Factors associated with cure and abandonment of leprosy treatment: A reflective analysis

To analyze trends, and the main socioeconomic and clinical factors related to treatment abandonment and the cure of leprosy in Sergipe. For the present study, data from all new cases of cure and abandonment of leprosy treatment notified by the health centers of the municipalities to the SINAN (Information System on Notifiable Diseases) in the state of Sergipe, Brazil, from 2007 to 2017, were used. This is an ecological study of cases of cure and abandonment of leprosy treatment, rates were calculated based on the "Guidelines for surveillance, care and elimination of leprosy as a public health problem".using timeseries analysis and multivariate logistic regression. Concerning multivariate regression, the young age group presents a higher risk for quitting the treatment (p = 0.429; OR = 2.75). Blacks/browns/indigenous were more likely to abandon treatment (p = 0.482; OR = 1.69), as well as multibacillary individuals (p = 0.541; OR = 2.26). Regarding the cure, the young age group has less chances of cure (OR = 0.34). The same happens for the operational classification; the multibacillary patients have a lower chance of cure (OR = 0.35). Finally, individuals with grade 2 of physical disability are less likely to be cured (OR = 0.54). Health services are noticeably weak, especially when it comes to clinical factors associated with treatment abandonment and a low proportion of cure. Multibacillary (Borderline and Lepromatous) are responsible for the active transmission of leprosy.

aimed to analyze the trend and the main socioeconomic and clinical factors related to treatment abandonment and the cure of the disease in Sergipe, taking into account that they express the effectiveness of services in ensuring treatment adherence until the discharge.

2.1-Study design
This is a descriptive study with the individual characterization of cases of cure and abandonment of leprosy treatment; and also ecological of the retrospective type of time-series, with the use of multivariate logistic regression techniques. In the present study, data from all new cases of cure and abandonment of leprosy treatment notified by the health centers of the municipalities to the SINAN (Notifiable Diseases Information System) in the state of Sergipe, Brazil, from 2007Brazil, from to 2017 used. This system consists of a database of the Health Secretariat of all states in Brazil, to report information on sociodemographic and clinical characteristics and the address of mandatory reporting diseases (Santos et al., 2019) The study took place in the state of Sergipe ( Figure 1). Sergipe is one of the nine states located in the Northeast region of Brazil whose capital city is Aracaju. It is the smallest Brazilian state with a territory of 21,962.10 km2, equivalent to 0.26% of the national territory, and an estimated population of 2,288,116, in the year 2017. In its administrative political organization, it has 75 municipalities grouped in three mesoregions and 13 microregions (IBGE, 2019) For the analysis of the tendency of leprosy cure and treatment abandonment, the percentage of cases cured and treatment abandonment among the cases reported in the year was calculated, and these rates were calculated based on the "Guidelines for surveillance, care and elimination of leprosy as a public health problem". For the percentage of cure, the numerator was the number of new leprosy cases, residing in a specific place, diagnosed in the years of the cohorts, and cured until 12/31 of the year of evaluation. The denominator was the total number of new leprosy cases residing in the same place and diagnosed in the years of the cohorts. This proportion is multiplied by 100 to obtain an indicator in percentage terms. The parameters adopted by the Ministry of Health vary between: Good: ≥90%; Regular: ≥75 to 89.9%; Precarious: <75% (Brazil, Research, Society andDevelopment, v. 10, n. 1, e15310111615, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i1.11615 4 The formula used to calculate the percentage of treatment abandonment consists of new cases of leprosy diagnosed in the years of the cohorts who abandoned treatment until 12/31 of the year of assessment, divided by the total of new cases diagnosed in the years of the cohorts, and multiply by 100. The parameters adopted by the Ministry of Health vary between Good <10%; Regular 10 to 24.9%; Precarious ≥25% (Brazil, 2016 A).

Statistics analysis
Polynomial regression was utilized to calculate the annual variation of the indicator, between 2007 and 2017. This method of analysis consists of a segmented linear regression, using dummy variables, to identify points where there is a change in the trend and estimate the Annual Percentage Change (APC), and the Average Annual Percentage Change (AAPC), considering the entire period of the series and with a 95% confidence interval. The trend was classified as increasing, decreasing, and stationary (Monteiro, Martins, Brito, Alencar & Heukelbah, 2015) The variables chosen for the analysis of the factors associated with the cure of leprosy and the treatment abandonment were: sex, age group, race, schooling, zone, operational classification, clinical form, degree of physical disability and bacilloscopy. The association of these variables with the dependent variables was verified using the Chi-Square test and the Odds Ratio (OR). The significant variables in the bivariate analysis were used as independent in a multivariate logistic regression model to adjust the occurrence or not of treatment abandonment and cure. All statistical analyzes were performed using software R 3.6.1, and the level of significance adopted was 5%.

Ethical aspects
The study was submitted to the Research Ethics Committee (CEP) of the Federal University of Sergipe and approved with the following approval opinion (No. 3,151,215), of February 18, 2019.

Results
In  Figure 2B). The results of the trend in operational health indicators showed a reduction in adherence to treatment and, consequently, a decrease in the proportion of cured patients, as shown in (Figure 2). Research, Society and Development, v. 10, n. 1, e15310111615, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i1.11615 The variables sex (p-value = 0.0963), schooling (p-value = 0.3688), zone (p-value = 0.4149) and bacilloscopy (p=0,1459), did not show statistical significance to the percentage of treatment abandonment (Table 1). Concerning the age group, young people had 2.65 chances (p-value = 0.0004; OR = 2.65) to abandon treatment when compared to children under 15 years old. Black, browns and indigenous people had 1.74 more chances (p-value = 0.0156; OR = 1.74) to abandon treatment in regard to white people. When it comes to clinical characteristics, it was observed that multibacillary individuals are 2 times more likely to abandon treatment (p-value < 0.0001; OR = 2.02) than paucibacillary ones. Another important point is that individuals with the Borderline and Lepromatous clinical forms manifested 1.74 and 1.91 more chances of abandoning the treatment (p-value = 0.0028; OR = 1.74; OR = 1.91, respectively) when compared to individuals who have an indeterminate form. Individuals with grade 2 of physical disability were twice as likely to abandon treatment (p-value = 0.0013; OR = 2.20) when compared to grade 0 disability. Adjustments were made to logistic regression models, assuming abandonment as a dependent variable (adopting a value of 1 for cases in which treatment was abandoned). The independent variables in each model were significant in the previous bivariate tests (Table 1). It is noted by the multivariate regression (   (Table 3).
Concerning clinical variables, paucibacillary patients (96.98%) had a higher percentage of cure when compared to multibacillary ones (89.90%) (p-value < 0.0001). Individuals with the Lepromatous form and Borderline (OR = 0.93, OR = 0.95, p-value < 0.0001) were less likely to be cured when compared to individuals who developed the indeterminate form of the disease. Regarding the degree of disability, the percentage of cure was higher in individuals with grade 0 of disability (95.47%) when compared to grade 1 (92.65%) and grade 2 (86.78%) (p-value < 0.0001). Negative intradermal bacilloscopy was considered a protective factor for healing (p-value < 0.0001), and this was evidenced by higher percentages of cure in individuals with negative test results (95.59%). (Table 3). It is noted by the multivariate regression, that the young age group has less chance of cure (OR = 0.34) when compared to children under 15 years old. The same happens for the operational classification; the multibacillary individuals have a lower chance of cure (OR = 0.35) when analyzed together with other independent variables (Table 4).
Lastly, individuals with grade 2 of physical disability are less likely to be cured (OR = 0.54) in opposition to the grade 1. It is inferred, then, that the young age group, the multibacillary operational classification, and the degree of physical disability were the main factors associated with the risk of not obtaining a cure from the analyzes (Table 4). Development, v. 10, n. 1, e15310111615, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i1.11615

Discussion
The results of this study demonstrate a vulnerability related to leprosy operational indicators, treatment abandonment, and cure, in the state of Sergipe, in Brazil. Some studies indicate that the organizational structure of the health system has a greater influence on the epidemiological situation of leprosy than the socioeconomic disparities, given that, greater coverage of the Estratégia Saúde da Família (The Family Health Strategy) effectively contributes to the promotion of greater adherence to treatment (Lapa et al.,2006;Brito et al., 2015) In this study, it was possible to observe a growing trend in Sergipe of people who abandoned treatment between 2011 and 2017. Sousa (2015) emphasize that the abandonment / non-adherence of leprosy treatment can be related to several reasons, such as lack of motivation, lack of knowledge about the disease and the norms, and non-credibility of the cure. In other epidemiological studies, such as de Souza et al. (2018) the leprosy operational indicators in Bahia, from 2001 to 2014, were analyzed, from a gender perspective; in this study, there was a reduction in the number of people who abandoned the treatment of leprosy in the aforementioned historical series.
Another epidemiological study, carried out by Oliveira et al. (2015) in the state of Paraná, from 2001 to 2010, also observed a decreasing trend in people who abandoned leprosy treatment. It is noteworthy that in Sergipe, unlike other locations in Brazil, there is a tendency to increase the proportion of people who abandoned treatment. These high rates may reflect the fragility that exists in the relationship between the user and the health services, as the same must project credibility with the treatment adopted by the patient.
It is important to emphasize that there is a difference between non-adherence and treatment abandonment. Nonadherence is configured when the diagnosed user fails to regularly attend appointments at the Health Unit that are previously scheduled. In this case, the health team must make an active search, aiming to rescue the user from treatment. Whereas treatment abandonment is when people who have not completed the number of doses within the scheduled time and who have not attended the health service in the last 12 months, are discharged for abandonment (Lira, Silva & Gonçalves, 2017).
Concomitant to the increase in the proportion of people who abandoned leprosy treatment, in 2013, the proportion of people cured decreased considerably until 2017. In an epidemiological study in Brazil conducted by Ribeiro et al. (2018) it was observed that between 2010 and 2015 there was a general reduction in the percentage of cure, thus showing a weakness in the health system. From these data, it is possible to infer that the Ministry of Health, over the years, has been concerned with early diagnosis, and in the active search for cases in children under 15, and in the general population; however, there is a notable weakness in treatment follow-up of leprosy, evidenced by national and local studies that reinforce the decreasing trend in the percentage of cure.
It is worth mentioning that in Sergipe, in the last epidemiological bulletin carried out from 2012 to 2016, the rate of new cases was 17.59 per thousand people, thus expressing high levels of incidence for the state (Brazil, 2018 B). A hypothesis for maintaining this high rate is precisely the failure to monitor the treatment of patients, as it has been seen that diagnosed and not cured individuals inflame the prevalence and contribute to the maintenance of active transmission of the disease (Barbosa et al.,2014). Another problem is that people who are not cured can evolve to a state of permanent physical disability, thus leading to an increase in social inequities and public spending.
contributing factor to greater treatment abandonment in this age group. This data is relevant because, as leprosy is a disabling and stigmatizing disease, there is a tendency for people to abandon their work functions and isolate themselves for fear of social judgment (Heukelbach, Chichava & Oliveira, 2011). In the same study by Araújo et al. (2014) children under 15 years old, corresponded to only 2.9% of the cases that abandoned treatment. In our study, this same group had a greater chance of cure when compared to other age groups.
Black, brown, and indigenous races were associated in this study as a risk factor for abandoning treatment. In the last Census Bureau, the majority of the Brazilian population defined themselves as brown and black (50.7%). Studies indicate that a detailed analysis of this factor is necessary as a contributor to treatment abandonment, since the analysis of color/race is subjective; which requires a more detailed study of the association of this variable related to the treatment abandonment and the cure (Ignotti et al., 2001), Regarding the studied clinical variables, multibacillary individuals with the Borderline and Lepromatous clinical forms, and with a grade 2 of physical disability, are more likely to abandon treatment. These results are similar to that of Araújo et al.(2014) in which 61.76% of patients who abandoned treatment belonged to the multibacillary operational classification. These data are remarkable since the multibacillary form is responsible for the active transmission of the disease.
Ignotii et al. (2001) reinforce that the abandonment of treatment by patients with the most severe clinical forms is not only related to the durability of the treatment, which is greater when compared to paucibacillary individuals, but also, to the perception that the individual has about the signs and symptoms related to the most complicated forms, resulting in disbelief in the prognosis of the cure.
In our analysis, the clinical characteristics related to the cure of leprosy were assessed. Multibacillary individuals with a grade 2 of physical disability are less likely to be cured, which reinforces the results of the bivariate and multivariate analysis of these same groups regarding treatment abandonment. It is worth stressing the importance of the first contact of the Family Health Team with patients with the most severe forms of leprosy; the reception, and monitoring of this patient are of fundamental importance for better understanding and motivation regarding the credibility of the treatment and cure disease (Luna et al.,2010;Araújo et al., 2014).

Conlusion
This study reveals that although leprosy has treatment and cure, the proportion of people who abandon treatment has grown, and accordingly, the proportion of cure has decreased. Through the results described, it is possible to observe the weakness of health services, especially when it comes to the clinical factors associated with treatment abandonment and the low proportion of cure. Multibacillary individuals with the most severe forms of the disease (Borderline and Lepromatous) are responsible for the active transmission of leprosy, and the most likely to abandon treatment. Therefore, the need for a more structured follow-up of these patients is emphasized, aiming at the integrality and the concretization of the bond as a fundamental principle of Primary Care.
Besides, the main sociodemographic factors associated with a higher rate of treatment abandonment and a lower proportion of cure were highlighted. It is up to the managers a greater concern with individuals who have less education, who are in the young age group, and who belong to the black/brown or indigenous races. The greater the social vulnerability, the greater the spread and emergence of diseases such as leprosy, and the barriers to effective treatment. The opening of new protocols targeting the most vulnerable population in health services could contribute to a lower rate of treatment abandonment for people with leprosy.
In conclusion, this study aims to encourage further research that better elucidates how sociodemographic and clinical factors can contribute to a lower cure rate and greater treatment abandonment.