1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A qualitative study of perspectives on access to tuberculosis health services in Xigaze, China

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Tuberculosis (TB) is a major global health threat and the leading infectious disease cause of death worldwide. Access to and retention in TB care remains a challenge for patients, particularly those living in rural and remote settings. This qualitative study explored barriers and facilitators to accessing and maintaining contact with TB care services in communities in Xigaze (Shigatse) prefecture, Xizang Autonomous Region (Tibet Autonomous Region), China from the perspective of persons impacted by TB.

          Methods

          We conduced in-depth interviews with 23 participants impacted by TB in four rural districts in Xigaze prefecture, Xizang Autonomous Region, China between April 2019 and November 2020. Interviews were conducted in Tibetan and Mandarin, transcribed in Mandarin and translated into English. Transcripts were checked against recordings by native Tibetan and Mandarin speakers. QSR NVivo12 software was used for framework analysis guided by an access to care conceptual framework by Levesque et al.

          Results

          Overall patients reported low awareness of and an indifferent attitude towards TB, although all reported understanding the need to adhere to treatment. Participants reported complex pathways to care, often requiring visits to multiple healthcare facilities. Some participants reported visiting traditional Tibetan medicine (TTM) providers. Participants reported various barriers to accessing care including challenges physically reaching care, out-of-pocket payments for tests, diagnostics and transport. Barriers to maintaining care included medication side effects and worry about treatment effectiveness. Enablers to accessing care identified included knowledge or past experience with TB, integrated models of TTM and western care, supportive village doctors who conducted home visits, free TB treatment and other subsidies, as well as having family support with care and social support as barriers and facilitators to maintaining treatment.

          Conclusions

          We identified barriers and facilitators to accessing services in rural communities in Xigaze from the perspective of persons impacted by TB. Challenges include complex pathways to care, travel distances, wait times and low awareness. Tuberculosis care in the region could be strengthened by ongoing culturally tailored educational campaigns to increase awareness, partnerships with TTM providers, providing comprehensive treatment subsidies and strengthening the role of family members in comprehensive TB care.

          Graphic abstract

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40249-021-00906-4.

          Related collections

          Most cited references 63

          • Record: found
          • Abstract: found
          • Article: not found

          Patient Adherence to Tuberculosis Treatment: A Systematic Review of Qualitative Research

          Introduction Tuberculosis (TB) is a global health concern, with an estimated 8.9 million new cases worldwide in 2004 and two million deaths each year [1]. It is a major contributor to the burden of disease, especially in low- and middle-income countries, where it is being fuelled by the HIV/AIDS epidemic [2]. DOTS (directly observed treatment, short course) is the internationally recommended control strategy for TB [3]. This strategy includes the delivery of a standard short course of drugs, lasting 6 mo for new patients and 8 mo for retreatment patients, to individuals diagnosed with TB. The delivery includes the direct observation of therapy (DOT), either by a health worker or by someone nominated by the health worker and the patient for this purpose (sometimes called a DOT supporter). The strategy has been promoted widely and implemented globally. Up to half of all of patients with TB do not complete treatment [4], which contributes to prolonged infectiousness, drug resistance, relapse, and death [5]. The difficulty experienced by patients following a particular treatment regimen has raised awareness of adherence as a complex behavioural issue, influenced by many factors [6], including gender and the impact of HIV/AIDS. WHO has attempted to classify factors that influence adherence to TB treatment based on a cursory review of key papers [6], but the impact of gender [7] and HIV status [8] on adherence are less well documented in the qualitative literature. Efforts to improve treatment outcomes require a better understanding of the particular barriers to and facilitators of adherence to TB treatment, and of patient experiences of taking treatment [9]. Qualitative research can contribute to this understanding and help interpret the findings of quantitative studies of the effectiveness of adherence-promoting interventions [10]. The volume of such qualitative research is growing and we believe that one way to draw useful lessons from this literature is by synthesising the findings of these studies. Systematic synthesis of relevant qualitative studies of TB treatment adherence can provide more complete knowledge than that derived from individual studies alone. It can assist in the interpretation of findings of single studies; help explain variation or conflicts in study findings; enable the development of new theories; and help inform the design of new interventions. In addition, it may allow the identification of gaps in existing adherence research. In this review we consider the perspectives of patients, caregivers, and health care providers regarding adherence to TB treatment. The findings of this review will have implications for a range of stakeholders including nongovernment organisations, national policy makers, and international bodies working towards reducing the global health burden of TB. Methods We followed a meta-ethnographic approach [11], the steps of which are outlined in Figure 1, to synthesise findings across included studies. This systematic approach translates ideas, concepts, and metaphors across different studies and is increasingly seen as a favourable approach to synthesising qualitative health research [11,12]. The research team included three social scientists (SM, SL, HS) and three clinical researchers (JV, AF, ME). The social scientists had different disciplinary backgrounds. Figure 1 Meta-ethnography Process Inclusion Criteria We included studies that examined adherence or nonadherence to preventive or curative TB treatments and described the perspectives of patients, care givers, or health care providers. We included studies from any discipline or theoretical tradition that used qualitative methods. We included papers that reported qualitative research only, as well as research using qualitative and quantitative methods (mixed method) that reported qualitative findings. Both published and unpublished studies reported in English were considered. Because of resource limitations, papers published in other languages were not considered. Search Strategy and Study Selection Figure 2 maps out the process by which articles were selected for our systematic review. We searched 19 databases, using the keywords: “TB AND (adherence OR concordance OR compliance)” from 1966, where available, until 16 February 2005 (see Table S1 for search results). This process was complemented by reviewing citations, searching in Google Scholar, and expert referrals. Additional articles were included as they became available. We used the search, assessment, and retrieval process outlined by Barroso et al. [13]. SM scanned more than 7,000 citations identified in the various databases and retrieved abstracts for potentially relevant studies (n = 2,162). Approximately 10% (n = 222) of these were also reviewed by JV to validate the selection of articles. Disagreements (n = 17 papers) were resolved by discussion and reference to the full article. Thereafter, SM screened the titles and abstracts of potentially relevant studies, excluding 1,536 papers and retrieving potentially eligible papers (n = 626). After scanning the full text, 560 of these articles were not considered eligible and 66 were considered potentially eligible, based on our inclusion criteria. The abstracts of these were assessed by SM and SL, and ineligible and duplicate papers were excluded, leaving 47 that were considered eligible. Two independent reviewers then read the full paper of each study, following which three more papers were excluded because they did not include qualitative data or because they had insufficient descriptions of data collection or analysis methods. The final synthesis therefore involved 44 papers. Figure 2 Search Process and Study Selection Quality Assessment We decided to assess the quality of individual studies using a checklist based on common elements from existing criteria for qualitative study quality assessment [10,14–17] (Table 1). These existing checklists are published and peer reviewed, but unlikely to be validated; only the Critical Appraisal Skills Programme criteria [17] have been used by other meta-ethnographers [18]. Evaluating study quality allowed us to describe the range of quality across included studies. Two reviewers independently assessed study quality using a pretested form and resolved differences by discussion. No studies were excluded on the basis of quality. This approach was taken for two reasons: first, both the original authors of the meta-ethnographic approach [11], and other users of the method [19], have found that poorer-quality studies tend to contribute less to the synthesis. The synthesis therefore becomes “weighted” towards the findings of the better-quality studies. Second, there is currently no consensus among qualitative researchers on the role of quality criteria and how they should be applied [10], and there is ongoing debate about how study quality should be assessed for the purposes of systematic reviews [20]. Table 1 Methodological Quality of Included Studies (n = 44) Synthesis Based on the meta-ethnography approach described by Noblit and Hare [11], we used reciprocal translation, analogous to constant comparison in primary qualitative research, to compare the themes identified in each study. We then conducted a “line-of-argument synthesis,” an approach similar to grounded theory in primary research, to determine a model of factors influencing treatment adherence. From this process we derived hypotheses relating to the reorganisation of treatment and care to improve adherence. The synthesis process is described below and illustrated in Figure 1. Identifying themes and concepts. We identified concepts, themes, and patterns by reading and rereading the included studies. In this process, we understood primary themes or first-order constructs as reflecting participants' understandings, as reported in the included studies (usually found in the results section of an article). Secondary themes or second-order constructs were understood as interpretations of participants' understandings made by authors of these studies (and usually found in the discussion and conclusion section of an article). However, we recognise that all reported data are the product of author interpretation [21]. One author (SM) extracted first- and second-order constructs from the articles, plus relevant data on study context, participants, treatment type, and methods using a standard form. The rest of the study team independently extracted data from half of the studies, but found no major differences. Although the foci of the studies were not all directly comparable, the study team identified a number of recurring first- and second-order constructs. Determining how the studies are related. We used thematic analysis to inductively develop categories from the first-order themes and concepts identified in the included studies. These categories represent related themes and concepts and initially included: family, community, and social support; professional practice and organisation of care; financial burden; personal characteristics as related to treatment adherence; access to services; disease progression; and knowledge, beliefs and attitudes towards treatment. We revised and merged these categories by discussing together as a team how they were related. We followed a similar process for second-order constructs identified from the included studies. Reciprocal translation of studies. Following the meta-ethnographic method closely, we compared the concepts and themes in one article with the concepts and themes in others. Translation involves the comparison of themes across papers and an attempt to “match” themes from one paper with themes from another, ensuring that a key theme captures similar themes from different papers (see Britten, et al. for further description [12]). We approached the reciprocal translation by arranging each paper chronologically, then comparing the themes and concepts from paper 1 with paper 2, and the synthesis of these two papers with paper 3, and so on. We began with the categories identified in the process described above, but incorporated others as they emerged. Two authors conducted the translation independently, returning to the full-text papers frequently throughout. In this review our aim was to explore adherence to TB treatment without confining this variable to a specific population or subgroup, but in doing so we were careful not to inappropriately synthesize the findings of heterogenous studies. In the process of comparing the studies against each other, we looked for explicit differences between the studies in relation to a range of factors including their geographic location, socioeconomic conditions, and the type of treatment programme. From the reciprocal translation we were able to construct tables showing each theme and related subthemes, and narratives to explain each theme. Synthesising translations. We chose to synthesise the results of the translation independently to account for different interpretations by disciplinary background. To develop an overarching framework (or third-order interpretation), we listed our translated themes and subthemes in a table, juxtaposed with secondary themes derived from author interpretations (see Table 2). Each member of the research team then independently developed an overarching framework by considering if and how the translations and authors' interpretations linked together. From this we produced a model (Figure 3) and generated hypotheses, in a “line-of-argument” synthesis. Line-of-argument syntheses create new models, theories, or understanding rather than a description of the synthesised papers [11]. Table 2 Primary and Secondary Themes Emerging from the Included Studies Figure 3 Model of Factors Affecting Adherence We attempted to explore systematically the influence of socioeconomic status and geographic location on the findings of our synthesis. However, it was difficult to determine many patterns except those highlighted specifically by authors of the primary research. We realised that synthesising studies from a variety of contexts would present challenges, but also felt that including these studies would provide an opportunity in the synthesis to explore the differences between the contexts, if these existed. Similarly, we chose to include studies examining adherence to latent TB treatment as well as adherence by injecting drug users (IDUs) and homeless people, with specific attention being paid to the ways that the issues raised in these studies differed from those focused on active TB in other populations. Again, few differences emerged. Results Description of Studies Forty-four studies published between 1969 and 2006 were included in the review. The studies were conducted in Africa (14), North America (9), South (8) and East Asia (8), Latin America (2), and Europe (2). It was difficult to discern the study setting from the published reports, but most were conducted within a clinic or health service setting (see Table 3). Most studies were concerned with curative TB treatment (33); others focused on preventive treatment (8) and some considered both (2). Most of the studies involved TB patients, often also including community members and health care workers. Three studies involved IDUs and homeless individuals. Approximately 3,213 individuals were involved in the included studies. We found few studies that justified their use of a qualitative approach (n = 13) or specified the underlying theoretical framework (n = 10), and few authors reported on their role as researcher (n = 12) (Table 1). In 12 papers the method of analysis was clearly described, but some derivation of thematic analysis appeared to be used in others. Although several studies seemed to have high face validity, they often scored poorly on our quality assessment instrument, possibly due to the instrument's ability to measure only the quality of reporting. Table 3 Characteristics of Primary Studies Included in this Review Table 3 Extended. Description of Themes Eight primary themes (identified from participants' understandings) and six secondary themes (derived from authors' interpretations) arose from the synthesis (Table 2). Each primary theme is described in Boxes 1–8 using direct quotes to illustrate meaning. Box 1: Organisation of Treatment and Care for TB Patients “The patients do not have the adequate means to go to the health centre to take their drugs. They just have camel, donkey or carts… And sometimes, the state of some patients prevents them from using these” (male family member of TB patient, Burkina Faso) [31]. “A dirty place can affect the psychology. It makes people lose heart and feel unenthusiastic about continuing treatment” (female participant with TB, Vietnam) [26]. “It just does not make sense as to why a grown up person should be given medicines by someone else. I felt very awkward, and tried to take my medicines myself” (male TB patient, Pakistan [22]. “…and I was afraid to go to the doctor, I thought he would scold me because I missed treatment for a day. For this reason, I didn't go back to get more pills. I was afraid…” (female participant, Bolivia) [32]. “The minute you tell them you're homeless they treat you real snobbish… They treat you like a dog down there once you get past the triage nurse…” (female TB patient, United States) [50]. ‘…It did help, cos I really needed assurance that it was definitely going to be [cured] and doctor spent a lot of time with me. And they were really, really um, they were outstanding there” (male TB patient, United Kingdom) [30]. Box 2: Interpretations of Illness and Wellness “…When I feel better, I don't take the tablets. Only when I feel pain” (completer, South Africa) [51]. “…She said ‘no no no I do not have TB any more' because she no longer has blood in her sputum” (provider, Indonesia) [46]. “Well, if you know a little bit about the disease and, like we say, if it's latent… you are not sick. It's only.. if it becomes active, then you are liable to be sick and probably very sick. So then you consider taking the medicine that is terribly bad: which is worse? That's when you weigh what is best for you” (provider, United States) [35]. “I think that I feel healthy, my lungs are good, but I have a bit of fear that the sickness will return… But as I told you, I don't want to take these pills, because they make me sick, they hurt me…. “ (female TB patient, Bolivia) [32]. Box 3: Financial Burden of TB Treatment “It's a bit difficult, because, as I told you, the radiography and the control smear cost more than 100B; the consult costs 15B…it will cost me almost 150B to start treatment again. At this moment, I don't even have the money for the trip to the hospital...” (male TB patient, Bolivia) [32]. “TB here is closely related to social and economic problems. People live in densely populated areas, their income is poor, and they don't understand about TB” (provider, Indonesia) [46]. “We cannot remain out of a job for long. As soon as we feel better we would like to go to work… If I cannot earn, my whole family will suffer” (male TB patient, South Africa) [51]. “Typically it [treatment] would be three months.. that's a long time for anyone to be available without any compensation… it's tremendously a matter of economics and economics only…” (male TB patient, Canada) [57]. Box 4: Knowledge, Attitudes, and Beliefs about TB Treatment “He believed that he should always use the expensive tablets and not the tablets from [the health care facility]. The … tablets were not correct with the problem inside, and the colour of the tablets doesn't look right” (participant, Indonesia) [33]. “No doctor is able to cure this” (patient, South Africa) [34]. “That's just like basic common sense, this is no test… if the doctor says to us take these tablets then that's common sense.” (male TB patient, UK) [30]. “…And when you take medications, these bugs will die, he told me. The medications kill the bugs. This is what I've been told, but I'm not sure. It seems uncertain to me. Because the pills didn't help me….” (female TB patient, Bolivia) [32]. “…a lot of people don't take the medicine because they feel that taking it doesn't do any good for their health” (female noncompliant patient on prophylaxis, US) [53]. Box 5: Law and Immigration “Because the nurse tells us that here they have a record of people who have TB, and when they go to apply for a job it shows up on the record that they have TB and it was untreated, they need [the completion record] for the job” (male Vietnamese refugee patient, US) [53]. Box 6. Personal Characteristics and Adherence Behavior “How would somone who starts drinking early in the morning visit the clinic? Some patients consume alcohol daily. They would rather decide to interrupt their treatment, than discarding their drinking habit” (male respondent, South Africa) [40]. “…When my husband went back home, he was angry with himself and he was upset about everything. He refused to eat and rejected his medicine. He threw his pills away. He did not take TB medicine at all” (female HIV+ TB patient, Thailand) [64]. “[interviewer: ‘Some people don't want to take their pills]’ Stupid people, sorry to say that” (male TB patient, UK) [30]. “I missed taking some pills because I was drunk or high on drugs” (female TB patient, US) [59]. Box 7: The Influence of Side Effects on Treatment Adherence “…Unpleasant metallic taste in his mouth… asked if a non-vegetarian diet would improve this problem. He was laughed at by the [provider] along with a number of others in the clinic and some personal remarks were made…he finally left treatment” (male TB patient, India) [24]. “I said no wonder they defaulted, many of them defaulted, you know, because it is [side effects] just too much, it is just too much …” (TB patient, UK) [30]. “These tablets let one's body itches for the whole day. I know someone who interrupted this treatment because of this problem.”(male TB patient, South Africa) [38]. “…I don't want to take these pills, because they make me sick, they hurt me…” (female TB patient, Bolivia) [32]. Box 8: Family, Community, and Household Influences “I arrive early in the morning so that people could not see me. I used to conceal my illness from people… People think that we are the filthiest people… it was really difficult to accept that I have TB” (male patient, South Africa) [40]. “We are two sisters and marriage arrangements have been made with men from one family. If my (future) family-in-law knows that I have TB they will be sure then to break the engagement...I'm worried for my sister. Her engagement also could break off because of my sickness” (female patient, Pakistan) [55]. “Just pick up the medication even if you don't use it” (patient advice to another patient on preventive treatment, US) [53]. “…I must have responsibility to take care of my child… If I die, who will take care of her? …. When I think of my child… I must be cured. This made me feel I must take the medicine” (female HIV-positive TB patient, Thailand) [64]. “…It was very important, I had my sister and my ex-girlfriend and it was really, really important to have someone, you know, to give you support especially when you don't know much about the disease” (male TB patient, UK) [30]. “…Since I have three children that I need to support… this worried me more” (male TB patient, Bolivia) [32]. We found no discernible patterns when we explored the influence of factors such as geographic location, socioeconomic status, latent or active TB, type of treatment programme, or special groups such as IDUs or the homeless. Although some studies differentiated between patients receiving treatment in urban and rural areas, no strong differences emerged between these settings, and we therefore judged it appropriate to synthesize findings across all studies. Any differences that emerged between studies with regard to specific factors are noted in the text below. Organisation of Treatment and Care for TB Patients For most patients, access to a health care facility depended on distance and available transport as well as their physical condition. One study indicated that, although the intention was for a DOT supporter to visit the patient's home, in practice the patient had to walk to the supporter's home [22]. This proved especially difficult for patients with severe symptoms [22–25]. One study noted that access to health care facilities was better in urban areas than rural areas [26], and both patients [27,28] and providers [29] noted that adherence was compromised if the distance from patients' homes to the nearest clinic was too great. If patients' homes were close to a clinic, however, the patients could attend regularly [30]. For patients on DOT, the time needed to present for direct observation of treatment-taking compromised their ability to attend to other daily tasks [25,31,32]. In one study, patients found private practitioners more accessible [26]. Problems manifesting specifically at health facilities included long waiting times, queues, lack of privacy, inconvenient appointment times [23,26–28,31–35], and the poor upkeep of clinics [26,27]. Many studies reported that patients experienced difficulty in accessing treatment at health care facilities because of inconvenient opening hours and provider absenteeism [22,23,31,37–38]. Poor TB medication availability at health care facilities was highlighted by patients [23,33,36,38] and providers [29]. For example, one study reported that a health care worker sold TB medication that should have been freely available [31]. A patient's relationship with the treatment provider also appeared to influence adherence. A large number of studies indicated that poor follow-up by providers [33,36,39], and maltreatment by providers [23,24,31,39–41], such as scolding a patient for missing appointments, resulted in nonadherence. In contrast, other studies noted the positive impact of increased provider–patient contact on adherence [26,39,42,43]. Some studies highlighted how treatment requirements could impact on patient attitudes towards treatment and thus on adherence behaviour. Patients could “become tired” of taking medications [26,30,40,44,45], discontinuing because of the length of treatment [38,40,45,46], the number of tablets [24], or fear of painful injections or drugs [29,47], as noted by both providers and patients. Some patients reported they found it difficult to meet the requirements of DOT [24,25,32,39,40]. In a number of studies conducted with patients being directly observed [22,24,34,42], adherence to treatment was facilitated by flexibility and patient choice. The continuity of the treatment process was important to patients [39,42], and irregular supervision by a family member sometimes compromised the treatment programme [22,23]. Some patients viewed direct observation negatively [22–25,40,45,48], interpreting it as distrust, and in one study describing the process as “doing time” [49]. In contrast, a study conducted with IDUs indicated that these patients appreciated the direct observation component of care because they received their treatment together with their methadone from a street nurse [50]. Interpretations of Illness and Wellness Studies in our synthesis reported that patients stopped treatment because they felt better and thought that they were cured [23,24,39,40,45,47,49,51] or because their symptoms abated [47,52,53]. Some studies noted that patients who felt worse than before treatment [23,24,32] or saw no improvement in their condition [22–24,46] might be more likely to interrupt treatment. A study conducted in The Gambia reported that migrants arrived in the country to receive TB treatment and returned home once they felt better [27]. This problem may be linked to patients' conceptions of recovery, and of the aetiology of TB. Treatment interruption was also reportedly related to perceptions about TB as a disease; some patients did not believe that they had TB, only wanted a cure for their symptoms and ceased treatment once these lessened [33,43,52]. Another study reported that patients were motivated to continue treatment as a consequence of symptom relief [30]. One study conducted in China noted that patients often continued to take medication after the necessary period of six months, and some patients would continue with treatment despite not having any symptoms, because they believed that the “roots” of the disease needed to be removed [54]. Some patients needed help in taking their medication when they were too weak [23], while others on preventive treatment and with no symptoms hesitated to even begin treatment, thinking that it could make them ill [35]. Three studies found that patients experiencing severe symptoms were more likely to adhere [39,43,54], possibly due to a fear of becoming more ill. Financial Burden of TB Treatment Several studies indicated that having TB had consequences for work [22–24, 26,27,29,32,34,42,52,54–56]. Studies suggested that patients hide their disease for fear that employers may discover that they have TB, with consequent effects on adherence. Additional work-related issues included difficulty in obtaining sick leave for treatment; fear of asking for money to purchase TB drugs; and fear of losing work or dismissal [26,29,36,55]. The reports showed how some patients prioritised work over taking treatment—and for many there appeared to be a “choice” between work and adherence [23,24,26,29,32,34,36,37,42,45,54]. More common in rural areas, this was not a real “choice” but rather a conflict between attending for clinic-based treatment and the need to earn a living. This was manifested in patients feeling “forced” to choose between work and attending treatment [26]; patients having “no choice” but to abandon treatment because it was too difficult to combine the two [29]; and patients not being able to afford treatment, but if they sought work, being unable to attend for treatment [32]. A study with inner-city homeless people on preventive treatment reported that treatment posed an economic barrier for them because they often worked out of town [57]. Patients also expressed guilt over the impact that the disease had on their family livelihoods [31]. Several studies found that patients had more pressing issues to attend to in everyday life [24,29,31,32,40,42,45,56], such as taking care of family. Economic constraints were especially noted in rural areas, especially for patients on preventive treatment [51]. Patients often explained treatment interruption by noting the costs of treatment [23,26,29,32,33]. In some settings, patients reported that drugs were expensive [29,36] and, where treatment itself was free, hidden costs such as hospital stays [29], reviews of X-ray results, and transport costs could be high. In some cases providers acknowledged patients' financial constraints [31]. However, there were examples of doctors not accepting that costs caused patients to stop taking treatment because, from the doctors' perspective, treatment was provided at no cost [32]. Failure to accept patients' reasons for nonadherence may contribute to the negative attitudes sometimes expressed by providers towards defaulting patients, resulting in difficulties in patients returning to treatment following missed appointments. Conflicts between treatment and work and the hidden costs of treatment, resulting in expenses exceeding resources [22,26–28,31,32,34,42,43,48,54,55], could push people into poverty. This possibility was cited both by health professionals and by patients as a reason for nonadherence [23,26,32,37,42,54–56]. Males (as head of households and often sole wage earners) tended to cite this reason more frequently than females [26,37,42,55]. In societies where female or adolescent patients depend on family for financial support (particularly India and Pakistan), poverty was reported as a major reason for nonadherence to treatment [22,23,36,51,55]. For patients living in poverty, the quality of food consumed while on TB treatment was reported to affect adherence [22,26,27,29,37,45,54]. Patients reported not being able to take medication on an empty stomach, or being unable to remain in hospital due to a lack of free food [26,29,37,45,54]. Knowledge, Attitudes, and Beliefs about TB Treatment Many studies centred on the influence of patients' understanding of treatment, including its duration and the consequences of defaulting, on adherence to treatment [23,24,26–28,33,34,36,38–40,42,44,46,52,57]. The long treatment period was poorly understood by patients [23,26,28,38–40,46,52]; and adherence appeared to be facilitated where patients understood the importance of completing treatment [24,26,32,36,39,44,55,58,59]. One study on adherence to prophylaxis reported that nonadherent patients had little information on TB as a disease, but were very aware of the potential adverse effects caused by treatment [44]. Patients' beliefs about the efficacy of treatment, both positive [39,41,52,59] and negative [22,23,26,28,32,34,36,39,44,52,54–56], may impact on adherence. Patients may question the efficacy of the pills or think that only injections are “medicine” [22], or even question the validity of diagnostic tests that are not considered sophisticated enough for such a dangerous disease [52]. Belief in treatment efficacy appeared to be related to patient confidence in the medical system [25,35,42]; in some cases community-based treatment programmes increased confidence among community members that TB could be cured [37,55]. Another study noted that patients preferred to consult traditional healers [34]. Fear and denial of diagnosis were common themes across the included studies. Some patients had difficulty accepting their diagnosis, often wanting to hide their disease [23,29,33,40,42,43,55,56]. In other studies, patients' desire to be cured was cited as a motivator for adherence in people presenting with TB symptoms [30,41,43,46,58,59], and patients' fear of the negative consequences of irregular treatment was associated with treatment adherence [30,32,39,54]. Patients could be nonadherent if they were taking other western [46] or traditional [51,52] medicines and perceived there to be negative consequences if these were taken concurrently with TB medication. Two studies mentioned a relationship between pregnancy and nonadherence [54,55], one of which noted that female patients believed that pregnancy would increase intolerance to drugs and make TB drugs ineffective. Law and Immigration In studies with IDUs and homeless people, mainly conducted in the US, legal and immigration requirements had an important influence on whether people adhered to prophylactic regimens. For refugees entering the US with inactive TB, obtaining certification of preventive treatment completion was a motivator for returning to the clinic [53]. Others also on preventive treatment were concerned that TB would affect their immigration status [60], that their illegal residence status would be discovered when accessing treatment [61], or that they would be incarcerated [62]. Some patients simply stated that they adhered because it was legally required [59]. In The Gambia, nonadherence was attributed by staff to Senegalese patients coming to the country for free treatment and returning home when feeling better [27]. Personal Characteristics and Adherence Behaviour Patients and providers thought that an individual's personal character determined whether they would adhere to treatment or not [24,25,28,36–38,49,57,63]. Substance abuse was noted frequently as a barrier [24,25,28,36–38,49,57,63]. Patients with mental illness [49,57]; particular ethnic groups, such as Hispanic patients in the US [49]; older and younger age groups [42,49]; and those who were residentially mobile [25,27,49,62] were considered to be at “high risk” for nonadherence by providers and patients. Religion [30,49] and personal motivation [22,27,37,39,46,54,57] were regarded as important influences on TB treatment adherence. Female patients were perceived as being more motivated [38,57], but in some countries they required permission from men or heads of household to attend treatment [27,51]. Two studies indicated that female patients who were, or wanted to be, pregnant were less likely to adhere to treatment as they perceived the medication to be harmful [54,57]. Some providers expressed the opinion that difficulties with adherence lay almost entirely with the patients [46], and used labels such as “difficult cases” for nonadherent patients [24,27,38,53]. Nonadherent patients were judged to lack interest [39], to be lazy and not care [53], or to want to remain sick to qualify for financial support [41]. Patients were criticised for not actively seeking treatment [26,29], and in one case patient characteristics were used to identify and exclude from treatment those considered at higher risk for nonadherence [25]. Wealthier, more educated people were deemed more likely to adhere [29], and illiterate patients more likely to default [22]. Two studies noted that a structured environment away from home could facilitate adherence [28,57]. Studies involving people living with HIV/AIDS noted the relationship between adherence and coping psychologically with their HIV diagnosis [64,65]. Personal agency was an important aspect of adherence behaviour; self-administering patients [22] and those who developed their own reminders adhered readily [54]. It appeared to be easier for male than female patients to be in control of the treatment process, but in one study patients felt the DOT system had transformed them from an adult to a minor, because it prevented them from managing their own treatment [42]. Treatment Side Effects and Adherence The influence of side effects—real, anticipated, or culturally interpreted—on adherence to treatment was mentioned in a number of studies [24,32,34,38,39,46,53,54,58]. Some patients reported stopping medication because of adverse effects [44,46] while others reported that they were not informed about side effects and what to do to counter them [25,34,58]. In some cases, patients had not communicated side effects to providers [38]; in others, the health care worker had not given attention to the side effects that patients reported [24,32,36], or had responded derisively to the patient's attempt to enquire about them [24]. Few patients acknowledged that side effects had influenced their decision to abandon treatment [51,54]. Cultural interpretations of side effects varied. For example, Vietnamese refugees with inactive TB interpreted treatment side effects as “hot” or “non-hot” and countered these effects differently [36]. Family, Community, and Household Influences A main theme across the included studies was the influence of community members or peers on treatment-taking behaviour [33,53,58], and the strong influence of stigma among family and friends [22,26–28,34,36,40,42,46,52,55,56,58,59,61,64]. TB patients may hide their diagnosis [26,27,29,34,37,38,40,42,56], and feel guilt and shame because of the disease [26,31,33,34,42,52]. Stigma may also make patients afraid to ask for support from their employer to purchase medication, thereby reducing adherence [29,65]. Sometimes a patient's role and responsibilities in the family could motivate them to adhere to treatment in order to recover and resume those duties [22,40,43,58,64,65]. But responsibilities in the home, such as providing income and caring for children, also reduced the likelihood of adherence for some [32]. Family support, including financial assistance, collecting medication, and emotional support, appeared to be a strong influence on patient adherence to treatment [22,26,27,29,34,36,38,40,42,52,55,56,58,59,61,64]. In some cases patients on treatment became increasingly demoralised and more likely to become nonadherent as family support weakened [23]. Providers in a study in Vietnam noted that support for the patients seemed to exist only in the family [29]. Having family members observe treatment taking was considered important for some patients, especially if the observer was a decision maker in the family [53], or a respected family member [48]. Husbands and other males' support was considered important for female patients [53]. Providers in one study noted that patients also could support each other through their treatment course [45]. Several studies reported that TB status could affect marriage [22,27,34,36,42,44,55,56]. In some cultures, females diagnosed with TB are at risk of divorce, of their husband taking a second wife, or of being sent to their natal homes [27,36,43,55]. In South Africa, red urine (a side effect of medication) was interpreted as harmful to the partner, causing abstinence from sex and thus familial disharmony and consequently potential nonadherence [34]. In Pakistan, parents' perceptions of marriage prospects influence treatment taking or avoidance among unmarried children [22,43,55]. Discussion The themes identified in this interpretive review were intricately linked and likely to have a combined effect on patient adherence to TB treatment. Secondary interpretations (by authors of included papers) allude to the complex, dynamic nature of adherence to TB treatment. One author suggested that patients experienced three layers of barriers to adherence: attending the health care facility initially, attending repeatedly, and experiences while there [31]. The layers were considered to be interlinked and exacerbated by geographic, economic, and gender inequalities; and patient decisions in relation to treatment taking were thought likely to shift for various reasons during the treatment course. Other authors considered adherence a chain of responsibilities including patients' behaviour, health care workers' conduct, and decision makers' and society's outlook [58]. These secondary (author) interpretations influenced our approach towards a higher-order interpretation (third-order interpretation), which distilled the translations into a whole, more complete interpretation. Based on the translated themes and secondary interpretations, we developed a model to depict our understanding of the main influences on adherence (Figure 3). Components of the model include structural, personal, and health service factors influencing adherence, as well as social context. We have presented structural factors and health service factors separately, instead of as a single “health systems” category, because we felt that some interventions could be directed towards wider society-level factors while others could intend to influence the person and the health care service. Structural Factors: Poverty, Gender, and Discrimination Structural factors are those factors present in society that influence treatment-taking behaviour, but over which a patient has little personal control. Structural factors have been defined as barriers or facilitators that relate to economic, social, policy, organisational, or other aspects of the environment [66]. Factors such as gender and poverty determine individual responses to treatment and subsequent behaviour; and they interact with a patient's social context, their personal characteristics, and the health care service. TB programme managers frequently assume that a willingness to adhere must be instilled in patients in order to improve adherence rates. Our synthesis has found that even where patients are willing to adhere, structural factors such as poverty and gender discrimination may prevent them from doing so. It is recognised that incorporating patients' views in medical practice often obscures the real constraints on agency that some patients experience [9]. In our synthesis, structural factors were discussed in various ways, with poverty remaining one of the most important of these for treatment taking, especially when linked to health care service factors, such as poorly accessible, poorly equipped, and distant clinics. Our findings support the assertion that interventions to increase adherence should focus not only on the patient but also on the wider context and the health care system [67]. There is a need for a shift in perspective to give greater attention to both the social and economic environment in relation to TB infection, of which the beginnings can already be seen in the international policy arena [68]. Patient Factors: Motivation, Knowledge, Beliefs, and Attitudes and Interpretations of Illness and Wellness Patient choice in taking treatment is framed by the physiological and psychological impacts of the disease and also by the social and cultural structures in which the person is immersed [68]. Patient motivation and willingness, and the effect of incentives on treatment taking, have received some attention [69]. However, it remains unclear whether the incentive, or the attention received by the patient, serves as the primary source of motivation [67]. Caution should therefore be exercised when attributing adherence solely to “personal motivation” [22,27,37,39,46,54,57], because not only can important influences be ignored, but this factor is difficult to modify or even operationalise. We found that personal and social factors, including poverty and social marginalisation, may be used by some providers to identify patients at risk of nonadherence to their medication regimen. However, it cannot be assumed that all individuals sharing a particular characteristic face the same barriers to adherence. Nonadherence can be a product of programme failures, such as an inadequate supply of drugs, rather than patient-related problems or failures [24]. Our synthesis also found that patient knowledge, attitudes, and beliefs about the disease TB, TB treatment, and patient interpretations of illness and wellness, can act as a “filter” for the information and treatment offered by the health services. The influence of patients' interpretation of various illnesses on their adherence behaviour is well documented, and it is recognised that patients may interpret the themes of illness, wellness, and disease differently from health professionals [70–73], highlighting the distinctions between lay and biomedical understandings of TB [10]. This is unlikely to be the only influence on treatment taking, however, and patient interpretations can interact with structural and health care service factors as well as with social context. Social Context The influence of social context on treatment adherence was apparent in all included studies. The community, household, and health care service helped in countering the shame and guilt that patients with TB experienced, and also offered support in maintaining treatment taking. Social support can help patients overcome structural and personal barriers, and may influence their knowledge, attitudes, and beliefs. Conversely, community and family members' attitudes may influence a patient's decision to stop taking TB treatment. In such circumstances, community-based TB treatment programmes and stronger involvement of local social networks to support TB patients may be justified [6]. Health Care Service Factors Factors related to the provision of health care services emerged strongly in the synthesis. Flexibility and choice in treatment, and options that maintain patient autonomy in treatment taking, appeared to run contrary to the traditional organisation of many TB services [6,10]. These problems were exacerbated by programme failures, such as inadequate supplies of drugs [23,33,36,38] and difficulties in consulting providers [22,23,31,36–38]. DOT at a health care facility often meant that a patient had to give up part of their working day to attend [22,23]. However, responsibilities in the home, including providing for their family, may be given priority over treatment adherence by patients. Other health care service factors, such as long waiting times and inconvenient opening times in clinics, add to economic discomfort and social disruption for patients [49], and negatively influence adherence. The studies suggest that patients often face a choice between employment and taking medication for TB; and there is evidence that patients consciously estimate the opportunity costs of taking treatment. Study Limitations The majority of studies included in this synthesis were conducted in developing countries; the findings are therefore most applicable to low- and middle-income countries that carry the greatest burden of TB disease and where interventions to improve treatment completion are needed urgently. The findings may also be applicable to countries with better resources; indeed, a meta-ethnography of treatment taking in high-income countries showed findings similar in many ways to those of our study [74]. The clustering of studies by region may have been due to the difficulties of locating primary studies, and may have produced some of the similarities between issues described by participants. Studies often included participants from several socioeconomic strata; did not always contain a detailed description of the treatment regimen; and did not explicitly consider gender in treatment adherence. Therefore it was not always possible to tease out similarities or differences in the identified themes based on these characteristics. We identified some patterns relating to the type of treatment intervention—for example, direct observation versus patient-administered treatment—but the majority of studies did not describe adequately interventions or treatment regimens. Our observations regarding gender differences in taking TB treatment are dependent largely on the information provided by original authors. Collecting author (secondary) interpretations proved difficult; most authors maintained a descriptive style in presenting their findings and so the distinction between findings and interpretation was often not clear. It is important to consider the effect on the review findings of combining studies from different theoretical traditions, and this is widely debated. We found that the level of interpretation in the included studies was fairly basic—most were descriptive studies that used thematic analysis to identify key themes and did not draw extensively on theory or on a particular theoretical tradition. While this made it more feasible to combine the study findings, it also meant we were unable to explore any differences in interpretation of factors affecting adherence in studies conducted within different theoretical frameworks. Implications for Policy and Practice Using the reconceptualised model of factors influencing adherence to TB treatment (Figure 3), we consider it important that policy makers, practitioners, and patient support groups acknowledge: patient autonomy in the treatment process; the importance of patient-centred interventions that encourage shared decision-making regarding treatment; the role of support systems tailored to patient needs; the role of informal, societal structures in reinforcing adherence through patient support; and the influence of poverty and gender on patients and their treatment adherence. New interventions to promote treatment adherence could be designed with these factors in mind. For example, when known barriers to adherence are mapped against the currently available interventions to promote adherence, it is interesting to note that very few interventions are designed to build on social and family support mechanisms. Most are targeted at overcoming barriers to health care delivery to the individual [75]. Based on our third-order interpretation, we identified a number of hypotheses that may guide policy makers and practitioners in developing and implementing specific measures to improve adherence, including influencing the behaviour of practitioners, the organisation of services, and the behaviour of individuals (Box 9). This review shows the usefulness of qualitative synthesis in informing policies for health interventions. Through bringing together data from multiple primary studies, and looking for commonalities across these studies, the approach provides fresh insights into the reasons for poor adherence and guidance on where the development of more patient-centred interventions to improve adherence could be useful. Such insights can be useful to both programme managers at local and national levels and also in facilitating the development of more appropriate international policies for the management of TB. Box 9. Factors Likely to Improve TB Treatment Adherence Increase the visibility of TB programmes in the community, which may increase knowledge and improve attitudes towards TB Provide more information about the disease and treatment to patients and communities Increase support from family, peers, and social networks Minimize costs and unpleasantness related to clinic visits and increase flexibility and patient autonomy Increase flexibility in terms of patient choice of treatment plan and type of support Increase the patient centredness of interactions between providers and clients Address “structural” and “personal” factors, for example through micro-financing and other empowerment initiatives Provide more information about the effects of medication to reduce the risk of patients becoming nonadherent when experiencing treatment side effects Implications for Research Based on the findings of this synthesis we believe that further research is needed both to understand people's experience of TB and its treatment and to develop more patient-centred approaches to improving treatment adherence among people with TB. By “patient-centred approaches” we mean interventions that focus on sharing decisions about interventions or the management of health problems with patients and that view the patient as a whole person who has individual preferences situated within a wider social context [76]. Key issues to be explored in this research include how gender shapes experiences of treatment taking and how differing gender roles may influence adherence. This aspect was reported less frequently than expected in the primary studies in this review and would benefit from further exploration. Patient experiences of side effects of treatment, and how these influence decisions to stop taking treatment, also warrant further research since the existing literature reports vary as to the influence of side effects on treatment adherence [77,78]. There is also little published evidence on the experiences of patients living with HIV/AIDS and taking treatment for TB or receiving concurrent treatment for both diseases; our review included only three reports of qualitative research in this area [51,63,64]. The small number of studies is surprising, given the high rates of TB–HIV coinfection, especially in sub-Saharan Africa [79]; the complex treatment regimens involved; and the need for high rates of treatment adherence for both diseases. There is also some evidence that where coinfection is common, a diagnosis of TB may be seen as a diagnosis of HIV and this “form” of TB may be seen as incurable, with consequent impacts on patient adherence to treatment [80]. Managing treatment for both HIV and TB is therefore likely to present unique challenges to patients, providers, and the health care system, and further research on the particular experiences of patients taking antiretroviral and anti-TB treatment would be very helpful. The process of data extraction and quality assessment identified a number of lacunae in the included study reports. Studies frequently failed to report the details of how treatment was delivered, for example whether direct observation of treatment was used; the treatment regimens used; and the sociodemographics of the included study populations. Greater attention to these areas would improve understanding of research findings and facilitate assessment of their transferability to other contexts. The reporting of a number of study quality issues also needs to be addressed in future reports, including the theoretical orientation of the research and sampling and analysis approaches (see Table 1). Finally, lay conceptualisations of illness and wellness, particularly of TB and its treatment, are not well understood. The TB treatment literature is almost entirely conceptualised from a biomedical perspective, and even studies of patient experiences are largely conducted with the aim of improving treatment adherence. Understanding lay conceptualisations will help in comprehending why people may stop taking treatment at particular times. This would involve acknowledging that patients have agency and are active [71] in shaping their own treatment decisions rather than seeing poor adherence simply as “irresponsible” behaviour. Research approaching TB adherence from a nonbiomedical perspective is required to further understand the impact of traditional beliefs [81] and perceptions of illness and wellness on adherence to treatment. Any further work on patient experiences of TB adherence should also acknowledge and explore the social, economic, and geographical contexts in which a patient is located. There are suggestions that the growing interest in the subjective experiences of health care consumers may result in these experiences being used as simply another tool with which to better promote treatment adherence. In addition, this focus, and its attendant notions of shared responsibility for treatment between consumers and providers, could be seen as acting to expand the surveillance of treatment taking from health care workers to consumers and the wider community [82,83]. We therefore believe it is important that this kind of evidence is used carefully by decision makers and practitioners. The extent to which new interventions come from biomedical rather than lay perspectives should be recognised to ensure that structural factors, as well as individual patient responsibilities in treatment taking, are considered. Conclusion This synthesis indicates that patients often take their TB medication under difficult circumstances and experience significant challenges, many of which are outside of their direct control. Taking a lengthy course of medication is not straightforward and frequently involves difficult decisions, sometimes at substantial personal and social cost to the patient. Adherence is a complex, dynamic phenomenon; a wide range of interacting factors impact on treatment-taking behaviour, and patient behaviour may change during the course of treatment. More patient-centred interventions, and far greater attention to structural barriers, are needed to improve treatment adherence and reduce the global disease burden attributable to TB. Supporting Information Alternative Language Abstract S1 Translation of the abstract into Norwegian by Atle Fretheim (48 KB PDF) Click here for additional data file. Table S1 Search Results (35 KB DOC) Click here for additional data file.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tuberculosis prevalence in China, 1990-2010; a longitudinal analysis of national survey data.

            China scaled up a tuberculosis control programme (based on the directly observed treatment, short-course [DOTS] strategy) to cover half the population during the 1990s, and to the entire population after 2000. We assessed the effect of the programme. In this longitudinal analysis, we compared data from three national tuberculosis prevalence surveys done in 1990, 2000, and 2010. The 2010 survey screened 252,940 eligible individuals aged 15 years and older at 176 investigation points, chosen by stratified random sampling from all 31 mainland provinces. All individuals had chest radiographs taken. Those with abnormal radiographs, persistent cough, or both, were classified as having suspected tuberculosis. Tuberculosis was diagnosed by chest radiograph, sputum-smear microscopy, and culture. Trained staff interviewed each patient with tuberculosis. The 1990 and 2000 surveys were reanalysed and compared with the 2010 survey. From 1990 to 2010, the prevalence of smear-positive tuberculosis decreased from 170 cases (95% CI 166-174) to 59 cases (49-72) per 100,000 population. During the 1990s, smear-positive prevalence fell only in the provinces with the DOTS programme; after 2000, prevalence decreased in all provinces. The percentage reduction in smear-positive prevalence was greater for the decade after 2000 than the decade before (57% vs 19%; p<0.0001). 70% of the total reduction in smear-positive prevalence (78 of 111 cases per 100,000 population) occurred after 2000. Of these cases, 68 (87%) were in known cases-ie, cases diagnosed with tuberculosis before the survey. Of the known cases, the proportion treated by the public health system (using the DOTS strategy) increased from 59 (15%) of 370 cases in 2000 to 79 (66%) of 123 cases in 2010, contributing to reduced proportions of treatment default (from 163 [43%] of 370 cases to 35 [22%] of 123 cases) and retreatment cases (from 312 [84%] of 374 cases to 48 [31%] of 137 cases; both p<0.0001). In 20 years, China more than halved its tuberculosis prevalence. Marked improvement in tuberculosis treatment, driven by a major shift in treatment from hospitals to the public health centres (that implemented the DOTS strategy) was largely responsible for this epidemiological effect. Chinese Ministry of Health. Copyright © 2014 Elsevier Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Financial burden for tuberculosis patients in low- and middle-income countries: a systematic review

              Introduction An estimated 100 million people fall below the poverty line each year because of the financial burden of disease [1]. Tuberculosis (TB), which mostly affects the poorest of the poor, is an example of a disease that can substantially contribute to the disease poverty trap [2, 3]. Most countries aim to provide TB diagnosis and treatment free of charge within public health services. Access to free TB care has expanded substantially over the past two decades through national efforts and global financial support [4]. However, many TB patients and families are still facing very high direct and indirect costs due to TB illness and care-seeking, hampering access and putting people at risk of financial ruin or further impoverishment [5, 6]. The World Health Organization (WHO) is developing a post-2015 Global TB Strategy, which highlights the need for all countries to progress towards universal health coverage to ensure “universal access to needed health services without financial hardship in paying for them,” [7] as well as social protection mechanisms for “income replacement and social support in the event of illness” [8, 9]. One of the tentative global targets for the strategy is “no TB-affected family facing catastrophic costs due to TB”, to be reached globally by 2020 [10]. This target reflects the anticipated combined financial risk protection effect of the progressive realisation of both universal health coverage and social protection. Universal health coverage has long been on the global TB control agenda, which stresses the need for universally accessible, affordable and patient-centred services [2, 11–13]. Social protection has emerged more recently as a key policy area for TB care and prevention [10, 14–17]. Social protection involves schemes to cover costs beyond direct medical costs, including compensation of lost income. Examples of social protection schemes include sickness insurance, disability grants, other conditional or unconditional cash transfers, food assistance, travel vouchers and other support packages [14]. Such schemes exist in most countries, but may not be fully implemented due to inadequate financing or insufficient capacities of the healthcare and social welfare systems [18]. Furthermore, they may not include TB patients among those eligible [10, 14, 17]. In order to inform the development of appropriate strategies for improved access and financial risk protection for people with TB, we have undertaken a systematic literature review on medical costs, non-medical costs, as well as income loss for TB patients and affected households in different settings, as well as the main drivers of those costs. Methods Eligibility criteria This review includes studies written in English, conducted in low- and middle-income countries and published from inception to March 31, 2013, reporting data on medical costs, non-medical costs and/or income loss incurred by TB patients during the process of seeking and receiving care for TB, as well as coping strategies. We excluded studies in which only total cost was reported without any disaggregation into direct and indirect costs and studies using secondary data derived from other published articles. Information sources and search strategies We searched the following electronic databases: PubMed; Global Information Full Text; Index Medicus for Africa, South-East Asia, Eastern Mediterranean region, and Western Pacific region; and Literatura Latinoamericana y del Caribe en Ciencias de la Salud. Furthermore, we checked reference lists of reviewed studies [19–22] and of documents and meeting reports from the World Bank and WHO websites. The search terms were “tuberculosis” (tuberculosis, TB, or tuberculosis as a MeSH Term in PubMed) and “cost” (cost(s), expense(s), economic, expenditure(s), payment(s), out-of-pocket, financial, impoverishment, or catastrophic). Data extraction We extracted the following background information: country, location, urban/rural, year of the publication and data collection, setting characteristics, and method of data collection and calculation of costs and income loss. We stratified, to the extent data allowed, into the following cost components: direct medical costs (consultations, tests, medicines and hospitalisation, etc.), direct non-medical cost (transport and food during healthcare visits, etc.) and indirect costs (lost income). If possible, cost was stratified by socioeconomic status, hospitalisation/ambulatory treatment, drug-resistant TB or drug-susceptible TB, and sex. The cost components were extracted separately for the pre- and post-TB diagnosis period, if available. Pre-TB treatment costs are those incurred between the onset of symptoms and the initiation of treatment for TB. In all studies, this data was collected retrospectively at a point in time after diagnosis. Post-diagnostic costs are those incurred from TB diagnosis to completion of treatment. Costs during treatment were either collected prospectively through repeat surveys of patients in treatment or retrospectively. If retrospectively collected at some point during treatment, the cost was then extrapolated to the planned treatment duration in most studies. We also extracted data on costs as a percentage of reported individual and/or household income, if available. For all studies done in countries for which both “gross average nominal monthly wage” in the International Labour Organization's global wage database [23] and “income share held by lowest 20%” in the World Bank's online data [24] were available, we also computed total costs as percentage of average annual income and percentage of annual income in the lowest quintile for each respective country. The latter was done under the assumption that TB mostly affects the poorest quintile in any given setting. We used the available data for the nearest year to a year of the data collection. Where available, we extracted information about mechanisms for coping with financial burden, such as taking a loan or selling property. Summary measures and synthesis of results The focus of the analysis was on the distribution of the magnitude and components of costs across settings. We also report descriptive analyses of the central tendencies of the data. For each variable we provide the range of reported means across studies, unweighted average of means (with standard deviation), and the median and interquartile range of means. When a mean value for all study subjects in a given study was not available, we re-calculated an unweighted mean across subgroup within the study. We also report the range and unweighted average of percentage distributions of different cost components. Under the assumption of large heterogeneity, we decided a priori to focus the analysis on the variations across studies, while providing summary estimates for some variables as an indication of central tendencies across studies. We opted not to calculate confidence intervals for the unweighted average of means, in order to avoid a false impression of precision for the measures of central tendency. If one study reported data from several different country surveys, each survey was analysed as a separate observation. Data availability for variables of interest varied across studies. Summary statistics are therefore based on different number of studies. Mean cost values were available from 44 studies (reporting 47 surveys) of the 49 studies (reporting 52 surveys). Only median values were reported in five studies. We therefore did not use median values for summarising the key variables across studies. However, where applicable, median values were used for comparison of different subgroups within studies. Costs in international dollars ($) were calculated by multiplying raw cost data in US dollars, the exchange rate with the local currency for the year of data collection and the cumulative inflation rate [25] from the year of data collection to 2010 (latest year of data availability), and divided it by the purchasing power parities conversion factor [26]. The exchange rates reported in reviewed articles were preferentially used for the calculation and, in the absence of them, we used the exchange rates from the “National Accounts Main Aggregates Database” of the United Nations Statistics Division [27] and the exchange rate of Sudan from UN data [28] as the data of Sudan in a studied year is missing in the former source. Results 49 studies fulfilled the inclusion criteria (fig. 1). One study without cost data was included since it provided data on coping strategies [29]. Details about included studies are provided in table 1. Figure 1– Flow chart of literature search. Table 1– Type of costs Study Mean/ median/both Phase coverage# Components of Breakdown of Disaggregation by Costs as percentage of annual income Coping mechanism Direct costs Direct med. costs Direct non-med. costs Hosp. cost Lost income Direct med. costs Direct non-med. costs Lost income Before/ during treatment¶ Hosp./amb. MDR/ non-MDR SES Sex Individ. House. LQ Muniyandi (India, 2000) [30] Both Both √ √ D&I √ √ √ √ √ Rajeswari (India, 1995+) [31] Both Both √ √ √ √ √ √ Mauch (Ghana, 2009+) [5] Both Both √ √ √ √ √ √ √ All √ √ √ √ Mauch (Vietnam, 2009+) [5] Both Both √ √ √ √ √ D&I √ √ √ √ Mauch (Dominican Republic, 2009+) [5] Both Both √ √ √ √ √ D&I √ √ √ √ Karki (Nepal, 2002) [32] Both Both √ √ √ √ √ √ √ √ √ √ Xu (China, 2002) [33] Both Both √ √ √ D √§ √§ √§ Kemp (Malawi, 2001) [34] Both Before √ √ √ √ √ √ √ √ Needham (Zambia, 1995) [35] Both Before √ √ √ √ √ √ √ √ √ Mesfin (Ethiopia, 2005) [36] Both Before √ √ √ √ √ √ √ √ √ √ Jacquet (Haiti, 2003) [37] Mean Both √ √ D&I √ Lönnroth (Myanmar, 2004) [38] Mean Both √ √ √ √ √ √ All √ √ √ Gibson (Sierra Leone, 1994) [39] Mean Both √ D Kamolratanakul (Thailand, 1996/97) [40] Mean Both √ √§ √§ √ √ √ D √ √ √ √ Wyss (Tanzania, 1996) [41] Mean Both √ √ √ √ √ √ Saunderson (Uganda, 1992) [42] Mean Both √ √ √ √ √ Sinanovic (South Africa, 1998) [43] Mean Both √ √ √ √ √ Jackson (China, 2002–2005) [44] Mean Both √ √ √ √ √ √ √ √ √ Pantoja (India, 2005) [45] Mean Both √ √ √ √ √ √ √ √ All √ √ √ √ Ananthakrishnan (India, 2007) [46] Mean Both √ √ √ √ All √ √ √ √ Othman (Yemen, 2008/09) [47] Mean Both √ √ √ √ √ √ Pichenda (Cambodia, 2008) [48] Mean Both √ √ √ √ √ √ All √ √ √ Ayé (Tajikistan, 2006/07) [49] Mean Both √ √ √ √ √ √ D&I √ √ √ √ Steffen (Brazil, 2007/08) [50] Mean Both √ √ √ √ √ √ √ √ All √ √ √ √ Rouzier (Ecuador, 2007) [51] Mean Both √ √§ √§ √ √ √ √ √ √ √ John (India, 2007) [52] Mean Both √ √ √ √ √ √ √ √ All √ √ √ √ √ Muniyandi (India, 2000) [53] Mean Both √ √ √ Elamin (Malaysia, 2002) [54] Mean Both √ √ √ √ √ √ Mahendradhata (Indonesia, 2004/05) [55] Mean Both √ √ √ √ √ √ Sinanovic (South Africa, 2002) [56] Mean Both √ √ √ √ √ Vassall (Ethiopia, 2005) [57] Mean Both √ √ √ √ √ All √ √ Costa (Brazil, 2000) [58] Mean Both √ √ √ √ √ √ √ √ √ √ El Sony (Sudan, 1998/99) [59] Mean Both √ √ √ Khan (Pakistan, 1997/98) [60] Mean Both √ √ √ Umar (Nigeria, 2008) [61] Mean Both √ √ √ √§ Vassall (Syria, 1999) [62] Mean Both √ √ √ Vassall (Egypt, 1999) [62] Mean Both √ √ √ Meng (China, 2000) [63] Mean Both √ √ √§ Zhan (China, 2000/01) [64] Mean Bothƒ √ √ √ Dƒ √§ √§ Ray (India, 2003) [65] Mean Before √ √ √ √ Datiko (Ethiopia, 2007) [66] Mean Before √ √ √ √ √ √ Croft (Bangladesh, 1996) [67] Mean Before## √ √ √ √ √ √ √ Okello (Uganda, 1998) [68] Mean During √ √ √ √ √ √ √ Wandwalo (Tanzania, 2002) [69] Mean During √ √ √ √ Prado (Brazil, 2005/06) [70] Mean During √ √ √ √ √ √ Mirzoev (Nepal, 2001/02) [71] Mean During √ √ √ √ Jacobs (Russia, 1997) [72] Mean During √ √ √ √ Total number of surveys 47 (44 studies) 44 31 29 9 42 18 16 14 17 6 3 11 9 25 13 36 10 Mauch (Kenya, 2008) [73] Median Both √ √ √ √ Laokri (Burkina Faso, 2007/08) [74] Median Both √ Umar (Nigeria, 2008) [75] Median Both √ √ √ √ √ √ √ Aspler (Zambia, 2006) [76] Median Both √ √ √ √ √ √ D √ √ √ Liu (China, 2004) [77] Median Both √ √ √ D Total number of surveys 5 (5 studies) 5 3 3 0 2 2 2 0 2 3 0 1 2 0 0 0 1 The years in which the majority of data collection took place are provided for each study. Hosp.: hospitalisation; amb.: ambulatory; SES: socioeconomic status; individ.: individual annual income; house.: household annual income; LQ: lowest quintile. #: before treatment, during treatment, or before and during treatment (both). ¶: only direct costs (D); direct and indirect costs without medical and non-medical subcomponents (D&I); or all costs including medical and non-medical subcomponents (all). +: estimated year of data collection using the average gap of 4 years calculated from other articles. §: data are only for part of the costs and were excluded from the calculation of the average and figure 3. ƒ: costs of diagnosis are included in post-diagnosis. ##: data is before reaching facilities of national tuberculosis programme. Mean total costs ranged from $55 to $8198 across 40 surveys for which mean costs and conversion values were available, with an unweighted average of $847, and a median of $379. The proportion of direct medical costs out of total cost ranged from 0–62% (unweighted average 20%) across the 25 surveys that provided disaggregated data on direct medical, direct non-medical, and indirect costs. Direct non-medical costs ranged from 0–84% (unweighted average 20%) and indirect costs (income loss) from 16–94% (unweighted average 60%) of total cost (table 2). Table 2– Patient costs and distribution of costs from 25 surveys with disaggregated medical direct costs, non-medical direct costs and income loss Cost category Direct costs Indirect costs Total costs Medical costs Non-medical costs Unweighted average of mean costs $ (sd) (range) 296.8 (376.0) 450.8 (553.4) 738.1 (821.3) (21.9–1316.4) (29.8–2184.0) (54.6–3500.4) 144.9 (206.8) 152.0 (275.9) (0–801.7) (0–1271.4) Median (IQR) of mean costs $ 136.2 (58.0–304.9) 206.9 (109.0–486.3) 397.1 (155.4–1097.2) 50.0 (14.2–140.0) 32.1 (22.8–120.7) Unweighted average contribution % (range) 39.8 (6.2–83.7) 60.2 (16.3–93.8) 100 20.1 (0–62.4) 19.8 (0–83.7) IQR: interquartile range. Costs are quoted in international dollars. Eight studies fully disaggregated direct and indirect costs both before and during treatment. On average, costs incurred before TB treatment was initiated represented 50% of the total cost (fig. 2). While indirect costs dominated both before and during treatment, direct costs were relatively more important before than during treatment. Direct costs were driven mostly by medical costs before treatment and by non-medical costs during treatment. Figure 2– Breakdown of direct and indirect costs before and during treatment (eight studies). Percentages are proportion of respective sub-component cost out of the total cost. Across 18 studies that further disaggregated direct medical costs, the proportion of drug costs out of direct medical costs ranged from 0% to 86% (unweighted average of 34%), while the contribution from diagnostic and follow-up test costs ranged from 0% to 94% (unweighted average of 27%,) and hospitalisation costs from 0% to 71% (unweighted average of 24%). Transport costs (range 11–96%, unweighted average 50%), and food costs (range 0–89%, unweighted average 37%,) were the largest contributors to direct non-medical costs in 16 studies that disaggregated the direct non-medical costs. There was a large variation across studies in the mean total cost as percentage of income, with skewed distributions due to a few studies reporting very high costs (table 3 and fig. 3). Total cost as percentage of reported annual individual income ranged from 5% to 306% (unweighted average 58%, median 44%), while the total cost as percentage of reported household income ranged from 4% to 148% (unweighted average 39%, median 23%). Total cost as percentage of the average annual income in the lowest income quintile of the country of study ranged from 3% to 578% (unweighted average 89%, median 21%). Table 3– Costs as percentage of annual income Surveys n Direct costs % Lost income % Total costs % Range of total costs % Individual  Reported income 22 Average of mean (SD) 21 (27) 37 (43) 58 (64) 5–306 Median of mean (IQR) 10 (5–23) 24 (12–37) 24 (12–37)  Annual wage 35 Average of mean (SD) 9 (14) 21 (29) 30 (42) 0–211 Median of mean (IQR) 3 (2–12) 3 (2–12) 7 (4–41)  Wage of lowest 20% 34 Average of mean (SD) 25 (42) 25 (42) 89 (139) 3–578 Median of mean (IQR) 8 (4–29) 14 (6–88) 21 (10–101) Reported household income 7 Average of mean (SD) 16 (17) 22 (29) 39 (46) 4–148 Median of mean (IQR) 11 (9–15) 14 (4–20) 23 (14–36) IQR: interquartile range. Figure 3– Costs as percentage of a) reported annual individual income, b) reported annual household income and c) annual wage of the lowest quintile. The far right bars are truncated and percentages are shown above. avg.: average across subgroups for which separate means were reported in the original study. MDR: multidrug resistant; TB: tuberculosis. In 12 studies that disaggregated data by socioeconomic status group, there was no consistent tendency of difference in the absolute total cost incurred. However, the five studies that reported the cost as percentage of the reported income specific to each group found that the cost was considerably higher among the lower socioeconomic status groups [30, 34, 38, 40, 46]. Among the three studies that disaggregated the total cost for patients with multidrug-resistant (MDR)-TB versus drug-susceptible TB, the cost was considerably higher for MDR-TB patients (fig. 3). The difference in indirect costs was larger than that of the direct costs in two studies [48, 51]. The total costs as percentage of reported individual income for MDR-TB patients and drug-susceptible TB patients in two of the three studies were 223% ($14 388) versus 31% ($2008) in Ecuador [51] and 76% ($2953) versus 24% ($923) in Cambodia [48]. For the third study, from Brazil, that calculated income loss based on reported income after TB diagnosis, the cost burden was similar for MDR-TB and drug-susceptible patients (34% versus 27% of reported annual income) [58]. In 11 studies that disaggregated the total costs between males and females there was no consistent tendency of difference in absolute total costs. However, in two studies in Nigeria and Zambia that also reported individual income by sex, the costs for females as percentage of reported income were significantly larger [75, 76]. Commonly reported coping mechanisms included taking a loan, selling household items, using savings, and transfers from relatives (table 4). The amounts were not reported. Table 4– Percentage of patients pursuing specific coping strategies Country, area, year of data collection Taking loan % Selling household items % Using own savings % Transfers from relatives % Ghana, urban and rural, 2009 [5] 47 37 Vietnam, urban and rural, 2009 [5] 17 5 Dominican Republic, urban and rural, 2009 [5] 45 19 Tajikistan, urban and rural, 2006/2007 [29] 30 49 30 India, rural, 2000 [30] 71 India, urban and rural, 1995 [31]  Governmental hospitals 76  NGO-run hospitals 58  Private health facilities 68 Myanmar, urban, 2004 [38]  Higher socioeconomic status 27  Lower socioeconomic status 55 Thailand, nationwide, 1996/97 [40]  Income below poverty line 12 16 22 23  Income below average 9 7 21 21  Income above average 8 8 14 17 China, rural, 2002-05 [44] 8 45 66 Bangladesh, 1996 [67] 14 38 Kenya, 2008 [73] 57 NGO: nongovernment organisation. Discussion This review demonstrates that the economic burden of seeking TB care is often very high for patients and affected households. Clearly, accessing TB care and continuing treatment comes with a high risk of financial ruin or further impoverishment for many people. In most settings, income loss is a dominating reason for the high costs. However, the financial burden varies considerably both between individuals in the same setting and between settings. This should be expected as the burden is determined by a range of factors, such as socioeconomic status, clinical needs, health system structure, TB service delivery model, distance to health services, insurance coverage, capacity to work, existence of any social protection scheme, and effectiveness of informal social networks supporting patients and families. This review shows that, while costs are catastrophic for many patients, they are minimal for others. It is crucial to identify the factors that contribute to costs incurred and to financial ruin. Unfortunately, few studies provided sufficient details about the models and context of care to allow us to quantify the relative importance of the different factors. However, the available data hint at some key explanations and intervention entry points. Cost of medicines and diagnostic tests were important drivers of direct medical costs, despite TB medicines and basic TB-specific tests being free of charge in services linked to the national TB programme in most countries. Detailed accounts of which medicines and tests were accessed were not available from any of the studies, but authors of some studies speculated about several possible reasons for cost incurred: patients may not have been offered free medicines for drug-resistant TB; some patients pay for services outside national TB programme facilities, e.g. in the private sector; and costs of adjuvant medicines may have contributed. Hospitalisation was another key driver of direct costs. In some settings, patients are routinely hospitalised, especially if MDR-TB is diagnosed. The necessity of some medical procedures and routine hospitalisation is not substantiated. Ensuring use of evidence-based cost-effective diagnostic and treatment routines can reduce direct medical costs [49, 52]. The costs of appropriate services, within national programmes as well as outside, should be fully subsidised given the public health implications of failure to ensure access and use of quality TB care, the known low socioeconomic status of most TB patients, and recommended prioritisation of coverage of priority health interventions like for TB under universal health coverage objectives [78]. Ensuring provision of free-of-charge TB diagnosis and treatment also in private facilities have been shown to reduce the direct costs for patients [45, 79]. Transport and food costs accounted for a major part of direct non-medical costs for patients. Provision of transport vouchers, reimbursement schemes and food assistance could be used to reduce or compensate for such costs. Furthermore, decentralisation of patient supervision (including directly observed therapy), e.g. through community-based [43, 66] or workplace-based treatment [43], can reduce transport costs as well as income loss for patients. Minimising costs during treatment does not guarantee financial risk protection since a large part of the cost is often incurred before treatment starts. In addition, costs during the first 2 months of treatment tend to dominate the costs incurred during treatment [29, 57, 74]. Peaking costs around the time of diagnosis and treatment initiation may constitute one of the most powerful barriers for people ill with TB to complete the diagnostic search, to start treatment once diagnosed, and to adhering to treatment to cure. Therefore, effective intervention at the time of diagnosis and treatment initiation may have significant impact. Affordable health services, as well as social protection schemes, are needed to enable access, reduce delays and to compensate for direct and indirect costs. Social protection schemes cover general categories of vulnerable persons, such as those with disabilities or sickness or other causes of limited or reduced income. TB patients may in some settings meet criteria for such support. In other settings, TB-specific targeting may be in place for provision of specific packages of social support such as food stuffs or cash transfers, with or without means testing. This review identified two groups of TB patients that require special attention: people with MDR-TB and people in the lowest income brackets. For the first group, the debilitating nature of the disease, its long-term care, and associated income loss may put them at special risk for catastrophic costs. For the second group, low-income means that the relative costs of direct medical care and non-medical costs, as well as income loss due to precarious informal employment in many cases, may exacerbate already serious economic vulnerability and catastrophic costs may carry relatively greater impact. This study has several limitations. First, there may be both publication and selection bias that could limit the representativeness of the findings. All studies included only people who have been diagnosed with TB. Costs for those ill with TB who seek care but never get diagnosed may be very different, and could for example be dominated by progressing income loss due to untreated illness. Furthermore, most of the studies only included persons diagnosed and started on treatment within national TB programmes. Many people are treated in the private sector. Direct costs are often higher in the private sector than in facilities linked to the national programme [31, 55]. There is thus a bias towards surveys of public sector patients. Furthermore, there is inclusion bias with regards to some publication languages. Finally, the search strategy was not optimal for the inclusion of studies that only reported on copying mechanism. Secondly, there were large variations in how data were collected analysed and reported. In particular, the methods for calculating the income loss varied considerably. To accurately measure income loss is more difficult than to measure direct costs [80]. We could not find any clear patterns of methods used which affected cost estimations, except that the indirect costs in studies using reported income after diagnosis was lower than in other studies [58, 73]. Additional research is needed to validate different measurement approaches. Thirdly, the studies provided limited information about the health system context. This review provides a cross-sectional snapshot of the financial burden of TB across very different settings. The relevant drivers of costs and interventions to minimise costs will have to be determined locally, based on further local operational research. There is a “TB patient-cost toolkit” available to guide the design of local surveys [6]. Fourthly, while studies reported mean values (and median to a lesser extent), no study reported the full distribution of costs, the costs as a percentage of income, or the percentage of patients that had faced “catastrophic costs”. However, several possible definitions of “catastrophic costs” were discussed in the reviewed papers, including “>10% of monthly household income” [52], “>10% of annual household income” [61, 74]; “>40% of non-subsistence household income” [5, 44]; or “using non-reversible coping strategies” [29]. The WHO has proposed that “catastrophic health expenditure” be defined as direct healthcare expenditures corresponding to >40% of annual discretionary income (income after basic needs, such as food and housing) [7]. The World Bank has proposed a similar definition but has not specified a cut-off value [81]. Indirect costs of care and income loss are not included in these measures. The WHO's Global TB Programme is considering development of TB-specific indicators and target for reduction in catastrophic costs due to TB for patients and their families [10]. Here, all care-related expenditures, as well as income loss, are being considered as relevant elements of overall catastrophic costs. A threshold for TB-related “catastrophic costs” needs to be defined. One possible option would be to adopt the definition of “total costs corresponding to >10% of annual household income”, which has been proposed by Ranson [82] as appropriate for measuring catastrophic total costs. Incidence of impoverishment may also be considered. Another option is to use generic or locally defined irreversible coping strategies as proxy indicators for catastrophic costs. Further work is needed to assess the correlation between high total cost in relation to income and seemingly irreversible coping strategies.
                Bookmark

                Author and article information

                Contributors
                xiaolin.wei@utoronto.ca
                sunnyhj@163.com
                Journal
                Infect Dis Poverty
                Infect Dis Poverty
                Infectious Diseases of Poverty
                BioMed Central (London )
                2095-5162
                2049-9957
                20 September 2021
                20 September 2021
                2021
                : 10
                Affiliations
                [1 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Institute of Health Policy, Management and Evaluation, , University of Toronto, ; 155 College St., Toronto, ON M5T 3M6 Canada
                [2 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Dalla Lana School of Public Health, , University of Toronto, ; 155 College St., Toronto, ON M5T 3M7 Canada
                [3 ]GRID grid.268079.2, ISNI 0000 0004 1790 6079, Weifang Medical College, ; Weifang, Shandong China
                [4 ]GRID grid.449428.7, ISNI 0000 0004 1797 7280, Jining Medical University, ; Jining, Shandong China
                [5 ]GRID grid.449525.b, ISNI 0000 0004 1798 4472, North Sichuan Medical College, ; Nanchong, Sichuan China
                [6 ]Xigaze Centre for Disease Control and Prevention, 7 Keji Road, Sangzhuzi District, Xigaze, Xizang China
                [7 ]GRID grid.464402.0, ISNI 0000 0000 9459 9325, Shandong University of Traditional Chinese Medicine, ; Jinan, 250355 China
                Article
                906
                10.1186/s40249-021-00906-4
                8451167
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                Funding
                Funded by: tb reach
                Award ID: STBP/TBREACH/GSA/W6–5
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Comments

                Comment on this article