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Article Type: Systematic Review
Treatment, prevention and public health management of impetigo, scabies, crusted scabies and
fungal skin infections in endemic populations: a systematic review
Philippa J. May1, Steven Y.C. Tong2,3, Andrew C. Steer4,5, Bart J. Currie3,6 , Ross M. Andrews3,8,
Jonathan R. Carapetis8,9,10, Asha C. Bowen3,8,9,10,11
1. Northern Territory Centre for Disease Control, Rocklands Drive, Casuarina, Australia
2. Victorian Infectious Diseases Service, Royal Melbourne Hospital, and The University of
Melbourne, at the Peter Doherty Institute for Infection and Immunity, Grattan Street, Parkville,
Australia
3. Menzies School of Health Research, Charles Darwin University, Casuarina, Australia
4. Royal Children’s Hospital, Parkville, Australia
5. Murdoch Children’s Research Institute, University of Melbourne, Parkville, Australia
6. Royal Darwin Hospital, Casuarina, Australia
7. National Centre for Epidemiology & Population Health, Australian National University, Canberra,
Australia
8. Princess Margaret Hospital for Children, Subiaco, Australia
9. Wesfarmers Centre for Vaccines and Infectious Diseases,University of Western Australia,
Subiaco, Australia
10. School of Medicine, University of Western Australia, Nedlands, Australia
11. University of Notre Dame Australia, Fremantle, Australia
Summary
We conducted a systematic review of the treatment, prevention and public health control of skin
infections including impetigo, scabies, crusted scabies and tinea in resource limited settings where
skin infections are endemic. The aim is to inform strategies, guidelines and research to improve skin
health in populations that are inequitably affected by infections of the skin and the downstream
consequences of these. The systematic review is reported according to the PRISMA statement. From
1759 titles identified, 81 full text studies were reviewed, and key findings outlined for impetigo,
scabies, crusted scabies and tinea. Improvements in primary care and public health management of
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skin infections will have broad and lasting impacts on overall quality of life including reductions in
morbidity and mortality from sepsis, skeletal infections, kidney and heart disease.
Keywords: impetigo, scabies, crusted scabies, tinea
Introduction
Children in developing countries and other resource-limited settings bear a disproportionate burden
of skin infections, owing to poverty, poorer living conditions, normalisation and limited access to
primary health care.1-4 More than 162 million children are estimated to have impetigo at any one
time5 and more than 110 million children with scabies.6 There are no estimates for the global burden
of tinea in children, although fungal skin infections were the leading skin disease and in the top 10
most prevalent diseases worldwide in 2010.7
Primary infection with impetigo and secondary bacterial infection of scabies, crusted scabies
and tinea with the bacteria Staphylococcus aureus and Streptococcus pyogenes (Group A
Streptococcus, GAS) lead to morbidity, mortality and socioeconomic costs via invasive infection.8,9
Invasive S. aureus has a global incidence estimate of 20 to 50 cases/100,000 population per year
with a case fatality rate of 5–30%.10,11 An estimated 163,000 people die from GAS bacteraemia each
year.8 Moreover, post streptococcal sequelae of acute rheumatic fever (ARF) and acute post
streptococcal glomerulonephritis (APSGN) can lead to long term consequences of chronic heart and
kidney disease.8,12,13 Due to differences in the social determinants of health, there exists a marked
disparity in the burden of skin infections and their sequelae between resource-rich and resource-
limited settings.14
Systematic reviews of skin infection treatments that have only included randomised clinical
trials (RCT),15-18 exclude a large body of available evidence from resource-limited settings where the
burden is highest.5-7 RCTs are often conducted in hospital outpatient departments (OPD) in high
income settings, and findings may not be directly applicable to resource-limited settings where
cultural practices, access, availability, cost and acceptability of treatments may differ. There remains
a lack of consensus on the best treatments and population health approaches for the prevention and
control of skin infections, both individual skin conditions and skin infections collectively, in these
resource-limited settings due to a lack of a review of the evidence that is externally valid to these
populations. We conducted a systematic review of studies from resource-limited and endemic
settings regarding the prevention, treatment and public health management of impetigo, scabies,
crusted scabies and tinea to inform the development of evidence-based guidelines and future
research priorities for skin infections in endemic populations.
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Methods
Search Strategy and Selection Criteria
This systematic review is reported according to the Preferred Reporting items for Systematic
Reviews and Meta-Analyses (PRISMA) statement.19 The methods and search strategy have been
described previously.20 Briefly peer reviewed and grey literature databases were searched. Studies
published in English since 1960 using any experimental study (RCTs, clinical controlled trials, before
and after studies and interrupted time series analyses) or observational study design (cohort and
ecological studies) were included. Eligible participant types included Indigenous peoples and
populations in resource-limited settings (low, low-middle and middle income countries and
resource-limited populations in Organisation for Economic Co-operation and Development (OECD)
countries) (see supplementary appendix for definitions) with a diagnosis of impetigo, scabies,
crusted scabies, tinea capitis, tinea corporis or tinea unguium (onychomycosis) in persons of any age
or sex. We reviewed any clinical or public health interventions aiming to reduce skin infections with
any type of comparator. Outcomes were categorised as primary (cure or decrease in prevalence for
population-based studies) or secondary (microbiological cure, symptom relief, recurrence,
adherence, acceptability, adverse events and spread to contacts). Two authors (AB and PM)
independently screened the titles and abstracts of all studies identified in the search process and
selected the studies for eligibility assessment. Full reports of these studies were obtained and
assessed by two independent reviewers (ten reviewers in total). Any discrepancies for inclusion were
resolved by consensus discussion.
Assessment of Methodological Quality and Data Extraction
Two reviewers independently scored for methodological quality of clinical trials using The Cochrane
Collaboration’s tool for assessing risk of bias.21 Observational studies were assessed for blinding,
completeness of outcome data, outcome reporting and other sources of bias including confounders.
All data were entered into data extraction forms using Covidence online software (Veritas Health
Innovation, Melbourne, VIC, Australia) by the two independent reviewers and discrepancies resolved
via discussion.
Statistical Analysis and Synthesis
The data are presented in a narrative synthesis. Meta-analysis was not performed due to the
heterogeneity of studies. Calculations were performed using STATA13 (Statacorp, Texas, USA). For
reading ease, results are presented in common theme groups in each area of clinical treatment or
public health prevention and control relevant to skin infections in resource-limited settings. As many
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population-based studies incorporate multiple strategies such as health education, treatment and
hygiene practices, it is recommended that all evidence is considered by the reader as a whole. We
used the GRADE approach to rate evidence across studies for specific clinical outcomes to link
evidence-quality evaluations to recommendations in clinical guidelines (Table 1).
Results
The search strategy identified 1,759 titles and 455 abstracts for screening, of which 193 met the
inclusion criteria. 81 full text studies were included (Figure 1), representing >27,633 participants
over a 40-year period (1976 – 2015). The study size, type, location and condition under study are
summarised (Figure 2, Supplementary Table 1). The study details and characteristics are summarised
in Table 2. There were 44 (54%) RCTs, four (5%) cluster RCTs, three (4%) controlled clinical trials,
three (4%) controlled before and after studies and three (4%) controlled population studies
(Supplementary Table 2). There were two (3%) before and after studies, four (5%) ecological studies,
14 (17%) prospective cohort studies and four (5%) retrospective observational studies appraised
(Supplementary Table 3).
Summary of clinical treatment recommendations for resource limited settings (Supplementary File
1)
1. Comprehensive community skin health programs
Moderate quality evidence that treatment combined with comprehensive skin control measures
(health promotion, environmental interventions and screening) add benefit in sustaining a reduction
in scabies prevalence alone (2B)22 and impetigo and scabies prevalence combined (2C).23-25 No
studies assessed the effect of a community skin health program on impetigo or tinea alone, whilst
one study described this for scabies,22 one for scabies and impetigo,23,24 and one for general skin
infections.25 High quality evidence from studies using control communities would be advantageous
in determining the measurable benefit over standard treatment (Table 3).
In Bangladesh, moderate quality evidence was provided from a study where permethrin MDA
was followed by randomisation of male boarding school students to a scabies control program
(repeat permethrin treatment for scabies, health promotion activities with a designated scabies class
monitor, daily bathing with soap, and bags for bedding and clothing storage) or control.22 At four
months, scabies prevalence was 5% (intervention) and 50% (control), p <0.001.22 In Australia, low
quality evidence was provided from a permethrin MDA that included a comprehensive skin control
program (annual treatment and community clean up days, health promotion and repeat treatment
with permethrin for scabies) in a remote Indigenous community.23,24 Scabies prevalence declined
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from 35% to 12%, p<0.0001 and impetigo from 11% to 2%, p=0.0005.23,24 In Kenya, ow quality
evidence was provided from a 5 year dermatology project within primary health care (training of
health care workers and school based treatments) that did not show a sustained reduction in
impetigo, scabies or tinea.25
2. Impetigo
I. Directed antimicrobial therapy
High quality evidence supports the use of oral co-trimoxazole or intramuscular (IM) benzathine
penicillin G (BPG) for the treatment of impetigo (1A).26,27 Oral amoxicillin or oral erythromycin are
suitable alternatives (2B).28 Oral penicillin G is not recommended for treatment of impetigo (2D).29
Although topical antibiotics are recommended as the preferred treatment for impetigo in
industrialised settings,16 there is no available evidence from resource limited contexts for topical
antibiotics or evidence to not treat impetigo.
High-quality evidence from two open label RCTs with Australian Indigenous children compared
oral co-trimoxazole versus IM BPG and found no difference in clinical or microbiological cure of
impetigo.26,27 Moderate quality RCT evidence reported clinical cure in 89% of patients in both groups
when oral amoxicillin and oral erythromycin for 7 days in Mali were compared.28 Low quality RCT
evidence in Canadian Indigenous children compared oral penicillin G for 10 days with IM BPG, with
treatment failure equivalent: 16% and 14% respectively.29 No studies assessed topical agents or used
a placebo controlled design for impetigo.
II. Mass Drug Administration (MDA)
No studies assessed MDA for impetigo alone. Impetigo was a secondary outcome in scabies MDAs
reported below
III. Complimentary/alternative therapies
No studies assessed complimentary therapies for impetigo.
IV. Handwashing and hygiene practices
High quality evidence supports daily handwashing with soap for the treatment and prevention of
impetigo, with no benefit found for antibacterial soap over regular soap (1A).30,31
In Pakistan, high quality evidence from two RCTs enrolling households with children assessed
handwashing with soap for impetigo and found a benefit for soap, but no difference between
antibacterial (triclocarbon 1.2%) and standard soap.30,31
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3. Scabies
All studies on scabies treatment used clinical cure or symptom relief as end points.
I. Directed anti-parasitic therapy
a. Topical treatment vs. topical treatment
Seven studies compared topical anti-parasitic agents for scabies,32-38 with low to moderate quality
evidence for either topical permethrin or topical ivermectin (2B).32,33 Permethrin is superior to
lindane (1A),34 topical crotamiton (2C)35 or Tenutex emulsion (disulphiram and benzyl benzoate[BB])
in those >4 years (2C).36 Topical ivermectin is superior to topical crotamiton in those >2 years (2C).37
Very low quality evidence from one study that topical BB or topical permethrin is safe in pregnant
women (2C).38 Without high-quality evidence to support modified applications of topical treatments
for scabies, the standard whole body application remains strongly recommended (1D).
High-quality RCT evidence from an Iranian hospital OPD found two applications of 5%
permethrin achieved a superior clinical cure (85%) compared to 1% lindane (49%), p<0.05.34 Clinical
cure was similar with topical ivermectin or topical permethrin in an Iranian dermatology OPD.33
When topical ivermectin 1% and topical permethrin 5% were compared with oral ivermectin, clinical
response at one week was superior with either topical treatment (69% and 75% v 30%, p<0.05)
whilst cure at 4 weeks was universal for all three agents.32 Topical permethrin35 and topical
ivermectin37 were superior to topical crotamiton at four weeks follow up. Topical permethrin was
superior to Tenutex emulsion.36 Very low quality evidence from a refugee camp on the Thai-Burmese
border assessed safety of permethrin and BB in pregnancy.38
b. Modified application of permethrin
Practice point Box: How is it best to apply topical scabicides?
Twenty-nine studies incorporated a topical scabicide/s, mostly permethrin. (Supplementary Table 4).
One study directly compared neck to toe application (head to toe in children) with application to
lesions only.39 Overall, head to toe or neck to toe was recommended in 26 studies, lesion only in four
(three of which were topical ivermectin and not specified in seven studies. Full body application of
topical scabicides is recommended (1D). The effective application of topical scabicides requires a
private setting where the clothes can be removed for application. This is not always practical or
achievable in overcrowded households and may limit the effect of topical therapy.
c. Oral treatment vs topical treatment
Moderate to high quality evidence supports the use of oral ivermectin or topical permethrin for the
treatment of scabies (1A).32,40-42
A comparison of topical 5% permethrin with oral ivermectin in a high quality RCT from India
found lesion count and pruritus significantly lower for permethrin at one week whilst clinical cure at
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four weeks was the same.40 Moderate quality evidence from India reached similar conclusions.32
From Iran, low quality evidence is provided from two studies that compared oral ivermectin with
topical permethrin and found superior symptom relief with permethrin at two weeks, whilst clinical
cure was the same.41,42 There is moderate-high quality evidence that oral ivermectin achieved
superior clinical cure than topical lindane43-45 or topical sulphur.46 Comparisons of oral ivermectin
with topical BB showed discrepant results: no difference in clinical cure based on high quality RCT
evidence from Vanuatu47 whilst oral ivermectin was superior for clinical cure in moderate quality
evidence from Senegal48 and Nigeria.49
II. Mass Drug Administration (MDA)
There is moderate quality evidence for MDA to control scabies in resource-limited communities
(1B),50-53 with high quality comparison studies needed to determine the best agent. Moderate
quality evidence for the population effect of MDA for scabies on scabies and impetigo prevalence
using either topical permethrin or oral ivermectin (1B).23,54-56 Oral ivermectin is superior to topical
permethrin and standard of care for community-wide use in children >5 years and non-pregnant
adults in isolated settings with high prevalence of scabies and impetigo (1B).57 High quality studies
conducted in mainland populations are required to determine the effectiveness of the MDA
approach in highly mobile populations.
a) Scabies only
Low to moderate quality evidence from four studies in Fiji,50 India52,53 and Tanzania51 assessed MDA
impact on scabies prevalence only. Two doses of oral ivermectin achieved a 95% reduction in scabies
in India52 whilst single dose ivermectin MDA was not superior to BB in Fiji.50 Ivermectin delivered in a
lymphatic filariasis MDA reported a 68-98% decline in scabies.51 When 25% BB was delivered in an
MDA to an Indian orphanage, cure was 100% at 6 weeks.53
b) Scabies and Impetigo
i. Permethrin MDA
Low quality evidence is provided from permethrin MDA’s, which were all ecological in design with
different populations reviewed at baseline and follow up. Four studies from Panama56 and remote
Australian Aboriginal communities23,54,55 showed a reduction in scabies and impetigo prevalence
following MDA with 5% permethrin. The first scabies MDA used permethrin in a remote Kuna Indian
population in Panama in 1986 and although interrupted by political tensions demonstrated a
sustained response.56 The permethrin MDAs were combined with impetigo treatment and broad-
based community skin programs including surveillance, health promotion, home cleaning and
retreatment of cases in Australia.23,54,55
ii. Ivermectin vs. Permethrin MDA
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Moderate quality evidence is provided from a cluster RCT where oral ivermectin and topical
permethrin MDAs were compared with standard case treatment with topical permethrin for scabies
in three Fijian island communities.57 Ivermectin was superior at 12 months for scabies and
impetigo.57
iii. Ivermectin MDA
Low quality evidence is provided from two studies that assessed the effect of oral ivermectin
MDA on scabies prevalence.58,59 In the Solomon Islands, two doses of oral ivermectin reduced the
prevalence of scabies at three years59 and this was sustained at a further follow up 15 years later.60
In contrast, an oral ivermectin MDA delivered in a remote Australian Aboriginal community did not
show significant or sustained declines in scabies prevalence.58
iv. Azithromycin MDA
Very low quality evidence from an azithromycin MDA for trachoma in a remote Australian Aboriginal
population reported impetigo reduction at 2 – 3 weeks which returned to baseline at 6 months.61
Scabies prevalence was unchanged.61
III. Complimentary therapy
Moderate quality evidence that cold cream can be used as an adjunct to topical sulphur for scabies
(2B).62
In a Mexican orphanage RCT, topical 10% sulphur in pork fat was compared with topical 10% sulphur
in cold cream with high rates of cure.62
IV. Communicable disease control and prevention
There is low quality evidence for treatment of household contacts for the community control of
scabies (2C).63 Treatment of cases and contacts is recommended in scabies outbreaks (2C), however,
high quality studies comparing treatments during outbreaks are required.
Low quality evidence for the treatment of household contacts as the primary intervention for
scabies control from one cohort of Australian Aboriginal households where a 6-fold reduction in
scabies in compliant households was found.63 Fifteen other studies treated close contacts, family
members or the household as co-interventions for scabies, however without a comparison group,
the effect cannot be reliably assessed. Moderate quality evidence found oral ivermectin halted a
scabies outbreak amongst health care workers and patients in Peru,64 and topical BB for cases and
contacts with community education terminated an outbreak in Israel.65
V. Environmental co-interventions
Although washing and storage measures are unlikely to cause harm and should be encouraged, high
quality studies assessing the clinical effectiveness of washing clothing and bed linen, storage of items
in plastic bags, exposure to sunlight and household spraying are required before these measures can
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be strongly recommended as adjuncts in the control of scabies. No studies used a control group to
assess the effect of environmental interventions for scabies. Twelve studies included washing of
clothing and bed linen,34,39,40,43,47-50,53,62-64 two studies included storage of items in plastic bags,22,64
four studies included exposing items to direct sunlight39,47,49,53 and one study included household
spraying,65 as co-interventions (Table 2).
4. Crusted scabies
Moderate quality evidence supports oral ivermectin with topical keratolytics and topical
antiparasitics for crusted scabies (1B).66,67 Comparative trials are needed to explore more effective
treatments. Patients with crusted scabies require intensive supportive treatment (1B).66,67
Coordinated case management in the home may be of benefit (2C).68
I. Directed antimicrobial therapy
Moderate quality evidence from a prospective cohort study of Australian Aboriginal inpatients
receiving oral ivermectin at days 0, 14 and 28 and daily topical permethrin alternating with
keratolytic therapy (topical urea 10% and lactic acid 5%), found 40% achieved complete cure at four
weeks.67
II. Standard treatment protocols
Moderate-quality evidence from a retrospective study used a standard treatment protocol in
Australian Aboriginal inpatients with crusted scabies achieving 55% without recurrence at eight
years.66
III. Coordinated case management
Low-quality evidence supports topical BB, regular keratolytics, moisturiser and regular screening for
new lesions in home-based case management to prevent crusted scabies.68
5. Fungal skin infections
I. Directed antimicrobial therapy
a. Tinea capitis
Moderate quality evidence for griseofulvin, terbinafine and fluconazole having similar efficacy for
tinea capitis (1B).69-72 Tinea capitis is difficult to treat, takes several months and mycological cure is
challenging.
High quality evidence of similar clinical and mycological cure was provided by a multicentre RCT
from Guatemala, Chile, Costa Rica, USA and India comparing daily oral fluconazole for 3 or 6 weeks
with daily griseofulvin.69 Low quality RCT evidence from Iran reported no difference between daily
fluconazole or daily griseofulvin at eight weeks.70 Low quality evidence from India found griseofulvin
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twice daily, fluconazole weekly and terbinafine daily all performed similarly.71 In addition, all used
Ketoconazole 2% shampoo and prednisolone prescribed for kerion.71 From China, low quality cluster
RCT evidence confirmed griseofulvin daily for four weeks or terbinafine daily for 2 – 4 weeks
performed similarly.72
b. Tinea corporis
Low to moderate quality evidence for topical sertaconazole, butenafine, miconazole or clotrimazole
over other agents for tinea corporis (2C).73-76 Low quality evidence that oral alternatives for tinea
corporis are terbinafine or fluconazole (2C).77 Although the systematic review on topical treatments
for tinea corporis recommends topical terbinafine as a first line agent,17 no high quality studies from
resource limited contexts were available to evaluate. Most included trials came from dermatology
outpatient clinics in India or Iran. Community setting, population level evidence is needed for tinea
corporis treatment.
Moderate quality RCT evidence from Iran confirmed similar clinical cure at eight weeks for
topical butenafine compared with topical clotrimazole75 and similar cure rates at four weeks for
topical miconazole and topical sertaconazole.73 Moderate quality RCT evidence from India found
sertaconazole outperformed miconazole with 62% and 45% cured at two weeks respectively,
p<0.05.74 Low quality evidence from India found topical clotrimazole and topical amorolfine were
comparable78 and that topical sertaconazole was superior to topical butenafine.76 Similarly, very low
quality pilot RCT evidence from India found superiority of topical sertaconazole over topical
terbinafine or topical luliconazole for clinical cure and symptom relief.79 Very low quality RCT
evidence also found no difference between topical sertaconazole and topical terbinafine80 and that
topical terbinafine and topical luliconazole could not be differentiated.81 Similarly, low quality RCT
evidence from India found daily oral terbinafine or weekly fluconazole achieved similar clinical
cures77 and topical butenafine was no better than weekly fluconazole combined with topical
Whitfield’s ointment (3% salicylic acid and 6% benzoic acid) at four weeks.82 Low quality evidence
from a prospective cohort of Australian Aboriginal people with tinea corporis and tinea unguium
found daily oral terbinafine cured 32%.83
c. Tinea unguium/onychomycosis
For tinea unguium, moderate to high quality evidence recommends oral terbinafine (1A),84-86 with no
added benefit of combination topical therapy in resource limited settings (1B).84,87 Surgical avulsion
prior to treatment of onychomycosis is not recommended (2D).87 High quality studies assessing
photo dynamic therapy (PDT) regimens for tinea unguium are required to determine the utility of
this therapy in resource-limited settings.
High quality RCT evidence from India trialled two different dosing regimens of terbinafine and
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showed no difference.84,85 Low quality RCT evidence from Brazil found monthly or second monthly
dosing of oral terbinafine had similar outcomes86 and photodynamic therapy (PDT) every 15 days for
6 months was superior to weekly oral fluconazole.88 No additional benefit of topical nail lacquer over
oral terbinafine alone was found in moderate quality evidence.84,87
II. Mass Drug Administration
No studies assessed the effect of antifungal MDAs on the prevalence of fungal skin infections.
III. Complimentary/alternative therapy
Further studies are needed to assess the role of aloe vera gel, as only very low quality evidence from
one study is available.89
IV. Communicable disease prevention and control
No studies assessed the effect of communicable disease control practices on fungal infections on
which to base relevant recommendations for resource-limited settings.
V. Hygiene practices
Daily soap use may be of benefit in the treatment of tinea capitis and tinea corporis. This is
recommended in combination with anti-fungal treatment (2C).90
From Tanzania, low quality RCT evidence found mycological cure at two months to be similar with
either daily washing with triclosan soap or placebo.90
6. Infrastructure including high quality water supply, swimming pools and housing improvement for
skin infections
I. Water provision
An adequate supply of water for washing and cleaning will reduce the burden of impetigo and
scabies (2C).91 From studies in remote Australian Indigenous communities, the installation of
community swimming pools may assist in the prevention of impetigo, along with other health
benefits (2C).92-94 No studies assessed the effect of quality water supply or swimming pools on
scabies or tinea on which to base recommendations for resource limited settings.
Low quality evidence from Panama found that when unlimited, high-quality water was
compared to a community with a limited water supply, declines in scabies and impetigo incidence
were reported.91 Low quality evidence from three studies in Australian Aboriginal communities
found a small benefit following the installation of swimming pools for impetigo and skin infections.92-
94
II. Housing improvement programs
Programs to improve housing may assist in the prevention and control of skin infections in resource-
limited populations (2C).95,96
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Low-quality evidence from a housing intervention evaluation of remote Australian Aboriginal
communities, found construction of new, standardised housing and the demolition of uninhabitable
dwellings did not change the prevalence of skin infections at 10 months.95 Low quality evidence from
a study that ran for 12 years showed reductions in skin infections following household
improvements based on health and safety priorities in a “survey and fix methodology.”96
Discussion
This is the first systematic review to comprehensively inform treatment, public health control and
areas for future research in the control of skin infections using evidence generated in and from
settings where skin infection burden is the highest. High quality evidence for treatment of the
individual and community with scabies and for the individual with impetigo is synthesised for
inclusion into evidence-based guidelines. Similarly, high quality evidence for comprehensively
addressing scabies and impetigo concurrently is presented, with further studies needed to
determine the measurable benefit of additional interventions over treatment alone. The integration
of oral antibiotics for treatment of impetigo, use of oral ivermectin or topical permethrin MDA for
scabies in endemic or outbreak settings and community education and health promotion activities in
skin health programs are supported by the evidence and should form the basis of skin control
programs when needed. Evidence gaps include community control of dermatophyte infections and
targeted environmental health interventions to improve skin health.
Progress towards the streamlined integration of data collection on skin infections when
planning MDAs for other infections needs ongoing prioritisation. MDA for trachoma and yaws with
azithromycin97-99 may also reduce the burden of impetigo,61 whilst ivermectin MDA for lymphatic
filariasis100 and scabies57 will reduce scabies and impetigo prevalence61 as part of the roadmap
towards defeating neglected tropical diseases.101 This pragmatic, evidence-based strategy is now
being tested in larger populations with results awaited (ACTRN12618000461291p) to inform
whether community control of scabies will prevent severe skin infections.
For impetigo, duration of treatment, the role of topical therapy and added benefit of
comprehensive skin disease control programs over treatment alone are gaps in the literature. Whilst
three or five days of cotrimoxazole for impetigo treatment in resource limited settings is effective,26
more comparison studies are needed to optimise treatment duration and utility of cheap, widely
available, palatable alternative agents in high burden contexts. Cephalexin for up to 10 days remains
in guidelines for impetigo, yet this is lengthy, costly and may be impractical with no evidence
supporting its use for impetigo in high burden contexts. Unlike developed settings where topical
mupirocin and fusidic acid are recommended,16 there are currently no trials using topical antibiotics
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for impetigo inhigh burden settings. Results from New Zealand comparing topical antibiotics or
antiseptics with placebo are awaited [ACTRN1261000356460].
Patient preference for agent to treat scabies and the additional benefit of comprehensive
control programs for scabies above treatment alone are knowledge gaps. Topical permethrin has
more rapid reduction in symptoms40,42 but requires a private space in which to apply the cream to
the full body. Conversely, clinical response is slower, but ease of administration and overall
community efficacy in MDA support the use of ivermectin.57 Future studies should address the role
of a second dose of ivermectin in asymptomatic individuals as unhatched eggs are refractory to
ivermectin.102 Moxidectin shows promise for future human scabies trials as it has a longer half-life
and is ovicidal.103
Most studies assessing antifungal treatments were from dermatology OPD in middle income
country hospitals, which limits the external validity to other resource limited settings. Studies
assessing the effectiveness of topical and oral (for severe disease) treatments of tinea in a range of
resource-limited populations would be of benefit to make recommendations applicable to real life,
uncontrolled settings at the individual and population level. Future integration of treatment of tinea
into comprehensive skin disease control programs that address scabies and impetigo may be a way
forward.
Despite practical advantages, we found limited evidence for environmental interventions to
control skin infections. Although sound attempts to evaluate housing programs have been made,95,96
we remain unable to recommend small scale environmental interventions due to a lack of
comparative studies. For example, no studies compared household spraying with no intervention to
eradicate the scabies mite. Similarly, there was no evidence for hot washing of clothing compared to
not washing clothing. Although environmental measures are unlikely to cause harm in combination
with treatment of the skin infection, research is needed to determine any measurable benefit above
standard treatment to inform environmental health teams tasked with managing scabies outbreaks,
clinicians managing skin infections or governments and communities intending to include
environmental policy recommendations in comprehensive skin health programs in endemic areas.
Although 1759 non-duplicate studies were found for potential inclusion in this systematic
review, most were excluded prior to the final appraisal of 81 studies meeting the full inclusion
criteria (see Figure 1). This is the complete synthesis of available literature on these four skin
conditions. It is possible that restriction to English language publications or being unable to find the
full text publication has been a limitation in the scope of this, although <30 full-text studies were
excluded for this reason.
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Conclusions
A summary of the evidence-based recommendations for skin infections in high burden contexts also
highlights the need for further rigorous, experimental studies to fill the evidence gaps. Pragmatic,
practical, high quality, well-funded RCTs are essential in the settings where the findings will have
external validity if meaningful progress is to be made towards reducing the gap in skin health
outcomes between the rich and poor. Acknowledging that RCTs may present ethical issues for some
groups,104 robust observational studies of appropriately funded public health interventions can be
tested across large populations with designs that control for confounders and in meaningful
partnership with the communities under study using participatory research methods.
Acknowledgements
We wish to thank the following for assistance with the conduct of this review: Marianne Mullane
and Claudia Sampson for secretarial support; Aleisha Anderson, Ingrid Duff, Claire Ferguson, Myra
Hardy, Therese Kearns, Ella Meumann, Lauren Thomas, Georgia Walker and Daniel Yeoh for data
extraction contributions.
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Correspondence: Asha Bowen, Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon
Kids Institute, 100 Roberts Road, Subiaco WA 6008, Australia. Phone +61 412 608 003, email
Asha.bowen@telethonkids.org.au
Supporting Information Legends
Box: Definitions for Indigenous peoples and Income groupings used
Supplementary File 1: Evidence Summary and Recommendations for skin infection related research
to guide practice in resource limited settings.
Supplementary Table 1: List of studies included in the systematic review.
Supplementary Table 2: Risk of bias table with overall quality ratings using the GRADE approach for
included experimental and controlled studies
Supplementary Table 3: Risk of bias table with overall quality rating using the GRADE approach for
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included observational studies
Supplementary Table 4. Method of application of topical scabicides in 29 included studies
Supplementary Checklist: PRISMA Checklist
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Figure 1. PRISMA Flow Diagram for study selection in the systematic review
Records identified through database
searching (n = 3647)
Screening
Included
Eligibility
Additional records identified through
other sources (n = 8)
Records after duplicates removed
(n = 1759)
Titles screened
(n = 1759)
Records excluded
(n = 262)
Full-text articles assessed
for eligibility (n = 193)
Full-text articles excluded
(n = 112)
Reasons:
No intervention/no assessment
of effect of exposure on the
outcome (n=31)
Wrong study design (n=27)
Not in English (n=19)
Unable to obtain full-text (n=8)
Wrong outcomes (n=8)
Wrong patient population (n=9)
Wrong setting (n=4)
Duplicate report of published
paper (n=3)
Wrong indication (n=1)
Studies included
(n = 81)
Duplicates
(n = 1893)
Abstracts screened
(n = 455)
Records excluded
(n = 1304)
Identification
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Figure 2. Selected summary characteristics of studies included in the systematic review.
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Table 1. Grading of Recommendations Assessment, Development and Evaluation Evidence Grades
and Strength of Recommendations
*1D and 2D recommendations are not routinely included by the GRADE approach as these are based
on expert consensus, rather than scientific evidence. These additional recommendation grades were
created due to lack of available supporting evidence but an identified need to make
recommendations to guide clinical and public health management.
Code
Quality of Evidence
Definition
A
High
Further research is very unlikely to change the level of
confidence in the estimate of effect. i.e.
Several high-quality studies with consistent results
B
Moderate
Further research is likely to have an impact in current
confidence in the estimate of effect and may change the
estimate. i.e.
One high quality study
Several studies with some limitations
C
Low
Further research is very likely to have an important
impact on the level of confidence in the estimate of
effect and would likely change the estimate. i.e.
One or more studies with severe limitations
D
Very Low
Estimate of effect is very uncertain. i.e.
No direct research evidence
One of more studies with very severe limitations
Code
Strength of
recommendation
Implications when combined with evidence grade
1
Strong
1A: Strong recommendation, applies to most patients
without reservation. Clinicians should follow a strong
recommendation unless a clear and compelling rationale
for an alternative approach is present.
1B: Strong recommendation, applies to most patients.
Clinicians should follow a strong recommendation unless
a clear and compelling rationale for an alternative
approach is present.
1C: Strong recommendation, applies to most patients.
Some of the evidence base supporting the
recommendation is, however, of low quality.
1D: * Strong recommendation, applies to most patients.
However, the recommendation is based on expert
consensus only.
2
Weak
2A: Weak recommendation and best action may differ
depending on circumstances or patients or societal
values.
2B: Weak recommendation and alternative approaches
likely to be better for some patients under some
circumstances.
2C: Very weak recommendation; other alternatives may
be equally reasonable.
2D: * Very weak recommendation based on expert
consensus. Further research is necessary.
Accepted Article
This article is protected by copyright. All rights reserved.
Table 2: Number of studies in each broad intervention group by skin condition. Gaps in the evidence
are shown as grey boxes.
*Communicable disease control activities= outbreak response or treatment of contacts. #Water
provision= swimming pools or clean water supply to homes. ~Hygiene practices= provision of soap
and hand washing education.
Intervention
Condition
Total
numbe
r of
studies
Impetig
o
Scabies
Scabies
and
impetigo
Crusted
scabies
Fungal
skin
infection
s
Multiple skin
conditions
under study or
“skin
infections” that
were not
otherwise
specified
Comprehensi
ve
community
skin health
programs
1
1
1
3
Coordinated
case
management
1
1
Standard
treatment
protocols
1
1
Directed
clinical
treatment
4
19
1
23
47
Mass Drug
Administrati
on
4
9
13
Compliment
ary/alternati
ve therapy
2
1
1
4
Communicab
le disease
control*
3
3
Hygiene
practices~
2
1
3
Water
provision#
1
1
2
4
Housing
programs
2
2
Total
7
29
11
3
25
6
81
Accepted Article
This article is protected by copyright. All rights reserved.
Table 3: Number of included studies with public health co-interventions for skin infections
*Total does not equate to 81 studies as some studies had more than one public health intervention.
Skin condition
Public health
co-interventions
Treatment of
contacts
Promotion of regular
bathing and/ or
hand-washing
Health education
Washing of clothing
and bed linen
Storage of items in
plastic bags
Exposing items to
direct sunlight
Household spraying
Impetig
o
2
2
1
Scabies
22
14
2
6
12
2
4
1
Scabies
and
impetig
o
5
1
1
3
2
1
1
Crusted
scabies
Fungal
skin
infectio
ns
1
1
General
skin
infectio
ns
4
2
2
Total
34
15
8
12
14
2
5
2
