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Abstract Background Scabies is a public health problem in many countries, with impetigo and its complications important consequences. Ivermectin based mass drug administration (MDA) reduces the prevalence of scabies and, to a lesser extent, impetigo. We studied the impact of co-administering azithromycin on the prevalence of impetigo and antimicrobial resistance. Methods Six communities were randomized to receive either ivermectin-based MDA or ivermectin-based MDA co-administered with azithromycin. We measured scabies and impetigo prevalence at baseline and 12 months. We collected impetigo lesions swabs at baseline, 3 and 12 months to detect antimicrobial resistance. Results At baseline, scabies and impetigo prevalences were 11.8% and 10.1% in the ivermectin-only arm and 9.2% and 12.1% in the combined treatment arm. At 12 months, the prevalences had fallen to 1.0% and 2.5% in the ivermectin-only arm and 0.7% and 3.3% in the combined treatment arm. The proportion of impetigo lesions containing Staphylococcus aureus detected did not change (80% at baseline vs 86% at 12 months; no significant difference between arms) but the proportion containing pyogenic streptococci fell significantly (63% vs 23%, P < .01). At 3 months, 53% (8/15) of S. aureus isolates were macrolide-resistant in the combined treatment arm, but no resistant strains (0/13) were detected at 12 months. Conclusions Co-administration of azithromycin with ivermectin led to similar decreases in scabies and impetigo prevalence compared to ivermectin alone. The proportion of impetigo lesions containing pyogenic streptococci declined following MDA. There was a transient increase in the proportion of macrolide-resistant S. aureus strains following azithromycin MDA. Clinical Trials Registration clinicaltrials.gov (NCT02775617). Scabies is a major cause of impetigo. We assessed the effect on impetigo prevalence of adding azithromycin to ivermectin mass drug. The decrease in impetigo did not differ between communities treated with ivermectin and communities treated with ivermectin and azithromycin.

This trial of strategies for scabies control in Fiji compared administration of permethrin to affected persons and their contacts with mass administration of either permethrin or ivermectin. The prevalence of scabies declined in all groups, with the greatest decline in the ivermectin group. Scabies, a skin condition that is recognized by the World Health Organization as a disease of public health importance, 1 is a substantial contributor to global morbidity and mortality. Scabies is caused by a microscopic mite ( Sarcoptes scabiei var. hominis ) and is transmitted primarily through person-to-person contact. Infestation can result in debilitating itchiness, with associated sleep disturbance, reduced ability to concentrate, 2 social stigmatization, 3 and ongoing health care expenses. 4 , 5 In many developing countries, scabies-related scratching is an important cause of impetigo, 6 – 10 which is most often due to Streptococcus pyogenes or Staphylococcus aureus infection and can lead to septicemia, . . .

Mass drug administration (MDA) based on two doses of ivermectin, one week apart, substantially reduces prevalence of both scabies and impetigo. The Regimens of Ivermectin for Scabies Elimination (RISE) trial assessed whether one-dose ivermectin-based MDA would be as effective. RISE was a cluster-randomised trial in Solomon Islands. We assigned 20 villages in a 1:1 ratio to one- or two-dose ivermectin-based MDA. We planned to test whether the impact of one dose on scabies prevalence at 12 and 24 months was non-inferior to two, at a 5% non-inferiority margin. We deferred endpoint assessment to 21 months due to COVID-19. We enrolled 5239 participants in 20 villages at baseline and 3369 at 21 months from an estimated population of 5500. At baseline scabies prevalence was similar in the two arms (one-dose 17·2%; two-dose 13·2%). At 21 months, there was no reduction in scabies prevalence (one-dose 18·7%; two-dose 13·4%), and the confidence interval around the difference included values substantially greater than 5%. There was however a reduction in prevalence among those who had been present at the baseline assessment (one-dose 15·9%; two-dose 10·8%). Additionally, we found a reduction in both scabies severity and impetigo prevalence in both arms, to a similar degree. There was no indication of an overall decline in scabies prevalence in either arm. The reduction in scabies prevalence in those present at baseline suggests that the unexpectedly high influx of people into the trial villages, likely related to the COVID-19 pandemic, may have compromised the effectiveness of the MDA. Despite the lack of effect there are important lessons to be learnt from this trial about conducting MDA for scabies in high prevalence settings. Registered with Australian New Zealand Clinical Trials Registry ACTRN12618001086257.

In small community-based trials, mass drug administration of ivermectin has been shown to substantially decrease the prevalence of both scabies and secondary impetigo; however, their effect at large scale is untested. Additionally, combined mass administration of drugs for two or more neglected diseases has potential practical advantages, but efficacy of potential combinations should be confirmed. The azithromycin ivermectin mass drug administration (AIM) trial was a prospective, single-arm, before-and-after, community intervention study to assess the efficacy of mass drug administration of ivermectin for scabies and impetigo, with coadministration of azithromycin for trachoma. Mass drug administration was offered to the entire population of Choiseul Province, Solomon Islands, and of this population we randomly selected two sets of ten sentinel villages for monitoring, one at baseline and the other at 12 months. Participants were offered a single dose of 20 mg/kg azithromycin, using weight-based bands. Children weighing less than 12·5 kg received azithromycin oral suspension (20 mg/kg), and infants younger than 6 months received topical 1% tetracycline ointment. For ivermectin, participants were offered two doses of oral ivermectin 200 μg/kg 7–14 days apart using weight-based bands, or 5% permethrin cream 7–14 days apart if ivermectin was contraindicated. Our study had the primary outcomes of safety and feasibility of large-scale mass coadministration of oral ivermectin and azithromycin, which have been previously reported. We report here the prevalence of scabies and impetigo in residents of the ten baseline villages compared with those in the ten 12-month villages, as measured by examination of the skin, which was a secondary outcome of the trial. Further outcomes were comparison of the number of all-cause outpatient attendances at government clinics in Choiseul Province at various timepoints before and after mass drug administration. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12615001199505). During September, 2015, over 4 weeks, 26 188 people (99·3% of the estimated population of Choiseul [n=26 372] as determined at the 2009 census) were treated. At baseline, 1399 (84·2%) of 1662 people living in the first ten villages had their skin examined, of whom 261 (18·7%) had scabies and 347 (24·8%) had impetigo. At 12 months after mass drug administration, 1261 (77·6%) of 1625 people in the second set of ten villages had their skin examined, of whom 29 (2·3%) had scabies (relative reduction 88%, 95% CI 76·5–99·3) and 81 (6·4%) had impetigo (relative reduction 74%, 63·4–84·7). In the 3 months after mass drug administration, 10 614 attended outpatient clinics for any reason compared with 16 602 in the 3 months before administration (decrease of 36·1%, 95% CI 34·7–37·6), and during this period attendance for skin sores, boils, and abscesses decreased by 50·9% (95% CI 48·6–53·1). Ivermectin-based mass drug administration can be scaled to a population of over 25 000 with high efficacy and this level of efficacy can be achieved when mass drug administration for scabies is integrated with mass drug administration of azithromycin for trachoma. These findings will contribute to development of population-level control strategies. Further research is needed to assess durability and scalability of mass drug administration in larger, non-island populations, and to assess its effect on the severe bacterial complications of scabies. International Trachoma Initiative, Murdoch Children's Research Institute, Scobie and Claire Mackinnon Trust, and the Wellcome Trust.

Background Impetigo is caused by both Streptococcus pyogenes and Staphylococcus aureus ; the relative contributions of each have been reported to fluctuate with time and region. While S. aureus is reportedly on the increase in most industrialised settings, S. pyogenes is still thought to drive impetigo in endemic, tropical regions. However, few studies have utilised high quality microbiological culture methods to confirm this assumption. We report the prevalence and antimicrobial resistance of impetigo pathogens recovered in a randomised, controlled trial of impetigo treatment conducted in remote Indigenous communities of northern Australia. Methods Each child had one or two sores, and the anterior nares, swabbed. All swabs were transported in skim milk tryptone glucose glycogen broth and frozen at –70°C, until plated on horse blood agar. S. aureus and S. pyogenes were confirmed with latex agglutination. Results From 508 children, we collected 872 swabs of sores and 504 swabs from the anterior nares prior to commencement of antibiotic therapy. S. pyogenes and S. aureus were identified together in 503/872 (58%) of sores; with an additional 207/872 (24%) sores having S. pyogenes and 81/872 (9%) S. aureus , in isolation. Skin sore swabs taken during episodes with a concurrent diagnosis of scabies were more likely to culture S. pyogenes (OR 2.2, 95% CI 1.1 – 4.4, p = 0.03). Eighteen percent of children had nasal carriage of skin pathogens. There was no association between the presence of S. aureus in the nose and skin. Methicillin-resistance was detected in 15% of children who cultured S. aureus from either a sore or their nose. There was no association found between the severity of impetigo and the detection of a skin pathogen. Conclusions S. pyogenes remains the principal pathogen in tropical impetigo; the relatively high contribution of S. aureus as a co-pathogen has also been confirmed. Children with scabies were more likely to have S. pyogenes detected. While clearance of S. pyogenes is the key determinant of treatment efficacy, co-infection with S. aureus warrants consideration of treatment options that are effective against both pathogens where impetigo is severe and prevalent. Trial registration This trial is registered; ACTRN12609000858291 .

In this 2-year follow-up report in Fiji, the single mass administration of oral ivermectin was more effective in reducing the prevalence of both scabies and impetigo than either the administration of topical permethrin to persons with scabies and their contacts or the mass administration of topical permethrin.

More than 3·5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year. We undertook a randomised controlled trial to assess the effect of handwashing promotion with soap on the incidence of acute respiratory infection, impetigo, and diarrhoea. In adjoining squatter settlements in Karachi, Pakistan, we randomly assigned 25 neighbourhoods to handwashing promotion; 11 neighbourhoods (306 households) were randomised as controls. In neighbourhoods with handwashing promotion, 300 households each were assigned to antibacterial soap containing 1·2% triclocarban and to plain soap. Fieldworkers visited households weekly for 1 year to encourage handwashing by residents in soap households and to record symptoms in all households. Primary study outcomes were diarrhoea, impetigo, and acute respiratory-tract infections (ie, the number of new episodes of illness per person-weeks at risk). Pneumonia was defined according to the WHO clinical case definition. Analysis was by intention to treat. Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (−65% to −34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (−65% to −41%) and a 34% lower incidence of impetigo (−52% to −16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap. Handwashing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally—namely, diarrhoea and acute lower respiratory infections. Handwashing with daily bathing also prevents impetigo.

Impetigo is the most common bacterial skin infection in children two to five years of age. There are two principal types: nonbullous (70% of cases) and bullous (30% of cases). Nonbullous impetigo, or impetigo contagiosa, is caused by Staphylococcus aureus or Streptococcus pyogenes, and is characterized by honey-colored crusts on the face and extremities. Impetigo primarily affects the skin or secondarily infects insect bites, eczema, or herpetic lesions. Bullous impetigo, which is caused exclusively by S. aureus, results in large, flaccid bullae and is more likely to affect intertriginous areas. Both types usually resolve within two to three weeks without scarring, and complications are rare, with the most serious being poststreptococcal glomerulonephritis. Treatment includes topical antibiotics such as mupirocin, retapamulin, and fusidic acid. Oral antibiotic therapy can be used for impetigo with large bullae or when topical therapy is impractical. Amoxicillin/clavulanate, dicloxacillin, cephalexin, clindamycin, doxycycline, minocycline, trimethoprim/sulfamethoxazole, and macrolides are options, but penicillin is not. Natural therapies such as tea tree oil; olive, garlic, and coconut oils; and Manuka honey have been anecdotally successful, but lack sufficient evidence to recommend or dismiss them as treatment options. Treatments under development include minocycline foam and Ozenoxacin, a topical quinolone. Topical disinfectants are inferior to antibiotics and should not be used. Empiric treatment considerations have changed with the increasing prevalence of antibiotic-resistant bacteria, with methicillin-resistant S. aureus, macrolide-resistant streptococcus, and mupirocin-resistant streptococcus all documented. Fusidic acid, mupirocin, and retapamulin cover methicillin-susceptible S. aureus and streptococcal infections. Clindamycin proves helpful in suspected methicillin-resistant S. aureus infections. Trimethoprim/sulfamethoxazole covers methicillin-resistant S. aureus infection, but is inadequate for streptococcal infection.