Leprosy in Southern Brazil : a twenty-year epidemiological profile

Introduction: This study evaluated leprosy rates in Rio Grande do Sul, an area with a historically low prevalence. However, recent studies are lacking. Methods: Data extracted from a National Database were analyzed for clinical features and compared to 1980s data. Tendency was assessed via stationarity analysis. Results: Between 1990 and 2011, 4,770 cases were reported (0.21/10,000 inhabitants; 95% CI = 0.19-0.24). Detection was slightly higher among males, 1.9% cases were among children and most multibacillary (74.7%) at diagnosis. Conclusions: Leprosy is controlled in RS, but most cases are multibacillary. Early identification is important to avoid disabilities due to late diagnosis.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that primarily affects Schwann cells and the skin.The upper airways are the main entry point and route of elimination of the bacillus 1 .Disease characteristics are dependent on host immune response, generating a wide clinical and histopathologic spectrum from a pole of resistance (tuberculoid pole) to a pole of susceptibility (lepromatous pole).Besides these opposing poles, there are two additional clinical forms: indeterminate and borderline, whose features may vary from one pole to another in the disease evolution 1,2 .The World Health Organization (WHO) also classifies leprosy operationally, for chemotherapeutic purposes as either paucibacillary (PB) (cases with up to five skin lesions and/or one impaired nerve) and multibacillary (MB) (cases with more than five skin lesions and/or one or more affected nerves).The PB and MB classifications correspond approximately to the tuberculoid and lepromatous poles, respectively 1 .
When not diagnosed and treated early, leprosy and its associated sequelae can cause disabilities and physical deformities, leading to occupational and psychosocial problems 3 .Leprosy is curable if diagnosed early which can prevent the development of long-term sequelae and reduce rates of transmission through disruption of the transmission chain 1 .
Leprosy is a major public health problem in Brazil 1 and in several countries globally.At the end of 2000, leprosy rates were still endemic in 15 countries (prevalence above 1.0/10,000 inhabitants).According to WHO, in 2009, Brazil remained one of six countries in the world with the highest prevalence of leprosy 4,5 .In 1991, the WHO elimination target was defined as a prevalence less than 1 case per 10,000 inhabitants.The same year, multidrug therapy (MDT) with rifampicin, clofazimine, and dapsone was implemented as the main strategy to combat and eliminate leprosy, in addition to early detection 6 .Around 80% of new cases are diagnosed in countries located in the intertropical area 7 .In Brazil, more than 30,000 new cases of leprosy are diagnosed annually.In 2014, the prevalence of leprosy in Brazil was 1.27/10,000 inhabitants.However, the Rio Grande do Sul (RS),Brazil's most Southern state (at the border with Uruguay and Argentina), is considered an area where the disease is eliminated, having the country's lowest prevalence at 0.16/10,000 inhabitants 8 .Thus, few recent studies have examined the epidemiology of leprosy in RS, making it difficult to evaluate disease trends for the last twenty years.Therefore, this study aimed to compare leprosy data from RS in the 1980s to that observed in the period from 1990 to 2011 and to assess the current situation of leprosy in RS.This was an ecological study, in which leprosy data in RS were analyzed for the period 1990-2011 by evaluating data included in the Notifiable Diseases Information System [Sistema de Informação de Agravos de Notificação (SINAN) database 5 .The SINAN is the national registration system for notifications and investigations of leprosy cases.Data were collected for cases with notification and residence in RS across the following variables: new cases by sex and age, WHO operational classification and clinical form.
Detection rates overall and for children younger than 15 years of age were extracted from population data collected by the 2000 Census and population estimates of the Brazilian Institute of Geography and Statistics [Instituto Brasileiro de Geografia e Estatística (IBGE)] 9 , available on the website of the Department of Informatics of the Unified Health System [Departamento de Informática do Sistema Único de Saúde (DATASUS)] 8 .Descriptive data analysis was performed through calculation of simple absolute and percentage frequencies for categorical variables.Results were compared with data published by Cestari et al 10 , referring to 1980s data and were presented as rates per 10,000 inhabitants using 95% confidence intervals (95% CI).To test the stationarity of graphically presented data, the Dickey-Fuller test was used through the R Project Package -t series.The results of this study showed that, during the period of 1990-2011, 4,770 cases of leprosy were registered in RS.The new-case detection rate identified was considered low by patterns normally observed in Brazil [(0.21 cases/year per 10,000 inhabitants (95%CI = 0.19-0.24)].This was similar to the 1980s rate of, 0.25 cases/year per 10,000 inhabitants (95% CI = 0.20-0.27).
This study identified a decrease in detection of new cases with the stationarity analysis showing no significant result (p = 0.701).However, parameters were softened to reduce variability among the evaluated years.Therefore, the data obtained shows a declining trend in the detection of new cases over the 30 years observed (Figure 1A).
The rate of new cases from the 1990s was slightly higher among males with a mean male/female (M/F) ratio of 1.09, reaching 1.5 in some years within the period.This pattern was not observed between 1975 and 1988 within which a M/F mean ratio of 1.00 was observed (Table 1).The new-case detection rate in children younger than 15 years of age decreased during the 1990-2011 period compared to the 1980s (1.9% vs 3.0%) (Table 1).
Throughout both periods, there was a higher average detection of lepromatous and borderline leprosy forms, from 77.5%/year in the 1980s to 80.4%/year during the period 1990-2011 (Table 2).Moreover, when grouped according to the WHO operational classification (Table 2), there was a 74.7%rate of MB detection during the period 1990-2011.This rate coincides with the classification according to clinical form if the MB classification is considered as the lepromatous and borderline leprosy forms.It was also observed -by stationarity analysis of the incidence percentage of MB cases within the last 22 years -that an upward trend in the proportion of these cases was identified in this study, because there was no significant stationarity (p = 0.342) (Figure 1B).No pattern was identified regarding percentage of diagnoses according to the disability grade 2. (Figure 1C).
According to Ministry of Health parameters, a geographical region can be classified as: (A) hyperendemic -4.00 cases or more/10,000 inhabitants; (B) very high -from 2.00 to 3.99 cases/10,000 inhabitants; (C) high -from 1.00 to 1.99 cases/10,000 inhabitants; (D) intermediate -0.20 to 0.99 cases/10,000 inhabitants; or (E) low -less than 0.2 cases/10,000 inhabitants 11 .As shown in Figure 1, RS has remained classified as low/intermediate endemicity during the past 30 years.The recent slight decrease in the incidence of leprosy in RS compared to the 1980s is likely due to the introduction of multidrug therapy (rifampicin + dapsone + clofazimine) in 1991, which reduced disease transmission through interruption of the transmission chain upon initiation of treatment.Detection rates serve as indicators of leprosy transmissibility in Brazil and, according to WHO, leprosy detection has showed no decline in recent years 1 .Despite this, regional indicators of RS have always remained below the national average.
Leprosy is a chronic, low mortality, and late mortality disease that often goes undiagnosed, especially in low endemicity areas.Additionally, stigma still surrounds a diagnosis of leprosy causing patients to avoid seeking health services for confirmed diagnosis and treatment.Owing to this, estimating the actual magnitude of leprosy is very difficult, given that a low number of new cases and low rate of registration could either mean that the disease is not significant in the area, or that there are operational problems (such as a high number of unreported cases) 12,13 .Therefore, to indirectly assess the real magnitude of the disease, WHO recommends the use of the proportion of MB patients and the proportion of new cases in children younger than 15 years of age as valid epidemiological indicators 12 .New cases of leprosy in children younger than 15 years of age are related to the bacillus transmission chain within the community and the existence of an active transmission focus 14 .Currently, detection rate among the 0-14-year age group is considered, by the Brazilian Ministry of Health, the primary disease control indicator 3 .However, this indicator is most useful for high prevalence areas with high rates of diagnosis in children and adolescents.In low prevalence areas, such as RS, the rate of newly affected children younger than 15 years of age is very low.The same limitation can be applied to the operational classification: high prevalence regions have mainly PB, while in low prevalence areas, the MB forms are more frequently identified 15 .
The later diagnosis and greater proportion of MB cases in areas with lower prevalence can also be explained by immunological factors.Approximately 80% of the population is potentially resistant to leprosy and able to develop cellmediated immunity against the bacillus 12 .However, such capacity is not present at birth but is developed over the years when the infection occurs early.It is therefore common, in endemic areas, to acquire cellular immunity, which occurs at the expense of PB infection.The younger the individual has contact with the disease, the greater the likelihood of developing the PB form, which explains the higher proportion of PBaffected young people in endemic areas 12,14 .As the number of potentially contagious patients in hyperendemic areas is greater, the probability of an individual receiving a sufficiently high bacterial load able to cause an infection before adulthood is greater in those regions.Consequently, PB forms will often be more commonly diagnosed in these areas.However, in low endemicity areas, individuals are less often exposed to the bacillus, so infection occurs later and thus the proportion of MB cases is higher 12,14 .This phenomenon is even more relevant in the current context where populations are aging and, therefore, may demonstrate impaired immunological responses.Studies have shown that among aged populations, there is also a greater risk of developing leprosy reactions 15 , which constitutes the primary cause of physical disabilities in patients with leprosy.Therefore, even in sites with low endemicity, the occurrence of leprosy would have potential socio-economic consequences not only to the individual, but also to families and communities.Issues such as leprosy reaction episodes and physical disabilities may be temporary or become permanent, including restriction of productive activities, which can even occur after completion of treatment.Nevertheless, the manner in which leprosy behaves in response to changes in immunity among older patients must be better evaluated because, in areas such as RS, patterns of leprosy are characterized by aged MB patients 10,12 .Observing these specific profiles among populations from other regions might generate insights to promote specific strategies of prevention and improvement in heath among these populations.
In conclusion, it can be confirmed that RS remains a low endemicity area for leprosy with the disease virtually eliminated.This is exhibited by low detection rates among patients younger than 15 years of age (lower than were recorded in the 1980s) and preponderance of MB cases (according to WHO operational classification) with an upwards trend.However, it is impossible to determine the true prevalence of leprosy using only these indicators because many cases are still underreported or diagnosed late.Considering this, WHO also recommends that the degree of disability at diagnosis is used as an epidemiological indicator to estimate the delay in diagnosis 12 .Thus, there is a growing trend in the diagnosis of cases with a degree of disability equal to 2 (Figure 1C), which allows inference that the case has been diagnosed late.
Despite the extremely high detection rates and high prevalence of leprosy in most of Brazil, RS has achieved the goal of eliminating the disease (<1.00/10,000 inhabitants) by reaching a prevalence of 0.16/10,000 in 2009 8 .However, care must be taken in the interpretation of this data because the diagnosis may be occurring late, which increases the potential for transmission.Furthermore, it should be noted that the more prevalent MB form predisposes to increased reactional cases, especially erythema nodosum leprosum (one of the main causes of disability and the most observed reaction in this form of the disease) 13 .
Finally, although leprosy is now considered to be eliminated from RS, the data presented highlight the need for intensified control activities, such as searching for active disease with available rapid tests for contacts to improve early diagnosis to avoid reaction outbreaks and subsequent disabilities.

TABLE 1
New cases of leprosy by sex and age group for the periods1982-1988 and 1990-2011.

TABLE 2
New cases of leprosy by clinical form for the periods 1982-1988 and 1990-2011, and according to the WHO classification for the period 1990-2011.