus
Demeticon (Dimet 20*) versus Dimeticon-Mono bei KopflausbefallIntegrierter Abschlussbericht. 2010. http://www.infectopharm.
com/login?ref=/egi-bin/dl.pl/downloads/dimet20studie_2010.pdf.
Assessed 21 July 2014.
58. Deeks LS, Naunton M, Currie MJ, Bowden FJ. Topical ivermectin 0.5 % lotion for treatment of head lice. Ann Pharmacother. 2013;47(9):11617.
59. Burgess I. Head lice. Clin Evid (Online). 2011;05:pii:1703.
60. Laguna MF, Risau-Gusman S. Of lice and math: using models to
understand and control populations of head lice. Plos One.
2011;6(7):e21848. doi:10.1371/journal.pone.0021848.
61. Greive KA, Lui AH, Barnes TM, Oppenheim VM. Safety and
efficacy of a non-pesticide-based head lice treatment: results of a
randomised comparative trial in children. Australas J Dermatol.
2012;53(4):25563.
62. Mumcuoglu KY, Miller J, Zamir C, Zentner G, Helbin V, Ingber
A. The in vivo pediculicidal efficacy of a natural remedy. IMAJ.
2002;4(10):7902.
63. Barker SC, Altman PM. A randomised, assessor blind, parallel
group comparative efficacy trial of three products for the treatment of head lice in children-melaleuca oil and lavender oil,
pyrethrins and piperonyl butoxide, and a suffocation product.
BMC Dermatol. 2010;10:6. doi:10.1186/1471-5945-10-6.
64. Chosidow O, Giraudeau G, Cottrell J, Izri A, Hofmann R, Mann
SG, Burgess IF. Oral ivermectin versus malathion lotion for
difficult-to-treat head lice. N Engl J Med. 2010;362(10):896905.
65. Pariser DM, Meinking TL, Bell M, Ryan WG. Topical 0.5 %
ivermectin lotion for treatment of head lice. N Engl J Med.
2012;367(18):168793.
66. Nofal A. Orales ivermectin gegen Kopflause: ein Vergleich mi
0,5 % topischer Malathionlotion. JDDG. 2010;8(12):9859.
67. Pilger D, Heukelbach J, Khakban A, de Oliveiera FAS, Fengler
G, Feldmeier H. Household-wide ivermectin treatment for head
lice in an impoverished community: randomized observer-blinded controlled trial. Bull World Health Org. 2010;88:906.
doi:10.2471/BLT.08.051656):90-96.
68. Burgess IF, Lee PN, Matlock G. Randomised, controlled, assessor blind trial comparing 4 % dimeticone lotion with 0.5 %
malathion liquid for head lice infestation. PLoS One.
2007;11:e1127.
69. Kurt O, Balcioglu C, Burgess IF, Limoncu ME, Girginkardesler
N, Tabak T, Muslu H, Ermis O, Sahin MT, Bilac C, Kavur H,
Ozbel Y. Treatment of head lice with dimeticone 4 % lotion:
comparison of two formulations in a randomised controlled trial
in rural Turkey. BMC Public Health. 2009;9:441.

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