Permethrin 5% cream

BACKGROUND: Scabies is a highly contagious parasitic skin disease and a recognised neglected tropical disease with substantial global burden. Permethrin and ivermectin are widely used treatments, yet uncertainty remains regarding their comparative effectiveness. AIM: To systematically evaluate and compare the effectiveness of ivermectin versus permethrin for the treatment of scabies in humans. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies comparing ivermectin with permethrin were identified through searches of PubMed, Embase, Cochrane CENTRAL, Scopus, CINAHL, and ClinicalTrials.gov. Risk of bias was assessed using the updated Cochrane Risk of Bias tool (RoB 2). A random-effects meta-analysis was performed using RevMan version 5.4.1 Only peer-reviewed RCTs involving human participants with clinically diagnosed scabies were included. RESULTS: Seven studies involving 1,216 participants were included. Compared with permethrin, ivermectin was associated with a lower probability of clinical cure at final follow-up (RR = 0.93, 95% CI 0.86-0.99; I² = 61%) and a higher risk of treatment failure (RR = 1.52, 95% CI 1.06-2.20; I² = 0%). CONCLUSION: Permethrin demonstrates a modest advantage over ivermectin in achieving clinical cure and reducing treatment failure. Ivermectin remains a useful alternative where topical therapy is unsuitable, but optimised dosing regimens are essential. CLINICAL TRIAL NUMBER: Not applicable.

Abstract licence: CC BY-NC-ND

Background and Objective: Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies. Methods: We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty. Results: Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve. Conclusion: Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.

Abstract licence: CC BY-NC-ND

Background: Scabies may cause community outbreaks without early diagnosis and appropriate treatment. Oral ivermectin offsets some of the challenges associated with topical 5% permethrin application for treating scabies. We aimed to evaluate the efficacy of two doses of oral ivermectin (200 µg/kg) on day one and day seven compared to 5% (weight/volume [w/v]) once whole-body application of permethrin lotion in treating scabies. Materials and Methods: We recruited 100 participants with mild or moderate scabies and randomized them into ivermectin and permethrin arms using computer-generated sequences. Participants and their contacts in the ivermectin arm received two doses of ivermectin (200 µg/kg) on day one and day seven. Participants and their contacts in the permethrin arm received treatment with 5% (w/v) permethrin application over the whole body. The participants were followed up after 4-6 weeks of the intervention to determine the cure rate. Results: We got a similar cure rate among the scabies patients who received either ivermectin (90.70%) or permethrin (93.33%). The cure rate was 100% after one dose of whole-body application of permethrin or two appropriate doses of ivermectin among mild to moderate cases of scabies. The cost was lower in the ivermectin arm than in the permethrin arm. Conclusion: The cure rates of scabies with one local application of 5% permethrin lotion and two doses of oral ivermectin tablets are similar. Ivermectin has an added advantage that the cost is lower and its usage is convenient.

Abstract licence: CC BY-NC-SA

Abstract Insecticide spraying is a common strategy for controlling dengue outbreaks, but its effectiveness is compromised by the development of resistance in mosquito populations. In this study, we subjected a strain of Aedes aegypti known for its exceptional ability to develop resistance to controlled permethrin and lambda-cyhalothrin insecticides pressure using two different concentrations. We analyzed resistance mechanisms that are enhanced at each concentration and used RNA sequencing to identify transcripts specifically associated with these exposure levels. Our objective was to uncover the molecular mechanisms triggered by different insecticide concentrations and to distinguish responses between type I and type II pyrethroids, which differ in chemical structure. Our results showed that kdr mutations confer only moderate levels of resistance, as do detoxifying enzymes. For lambda-cyhalothrin, we identified genes involved in the electron transport chain, mitochondrial function, and overall responses to oxidative stress. tRNA transcripts were also upregulated, along with mitochondrial and stress-response transcripts, suggesting a metabolic shift, particularly toward maintaining homeostasis under oxidative stress. These changes point to mechanisms that sustain resistance to this type II insecticide beyond direct detoxification in this population. On the contrary, permethrin induced marked overexpression of cuticle genes, CYP450 genes (especially CYP4), and Odorant Binding Proteins. These expression patterns, together with metabolic enzymes, point to detoxification, reduced penetration, or even sequestration of insecticide, all of which intensify with increasing concentrations. This overregulation of genes suggests an integrated response complemented by classical metabolic detoxification and accompanied by overregulation of mitochondrial complexes. We showed that despite the shared mode of action of the insecticides permethrin and lambda-cyhalothrin, they elicit distinct responses in this Ae. aegypti population. We also showed that the transcriptomic response depends on insecticide concentration and may modulate insecticide tolerance. This article advances understanding of the complexity of pyrethroid resistance in Aedes aegypti and underscores the importance of considering both the insecticide type and the concentration used in vector control programs. Author summary Aedes aegypti mosquitoes transmit dengue and other arboviruses, being a major public health problem in tropical regions like Colombia, where control relies on pyrethroid insecticide spraying. Based on reports of inconsistent results in the field due to different effects of insecticide concentrations, we recreated variable doses by exposing a resistant Colombian Aedes aegypti strain to low (LC25) and high (LC75) concentrations of permethrin (type I) and lambda-cyhalothrin (type II) to identify concentration-dependent resistance mechanisms. Using genetic mutation analysis, enzyme activity assays, and RNA sequencing, we identified the molecular mechanisms these mosquitoes use to survive. Knockdown resistance (kdr) and detoxification enzymes contributed to some extent to resistance but varied by insecticide type and concentration. RNAseq identified that lambda-cyhalothrin upregulated genes for mitochondrial energy production, oxidative stress defense, immune signaling, and transfer RNAs, facilitating homeostasis under chemical stressors. Permethrin instead upregulated genes for cuticle thickening, cytochrome P450 enzymes, and odorant-binding proteins, which are associated with improved penetration barriers, and metabolic breakdown that intensified with higher concentrations. This reveals pyrethroid resistance as complex beyond classic mechanisms, as even low field doses favor stress tolerance or physical defenses to evade sprays. We detected transcripts that improve survival at high concentrations and could be selected in these mosquitoes. Carefully selecting the type of pyrethroid to be used and the dose should be an important factor in vector control. This optimizes current interventions, prolongs their efficacy, and aids researchers in modeling resistance to protect communities.

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This is a cross‐sectional study that is aimed at evaluating the efficacy of antilice shampoo against head lice infestation in primary schoolgirls at level 3–6 (aged between 9 and 12 years) with a high prevalence of infestation in Pathum Thani Province and which also reported a current prevalence of lice infestation in this school. The study was conducted during January–March 2023. A total of 356 schoolchildren were screened for lice infestation. The prevalence rate of lice infestation was found in 78 students (21.9%) from all schoolchildren. Girls (50.3%) showed a higher rate of lice infestation than boys (0.5%) with a significant difference ( p < 0.05). Most lice‐infested girls (100%) reported itching. Seventy‐two of 77 infested girls (93.5%) agreed to use shampoos for lice treatment. Two types of commercial shampoos were considered for lice treatment: (1) chemical (permethrin 0.5% W/V) antilice shampoo and (2) herbal antilice shampoo, since it is cheap and available in the market. The results of chemical (permethrin 0.5% W/V) antilice shampoo showed similar efficacy for lice treatment as herbal antilice shampoo with no significant difference in statistics ( p > 0.05). Using the antilice shampoos consecutively 3 times demonstrated the highest efficacy of treatment (73.0%), followed by 2 times (34.3%), and the lowest efficacy of treatment was a single application (5.6%). No serious side effects from both shampoos in participants: 2 cases of itching and 1 case of the burning sensation. This indicated that in the area of the high prevalence of lice infestation, herbal antilice shampoo might be an alternative choice for lice treatment. However, we recommended using it once a week 3 times consecutively to reach the highest efficacy for treatment. In addition, this treatment should be extended to family members with lice infestation.

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Mosquito-borne viral diseases such as dengue fever, chikungunya, and yellow fever have been documented in Ethiopia since the 1960s. However, the efficacy of public health insecticides against Aedes aegypti that transmits these viruses remains poorly understood in the country, particularly in the Afar Region. Thus, the aim of the study was to assess the susceptibility status of Ae. aegypti to deltamethrin, permethrin, alpha-cypermethrin, pirimiphos-methyl, bendiocarb, and propoxur insecticides. Larvae and pupae of Aedes species were collected from Awash Arba, Awash Sebat, and Werer towns of the Afar Region of Ethiopia during July-October 2022, brought to the Aklilu Lemma Institute of Pathobiology, insectary and reared to adults. Non-blood-fed, 3-5 days-old females Ae. aegypti were exposed to pyrethroid, carbamate, and organophosphate insecticide impregnated papers in tube test following the standard guidelines. Knockdown rates were noted at 10 minutes interval until one hour. The mortality in mosquitoes was recorded 24 hours after 60 minutes of exposure. The mortality rates of Ae. aegypti exposed to propoxur were 87% in all the study towns. Similarly, 88% mortality in Ae. aegypti was recorded when tested with bendiocarb in Awash Sebat and Awash Arba towns. Suspected resistance of Ae. aegypti (95% mortality) to alpha-cypermethrin was observed in Awash Arba town. However, Ae. aegypti collected from all the three sites was observed to be susceptible to deltamethrin, permethrin, and pirimiphos-methyl. Ae. aegypti was resistant to 0.1% bendiocarb and 0.1% propoxur and possibly resistant to 0.05% alpha-cypermethrin. On the other hand, it was susceptible to 0.05% deltamethrin, 0.75% permethrin, and 0.25% pirimiphos-methyl. Thus, vector control products with deltamethrin, permethrin, and pirimiphos-methyl can be used in the control of adult Ae. aegypti in the Afar Region of Ethiopia. However, further studies should be carried out to evaluate the susceptibility status of Ae. aegypti to alpha-cypermethrin in the Awash Arba area.

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BACKGROUND: Plague, caused by the bacterium Yersinia pestis, remains an important disease in Madagascar, where the oriental rat flea, Xenopsylla cheopis, is a primary vector. To control fleas, synthetic pyrethroids (SPs) have been used for >20 years, resulting in resistance in many X. cheopis populations. The most common mechanisms of SP resistance are target site mutations in the voltage-gated sodium channel (VGSC) gene. METHODOLOGY/PRINCIPAL FINDINGS: We obtained 25 collections of X. cheopis from 22 locations across Madagascar and performed phenotypic tests to determine resistance to deltamethrin, permethrin, and/or dichlorodiphenyltrichloroethane (DDT). Most populations were resistant to all these insecticides. We sequenced a 535 bp segment of the VGSC gene and identified two different mutations encoding distinct substitutions at amino acid position 1014, which is associated with knockdown resistance (kdr) to SPs in insects. Kdr mutation L1014F occurred in all 25 collections; a rarer mutation, L1014H, was found in 12 collections. There was a significant positive relationship between the frequency of kdr alleles and the proportion of individuals surviving exposure to deltamethrin. Phylogenetic comparisons of 12 VGSC alleles in Madagascar suggested resistant alleles arose from susceptible lineages at least three times. Because genotype can reasonably predict resistance phenotype, we developed a TaqMan PCR assay for the rapid detection of kdr resistance alleles. CONCLUSIONS/SIGNIFICANCE: Our study provides new insights into VGSC mutations in Malagasy populations of X. cheopis and is the first to report a positive correlation between VGSC genotypes and SP resistance phenotypes in fleas. Widespread occurrence of these two SP resistance mutations in X. cheopis populations in Madagascar reduces the viability of these insecticides for flea control. However, the TaqMan assay described here facilitates rapid detection of kdr mutations to inform when use of these insecticides is still warranted to reduce transmission of plague.

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Pyrethroid resistance continues to undermine malaria vector control across Africa, particularly in agricultural hotspots where insecticide pressure is high. However, the molecular mechanisms enabling Anopheles gambiae to survive extreme pyrethroid doses remain poorly understood. This study investigates transcriptomic responses, allele‑frequency shifts, and selection signatures associated with high‑ permethrin resistance intensity in An. gambiae from Mangoum, Cameroon. RNA‑seq analyses revealed strong overexpression of detoxification genes in both unexposed and permethrin‑exposed field mosquitoes. The UDP‑glycosyltransferase UGT308G1 showed the highest expression levels (FC = 105.1 in C–S; 50.8 in R–S). Within the P450 family, members of the CYP6Z cluster were markedly overexpressed, notably CYP6Z3 (FC = 68.8 in C–S; 41.4 in R–S), CYP6Z2 (FC = 29.0; 17.2), and CYP6Z1 (FC = 12.3; 6.0). Additional detoxification genes such as CYP9K1 (FC = 11.3; 4.7), CYP6M2 (FC = 8.5; 3.8), and the cuticle‑associated CYP4G17 (FC = 2.9; 2.5) were strongly upregulated. Increasing permethrin doses (1 × , 5 × , 10 ×) induced further upregulation of oxidative‑stress, mitochondrial, and translational pathways. Gene‑level population‑genetic metrics revealed strong selective sweeps at VGSC and across the rp1 region. High‑frequency nonsynonymous variants in CYP6AA1 (Ser395Thr), CYP6AA2 (Asn327Asp), CYP6P1 (Ile168Val and Leu374Met), and the validated marker Glu205Asp-CYP6P3 were nearly fixed in field populations and absent in lab susceptible strain, consistent with long‑term selection and hitchhiking. Additional metabolic variants in CYP12F2, UGT49A3, UGT308A2, and ABCA2 occurred at moderate to high frequencies and distinguished resistant from susceptible genetic backgrounds. RNAi‑mediated silencing of CYP6Z1, CYP6Z2, CYP6Z3, and CYP6Z4 significantly increased mortality under permethrin and alpha‑cypermethrin 1X, 5X and 10X exposure, confirming the functional involvement of the CYP6Z family in resistance escalation. High pyrethroid resistance intensity in An. gambiae arises from strong target‑site selection coupled with extensive metabolic adaptation. The convergence of transcriptomic signals, allele‑frequency patterns, and RNAi assays highlights the CYP6Z genes cluster, together with key P450, UGT, and ABC variants, as central components of a polygenic resistance architecture. These findings underscore the need to integrate metabolic markers into resistance surveillance to detect and manage escalating pyrethroid resistance.

Abstract licence: CC BY-NC-ND

BACKGROUND: Anopheles mosquito resistance to insecticide remains a serious threat to malaria vector control affecting several sub-Sahara African countries, including Côte d'Ivoire, where high pyrethroid, carbamate and organophosphate resistance have been reported. Since 2017, new insecticides, namely neonicotinoids (e.g.; clothianidin) and pyrroles (e.g.; chlorfenapyr) have been pre-qualified by the World Health Organization (WHO) for use in public health to manage insecticide resistance for disease vector control. METHODS: Clothianidin and chlorfenapyr were tested against the field-collected Anopheles gambiae populations from Gagnoa, Daloa and Abengourou using the WHO standard insecticide susceptibility biossays. Anopheles gambiae larvae were collected from several larval habitats, pooled and reared to adulthood in each site in July 2020. Non-blood-fed adult female mosquitoes aged 2 to 5 days were exposed to diagnostic concentration deltamethrin, permethrin, alpha-cypermethrin, bendiocarb, and pirimiphos-methyl. Clothianidin 2% treated papers were locally made and tested using WHO tube bioassay while chlorfenapyr (100 µg/bottle) was evaluated using WHO bottle assays. Furthermore, subsamples of exposed mosquitoes were identified to species and genotyped for insecticide resistance markers including the knock-down resistance (kdr) west and east, and acetylcholinesterase (Ace-1) using molecular techniques. RESULTS: High pyrethroid resistance was recorded with diagnostic dose in Abengourou (1.1 to 3.4% mortality), in Daloa (15.5 to 33.8%) and in Gagnoa (10.3 to 41.6%). With bendiocarb, mortality rates ranged from 49.5 to 62.3%. Complete mortality (100% mortality) was recorded with clothianidin in Gagnoa, 94.9% in Daloa and 96.6% in Abengourou, while susceptibility (mortality > 98%) to chlorfenapyr 100 µg/bottle was recorded at all sites and to pirimiphos-methyl in Gagnoa and Abengourou. Kdr-west mutation was present at high frequency (0.58 to 0.73) in the three sites and Kdr-east mutation frequency was recorded at a very low frequency of 0.02 in both Abengourou and Daloa samples and absent in Gagnoa. The Ace-1 mutation was present at frequencies between 0.19 and 0.29 in these areas. Anopheles coluzzii represented 100% of mosquitoes collected in Daloa and Gagnoa, and 72% in Abengourou. CONCLUSIONS: This study showed that clothianidin and chlorfenapyr insecticides induce high mortality in the natural and pyrethroid-resistant An. gambiae populations in Côte d'Ivoire. These results could support a resistance management plan by proposing an insecticide rotation strategy for vector control interventions.

Abstract licence: CC BY