Efficacy of monthly treatment with oral fluralaner (Bravecto® 1-Month) against Tunga penetrans in dogs in Brazil: a randomized, double-blind, controlled field study.

BACKGROUND: Tungiasis is a neglected tropical disease caused by the adult female sand flea (Tunga penetrans). Dogs are considered important reservoirs of T. penetrans in Brazil. The aim of this study was to determine the monthly insecticidal efficacy of a single oral administration of fluralaner at a dose of 10-18 mg/kg (Bravecto® 1-Month, also registered as Defenza® in some countries; MSD Animal Health) in dogs naturally infested with T. penetrans. METHODS: This clinical trial was conducted in a rural community located in Ilhéus, Bahia, Brazil. A total of 64 dogs were selected and distributed in a completely randomized design between a treated group (TG) that received one single dose of Bravecto® 1-Month (Defenza®) and a negative control group (CG) that received no treatment. Each group was composed of 32 dogs. The evaluations took place on days 0, 7 ± 2, 14 ± 2, 21 ± 2, 28 ± 2, 35 ± 2, and 42 ± 2 post treatment, in which the dogs were inspected to evaluate the infestation stage and classify lesions associated with tungiasis. The primary efficacy was determined from the percentage of treated dogs free of fleas (stage II and III lesions) after administration of the formulation at each evaluation time. Secondary efficacy was based on the number of active lesions (stages II and III) in each group at each evaluation time. The clinical condition of the animals was defined based on the Severity Score for Acute Dog Tungiasis (SCADT), which is related to the number and severity of lesions. RESULTS: The primary efficacy of the product was greater than 95.0% from days 7 to 21 and reached 100.0% between days 28 and 42, with a significant association between treatment and infestation decline (P < 0.025) between days 7 and 42. Secondary drug efficacy was greater than 99.9% from days 7 to 21, reaching 100.0% between days 28 and 42 (P < 0.05). The treated dogs also scored lower on the SCADT than the control animals did during the entire clinical evaluation period (P < 0.05). CONCLUSIONS: A single administration of Bravecto® 1-Month (Defenza®) was effective in eliminating Tunga penetrans infestations, as well as in preventing parasitism for at least 42 days after treatment.

Successful treatment of 3 naturally acquired cases of canine cheyletiellosis with fluralaner.

Three dogs were diagnosed with naturally occurring cheyletiellosis based on clinical signs and visualization of parasites and ova. Treatment with fluralaner (orally) resulted in a rapid resolution of clinical signs with no evidence of mites or ova at 1 or 2 mo post-treatment. This is apparently the first published report of an isoxazoline being used to successfully treat cheyletiellosis in veterinary medicine. Therefore, fluralaner may be an effective option for treatment or prevention of canine cheyletiellosis, although research is needed to confirm its effectiveness for treatment of cheyletiellosis in dogs and other species. Key clinical message: This is apparently the first published report of an isoxazoline being used to successfully treat cheyletiellosis in companion animal practice. These parasites are both contagious and zoonotic and there are currently no approved products for treatment or prevention of cheyletiellosis.

Traitement réussi de 3 cas de cheylétiellose canine acquis naturellement avec du fluralaner. Trois chiens ont été diagnostiqués avec une cheylétiellose acquise naturellement sur la base des signes cliniques et la visualisation des parasites et des œufs. Un traitement avec du fluralaner (oralement) a résulté en une résolution rapide des signes cliniques sans aucune évidence de mites ou d'œufs à 1 ou 2-mois post-traitement. Ceci semble être le premier rapport publié d'un isoxazoline utilisé pour traiter avec succès la cheylétiellose en médecine vétérinaire. Ainsi, le fluralaner serait une option efficace pour le traitement ou la prévention de la cheylétiellose canine, bien que de la recherche soit nécessaire pour confirmer son efficacité pour le traitement de la cheylétiellose chez les chiens et les autres espèces.Message clinique clé :Ceci semble être le premier rapport publié de l'utilisation d'un isoxazoline pour traiter avec succès la cheylétiellose en pratique des animaux de compagnie. Ces parasites sont contagieux et zoonotiques et il n'y a à l'heure actuelle aucun produit approuvé pour le traitement ou la prévention de la cheylétiellose.(Traduit par Dr Serge Messier).

The effect of educational intervention on efficacy of 1% permethrin shampoo and 4% dimeticone lotion to treat head lice infestation using propensity score matching (PSM).

BACKGROUND: Head lice are a main public health problem and the most important human ectoparasites and the use of pediculicides is the most common way to control it. One of the possible causes of treatment failure is the lack of improper application of pediculicide. The aim of this study was to assess the effect of education on efficacy of 1% permethrin or 4% dimeticone lotion to treat head lice infestation. METHODS: This quasi-experimental study included 100 individuals with head lice infestation from comprehensive urban health centers in Ardabil as the intervention group, and 400 individuals from East Azerbaijan and West Azerbaijan provinces as the control group, from April to March 2019. The data collection tools included a demographic questionnaire and an examination recording sheet, which documented the presence of adult lice or nits. Due to the inability to perform random assignment and control for numerous observed covariates, propensity score matching (PSM) was used. RESULTS: The outcome of treatment included elimination of head lice infestation on is 7, and in the case of recurrence, it was considered on days 14 and 30 after treatment. The results showed that the educational intervention program had a significant positive effect on the efficacy of both treatments. The likelihood of improvement was approximately three times greater in the intervention group compared to the control group. CONCLUSION: Participants who received the training intervention (OR = 3.29; CI 95%: 2.21-4.88) were more likely to have a successful treatment than control group. In the case of providing proper training on the use of pediculicides and observing hygiene tips to patients with pediculosis, could help to successful treatment of pediculosis.

Suspected intermediate syndrome in a dog after organophosphate poisoning.

OBJECTIVE: To discuss the clinical presentation and successful treatment of a suspected case of intermediate syndrome due to organophosphate (OP) poisoning in a dog. CASE SUMMARY: Two dogs presented with acute cholinergic signs after ingesting an OP insecticide containing 50% acephate. Clinical signs consistent with acute cholinergic crisis resolved in both dogs within 24 hours postingestion. One dog developed an onset of neurological signs consistent with intermediate syndrome approximately 24 hours postingestion. This patient's clinical signs resolved with the use of pralidoxime chloride. NEW OR UNIQUE INFORMATION PROVIDED: OP poisoning most commonly presents as an acute cholinergic crisis, with rare instances of animals developing intermediate syndrome. Few reports of successful treatment and recovery from intermediate syndrome exist in the veterinary literature, particularly with instances in which 2 dogs within the same exposure setting were treated for acute cholinergic signs and only 1 progressed to an intermediate syndrome. This report also highlights the importance of early intervention with pralidoxime chloride prior to the onset of aging.

Malaria.

Malaria is resurging in many African and South American countries, exacerbated by COVID-19-related health service disruption. In 2021, there were an estimated 247 million malaria cases and 619 000 deaths in 84 endemic countries. Plasmodium falciparum strains partly resistant to artemisinins are entrenched in the Greater Mekong region and have emerged in Africa, while Anopheles mosquito vectors continue to evolve physiological and behavioural resistance to insecticides. Elimination of Plasmodium vivax malaria is hindered by impractical and potentially toxic antirelapse regimens. Parasitological diagnosis and treatment with oral or parenteral artemisinin-based therapy is the mainstay of patient management. Timely blood transfusion, renal replacement therapy, and restrictive fluid therapy can improve survival in severe malaria. Rigorous use of intermittent preventive treatment in pregnancy and infancy and seasonal chemoprevention, potentially combined with pre-erythrocytic vaccines endorsed by WHO in 2021 and 2023, can substantially reduce malaria morbidity. Improved surveillance, better access to effective treatment, more labour-efficient vector control, continued drug development, targeted mass drug administration, and sustained political commitment are required to achieve targets for malaria reduction by the end of this decade.

Prevalence and determinants of malaria infection among pregnant women attending antenatal clinic in Ejisu government hospital in Ghana: A cross-sectional study.

INTRODUCTION: Malaria in pregnancy is a global public health problem with the majority of its impact seen in sub-Saharan Africa. Pregnant women with malaria infection are at risk of adverse maternal outcomes. In Ghana, malaria in pregnancy accounts for about 17.6% of outpatient department attendance. Ashanti region is among the three regions with the highest malaria prevalence in pregnancy, particularly in the Ejisu Municipality. The study, therefore, assessed the prevalence and determinants of malaria infection among pregnant women seeking antenatal care at the Ejisu Government Hospital in Ghana. METHODS: A cross-sectional study design with a convenience sampling technique was used to select 140 respondents for the study. Primary data such as age and residence of respondents were collected using a questionnaire and secondary data such as gestational age and Sulphadoxine Pyrimethamine (SP) administration were collected from clients' maternal health record booklet. Bivariate and multivariate logistic regression analysis were used to assess the association between the malaria infection and the independent variables, and a p-value of < 0.05 was considered statistically significant. RESULTS: The overall prevalence of malaria in pregnancy was 24 (17.1%). Most of the respondents had received counselling and health education 126 (90%), two or more doses of SP 95 (87.2%), Insecticide Treated Net (ITN) 99 (70.7%) and were sleeping under ITN 104 (74.3%). Multivariate logistic regression analysis showed a statistically significant association between malaria infection and sleeping under ITN (AOR = 0.05; 95% CI = 0.01-0.28, p< .001), the use of insecticide mosquito spray (AOR = 0.27; 95% CI = 0.09-0.84, p = .045) and reason for not using ITN due to the use of other preventive measures (AOR = 0.06; 95% CI = 0.01-0.61, p = .017). CONCLUSION: There was a high prevalence of malaria infection among study respondents despite the high usage of preventive measures for malaria in this study. It is therefore crucial that stakeholders in malaria control identify effective strategies to curb malaria transmission globally.

Canine Systemic Insecticides Fluralaner and Lotilaner Induce Acute Mortality of Triatoma gerstaeckeri, North American Vector of the Chagas Disease Parasite.

Chagas disease is a health concern for humans and animals across the Americas, and control options targeting the triatomine vectors of Trypanosoma cruzi, the causative agent of Chagas disease, are limited. Host-targeted interventions may be a useful and underused tool in controlling the spread of T. cruzi from vectors to hosts. Domestic dogs are known to be key bloodmeal hosts for triatomines as well as T. cruzi reservoirs and may be an effective and practical target for host-targeted insecticide deployment. We hypothesized that treating dogs with commercially available systemic insecticides (labeled for flea and tick control) would result in mortality of triatomines after consuming treated blood. We enrolled 16 privately owned dogs into five treatment groups to receive either fluralaner (Bravecto) or lotilaner (Credelio), alone or in combination with ivermectin. Blood from dogs before the initiation of treatment served as controls. Blood was collected 0, 7, 30, 45, and 90 days after the initial canine insecticide treatment and fed to 10 Triatoma gerstaeckeri nymphs through a membrane feeder, and survival was tracked daily for 7 days and weekly thereafter. All triatomines in the control and ivermectin groups survived the initial period, with no significant difference in long-term survival. In contrast, 99.7% of triatomines that fed on blood from dogs treated with either fluralaner or lotilaner died within 3 days. Although the impact of canine treatment on suppressing vector populations is unknown, fluralaner and lotilaner appear to be a compelling option for an integrated vector management approach to triatomine control.

[Epidemiology of malaria in the French Armed Forces]. / Épidémiologie du paludisme dans les armées françaises.

Because of the individual morbidity and lethality and the resulting collective incapacity, malaria has always been a risk for the Armed Forces in operation. The fight against malaria is a real public health plan carried out by the Armed Forces Health Service (SSA) for the benefit of the Forces. This plan has four main components: vector control, which targets larvae and adult mosquitoes of the genus Anopheles, personal vector protection, which limits human-vector contact, chemoprophylaxis, and early diagnosis and treatment of malaria.Since 2001, the epidemiology of malaria in the Armed Forces have suffered from large-scale epidemics during operational engagements in Côte d'Ivoire, Guyana and the Central African Republic. The start of a military operation is accompanied by strategic and logistical priorities that take precedence over prevention. In addition, the rigorous application of personal protection measures remains difficult and even more so in a combat situation.The development of urban malaria in Africa, the use of causal chemoprophylaxis, the alternative to "nothing but insecticides", and the development of efficient diagnostic tools allowing for early and adapted management are the challenges ahead for the SSA.

Effectiveness of a fixed-dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) against Rhipicephalus microplus and sucking lice infesting cattle.

Unmanaged tick and sucking lice infestations negatively impact the health and production potential of cattle. Described herein are two non-interference dose confirmation studies evaluating the efficacy of a single administration of a new fixed-dose combination injectable (FDCI) endectocide consisting of 0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride, against either laboratory-induced Rhipicephalus microplus infestations in Australia or naturally acquired sucking lice (Linognathus vituli) infestations in the US. This FDCI is available as Dectomax V® in Australia and New Zealand and as Valcor® in the United States. To evaluate therapeutic efficacy against R. microplus, 12 calves were each exposed to 10 infestations of ∼5000 larvae per infestation between Days -24 and -2. Calves were either treated on Day 0 with the FDCI or left untreated (control). Additional R. microplus infestations of ∼5000 larvae were conducted on Day 2 and then three times weekly to also evaluate persistent efficacy of the FDCI. Tick collections were conducted daily from Day -3. Group mean live tick counts, egg production, and egg viability were analyzed for significant differences between the two groups. To determine efficacy of the FDCI against lice, 24 cattle with active sucking lice infestations based on Day -7 counts were allocated to two groups and treated on Day 0 with either saline (control) or the FDCI. Lice counts were conducted weekly from Day 14 through 42 and again on Day 56. Mean group lice counts on each count day were compared between treatment groups. In the R. microplus study presented here, cattle in Queensland, Australia treated with the FDCI (Dectomax V®) showed > 90 % reduction in tick counts based on arithmetic means within 48 h of treatment when compared to untreated cattle, and counts were > 95 % reduced from post-treatment Day 5 through Day 30. In the sucking lice study conducted in the US, the FDCI (Valcor®) displayed 100 % efficacy against sucking lice infestations (L. vituli) from first count day (Day 14 post-treatment) through Day 35 and then 99.9 % efficacy through Day 56 post-treatment. No treatment-related adverse events were reported for cattle in either study. Using R. microplus and sucking lice as representative ectoparasites, these studies demonstrate the ectoparasite activity of doramectin is retained in the new FDCI.

Pseudoresistance to permethrin in scabies.

Reports of permethrin resistance of Sarcoptes scabiei var. hominis are emerging. We propose that this may be pseudoresistance. The resistance is due to inadequate counselling by physicians, incorrect treatment (insufficient quantity of permethrin; too short length of treatment), and poor adherence and compliance by patients. Other reasons include single application of permethrin, suggestion to apply the drug for 6-8 hours, failed application on subungual folds, irritant contact dermatitis, in particular on genitals, for which some patients stop the treatment, and unexplainable use of permethrin in post-scabies prurigo. Thus, we believe that several cases of resistance to permethrin are actually cases of pseudoresistance.

Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites.

BACKGROUND: Increasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites. OBJECTIVES: To identify factors contributing to therapy failure. METHODS: Sixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained. RESULTS: Sequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary. CONCLUSIONS: The kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.

Comparative efficacy of chemical and botanical pediculicides in Thailand and 4% dimeticone against head louse, Pediculus humanus capitis.

Head louse infestations remain a global public-health concern due to increased resistance of lice to artificial pediculicides. In Thailand, there is a lack of comparative data on the current efficacy of pediculicides for treating head lice. In this study, we explored the status of botanical and toxic synthetic pediculicides with that of 4% dimeticone liquid gel for treating head lice in Thailand. The ex-vivo pediculicidal activity of various pediculicidal shampoos available at drugstores in Thailand was assessed and compared with that of 4% dimeticone liquid gel. The shampoos chosen were based on active ingredients toxic to lice (1% permethrin, 0.6% carbaryl, 0.15% Stemona root crude extract, or mixed plant extracts), whereas dimeticone acts physically on lice. We found that exposure to 4% dimeticone liquid gel following the manufacturer's instructions completely killed 100% of head lice in 15 min, whereas other pediculicide products failed to kill the great majority of head lice, whether treatment was for 10 min (resulting in 0% to 50.0% mortality) or 30 min (resulting in 17.0% to 60.0% mortality). We also extended a clinical assessment to confirm the efficacy of 1% permethrin for treating head lice in infested schoolchildren. In this clinical assessment, none of the 26 children treated with 1% permethrin shampoo achieved a cure after two applications. These results highlight that 4% dimeticone demonstrated a higher ex-vivo pediculicidal efficacy compared to both chemical and botanical pediculicides in Thailand. Conversely, 1% permethrin showed low efficacy in both laboratory and clinical assessments. Given its physical mode of action, 4% dimeticone merits consideration as an alternative treatment option for lice in Thailand, particularly in cases where treatment with toxic pediculicides has proven ineffective.

The current available diagnostic tools and treatments of scabies and scabies variants: An updated narrative review.

Scabies is a neglected tropical disease that continues to have global impacts and long-term health consequences. It is caused by the mite Sarcoptes scabei var. hominis, which is an obligate ectoparasite that lives in the epidermis of the human skin. Scabies is common in poor communities due to overcrowding in places like old age homes, prisons, and homeless and displaced children. However, developed countries are also susceptible to scabies infestations, such as in institutional outbreaks or small epidemics under war conditions or during natural disasters. The diagnosis of scabies may be assisted by invasive and noninvasive tools; However, the history and examination findings are usually adequate to confirm the clinical suspicion. Here, we present an updated review of scabies by focusing on the diagnostic approaches, treatment, and prevention of scabies.

Permethrin-treated baby wraps for the prevention of malaria in children: Protocol for a double-blind, randomized placebo-controlled controlled trial in western Uganda.

This article details the study protocol for a double-blind, randomized placebo-controlled trial to determine the effectiveness of permethrin-treated baby wraps to prevent Plasmodium falciparum malaria infection in children 6-24 months of age. Participating mother-infant dyads will be randomized to receive either a permethrin-treated or a sham-treated wrap, known locally as a "lesu." After a baseline home visit, during which time all participants will receive new long-lasting insecticidal nets, participants will attend scheduled clinic visits every two weeks for a period of 24 weeks. In the event of an acute febrile illness or other symptoms that may be consistent with malaria (e.g., poor feeding, headache, malaise), participants will be instructed to present to their respective study clinic for evaluation. The primary outcome of interest is the incidence of laboratory-confirmed, symptomatic malaria in participating children. Secondary outcomes of interest include: (1) change in children's hemoglobin levels; (2) change in children's growth parameters; (3) prevalence of asymptomatic parasitemia in children; (4) hospitalization for malaria in children; (5) change in the mother's hemoglobin level; and (6) clinical malaria in the mother. Analyses will be conducted using a modified intent-to-treat approach, with woman-infant dyads who attend one or more clinic visits analyzed according to the arm to which they were randomly assigned. This is the first use of an insecticide-treated baby wrap for prevention of malaria in children. The study began recruitment in June 2022 and is ongoing. ClinicalTrials.gov Identifier: NCT05391230, Registered 25 May 2022.

Effectiveness of fluralaner treatment regimens for the control of canine Chagas disease: A mathematical modeling study.

BACKGROUND: Canine Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and transmitted by insect triatomine vectors known as kissing bugs. The agent can cause cardiac damage and long-term heart disease and death in humans, dogs, and other mammals. In laboratory settings, treatment of dogs with systemic insecticides has been shown to be highly efficacious at killing triatomines that feed on treated dogs. METHOD: We developed compartmental vector-host models of T. cruzi transmission between the triatomine and dog population accounting for the impact of seasonality and triatomine migration on disease transmission dynamics. We considered a single vector-host model without seasonality, and model with seasonality, and a spatially coupled model. We used the models to evaluate the effectiveness of the insecticide fluralaner with different durations of treatment regimens for reducing T. cruzi infection in different transmission settings. RESULTS: In low and medium transmission settings, our model showed a marginal difference between the 3-month and 6-month regimens for reducing T. cruzi infection among dogs. The difference increases in the presence of seasonality and triatomine migration from a sylvatic transmission setting. In high transmission settings, the 3-month regimen was substantially more effective in reducing T. cruzi infections in dogs than the other regimens. Our model showed that increased migration rate reduces fluralaner effectiveness in all treatment regimens, but the relative reduction in effectiveness is minimal during the first years of treatment. However, if an additional 10% or more of triatomines killed by dog treatment were eaten by dogs, treatment could increase T. cruzi infections in the dog population at least during the first year of treatment. CONCLUSION: Our analysis shows that treating all peridomestic dogs every three to six months for at least five years could be an effective measure to reduce T. cruzi infections in dogs and triatomines in peridomestic transmission settings. However, further studies at the local scale are needed to better understand the potential impact of routine use of fluralaner treatment on increasing dogs' consumption of dead triatomines.

Does a One Health approach to human African trypanosomiasis control hasten elimination? A stochastic compartmental modeling approach.

BACKGROUND: . In response to large strides in the control of human African trypanosomiasis (HAT), in the early 2000s the WHO set targets for elimination of both the gambiense (gHAT) and rhodesiense (rHAT) forms as a public health (EPHP) problem by 2020, and elimination of gHAT transmisson (EOT) by 2030. While global EPHP targets have been met, and EOT appears within reach, current control strategies may fail to achieve gHAT EOT in the presence of animal reservoirs, the role of which is currently uncertain. Furthermore, rHAT is not targeted for EOT due to the known importance of animal reservoirs for this form. METHODS: . To evaluate the utility of a One Health approach to gHAT and rHAT EOT, we built and parameterized a compartmental stochastic model, using the Institute for Disease Modeling's Compartmental Modeling Software, to six HAT epidemics: the national rHAT epidemics in Uganda and Malawi, the national gHAT epidemics in Uganda and South Sudan, and two separate gHAT epidemics in Democratic Republic of Congo distinguished by dominant vector species. In rHAT foci the reservoir animal sub-model was stratified on four species groups, while in gHAT foci domestic swine were assumed to be the only competent reservoir. The modeled time horizon was 2005-2045, with calibration performed using HAT surveillance data and Optuna. Interventions included insecticide and trypanocide treatment of domestic animal reservoirs at varying coverage levels. RESULTS: . Validation against HAT surveillance data indicates favorable performance overall, with the possible exception of DRC. EOT was not observed in any modeled scenarios for rHAT, however insecticide treatment consistently performed better than trypanocide treatment in terms of rHAT control. EOT was not observed for gHAT at 0% coverage of domestic reservoirs with trypanocides or insecticides, but was observed by 2030 in all test scenarios; again, insecticides demonstrated superior performance to trypanocides. CONCLUSIONS: EOT likely cannot be achieved for rHAT without control of wildlife reservoirs, however insecticide treatment of domestic animals holds promise for improved control. In the presence of domestic animal reservoirs, gHAT EOT may not be achieved under current control strategies.

Permethrin Steal Effect by Unmasked Corneocytic Keratin in Topical Therapy of Scabies.

INTRODUCTION: The use of epicutaneously applied permethrin in the treatment of common scabies is considered to be the first-line therapy. Due to increasing clinical treatment failure, the development of genetic resistance to permethrin in Sarcoptes scabiei var. hominis has been postulated. In addition, metabolic resistance and pharmacokinetic limitations by parasitic digestion and reactive thickening of stratum corneum are suspected to cause a reduction in cutaneous bioavailability. METHODS: Since lipophilic permethrin is known to form hydrophobic interactions with proteins via van der Waals interactions, a similar interaction was assumed and investigated for permethrin and the protein keratin. Using keratin particles extracted from animal material, a model for hyperkeratotic and parasitic digested scabies skin was developed. Using fluorescence-labeled keratin and ³H-permethrin, their interaction potential was validated by loading and unloading experiments. Additionally, the impact of keratin to permethrin penetration was investigated based on an in vitro model using Franz diffusion cells. RESULTS: For the first time, keratin particles were introduced as a model for dyskeratotic skin, as we were able to show, the keratin particles' interaction potential with permethrin but no penetration behavior into the stratum corneum. Moreover, comparative penetration experiments of a reference formulation with and without added keratin or keratin-adherent permethrin showed that keratin causes a steal effect for permethrin, leading to a relevant reduction in cutaneous bioavailability in the target compartment. CONCLUSION: The results provide further evidence for a relevant pharmacokinetic influencing factor in the epicutaneous application of permethrin and a rationale for the necessity of keratolytic pretreatment in hyperkeratotic skin for the effective use of topical permethrin application in scabies.

Assessment of Dermal and Inhalation Exposure to Permethrin During Field Treatment of Military Uniforms.

INTRODUCTION: Permethrin is a common pesticide spray-applied to civilian clothing and military uniforms for protection against biting arthropods in an effort to reduce risks to arthropod-borne diseases. During mass clothing spray events, exposure is possible through the dermal, inhalation, and ingestion routes. The potentially exposed population during a spray event includes the pesticide applicator(s) and working party (personnel who handle clothing/uniforms by positioning on the ground, flipping, and removing after spraying is complete). Previous investigation is limited regarding permethrin exposure via multiple routes of entry. Additionally, most exposure assessments are limited to pesticide applicators rather than working party that support applicator personnel. The purpose of this investigation was to conduct a multi-route exposure assessment for all personnel normally participating in mass permethrin military uniform treatments. MATERIALS AND METHODS: The protocol and Informed Consent Document were approved by the Uniformed Services University of the Health Sciences (USUHS) Institutional Review Board (IRB) before fieldwork initiation (IRB number: USUHS.2019-032). Sampling occurred during routine spray events performed by 14 U.S. Navy personnel (3 applicators and 11 working party) over 2 days. Personal exposures were measured with dermal sampling, and airborne concentrations were measured with area air sampling. Permethrin area air sampling and analysis were conducted using OSHA Versatile Sampler-2 sampling media (n = 36). Dermal exposure was measured using dosimeter gloves (n = 26) and a dermal patch (n = 26) worn by study participants. RESULTS: All air samples were reported below the 0.4 µg limit of quantification. Glove sample results ranged from 45 to 120,000 µg and patch results ranged from 0.57 to 45 µg. A repeated-measures ANOVA showed non-statistically significant differences in dermal concentrations (P-value = .8340) between the applicators and working party in patches and gloves. CONCLUSIONS: Results suggest dermal contact is the primary route of exposure compared to inhalation when mass spraying clothing with permethrin. Similar dermal exposures between these two occupations may necessitate reconsidering risk assessment procedures, training and personal protective equipment (PPE) requirements for mass spray uniform treatments. Specifically, while PPE requirements for applicators are highly regulated by the Armed Forces Pest Management Board and include items such as Tyvek suits, chemical protective gloves, and air-purifying respirators, PPE was not regulated for working party personnel before this investigation.