Hope, disappointment and perseverance: Reflections of people with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis participating in biomedical research. A qualitative focus group study

Abstract Background The Clinical Understanding and Research Excellence in ME/CFS group (CureME) at the London School of Hygiene & Tropical Medicine has supported and undertaken studies in immunology, genetics, virology, clinical medicine, epidemiology and disability. It established the UK ME/CFS Biobank (UKMEB), which stores data and samples from three groups: participants with ME/CFS, Multiple Sclerosis (MS) and healthy controls. Patient and public involvement have played a central role from its inception. Aim To explore the views of participants with ME/CFS and MS on CureME research findings, dissemination and future biomedical research priorities. Method Five ME/CFS and MS focus groups were conducted at two UK sites. Discussions were transcribed and analysed thematically. Results A total of 28 UKMEB participants took part: 16 with ME/CFS and 12 with MS. Five themes emerged: (a) Seeking coherence: participants’ reactions to initial research findings; (b) Seeking acceptance: participants explore issues of stigma and validation; (c) Seeking a diagnosis: participants explore issues around diagnosis in their lives; (d) Seeking a better future: participants’ ideas on future research; and (e) Seeking to share understanding: participants’ views on dissemination. Focus groups perceived progress in ME/CFS and MS research in terms of “putting together a jigsaw” of evidence through perseverance and collaboration. Conclusion This study provides insight into the emotional, social and practical importance of research to people with MS and ME/CFS, suggesting a range of research topics for the future. Findings should inform biomedical research directions in ME/CFS and MS, adding patients’ voices to a call for a more collaborative research culture.


| INTRODUC TI ON
The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/ CFS) research group at the London School of Hygiene and Tropical Medicine has been a pioneer in the field of participant-led research, with patients, carers and charity stakeholders working alongside medical researchers in the planning and development of research projects. 1,2 The group has developed the UK ME/CFS Biobank 2 (UKMEB), a biomedical research resource to maximize research efforts, using a similar participatory approach. 1 Blood samples collected from people with ME/CFS (PWME) are stored alongside those from participants with Multiple Sclerosis and healthy controls, with detailed clinical and socio-demographic data on each participant.
Our research team (CureME) uses the data and samples from the UKMEB for studies in immunology, genetics, virology, clinical medicine, epidemiology and disability in ME/CFS. We also receive applications from national and international research teams wishing to use biosamples and/or data for studies. Decisions on whether to release samples consider not only the quality of scientific design, but also the potential benefit for PWME. 3 Within this context, we consider the understanding of the meaning and importance of research findings to PWME of paramount importance, and their resultant views on biomedical research priorities. ME/CFS is a disease characterized by unexplained incapacitating fatigue for over 6 months accompanied by other variable symptoms, leading to substantial reductions in functional ability; 4,5 population prevalence rates are estimated at around 0.2% to 0.4%. 6 At its most severe, it can result in patients becoming housebound, unable to mobilize without support, or sometimes bedridden. 7 ME/CFS often affects young people and has considerable social and economic impacts, due to its chronic nature. 8,9 The question of interventions for ME/CFS remains complex and controversial, with differing interpretations of existing research evidence and no universally accepted treatment approach. 10 Biomedical studies in immunology, 11-13 virology 8,14 and neurology [15][16][17] and other specialty fields [18][19][20] have attempted to explain disease pathways in ME/CFS, but research findings are not always reproducible. 21 The aetiology remains elusive, and in the absence of any confirmatory diagnostic tests, diagnosis is based on clinical history when other possible causes of fatigue have been excluded.
The lack of a diagnostic test or biomarker means that many patients experience scepticism from health professionals, employers and others; this sense of stigma is a substantial emotional burden for many patients. 22 Multiple sclerosis (MS) was chosen as a comparison disease for ME/CFS, because while MS patients also experience chronic fatigue and disabling symptoms, the aetiology of MS is comparatively well understood with definitive diagnostic tests.
People with MS have a broadly similar experience of disability, restricted lifestyle and stress contingent to the illness, but without the specific challenges presented by lack of a diagnostic test or social stigma.
For this study, we explored the ideas of the UKMEB participants with MS and ME/CFS on our preliminary biomedical research findings and their dissemination, and on future biomedical research priorities. The engagement of both groups of study participants was critical to fully explore the different perspectives that might be offered according to their disease narratives.

| Aim
To contribute to empowering the voices of the communities involved by exploring the reactions of research participants with ME/CFS and MS to preliminary research findings, their reflections on approaches to dissemination and their views on future biomedical research priorities, building on our established participatory approach in ME/ CFS research.

| ME THODS
We conducted five focus group interviews in July 2017. Three groups were held in London and two in Norwich. The groups comprised 28 research participants, n = 16 with ME/CFS (nine females and seven males) and n = 12 with MS (seven females and five males).
A moderator led each group supported by a second researcher; no other observers were present. In London, the ME/CFS participants were grouped by gender with the men's group led by a male moderator (LN) and the women's group led by a female moderator (EL). All other groups were mixed gender and led by female researchers (CK and EL).
Participants gave written, informed consent prior to taking part. The London and Norwich groups were held on different days with participants attending a presentation of preliminary research findings from CureME prior to their focus group. The programme for the day is shown in Box 1. The questions provided were previously discussed and refined among the authors, with input from an external qualitative researcher.
The research team, together with their qualifications and experience are listed at the end of the paper.

| Patient and public involvement in study design
The CureME Steering Committee, which includes expert stakeholder advisors, ME/CFS charity representatives, PWME and carers, provided feedback on the design of the study and the program for the focus group days.

| Participant selection
Participants were drawn from the 380 people who had contributed data and blood samples to the UKMEB. Initially, 100 potential recruits were randomly selected to include a range of illness severity, illness duration, age and gender with selection thereafter purposive.
The research nurse approached participants by telephone and/or email; 13 individuals who were too unwell to participate, declined or subsequently dropped out.

| Venues
The presentations and focus groups in London were held at the London School of Hygiene and Tropical Medicine, and those in Norwich at a conference/event centre. Participants travelling to London were offered reimbursement for overnight accommodation in recognition that some would be too unwell to return home the same day. Both venues were wheelchair friendly, and quiet rooms with sofas were provided for rest breaks.

| Content of research presentation
Prior to each focus group, participants viewed a 30-min presentation (by LN, EL and CK in Norwich; and by LN and JC in London), which included the rationale for carrying out the studies, the recruitment process, and the preliminary study findings. All analyses compared the UKMEB data and samples from PWME, people with MS and healthy participants. ME/CFS participants were subgrouped as mild/moderately and severely affected. The sociodemographic and symptom progression findings resulted from analyses of a bespoke questionnaire previously piloted by the research group, 3 while disability and quality of life were measured using the SF-36v2 TM Health Survey. 23 The laboratory-based findings included: reports on immune responses (particularly on the number and functioning of natural killer (NK) cells), the presence or absence of antibodies against herpes viruses, and the gene expression profiling of the groups.

| Data collection
Focus groups were audio-recorded and transcribed verbatim. All transcriptions were anonymized using numbered codes for each participant, replacing personal identifiable data with bracketed generic titles. Field notes were taken during the focus groups.

| Data analysis
The data analysis was conducted by two qualitative researchers (EL and CM), using thematic analysis to identify "patterns of meaning" across the transcripts of the focus group discussions. This inductive approach followed the procedures for Thematic Analysis recommended by Braun and Clarke. 24 After listening to the audio-recordings and reading the transcripts to become familiar with the materials, the researchers (EL and CM) carried out a preliminary analysis on paper to draft initial codes and note issues of interest. The transcripts were then uploaded onto NVivo 11. 25 This software programme facilitated data management and enabled an audit trail in which decisionmaking processes could be tracked throughout the analysis in a transparent manner. Audit trails provide a recognized strategy for increasing the credibility and reliability of qualitative research. 26 After data coding and coding-scheme generation, codes were organized into potential themes to describe the analysed data. In an iterative process, these themes were checked for consistency, co-  After 10 min, each pair were asked to present their ideas. The full group was then asked to discuss the key messages that need to be conveyed and on the best means to communicate them. safeguarded against reaching a final thematic scheme prematurely and ensured we represented all views. 27

| RE SULTS
We conducted five focus groups in which 28 participants took part (17 ME/CFS, 11 MS). Table 1 summarizes the composition of the focus groups, and Table 2 summarizes participant characteristics.
We present here the five key themes emerging from the thematic analysis, supported by verbatim quotes (Table 3). For ease of reference, quotes are numbered within the text using the label (Q1), (Q2), etc.

| Theme 1: Seeking coherence: Participants' reactions to initial research findings
All participants express a compelling need to make sense of their illness experience. Research was seen as a means to achieve this, offering hope of putting together a "jigsaw" of evidence which might provide answers (Q1). Participants seemed to be critically examining the research findings in the light of their own knowledge and personal experience, taking on an "investigator" role, rather than being passive recipients of research information.
Participants suggested that ME/CFS and MS are complex illnesses and that finding answers was also likely to be complex (Q2).
They emphasized a need for interconnected thinking in which different physiological factors might contribute to the illness, including immune function (Q3), pathogens, particularly viruses (Q4, Q5), physical or emotional trauma and genetics (Q6). The role of environmental factors, food and chemicals in triggering CFS/ME onset and/ or worsening symptoms was of particular interest (Q7).
A major concern voiced by PWME, was the need to differentiate between people whose ME/CFS is defined according to specific diagnostic criteria, and those with other forms of chronic fatigue (Q8), as without such clarification, research results could be distorted or diluted. ME/CFS participants requested that it would be made clear in publications that people with chronic fatigue who do not fulfil the criteria for ME/CFS are differentiated in UKMEB studies.
Participants also noted that subgroups within ME/CFS had differences in onset patterns (eg, viral onset or non-viral), predominating symptoms (Q9) and levels of severity (ie, mild/moderate or severe).
Participants showed particular interest in gene expression results, in which those with severe ME/CFS appeared to be more similar to those with MS than those with mild/moderate ME/CFS (Q10). There was ensuing debate on whether severe ME/CFS might have fundamental differences to mild/moderate ME/CFS, or whether severity in ME/CFS should be regarded as simply a continuous spectrum.
Differentiating different subgroups within MS also emerged as a core interest, with participants citing the categories of "relapsingremitting MS," "primary-progressive MS" and "secondary-progressive MS" (Q11). Overall, MS participants felt they had reasonable clarity about illness mechanisms, but wanted to know why MS might be triggered, discussing factors such as genetic susceptibility, viruses and other pathogens and physical or emotional trauma (Q12).
Within an overarching need to find coherence by making sense of often confusing symptoms, one of the most vividly expressed issues was the need for a proven diagnostic test for ME/CFS, which is the focus for the next theme.

| Theme 2: Seeking a diagnosis: Participants explore issues around diagnosis in their lives
Participants with ME/CFS described a situation in which lack of a diagnostic test and uncertain aetiology left individuals feeling lost, desperate to make sense of their symptoms, and often unsupported by health professionals (Q13, Q14). Research was depicted not only as offering hope of understanding their symptoms, but also of being able to demonstrate proof of disease to regain self-respect and respect from others.
In contrast, as MS participants noted, MS is an illness with a known disease process. Nevertheless, during the first years of their illness, three of the MS participants had been mistakenly diagnosed with ME/CFS (Q15), and two had their symptoms attributed to psychological causes. Their accounts of these experiences mirrored those of the ME/CFS participants, describing a sense of "limbo" (Q16), with loss of self-confidence and feelings of despair. The turning point in their illness trajectory appeared to be receiving a definite diagnosis of MS. One MS participant vividly described his sense of relief at feeling that he was "not going mad," and to have a label for his illness (Q17). Others described similar feelings of restored coherence, being able to deal with the situation, and being able to communicate their illness to others without fearing judgmental reactions (Q18, Q19). MS participants linked receiving a diagnosis not only with a sense of validation and restored social acceptance, but also the ability to access support (Q20). It is important to emphasize, however, that for some, diagnosis of MS had felt completely devastating, with no positive aspects, described by one as "the biggest kick in the teeth ever" (Q21).
While some participants with MS had experienced diagnosis as pivotal to regaining coherence, validation and self-respect, participants with ME/CFS were still hoping for a similar turning point. When exploring the meaning of research for their lives, the relationship between physical proof of illness and social acceptance emerged as a central concept, and this will be explored further in the next theme.

| Theme 3. Seeking acceptance: Participants explore issues of stigma and validation
For many of the participants with ME/CFS, a central figure from whom they sought acceptance and support was their primary care doctor (GP). In the absence of biomedical tests to prove illness, many of the participants felt that they had struggled to convince their GP that they were physically ill and relationships had become strained.
Some participants described experiences of feeling disbelieved, un supported or not "held" within medical relationships, although others reported that they had a good relationship with their current GP who gave them valued support (Q22).
Illuminating reflections were offered by one participant who had been a GP prior to having ME/CFS. Recalling personal experiences, he described some of the difficulties experienced by GPs when presented with a patient with medically unexplained symptoms. The participant noted how much he had learned as a doctor since experiencing ME/CFS himself (Q25).
Feeling judged as not genuinely ill by employers, benefits agencies and friends or family were also highlighted by ME/CFS participants as well as by MS participants, who recalled similar experiences prior to diagnosis (Q26). ME/CFS and MS participants were intrigued by results from the SF36v2™ questionnaire viewed earlier in the day, suggesting that the impact of illness on social function was worse for participants with ME/CFS than MS (Q27). Both ME/CFS and MS participants hypothesized that this might be due to PWME finding it harder to feel acceptance from others and/or self-acceptance without biomedical proof of illness (Q28). Yet, it is important to note that participants diagnosed with MS also described situations in which their illness impacted their social confidence. Unpredictable episodes of incontinence or problems with being misjudged as drunk due to poor-balance could lead to considerable social embarrassment and distress (Q29).
Overall, the impact of illness on social acceptance and confidence emerged as a major concern, which, in addition to the illness symptoms, adversely affected quality of life. Research was widely perceived as offering hope for improved quality of life, and the next theme explores participants' views on this.

| Theme 4. Seeking a better future: Participants' ideas on future research
Participants' suggestions on research topics tended, perhaps unsurprisingly, to be illness-specific. Both ME/CFS and MS participants were intrigued by results which had found impact of illness on pain, fatigue and social function to be worse in ME/CFS than MS. Several ME/CFS participants wanted to see such comparisons extended, for example, to compare electronically measured activity and sleep (Q37 Q38).
Dissemination of research results was perceived as a crucial route to influencing attitudes, and this is the subject of our final theme.

| Theme 5: Seeking to promote understanding; participants views on dissemination
We asked participants to share their ideas about how research results might best be disseminated, considering target audiences, suggested strategies, hopes and concerns.
Recommended target audiences, predictably, included doctors (especially GPs), PWME or MS and their families or carers, social workers, benefits agency professionals and the general public, especially young people.
Tailoring the style of dissemination to the audience was consid- Strategies for publicizing results included mainstream media, such as newspapers, radio and TV. Patient organisations were also thought a valuable conduit for communicating research results.
While social media was discussed as a means of communication, this raised more concerns than enthusiasm, due to the challenge of condensing complex topics into relatively few words.
For participants with MS, an overarching priority for dissemination appeared to be updating doctors, people with MS, and their families and friends on research progress without raising unrealistic hopes of cure, which some found distressing or frustrating in the past (Q43). A priority was to ensure that any dissemination was concise, positive and realistic (Q44).
Participants suggested that dissemination of early results, even unspectacular ones, could provide hope, tempered by the realistic acknowledgement that small knowledge increments could gradually lead towards greater understanding (Q47). Participants emphasized the importance of collaboration rather than competition between research teams (Q48).
The concept of research collaboration recurred throughout the discussions, underpinning participants' hopes for the future. Within this context, they appreciated being treated as respected partners by the research team, listening to their views and keeping them informed (Q49). Participants reflected on their own place within the quest for a better future through scientific understanding, as people who had "bought into" the research process (Q50, Q51) through contributing not only blood samples, but their time and effort, ideas, experiences and hopes; expressing enthusiasm by the possibility that they too could genuinely "make a difference" to the research journey ahead (Q52, Q53).

| Summary of key results
In recent years, patient perspectives have become increasingly important in informing the is planning, conduct and dissemination of research. 28 In this study, participants with ME/CFS and MS illustrated the importance of research as means of seeking coherence to make sense of their illness (Theme 1), seeking diagnostic clarity (Theme 2) and proof of illness by which they could gain acceptance and from the medical profession and from society (Theme 3).

Participants offered ideas on future research priorities (Theme 4)
and recommendations for dissemination (Theme 5).
A key aim in this study was to elicit patient views on biomedical research priorities for the future. Overall, the research topics pro- Q3 My understanding was that there seems to be a difference in the way the immune system reacts to the introduction of a pathogen, and this is something to do with the answer we need to find in the future, what's happening to Q7. During that time, in a few weeks leading up to me with months being diagnosed with ME, there were several chemicals used in the house usually by myself, paint strippers to take off all wallpapers, moulds, paints….I just wondered whether there was any connection with chemicals, moulds, on the immune system or that sort of thing? (P19, male, ME, group 4) Q8. The fact that Biobank breaks down Canadian criteria and non-Canadian criteria was important. (P3, male with ME, FG1) Q9. There needs to be a lot more grouping. ME is just too wide a term…His is more brain-based, mine is more, for me it feels more muscle and that sort of side. (P5, male with ME, FG1) Q10. There seems to be a fairly big distinction between mild, moderate and severe, and from that last graph it almost looked as if they were two separate conditions because they were so different between the severe section and the mild-moderate section. Q25. I learnt an awful lot more about it after suffering and as time goes on you think, "Oh yes, that symptom is compatible," and understand a lot more. (P19, male, ME, group 4) Q26. I'm mentally far stronger now than I was when I was in that two to three year period where work were telling me there was nothing wrong with me and I was only pulling a sickie… Eventually the diagnosis, I was like, "Oh, thank God for that. Now I can move on." (P27, male, MS, group 5) Q27. That was the thing that came up for me as well that I anticipated that people with MS would have probably more fatigue and more restriction socially, but it seemed to be the ME group that were more affected. (P20, female, ME, group 4) Q28. When they had the right-hand chart-and I think it said that socially and mentally we became a bit stronger, if I read the chart correctly-in seeing that I thought, "Well, it's probably because we do have a definite diagnosis of a definite condition that you can definitely get your head round, however long that takes and whatever adaptations you have to make. (P25, female, MS, group 5) Q29. You go out on a social event, like a bar you're in or something else, and I still really think harder, "I need a wee, but I don't want to get up because they'll think I'm drunk." (P24, male, MS, group 5) Q33. That was the point of doing the gene expression work, is, rather than following up the knowns, and the unknown knowns, etc., is to actually try to look globally at everything we can. There will always be things that we don't even think of to look at, but it is an unbiased approach to try to pull things out. (P8, female, MS, group 2) Q34. I'm sat here thinking, "What did I expect out of this?" Maybe somebody's going to say, "Okay, we've found a magical cure," and obviously what is coming back to me is telling me that I'm not going to get that cure within my lifespan, so possibly a bit sad. (P9, female, MS, group 2) Q35. I think most of us realize that probably we're a little bit past the point where we're going to be miraculously cured. Well, I always think that if it happens it's great, but I'm not banking on it happening because then I'm going to be disappointed if it doesn't. (P25, female, MS, group 5) Q36. I'm glad I'm participating in this and that, even if I don't get the benefit, the future generations will benefit from it.(P11, female, MS, group 2) Q37. It was quite interesting, not positive, I wouldn't say, but interesting to see that the pain with ME, according to your research, is more severe than MS. I found that really bizarre in a 'We need to study this now,' kind of way. (P13, female, ME, group 3) Q38. An objective measure of that would be to use technology that they have now where you could have the actimeters, like they were showing on the Doctor in the House where they had a watch that measured their activity, their night, their sleep and that sort of thing would then back up actually what has been shown by those questionnaires. Then that would surely be a very good measure of a longitudinal measure of each individual and then compare it with MS. (P14, female, ME, group 4) Theme 5: Seeking to share understanding Q39. If it's going out in any form to the general public it wants to be in a readable format, not 500 pages of medical comments that nobody who's going to read it can actually understand. (P6, male, ME, group 1) Q40. But you do need to thread a personal story through it somehow, that's the formula, that's what we've always seen, a personal story that illustrates the actual research but it's the kind of story that illustrates.

| Strengths and weaknesses
As far as we know, this is the first in-depth qualitative study to examine the views of both participants with ME/CFS and MS on what biomedical research means to them, on future research priorities, and approaches to sharing and publicizing results.
A strength of using focus groups rather than individual interviews was the extent to which participants were able to interact in their reflections, often eliciting richer and more complex exploration of ideas as the discussions progressed 29 However, our ability to include individuals who were housebound was limited by using this approach as it required patients to be well enough to travel to a venue for the group. Focus groups may also limit the extent to which individuals shared opinions differing from those held by the rest of the group. 30 Purposive sampling ensured that the groups included men and women of different ages, illness durations and severities of illness.
However, we acknowledge that recruiting participants from individuals already participating in the biomedical research of the UKMEB might lead to higher levels of awareness/comprehension of research than the wider patient population, and that patients who were new/ naive to research might have expressed different views. 31 In this study, all focus group facilitators were from CureME, whose remit is biomedical research. Analysis of transcripts suggested that participants appeared to concur with that approach for ME/CFS research. This is perhaps unsurprising, since participants were recruited from the larger sample of those taking part in the UKMEB. The remit of this study was to elicit participants' views The study included more ME/CFS than MS participants in a 3:2 ratio. This design was in accordance with the remit of CureME and UKMEB, which were established for accelerating research into ME/ CFS. MS participants were made aware from the outset that the research to which they were contributing was primarily aimed at ME/ CFS, though with the possibility that results might also help people with MS. We are particularly grateful for their contributions within this context.

| How do these findings relate to existing literature?
Placing patient perspectives at the centre of healthcare research has been strongly promoted by many international policy makers, 28 as well as funders 33 45 and expert panels, 46 as well as structured consensus seeking methodologies such as the Delphi technique. 39,46,47 In this study, the use of focus groups permitted us not only to explore patient views on research priorities, but also to shed light on some of the emotional and experiential reasons behind these priorities, helping to inform our understanding of this complex topic. At the same time, more systematic methodologies, such as the Delphi technique, 46 could provide more structured conclusions on research priorities than was possible in this study.
In 2017, CureME published a study documenting patient participation in designing the UKMEB. 2 The current study follows on from that work, illuminating patient reactions to what has been achieved, as well as signposting directions for the future, enabling, participants to become active partners with researchers, rather than passive "research subjects" or recipients of information. Several of the MS participants with a delayed diagnosis described how they had felt judged by medical professionals and others as inventing or exaggerating symptoms, an attitude which transformed into supportive acceptance with a confirmed diagnosis of MS.

| Implications for clinical practice
Participants with ME/CFS longed for a research breakthrough to achieve a similar transformation. These mirrored narratives raise the question of whether more progress might be made in treating the patients' accounts as trustworthy, allowing patients, with or without current diagnosis, to feel validated as people deserving of credence and compassion in the medical relationship.

| Recommendations for future research
A key study objective was to find out what patients viewed as important in choosing directions for future research. The findings signpost a diversity of specific topics, including investigating subgroups within ME, immunological and mitochondrial dysfunction the role of chemical and environmental triggers in ME/CFS, and genetic, viral and immunological factors for MS. These research topics are congruent with the intentions of CureME and UKMEB, though the study adds specific suggestions which the team will endeavour to find ways of including within future research collaborations.
Participants called for researchers to be less concerned about claiming a "breakthrough" in medical science for their own work, and to put greater emphasis on contributing to a collaborative integration of research knowledge which might one day lead to a biomedical test, effective treatments or cure. CureME hopes to fulfil that request, not only in future dissemination, but in all interactions with the wider research community. Ours and other similar initiatives appear to indicate that the prevailing research culture is changing gradually towards the collaborative ethos participants wish to see.
This study offers a compelling, patient-centred argument for a paradigm shift within research culture towards collaboration, not only between different research teams but between patients and researchers.
How specifically this might be achieved remains a subject for ongoing discussion and development within the ME/CFS and MS research communities, but the participants expressed hope that their contributions might help build a better future for current and future generations, resonates with the ethos we share with many other researchers.

| CON CLUS ION
The findings of this study provide insight into the emotional, social and practical importance of research to MS and ME/CFS patients as well as suggesting a range of specific research topics for the future. Findings should inform the future direction not only of the UKMEB, but also of researchers across ME/CFS and MS research, adding the voices of patients to a call for developing a more collaborative research culture.

ACK N OWLED G EM ENTS
We would like to thank all participants who have generously contributed to the studies, by donating their samples, time, and energy. We also thank the Steering Committee members for their support, and Dr. Alicia Renedo, our colleague at the LSHTM, for her generous and insightful comments to the study design.

AUTH O R S' CO NTR I B UTI O N S
The

CO N FLI C T O F I NTE R E S T
All authors confirm that they have no financial, personal, politic or academic conflict of interest.

E TH I C A L A PPROVA L
This study received approval from the London School of Hygiene