Prevalence of Treatment Failure Among Patients With Scabies

These authors reviewed 147 studies that assessed treatment failure of scabies with permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur, or lindane, and they performed a random-effects meta-analysis for all outcomes reported by at least 2 studies. It should be noted that random-effects models give disproportionate weight to small studies, which can skew results, and some journals require both random and fixed effects models of meta-analysis.    

Regardless of the methods used, their findings make perfect sense and are relevant to practicing clinicians. As most scabicides are neurotoxins and ova lack a nervous system, it is not surprising that two treatments with agents such as ivermectin were more effective than a single treatment. Once ova mature and begin to hatch, the second treatment will help to eliminate those that survived. Similar to the trend with lice, scabies treatment failure with permethrin increased over time, suggesting emerging resistance. As only 3 of the included studies conducted a multivariable risk factor analysis and none directly assessed resistance, one is left to speculate on the relative contributions of chemical resistance, compliance, failure to treat close contacts, and reinfection from another source. Oral ivermectin, topical ivermectin, and permethrin were least likely to fail, but single versus repeated dosing and the order of agents used might have influenced the results.

Scabies continues to be a significant public health issue, particularly in developing countries, affecting 130 million people globally. Treatment failure, which can occur in up to 30% of cases, is considered a major factor in the increasing incidence of scabies. Immune status of the host, choice of treatment, exposure to future transmission events, and drug-resistance have been suggested to be the predictors of treatment failure.

This study is a comprehensive systematic review and meta-analysis of randomized clinical trials and observational studies (a total of 147 studies published between 1983 and 2021) in adults and children on the prevalence of scabies treatment failure and associated factors. Treatments included in the review were permethrin, ivermectin, crotamiton, benzyl benzoate, malathion, sulfur, and lindane. The most common treatments given were ivermectin and permethrin. Limitations of the review included a moderate to high risk of bias in most of the included studies and the lack of inclusion of more recent studies, as their search was completed in 2021.

The overall prevalence of treatment failure was 15.2%. Pooled prevalence of treatment failure varied greatly across drugs, with the lowest being topical ivermectin, followed by permethrin and oral ivermectin. Oral ivermectin when used in two doses was associated with lower treatment failure prevalence compared with a single dose (although not statistically significant). The lowest levels of treatment failure were in studies conducted in Europe; the highest were from studies conducted in the Western Pacific Region. Studies that used objective measures (microscopy or dermatoscopy) to confirm scabies were more likely to report treatment failure compared with those that used clinical examination and/or patient history.

Treatment failure has increased progressively over time. Overall treatment failure was more likely in recent studies compared with the ones published before 2011. Analysis revealed a significant increase over time in overall permethrin treatment failure and higher (although not statistically significant) ivermectin treatment failure in studies published in 2011 or later. Drug resistance has not been formally assessed in studies. Resistance phenomena were reported for ivermectin-refractory cases and suggested for permethrin in recent case reports. This suggests that combinations of treatments may be an option to reduce treatment failures.

The reasons for treatment failure were investigated in only a few studies. None assessed the susceptibility of mites. Mite susceptibility was not determined in larger studies likely due to the lack of suitable methods. In future studies, genotyping of mites from treatment-responsive versus treatment-refractory groups may be a feasible approach to provide an insight into resistance-associated genotypes.

Based on the study findings, the authors suggest: 1) scabies treatment guidelines consider incorporating a second dose of ivermectin; 2) consideration be given to the use of combined treatments to reduce treatment failures; and 3) future studies to assess the reasons for treatment failure, including assessment of mite susceptibility to scabies treatments.