JEADV ISSN 1468-3083 High in vitro efficacy of Nyda® L, a pediculicide containing dimeticone FAS Oliveira,† R Speare,‡ J Heukelbach*†‡
† Department of Community Health, School of Medicine, Federal University of Ceará, Fortaleza, Brazil‡ School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland, Australia
Keywords Abstract
dimeticone, efficacy, head lice, in vitro testing,
Background The therapy of pediculosis remains a common problem in clinical
practice. As resistance to commonly used chemical pediculicides is constantly
increasing, there is a need for new effective compounds.
Saúde Comunitária, Faculdade de Medicina, Uni-
Study design The efficacy of Nyda® L, a new pediculicide containing a high
versidade Federal do Ceará, Rua Prof. Costa
concentration of dimeticone, was assessed in an in vitro trial and compared with
Mendes 1608, 5. andar, Fortaleza CE 60430-140,
three reference products (Hedrin® containing 4% dimeticone, Lyclear® contain-
Brazil, tel. +55 85 33668045; fax + 55 85
ing 1% permethrin, and Prioderm® containing 1% malathion) and a negative
control group. Head lice were collected from heavily infested patients in a resource-poor community in Northeast Brazil, where no resistance against pediculicides
Received: 12 December 2006, accepted 20 December 2006
has been reported thus far. In each of the five groups, 50 adult fully vital licewere tested. We used a dip test (immersing head lice in the undiluted products
for 3 min, washing off products after 20 min). Using predefined criteria for mortality, the lice were monitored at different points in time, for a period of 24 h. Results Nyda® L and Prioderm® killed all head lice already after 5 min. The efficacy of Nyda® L was better than of Lyclear®. Lice treated with Hedrin® resurrected after several hours and did not show a significantly higher mortality compared with the control group after 24 h. Conclusion Nyda® L can be regarded as a very efficacious pediculicidal compound, killing all lice in vitro within 5 min.
(lindane), organophosphates (malathion), carbamates
Introduction
(carbaryl), and benzyl benzoate, as well as formulations
Head lice (Pediculus humanus var. capitis) are insects that
have parasitized human beings for many thousands of
In the last decades, as a result of extensive use, resist-
years.1 In spite of therapeutic advances, pediculosis remains
ance to pediculicides with a neurotoxic mode of action has
a problem throughout the world, particularly in developed
increased, particularly to permethrin.8,10–13 Permethrin is
countries. Although the clinical effects of head lice seem
used in many countries as first-line therapy, and resist-
to be minor,2–4 pediculosis has been considered an important
ance is frequent. This pertains not only to industrialised
cause of impetigo in developing countries and may result
countries, such as the USA, UK, France, Denmark, Israel,
in stigmatization.3,5 Possibly, head lice play a role in the
and Australia, but also to less developed countries, such as
transmission of vector-borne diseases, such as bartonellosis
Argentina. Where resistance will develop in the future
Chemical pediculicides have been used extensively for
Additional reasons to investigate alternative products
the treatment of infestations since the early 20th century.
are failure of current chemical treatments to kill embryos
Today, topical chemical insecticides still remain the main-
in eggs, environmental and food safety, and potential
stay of head lice treatment, such as pyrethrins and syn-
toxicity of the chemical pediculicides, particularly organ-
thetic pyrethroids (permethrin and allethrin), organochlorines
ophosphates and organochlorines. Thus, there is a clear
JEADV 2007, 21, 1325–1329 Journal compilation 2007 European Academy of Dermatology and Venereology
Dimeticone-based product against head lice
need for compounds effectively killing adult lice and eggs
filter paper was moistened by 200 μL tap water. Control
lice were placed directly on moistened filter paper without
Recently, Burgess et al.14 published a clinical trial com-
any treatment. After lice were placed on the filter paper;
paring Hedrin®, a 4% dimeticone lotion, with Full Marks
obvious pools of the product were wiped from the lice
Liquid® (0.5% phenothrin). The cure rate was similar in
with a jeweller’s forceps directed under a dissecting
both groups (70% and 75%, respectively).
microscope. Head lice were washed after 20 min by
Here, we show in an in vitro study that the product
immersing the hair strands in tap water for 1 min and
Nyda® L (G. Pohl-Boskamp GmbH & Co. KG, Hohenlock-
then placing them on unused filter paper in unused Petri
stedt, Germany), which has a high concentration of
dimeticone, is highly effective in killing head lice.
We tested lice in batches of 10 for each treatment and
control group, repeating the tests five times to give a totalof 50 lice in each group. The relative frequencies of mor-
tality were compared using the chi-squared test.
The lice were examined after 5, 10, 20, 30, 60, 120, and
Head lice
180 min as well as after 6 and 24 h. Pre-defined criteria
Adult head lice were obtained by dry combing from
for evaluation of the survival of lice were used, based on
individuals living in the township Vicente Pinzón in the
activity, ataxic signs, ability to stay on hair, as well as gut
outskirts of Fortaleza, the capital city of Ceará State in
and leg movements.15 The vital state of each louse was
Northeast Brazil. Resistance to commonly used pediculicidal
classified according to the following categories: vital lice,
agents has never been reported in the area, but formal
fully active lice with normal movements; lice with major
susceptibility testing has not been done.
vital signs, walking, but unable to walk in a progressive
The individuals participated in a head lice control cam-
fashion or no righting reflex when rolled onto the back; lice
paign based on combing, and we used the lice that were
with minor vital signs, not walking, but presence of internal
obtained during this campaign. Only lice were used from
(gut) movements, movements of antennae, or leg movements
individuals who had not applied chemical pediculicides
(with or without stimulation by a forceps); lice with no
nor received ivermectin during the previous 4 weeks. All
vital signs at all, even after stimulation by a forceps.
lice were examined for activity and morphological inte-
For the calculation of mortality, highly stringent criteria
grity under a dissecting microscope, and only fully active
were used: head lice were only judged as ‘dead’ if they
lice were tested within 60 min after collection. We used
were in categories 3 or 4 (i.e. no or minor vital signs
female and male adult lice and did not blood-feed the
All lice were examined under a dissecting microscope
by the same observer to prevent interobserver variation. Lice were maintained at 27 °C to 29 °C during the tests. Products
The following products were tested: Nyda® L (G. Pohl-
Boskamp GmbH & Co. KG, containing a high concentrationof dimeticone, as well as medium-chained triglycerides,
All four commercial products killed lice, but efficacy
jojoba oil, and fragrances); Hedrin® lotion (Thornton &
differed, with Nyda® L and Prioderm® having 100% mortality
Ross Ltd, UK, containing dimeticone 4%); Lyclear®
at all test times (fig. 1). After 5 min, 100% of test lice had
Creme Rinse (Chefaro Ltd, UK, containing permethrin
no or minor vital signs, irrespective of the product applied,
1%); and Prioderm® Shampoo (Norpharma A/S, Denmark,
compared with 0% in the negative control group. However,
recovery of lice occurred over time in the Lyclear® andHedrin® groups. The detailed vital states of the tested headlice in the five groups over time are depicted in Table 1. In vitro testing
Despite showing no major vital signs during the first
To allow a direct comparison, all products were tested
hour, lice treated with Hedrin® recovered after several
according to a standard procedure. We used a dip technique
hours, with a mortality of only 74% (95% confidence
in which lice attached to strands of human hair were
interval, 59.7–85.4) after 6 h, which is significantly lower
immersed completely in the undiluted products for 3 min.
than the mortality for lice treated with Nyda® L
The hair strands with lice were held with a forceps under
(P < 0.001). After 24 h, the mortality of Hedrin®-treated
the solution. We checked for the presence of air bubbles.
lice (78%; 95% confidence interval, 64.0–88.5) was not
Then, the lice were placed with hairs on Whatman filter
statistically different from the control lice (68%; 95%
paper in 5-cm Petri dishes. To prevent lice desiccating, the
confidence interval, 53.3–80.5; P = 0.3). JEADV 2007, 21, 1325–1329 Journal compilation 2007 European Academy of Dermatology and Venereology
Dimeticone-based product against head lice
Table 1 Vital state of head lice in four test groups and a negative control group over time (n = 50 in each group) Prioderm® Hedrin® Lyclear® Negative control
At all points in time, Nyda® L, Lyclear®, and Prioderm®
showed significantly higher mortality than the negativecontrol lice receiving no treatment (P < 0.001 in all cases).
In the control group, mortality due to desiccation
started after 6 h and was high after 24 h. Discussion
Our data show that Nyda® L, based on a highconcentration of dimeticone, is highly effective in vitroagainst head lice. Other components of the product aremedium-chained triglycerides and jojoba oil. However,the exact concentration of dimeticone and the otheringredients is not publicly available, as the composition ofNyda® L, a medical device in the European Union, is a
fig. 1 Mortality of head lice in four test groups and a negative control group
corporate secret of the manufacturer G. Pohl-Boskamp
over time. Results of Nyda® L and Prioderm® are identical at all times of
The mortality of lice treated with this product was
similar to Prioderm® (1% malathion) and higher than
Nyda® L performed slightly better than Lyclear®. This
Lyclear® (1% permethrin). In the first hour, mortality was
difference was statistically significant after 10 min (P = 0.04),
similar to Hedrin® (4% dimeticone). However, lice resur-
30 min (P = 0.02), 60 min (P = 0.006), 120 min (P = 0.02),
rected after several hours in the Hedrin® group and did
180 min (P = 0.02), and 6 h (P = 0.04).
not show a significantly higher mortality compared with
JEADV 2007, 21, 1325–1329 Journal compilation 2007 European Academy of Dermatology and Venereology
Dimeticone-based product against head lice
the negative control after 24 h, although mortality in con-
Commonly, less stringent criteria are used for the defini-
trol lice was high due to desiccation.
tion of ‘mortality’ of head lice: a state of reduced activity
Burgess et al.14 reported a cure rate of about 70% after
judged by the inability of the insect to walk in a progressive
treating head lice infestation with Hedrin®, a 4% dimeti-
fashion or to show a righting reflex when rolled onto its
cone lotion. The lotion was left to dry naturally and not
back.22,23 Such outcome measures are prone to overestimate
washed out; thus, the contact time was prolonged.
mortality. Therefore, Burkhart and Burkhart18 suggested
We immersed the lice only for 3 min in the respective
to apply indicators of irreversible morbidity for the assessment
solutions and washed the substances away after 20 min,
of efficacy. In this study, we defined death as the absence
simulating a standard treatment with an insecticide-
of any vital signs or merely the presence of minor vital signs.
based pediculicide. The differences in contact time could
It has been suggested that in vitro testing done in a manner
be the reason why Hedrin® lotion was effective in a
resembling the clinical application of a pediculicide may
clinical trial but did not perform well after several hours
be a proxy for the results of clinical trials.24 In this case,
Nyda® L should be highly effective in vivo particularly
As the instructions of the producers for the in vivo use
because the usual contact time will be considerably longer
of pediculicides vary considerably, our approach allowed
than in our in vitro study. Albeit, clinical trials are warranted
the comparison of different products in a standardized
to corroborate our findings, and future studies will also
manner. In addition, we could detect the products with
have to test the efficacy of the product on head lice eggs.
the highest efficacy (i.e. killing most lice after a short
In conclusion, our data show that Nyda® L is highly
effective in killing head lice in vitro. Such products that
An approach of killing head lice by suffocation has been
probably kill head lice by physical means may prevent the
described recently by Pearlman.16 He reported excellent
clinical results with a so-called ‘dry-on suffocation-basedpediculicide’ (DSP). The DSP lotion seems to coat the lice
Acknowledgments
with a film layer after drying, consequently blocking theinsect’s spiracles and suffocating the lice.
We thank the community leaders and inhabitants of
Pearlman’s clinical study has been criticized due to the
Morro do Sandra’s/Vicente Pinzón II for collaboration. J.
uncontrolled and open design, the outcome measures
Heukelbach was supported by an Endeavour Australia
used, and a putative conflict of interest of the author.17,18
Research Fellowship. F.A.S. Oliveira received a postgradu-
In addition, there are no in vitro data available to corrob-
ate scholarship from Coordenação de Aperfeiçoamento de Pes-
orate the clinical findings. However, the strategy to kill
soal de Nível Superior, Brazil.
head lice by physical measures is a promising approachbecause the compounds used for this purpose are consid-
Conflicts of interest
ered non-toxic if applied topically, and resistance probablycannot develop.
J. Heukelbach has been a scientific consultant to G. Pohl-
A possible mode of action of lowly viscous dimeticones
Boskamp GmbH & Co KG. The company had no role in the
is the penetration into the spiracles of the lice, causing
design, execution, or interpretation of the study. R. Speare
asphyxia and death. The substance group of dimeticones
has been a consultant to an Australian producer of
(polydimethylsiloxane) are silicon oils also used in cos-
pediculicides in the past, but currently has no links to the
metic products (e.g. to facilitate the use of a comb and to
make the hair silky and soft).19 In addition, oral dimeti-cone is used as an anti-flatulent to alleviate gastrointesti-nal discomfort. Dimeticone is physiologically inert and
References
non-toxic, and after oral ingestion, the oil is not absorbed
1 Araujo A, Ferreira LF, Guidon N, Maues Da Serra Freire N,
but eliminated unaltered in the faeces. Topical use in
Reinhard KJ, Dittmar K. Ten thousand years of head lice
humans is considered safe. In the animal model, no
infection. Parasitol Today 2000; 16: 269.
adverse events were observed after topical use of concen-
2 Speare R, Canyon DV, Melrose W. Quantification of blood
intake of the head louse: Pediculus humanus capitis.
Head lice may ‘resurrect’ after a period without any
Int J Dermatol 2006; 45: 543–546.
vital signs, and pediculicidal testing has been recom-
3 Burgess IF. Human lice and their management. Adv Parasitol
mended to be monitored for 24 h.12,21 Therefore, we
1995; 36: 271–342.
obtained mortality data over 24 h. However, many lice in
4 Mumcuoglu KY, Klaus S, Kafka D, Teiler M, Miller J. Clinical
the control group died due to desiccation, negating the
observations related to head lice infestation. J Am Acad
value of 24-h testing without feeding. Dermatol 1991; 25: 248–251. JEADV 2007, 21, 1325–1329 Journal compilation 2007 European Academy of Dermatology and Venereology
Dimeticone-based product against head lice
5 Feldmeier H. Pediculosis capitis – die wichtigste Parasitose
16 Pearlman DL. A simple treatment for head lice: dry-on,
des Kindesalters. Kinder-Jugendmedizin 2006; 6: 211–214.
suffocation-based pediculicide. Pediatrics 2004; 114:
6 Sasaki T, Poudel SK, Isawa H et al. First molecular evidence
of Bartonella quintana in Pediculus humanus capitis
17 Roberts RJ, Burgess IF. New head-lice treatments: hope or
(phthiraptera: pediculidae), collected from Nepalese
hype? Lancet 2005; 365: 8–10.
children. J Med Entomol 2006; 43: 110–112.
18 Burkhart CG, Burkhart CN. Asphyxiation of lice with topical
7 Robinson D, Leo N, Prociv P, Barker SC. Potential role of
agents, not a reality . yet. J Am Acad Dermatol 2006; 54:
head lice, Pediculus humanus capitis, as vectors of rickettsia
prowazekii. Parasitol Res 2003; 90: 209–211.
19 Yahagi K. Silicones as conditioning agents in shampoos.
8 Heukelbach J, Feldmeier H. Ectoparasites – the
J Soc Cosmet Chem 1992; 43: 275–284.
underestimated realm. Lancet 2004; 363: 889–891.
20 Nair B. Final report on the safety assessment of stearoxy
9 Heukelbach J, Speare R, Canyon D. Natural products and
dimethicone, dimethicone, methicone, amino bispropyl
their application to the control of head lice: an evidence-
dimethicone, aminopropyl dimethicone, amodimethicone,
based review. In: Brahmachari G, ed. Chemistry of Natural
amodimethicone hydroxystearate, behenoxy dimethicone,
Products, pp. 277– 302. Research Signpost, Kerala, India,
C24–28 alkyl methicone, C30–45 alkyl methicone,
C30–45 alkyl dimethicone, cetearyl methicone, cetyl
10 Burgess IF. Human lice and their control. Annu Rev Entomol
dimethicone, dimethoxysilyl ethylenediaminopropyl
2004; 49: 457– 481.
11 Downs AM, Stafford KA, Hunt LP, Ravenscroft JC,
hydroxypropyldimethicone, stearamidopropyl
Coles GC. Widespread insecticide resistance in head lice to
dimethicone, stearyl dimethicone, stearyl methicone, and
the over-the-counter pediculocides in England, and the
vinyldimethicone. Int J Toxicol 2003; 22: 11–35.
emergence of carbaryl resistance. Br J Dermatol 2002; 146:
21 Burkhart CN, Burkhart CG. Recommendation to
standardize pediculicidal and ovicidal testing for head
12 Burkhart CG, Burkhart CN. Safety and efficacy of
lice (Anoplura: Pediculidae). J Med Entomol 2001; 38:
pediculicides for head lice. Expert Opin Drug Saf 2006; 5:
22 Mougabure CG, Gonzalez AP, Vassena CV, Picollo MI,
13 Kristensen M, Knorr M, Rasmussen AM, Jespersen JB.
Zerba EN. Toxic effect of aliphatic alcohols against
Survey of permethrin and malathion resistance in human
susceptible and permethrin-resistant Pediculus humanus
head lice populations from Denmark. J Med Entomol 2006;
capitis (Anoplura: Pediculidae). J Med Entomol 2002; 39: 43: 533–538.
14 Burgess IF, Brown CM, Lee PN. Treatment of head louse
23 Hunter JA, Barker SC. Susceptibility of head lice (Pediculus
infestation with 4% dimeticone lotion: randomised
humanus capitis) to pediculicides in Australia. Parasitol Res
controlled equivalence trial. BMJ 2005; 330: 1423.
2003; 90: 476–478.
15 Heukelbach J, Oliveira FA, Speare R. A new shampoo based
24 Meinking TL, Taplin D, Kalter DC, Eberle MW. Comparative
on neem (Azadirachta indica) is highly effective against head
efficacy of treatments for pediculosis capitis infestations.
lice in vitro. Parasitol Res 2006; 99: 353–356. Arch Dermatol 1986; 122: 267–271. JEADV 2007, 21, 1325–1329 Journal compilation 2007 European Academy of Dermatology and Venereology
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