Parasitology Research (2024) 123:285

[Link]

REVIEW

Scabies vaccines: where we stand and challenges ahead

Mahmoud S. Sharaf1

Received: 7 May 2024 / Accepted: 10 July 2024 / Published online: 24 July 2024
© The Author(s) 2024

Abstract
Scabies is an itchy skin disease caused by the burrowing mite, Sarcoptes scabiei. During their lifespan, female mites invade
the stratum corneum and create tunnels in which they reside, move, feed, deposit fecal pellets, and lay eggs. Globally, more
than 200 million people are estimated to be affected by scabies annually. Currently, using scabicidal agents is the only
approved method for treating scabies. However, resistance to commonly used agents such as permethrin and ivermectin
has been observed in scabies mites. Therefore, the development of vaccines for scabies, either as a preventative measure or
for treatment, is crucial to control such neglected diseases. Since the host could evolve a protective immune response that
could prevent re-infestation by scabies mites, vaccine development is theoretically possible. This review aims to provide a
comprehensive overview of the ongoing challenges regarding the currently available control measures for scabies. It also
explores the promising path of scabies vaccine development, highlighting the current state of research and challenges that
need to be addressed to develop new and innovative measures for both treating and preventing scabies infections.

Keywords Scabies · Sarcoptes scabiei · Immunity · Treatment · Vaccines

Background Sarcoptes scabiei goes through five developmental

stages in its life cycle, including egg, larva, protonymph,
Scabies is an itchy skin disease caused by a burrowing mite tritonymph, and adult. The adult scabies mite has a char-
called Sarcoptes scabiei (S. scabiei). It is now included in acteristic tortoise-like body, with a gnathosoma anteriorly
the World Health Organization roadmap for neglected tropi- and an idiosoma posteriorly. The gnathosoma is the head-
cal diseases 2021–2030. Globally, it is estimated to affect like structure that surrounds the mouth opening, while the
more than 200 million individuals at any given time and idiosoma is the oval body of the mite, which is ventrally
more than 400 million individuals cumulatively every year flat and dorsally arched, with four pairs of legs arising from
(WHO 2024). While scabies can affect individuals of any its ventral aspect. The dorsal surface of the idiosoma is not
age, it is particularly prevalent among children and the smooth, since it shows transversely arranged ridges, scales,
elderly residing in low-resource areas. Although scabies is setae, and spines (Sharaf et al 2023b) (Fig. 1).
more common in tropical countries, it can also occur in other During its lifespan (4–6 weeks), the fertilized female
regions with cold weather due to increased direct personal lays eggs within the burrow formed in the stratum corneum.
contact and increased mites’ survival (Liu et al. 2016). Sca- After hatching, the released larvae dig new pocket burrows
bies is more likely to spread in crowded environments and and wander on the surface of the host’s body until matu-
is not necessarily a result of poor hygiene. This is why it is ration. Secondary bacterial infections can lead to serious
common in places like prisons, military camps, and boarding health issues like sepsis, glomerulonephritis, and rheumatic
schools (Del Campillo et al. 2021). fever. As a result, many countries have considered scabies as
a public health concern that requires effective intervention
Section Editor: Van Lun Low (van der Linden et al. 2019).

* Mahmoud S. Sharaf
[Link]@[Link];
[Link]@[Link]
1
Parasitology Department, Faculty of Medicine, Tanta
University, Tanta, Gharbia, Egypt

Vol.:(0123456789)
285 Page 2 of 7 Parasitology Research (2024) 123:285

proinflammatory cytokines, such as TNF-α, IFN-γ, and

IL-2 (Liu et al. 2014). This could, in part, explain the
incubation period of a primary infestation caused by S.
scabiei. Moreover, there is a negative correlation between
the activity of Treg cells and the severity of lesions in
scabies (Abd El-Aal et al. 2016). This is why skin pathol-
ogy is severe in cases of CS, where IL-10 production is
significantly reduced, leading to the expansion of Th17
cells and a dysfunctional immune response involving Treg/
Th17 cells (Gonzalez-Lombana et al. 2013).
Sarcoptes scabiei mites have been reported to trigger
strong antibody-mediated immune responses, especially in
cases with crusted forms of scabies, which have extremely
high levels of antigen-specific IgG and IgE when compared
with the ordinary form. Such difference can be attributed to
Fig. 1  Microscopic appearance motile stages of scabies mites (× 100) the high levels of IL-4 and IL-13 in CS, which play crucial
roles in B-cell class switching and the induction of IgE and
IgG4 co-expression. However, the timing of the antibody-
The entangled dance between immunity mediated immune responses and their relative importance
and the scabies mite in establishing protective immunity are still poorly defined
(Walton et al. 2010; Arlian et al. 2015).
The immune response to scabies mites involves coordi- Scabies mites have developed various evasion strategies
nated responses between different immune system compo- to evade the host’s immune responses, making it difficult
nents like natural killer cells, macrophages, neutrophils, for the host to fight the mite. Live scabies mites induce skin
dendritic cells, mast cells, eosinophils, lymphocytes, fibroblasts and keratinocytes, which are the major cell types
antibodies, complement system, and different cytokines. in the skin, to release the anti-inflammatory cytokine inter-
Although the exact roles and ideal balance of these com- leukin-1 receptor antagonist (IL-1ra). This cytokine binds
ponents for complete protection are not fully understood, to the IL-1 receptor present in a variety of cells, including
it is now well established that the clinical severity of the T-cells, B-cells, natural killer cells, macrophages, and neu-
disease depends on the type and the amplitude of the asso- trophils, thereby inhibiting the activity of the proinflamma-
ciated cellular and humoral immune responses (Mounsey tory cytokine IL-1. This makes it easier for the mites to sur-
et al. 2015; Abd El-Aal et al. 2016; Sharaf et al. 2023b). vive on the host’s skin without being damaged by immune
Generally, there are two main forms of scabies: ordinary mechanisms (Morgan et al. 2013).
scabies (OS) and crusted scabies (CS). Ordinary scabies is It has also been reported that scabies mite extract stimu-
characterized by a protective local immune response domi- lates human T-regulatory cells to produce IL-10, a potent
nated by C ­ D4+ T-lymphocytes with a T helper-1 (Th1) anti-inflammatory cytokine. IL-10 reduces the release of
cytokine profile, including interferon-gamma (IFN-γ), proinflammatory cytokines and the expression of MHC-II
tumor necrosis factor-alpha (TNF-α), and interleukin-2 molecules on antigen-presenting cells, which in turn inhib-
(IL-2), while the immune response in CS is non-protec- its or reduces the interaction between the MHC-II-antigen
tive and dominated by ­C D8 + T-lymphocytes and a Th2 complex and the T-cell receptor necessary for B-cell activa-
cytokine profile, including IL-4, IL-5, and IL-13. Th17 tion and differentiation into antibody-secreting plasma cells
cells are a crucial subset of T-cells that contribute to the (Arlian et al. 2006). Furthermore, exposure to live scabies
local immune response in CS by recruiting and activating mites and their extracts has been reported to increase the
neutrophils at sites of inflammation, as well as stimulating production of vascular endothelial growth factor in human
endothelial cells, keratinocytes, and fibroblasts to produce skin equivalents and monocultures of normal human epider-
inflammatory cytokines like IL-1, IL-6, and TNF-α. Their mal keratinocytes and dermal fibroblasts. This growth fac-
role in CS is supported by high levels of IL-17 and IL-23 tor would likely promote vascularity and the influx of fluid
(Mounsey et al. 2015). (plasma) to the area around the mite’s mouthparts within the
T-regulatory lymphocytes (Treg) could potentially con- burrow, providing the mite with essential water and nutri-
tribute to the immune response against Sarcoptes scabies ents from the otherwise arid stratum corneum (Morgan and
mites by suppressing the inflammatory reaction to the Arlian 2010).
mite through the secretion of IL-10 and the inhibition of Sarcoptes scabiei are known to utilize gut serine protease
inhibitors to attach to numerous plasma proteins that are part
Parasitology Research (2024) 123:285 Page 3 of 7 285

of the complement activation pathways, thereby blocking the and even an expert’s negative test does not rule out scabies
classical, alternative, and lectin pathways of the human com- since selecting the right site for sampling is critical. Skin
plement system. As mites feed on plasma, deactivating the biopsy is an invasive procedure and time-consuming (may
host’s complement protects their gut from damage mediated take 2–7 days to obtain a result). In many cases, the histo-
by the complement system. Overall, the intricate interac- logical appearance is nonspecific, usually showing delayed
tions between mites and host immune mechanisms highlight hypersensitivity with superficial and deep perivascular
the complex arms race between parasites and their hosts. inflammatory eosinophilic and mononuclear cell infiltrates,
Understanding these mechanisms is crucial for developing papillary edema, and epidermal spongiosis. Hence, it is not
effective strategies to combat mite infestations and related used as a routine test for diagnosing scabies and is reserved
skin conditions (Fernando et al. 2023). for the confirmation of challenging or atypical cases (Foo
et al. 2013).
Although dermoscopy can be helpful in diagnosing sca-
Time to rethink scabies control: why bies, there are some limitations that hamper its use, par-
vaccines should be our top priority? ticularly for inexperienced operators. One drawback is
that the low magnification can make it hard to differentiate
Challenges regarding diagnosis between dermoscopic signs of scabies and artefacts caused
by scratching, crusts, bleeding, or microscopic dirt particles.
Clinical signs and microscopic evaluation of skin scrapings Additionally, the low magnification does not allow the detec-
are currently used for the diagnosis of scabies, although tion of eggs and feces, which are sometimes the only diag-
experience has shown that these traditional methods have nostic signs. Furthermore, the dermoscopic signs of scabies
a sensitivity of less than 50%. It might be challenging to are hardly visible on dark skin, limiting the effectiveness
detect visible lesions since they are often masked by eczema of dermoscopy in many countries, and in hairy body areas,
or impetigo or are atypical. Additionally, the disease can where a clear visualization of the skin may be restricted.
exhibit different clinical forms, including classic scabies, Finally, using handheld dermoscopy in sensitive areas like
crusted scabies, nodular scabies, bullous scabies, scabies the genital region may cause discomfort for both the patient
incognito, and animal scabies. These forms can be easily and the healthcare provider (Dupuy et al. 2007; Micali and
confused with other skin conditions such as eczema, allergic Lacarrubba 2011; Walter et al. 2011).
dermatitis, or even insect bites (Thompson et al. 2017). Developing a diagnostic serological blood test for scabies
A typical history of contact with other scabies patients, is complicated by the problem of co-sensitization or cross-
pruritus that worsens at night, and the distribution of inflam- reactivity with antigens from ubiquitous house dust mites,
matory papules can all be used to make a presumptive diag- such as Dermatophagoides farinae, Dermatophagoides pter-
nosis. Presumptive therapy is sometimes used to diagnose onyssinus, and Euroglyphus maynei. House dust mites have
scabies, but its reliability is uncertain since a favorable been reported to produce over 25 antigenic proteins, many of
response to treatment does not definitively confirm scabies, which cross-react with those from scabies mites, as reported
as other skin conditions can also improve spontaneously. by Chan et al. (2015). In a study conducted by Arlian et al.
Conversely, a lack of response to treatment does not nec- (2015) to profile the Sarcoptes mite-specific antibodies
essarily rule out scabies, especially in cases of treatment- present in the sera of 91 patients with ordinary scabies, all
resistant mites (Engelman et al. 2018). patients except one showed circulating Ig, IgG, and/or IgM
Although a definitive diagnosis of scabies can be obtained to all three house dust mite extracts, and no scabies patient
by identifying mites, eggs, eggshell pieces, or mite fecal pel- had antibodies exclusively to scabies mites. Since a signifi-
lets in scrapings obtained from skin lesions, the sensitivity cant percentage of people are usually sensitized to the ubiq-
of this approach for diagnosing classic scabies is low owing uitous house dust mites, therefore, identifying a limited and
to the limited number of mites in such cases. The accuracy defined set (used as a cocktail) of scabies proteins (or protein
of the diagnosis can also be influenced by factors such as the fragments) that do not share cross-reacting epitopes with
clinical appearance of the skin lesions (unscratched lesions those on house dust mite proteins is crucial for developing a
are more useful), the number of sites sampled, and the diagnostic test that possesses both specificity and sensitivity.
expertise of the person collecting the samples. A negative To achieve this goal, a detailed and comprehensive prot-
test result does not necessarily rule out scabies, especially if eomic and genomic analysis of scabies mites is necessary.
the scraping is not done from an active burrow (Kandi 2017; Other newer diagnostic tests like polymerase chain
Thompson et al. 2017). reaction or isothermal amplification techniques are being
A skin biopsy can also confirm the diagnosis of scabies explored; however, such tests are not yet widely available
if the mites or portions of it are found during histopatho- or definitive (Fraser et al. 2018; Hahm et al. 2018). Until
logical evaluation. However, detecting mites can be difficult, now, scabies diagnosis largely depends on a high index of
285 Page 4 of 7 Parasitology Research (2024) 123:285

suspicion, careful examination, utilizing various diagnostic to certain areas like the scalp, groin, interdigital spaces,
tools, and consulting with a dermatologist experienced in nails, and behind the ears. Furthermore, repeated applica-
diagnosing scabies. tions are generally indicated for effective management of
scabies. Such a method is exhausting, time-consuming, and
Challenges regarding treatment not preferable by most patients. Consequently, it is not ideal
especially for mass drug administration during outbreaks of
The treatment of scabies should include the pharmacological scabies (Salavastru et al. 2017). Additionally, resistance to
elimination of mites, preventing the infestation from spread- various topical scabicides, including permethrin, lindane,
ing to contacts and managing any complications that may and crotamiton, has been reported (Bernigaud et al. 2020).
arise (e.g., secondary bacterial infections). Theoretically, The use of molecular tools could help identify drug resist-
Sarcoptes scabiei mites can be effectively targeted with a ance early and accurately, as well as detect genetic changes
single therapy since they do not have free-living stages or associated with resistance.
intermediate hosts in their life cycle. However, most scabi- In contrast to the human scenario, where acaricides are
cides currently available do not kill the eggs, allowing the few, more acaricidal agents are available for the treatment
life cycle to continue and potentially worsen the infection. of sarcoptic mange in livestock and companion animals.
Additionally, the epidermal cell growth shifts eggs away Furthermore, the vast majority of medications utilized in
from the dermal host defense system and/or the systemic humans are taken from the veterinary arsenal. The clear dis-
acaricidal agents diffusing from the dermis, making it dif- parity between human and animal scabies treatment avail-
ficult to kill the mites (Sharaf et al. 2023b). ability is mostly due to the companion animal and livestock
Unless the given non-ovicidal scabicide has a long half- health sectors being a more profitable market for companies
life that spans the mite’s whole cycle, or multiple doses are than the neglected tropical diseases sector. Recently, treat-
given at the appropriate times, eggs and newly hatched lar- ment of sarcoptic mange in domestic animals (particularly
vae will not be affected, allowing the infection to progress. cats and dogs) has moved to moxidectin and the novel fam-
Consequently, new scabicides are urgently needed, particu- ily of isoxazolines, a novel class of acaricides that includes
larly those that could kill all the developmental stages of the afoxolaner, fluralaner, sarolaner, and lotilaner, due to their
scabies mite. The availability of such medications would documented safety, efficacy, and long-lasting protection of
improve control strategies and decrease scabies recurrence the animal. Hence, such agents may be a promising target for
rates (Bernigaud et al. 2016; Sharaf et al. 2020). human scabies research (Sharaf et al. 2020, 2023a, 2023b).
Currently, there are just a few treatment options for
human scabies. Traditional broad-spectrum drugs of choice,
like permethrin and ivermectin (IVR), are still used mostly The scabies vaccine enigma: will we finally
owing to their low cost. Currently, ivermectin is the only kick the itch?
oral scabicide available for human use, mostly used to treat
crusted scabies. Unfortunately, ivermectin has a short half- As mentioned before, using scabicidal agents is the only
life in the skin, and multiple doses are generally needed for approved method for treating scabies until now, and resist-
the effective management of scabies (Bernigaud et al. 2016). ance against commonly used agents such as permethrin and
Additionally, it is not approved for infants and children less ivermectin has been observed in scabies mites. Therefore,
than 15 kg. Furthermore, its safety for pregnant women is the development of vaccines for scabies, either as a preven-
still uncertain, so it is recommended to be avoided during tative measure or for treatment, is crucial to control such
pregnancy. Instead, topical scabicidal agents should be con- neglected diseases. Since the host could evolve a protective
sidered the preferred option in such cases (Nicolas et al. immune response against the scabies mites, vaccine devel-
2020). Another ongoing issue with IVR is the evidence of opment is theoretically possible (Abd El-Aal et al. 2016).
treatment failure despite multiple doses, as well as in vitro Unfortunately, there are no available approved effective sca-
resistance. As a result, IVR monotherapy is not recom- bies vaccines until now owing to the complexity of the host-
mended for cases of crusted scabies. It is recommended to parasite interactions in scabies, lack of adequate knowledge
use a combination of IVR with a topical acaricide like per- about the protective immune mechanisms employed by the
methrin and keratolytic supplements in such cases (Niode host, and the vast array of proteins encoded by the parasite,
et al. 2022). which makes it challenging to identify proteins that could
Although various topical acaricidal agents are available induce protective immunity (Shen et al. 2023). Designing
for treating human scabies (e.g., permethrin 5% cream, and developing a successful vaccine against Sarcoptes sca-
benzyl benzoate 10–25% lotion or emulsion, crotamiton biei mites is currently a subject of extensive research.
10% cream, and precipitated sulfur cream or lotion), they Various studies have been conducted to develop vaccines
must be applied to the entire body, with special attention against scabies mites, including whole-body extract vaccines
Parasitology Research (2024) 123:285 Page 5 of 7 285

(Tarigan and Huntley 2005), DNA vaccines (Gu et al. 2014), IgE usually fail to elicit a protective response against scabies
and recombinant protein vaccines. For a complex parasite mites. Likewise, vaccination with a mixture of rSsCLP5 and
like Sarcoptes scabiei, immunization with a total extract rSsCLP12 induced high levels of IgG and IgE antibodies
of scabies mites would be advantageous over recombinant in rabbits, with subsequent protective response against the
proteins since all structural and immunogenic characteris- scabies mites (Shen et al. 2020).
tics that are native to the mite are displayed in the vaccine. Multi-epitope peptide vaccines are another attractive
However, the in vitro cultivation of the mite is not feasible option for inducing a specific immune response, being
until now, making the availability of native proteins at the cost effective and easy to synthesize and use, with mini-
required quantity challenging. Hence, recombinant protein mal risk of antigen-induced anaphylaxis (Li et al. 2014).
subunit vaccines are easily available candidates to test the Since peptides alone are not very effective at stimulating an
protective potential of various immunodominant antigens of immune response, adjuvants are often added to enhance their
the mite (Casais et al. 2016). immunogenicity (Mittal et al. 2020). The GPGPG linkers
Chitinase-like proteins (CLPs) and serine protease are commonly used since they aid in presenting epitopes to
inhibitors (serpins) are reported to be involved in various the immune system and enhance effective immune process-
fundamental physiological functions in mites and are also ing (Saadi et al. 2017). Additionally, they keep the epitopes
involved in the host-parasite interaction (Sutherland et al. separate and do not allow them to fold (Nezafat et al. 2014).
2009; Mika et al. 2012; Swe and Fischer 2014). In a recent Paramyosin, a structural protein only found in inverte-
study on mangy rabbits, Shen et al. (2018) reported that brate muscles and involved in immune regulation, is another
immunization with recombinant S. scabiei chitinase-like promising vaccine candidate. Using immunoinformatics
protein 5 (rSs-CLP5) induced a protective immune response, tools, Naz et al. (2020) developed an in silico protocol for
evidenced by high levels of specific antibodies and reduced designing a vaccine against scabies, in which the paramyosin
mite burden. In another study on mangy rabbits, Shen et al. amino acid sequence of S. scabiei var. hominis was used to
(2020) used a mixture of rSs-CLP5 and rSs-CLP12 for design a multi-epitope peptide vaccine with different lengths
immunization. Interestingly, the authors reported that the of epitopes for potential B- and T-cell receptor activation.
rabbit’s immune protection rate and the rate of mite reduc- The vaccine also included a β-defensin-3 adjuvant. However,
tion improved, and concluded that a combination of differ- additional in vitro and in vivo studies are needed to validate
ent candidate vaccine molecules could enhance the level of and further explore this computational vaccine model for
immune protection provided by the vaccine. Along similar scabies.
lines, Shen et al. (2023) used a cocktail of three recombinant Notably, Shen et al. (2023) used a multi-epitope vaccine
vaccine candidate molecules, rSsCLP5, rSsCLP12, and rSs- comprising a recombinant fusion protein containing epitopes
serpin, to immunize mangy rabbits, and reported that the of the three proteins, Ss-serpin, Ss-CLP5, and Ss-CLP12,
protection rate was higher than the effects of combined use on mangy rabbits. Unfortunately, the reported protective
of rSsCLP5 and rSsCLP12. immune response was much lower than that noticed in rab-
Surprisingly, Casais et al. (2016) reported that no sig- bits immunized with a cocktail of three recombinant vaccine
nificant protective response was induced when a mixture candidate molecules, rSsCLP5, rSsCLP12, and rSs-serpin.
of two recombinant antigens, Ssλ15 and Ssλ20∆B3, was The authors emphasized the importance of selecting the
used to immunize mangy rabbits although high levels of right adjuvant for a multi-epitope vaccine to effectively trig-
antibodies were noticed after vaccination. Instead, immu- ger a protective immune response against S. scabiei. They
nized rabbits exhibited higher lesion scores, indicating that also highlighted the significance of screening vaccine can-
the vaccine-induced exacerbated immune response shared didates, optimizing the vaccine, and determining the appro-
in the pathogenesis of such lesions. The lack of protection priate immune dose of the fusion protein to enhance the
from vaccination may be related to the type and the levels effectiveness of scabies vaccines.
of the specific antibodies produced by the candidate recom-
binant protein. Different recombinant vaccines can induce
varying levels of protective antibodies, with some being Conclusions
effective in providing immune protection while others are
not. Shen et al. (2023) suggested that protective response is While existing scabicide treatments offer relief, the limita-
possibly related to the levels of the specific IgE antibodies tions of these methods highlight the urgent need for a scabies
produced after immunization. Furthermore, coordination vaccine. The ongoing research into scabies vaccines paints
of IgG and IgE is essential for such a protective response a promising picture for the future. Scientists are actively
to be accomplished. Hence, hosts immunized with specific exploring potential antigens and delivery methods and over-
S. scabiei recombinant protein fractions that induce high coming challenges related to large-scale mite cultivation
levels of specific IgG antibodies but fail to induce specific and animal models. Animal studies are already underway,
285 Page 6 of 7 Parasitology Research (2024) 123:285

signifying a crucial step towards a readily available vaccine. Arlian LG, Feldmeier H, Morgan MS (2015) The potential for a blood
Global collaboration between researchers, public health test for scabies. PLoS Negl Trop Dis 9(10):e0004188
Bernigaud C, Fang F, Fischer K, Lespine A, Aho LS, Dreau D et al
agencies, and funding bodies is essential to ensure success- (2016) Preclinical study of single-dose moxidectin, a new oral
ful vaccine development, implementation, and equitable treatment for scabies: efficacy, safety, and pharmacokinetics com-
access in all regions. With continued research and interna- pared to two-dose ivermectin in a porcine model. PLoS Negl Trop
tional cooperation, scabies vaccines have the potential to Dis 10(10):e0005030
Bernigaud C, Fernando DD, Lu H, Taylor S, Hartel G, Guillot J et al
revolutionize scabies control strategies, leading to a future (2020) In vitro ovicidal activity of current and under-development
where this itchy enemy becomes a relic of the past. scabicides: which treatments kill scabies eggs? Brit J Dermatol
182(2):511–513
Abbreviations CLPs: Chitinase-like proteins; CS: Crusted scabies; Casais R, Granda V, Balseiro A, Del Cerro A, Dalton KP et al (2016)
IFN-γ: Interferon-gamma; IL: Interleukin; IVR: Ivermectin; OS: Ordi- Vaccination of rabbits with immunodominant antigens from Sar-
nary scabies; rSs-CLP5: Recombinant S. scabiei chitinase-like protein coptes scabiei induced high levels of humoral responses and pro-
5; S.: scabiei Sarcoptes scabiei; TNF-α: Tumor necrosis factor-alpha; inflammatory cytokines but confers limited protection. Parasit
Treg: T-regulatory lymphocytes Vectors 9:435–447
Chan TF, Ji KM, Yim AK, Liu XY, Zhou JW, Li RQ et al (2015) The
draft genome, transcriptome, and microbiome of Dermatopha-
goides farinae reveal a broad spectrum of dust mite allergens. J
Author contributions The manuscript was written and revised by Allergy Clin Immunol 135(2):539–548
Mahmoud S. Sharaf. Del Campillo AB, Lleopart N, ChQR G, Álvarez M, Montilla M, Mar-
tínez-Carpio PA (2021) Intervention protocol to improve scabies
Funding Open access funding provided by The Science, Technology & control in enclosed communities: a case report. Rev Esp Sanid
Innovation Funding Authority (STDF) in cooperation with The Egyp- Penit 23(1):37–42
tian Knowledge Bank (EKB). Dupuy A, Dehen L, Bourrat E, Lacroix C, Benderdouche M, Dubertret
L et al (2007) Accuracy of standard dermoscopy for diagnosing
Data availability No datasets were generated or analyzed during the scabies. J Am Acad Dermatol 56:53–62
current study. Engelman D, Fuller LC, Steer AC (2018) International Alliance for
the Control of Scabies Delphi Panel. Consensus criteria for the
Declarations diagnosis of scabies: a Delphi study of international experts. PLoS
Negl Trop Dis 12(5):e0006549
Ethical approval Not applicable. Fernando D.D., Nammunige N.A., and Fischer K. (2023): Biochemi-
cal research of Sarcoptes scabiei. In: Fischer K., Chosidow O.
Consent to participate Not applicable. (eds), Scabies, Brisbane, Australia, Springer, Chapter 5, p. 75–90.
[Link]
Consent for publication Not applicable. Foo CW, Florell SR, Bowen AR (2013) Polarizable elements in scabies
infestation: a clue to diagnosis. J Cutan Pathol 40(1):6–10
Competing interests The author declares no competing interests. Fraser TA, Carver S, Martin AM, Mounsey K, Polkinghorne A, Jeloc-
nik M (2018) A Sarcoptes scabiei specific isothermal amplifica-
tion assay for detection of this important ectoparasite of wombats
Open Access This article is licensed under a Creative Commons Attri- and other animals. Peer J 6:e5291. [Link]
bution 4.0 International License, which permits use, sharing, adapta- 5291
tion, distribution and reproduction in any medium or format, as long Gonzalez-Lombana C, Gimblet C, Bacellar O, Oliveira WW, Passos
as you give appropriate credit to the original author(s) and the source, S, Carvalho LP et al (2013) IL-17 mediates immunopathology in
provide a link to the Creative Commons licence, and indicate if changes the absence of IL-10 following Leishmania major infection. PLoS
were made. The images or other third party material in this article are Pathog 9(3):e1003243
included in the article’s Creative Commons licence, unless indicated Gu X, Xie Y, Wang S, Peng X, Lai S et al (2014) Immune response
otherwise in a credit line to the material. If material is not included in induced by candidate Sarcoptes scabiei var. cuniculi DNA vac-
the article’s Creative Commons licence and your intended use is not cine encoding paramyosin in mice. Exp Appl Acarol 63:401–412
permitted by statutory regulation or exceeds the permitted use, you will Hahm JE, Kim CW, Kim SS (2018) The efficacy of a nested polymer-
need to obtain permission directly from the copyright holder. To view a ase chain reaction in detecting the cytochrome c oxidase subunit
copy of this licence, visit [Link] 1 gene of Sarcoptes scabiei var. hominis for diagnosing scabies.
Br J Dermatol 179(4):889–895
Kandi V (2017) Laboratory diagnosis of scabies using a simple saline
mount: a clinical microbiologist’s report. Cureus 9(3):e1102
References Li Y, Zhang F, Althunayan MH, Hu XA, Xin Y et al (2014) Con-
struction and identification of the recombinant plasmid pET30a-
Abd El-Aal AA, Hassan MA, Gawdat HI, Ali MA, Barakat M (2016) EgA31-Eg95 of Echinococcus granulosus. Exp Ther Med
Immunomodulatory impression of anti and proinflammatory 7:204–208
cytokines in relation to humoral immunity in human scabies. Int Liu X, Walton SF, Murray HC, King M, Kelly A, Holt DC et al (2014)
J Immunopathol Pharmacol 29(2):188–194 Crusted scabies is associated with increased IL-17 secretion by
Arlian LG, Morgan MS, Paul CC (2006) Evidence that scabies mites skin T cells. Parasite Immunol 36(11):594–604
(Acari: Sarcoptidae) influence production of interleukin-10 and Liu J, Wang H, Chang F, Liu Y, Chiu F et al (2016) The effects of
the function of T-regulatory cells (Tr1) in humans. J Med Entomol climate factors on scabies. A 14-year population-based study in
43(2):283–287 Taiwan. Parasite 23:54–61
Parasitology Research (2024) 123:285 Page 7 of 7 285

Micali G, Lacarrubba F (2011) Augmented diagnostic capability using fluralaner in a rabbit model of crusted scabies. Parasitol Res
videodermatoscopy on selected infectious and non-infectious 122(11):2477–2490
penile growths. Int J Dermatol 50:1501–1505 Shen N, Zhang H, Ren Y, He R, Xu J et al (2018) A chitinase-like
Mika A, Reynolds SL, Mohlin FC, Willis C, Swe PM, Pickering DA protein from Sarcoptes scabiei as a candidate anti-mite vaccine
et al (2012) Novel scabies mite serpins inhibit the three pathways that contributes to immune protection in rabbits. Parasit Vectors
of the human complement system. PLoS ONE 7(7):e40489 11:599–609
Mittal A, Sasidharan S, Raj S, Balaji SN, Saudagar P (2020) Explor- Shen N, Wei W, Chen Y, Ren Y, Xiong L et al (2020) An antibody per-
ing the Zika genome to design a potential multiepitope vaccine sistent and protective two rSsCLP-based subunit cocktail vaccine
using an immunoinformatics approach. Int J Pept Res Ther against Sarcoptes scabiei in a rabbit model. Vaccines 8:129–144
26:2231–2240 Shen N, Wei W, Chen Y, Liu S, Xiong L et al (2023) Vaccination with
Morgan MS, Arlian LG (2010) Response of human skin equivalents to a cocktail vaccine elicits significant protection against Sarcoptes
Sarcoptes scabiei. J Med Entomol 47(5):877–883 scabiei in rabbits, whereas the multi-epitope vaccine offers limited
Morgan MS, Arlian LG, Markey MP (2013) Sarcoptes scabiei mites protection. Exp Parasitol 245:108442. [Link]
modulate gene expression in human skin equivalents. PLoS ONE exppa​ra.​2022.​108442
8(8):e71143. [Link] Sutherland TE, Maizels RM, Allen JE (2009) Chitinases and chitinase-
Mounsey KE, Murray HC, Bielefeldt-Ohmann H, Pasay C, Holt DC, like proteins: potential therapeutic targets for the treatment of
Currie BJ et al (2015) Prospective study in a porcine model of T-helper type 2 allergies. Clin Exp Allergy 39:943–955
Sarcoptes scabiei indicates the association of Th2 and Th17 path- Swe PM, Fischer K (2014) A scabies mite serpin interferes with com-
ways with the clinical severity of scabies. PLoS Negl Trop Dis plement-mediated neutrophil functions and promotes staphylococ-
9(3):e0003498 cal growth. PLoS Negl Trop Dis 8(6):e2928
Naz S, Ahmad S, Walton S, Abbasi SW (2020) Multi-epitope based Tarigan S, Huntley JF (2005) Failure to protect goats following vac-
vaccine design against Sarcoptes scabiei paramyosin using immu- cination with soluble proteins of Sarcoptes scabiei: evidence for
noinformatics approach. J Mol Liq 319:114105 a role for IgE antibody in protection. Vet Parasitol 133:101–109
Nezafat N, Ghasemi Y, Javadi G, Khoshnoud MJ, Omidinia E (2014) Thompson MJ, Engelman D, Gholam K, Fuller LC, Steer AC (2017)
A novel multi-epitope peptide vaccine against cancer: an in silico Systematic review of the diagnosis of scabies in therapeutic trials.
approach. J Theor Biol 349:121–134 Clin Exp Dermatol 42(5):481–487
Nicolas P, Maia MF, Bassat Q, Kobylinski KC, Monteiro W, Rabi- van der Linden N, van Gool K, Gardner K, Dickinson H, Agostino
novich NR et al (2020) Safety of oral ivermectin during preg- J, Regan DG, Dowden M, Viney R (2019) A systematic review
nancy: a systematic review and meta-analysis. Lancet Glob Health of scabies transmission models and data to evaluate the cost-
8:e92–e100 effectiveness of scabies interventions. PLoS Negl Trop Dis
Niode NJ, Adji A, Gazpers S, Kandou RT, Pandaleke H, Trisnowati 13(3):e0007182
DM et al (2022) Crusted scabies, a neglected tropical disease: Walter B, Heukelbach J, Fengler G, Worth C, Hengge U, Feldmeier H
case series and literature review. Infect Dis Rep 14(3):479–491 (2011) Comparison of dermoscopy, skin scraping, and the adhe-
Saadi M, Karkhah A, Nouri HR (2017) Development of a multi-epitope sive tape test for the diagnosis of scabies in a resource-poor set-
peptide vaccine inducing robust T cell responses against brucel- ting. Arch Dermatol 147:468–473
losis using immunoinformatics based approaches. Infect Genet Walton SF, Pizzutto S, Slender A, Viberg L, Holt D, Hales BJ et al
Evol 51:227–234 (2010) Increased allergic immune response to Sarcoptes scabiei
Salavastru CM, Chosidow O, Boffa MJ, Janier M, Tiplica GS (2017) antigens in crusted versus ordinary scabies. Clin Vaccine Immunol
European guideline for the management of scabies. J Eur Acad 17(9):1428–1438
Dermatol Venerol 31(8):1248–1253 World Health Organization (2024): Scabies. Available at: [Link] ​ ww.​
Sharaf M, Antonios S, Mina S, Eliwa K, Rayia DA (2020) The scabi- who.​int/​news-​room/​fact-​sheets/​detail/​scabi​es. Accessed 7 March
cide effect of moxidectin in vitro and in experimental animals: 2024
parasitological, histopathological and immunological evaluation.
Exp Parasitol 217:107961. [Link] oi.o​ rg/1​ 0.1​ 016/j.e​ xppar​ a.2​ 020.​ Publisher's Note Springer Nature remains neutral with regard to
107961 jurisdictional claims in published maps and institutional affiliations.
Sharaf MS, Othman AA, Abd El Ghaffar AE, Ali DM, Eid MM
(2023a) Crusted scabies in a rabbit model: a severe skin disease
or more? Parasit Vectors 16(1):413. [Link]
s13071-​023-​05995-8
Sharaf MS, Othman AA, Abd El Ghaffar AE, Ali DM, Eid MM
(2023b) Evaluation of the scabicidal effect of a single dose of