Scabies in infants and children - a narrative review.

Scabies is a human ectoparasitosis caused by Sarcoptes scabei var. hominis. World-wide around 300 million patients are affected. Infants and children have the highest incidence rates. Poverty and overcrowding are social factors contributing to a higher risk of transmission and treatment failure. The leading symptom of the infestation is itch. Complications are bacterial infections that are responsible for mortality. Diagnosis is clinical. Non-invasive imaging technologies like dermoscopy can be used. Polymerase chain reaction (PCR) is less sensitive and specific than microscopy of skin scrapings. Treatment of choice is topical permethrin 5%. Ivermectin is the only oral drug FDA-approved for scabies. It should be used in cases non-responsive to topical therapy and in case of high number of infested patients in addition to topical therapy. Pseudo-resistance to treatment is not uncommon. New drugs are on the horizon. What is Known: • Pruritus is the leading symptom causing sleep disturbances and scratching with the risk of secondary bacterial infections. • Treatment failure is related to inappropriate application of topical drugs and asymptomatic family members. What is New: • COVID-19 pandemic and migration are contributing to an increased incidence of scabies. • New compounds to treat scabies are on the horizon.

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.

An assessment of canine ectoparasiticide administration compliance in the USA.

BACKGROUND: This study evaluated the timing of dog owner ectoparasiticide purchases to estimate administration compliance and assess the consequent impact of dose purchase gaps on the proportion of time that dogs were protected over a 12-month period. METHODS: Ectoparasiticide purchase transactions over a 12-month period were evaluated for 626 US veterinary hospitals to determine dose purchase timing and identify consequent gaps between dose administration in dogs. Orally administered prescription ectoparasitic medications with active ingredients from the isoxazoline family (afoxolaner, fluralaner, lotilaner, or sarolaner) were included in the analysis. A period was calculated for each of the four isoxazoline-containing medications that represented the duration of protection provided by two doses of ectoparasiticide plus the average gap between these two doses. The maximum percentage of time possible for ectoparasiticide protection for this aggregate period was then calculated for each active ingredient. RESULTS: Ectoparasiticide transaction records of owners were analyzed for 506,637 dogs. These showed that 43% of dog owners purchased just one dose over the 12-month period considered. If a dog owner purchased more than one dose, then the timing of their transactions could create a time gap between the completion of ectoparasite protection from the first dose and onset of protection from the subsequent purchase and administration of the second dose. Such gaps were observed in purchases made by 31-65% of dog owners, depending on the selected active ingredient and number of doses. The average gap duration between dose purchases was calculated for all possible dose combinations over 12 months of ectoparasite protection. Time gaps between the first and second doses are as follows: for sarolaner, 20.3 weeks; for afoxolaner, 12.9 weeks; for fluralaner ,12.8 weeks; and for lotilaner, 8.9 weeks. The proportion of time when protection was provided during the aggregate period between administration of the first and second doses was as follows: for fluralaner, 65%; for lotilaner, 49%; for afoxolaner, 40%; and for sarolaner, 30%. CONCLUSIONS: Dog owner ectoparasiticide purchase transactions showed that there were time gaps between doses leading to reduced ectoparasite protection. The longer re-administration interval for fluralaner, a consequence of its extended duration of activity, resulted in dog owners gaining the greatest proportion of ectoparasite protection time with this medication compared with shorter-acting monthly re-treatment medications.

Fluralaner as a novel treatment for sarcoptic mange in the bare-nosed wombat (Vombatus ursinus): safety, pharmacokinetics, efficacy and practicable use.

BACKGROUND: Sarcoptic mange causes significant animal welfare and occasional conservation concerns for bare-nosed wombats (Vombatus ursinus) throughout their range. To date, in situ chemotherapeutic interventions have involved macrocytic lactones, but their short duration of action and need for frequent re-administration has limited treatment success. Fluralaner (Bravecto®; MSD Animal Health), a novel isoxazoline class ectoparasiticide, has several advantageous properties that may overcome such limitations. METHODS: Fluralaner was administered topically at 25 mg/kg (n = 5) and 85 mg/kg (n = 2) to healthy captive bare-nosed wombats. Safety was assessed over 12 weeks by clinical observation and monitoring of haematological and biochemical parameters. Fluralaner plasma pharmacokinetics were quantified using ultra-performance liquid chromatography and tandem mass spectrometry. Efficacy was evaluated through clinical assessment of response to treatment, including mange and body condition scoring, for 15 weeks after topical administration of 25 mg/kg fluralaner to sarcoptic mange-affected wild bare-nosed wombats (n = 3). Duration of action was determined through analysis of pharmacokinetic parameters and visual inspection of study subjects for ticks during the monitoring period. Methods for diluting fluralaner to enable 'pour-on' application were compared, and an economic and treatment effort analysis of fluralaner relative to moxidectin was undertaken. RESULTS: No deleterious health impacts were detected following fluralaner administration. Fluralaner was absorbed and remained quantifiable in plasma throughout the monitoring period. For the 25 mg/kg and 85 mg/kg treatment groups, the respective means for maximum recorded plasma concentrations (Cmax) were 6.2 and 16.4 ng/ml; for maximum recorded times to Cmax, 3.0 and 37.5 days; and for plasma elimination half-lives, 40.1 and 166.5 days. Clinical resolution of sarcoptic mange was observed in all study animals within 3-4 weeks of treatment, and all wombats remained tick-free for 15 weeks. A suitable product for diluting fluralaner into a 'pour-on' was found. Treatment costs were competitive, and predicted treatment effort was substantially lower relative to moxidectin. CONCLUSIONS: Fluralaner appears to be a safe and efficacious treatment for sarcoptic mange in the bare-nosed wombat, with a single dose lasting over 1-3 months. It has economic and treatment-effort-related advantages over moxidectin, the most commonly used alternative. We recommend a dose of 25 mg/kg fluralaner and, based on the conservative assumption that at least 50% of a dose makes dermal contact, Bravecto Spot-On for Large Dogs as the most appropriate formulation for adult bare-nosed wombats.

Rapid shifts in the age-specific burden of malaria following successful control interventions in four regions of Uganda.

BACKGROUND: Malaria control using long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) has been associated with reduced transmission throughout Africa. However, the impact of transmission reduction on the age distribution of malaria cases remains unclear. METHODS: Over a 10-year period (January 2009 to July 2018), outpatient surveillance data from four health facilities in Uganda were used to estimate the impact of control interventions on temporal changes in the age distribution of malaria cases using multinomial regression. Interventions included mass distribution of LLINs at all sites and IRS at two sites. RESULTS: Overall, 896,550 patient visits were included in the study; 211,632 aged < 5 years, 171,166 aged 5-15 years and 513,752 > 15 years. Over time, the age distribution of patients not suspected of malaria and those malaria negative either declined or remained the same across all sites. In contrast, the age distribution of suspected and confirmed malaria cases increased across all four sites. In the two LLINs-only sites, the proportion of malaria cases in < 5 years decreased from 31 to 16% and 35 to 25%, respectively. In the two sites receiving LLINs plus IRS, these proportions decreased from 58 to 30% and 64 to 47%, respectively. Similarly, in the LLINs-only sites, the proportion of malaria cases > 15 years increased from 40 to 61% and 29 to 39%, respectively. In the sites receiving LLINs plus IRS, these proportions increased from 19 to 44% and 18 to 31%, respectively. CONCLUSIONS: These findings demonstrate a shift in the burden of malaria from younger to older individuals following implementation of successful control interventions, which has important implications for malaria prevention, surveillance, case management and control strategies.

Ectoparasites: Scabies.

Scabies is an ectoparasitic dermatosis caused by Sarcoptes scabiei var. hominis and is a public health issue in all countries regardless of socioeconomic status. In high-income countries, delays in diagnosis can lead to institutional outbreaks; in low- and middle-income countries, poor access to health care contributes to disease undertreatment and long-term systemic sequelae. With scabies now recognized as a neglected tropical disease by the World Health Organization, increased awareness and systematic efforts are addressing gaps in diagnosis and treatment that impede scabies control. This review summarizes the available data and provides an update on scabies epidemiology, clinical features, diagnosis, management, and public health considerations.

Assessment of the insecticidal activity of oral afoxolaner against Phlebotomus perniciosus in dogs.

Twelve healthy dogs were included in this laboratory efficacy study. Six dogs were randomly allocated based on body weight to an untreated control group and six to an afoxolaner (NexGard®) treated group. In the treatment group, afoxolaner was administered orally on Day 0 in accordance with label instructions. On Days 1, 14 and 28, each dog was exposed to 60 unfed female and 10 male Phlebotomus perniciosus sandflies for 1 h. At the end of each exposure period, sandflies were counted and assessed for viability and feeding status. There was no statistical difference in mortality (0.0-5.4%), nor in feeding proportion (61.6-78%) between the control and the treated groups at all 1-h post-exposure assessments. After collection, live fed and unfed sandflies were kept for viability assessments at 48 and 72 h post-exposure. In the untreated control group, the average percentages of live, fed, female sandflies after exposure, on Days 1, 14 and 28, ranged from 51% to 74% at 48 h and from 46% to 57% at 72 h, demonstrating model robustness over the 28 days of the study. Significantly fewer live fed sandflies were recorded for the afoxolaner treated group (p < 0.01). The insecticidal efficacy was 100%, 95.9% and 75.2% at 48 h post Days 1, 14 and 28 exposures, respectively, and 100%, 100% and 86.3% at 72 h post Days 1, 14, and 28 exposures, respectively. A single administration of oral afoxolaner (NexGard®) to dogs significantly killed P. perniciosus sandflies 48 and 72 h after blood feeding for 1 month.

TITLE: Évaluation de l'activité insecticide de l'afoxolaner par voie orale contre Phlebotomus perniciosus chez le chien. ABSTRACT: Douze chiens en bonne santé ont été inclus dans cette étude d'efficacité en laboratoire. Six chiens ont été répartis au hasard en fonction de leur poids corporel dans un groupe témoin non traité et six dans un groupe traité par afoxolaner (NexGard®), administré par voie orale le jour 0 conformément aux instructions de l'étiquette. Les jours 1, 14 et 28, chaque chien a été exposé à 60 femelles à jeun et 10 mâles de Phlebotomus perniciosus pendant une heure. À la fin de chaque période d'exposition, les phlébotomes ont été évalués en termes de viabilité et de statut alimentaire. Il n'y avait pas de différence statistique dans la mortalité (0,0 à 5,4 %), ni dans le taux d'engorgement (61,6 à 78 %) entre le groupe témoin et le groupe traité lors de toutes les évaluations après une heure. Après la collecte, les phlébotomes vivants gorgés et non gorgés ont été conservés aux fins d'évaluation de la viabilité 48 et 72 heures après l'exposition. Dans le groupe témoin non traité, le pourcentage moyen de phlébotomes femelles gorgées et vivantes après l'exposition aux jours 1, 14 et 28 variait de 51 à 74 % à 48 heures et de 46 à 57 % à 72 heures, démontrant la robustesse du modèle au cours des 28 jours de l'étude. Un nombre significativement moins important de phlébotomes gorgés vivants ont été enregistrés dans le groupe traité par afoxolaner (p < 0,01). L'efficacité insecticide était de 100 %, 95,9 % et 75,2 % 48 heures après les expositions des jours 1, 14 et 28, respectivement, et 100 %, 100 % et 86,3 % à 72 heures après les expositions des jours 1, 14 et 28, respectivement. Une seule administration d'afoxolaner (NexGard®) par voie orale à un chien tue de manière significative les phlébotomes P. perniciosus 48 heures et 72 heures après la prise de sang pendant un mois.

Geographical variations of the associations between health interventions and all-cause under-five mortality in Uganda.

BACKGROUND: To reduce the under-five mortality (U5M), fine-gained spatial assessment of the effects of health interventions is critical because national averages can obscure important sub-national disparities. In turn, sub-national estimates can guide control programmes for spatial targeting. The purpose of our study is to quantify associations of interventions with U5M rate at national and sub-national scales in Uganda and to identify interventions associated with the largest reductions in U5M rate at the sub-national scale. METHODS: Spatially explicit data on U5M, interventions and sociodemographic indicators were obtained from the 2011 Uganda Demographic and Health Survey (DHS). Climatic data were extracted from remote sensing sources. Bayesian geostatistical Weibull proportional hazards models with spatially varying effects at sub-national scales were utilized to quantify associations between all-cause U5M and interventions at national and regional levels. Bayesian variable selection was employed to select the most important determinants of U5M. RESULTS: At the national level, interventions associated with the highest reduction in U5M were artemisinin-based combination therapy (hazard rate ratio (HRR) = 0.60; 95% Bayesian credible interval (BCI): 0.11, 0.79), initiation of breastfeeding within 1 h of birth (HR = 0.70; 95% BCI: 0.51, 0.86), intermittent preventive treatment (IPTp) (HRR = 0.74; 95% BCI: 0.67, 0.97) and access to insecticide-treated nets (ITN) (HRR = 0.75; 95% BCI: 0.63, 0.84). In Central 2, Mid-Western and South-West, largest reduction in U5M was associated with access to ITNs. In Mid-North and West-Nile, improved source of drinking water explained most of the U5M reduction. In North-East, improved sanitation facilities were associated with the highest decline in U5M. In Kampala and Mid-Eastern, IPTp had the largest associated with U5M. In Central1 and East-Central, oral rehydration solution and postnatal care were associated with highest decreases in U5M respectively. CONCLUSION: Sub-national estimates of the associations between U5M and interventions can guide control programmes for spatial targeting and accelerate progress towards mortality-related Sustainable Development Goals.

Quantifying Positive Health Externalities of Disease Control Interventions: Modeling Chikungunya and Dengue.

Purpose. Health interventions can generate positive externalities not captured in traditional, single-disease cost-effectiveness analyses (CEAs), potentially biasing results. We illustrate this with the example of mosquito-borne diseases. When a particular mosquito species can transmit multiple diseases, a single-disease CEA comparing disease-specific interventions (e.g., vaccination) with interventions targeting the mosquito population (e.g., insecticide) would underestimate the insecticide's full benefits (i.e., preventing other diseases). Methods. We developed three dynamic transmission models: chikungunya, dengue, and combined chikungunya and dengue, each calibrated to disease-specific incidence and deaths in Colombia (June 2014 to December 2017). We compared the models' predictions of the incremental benefits and cost-effectiveness of an insecticide (10% efficacy), hypothetical chikungunya and dengue vaccines (40% coverage, 95% efficacy), and combinations of these interventions. Results. Model calibration yielded realistic parameters that produced close matches to disease-specific incidence and deaths. The chikungunya model predicted that vaccine would decrease the incidence of chikungunya and avert more total deaths than insecticide. The dengue model predicted that insecticide and the dengue vaccine would reduce dengue incidence and deaths, with no effect for the chikungunya vaccine. In the combined model, insecticide was more effective than either vaccine in reducing the incidence of and deaths from both diseases. In all models, the combined strategy was at least as effective as the most effective single strategy. In an illustrative CEA, the most frequently preferred strategy was vaccine in the chikungunya model, the status quo in the dengue model, and insecticide in the combined model. Limitations. There is uncertainty in the target calibration data. Conclusions. Failure to capture positive externalities can bias CEA results, especially when evaluating interventions that affect multiple diseases. Multidisease modeling is a reasonable alternative for addressing such biases.

A Review of Scabies: An Infestation More than Skin Deep.

Human scabies, a common infestation, has a worldwide distribution with a variable impact and presentation depending on the clinical situation. In developed, high-income settings, health institution and residential home outbreaks challenge health and social care services. In resource-poor settings, it is the downstream sequelae of staphylococcal and streptococcal bacteraemia, induced by scratching, which have a significant impact on the long-term health of communities. Over the past decade scabies has been recognised as a "neglected tropical disease" (NTD) by the World Health Organisation, has an accepted practical system of global diagnostic criteria and is being adopted into integrated programmes of mass drug administration for NTDs in field settings. This review seeks to summarise the recent advances in the understanding of scabies and highlight the advocacy and research headlines with their implication for diagnosis and management of outbreaks and individuals. In addition, it will indicate the priorities and questions that remain.

Assessment of the speed of flea kill of lotilaner (Credelio™) throughout the month following oral administration to dogs.

BACKGROUND: Lotilaner (Credelio™, Elanco), a novel isoxazoline, is a systemic insecticide and acaricide that is rapidly absorbed following oral administration to dogs and has a half-life of 30 days. As part of a development program, studies were undertaken to investigate lotilaner's initial and sustained efficacy and speed of kill against fleas. METHODS: Four studies were conducted to evaluate the onset of lotilaner's speed of flea knockdown at the time of treatment, and to determine the sustained speed of flea kill (SOK) up to 35 days post-treatment. Each study assessed one or two specific time points (4, 6, 8 and 12 h) post-treatment and following weekly re-infestations. In each study, dogs were randomised to a lotilaner or an untreated group based on pre-administration flea counts, and before treatment were infested with adult Ctenocephalides felis. Dogs randomised to a lotilaner group received a single treatment on Day 0, at the minimum recommended dose rate of 20 mg/kg, 30 (± 5) minutes after being fed. Efficacy was calculated using geometric, and arithmetic mean flea counts in treated versus untreated groups. RESULTS: On Day 0, lotilaner efficacy was 89.9% at 4 h, 99.2% at 6 h, 99.9% at 8 h, and 100% at 12 h post-treatment. At each weekly assessment, lotilaner efficacy at 4 h remained at > 97%, at 8 h remained at > 99%, and at 12 h remained at 100% through Day 35. Across all studies, there were no treatment-related adverse events. CONCLUSION: Lotilaner's rapid flea knockdown immediately following treatment and sustained SOK through 35 days post-treatment offers a new solution for helping to eliminate the health risks that accompany flea infestations on dogs. The consistency of the rapid, sustained flea SOK demonstrated in these studies generates confidence that monthly use of lotilaner in dogs can be valuable in disrupting the flea life cycle in a contaminated environment, and that newly acquired fleas will die quickly, thereby reducing the discomfort of flea bites. The sustained lotilaner SOK also provides confidence that there will be no "end-of-dose" resurgence in flea burdens with the potential accompanying consequence of flares in flea-bite hypersensitivity.

Assessment of the onset of lotilaner (Credelio™) speed of kill of fleas on dogs.

BACKGROUND: Lotilaner (Credelio™) is the newest member of the novel isoxazoline chemical class to be developed to treat canine ectoparasitism. Administered orally, lotilaner is rapidly absorbed with peak blood levels occurring within 2 h post-treatment. A study was undertaken to determine the earliest onset of lotilaner's efficacy against existing flea infestations. METHODS: From 72 Beagles, 64 qualifying dogs were ranked in descending order of flea counts from a Day -8 infestation and placed into eight blocks. Within blocks, eight dogs were randomly allocated among eight groups: Groups 1 to 4 were treated orally with lotilaner, at as close as possible to the minimum dose rate of 20 mg/kg within 30 (± 5) minutes after feeding; Groups 5 to 8 were untreated controls. All dogs were infested with 100 ± 5 fleas on Day -2, and whole-body flea counts were completed at 30 min and one, two and 8 h after treatment. Efficacy calculations were based on arithmetic and geometric means if an adequate infestation (at least six of eight untreated dogs with a flea retention of ≥ 50%) was demonstrated in the equivalent control group. RESULTS: Adequate infestations were established in all control groups. At 30 min and 1 h post-treatment, relative to the matching untreated control group, there were no significant reductions in mean flea counts in lotilaner-treated dogs, although moribund fleas were evident at 1 h post-treatment. At 2 h after treatment, compared with the equivalent control group, the geometric mean flea count reduction in the lotilaner group was 64.0% (t (7) = 2.86, P = 0.0242). At 8 h after treatment, lotilaner efficacy was 99.6%. There were no treatment-related adverse events. CONCLUSION: This study demonstrates that lotilaner flavored chewable tablets are well tolerated and begin to kill fleas within 2 h of treatment, achieving 99.6% efficacy within 8 h. Lotilaner can therefore be used to quickly alleviate the flea irritation that arises from existing infestations.

Assessment of afoxolaner efficacy against Otodectes cynotis infestations of dogs.

BACKGROUND: The efficacy of a single 2.5 mg/kg dose of afoxolaner (NexGard®, Merial) against induced Otodectes cynotis infestations was assessed in eight afoxolaner-treated dogs, compared to eight untreated dogs. METHODS: After O. cynotis infestations were established and confirmed by otoscopic assessments in 16 dogs, all of the dogs were included in the study and allocated to two separate treatment groups. The first group of eight ear mite-infested dogs remained untreated, while afoxolaner was administered orally to the second group of dogs at the minimum recommended dose once on Day 0. Otoscopic assessments performed on all dogs (Days -7, -2, 14 and 28) confirmed the presence or absence of live mites throughout the study. No serious adverse events were recorded throughout the study, and no adverse events were likely related to the administration of NexGard. RESULTS: By Day 28, seven out of eight untreated dogs were still infested with ear mites, while only two out of eight afoxolaner-treated dogs were infested, with one and four ear mites, respectively. On Day 28, the reductions of mite counts in the afoxolaner-treated group versus those of the control dogs were 98.5% based on geometric means, and 99.4% based on arithmetic means. Significantly fewer (P < 0.05) live mites were present in the afoxolaner-treated group than the untreated group on Day 28. CONCLUSION: The results of this study demonstrated that a single oral administration of afoxolaner at the minimum recommended dose is highly effective (>98%) in treating dogs with induced O. cynotis infestations.

Malaria burden and costs of intensified control in Bhutan, 2006-14: an observational study and situation analysis.

INTRODUCTION: The number of malaria cases has fallen in Bhutan in the past two decades, and the country has a goal of complete elimination of malaria by 2016. The aims of this study are to ascertain the trends and burden of malaria, the costs of intensified control activities, the main donors of funding for the control activities, and the costs of different preventive measures in the pre-elimination phase (2006-14) in Bhutan. METHODS: We undertook a descriptive analysis of malaria surveillance data from 2006 to 2014, using data from the Vector-borne Disease Control Programme (VDCP) run by the Department of Public Health of Bhutan's Ministry of Health. Malaria morbidity and mortality in local Bhutanese people and foreign nationals were analysed. The cost of different control and preventive measures were calculated, and the average numbers of long-lasting insecticidal nests per person were estimated. FINDINGS: A total of 5491 confirmed malaria cases occurred in Bhutan between 2006 and 2014. By 2013, there was an average of one long-lasting insecticidal net for every 1·51 individuals. The cost of procuring long-lasting insecticidal nets accounted for more than 90% of the total cost of prevention measures. The Global Fund to Fight AIDS, Tuberculosis and Malaria was the main international donor, accounting for more than 80% of the total funds. INTERPRETATION: The malaria burden in Bhutan decreased significantly during the study period with high coverage of long-lasting insecticidal nets. The foreseeable challenges that require national attention to maintain a malaria-free status after elimination are importation of malaria, especially from India; continued protection of the population in endemic districts through complete coverage with long-lasting insecticidal nets and indoor residual spraying; and exploration of local funding modalities post-elimination in the event of a reduction in international funding. FUNDING: None.

Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 µg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient.

Eprinomectin accumulation in Rhipicephalus (Boophilus) microplus: Pharmacokinetic and efficacy assessment.

Eprinomectin (EPM) is a macrocyclic lactone used against endo-ectoparasites without withdrawal time in milk and meat after its pour-on administration at 0.5mg/kg. Previous experiments evaluated the efficacy of EPM against Rhipicephalus (Boophilus) microplus in cattle. This study assessed EPM efficacy against R. (B.) microplus after topical administration at two dose rates and investigated the relationship between EPM systemic exposure in the host and drug concentrations accumulated in ticks recovered from treated animals. A standardized pharmaco-parasitological study was performed in two phases. In phase 1 eighteen Braford cattle naturally infected with R. (B.) microplus were divided into three experimental groups with a similar level of infestation (Kruskal-Wallis test, P>0.05): control group and treated groups with EPM pour-on (1 and 1.5mg/kg). Samples of heparinized blood and ticks at different life stages were taken between 0 and 21 days (d) post-administration to measure EPM concentrations by HPLC. The efficacy trial (phase 2) included eighteen Braford calves naturally infected with R. (B.) microplus divided into control group and 1mg/kg and 1.5mg/kg EPM treated groups. Female ticks (4.5-8mm) on cattle were counted between 1 and 23 days post-treatment to evaluate the efficacy of EPM. The reproductive efficiency index (REI) and the fertility efficiency index (FEI) were evaluated. Plasma concentrations of EPM showed a linear relationship with the level of dose rate administered. Peak plasma concentrations were within a range between 13.8 and 90ng/ml, which guarantee milk drug concentrations below the maximum residues level. High EPM concentrations were detected in ticks. EPM concentrations in R. (B.) microplus were correlated to plasma concentrations between 1.25 days and 21 days post-administration (r 0.84; P<0.05). EPM efficacy calculated using the Henderson-Tilton formula was 98.9% and 99.1% (7 days post-administration) and 100% (23 days post-administration) after EPM treatment at 1 and 1.5mg/kg, respectively. EPM administered at 1.5mg/kg also showed a significantly higher deleterious effect on tick fertility as measured by FEI (P<0.01). Therefore, treatment with EPM may be useful for controlling ticks in cattle, particularly in dairy production systems.

Optimizing insecticide allocation strategies based on houses and livestock shelters for visceral leishmaniasis control in Bihar, India.

Visceral leishmaniasis (VL) is the most deadly form of the leishmaniasis family of diseases, which affects numerous developing countries. The Indian state of Bihar has the highest prevalence and mortality rate of VL in the world. Insecticide spraying is believed to be an effective vector control program for controlling the spread of VL in Bihar; however, it is expensive and less effective if not implemented systematically. This study develops and analyzes a novel optimization model for VL control in Bihar that identifies an optimal (best possible) allocation of chosen insecticide (dichlorodiphenyltrichloroethane [DDT] or deltamethrin) based on the sizes of human and cattle populations in the region. The model maximizes the insecticide-induced sandfly death rate in human and cattle dwellings while staying within the current state budget for VL vector control efforts. The model results suggest that deltamethrin might not be a good replacement for DDT because the insecticide-induced sandfly deaths are 3.72 times more in case of DDT even after 90 days post spray. Different insecticide allocation strategies between the two types of sites (houses and cattle sheds) are suggested based on the state VL-control budget and have a direct implication on VL elimination efforts in a resource-limited region.

Guidelines for treatment of lice in sheep with long wool based on a model of the development of wool damage.

OBJECTIVE: This study used a model of the development of wool damage caused by lice in long wool to examine the conditions under which treatment of the sheep is advisable on an economic basis. METHODS: The model uses the proportion of a flock showing visible signs of rubbing and the number of days until the next shearing to compare the cost of treatment (product plus labour) with production losses because of the reduction in wool value caused by lice. From the model output, guidelines are provided to inform producers of the most cost-effective option for lice control. RESULTS: Under normal conditions, if there are any signs of rubbing ≥140 days before shearing, then treatment was the best option. If signs of wool damage are not observed until there are ≤70 days before shearing, then the most cost-effective option is to not treat at all. Between these two periods, the time period in which not treating is the most cost-effective option decreases as the number of sheep visibly affected by lice increases. At higher wool values (A$70/head vs A$35), the option to treat is brought forward approximately 25 days, whereas at a low wool value (A$17.50/head) the period in which no treatment is the most cost-effective is extended by approximately 25 days. Treating only the visibly affected sheep is the best option only for a very short time for all wool values and treatment costs. CONCLUSION: The model provides guidelines for control of lice in long wool to minimise the net cost of infestation and limit unnecessary pesticide use.