Treatment of close contacts of people with scabies for preventing re-infestation or spread of infestation in contacts

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of treating contacts of people with scabies in order to prevent the development of symptoms of infestation in the contacts, and to prevent the recurrence of scabies in the index case and further spread to additional contacts and beyond.

Background

Description of the condition

Scabies is a common parasitic infection. It is present worldwide, and up to 300 million cases are thought to occur each year (Chosidow 2006). It is caused by a mite, Sarcoptes scabiei variety hominis (Green 1989), also known as the human itch mite. Crusted scabies (or Norwegian scabies) is caused by the same mite, but is associated with very large numbers of mites and tends to occur in immunocompromised hosts, e.g. transplant patients on immunosuppressive therapy, alcoholics, the elderly or other debilitated people.

Sarcoptes scabiei is a mite which depends on humans for survival, and infection occurs by human to human spread (Hengge 2006). Thus, it tends to be more prevalent in areas with poor sanitation or in circumstances where there is frequent close person to person contact, as in overcrowding. In developed countries where sanitation problems and overcrowding are not as prevalent, it tends to spread between family contacts, between residents in residential care, or between patients and staff in hospitals.

Mites crawl on the skin surface at approximately 2.5 cm per minute (Hengge 2006) but can neither fly nor jump. They can survive three to four days off the host, depending on environmental conditions (Green 1989). Mating occurs on the skin surface (Chouela 2002), before the gravid female mites burrow into the skin (Chosidow 2006), where eggs are laid. Several days later, the eggs hatch, and nymphs emerge; three moults are required before the mite reaches maturity (Chouela 2002).

Direct skin to skin contact is required for transmission to occur. Whether transmission can occur via fomites (object or substance capable of carrying infectious organisms, for example, clothing, bedding, etc.) is uncertain, and conflicting opinions exist (Blumenthal 1976; Chosidow 2006; Chouela 2002; Orion 2006). Individuals with classical scabies are typically infected with up to 50 mites (Orion 2006). In immunocompromised hosts, however, crusted scabies can develop, and the individual is likely to be infected with a minimum of several thousand mites. Crusted scabies is thought to be more infective than classical scabies. This higher infectivity is attributed to the higher "volume" of infection, and the increased shedding of skin scales which carry the mites, which some believe could facilitate the spread of infection via fomites (Arlian 1989; Chosidow 2006).

Itch is the most prominent symptom, although this is often limited in immunocompromised hosts with crusted scabies (Scheinfeld 2004). The itch tends to be worse at night (Green 1989). Those affected can develop a cutaneous eruption, consisting of a variety of lesions, over most of the body. Some patients may develop secondary bacterial infections, such as impetigo, as a consequence of the disrupted skin barrier from scratching due to the profound itch. In crusted scabies, patients typically develop a psoriatic type eruption, which can be present on the hands, feet, trunk and face (Orion 2006).

The symptoms experienced are generally attributed to the development of an allergic reaction to the mite or its excreta. Consequently, symptoms are not likely to develop until four to six weeks after primary infection (Green 1989). On subsequent infections, symptoms generally develop within hours to days (Chouela 2002). Additionally, successful treatment does not always result in elimination of symptoms until several weeks later, as patients can continue to have a hypersensitive response to the mite or its products (i.e. post-scabetic itch).

On examination, lesions may be noted in particular in the finger web spaces, on the elbows, in the axilla, on breasts, and on the buttocks and genitalia. Burrows, nodules and vesicles may be seen. In adults, lesions do not generally occur above the neck. In young children and in vulnerable populations, lesions can occur above the neck, and mites can occasionally be observed in the retroauricular fold (Chouela 2002). Skin scales are commonly associated with crusted scabies.

Skin scrapings may facilitate direct observation of mites, eggs, or mite faeces pellets (Chosidow 2006; Hengge 2006). This is achieved by applying a drop of mineral oil to the suspected lesion, then using a scalpel blade to scrape away the oil and the entire lesion, which are transferred onto a slide for microscopic examination (Chouela 2002). Alternatively, a shave biopsy can be performed, whereby the top of the papule is removed and placed on a microscopic slide for further examination (Chouela 2002). The "burrow ink test" on the other hand depends on the burrows absorbing ink (Hengge 2006).

There are several recommended treatments for scabies. These have been extensively discussed in another Cochrane review (Strong 2010). Both oral (e.g. ivermectin, thiabendazole, flubendazole) and topical therapies (e.g. lindane, permethrin, sulfur-containing products, crotamiton, malathion benzyl benzoate) are available (Chouela 2002; Scheinfeld 2004). Oral Ivermectin (Guay 2004), is not widely available and has not been approved in some jurisdictions for the treatment of scabies (Bouvresse 2010). The usual treatments are topical, and typically require application over all of the body for many hours duration. There is no international consensus on the appropriate schedule of treatment, and recommendations in one jurisdiction may not be appropriate in others (Bouvresse 2010). Multiple treatment doses are often recommended over days to weeks. Some patients require symptomatic treatment for the itch, including post-scabetic itch or itch caused by medication. Antihistamines and emollients have been recommended in this regard (Chouela 2002).Topical or systemic antibiotics may be required if secondary skin infection has developed.

It is also advised that close contacts of those with scabies should be treated concurrently (Chouela 2002; Paasch 2000; Scheinfeld 2004), as they may be infected without yet manifesting symptoms, and so act as a reservoir of infection. Treating the contacts may prevent reinfection of the index case following treatment. Although the treatments used are generally safe, allergies to treatment are possible, and adverse events including death have been reported (Nolan 2011). The logistics required to treat all contacts simultaneously are considerable (Scheinfeld 2004; Stoevesandt 2012). For example, this would be very difficult to co-ordinate in an institutional setting where, along with the index case, other patients, family members, and all staff who had contact with the index case are all advised to also have treatment.

Description of the intervention

Following contact with an index case, where the contact has not been infected with scabies previously, symptoms often take up to four to six weeks to develop. During this long incubation period, the contact may act as a reservoir for onward infection to their contacts (Green 1989), or may cause re-infection in the index case (Buehlmann 2009). Therefore, treatment is recommended for contacts of the index cases, simultaneously to treating the index case, even in the absence of symptoms, for two reasons. FIrstly, early treatment will reduce the chance that the contact will develop symptoms of scabies infestation. Secondly, the contact may not have any symptoms in early infection, but may still be able to transmit the infection.

There has been some success with the provision of scabies treatment for the whole community, in settings where there is a high prevalence of scabies (Carapetis 1997). Such community initiatives have assisted in the eradication of scabies, and require screening, health education regarding the risk of scabies infestation, provision of drug treatments, and advice and support with non drug treatments (Kanaaneh 1976). Consequently, guidelines have been developed in some areas that recommend community-wide treatment to control scabies (Currie 2000).

This review will focus on localised secondary preventative measures, where scabies treatment is used to prevent the spread of infestation or to prevent re-infestation. It is generally recommended that along with the index case, contacts of the index case should be considered for prophylactic treatment (Chouela 2002; Scheinfeld 2004). This recommendation is made for several reasons:

  • infection may have been transmitted to contacts who may remain asymptomatic but develop symptoms at a later stage,

  • untreated contacts may act as a reservoir of infection and may re-infect the index case, and

  • untreated contacts may be a source of onward transmission of infection to others.

Onward transmission to others would be particularly problematic in healthcare or residential settings, where infection may be spread to vulnerable patients. Additionally, where employees are infected, they may require restriction from work until treatment has been initiated to limit the chance of onward transmission. This has implications for the staffing levels and the workforce in general (Bouvresse 2010).

Generally, contacts of the index case are prescribed treatment (either the same treatment as the index case, or a shorter regimen, or a different treatment), and are provided with advice regarding washing of clothes and bedding (Buehlmann 2009).

How the intervention might work

Treating the contacts of the index case potentially limits the development of infection (both asymptomatic and symptomatic) in the contacts of the index, and restricts onward transmission of infection to others, and re-infection of the index case (Chouela 2002). This is particularly important in settings where there are a large number of people in close proximity to each other or in settings where there are vulnerable populations, such as nursing homes, residential care homes, or other healthcare settings.

Why it is important to do this review

Prophylactic treatment continues to be recommended for all types of contacts, including family contacts, residential or institutional contacts, and healthcare exposures. The level of exposure of the contact to an index case in these settings, however, is subject to considerable variation: shaking hands; cuddling a baby for a prolonged period; assisting a nursing home resident with bathing and dressing; sexual contact; holding hands; and children playing sports together.

It is not clear whether prophylaxis is more appropriate than a "wait and see" approach (Chouela 2002), whereby contacts are educated regarding the possibility of infection, and advised to seek medical attention should they develop symptoms suggestive of infection.

Concerns regarding prophylaxis include:

  • considerable commitment on the part of the exposed contacts of index cases of scabies and their required willingness to take treatment (Buehlmann 2009),

  • recommending prophylaxis where the contact may not be able to describe the level of contact they had with the index case, or may not be able to consent to treatment (Ejidokun 2007),

  • recognised side-effects associated with some of the treatments recommended, some of which are serious (Bouvresse 2010),

  • possibility of resistance to anti-scabicitic treatments (Chouela 2002; Currie 2004),

  • the stigma associated with a diagnosis of scabies, which may lead to non-compliance and a reluctance to disclose the diagnosis to close contacts (Heukelbach 2006), (as society frequently associates scabies with poor hygiene and poverty),

  • considerable cost associated with providing medical treatments to contacts (e.g. a whole family, other patients and staff in a residential care setting) (Vorou 2007), and

  • frequently, there are logistic difficulties in identifying all contacts of an index case (e.g. a child with scabies infestation may attend school, after school care, and other recreational activities) (Buehlmann 2009).

The results of this review will particularly influence occupational health policy and practice in the treatment of contacts of scabies in the healthcare and residential care settings, and may possibly be wider reaching, for example, school and prison workers.

This review will summarise the effectiveness and safety of prophylactic treatment in various settings, and will be updated as further new evidence becomes available.

Objectives

To assess the effects of treating contacts of people with scabies in order to prevent the development of symptoms of infestation in the contacts, and to prevent the recurrence of scabies in the index case and further spread to additional contacts and beyond.

Methods

Criteria for considering studies for this review

Types of studies

We will include in this review all randomised controlled trials in which prophylactic interventions (both drug treatments and non-drug treatments) are compared with another treatment or with no treatment or placebo treatment. In addition, we will include any cluster-randomised controlled trials, where groups of individuals have been randomised to receive treatment.

Types of participants

We will include trials involving people who had contact with an index case with scabies infestation within the previous six weeks.

Diagnosis of the index case will have been made by a physician, or other suitably qualified healthcare professional, in those with symptoms suggestive of infection (e.g. itch that is worse at night), and either a positive dermatological examination (burrows, papules, vesicles), or a positive microscopic parasitological examination.

The population of interest is people of all ages, both male and female.

We will exclude studies where:

  • greater than 10% of the study population had symptoms suggestive of scabies infestation prior to the administration of prophylaxis, or

  • study participants were diagnosed with and treated for scabies within three months prior to the reported exposure (to limit the potential of including people with possible treatment failure).

Types of interventions

We will include all studies where a prophylactic intervention was recommended for people who were exposed to an index case of scabies.

Prophylactic interventions can include medical treatment (medication which would generally be prescribed as a treatment for scabies) and non-medical conservative management.

We will group the conservative interventions according to their working mechanism, e.g.

  • barrier precautions (including patient isolation, patient cohorting, etc.),

  • personal hygiene measures (including hand washing), and

  • environmental decontamination (including advice to wash clothing and bedding).

Trials may include one treatment or combinations of treatments versus placebo, no treatment, or other treatment(s).

Types of outcome measures

We are interested in the following outcome measures.

Primary outcomes

The primary outcome is the incidence of scabies in contacts of index cases who were advised to use some prophylactic treatment, within eight weeks of being recommended to use the prophylactic treatment. Diagnosis of scabies in contacts is based on the clinical opinion of a physician or other suitably qualified health professional, on the basis of the development of clinical symptoms suggestive of scabies and either positive physical examination findings or positive microscopy.

Secondary outcomes

Secondary outcomes consist of reported adverse events in people treated with prophylaxis which is attributed to the prophylactic treatment. These include:

  • serious adverse events e.g. toxicity, hospital admission, fatality,

  • minor adverse events e.g. transient skin irritation,

  • patient acceptability e.g. complaints regarding application, and

  • compliance.

Search methods for identification of studies

Electronic searches

We will search for studies from the following electronic databases from their earliest record to date:

  • Cochrane Occupational Safety and Health Review Group Specialised Register,

  • Cochrane Central Register of Controlled Trials (CENTRAL),

  • MEDLINE,

  • EMBASE,

  • LILACS,

  • CINAHL (Cumulative Index to Nursing and Allied Health Literature),

  • OpenGrey (System for Information on Grey Literature in Europe), and

  • WHO ICTRP (World Health Organization International Clinical Trials Registry Platform).

Strategies for all the databases to be searched will be based on the MEDLINE search strategy presented in Appendix 1 using the sensitivity-maximising version of the Cochrane Highly Sensitive Search Strategy (Higgins 2011), and will be modified for use in other databases. We will not limit the search by language.

Searching other resources

We will scan the reference lists of all relevant studies for possible additional studies. We will not undertake any additional handsearching of journals.

Data collection and analysis

Selection of studies

Two review authors (DF and FK) will be involved in the study selection. Where it is clear from the title and/or abstract that a study does not include details of a study that involves treating asymptomatic contacts of an index patient, we will exclude the study. The two review authors will form their opinions regarding whether the study meets the pre-defined criteria independently. Where any differences of opinions arise, we will have a third review author (AR) make the final decision. For non-English language articles, we will seek translation of the title and abstract, and subsequently the original article into English if necessary.

We will exclude articles if it is clear from the title and/or abstract that:

  • the study was not a randomised controlled trial, or

  • the trial did not provide treatment to contacts of an index case of appropriately diagnosed scabies infection, or

  • the trial did not investigate the incidence of scabies in those contacts who were treated with prophylactic treatment.

Two review authors (DF and FK) must agree on the studies selected for exclusion. Where there is disagreement regarding the excluded selection, further opinion will be sought from a third review author (AR).

Data extraction and management

Two review authors (DF and FK) will independently extract the required data from the selected studies, and record this data on an agreed data collection form. One review author (DF) will generate this data collection form. Two review authors (DF and FK) will pilot the data collection form regarding it's applicability and ease of use. Where necessary, we will make changes prior to formal commencement of data extraction. Where there are differences of opinion regarding the extracted data, we will seek further opinion from a third review author (AR). Where identified, we will compile data from multiple articles regarding the same study to ensure complete data extraction. One review author (DF) will enter statistical data into Review Manager 5.1 software (RevMan 2011). A second review author (FK) will check the data.

Assessment of risk of bias in included studies

Two review authors (DF and FK) will independently assess the risk of bias of included studies.

We will judge the risk of bias of the included randomised trials using the Cochrane Collaboration’s tool as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will grade each study for risk of bias in each of the following seven domains, with ratings of low risk of bias, high risk of bias or uncertain risk of bias.

  1. Random sequence generation.

  2. Allocation concealment.

  3. Blinding of participants and personnel.

  4. Blinding of outcome assessment.

  5. Incomplete outcome data.

  6. Selective reporting.

  7. Other sources of bias.

We will refer to a third review author (AR) to resolve disagreements.

It may be difficult to blind participants for some prophylactic treatments (both drug treatments and non drug treatments). We will discuss the blinding applied in the included studies in our review, including details of who of the participants or personnel were blinded.

Measures of treatment effect

In order to assess the effectiveness of the different pharmacological interventions, we will extract dichotomous data from the included studies (e.g. did or did not develop infection). We will undertake a meta-analysis of the dichotomous data and express the results as risk ratios (RRs) with 95% confidence intervals (CIs).

We will record the occurrence of adverse events as dichotomous data, and we will calculate RRs (with 95% CIs) for each adverse outcome associated with each prophylactic treatment used.

Unit of analysis issues

Some of the studies may have used a cluster-randomised controlled trial study design. To account for problems with cluster-randomised controlled trials (Eldridge 2004), if any meet our inclusion criteria, we will assess the trials for unit of analysis error, and where necessary, we will re-analyse outcomes as per the methods outlined in the Cochrane Handbook for Systematic Review of Interventions (Higgins 2011), and report this in our review. Where clustering has not been considered, and it is not possible to re-analyse the results, we will report this in our review.

Dealing with missing data

If data appear to be missing, we will seek to obtain the missing data through correspondence with the study authors. If the authors cannot provide the missing data we will try to calculate them ourselves, such as standard deviations (SDs) from P values or CIs, according to the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). If this is not possible, we will use imputation methods, such as Last Observation Carried Forward (LOCF) or we will take values from other studies if the data are needed for meta-analysis. We will evaluate the impact of these decisions on the results of the meta-analysis in a sensitivity analysis.

Assessment of heterogeneity

Two review authors (DF and FK) will assess studies for clinical heterogeneity, based on the interventions, control interventions, and outcomes. We will only conduct meta-analysis where the study population and interventions are sufficiently similar. Furthermore, heterogeneity will be assessed using the I2 test. If the I2 test is < 50%, we will use a fixed-effect model. If the I2 is > 50% we will use a random-effects model.

Assessment of reporting biases

We will reduce the effect of reporting bias by including studies and not publications in order to avoid the introduction of duplicated data (i.e. two articles could represent duplicate publications of the same study). Following the (Cho 2000) statement on redundant publications, we will attempt to detect duplicate studies and, if more articles report on the same study, we will extract data only once. We will prevent location bias by searching across multiple databases. We will prevent language bias by not excluding any article based on language. If sufficient data are available, we will assess publication bias by using a funnel plot.

Data synthesis

We will pool data from studies judged to be clinically homogeneous using Review Manager 5.1 software (RevMan 2011). If sufficient data are available, we will perform meta-analyses. When studies are statistically heterogeneous, we will use a random-effects model; otherwise we will use a fixed-effect model. When using the random-effects model, we will conduct a sensitivity check by using the fixed-effect model to reveal differences in results. We will include a 95% CI for all estimates.

We will use the GRADE approach as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and as implemented in the GRADEPro 3.2 software (GRADEpro 2008) to present the quality of evidence and ‘Summary of findings’ tables.

The downgrading of the quality of a body of evidence for a specific outcome will be based on five factors.

  1. Limitations of study.

  2. Indirectness of evidence.

  3. Inconsistency of results.

  4. Imprecision of results.

  5. Publication bias.

The GRADE approach specifies four levels of quality (high, moderate, low and very low).

Subgroup analysis and investigation of heterogeneity

If there are sufficient data we will perform subgroup analysis to investigate the outcome in various specific defined populations (household, residential, nosocomial, non-healthcare work exposures). In addition, if possible, we will perform subgroup analysis on groups exposed to crusted (Norwegian) scabies, as opposed to classical scabies.

Sensitivity analysis

We will use sensitivity analysis to assess the impact of the following:

  • decisions regarding the prophylactic dose of drug treatments chosen,

  • duration of study follow-up,

  • loss to follow-up data. i.e. impact of excluding studies with an attrition rate greater than of equal to 20%,

  • Were data is imputed (e.g. in included studies where a poor outcome is assumed as the primary outcome), we will assess the impact this has on the results, and

  • blinding status of participants and personnel.

Acknowledgements

The authors are grateful for the support provided by the Cochrane Occupational Safety and Health Group's Co-ordinating Editor Jos Verbeek, and Managing Editor Jani Ruotsalainen. We would also like to thank the following people for their constructive feedback: Prof Hywel Williams, Dr Mark Strong, Dr Ira Madan, Mr Wim van Veelen, Ms Anneli Ojajärvi and Ms Sharea Ijaz.

Appendices

Appendix 1. MEDLINE search strategy

1.    randomised controlled trial.pt

2.    controlled clinical trial.pt

3.    randomized.ab

4.    placebo.ab

5.    drug therapy.mp

6.    randomly.ab

7.    trial.ab

8.    groups.ab

9.    1 or 2 or 3 or 4 or 5 or 6 or 7 or 8

10.  animals.sh not/ (humans.sh and animals.sh)

11.  9 not 10

12.  Scabies.mp

13.  Sarcoptes scabiei.mp

14. Human itch mite.mp

15.  (crusted adj6 scabies)

16.  (Norwegian adj6 scabies)

17.  12 or 13 or 14 or 15 or 16

18.  Prophyla*.mp

19.  Prevent*.mp

20.  Control*.mp

21.  Treat*mp

23.  Decontaminat*.mp

24.  Therap*.mp

25.  Lindane OR hexachlorocyclohexane.mp

26.  Permethrin.mp

27.  Ivermectin.mp

28.  Crotamiton.mp

29.  Sulphur.mp

30.  Malathion.mp

31.  Benzylbenzoate.mp

32.  18 or 19 or …..or 31

33.  11 AND 17 AND 32

 

History

Protocol first published: Issue 7, 2012

Contributions of authors

DF initiated and designed the review and drafted the protocol. FK critiqued the draft protocol, and made modifications to the protocol. AR provided advice on the design of the review, critiqued the draft protocol, and made amendments to the protocol.

Declarations of interest

None of the researchers have a commercial for profit interest in the outcomes of this review.

Sources of support

Internal sources

  • Occupational Health Department, Adelaide and Meath Hospital incorporating the National Children's Hospital, Tallaght, Dublin 24, Ireland.

    IT access

External sources

  • No sources of support supplied

Ancillary