The Management of Scabies in the 21St Century

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Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV in the19 This isan open access article under the CC BY-NC license.www.medicaljournals.se/acta for themanagementofscabies increasedconsiderably rimental animalmodels(7, 8). The therapeutic options 17 nature. The mite was first identified and illustrated in the contagious its about write to first the were Romans and beenknownforover2,500years;the Greeks has disease intense itching,associatedwithtypicalskinlesions. The tes scabieivar. hominis(1). The burrowingmitecauses S France. E-mail:[email protected] Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, FR-94010 Créteil, Corr: Acta DermVenereol 2020;100:adv00112 Accepted Mar19,2020;Epubaheadofprint24,2020 and development; ovicidal. sease; ivermectin; permethrin; moxidectin; acaricide discovery Key words: scabies; Sarcoptes scabiei; neglected tropical di- es, andoutlines prospects forpotential improvements. anupdate advanc onmanagement ofscabies, recent view givesanoverview of limitations thecurrent inthe isurgently leadingto needed.Thisre cure measures and progress in the development of new therapeutic mains largelysuboptimal fromto diagnosis treatment, re Management of scabies sis secondaryto scabies. rheumaticnephritis, fever,or acute fatalinvasivesep with reports aureusbacterialsuperinfections, ofcus zed, including group A Streptococcus and tions. Theburdenof the diseaseisnow well characteri 1 Charlotte BERNIGAUD The Management of Scabies in the 21 years (5,6),mainlythrough thedevelopmentofexpe host-parasite interactionshave beenmadeinthelast30 II (3,4).Furtheradvances in thephysiopathologyand a British entomologist, in the 1940s during World War and transmissionwasprovidedbyKennethMellanby, the poor. The earliestunderstandingofthemitebiology and bylowinterestinanectoparasitethatmainlyaffects been hamperedlargely bylimited accesstotheparasite Est University, Créteil, France, Infectious DiseasesProgram,Herston,Brisbane, Australia, the greatest impactinpoor overcrowdedliving condi young affects in Scabies children and particular, has 150–200millionaffecting worldwide, peopleyearly. isone ofScabies themost commonskindiseases – Infections Sexuellement Transmissibles, French Society of Dermatology and Potentials Journal Compilation ©2020ActaDermato-Venereologica. Dermatology Department, AP-HP, Henri Mondor hospital, Paris-Est University, Créteil, France, th century (2). Despite marked advances in parasitology century (2). Despite marked advances in parasitology sitic diseasecausedbythemicroscopicmiteSarcop cabies (Latinscabere “toscratch”)isacommonpara Charlotte Bernigaud, Department of Dermatology,Henri Hôpital th and20 th centuries,researchintoscabieshas 1–5 , Katja FISCHER 4 IACS (International Alliance for the Control of Scabies, and Centenary theme section:CUTANEOUS ANDGENITALINFECTIONS 2,4 andOlivier CHOSIDOW Staphylococ REVIEW ARTICLE 3 3Research groupDynamyc,EA7380,FacultédeSanté,EnvA,USCANSES,Paris------(16). Young childreninunderprivilegedpopulations particularly highin Asia, Oceania,andLatin America in the world every year, and that the scabies burden is mates suggest that 150–200 million people have scabies and has a documented significant burden. The latest esti populations livingintropicalandsubtropicalregions, of theworld,withgreatestprominenceindisadvantaged Scabies isaprevalentdisease,whichpresentinallparts TREATMENT? WHY DOWENEEDTOIMPROVE SCABIES large-scale actiontoachievecontrolanderadication(15). the listofneglectedtropicaldiseasesandhascalledfor (14). Thus, in2017,the WHO decidedtoaddscabies (IACS), havegivenscabiestherecognitionitdeserves the International Alliance forthe Control ofScabies efforts, madebyagroupofexpertsbroughttogether in to be a truehealth target. Inthe past 10years, stupendous Scabies was, fora long time, not appropriately considered diagnostic toolsortreatmentsinthenearfuture(10–13). host molecular and biochemical analyses to develop new ques will enable scientists to design large-scale mite and Medicine (9). its discovery, the2015NobelPrizeforPhysiology and the researcherswererecentlyawarded,35yearsafter the mostimportantdrugscurrentlyusedtotreatscabies; withthediscoveryofivermectin,one in the1970–80s scabies, and has opened doorstonew strategies. knowledge of the biology, pathology and management of resulting inhigh-impactpublications, has increased our disease. This additional and increased research activity, of documenting the morbidities and burden caused by the ted tropical diseases after a long and still ongoing process nally, in 2017, scabies was addedtothe WHO listof neglec have worked toimprove the management of scabies. Fi and public health physicians, together with policymakers, dous itch. For more than a century, researchers, clinicians Scabies is more than just a disease that provokes a horren SIGNIFICANCE Currently, therecentexpansionofmulti-omicstechni 1,4,5 st Century: Past, Advances 5 GrIDIST, Groupe Infectiologie Dermatologique 2 QIMR Berghofer Medical Research Institute, Acta DermVenereol 2020;100: adv00112 doi: 10.2340/00015555-3468 - - - - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Theme issue: Cutaneous and genital infections Africa (35)contemporaneously withscabiesoutbreaks, of acute glomerulonephritis in Trinidad (34)orSouthern 1970s, withepidemiological studiesshowingepidemics (32, 33). This particularlinkwas establishedearlyinthe be linkedwithscabies,especially amongyoungchildren data suggestingthatupto40%ofimpetigolesionscan areas oftheglobeandinremotelocations(17);withsome pathogens isobservedmainlyintropicalorsubtropical This associationbetweenscabiesparasitesandbacterial rheumatic fever(31),bothofwhichcanbecomechronic. ing infection,suchasglomerulonephritis(30)oracute some cases, immune-mediated diseasescan occur follow septicaemia, ormoreinvasivebacterialinfections(24).In and soft-tissueinfections(includingnecrotizingfasciitis), impetigo, which can become more severe andcause skin infection oftheepidermis,alsoknownaspyodermaor and become invasive,suchasgroup A Streptococcus (GAS) opportunistic commensal or pathogenic bacteria that can breaches inskinbarrierthatcreatesanentrypointfor life (28). Scratching scabies lesions themselves leads to impact onattendance,performance(27)andqualityof concentration atworkorschool,leadingtoanegative i.e. deprivingpatientsofsleep(26),interferingwith caused bytheintenseitchcanhavedirectconsequences, in any other pruritic skin affections (25). The discomfort to the immense itch is present more often in scabies than been hypothesizedthatscratchingoflesionsinresponse appearing withtheparasiticinfestation(14,24).Ithas to scabies infection, mostly caused bybacterial infections ingly substantialmorbidity, andevenmortality(23),due wever, recentepidemiological studies indicateincreas perceived asanectoparasitethatjustcausesitching.Ho camps (20–22). populations,andrefugee homeless schools, prisons, child-care andelderly-careresidentialfacilities(18,19), communities and institutional settings, such as hospitals, high endemicityofscabiesisoftenreportedinclosed risk ofscabiesandoutbreaks.Inhigh-incomenations, munities orincrowdedhousingconditionsareathigher with eachother. Indeed,peoplelivinginclusteredcom population concentration,andhowindividualsinteract depend onthepatient’s miteload,householdsizeand transient lifestyles. The riskoftransmissionisknownto develop, and are fuelled by overcrowded households and creased, smallepidemicsaroundasinglecasecaneasily in whichthemiteburdenperpersonisdramatically the case inseverescabies,i.e.profuseorcrusted scabies, patients mayfrequentlybeaffected. This isespecially is contagious,personssharingthesamehouseholdwith text ofsevereformsscabies;seebelow). As scabies mite-contaminated environment(generallyinthecon contact and, less frequently, via fomites within a patient Transmission ofscabiesoccursmainlyviaskin-to-skin living in crowded conditions are more often at risk (17). 226 For alongtime, thescabies mite hasbeenerroneously S. aureus (29). These bacteria lead to secondary C. Bernigaudetal. - - - - or feet(1).Inadultpatients,theheadisusuallynotaf skin, buttocks,genitals,periareolarregioninfemales, periumbilical wrists, hands, webs, finger as such sites, epidermis. Mostscabieslesionsarefoundinclassical by thepenetrationandprogressofmitethrough that worsens at night (44) and typical skin lesions caused itch severe are scabies Typically, of symptoms first the WHO DOWENEEDTOTREAT? its management. in improvement global justify to sufficient are but red, economic and psychological ramifications are undersco senteeism amongstinfestedpatients.Itsmarkedsocial, impact, affecting qualityoflifeandschoolorjobab social significant a causes still scabies itch, the Beyond (39–43). flourish to bacteria associated allowing mite, thereby modulating the microenvironment around the including complementdefenceandneutrophilfunction, proteases) indownregulatingtheinnatehostimmunity of directeffects ofmitegutproteins(serpinsandserine and, inpart,explainedtheseobservationswithevidence recent fundamentalexperimentalworkhassupported drug administration (MDA) campaigns (36–38). More paralleling areductioninscabiesnumbersduringmass (30), orreductioninimpetigoskinsoresprevalence tion in childhood haematuria following scabies treatment aids, whichhaveprovedreliable inendemicregions, itching inhouseholdmembers (49,50). These diagnostic diffuse and areas, intypicalskin itch,presenceoflesions and clinicalarguments, suchas,forexample,ahistory of bies usingacombinationof parameters ofpatienthistory been created to assisthealth-workers inrecognizing sca have algorithms Clinicaldiagnostic and mismanagement. of scabiescanbechallenging,leadingtomisdiagnosis tion. However, burrowsmaynotbevisibleanddiagnosis lesion ofscabies,isobservedatatypicalsitepredilec 1-infested patients)(46–48). including topically-appliedmedication,HIV-, orHTLV- from anycause(transplantrecipients,corticosteroiduse elderly or in patients with underlying immunodeficiency and palmssoles(1). This conditionisseeninthe or diffusely affect multipleskinsites,includingtheface example, for scalp, the or toe, finger, a to restricted be scabies, hyperkeratoticskin(ratherthanrealcrusts)may the developmentofextensivelesions.Insuchforms orevenmillionsofmitesperpatient,andthousands racterized byaveryhighparasiteburden,withhundreds, profuse andcrustedscabies.Bothpresentationsarecha epidermis (Fig. 1A). The severe forms ofscabies include all ofwhichindicatethepresenceamitewithin pruritic papulesarethemostcommonlesionsobserved, (45). Burrows,vesicles,pustules,nodules,orexcoriated fected, although itmay be involved in infants,andbabies or in interventional studies in the field showing reduc showing field the in studies interventional in or The diagnosis of scabies is easy if a burrow, the specific ------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Table I. Comparison of the specificity and sensitivity of the different currently available diagnostic non-invasive methods for scabies. for Adapted fromChosidow&Sbidian(62)andMicalietal.(53) methods non-invasive diagnostic available currently different the of sensitivity and specificity the of Comparison I. Table or epiluminescencemicroscopyaretoolsusedindaily as repeated scrapings maybe necessary. Dermoscopy is highlyoperator-dependent andistime-consuming, but 1B), (Fig. specificity excellent an has examination specificity are summarized in nologies havebeencustomized. Their sensitivityand microscopic examinationofaskinscraping.Newtech eggs, eggshellfragmentsormitefaecalpelletsbylight visualization oftheparasite(adultsorimmatureforms), diagnostic scrapings (53). The gold standard remains the have beendevelopedfordirectlyidentifyingthemitein markers isstillnotavailable.Non-invasivemethods other specialties,andnon-experthealth-workers(52). the easeofusingitforGPs,expertsindermatologyand using thesecriteriahaveyettobevalidated,aswell The accuracy and reproducibility of scabies diagnosis scabies, andsuspectedscabiescase)8subcategories. includes 3 levels of definition (confirmed scabies, clinical under theaegisofIACS(51). The IACS2019Criteria 4-round Delphiprocessincluding34internationalexperts diagnosis ofscabiesweredevelopedrecentlyusinga prevalence. With thisinmind,consensuscriteriaforthe offices to resource-poor field settings, regardless of local range ofsettings,fromthedermatologist’s dailypractice have tobeextrapolatedandoptimizedacrossalarger lactophenol (x10, mite cotton bluestaining). scabies adult an showing (A), in patient from scraping skin of examination Direct (C) magnification). (10-fold jet” “deltawing lesions. (B) A burrow lesionfrom patient in (A) using dermoscopy showing the “jet-with-contrail” and an image of a brown triangle at the end, the (A) 1. Typical lesionsofordinaryscabies. Fig. Scabies lesions on the palm of the right hand with linear burrows, tiny vesicles and papular scabies Prices, USD Duration of the procedure Negative predictive value, % Positive predictive value, % Specificity, % Sensitivity, % References As yet,asimpletestforscabiesbasedonmolecular – entire body 15 min for the 99.4 87.7 98 96.2 algorithm diagnosis Clinical (49) Table I.Lightmicroscopy US$ 500 30 min 90/77 100/100 100/100 90/46 (55)/(63) microscopy and light Skin scraping – 5 min – – 100 36.6 (64) test Burrow ink - US$ 10 10 min 85 100 100 68 (63) tape test Adhesive living mites. These areexpensivetechniquesandthe magnification and can be used to assess the viability of camera connectedtoacomputerthatallowsveryhigh Videodermatoscopy utilizesadermoscopewithvideo sign representingtheheadofmite(Fig.1C)(55). image ofablackorbrowntriangle,the“delta-wingjet” in theskin,representingamiteanditsburrow, oran by the observation ofthe “jet-with-contrail” pattern The diagnosis of scabies using dermoscopy is confirmed taneous disorders,includingparasiticinfestations(54). while most studies have found a very high specificity,high very a found have studies most while or PCR specifically targeting scabies DNA. With PCR, – time of flight (MALDI-TOF), antigen detection system tools, such as matrix-assisted laser desorption ionization tried to develop diagnostic techniques using molecular this devicehasbeendescribed(57). Some authorshave the skin.Imagingofscabiesmitesandeggsusing resolution to penetrate to a depth of 200–300 µm into nm wavelength diode laser and provides high optical melanoma from benign naevi. The system uses an 830- for pigmentedskinlesions,todifferentiate malignant confocal microscopy has been developed more recently Reflectance (56). scabies of assessment medical the in used inbotanicalorentomologyinvestigation,foruse refore someauthorshaveadaptedlow-costequipment, clinical practicebydermatologistsforavarietyofcu US$ 500–700 entire body 5–10 min for the 90/85 88/47 86/46 91/83 (55)/(63) (dermoscopy) microscopy Epiluminescence Management ofscabiesinthe21 Theme issue: Cutaneous and genital infections US$ 25,000 entire body 5–10 min for the 95 97 97 95 (65) Videodermatoscope US$ 150,000 for each lesion 60 s to10 min 92 100 100 92 (65) microscopy confocal Reflectance st century

US$ 200 Half a day –/61.7 –/100 100/100 75.7/37.9 (59)/(66) method PCR-based 227 - - Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Theme issue: Cutaneous and genital infections evaluation, buttheconclusions weredifferent basedon in 2010 and 2017, no newer trials were included in the ments. Betweenthese2systematic reviews,performed and areconsequentlyconsidered asthereferencetreat safety, and efficacy of level same the at ivermectin and controlled trials (RCTs) placed topical 5% permethrin data fromrespectively22(76)and15(77)randomized day 15). Two recent Cochrane systematic reviews of adult stagethatcanbefertilized(atday5–8,maximum 2–4 ofthemitelife-cycle)anddevelopment a shortwindowbetweenlarvalhatching(occurringatday 2-dose regimenstillneedstobeoptimizedandshould not eggs(13). The optimalintervalbetweendosing inthe only against mobile stages(larva,nymphand adults) and and muscle function of the parasite, and they are active cacy (74,75).Mostscabicidesactbyaffecting thenerve absorption and,accordingly, thismightincreaseitseffi content mealhasbeenproposedinordertoincreaseits scabies model(72,73).Givingthedrugwithahigh-fat which was shown in 2 experimental trials in a porcine drug (71)andtheshorthalf-lifeofivermectininskin, could beexplainedbythelimitedovicidalactivityof rates ofcompletecureifgivenonlyonce(68–70). This dard doseof0.2mg/kgandmaybeassociatedwithlower appear tobelimited.Oralivermectinisgivenatastan reported withalltopicalmedicinesforscabies,butthey instructions from the manufacturer. Adverse eventsare specific the on depends period application The mouth. surface, from“head-to-toe”,avoidingtheeyes,nose,and (67). Topical agents should be applied to the entire skin or eczematousskin,forpatientswithcrustedscabies recurrent, difficult-to-treat cases, those with superinfected oral ivermectin in 1981, which was, at first, reserved for of arrival the until treatment first-line considered were scabies aresummarizedinTable II.Topical medicines family contacts. The optionsavailablefortreatment of of scabies,andshouldbegiventoallhousehold cases confirmed all for prescribed be must Treatment Treatment ofsmallclusters(individualandfamilylevel) HOW CANWETREAT SCABIES? further. tools havebeendeveloped,butwilltobeimproved diagnosis ofscabiesiscrucial.Non-invasivediagnostic definitive and accurate the Thus, treated. be to need patients which of identification better from come will dermatological skills. and rapidmethodtoidentifymiteinfectionwithout diagnostic kits have been developed for use as a simple examination(61).Nobiomarker-baseddermoscopic with parasiteobservationeitherbymicroscopicor ranging from30%to60%(58–60),poorercompared often closeto100%,sensitivitywascontinuallylow, 228 Improvement in scabies management is essential and C. Bernigaudetal. - - -

Table II. Comparison of treatments in use to treat scabies in humans

Efficacies Use during Use in breastfeeding Drugs Formulations Recommended treatments Cost (Euros) (%)* Main adverse reactions Use in children pregnancy women

Ivermectin 200 µg/kg Repeat after 7 days €19 for 4 tablets at 3 mg=€38 70–100 Nausea, rash, dizziness, itching, Not approved in Only Only recommended in Pills for a complete treatment (weight eosinophilia, abdominal pain, fever, children <15 kg or 5 recommended in France 70 kg) tachycardia years of age France 1% Overnight (8–12 h) – from €20 for 15 g cream=€80 for a 69–85 Pruritus, burning, stinging, eczema Not approved in Not Not recommended Cream/lotion head-to-toe – repeat once after complete treatment children recommended 7–14 days Permethrin 5% Overnight – from head-to-toe – €19 for 30g cream=€38 for a 86–100 Pruritus, burning, stinging, eczema Safe in children ≥2 Approved Not recommended Cream repeat once after 7–14 days complete treatment months of age Benzyl benzoate 10–25% Apply from head-to-toe for 24 €15 for 125 mL emulsion=€30 48–92 Pruritus, burning, stinging, pustules, Safe in children ≥ 1 Authorized if Not recommended Lotion or emulsion h On days 1, 2 and repeat after for a complete treatment skin irritation, eczema month of age necessary 7 days Crotamiton 10% Overnight on days 1 and 2 €7 for 40g cream 63–88 Pruritus, skin irritation, eczema, Safe in children Not Not recommended Cream erythema, anaphylactic reaction recommended Precipitated 6–33% Apply from head-to-toe for 3 – 39–100 Messy application, malodour Safe in children Authorized – sulphur Cream or lotion consecutive nights Malathion 0.5% Repeat after 7 days €12 for 100 ml=€24 for a 47–72 Pruritus, burning, stinging, skin Not approved in Withdrawn from Withdrawn from the Aqueous lotion complete treatment irritation, CNS toxicity, dizziness, children <2 years the European European market seizure of age market Lindane 1% Overnight Repeat after 7 days – 64–96 CNS toxicity, dizziness, seizures, Withdrawn from the Withdrawn from Withdrawn from the Lotion or cream renal and hepatic toxicity reported European market the European European market with overdosage market

*Efficacies according to Strong & Johnstone (76). Updated from Bernigaud C. et al. (13). CNS: central nervous system. Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV two weeks.Itchingcanpersistforuptoonemonthaf Treat the cureofpatientandtopreventre-infestation. algorithms, based on high-throughput experimental data algorithms, basedonhigh-throughput experimentaldata order to optimize cure rates. Simplified and generalized and incasesofseverescabies withhighmite-load,in of the treatment (88) in non-profuse cases of scabies environment-decontamination proceduresonthesuccess scabies. Studiesareneededtoevaluatetheimpactof fomites isthoughttoberare(3),atleastincommon with scabies(87),theindirecttransmissionofmitesby environmental dust from floors and furniture of patients failure. While livingmitescanbefoundinsamplesof of furnitureorfomiteswasakeyfactorintreatment These 2studiesfoundthatincorrectdecontamination factors were associated with treatment failure (85, 86). (77)). Someauthorsrecentlytriedtodeterminewhich is observedwithpermethrinand68–86%ivermectin arenot100%effective drugs because (74– 93%clearance warranted. Treatment failurehasbeen observed,mainly are lackingandsurveillanceforbetterdocumentationis clinical importance remains a matter of debate. Studies both permethrin (81, 82) and ivermectin (83, 84), but its contacts (80).Parasiteresistancehasbeenreportedfor nails, andre-infestationfromscabies-infestedclose penetration of the agent into hyperkeratotic skin or agent, incorrectapplicationofthetopicalpoor diagnosis,dermatitis secondary to themite or topical failure withaneffective treatmentincludeincorrect ter successfultreatment.Causesofapparenttreatment the 21 medication, inJune2019the WHO addedivermectinto and benzyl benzoate. To widen access to this keyeffective medications are preferred, such as sulphur preparations other countries.Inthosecountries,availableandcheaper mostly usedoff-label andmaynotevenbeaccessiblein this indication in 10 nations as first-line treatment, and is scabies in2001,oralivermectinhas been licensed only for since it was first approved in France for the treatment of lability ofthedrugindifferent countries.Forexample, NCT02407782) (78). Treatment also depends on the avai (SCRATCH,days’efficacious 10 most at the is interval permethrin or0.2mg/kgoralivermectin,bothgiventwice topical 5% treatment, which finally establish to scabies protocol, is currently recruiting patients with common randomized clinical trial,cluster-designed with a robust French evaluate. A to difficult conclusions the making in themethodsandoutcomemeasurementswasfound, the therapeutic trials analysed, a significant heterogeneity ivermectin when 2 doses were given. Overall, among all in 2010,concludedthattopicalpermethrinwasequalto sumeck etal.in2017(77),reviewingthesametrialsas Ro scabies. of treatment the for agent efficacious most concluded, in2010,thattopicalpermethrin5%wasthe the regimenofdrugsused.Strong&Johnstone(76) Follow-up isnecessaryaftertreatment,toevaluate ment success should be expected in approximately st WHO EssentialMedicinesList(79). - - -

children (aged1–64months,bodyweight4–14.5kg) reports using ivermectinoff-label in infants andyoung if thepatient’s bodyweightislessthan15kg.Recent differ fromthatinadults.Oralivermectincannotbeused have beenapproved. The application timeinchildrencan permethrin andkeratolytictherapy. multiple dosesoforalivermectinwithrepeatedtopical fested patientsareseen(47). They suggestaregimenof and experienceinnorthern Australia, wherehighlyin been performed.Mostrecordscomefromsmallstudies, sensus as,todate,norandomizedcontrolledtrialshave The first MDA was performed in a scabies-endemic a in performed was MDA first The has emerged tocontrolscabiesinendemicspaces(96). high insomecommunities, theopportunityofMDA at thesametimeandbecause prevalencecanbevery patients andtheirclosecontacts havetobetreatedall at greaterrisk.In these collectivitysettings,because skin contact, people living in crowded communities are As scabiesisacontagiousdiseasespreadbyskin-to- Treatment oflarge clusters(collectivitylevel) target populationtobetreatedadequately. sary, aswellmorefundamentalworktoenablethis neces is surveillance Continued 95). (94, significantly birth defectsinthereferencepopulationdidnotdiffer mes in Africa. Occurrenceofmiscarriage,stillbirth,or becomes knowninonchocerciasiseradicationprogram have been treated inadvertently before their pregnancy cipated foetaltoxicity. Inpractice,thousandsofwomen treatment areforbasicprecautionratherthananyanti tion (93).Mostexclusionsofwomenfromivermectin of thepregnancysupportedbyanexpertrecommenda treatment after5%topicalpermethrin,atanytrimester country allowstheuseofivermectin,asasecond-line future. Forthetreatmentofpregnantwomen,onlyone for use of ivermectin in infants may change in the near treatment inthisagegroup(92).Recommendations this of efficacy and safety the on reassuring highly are an anti-pruriticmechanism(91). is theirsedativepropertiesthatareeffective, ratherthan is no specific treatment. Antihistamines can assist, but it may beusedinnon-tropicalregions.Fortheitch,there pristinamycin, amoxicillin/clavulanicacidorcephalexin G areusedintropicalendemicregions(90),whereas (cotrimoxazole) orintramuscularbenzathinepenicillin trimethoprim-sulphamethoxazole Oral areas). specific have totarget GASandS.aureus (includingMRSA in in caseswithprofuselesions.Systemicantibiotics (e.g. mupirocinorfusidicacid)arenotrecommended secondary bacterialinfection. Topical antibioticcreams resource-poor population, were suggested recently (89). that canbeusedinalarge rangeofsettings,including For thetreatmentofchildren,onlytopicaltreatments For thetreatmentofcrustedscabies,thereisnocon Appropriate treatmentshouldalsobegivenforsevere Management ofscabiesinthe21 Theme issue: Cutaneous and genital infections st century 229 ------

Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV Theme issue: Cutaneous and genital infections 1 to understand factors associated with success, defining mization ofthese programmes will be required in order in highlyendemicpopulationsonalarger scale.Opti to encourageMDA withivermectintocontrolscabies grammes providepositiveresultsandrobustevidence the SolomonIslands(106). All theseinterestingpro (105) and Anopheles farauti,thevectorofmalariain have been found to be efficient in controlling head lice had additionalunintendeddownstreameffects, asthey (104). Remarkably, MDAsforscabies control have feasible andsecurein26,188enrolledparticipants vince, SolomonIslands,wasalsofoundtobeeffective, for targeting trachomaandscabiesintheChoiseulPro the co-administrationofazithromycinandivermectin were foundtobeeffective andsafe.Onalarger scale, (103) strongyloidiasis and scabies or (102), filariasis filariasis and onchocerciasis, or scabies and lymphatic and albendazole administration to treat both lymphatic helminths. Onasmallerscale,combiningivermectin orinfectionwithsoil-transmitted yaws, schistosomiasis, such as onchocerciasis, lymphatic filariasis, trachoma, ted tropical diseases eradication programmes (101), ported onlyfrom Australia (see of oral ivermectin (summarized in with lindane,topicalpermethrin,followedbytheuse firstly MDA, by scabies control to world the of parts Successively, multipleprogrammeshaveevolvedinall region 230 or endemicsettings.Controversialresultshavebeenre reduction intheprevalenceofscabieshighlyendemic programmes have resulted in successful and significant 67% inimpetigo.Duringalltheseyears,manyMDA 94% from baseline in the prevalence of scabies and to bethemosteffective, witharelativereductionof months, masstreatmentwithivermectinwasfound compared with standard care as control (36). At 12 strategies, i.e.oralivermectinandtopicalpermethrin, has randomized3islandsinFijito1of2intervention trial, theSkinHealthInterventionFiji Trial (SHIFT) to integratescabiesMDA inotherschemesforneglec disease, some programmes have looked at the potential impetigo (37). Although, as most MDAstarget onlyone during MDA forscabiestoreducetheprevalenceof indicated that it is not necessary to add antibiotics the reductioninhaematuria(30). A recentstudyhas by signified complications, kidney and (36) impetigo GAS in reduction significant a in result to seems also 5% (100).Interestingly, thetreatmentofscabies alone in communitieswithascabiesprevalencehigherthan this approach seems to be efficient (98, 99), especially ofMDA ofsuccess sustainability inthelongerterm,but treatment regimenwaspoor. Fewerdataexistonthe because the adherence of the target population with the https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3468 C. Bernigaudetal. of Panamainthe1970sby Taplin etal.(97). Table SI Table SI 1 ), presumably 1 ). Only one - - - - - As mentionedabove,treatmenteitherwithatopicalaca FUTURE? HOW WILLWETREAT SCABIES INTHENEAR seekers (109). age-care facilities(18),and,morerecently, inasylum closed institutions,suchasschools(107),prisons(108), MDAs hasbeenextrapolatedforsmalleroutbreaksin potential toconducttranslationalpreclinicalandphar an experimental porcine scabies model provides real life cycleofthemite(13). The recentdevelopment of eggs, andhalf-livestooshorttocoverthewhole14-day ance withrepeatedtreatments,limitedactivityagainst major limitationsofcurrenttherapiesarepoorcompli and/or acombinationoftopicalandsystemicdrugs. The tervention, but patients often require multiple treatments scabies infectionwillrecoverwithasuitablemedicalin standards ofcare forcommon scabies. Most patients with ricide ororaltreatmentwithivermectinarethecurrent found tobepoorlyeffective. Furtherstudiesfoundthat of oral ivermectin (0.2mg perkgbodyweight) was first raised for head lice infestation, as the standard dose dose ofivermectintoachieve acure. This concept was thesis is that theparasite infection may need a higher a reasoned,butarbitrary, decision. An emerging hypo after high-leveldose-rangingstudies;itwasbasedon been rushed,andthedoseof0.2mg/kgwasnotderived ivermectin forscabiesandotherparasitesmighthave under investigation(118). The clinicaldevelopmentof of scabies is also an interesting option and currently single-dose treatmentforscabies(NCT03905265)(117). France, withtheaimofdevelopingmoxidectinasanew phase IItrialinhumansisprogress Australia and 1-week interval(0.2mg/kg)(72). A multicentreclinical fective than the conventional 2 doses of ivermectin at at asingledoseof0.3mg/kg,wasfoundtobemoreef for scabiesperformedinFrance,moxidectinusedorally, bies mite.Inapilottrialintheexperimentalpigmodel (72), potentiallycoveringtheentirelife-cycleofsca in plasmaand,importantly, intheskinthanivermectin absorption, large distribution,andamuchlongerhalf-life rapid profile: pharmacological interesting very a has tion (FDA)fortreatmentofonchocerciasis.Moxidectin ped andapprovedbytheUSFoodDrug Administra the samefamilyasivermectin,andwasrecentlydevelo pound suitable for oral administration. It is a member of was investigated(72,73).Moxidectinisamoleculecom existing drugsusedintheveterinaryclinictohumans options for scabies treatment,the concept of translating macokinetic studieswithnewdrugcandidates. numbers ofroundsMDA (24). the appropriate regimen to use, and determining the Similarly, controllingscabiesatalarger scaleby The useofhigherdosesivermectinfortreatment In ordertooptimizeandimprovethetherapeutic

------Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV REFERENCES authors havenootherpotentialconflictsofinteresttodeclare. tific advisors for Medicines Development for Global Health. The Dermatologie andMSDFrance.CBOCactasunpaidscien Dermatologie and lecture fees from Zambon Laboratoire, Codexial ceived drugs,donatedfreeofcharge, forresearchfromCodexial Laboratoire DermatologiqueandCodexialDermatologie.OCre Conflicts of interest: CBreceivedresearchsupportfromBioderma ACKNOWLEDGEMENTS and theirfamilies. enhance the therapeutic options for the benefit of patients with scabies,andthatnewdrugsdiagnosticswill infested patients for improvement significant a provide body formedin2012. We hopethatthenext10yearswill of scabies, mainly driven by IACS, a global advocacy work hasbeencompletedconcerningthemanagement at thebeginningof21stcentury, alotofimportant effective tocontrolthedisease.Duringpast20years, sufficiently be not may treatments available currently The worldwideprevalenceofscabiesremainshigh,and CONCLUSION immediately andshouldbetailoredtoscabiesmites. therapeutic tools. These next-generation drugs are needed and biochemical technologies will help to design new genic fungus(123). 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