Características

Background

Adherence to the full course of TB treatment is essential for achieving complete cure and reducing the development of drug resistant TB (Frieden, Sterling et al. 2003). Non- adherence, and not just default, can lead to persistent infectiousness, treatment failure, disease relapse, drug resistance, or death (Chaulk and Kazandjian 1998; Gelmanova,

Keshavjee et al. 2007). The development of standardized short course therapy, usually six to eight months, and implementation of directly observed therapy have greatly improved

adherence. Typically, patients take four anti-TB drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol) either three or seven days a week for two months (WHO 2003). This is referred to as the intensive phase of treatment. It may be extended to a third month if the patient remains smear positive after the initial two months of treatment. This is followed by a regimen of isoniazid and rifampicin taken three, or seven days a week for four to six months. This is referred to as the continuation phase of treatment.

Defaulting from treatment is the most extreme form of non-adherence and is defined by the WHO as two or more consecutive months without treatment (WHO 2003). Default is a common definition of non-adherence because it is a standard treatment outcome recorded in patient records. However, it is not the only form of non-adherence. A recent study found that adherence to less than 80% of the prescribed treatment is associated with poor outcomes including treatment failure, death, or subsequent default (Gelmanova, Keshavjee et al. 2007). Thus, efforts to improve any level of non-adherence will likely improve treatment success and patient outcomes.

A number of barriers to full adherence have been reported. In a recent review of qualitative studies, Munro et al. (Munro, Lewin et al. 2007) identified eight major factors affecting adherence to TB treatment: Organization of treatment and care, including access to care; interpretation of illness and wellness; financial burden; knowledge, attitudes, and beliefs about treatment; law and immigration; personal characteristics; side effects; and family, community, and household influence. These factors have been generally supported through quantitative studies which report that longer distances to the health center (Shargie and Lindtjorn 2007), type of transportation (Shargie and Lindtjorn 2007), travel cost (Mishra, Hansen et al. 2005), perceived health status as good (Lertmaharit, Kamol-Ratankul et al. 2005), HIV infection (Connolly, Davies et al. 1999), young and old age (Connolly, Davies et al. 1999; Santha, Garg et al. 2002; Shargie and Lindtjorn 2007), male gender (Connolly, Davies et al. 1999; Santha, Garg et al. 2002; Lertmaharit, Kamol-Ratankul et al. 2005), low income (Mishra, Hansen et al. 2005), employment (Mishra, Hansen et al. 2005; Hasker, Khodjikhanov et al. 2008), and alcohol or drug use (Santha, Garg et al. 2002; Cayla,

Caminero et al. 2004; Gelmanova, Keshavjee et al. 2007; Hasker, Khodjikhanov et al. 2008) were associated with default. As with the studies on delay in seeking care for TB symptoms, it is difficult to draw definitive conclusions about the role of many of these factors because different definitions of adherence are used, there are variations in analytic methodologies, and variation in the designation of directly observed therapy and the overall treatment regimen.

The presence of stigma was identified in half of the qualitative studies and included patients trying to hide their diagnosis from family, friends, or employers. More specifically, stigma may adversely affect adherence because patients do not want others to find out they

have the disease, much the same as when patients delay seeking care in order to avoid being labeled as a TB patient. Patients reported the strain of trying to keeping their disease secret from others (Liefooghe, Michiels et al. 1995; Nair, George et al. 1997), and not complying with treatment visits helped remove some of the suffering because they would no longer be seen going to the clinic (Mata 1985; Barnhoorn and Adriaanse 1992; Johansson, Long et al. 1999; Dimitrova, Balabanova et al. 2006). In other cases, fear of transmission and social consequences led to social isolation at home, rather than being encouraged to seek and continue treatment (Demissie, Getahun et al. 2003). And some patients reported fear that their employer would know of their disease (Johansson, Diwan et al. 1996). In contrast to stigma, family support was overwhelmingly noted as helping patients remain adherent (Munro, Lewin et al. 2007).

Only two studies have quantified the association between TB stigma and adherence to TB treatment.

Review of quantitative studies of tuberculosis stigma and adherence

Comolet et al. (1998) (Comolet, Rakotomalala et al. 1998) performed a case-control study of demographic, knowledge, attitude, and psycho-social factors associated with default from treatment in Madagascar. Patients were eligible if they had pulmonary TB and had either completed treatment or been lost to follow-up. Default was defined as missing more than a month of treatment during the prescribed period. Controls were patients who

completed treatment without interruption. Because none of the patients were currently receiving treatment, all eligible participants had to be traced, contacted, and interviewed. Only 38 (40%) of 95 eligible defaulters were traced and interviewed, while 111 (75%) of 150

eligible completers were interviewed. All patients were interviewed using an extensive questionnaire. While no formal measure of stigma was used, the questionnaire did include the statement “Felt that TB was a shameful disease”. Odds ratios and the Chi-square test was used to analyze the association between each factor of interest and default. The crude odds ratio for feeling that TB was shameful and default was 2.97 (95% CI: 1.26, 6.99).

This study was performed prior to the implementation of standardized, directly observed therapy and is therefore not comparable to more recent studies. Additionally, less than half of eligible defaulters were included in the study. Selection bias could have been introduced if feeling shame was related to why they could not be contacted. The authors do state that bias may have been introduced if defaulters felt shame due to defaulting rather than from having the disease.

Woith and Larson (2008) (Woith and Larson 2008) performed a study of delays in seeking treatment (see section on TB stigma and delay) and adherence to treatment among patients with pulmonary TB in Russia. Quantitative measures of illness representation and TB stigma (see section on measures of TB stigma) were the predictors of interest. Patients were eligible if they were ≥18 years old, diagnosed with pulmonary TB, had completed the intensive phase of treatment, and had received at least four weeks of continuation phase treatment. A total of 105 patients were enrolled from two outpatient clinics. Adherence was defined as the proportion of doses taken out of the total doses prescribed from beginning of the continuation phase until the interview time. Data were collected from the patients’ medical records. Patients also responded to the TB stigma scale, which captured four components of stigma: social rejection, financial insecurity, internalized shame, and social isolation. Adherence and stigma scores were both analyzed as continuous variables using

multivariable linear regression that also included illness representation scores but no other covariates. Adherence was highly skewed with 54% of patients having 100% adherence. Financial insecurity was associated with a 2.78 (95% CI: -5.09, -0.47) point decrease in adherence, while internalized shame was associated with a 2.49 (95% CI: 0.51, 4.47) point

increase in adherence.

This is the only study of adherence where stigma is the primary exposure of interest. However, caution should be taken when interpreting these results for the same reasons mentioned above in their analysis of delay, namely concerns with scale reliability, violation of the assumption of normality in the adherence distribution, lack of covariates to adjust for confounding, and uncertainty of the magnitude and precision of the stigma effects.

Therefore, while the results are intriguing, particularly for internalized shame, the

methodologic issues suggest that conclusions about the effect of stigma on adherence cannot be made.

Summary of tuberculosis stigma and adherence

Only two studies assessed the quantitative association between stigma and adherence to treatment. One found stigma to be associated with defaulting from treatment, but suffered from poor participant recruitment and potential selection bias. It also was performed in a setting where current recommendations on directly observed therapy had not been

implemented. The other found that increased financial insecurity was associated with poor adherence, but that increased shame was associated with better adherence. This study, however, suffered from many limitations including poor reliability of the shame

measurement and violation of linear regression normality assumptions. Conclusions on the effect of stigma on adherence cannot be made based on current literature.