In Africa, an estimated 300-500 million cases of malaria occur each year resulting in approximately 1 million deaths. More than 90% of these are in children under 5 years of age. To identify commonly held beliefs about malaria that might present barriers to its successful treatment and prevention, we conducted a systematic review of qualitative studies examining beliefs and practices concerning malaria in sub-Saharan African countries.We searched Medline and Scopus (1966-2009) and identified 39 studies that employed qualitative methods (focus groups and interviews) to examine the knowledge, attitudes, and practices of people living in African countries where malaria is endemic. Data were extracted relating to study characteristics, and themes pertaining to barriers to malaria treatment and prevention.The majority of studies were conducted in rural areas, and focused mostly or entirely on children. Major barriers to prevention reported included a lack of understanding of the cause and transmission of malaria (29/39), the belief that malaria cannot be prevented (7/39), and the use of ineffective prevention measures (12/39). Thirty-seven of 39 articles identified barriers to malaria treatment, including concerns about the safety and efficacy of conventional medicines (15/39), logistical obstacles, and reliance on traditional remedies. Specific barriers to the treatment of childhood malaria identified included the belief that a child with convulsions could die if given an injection or taken to hospital (10/39).These findings suggest that large-scale malaria prevention and treatment programs must account for the social and cultural contexts in which they are deployed. Further quantitative research should be undertaken to more precisely measure the impact of the themes uncovered by this exploratory analysis. Plasmodium falciparum malaria infection, and more than two thirds of these cases were in Africa [Each year, malaria accounts for up to 1 million deaths worldwide, mostly in children under five [n Africa . More ren Africa .During the past decade, numerous large-scale initiatives have been undertaken with the goal of reducing or eradicating the burden of malaria in the developing world. These include among others the Global Fund for AIDS, Tuberculosis, and Malaria (GFATM), the Roll Back Malaria Partnership (RBM), and the Medicines for Malaria Venture (MMV). The ambitious goals set by these programs for reducing the burden of malaria in the near future appear unlikely to be met .The success of antimalarial interventions requires appropriate coordination of efforts, as well as acceptance at the community and individual levels. Numerous barriers to adequate malaria control programs now exist, including the increasing prevalence of drug and insecticide resistance, the high rate of HIV co-infection, climate change, and civil unrest . Added tQualitative studies provide greater insights into personal experiences than quantitative methods . An exceWe conducted a systematic review of qualitative studies using methods previously described . We idenTo identify articles for inclusion in our analysis, we searched Medline  and Scopus . The complete search strategy is outlined in the Appendix. Reports produced by government, non-governmental organizations, and industry that were not subject to peer review, so-called "grey literature", were not included because the methodological quality of such accounts is difficult to ascertain.Two of us  independently screened a representative sample of 250 articles, in order to develop inclusion and exclusion criteria. The primary author then screened the remaining articles, using the criteria developed. We retrieved all the articles describing studies that made any use of qualitative methods  to investigate the knowledge, beliefs, attitudes, and practices related to malaria amongst residents of an area where malaria is prevalent. Where no abstract was available, we retrieved articles if they included the term "malaria" in the title, with at least one of "beliefs", "knowledge", "attitudes", or "practice". We added to these the papers that were identified through a review of references.To ensure we included purely observational qualitative data representing the views of the majority of patients and caregivers, we examined in detail the methods sections of all of the articles selected from the review of abstracts. We excluded the remaining quantitative studies, the second instances of articles found in both databases, those in which an experimental or interventional design was used, and those focused on either travellers, drug sellers, adverse drug events, or malaria in pregnancy. Of the remaining articles, we selected only those written in English, describing studies conducted in sub-Saharan African countries.Two of us  independently reviewed the results sections of a representative sample of the articles selected for analysis, and extracted themes relating to beliefs about the causes, treatment, and prevention of malaria. A separate author (KW) categorized the extracted themes to produce a scoring checklist. With this checklist, all of the included articles were reviewed, to determine which articles identified each of the themes. Discrepancies were resolved by consensus.For studies carried out amongst a population where there is no direct translation of the term "malaria", the local terminology for febrile illness was assumed to refer to malaria. This assumption was only made in cases in which the original authors indicated that this was warranted, and in which they themselves had used the terms interchangeably. For articles in which both qualitative and quantitative data were reported, only the qualitative data were used in the analysis.For a representative sample of articles, we also extracted data on study methodology and assessed quality by means of the CASP critical appraisal tool . As the For the initial selection of abstracts, we estimated level of agreement between reviewers using the κ statistic.Our search identified 1017 articles , homa (Tanzania and Kenya), soumaya (Burkina Faso), and omusujja (Uganda). While these terms translate roughly to the English word "fever", their meanings encompass a number of other symptoms, such that they correspond closely to the clinical presentation of malaria [In many of the studies included in the analysis, the local vernacular of disease terms was used. While these languages often lacked a direct translation for the English word "malaria", they included a single-word term or phrase of similar meaning. Examples of this include the terms  malaria ,31.The themes extracted from the articles are shown in Tables 3 and 4 [see additional file Twelve articles reported the use of ineffective prevention practices, such as eating a balanced diet, drinking herbal teas, wearing charms or amulets, and vaccinating children. Seven articles identified the belief that malaria cannot be prevented.Plasmodium parasites (median publication year 2002). Of these, the most frequently identified included environmental factors , dietary factors , drinking or bathing in dirty water, and supernatural causes .Twenty-seven out of the 39 articles analyzed described the belief that malaria is caused by factors other than mosquitoes and In 6 articles, mosquitoes were not mentioned amongst the causes of malaria reported by the study participants. These beliefs were shown in some studies to have an important impact on prevention:Malaria cannot be prevented because we were all born with it and it grows in us once a while, it manifests itself by giving us fever. When we treat it, we get better but the malaria is still there and will come again but to prevent it from coming you have to take an enema every day [very day .A related theme that was identified in 19 of the articles was the tendency to ascribe syndromes that likely represent severe or complicated malaria, including convulsions and anemia, to non-malarial causes (median publication year 2002). Specifically, convulsions were frequently ascribed to witchcraft, possession by spirits, or exposure to birds and animals with supernatural properties. This theme was identified most frequently in articles focused on malaria in children.Thirty-seven of the 39 articles identified barriers to active treatment. The most frequently identified concern about conventional therapy, reported in 10 of the articles analyzed, was the belief that a child with convulsions could die if given an injection. Three of these articles also identified the belief that a sick child could die if taken to hospital. Yet another article reported the belief that antimalarials should be withheld from a child with fits. Nearly all of the studies that identified these themes were conducted in East Africa (median publication year 2000).Other reported barriers to treatment included beliefs about the efficacy and use of conventional medicines, and beliefs about the role of traditional therapies. A total of 17 articles described a preference for traditional remedies in cases where the illness was believed to be caused by spirits or witchcraft, when complications occurred, or as a means of removing the root cause prior to supportive care in hospital. This was particularly evident in the case of childhood convulsions, which were often believed to be due to spirits or witchcraft, and were accordingly treated by traditional means:"Degedege is caused by bad spirits. In this realization, spirits that cause convulsion must be removed first so that Western and other medication can work in treating the child. That is why we start at the traditional healer for treatment of a convulsed child and later we take him or her to hospital" [ospital" .Failure of hospital treatment was identified in 2 studies as an indication that the illness was due to witchcraft. Three studies reported beliefs that the taste and colour of pills was a reflection of their efficacy, specifically that bitter medications such as chloroquine were more effective.We identified numerous behavioural and pragmatic barriers to the use of conventional medicines. Barriers reported about use of treatment facilities included distance from the facility, perceived quality of treatment provided, and fear of scolding from clinic staff:During the time the child was sick, I was also sick. The other thing is that it is very far to the health center. Unless I had a bicycle, I could not have taken her there....And those people at the clinic never really examine our children. They just write what we tell them. If you ask questions, they just shout at you... [t you... .The prohibitive cost of treatment was described in 12 articles. Six articles identified the practice of stopping medications once symptoms had ceased, often as a means of rationing pills to preserve a supply for future illness episodes:...sometimes just after administering two times you find the child recovers, starts playing. So you stop and keep the medicine, in case the child falls ill again [ll again .A total of 23 articles described conventional medicines and health care clinics as second line treatment options. Nearly all of the articles described the use of traditional healing methods, including consultation with traditional healers, use of herbal remedies, sponging and bathing, and various forms of fumigation. These methods were often described as first line treatment for malaria, before conventional treatments are employed:Usually patients are first given herbs especially mululuza (a popular herb used for omusujja) then they go on to tablets from shops and eventually they take the patients to the hospital, especially if the omusujja fails to respond to the herbs/tablets [/tablets .We systematically reviewed qualitative studies examining the local understanding of malaria in sub-Saharan African countries, as a means of identifying important beliefs and practices that might pose barriers to effective malaria treatment and prevention. To our knowledge, ours is the first systematic review of qualitative studies in this area. While qualitative methods remain useful in exploratory research and hypothesis generation, their results when taken in isolation are of limited value in making more general claims. Our method addresses this shortcoming by using a content analysis approach to combine the results of many qualitative studies conducted in different settings amongst various populations .Our results have importance for public health planners and local physicians. We found that cultural beliefs regarding the cause of malaria may differ from scientific explanations, and that first-line treatments are frequently based on traditional practices. These findings indicate that public health prevention and treatment campaigns need to include culturally sensitive strategies that provide education in the context of local understanding and beliefs.The results of our analysis show that while the malaria-mosquito link is recognized in malaria-endemic regions of sub-Saharan Africa, a number of alternate causative mechanisms are also endorsed. Quantitative data from the studies included in our analysis support this finding, showing that up to 80% of survey respondents cite causes of malaria that do not implicate transmission by mosquitoes ,37,45,50Improved understanding of malaria transmission is also likely to result in better adherence to effective prevention strategies. For one example, a study of post-partum women in Tanzania showed that a high level of knowledge of malaria transmission was positively correlated with the use of ITNs . Taken tWe also identified a number of unproven prevention practices that are potential consequences of the beliefs about causation. Quantitative data from one of the studies included in our analysis showed that while 19% of mothers believed charms or amulets could prevent convulsions in their children, only 9% subscribed to mosquito avoidance for this purpose . While mArtemisia annua - many traditional therapies may be ineffective, or even harmful. Their use as first-line treatment should be countered with the implementation of available and effective antimalarials.The WHO malaria treatment guidelines currently recommend artemisinin-based combination therapies (ACTs) as first-line treatment for both uncomplicated and severe malaria . Access Our analysis also shows that traditional healers are frequently consulted in the treatment of malaria, likely as a consequence of their role within local cultures, and of geographic and financial barriers to accessing treatment from health clinics. Survey data from one study in our analysis indicated that 70% of mothers sought treatment for febrile children from traditional healers . As suchThe results of this review describe significant scepticism around the use of conventional medicines in the treatment of malaria, and in particular in the treatment of severe malaria in children. We identified the concern amongst caregivers of young children that giving an injection to a child with convulsions can be fatal. This belief may in fact be a consequence of local treatment practices, in which seeking hospital care is delayed in deference to traditional treatments. Death following an injection may therefore be a result of the high mortality of late-presenting severe malaria, rather than of the injection itself. Current guidelines continue to support the use of parenteral antimalarials in children with severe malaria, as well as the use of rectal or parenteral benzodiazepines for convulsions whenever this is feasible .We found 6 articles that described the practice of discontinuing malaria treatment once symptoms were seen to resolve, often as a means of rationing medicines for future illness episodes. This finding is particularly worrisome, as poor adherence to treatment is a risk factor for treatment failure , and courd party arbitration or consensus [degedege, which was assumed to refer to severe malaria or cerebral malaria in children, it is possible that non-malarial causes of febrile convulsions in children  were inadvertently included in our analysis. Our justification for using local terminology in our analysis is two-fold. First, the substitution was carried forward only for those studies in which the original authors, with significant exposure to the local language and culture under investigation, also made the substitution. Second, given that the studies included were conducted in malaria-endemic stable high-transmission areas, it is likely that malaria accounts for more episodes of fever in these regions than any other cause. Indeed, the current WHO treatment guidelines for malaria recommend empirical antimalarial treatment for children under five with a temperature of >37.5°C, as malaria is the most frequent cause of fever in this age group [Our study has several strengths and limitations to consider in the interpretation of its findings. We used established systematic review techniques to identify and extract data in an unbiased manner. Using a methodology published elsewhere, we coded and extracted themes, resolving disagreements through 3onsensus . Howeverge group .Other potential limitations are related to the studies included in our analysis. First, it is possible that the search strategy used did not adequately capture the most appropriate studies for inclusion, especially since many of these may have been published in smaller journals and may not have been included in the indexes we searched. Our review of key references was used to mitigate against this possible bias. Second, there were limited data in the included studies by which to assess the rigor of the experimental methods used. The extracted data may therefore be of heterogeneous quality. Nonetheless, consistency of themes was observed amongst the various studies included. Moreover, amongst those studies that did include quantitative data (23/39), these tended to support the findings of the qualitative components. Third, the countries in which the included studies were carried out are themselves a heterogeneous group, with significant cultural and linguistic differences between them. Though consistency of themes from studies in different countries was found, our findings should be interpreted and applied on a case-by-case basis according to the cultural context of a particular region. Finally, while it is likely that the themes identified in this study are important amongst the populations included, little can be gleaned about beliefs that were not reported. Thus, our method is specific, but not sensitive, for the identification of beliefs about malaria amongst the populations studied. Furthermore, the degree to which these findings can be applied more broadly to other populations remains unknown.We systematically identified barriers to effective malaria treatment and prevention that are consequences of logistical impediments, scepticism of conventional treatments, preference for traditional modalities, and incomplete understanding of malaria causation and transmission. Our findings from these qualitative studies should be used to formulate questionnaires and other research tools for use in larger quantitative studies, in order to better determine the impact of these important cultural perceptions on the prevention and treatment of malaria in sub-Saharan Africa. Accounting for the cultural beliefs and practices of sub-Saharan populations at risk of malaria is likely to enhance the effectiveness of large-scale aid programs, and ensure that the financial and logistical resources being committed to combat malaria are being appropriately allotted.The authors declare that they have no competing interests.DM contributed to the conception and design of the study, acquisition, analysis, and interpretation of data, and drafting and revision of the manuscript. AM contributed to the conception of the study, and the acquisition and analysis of data. EJM contributed to the conception and design of the study, interpretation of data, and revision of the manuscript. JM contributed to the acquisition of the data. AA contributed to the conception of the study and interpretation of data. KW contributed to the conception and design of the study, analysis and interpretation of data, and revisions of the manuscript. All authors read and approved the final manuscript.We searched both Medline and Scopus from 1996 to May, 2009, using MeSH terms and textwords for "malaria", and combined these with MeSH and textwords terms for "National Health Programs", "communicable disease control" and "referral and consultation." This set of results was further focused by combining its results with MeSH terms for "health knowledge, attitudes, Practice" and "cultural characteristics" and textwords for "attitudes" and "beliefs". To mitigate any potential publication bias, we also reviewed the references of key papers.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-698X/9/26/prepubThemes identified from articles focused on children. Table shows the themes extracted from articles focused on children.Click here for fileThemes identified from articles focused on adults, and with mixed focus. Table shows the themes extracted from articles focused on adults, and with mixed focus.Click here for file


Recruiting and retaining GPs for research can prove difficult, and may result in sub-optimal patient participation where GPs are required to recruit patients. Low participation rates may affect the validity of research.This paper describes a multi-faceted approach to maximise participation of GPs and their patients in intervention studies, using an Australian randomised controlled trial of a depression/suicidality management intervention as a case study. The paper aims to outline experiences that may be of interest to others considering engaging GPs and/or their patients in primary care studies.A case study approach is used to describe strategies for: (a) recruiting GPs; (b) encouraging GPs to recruit patients to complete a postal questionnaire; and (c) encouraging GPs to recruit patients as part of a practice audit. Participant retention strategies are discussed in light of reasons for withdrawal.The strategies described, led to the recruitment of a higher than expected number of GPs (n = 772). Three hundred and eighty three GPs (49.6%) followed through with the intent to participate by sending out a total of 77,820 postal questionnaires, 22,251 (28.6%) of which were returned. Three hundred and three GPs (37.0%) participated in the practice audit, which aimed to recruit 20 patients per participating GP . In total, 5,143 patients (84.9%) were represented in the audit.Inexpensive methods were chosen to identify and recruit GPs; these relied on an existing database, minor promotion and a letter of invitation. Anecdotally, participating GPs agreed to be involved because they had an interest in the topic, believed the study would not impinge too greatly on their time, and appreciated the professional recognition afforded by the Continuing Professional Development (CPD) points associated with study participation. The study team established a strong rapport with GPs and their reception staff, offered clear instructions, and were as flexible and helpful as possible to retain GP participants. Nonetheless, we experienced attrition due to GPs' competing demands, eligibility, personnel issues and the perceived impact of the study on patients. A summary of effective and ineffective methods for recruitment and retention is provided. Intervention studies in the general practice setting are increasing in number, in recognition of the fact that such studies can provide knowledge that improves clinical care and the overall health of the population -5. These"... provide an explicit and detailed description of our recruitment methods" (p 979); stating that research is needed to advance this field. In this paper, we describe a large-scale Australian randomised controlled trial as a relevant case study. By way of context, Australia comprises eight states and territories and has a population of 21,000,000 which is served by 21,671 GPs [The current paper describes a multi-faceted approach to facilitate and promote participation in clinical research by GPs and their patients within the practice setting. This is in line with the call by Croughan  for rese,671 GPs . These GDivisions of General Practice  provide a range of services for Australia's GPs, including advocacy, educational programs, and opportunities to work with other stakeholders on issues of common interest via specific projects.beyondblue: the National Depression Initiative, and is being conducted by investigators from eight universities across five Australian states . It has ethics approval from the participating universities and from the Royal Australian College of General Practitioners (RACGP), the registration body for GPs in Australia. The study is designed to test an educational intervention aimed at increasing awareness about depression and suicidality in later life, with a particular emphasis on screening and management. Participating GPs have been randomly allocated according to a computer-generated list of random numbers into an intervention and a control group. Participating GPs have not been advised about their group membership. Intervention GPs receive a personalised education program (tailored to meet their specific requirements) and control GPs receive generic information about depression and suicide prevention. Patient outcomes are being measured by a postal questionnaire administered to all older patients of each participating GP at baseline, 12 months and 24 months, and designed to assess the prevalence of depression and suicidality among patients of participating practitioners. GP outcomes are being measured by a practice audit conducted at baseline and 24 months, in which GPs' assessments of 20 consecutive older patients' mental health status are compared with these patients' self-reported mental health status.The trial, known as the DEPS-GP project, is funded by the National Health and Medical Research Council and The DEPS-GP project is currently part-way through its three year data collection period. This paper outlines a critical reflection on the strategies and processes used in the recruitment and retention of GPs and patients during the baseline postal questionnaire and practice audit. The following sections pertain only to recruitment and retention and not the overall research project.This section covers some of the strategies used in recruitment and retention of GPs and their patients to this point in the study. Specifically, the section describes the strategies used to: (a) recruit GPs to the study; (b) encourage them to recruit patients for the postal questionnaire; and (c) encourage them to recruit patients for the practice audit and participate in the audit themselves.We purchased and used the list of GPs held by the Australasian Medical Publishing Company Proprietary Limited as the base for our sampling frame. To ensure sufficient statistical power to detect expected effects, we aimed to recruit a sample of 480 GPs. Initially, we invited a stratified random sample of 4,900 GPs to participate, but only 225 agreed to do so. To counter this, we invited the remaining GPs on the database to take part, bringing the total to 19,046. This number is greater than the total number of GPs across the five study states, due to the fact that the database included the names of some non-GPs and contained some inaccuracies .The invitation letter included a document describing the project, ethics information and a consent form. It also explained that the project qualified for RACGP Continuing Professional Development (CPD) points, the Better Outcomes in Mental Health Care program CPD points and the Australian College of Rural and Remote Medicine Professional Development Program CPD points. As a requirement of vocational registration, GPs are required to participate in the RACGP's quality assurance and continuing medical education program by obtaining CPD points. Other programs offer similar points systems in order for GPs to be able to claim extra benefits from Medicare for services, but these are not compulsory. A brief practice survey was also included with the invitation and was designed to assess whether potential participants met various inclusion criteria. Specifically, the survey asked whether the GP worked at least four sessions or the equivalent of two days a week, had at least 50 patients aged 60+ who spoke English, and was not planning to retire or move practice within the next two years.Infonet. This is a national bimonthly newsletter about primary health care practice, policy and research, published by Primary Health Care Research and Information Service (PHC RIS).During the recruitment phase, details about the project were published in Research assistants were employed in each state as the primary means of communication between the research team and the participating GPs. During the recruitment phase, the research assistants' role was to answer any questions about involvement from potential participants, referring questions on to one of the chief investigators, if necessary. To ensure consistency of information, the research assistants and chief investigators worked from a study manual, which contained background literature, the study protocol, information on administrative procedures and all documents relating to the project.In order for the study team to administer the postal questionnaire, GPs were required to identify their regular patients aged 60 years or over. This typically involved generating a list of names and addresses from relevant electronic record systems. The process was sometimes more labour intensive in instances where records were not electronic or in shared practices where patients of one GP could not be distinguished from patients of another.GPs were then given two choices regarding the mailout of the questionnaire. They could provide the above list to the study team, in which case the study team conducted the mailout. Alternatively, they could elect to conduct the mailout themselves, in which case the study team provided them with the requisite number of questionnaires in pre-prepared envelopes for them to address and post themselves. Irrespective of the mailout method, each patient received the questionnaire in an envelope which also contained a personalised cover letter from their GP, project information, a consent form and a reply-paid envelope addressed to the study team.All participating GPs and their reception staff were provided with detailed instructions regarding the postal questionnaire. These were specifically designed to equip them to field any questions from patients involved in the postal questionnaire. A poster describing the study and providing contact information about local study staff was also displayed in the GPs' waiting rooms. The poster made it clear to patients that they had not been targeted to participate in the postal questionnaire (or the audit) for any reason other than their being aged 60+ and a patient of the participating GP.The research assistants kept ongoing contact with the GPs and reception staff to maintain their commitment to the project. Much effort was made by the project team to facilitate participation in any way possible, such as personal visits to practices to help staff generate the list of eligible patients and/or assist with the mailout. Numerous telephone calls were made throughout the process. In Victoria, for example, GPs were phoned an average of four to five times . Those who elected to send out the questionnaire themselves required an average of five calls to ensure that the task was completed, whereas those who chose to let the study team send the questionnaire out on their behalf required an average of three calls.GPs were not offered financial incentives at any time during the study. However, as a token of appreciation and in order to promote the retention of participants in the study, we posted book vouchers to GPs and their staff once the mailout had been completed successfully.After completing the postal questionnaire stage, GPs were required to undertake a practice audit. This involved each GP  recruiting 20 consecutive patients aged 60+ who attended the practice for any presenting problem during the audit period. Consenting patients were invited to complete a brief questionnaire assessing their mental health status prior to seeing their GP. The questionnaire was then placed in a sealed envelope. After seeing the patient, the GP completed a brief summary regarding the visit. The patient questionnaire and the GP summary form were then returned to the study team. The patient and the GP were each blind to what the other had written. Patients' names were not collected on either the patient questionnaire or the GP summary form; these were subsequently matched for analysis by sex and date of birth only.All participating GPs were sent a package of materials and instructions which asked them to complete the practice audit within six to eight weeks of receipt. As with the postal questionnaire, detailed instructions and an information sheet were also provided to reception staff in order to equip them to field any questions from patients involved in the audit.As with the postal questionnaire, the role of the research assistants during the practice audit involved energetically pursuing personal contact with participating GPs and their reception staff to keep them 'on board', and encouraging them to complete tasks within the prescribed time frame. Each research assistant kept consistent and thorough records of these contacts. In Victoria, for example, each GP was contacted by telephone three or four times on average .Routinely-collected data on recruitment and retention of GPs were collated and analysed. Telephone logs were also coded and analysed, in order to determine the reasons for GPs withdrawing. There were some stylistic differences in record keeping between the different research assistants, but the logs were sufficiently thorough and coding categories were broad enough to allow for these differences. All data were analysed manually and are presented as simple frequencies and percentages.The results reported here offer a numerical picture of the successes and limitations of the methods described above. The discussion section below provides further detail of these results and relates them to each method in turn, making inferences based on participants' reason for withdrawal.Figure Figure Figure Table The DEPS-GP project has been successful in recruiting a large sample of GPs and their older patients. However, the retention rate of participants to date highlights the challenges of maintaining GPs' participation and commitment. Critical reflection on the recruitment processes, strategies to maintain participation, and the reasons given by the GP at the time of withdrawal provides valuable insight to other researchers experiencing the challenges of recruiting within the general practice setting. Various aspects of these processes, strategies and reasons are considered in turn below, and a summary of these can be found in Table Recruitment relied on the use of an existing database to identify the sampling frame. There may have been several alternative approaches. One approach would have been to use an alternative database, but the options were limited. For example, the 119 Divisions of General Practice in Australia each hold information about their own networks of GPs and have local knowledge that assists in maintaining the accuracy of their lists, but these data are not aggregated nationally so drawing on Divisional data was impractical . AnotherInfonet and a letter of invitation, both of which have been cited in the literature as successful recruitment methods [Having identified the sampling frame, we pursued a recruitment strategy that involved minor promotion through  methods ,3,8,14.  methods ,3,5,8,14 methods ,3,5,8, a methods ,14.Although we did not explicitly collect data on why our study GPs chose to participate, some inferences can be made. Studies that have looked at reasons for participation and non-participation have consistently found an interest in the research topic, minimal time commitment and professional recognition as influential ,6. AnecdOnce GPs agreed to participate, establishing a relationship with them and their reception staff was crucial, as were providing clear instructions and maintaining regular contact and support. Frequent calls were made to check on progress and provide encouragement. Often the GPs had varying preferences with regard to communication, with some preferring fax or email communication over telephone contact and vice versa, and some choosing ad hoc contact and others preferring to set specific times for teleconferences. As it was not always possible to speak to the GP directly, the reception staff became an important point of contact. Our research assistants were dedicated to establishing rapport with both GPs and reception staff, providing them with clear instructions and protocols, and 'fitting in' with their stated preferences.In addition, we endeavoured to make the tasks required of the GPs and reception staff as simple as possible. For example, a number of GPs had difficulty generating lists of patients eligible to receive the postal questionnaire (either directly or via the study team). Consistent with technological barriers identified in other studies , this waThe slightly higher response rate of questionnaires sent directly by the GP (29.8%) compared to the response rate of those posted by the research team on behalf of the GP (26.0%) suggests that a direct method would be preferable in future studies. This would have to be weighed against the extra time required by the research assistant in ensuring the GP completed the mailout within project timeframes and whether or not the GP would have participated had the indirect method not been offered. As recommended by Edwards et al , we inclAnalysis of telephone logs from each state showed the reasons for withdrawal stated in Table Most notably, and consistent with other studies ,17, withSome GPs were 'lost' to the study by virtue of ineligibility, despite the study team's best efforts to provide clear instructions regarding eligibility at the outset. Some GPs were found to be ineligible once the project began because it transpired that they had over-estimated the numbers of English-speaking patients aged 60 or over attending their practice. Others ruled themselves out by not adhering to study protocols .Further retention difficulties arose because of issues with personnel in the given GP's practice. In some instances reception staff acted as 'gate keepers', making it difficult for the study team to establish and maintain contact with the GP directly. In other cases, lack of available reception staff was a problem, particularly for GPs in solo practices. In addition, non-participating GPs in the participating GP's practice directly or indirectly raised barriers either by actively objecting to their colleague's participation, or because the shared patient record system rendered it impossible to identify patients of the participating GP.In a small minority of cases, GPs withdrew during the postal questionnaire stage because they were concerned the project could have a negative impact on some of their patients. In one case, the situation arose because recipients of the postal questionnaire (or their carers) raised concerns about the content of the questionnaire . This GP felt that continued participation would interfere with their practice and therefore withdrew.To summarise, we believe that our experience with recruitment and retention of GPs in the DEPS-GP project can provide valuable lessons for future projects. We chose inexpensive methods to identify and recruit GPs, relying on an existing database, minor promotion and a letter of invitation, and succeeded in recruiting a substantial sample of GPs. Anecdotally, our participating GPs agreed to be involved because they had an interest in the topic, believed the study would not impinge too greatly on their time, and appreciated the professional recognition afforded by the CPD points associated with study participation. Our study team was dedicated to retaining these GPs in the study, establishing a strong rapport with them and their reception staff, offering them clear instructions, and being as flexible and helpful as possible. Nonetheless, our retention rates were not as good as our recruitment rates, and we experienced attrition due to reasons of competing demands, eligibility, personnel issues and the perceived impact of the study on patients. We would recommend that strategies to maximise recruitment and retention, such as those found under the heading 'enablers' in Table The author(s) declare that they have no competing interests.MKW and JP originated the idea for this paper and led the drafting of the manuscript. JP, JJP, OT, MS, NK, NTL, NPS, and OPA contributed to the conception and drafting of the manuscript. JP, JJP, NK, NTL, MS, NPS and OPA are leading investigators of the DEPS-GP Project. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Premature ejaculation (PE) is a common sexual dysfunction among men which affects men and their partners. Little qualitative data are available to characterize the impact of PE on men and their partners about ejaculatory control, sexual satisfaction, emotional distress and relationships. The objective of this study was to assess the impact of PE from the perspective of men with PE and the female partners of men with PE on their sexual experience, distress and relationships.Qualitative data were collected through 14 focus groups in the US and through one-on-one interviews in the US, UK, Italy, France, Germany, and Poland. Study participants included heterosexual men with PE and female partners of males with PE. All participants were asked about how PE affects their daily life, including emotional impacts. One-on-one interviews also included obtaining feedback on the male and female versions of 4-single item measures of PE focusing on ejaculatory control, satisfaction with intercourse, interpersonal distress, and relationship difficulty.Participants included 172 males with PE and 67 female partners of men with PE. Lack of control over ejaculation and dissatisfaction with intercourse emerged as central themes of PE. Lack of ejaculatory control resulted in greater dissatisfaction and greater emotional distress, including feelings of inadequacy, disappointment, and anxiety. Continued PE ultimately leads to greater problems with partners and often disrupts partner relationships. Participants indicated that PE was keeping them from attaining complete intimacy in their relationships even when their partners were generally satisfied with sexual intercourse. Impacts of PE on sexual satisfaction, emotional distress and partner relationships were consistent across countries. Feedback on the single-item PE measures confirmed relevance of the item content and further confirmed major themes identified from the qualitative data.This qualitative study provides valuable insights on the substantial psychosocial burden of PE in the US and the Europe. Lack of control over ejaculation resulted in dissatisfaction with intercourse and increased emotional distress, and wide-ranging impact for both men with PE and their partners of men with PE. Data collected in this study may help inform the content of new patient reported measures for use in PE research. Research on the understanding and assessment of premature ejaculation (PE) has increased over the past five years . AlthougPE is the most frequent male sexual dysfunction with an estimated 20% to 30% of men reporting PE (variously defined) at some time in their life -11. DespIntravaginal ejaculatory latency time (IELT) is the most frequently used endpoint in clinical trials of PE treatments ,5,13,14.Previous research has indicated that patient-reported outcomes (PROs) are important for PE assessment and should measure different aspects of the disorder, including perception of ejaculatory control, satisfaction with ejaculatory control, and satisfaction with sexual intercourse ,6,15-18.Given that patient perceptions and the psychological component of PE can be a significant factor in diagnosis and that PROs are important for PE assessment, direct patient input adds critical insight for characterizing the condition and its impacts. However, studies involving open-ended discussions among males with PE and their partners are lacking.The purpose of this study was (1) to characterize the psychosocial burden of having PE from the perspectives of heterosexual males with PE and female partners of males with PE in the US, UK, Italy, France, Germany, and Poland and (2) to cognitively debrief males with PE and female partners of males with PE about their understanding of the recently developed single item measures of four dimensions of PE. The qualitative research was conducted using focus groups and one-on-one interviews with participants which first examined the burden and problems associated with PE in US participants. In the next study phase, in-person interviews examined the burden associated with PE and cognitively debriefed participants in different countries on the single-item PE measures in European participants. This research was completed before the publication of more recent PE measures, such as the Index of Premature Ejaculation  and otheFourteen focus groups were convened in the US  with heterosexual males with PE and female partners of males with PE to explore the psychosocial impact and burden of PE. Separate groups were conducted for male and female participants. In addition, one-on-one in-depth interviews were conducted with males with PE and female partners of men with PE in the UK, Italy, France, Germany, and Poland . In addition to discussion on the psychosocial impact of PE, the in-depth interviews also included obtaining feedback on a male and female version of a brief PRO measure, the Premature Ejaculation Profile ,15, whicStudy participants  met the following criteria: (1) 18–70 years of age; (2) heterosexual; (3) had one sexual partner for past six months; (4) not taking medication that impairs sexual function; (5) experiences PE in greater than 50% of sexual intercourse events based on self-report; and (6) no self-reported problems associated with erectile dysfunction or sexual impotence, low libido, previous pelvic surgery or injury, previous spinal surgery or injury, chronic prostates, or urethritis. For the men, they needed to report that their average IELT was < 2 minutes and that they reported distress associated with their PE. For this study, the female partners of men with PE were not required to be in relationships with the men with PE participating in this study. Heterosexual couples were not recruited, and male or female participants only needed to report that they  or their male partners  experienced PE in the majority of their sexual intercourse events.The moderators used interview guides that included open-ended questions on the following topics: general comments or concerns regarding PE, development and experience of PE for the male partner, emotional distress and impact of PE, partner communication about PE, PE effect on physical and emotional intimacy with their partners, impact of PE on the overall partner relationship, and characteristics of a successful treatment for PE.In addition to inquiring about the general impact of PE, the in-depth interviews included administration of the male and female partner versions of the single item PE measures to male and female participants, respectively. Each version contains four items that ask about control over ejaculation, satisfaction with sexual intercourse, personal distress over PE, and relationship difficulty because of PE ,15. RespThe objective of the analysis was to review the qualitative data to characterize the functional, emotional, and interpersonal impacts of PE from the patient and partner perspective. A grounded theory approach was applied for the analysis ,24. ThisThe cognitive debriefing interviews for the single item PE measures were content analyzed and summarized to determine the participants' understanding and comprehension of each item and response scale.A total of 172 males with PE and 67 female partners of men with PE participated in this study. A total of 51 men and 17 women participated in the US focus groups, and 85 men and 46 women, who were recruited from the UK , Italy , France , Poland , Germany , and the US (19 men only), participated in the one-on-one interviews. An additional 36 men and four women from the European countries provided feedback on the PE measures, but did not participate in the open-ended qualitative component of the interviews. Demographic characteristics are summarized in Table A common issue arising from review of the focus group and in-depth interview data was that all participants felt that, because of PE, they lacked something that could bring more fulfillment into their lives. Lack of control over ejaculation led to dissatisfaction with sexual intercourse for the males and partners of men with PE and, in many cases, resulted in the disruption of their relationship. Even among those participants who stated that they were sexually satisfied, the male and female participants indicated that they felt something was missing from their relationship, and this affected their sense of intimacy. The participants employed numerous coping strategies to attain sexual satisfaction, and many sought medical or psychological therapy to help address the effects of having PE. However, based on the feedback, it appears that some individuals affected by PE were reluctant to seek help given the stigma associated with this problem.The major themes raised by the study participants included control over ejaculation, satisfaction with intercourse, emotional impact and distress, relationship problems, and partner reactions Table . These tControl of ejaculation emerged as a central concept and represented an essential component of PE. The absence of ejaculatory control was the principal problem identified by the male and female participants. Participants felt that they did not have control: "Well, for me, I don't feel like I really ever have control"; "If I had the control as to when I did it. That's what I'd want." In response to the question about how to determine whether a treatment for PE would be considered successful, respondents indicated that control of ejaculation was critical: "If it increases – if it doubles it, yeah that's success"; "I feel if I had control, then this wouldn't be an issue at all"; "I mean, the ultimate success would be unlimited control."Latency time was directly connected with the men's viewpoint about control of ejaculation. The experience of PE was essentially based on lack of control over ejaculation and the other related PE problems were directly associated with ejaculatory control. Figure Satisfaction with sexual intercourse was another important concept, and the perception of satisfaction with the sex act was directly associated with the sense of ejaculatory control. For the men, their level of satisfaction was directly linked to their partner's satisfaction with sexual intercourse. A common comment was: "That's the goal, is for both of us to be satisfied". However, even when men discovered ways for their partners to attain orgasm, they still felt that PE affected both their own and their partner's overall satisfaction. This concept is illustrated by the following: "Orgasm isn't what she's looking for. She's looking for the whole piece"; "But even when she's completely happy, I feel like I'm still not lasting as long as I should"; "I'd say sex is generally satisfying, but I think it could be better"; and "I mean, it's satisfying, but maybe it's, you know, not as much so."The participants felt that they were missing out on an important factor in feeling close to their partners because of their lack of control over ejaculation. The male participants stated that: "It definitely takes the intimacy out, and it just becomes physical at that point"; "I would say it affects my love life, not my sex life so much"; "It prevents that closeness from being, you know, fully consummated"; and "I'm looking for the intimacy that we lost." The impact of PE on this sense of intimacy and closeness was important to men even if their partners lose interest in the problem. Many of the male participants in long-term relationships have learned to adjust to the problem but they still felt unfulfilled: "She really never complains, but I felt it myself"; "It's time to ...try and fix it; She seems to really enjoy sex, and I'd like to have that same degree of enjoyment"; "I think, if she was honest herself, she would as well [believe that PE was a problem]"; and "It's something that's very important to me, and in the case of my wife, it's not important to her anymore."Both men and women expressed that they sometimes felt that initiating sex was not worthwhile because they would not achieve sexual satisfaction and they did not want to feel disappointed or cause their partners to feel disappointed. The female participants reported that their male partners reduced the number of sexual advancements due to fear and anxiety related to PE. The Polish women specifically reported feelings of low self-worth and unattractiveness due to the lack of sexual advancements from their partners. Some women in the UK and Poland reported finding sexual satisfaction with others because of their partner's PE.Many of the men reported significant emotional distress associated with their sexual dysfunction. PE affected them emotionally and clearly impacted their self-confidence: "Your lack of control there in that situation makes you feel inferior"; and "When you can't satisfy your woman, you somehow feel like there's a large part of you that is missing or failed." In addition to inadequacy, many of the men reported feeling anxious, frustrated, angry, and disappointed. The men felt frustrated about their PE and how it affected their intimacy with their partners and sexual relationship. In general, the emotional impacts were associated with not feeling manly as defined by societal expectations. Common statements from men were: "And it all links to not having control. You're angry because you can't control the situation"; and "I would like to be able to enjoy the whole sexual experience without having an uptight feeling."The women perceived their male partner's emotional distress but some noted that this made it difficult to address the problem. Illustrative comments from women included: "I realize I can't say anything because he's feeling inadequate"; "I don't want to bring it up, because I don't want to affect his ego"; and "You don't want to say too much because you don't want to offend them." In general, the women perceived anxiety, reluctance, and avoidance from their partners regarding sex. A predominant perception among the men across different countries was that their partners were reluctant to discuss PE. Alternatively, several of the women indicated that their partners were in denial and would not discuss problems associated with PE: "He's like, we don't have that problem"; and "Because he doesn't think it's big deal, and he doesn't – that annoys me." Women in the US, Italy, and Poland mentioned that their partners were most often in denial about their PE and would not admit that there was a problem at all.Some men indicated that they found it very difficult to raise the topic of PE, and it was not easy for some of the men to volunteer for the study: "It's generally not something I talk about"; "I needed a little bit of courage to come in." Many of the female participants indicated that their partners would be too self-conscious to seek help: "He wouldn't be able to take it"; and "I asked him to come here, and he says 'there's no way I could do that."' Many of the men did indicate though that they tried to seek help in various ways, including buying relevant books, seeing a psychiatrist, going to hypnotherapy, and discussion with their doctors. Some struggled with whether or not they should see a psychologist versus a medical doctor, and many indicated that "It's hard to find information on this kind of stuff."The negative effects of PE had profound impacts on the relationship between the men and their partners. For many men "You feel like you're not connecting in your relationship." In some cases, issues with PE led to concerns about the stability of the relationship: "I kind of question, you know, how good the relationship is when my girlfriend says, you know, this is not going to continue... this relationship is over if things don't improve." Men in long-term relationships generally had less anxiety about PE and reported better communication with their partners about PE. However, among women in long-term relationships, only those in Germany and France reported minimal anxiety and good communication about PE. Many younger male respondents reported feeling that their relationship could be in jeopardy, and specifically some males in the UK, Italy, Germany, and France were worried about losing their partners because of PE: "She said this relationship is going to be over if I don't do something about it".Most women expressed disappointment, dissatisfaction and frustration in their sexual relationship and level of intimacy because of PE: "So then there's just kind of a disappointment." Some expressed anger, particularly when their partners denied that there was a problem: "You feel like you don't get his attention or anything." Many of the women were reassuring, which helped the males feel less anxious about sex. However, many of the men noted that they felt this reassurance was not always genuine; they sensed that the women did not want to undermine their self-confidence: "I think she's being sensitive not to shatter my precious male ego." One reaction identified only among some female partners was a feeling of relief because, given that they had busy schedules, they did not have time for lengthy sex.The men employed various physical and mental strategies to try and deal with their PE. These strategies included trying to detach themselves and think of other things during sex, using humor to decrease the embarrassment of PE, pacing themselves during sex, and interrupting intercourse to prolong latency time and to improve ejaculatory control. For some, it was helpful to discuss their problems with others, including their partners or physicians. In general, these coping strategies were perceived to have varied success and the underlying problems associated with PE remained.The cognitive debriefing interviews on the male and female versions of the PE measures substantiated the relevance of control of ejaculation, satisfaction with intercourse, personal distress, and relationship difficulty among the participants. The participants believed that the PE measures focus on important consequences of PE, and they did not have difficulty understanding the item content or in responding to the questionnaire. Control over ejaculation was described by males as being able to stop or hold back ejaculation if desired and the time to ejaculation. Women uniformly reported this item was associated with time to ejaculation. In some cases, men and women included in their descriptions of control the ability of the man to prevent ejaculation until his partner attained orgasm.In response to the satisfaction with sexual intercourse item, most of the men thought about the pleasure they experience during sexual intercourse, and this was directly related to the ability of bringing their partners to climax during vaginal intercourse. The women reported that the meaning of this item was based on their ability to achieve orgasm through vaginal penetration and sexual intercourse. Some respondents also indicated that their satisfaction was related to the entire sexual encounter including both the physical and emotional response.For the item on personal distress related to PE, all participants understood distress to be negative emotions resulting from PE although there was variation in how "distress" was defined. Distress was generally interpreted to include a range of possible emotions, including feeling inadequate, disappointed, annoyed, like a failure, frustrated, and anxious. The women defined "distress" as sexual frustration, irritation, sexual dissatisfaction, or decreased sexual interest. Some variation was observed among countries with respect to interpreting degrees of distress. Specifically, in the US sample, "distress" was understood in levels of severity. In Germany, a few participants did not attach different levels of severity to "distress" – one was either distressed or not distressed. In France, most participants identified "distress" as feeling upset.The "relationship difficulty due to PE" item generally was interpreted similarly across participants. The majority of participants explained that this item referred to problems in their partner relationships because of PE. These problems included being disappointed in the relationship, experiencing tension, being frustrated or sensing frustration in a partner, arguing, and disruption in the stability of the relationship. In responding to this item, some participants made a distinction between their sexual relationship and their overall relationship. For example, some participants in long term relationships, or who were older, focused on their sexual relationship when responding. In contrast, younger males or those in shorter relationships expressed focused on their overall relationship when responding. Most French participants thought about this item in terms of the effects on their sexual relationship versus the effects on their overall relationship.The findings from this study suggest that there is a substantial psychosocial burden associated with PE on heterosexual males and partners of men with PE, and that the major impacts appear to be consistent in the US and Europe. The findings identified control of ejaculation as a central concept for PE. The absence of ejaculatory control results in dissatisfaction with sexual intercourse and personal distress. The level of satisfaction with sexual activities and personal distress associated with PE, leads to increased general emotional distress and relationship problems. Even in relationships where the participants noted that they were generally satisfied with sexual activities, both males and females indicated that PE was keeping them from feeling fulfilled or attaining complete intimacy in their relationship.This multi-country study, which included both males with PE and female partners of males with PE, expands on previous qualitative research conducted by Symonds and colleagues in a US-based study of 28 males with PE . ConsistThe results further confirm the central role of ejaculatory control in understanding the impact of PE on men and their partners. Latency time and the perception of control over ejaculation affect the men's satisfaction with sexual intercourse and their distress related to PE. The qualitative research is consistent with the findings of a large study of men with PE ,6 and otSome researchers question the need for patient reported measures for PE outcomes assessment ,5. The cBased on the discussion by participants, sexual satisfaction for men is strongly influenced by their female partner's report of satisfaction with sexual activities. The men reported feeling anxiety and reluctance about sex for fear of disappointing their partner. Men also felt like failures because of their inability to affect their ejaculatory control.The cumulative effects of PE disrupt the partner relationship, causing instability. Female partners of men with PE react in various ways, and many experience disappointment and frustration. In some cases, the women in this study were concerned about damaging their partner's ego and self-esteem so they avoided direct communication. Communication was a significant issue between couples and was associated with age and length of relationship. In general, couples in longer and stable relationships found ways to communicate about and adapt to the male's PE. For younger men and those in shorter relationships, the extent and nature of the communication between partners was an important driver in perceptions of personal and relationship difficulty.Consistent to the finding by Symonds and colleagues , many ofThe participants confirmed that the four single-item PE measures were relevant for capturing the major impacts of PE. These findings are consistent with newer patient-reported PE outcome measures . The parLimitations of this study are primarily associated with the generalizability of the findings to the larger PE population. First, this study relied on self-report to identify subjects with PE. Research has indicated that subjective self-reports of latency time may be inconsistent with prospective latency time measurement ,25,26. TThis in-depth qualitative study provides valuable insight on the substantial psychosocial burden of PE in the US, UK, Germany, Italy, France, and Poland. The concept of ejaculatory control was central for understanding the effects of PE on men and their partners, with consequent impact on satisfaction with sexual intercourse and personal distress. PE was associated with wide-ranging impacts for both men with PE and their partners. This study confirms the importance of patient perceived aspects of PE and demonstrates that the single-item PE measures cover the key and relevant content for men with PE and their partners. Further, the qualitative data collected in this study can help inform the content of new and expanded PRO measures for use in PE research.PE: Premature ejaculation; DSM-IV-TR: Diagnostic and Statistical Manual of Mental Disorders; PRO: Patient-reported outcomes; IELT: Intravaginal ejaculatory latency timeDr. Revicki, Ms Howard, Hanlon and Mannix are consultants and at the time the work was performed were all employed by United BioSource Corporation. This project was funded by Johnson & Johnson Pharmaceuticals under the direct of Dr. Rothman and Ms Greene.DR, KH, SM and JH designed the qualitative research study, completed the content analyses, interpreted the qualitative data, and drafted and revised the manuscript. KH, SM and JH conducted the qualitative research and analyzed the data. MR and AG conceptualized and designed the study, interpreted the qualitative data and drafted and revised the manuscript. All authors reviewed and approved the final version of this manuscript.


The growing scarcity of potable water supplies is among the most important issues facing many cities, in particular those using single sources of water that are climate dependent. Consequently, urban centers are looking to alternative sources of water supply that can supplement variable rainfall and meet the demands of population growth. A diversified portfolio of water sources is required to ensure public health, as well as social, economical and environmental sustainability. One of the options considered is the augmentation of drinking water supplies with advanced treated recycled water. This paper aims to provide a state of the art review of water recycling for drinking purposes with emphasis on membrane treatment processes. An overview of significant indirect potable reuse projects is presented followed by a description of the epidemiological and toxicological studies evaluating any potential human health impacts. Finally, a summary of key operational measures to protect human health and the areas that require further research are discussed. Worldwide, 1.1 billion people lack access to adequate water supplies –4. Thereplanned IPR. The use of environmental buffers such as rivers, dams, lakes or aquifers is considered world’s best practice given that natural systems have a high capacity to further purify water [Indirect potable reuse (IPR) is one of the water recycling applications that has developed, largely as a result of advances in treatment technology that enables the production of high quality recycled water at increasingly reasonable costs and reduced energy inputs. In IPR, municipal wastewater is highly treated and discharged directly into groundwater or surface water sources with the intent of augmenting drinking water supplies . In thisfy water . RetentiCities with limited water resources are considering IPR as a feasible option for the sustainable management of water because it is a water supply alternative not dependent on rainfall and it is possible to achieve high quality recycled water in compliance with drinking water standards and guidelines. IPR has the potential to make a significant contribution to urban water resources needs but a cautious approach is required to manage the health risk associated with recycled water for drinking. The number and concentration of chemical and biological hazards in wastewater is far higher than the potential hazards that could be found in pristine waters. Contaminants have been detected at low concentrations in highly treated recycled water and any potential health impacts need to be evaluated. Moreover, there are currently no health values for most of these contaminants and usually there are limited toxicological information available. Therefore, an analysis of potential human and environmental risks and the involvement of the community before any implementation proceeds need to be carefully undertaken on a case-by-case basis. This paper presents the “state of the art” context of water treatment, the lessons learned from existing projects and the issues that require further research from the public health perspective. Three supporting tables are provided; Demonstration and full-scale IPR projects , Epidemi2.IPR is not new and has been successfully implemented in the United States (US), Europe and Singapore. In the US, California is the leading state with the highest number of IPR projects and more than 40 years experience; other states with demonstration or full-scale IPR projects include Arizona, Colorado, Texas, Florida and Virginia. In California, Water Factory 21, in the Orange County Water District (OCWD), is the oldest project, with a production capacity of 19 megalitres per day (ML/day). Water Factory 21 was closed in 2004 and the upgraded groundwater replenishment system (GRS) plant was completed in 2007. The GRS produces 265 ML/day with an ultimate capacity of 492 ML/day .Other projects in the US have also implemented IPR , Perth , Goulburn  and South East Queensland . In the The Toowoomba project, which aimed to add recycled water to supplement the drinking water supply of the Cooby Dam, did not receive community support in a referendum held in July 2006, with 62% of votes against IPR . Neverth3.Despite variations in treatment technologies, environmental buffers used, proportions of recycled water blended with the raw drinking water sources (from 1% to 100%), and estimated retention times in the receiving waters , none of the projects listed in In 1998 the US National Research Council (NRC) published the evaluation and recommendations of a multidisciplinary team of experts that explored the viability of augmenting potable water supplies with recycled water. The report concluded that, from the information available, the risk from IPR projects were similar to or less than the risks from conventional sources, but nonetheless considered that IPR should be an option of last resort .3.1.There are few published epidemiological studies on potable reuse and a summary is presented in In the Montebello Forebay project, three epidemiological studies were published, two of them using an ecological design. The latest ecological study was published in 1996 . In thisNo prospective studies have been conducted examining the potential adverse health effects of long-term exposure to low concentration of chemical contaminants from potable reuse. However, assessment of exposure is especially challenging in studies with long latency periods, such as cancer. In the late 1990s the OCWD and an independent scientific advisory panel suggested conducting a case-control study on the use of Santa Ana River water. However, the study was found to be non-feasible due to limitations in assessing historical exposures. The panel did not recommend any additional epidemiological studies because any incremental risk due to recycled water is likely to be extremely small and difficult to differentiate from normal background risk . The panGiven that epidemiological studies of long latency (such as cancer outcomes) are associated with many competitive risk factors and are complicated by limitations in the assessment of the exposure, epidemiological studies with health endpoints of short latency  may be more appropriate as a means of elucidating possible disease pathways. A critical aspect for projects considering the implementation of epidemiological studies is the need to carefully assess the exposure to recycled water in the study population during the period of interest. Hydrogeological modeling, geographic information systems and exposure data at the individual level may be required to link health outcomes with levels of exposure to recycled water.3.2.Toxicological testing is the primary component of chemical risk assessments of IPR projects. Estimations of human health risks from exposure to specific chemicals are generally based on extrapolations of toxicological analyses on animals. Given that toxicological information exists only for a small percentage of chemicals and that toxicological data for individual compounds are not adequate for predicting risks posed by chemical mixtures, it is usually the concentrates of recycled water which have been used to assess potential health risks . OverallIn the US, only the Denver and Tampa studies assessed a wide range of toxicological endpoints. These studies included sub-chronic and chronic toxicity testing, as well as specific health effects . In these two demonstration projects and in Singapore, toxicological analyses have been performed by comparing the health effects on animals  fed over several generations with recycled water concentrates, compared with control groups. The Denver report concludes “no adverse health effects were detected from lifetime exposure to different concentrate samples during a two-generation reproductive sample” . In SingSalmonella typhimurium, were performed in the San Diego, Tampa, Potomac Estuary, OCWD and Montebello Forebay projects. In general, less mutagenic activity was observed in recycled waters compared to other water sources. In the Montebello Forebay project, mutagenic activity was detected in 43 of the 56 samples from both recycled and control waters tested. The observed level of mutagenic activity was maximal for storm runoff, but lower (in declining order) for dry weather runoff, recycled water, ground water and imported water [Mutagenic studies using the Ames test, which is used to determine whether a chemical is able to cause cell mutations to the bacteria ed water . The Ameed water .et al. reported low estrogenic activities  of 0.23 and 0.05 ng-EEQ/L after MF and RO respectively. The estrogenic activities were at markedly reduced values compared with the value of 1.2 ng-EEQ/L in the plant influent. The bioassay EEQ measurement and the EEQ calculated from chemical analysis of known estrogenic chemicals were similar for samples taken both after MF and after RO. However, the EEQ in the influent was twice as high when calculated by chemical analysis compared with the bioassay, due in part to antagonistic effects between chemicals. Consequently, the removals of endocrine disrupting compounds in terms of the EEQ value from the biological and chemical determinations were 80 and 96% for MF and RO respectively [Bioassays conducted for estrogen, androgen, and thyroid activity have shown a progressive endocrine activity reduction during the treatment train and a very low endocrine activity in the product water . Lee et ectively .4.A variety of factors must be carefully assessed to ensure public health protection. Some of the fundamental practices and lessons learned from the implementation of IPR projects are presented in this section. These factors include the treatment processes required to achieve high water quality; the quality of the existing water supply and any changes in this source after recycled water is blended; system reliability; the regulatory framework and risk management practices.4.1.Analytical monitoring programs of existing IPR projects listed in Characterization of biological and chemical agents in the product water has been carried out in all projects described in Cryptosporidium, 9.5−10 log for enteric viruses and 8 log for Campylobacter [Various guidelines suggest that the minimum log reductions required for IPR are: 8 log for lobacter . MF is alobacter . Viruseslobacter  and ultrlobacter ,34 MS2 hlobacter . In addilobacter  and the lobacter . These iChemicals that have been detected in secondary effluents include household and industrial chemicals such as detergents, flame retardants, plasticizers, personal care products and pharmaceuticals. Some of these compounds are known or suspected carcinogens, others are estrogenic and have the potential to adversely affect the endocrine system. Advanced treatment technologies such as MF/RO followed by advanced oxidation processes and/or UV are able to remove most of these contaminants to levels below limits of detection (ng/L) –38. It iMany IPR recycled water projects implement monitoring programs to evaluate the treatment efficiency in rejecting organic contaminants, including endocrine disrupters, pharmaceuticals and personal care products and other unregulated compounds. Antibiotics are of special interest because of growing concerns over antimicrobial resistance in human medicine. Disinfection by-products may be generated during the treatment process and some of them can be stable, polar and toxic, such as N-nitrosamines and trihalomethanes. Their formation should be avoided or their removal accomplished as far as possible in any potable reuse project. Endocrine disrupters (particularly those with an estrogenic effect) produce adverse effects in fish and other species at low concentrations. Within the framework of the precautionary principle, the reliability of advanced treatment in removing such compounds to the maximum extent achievable needs to be demonstrated for the protection of human health.et al. recommended the use of chemical indicators and surrogates to monitor treatment performance. They selected a list of wastewater-derived contaminants to determine the treatment removal efficiency of individual unit processes commonly used in IPR . The authors validated the removal efficiency of the selected chemicals for each unit process through laboratory, pilot, and full-scale experiments. Different groups of chemicals, sharing similar physicochemical characteristics, were detected at low concentrations (ng/L) for each one of the unit processes. The report concludes that, by selecting multiple chemical indicators with different physicochemical properties, it is possible to account for compounds currently not identified and new compounds synthesized and entering the environment in the future, provided they fall within the range of properties covered. The underlying concept is that absence or removal of an indicator compound during a treatment process would also assure the absence or removal of other compounds with similar properties. For example, the authors recommended the use of sulfamethoxazole, N-nitrosodimethylamine (NDMA), tris(2-chloroethyl)-phosphate (TCEP) and chloroform as chemical indicators during the initial phase of the IPR project and the use of conductivity, total organic carbon (TOC), and boron as surrogate parameters for the MF/RO system [Drewes O system .4.2.Ultrafiltration or MF as pre-treatment for RO followed by UV treatment or advanced oxidation are the commonly used treatment steps in IPR. Secondary effluent from conventional wastewater treatment plants is treated by MF, which is a low-pressure membrane with a pore size of 0.01 μm. MF can remove most of the fine suspended solids (more than 99% rejection), colloidal solids, bacteria and protozoa. ,41–43. AIn the studies conducted so far, high percentages of organic contaminant removal are commonly reported. RO can remove up to 95 to 99% of hormones ,46, and As in drinking water treatment, the multiple barrier approach is also used in IPR. The approach includes source control, use of multiple water treatment processes, use of environmental buffers and conventional drinking water treatment. The basis of this approach is to ensure that there are several independent steps in place to remove contaminants given that no single barrier is able to remove all contaminants from wastewater. The multiple barriers also minimize the risk by producing less variation in the final water quality and by providing some protection in the event of poor performance of one barrier, provided some degree of adjustment can be achieved in other treatment barriers to compensate for temporary failures (e.g. disinfectant doses can be increased if membrane filtration underperforms).Source wastewater assessment and protection is the first barrier and it is critical to prevent contaminants from entering the wastewater. Source control requirements should be part of the formal approval process to utilize recycled water for IPR as such requirements identify and minimize the introduction of contaminants into the wastewater, minimising the need for them to be removed through treatment. In Australia, the National Waste water Source Management Draft Guideline provides a framework for good management of the quality and quantity of all wastewater source inputs to a wastewater collection, transfer, treatment and disposal/reuse systems. The framework has been ordered into five key wastewater input management objectives which cover the quality of all possible source inputs with the potential to impact on sewage quality. These objectives address protection of safety in sewers, infrastructure assets, treatment plants, regulatory compliance and recycling . TherefoFor the protection of human health, each treatment process must be evaluated to establish its performance against the different categories of contaminants. A timely and effective monitoring program is fundamental to detect the unexpected appearance of contaminants in the recycled water. For example, additional treatment barriers after RO were implemented in the GRS (OCWD) project after the detection of NDMA and 1,4 dioxane, both of which are potentially carcinogenic . An adva4.3.Different regions using IPR have developed various approaches to ensure health and environmental protection. In the US, there are no federal regulations governing IPR and criteria are developed at the state level. Therefore, states operating IPR projects, such as California, Washington, Arizona and Florida, have each developed various guidelines. Criteria among states are generally similar and tend to be conservative with an emphasis on maintaining protection of public health . In CaliRecycled water guidelines include both monitoring and performance requirements . The DepRecycled water guidelines are now incorporating several approaches using a risk management framework to ensure minimum levels of risk and maximum quality of the final product water. Best Available Technology , Life CyThe HACCP approach includes hazard identification and risk assessment, identification of appropriate preventive measures, and operational monitoring of the preventive measures. The aim of operational monitoring is to measure ongoing performance of preventive measures and to ensure that, where required, corrective action is implemented prior to the water being released. In some cases, monitoring can be continuous, whereas in other contexts, discrete sampling at lower frequencies is employed. Because the efficiency of the treatment is variable and depends primarily on the quality of the influent water the pressure of the water through the membranes, and the porosity of the membranes , a well-after contaminated water has already been supplied; that is, it constitutes a “retrospective” assessment. Many contaminants present at low concentrations are not directly or easily measurable. Therefore, a coherent and structured evaluation of the hazards, and the management of the critical control points plays a central role in the safe operation of recycled water projects. Consequently efforts to protect public health should focus on failure detection systems that measure the performance of key process units rather than just monitoring the final effluent or the end-use point. For example, the parameters to identify failures in the performance of the MF and RO processes are generally indicated by turbidity and conductivity respectively, that can both be monitored continuously using appropriate plumbed-in instrumentation.Compliance testing alone is not enough to protect public health . FirstlyIn summary, in order to conform to the HACCP management approach, very stringent water quality and monitoring requirements are imposed for IPR. Typical requirements include advanced treatment of the secondary effluent using MF/RO and in some cases also UV and/or advanced oxidation processes to remove chemical and biological hazards, conformance with drinking water guidelines in the product water, extensive monitoring for known or suspected contaminants, and minimum residence time in the receiving aquifer or surface water body. Other requirements include monitoring and site-specific controls on the operation, maintenance and management of the plants.5.5.1.th European Union framework funded the Norman Project, which aims to create a network of reference laboratories and related organizations for chemical monitoring and biomonitoring of emerging environmental pollutants [Analytical methods have been developed for a wide variety of compounds and isotopically labelled standards have become commercially available in recent years. However, large-scale method comparison and validation exercises to improve the accuracy and precision of quantitative measurements have not yet been conducted. It is currently difficult to interpret and compare treatment efficiency in the removal of emerging contaminants. More research is needed not only to identify new potential contaminants of concern in recycled water, but also to develop validated methods and implement harmonized analytical methods. Validated methods for emerging and other unregulated contaminants will: (i) facilitate the risk assessment and regulatory process by providing better quality data; (ii) provide comparative information about contaminant fate and removal during the treatment barriers; and (iii) assist the analysis of different treatment options for removing contaminants. In 2005, the 6llutants –73. In fA greater research focus to manage health risks from trace organic compounds in recycled water is needed, with a particular emphasis on investigating the toxicological relevance of endocrine disrupters and pharmaceuticals in recycled water. The impact of endocrine disrupters in fish and other species exposed to wastewater have been documented –76, but Validated monitoring approaches are required to ensure adequate health protection for a number of reasons: (i) several unregulated chemicals of concern are not routinely included in monitoring programs; (ii) many emerging chemicals of demonstrated or suspected health concern as yet have no standard analytical methods; (iii) some current analytical methods have detection limits above the toxic threshold; (iv) the possibility of other unknown toxic chemicals in the recycled water; and (iv) combinations of toxic chemicals may exert mixture effects that remain poorly characterized.On-line biomonitoring systems using fish have been developed in recent years to evaluate potential health impacts without using concentrates of recycled water . BehavioBiomarkers for endocrine, developmental, and potential reproductive effects in aquatic organism exposed to recycled water are also under development and seem to be a promising area .On-line sensor technologies for triggering contaminant warning systems have proven feasible in the laboratory. For example, the USEPA studied 20 on-line commercial sensors for their ability to identify 25 injected contaminants into the distribution system by testing of 17 water quality parameters. They found that free chlorine and total organic carbon detected the widest array of contaminants and produced the largest, and most easily detectable, water quality changes . HoweverQuantitative structure activity relationship (QSAR) methods are being used not only to predict the potential toxicity of compounds based on their physical and chemical properties ,81 but aVarious monitoring approaches are available or in development, but are not in use with IPR projects, include:Potential human health effects of previously untested contaminants may necessitate additional regulations. It is fundamental to establish whether these emerging contaminants of concern may pose an additional risk to human health at the concentrations reported in recycled water. A systematic approach is required to evaluate the measured concentrations of contaminants in recycled water against benchmark values ,82. This5.2.Although many water authorities are aware of research into the various treatments and contaminant rejection fractions personnel must also be provided with ongoing training in the emerging technologies in IPR. More research and reports are expected in the future regarding the operation of IPR projects and the implementation of management systems, such as the HACCP approach. Moreover, monitoring of parameters, both online, and in the laboratory will identify performance compliance and when threshold values are exceeded enable emerging problems to be detected and corrective actions taken.Separating drinking water from sewage was a major achievement in the conquest of infectious diseases, and remains a challenge to be overcome in much of the developing world. Now with the intentional and planned augmentation of drinking water supplies with recycled water, it is fundamental to ensure that the community remains protected. Therefore, there is a need to integrate both recycled water and drinking water at the regulatory level. It is not enough to rely on drinking water standards and guidelines to ensure the safety of the recycled water. This may result in a modification to the approach to dealing with emerging contaminants in regulation of traditional drinking water sources. It is also possible that additional chemicals may need to be monitored at drinking water treatment plants once recycled water is introduced to the source water catchment. It is expected that with the continuous development of treatment technologies, analytical methods, monitoring techniques, toxicological studies and risk assessment approaches, the use and regulation of recycled water for IPR will continue to evolve.5.3.Regulators approving IPR projects need to implement a well-coordinated public health surveillance system to document possible warning signs of any adverse health events associated with the ingestion of recycled water. Existing surveillance systems, such as those for notifiable communicable diseases, should be used and/or enhanced to meet these needs. Surveillance systems must be jointly planned and operated by health departments, water utilities and other relevant agencies. Key individuals in each agency need to be appointed to coordinate planning and rehearse emergency procedures. The surveillance plan, its purpose, the monitoring results, and the system process performance should be available to the community and interested stakeholders. Surveillance systems may indicate whether an epidemiological study is required. However, epidemiological surveillance is considered relatively slow and is reactive as it is based on disease outcomes.In addition to the health surveillance program, the research capacity in regions considering IPR needs to be enhanced to implement a monitoring program that provides an early warning system of potential health risks from newly detected or emerging contaminants. In order for monitoring systems to be effective, a multi-institutional commitment is required for the documentation and monitoring of all significant chemical wastewater inputs from household, commercial, agricultural and industrial sources. Pre-established risk mitigation measures also need to be in place.5.4.Although communities have accepted recycled water for non-drinking purposes such as irrigation of parks, they are less likely to accept the use of recycled water as a drinking water source. The perceived decrease in temporal and geographical distance between wastewater and recycled water in IPR raises reservations amongst the community about the safety and quality of the recycled water. Emotions, or the ‘yuck’ factor, play a major part in people’s lack of acceptance. Nevertheless, increased community support has occurred in the last decade and important progress has occurred in identifying factors of success or failure in the implementation of IPR projects –85. FiveEffective communication between the community, key stakeholders and the project proponent is crucial to achieve community support. All recycled water projects need to be accompanied by community education to demonstrate that the current technology is adequate to protect human health. A timely and active communication program to discuss the treatment processes, the risks, the measures in place to control risks and the safety of the water, may help to increase trust in the project. The experience in the US has indicated that community understanding and acceptance may take several years, but that a broad community communication approach is fundamental for the successful implementation of IPR projects. There are many examples where local communities have rejected IPR proposals because they were poorly informed or insufficiently confident in the process. Some examples include the Dublin San Ramon Services District in California ,85 and tCommunity attitudes to water recycling are dependent on numerous factors, including the degree of water scarcity, the supply costs, the quality of the consultative processes, the perceived management of health risks, and the accountability of, and trust in, the regulator, the government and the water utility. Therefore targeted social research is needed in communities where IPR is proposed to understand the influence of psychological factors related to: perception of risk, motivations, attitudes, beliefs and behavior on the use of recycled water to supplement existing water supplies and IPR project acceptance.6.IPR has been in practice for over 30 years. The projects presented have used advanced treatment technologies and applied the treated recycled water into an environmental buffer where naturalisation and dilution occur. Although few epidemiological studies have been conducted, there is no conclusive evidence that communities using drinking water supplemented with recycled water are at any increased risk of disease compared with those who do not drink recycled water.IPR is a viable option for supplying reliable potable water to those urban regions with increased water demand and/or decreasing alternative supplies. The use of IPR needs to be evaluated in conjunction with other potential water supply alternatives, and the potential health impacts need to be carefully considered before implementation. This process requires an understanding of how water quality and health standards can be maintained through rigorous controls and monitoring techniques, based on sound science and proven treatment technologies. IPR projects need to demonstrate effectiveness of available barriers, guarantee safety by on-line monitoring systems, process control, testing, and source control programs.No water treatment is ever without risk, including conventional drinking water treatment and traditional drinking water sources. Similarly, IPR as a new water source will never be a totally risk-free practice. However, using best available technologies, risk assessment and risk management practices, water agencies, health regulators and other stakeholders can evaluate and mitigate the potential public health risks from the biological or chemical contaminants found or likely to be found in the recycled water. Mitigation of hazards to their acceptable risk is critical to balance public health protection and resources. Risk reduction below the acceptable risk will not result in significant reduction in risk and at the same time additional expenditure of resources will not result in significant advances towards increased safety.It is essential to maintain ongoing research in hazard mitigation and control in IPR projects, coupled with appropriate toxicological and epidemiological studies. The reviewed literature supports the practice of IPR as a reliable and safe addition to existing drinking water supplies, and it is anticipated that IPR will represent an essential element of sustainable urban water resources management in many more regions of the world in the future.