Recurrence of Leprosy Cases in the State of Mato Grosso, Central-west Brazil

OBJECTIVE: To compare new registrations of recurrences of leprosy cases in primary healthcare units (PHUs) and in specialized units in the State of Mato Grosso. METHODS: This was a cross-sectional study based on all new registrations (N = 323) of recurrences of leprosy cases within the Notifi able Disease Information System (SINAN) between 2004 and 2006 that were made in the State of Mato Grosso, Central-West Brazil. The cases diagnosed were compared regarding sex, age, clinical-laboratory characteristics and geographical distribution among the municipalities. To compare and calculate the proportions of the variables, the chi-square test at the signifi cance level of 5% was used. RESULTS: Among the new registrations of recurrences, 20% were confi rmed at specialized units and 80% at PHUs. However, most of the diagnoses at PHUs presented negative bacilloscopy fi ndings (c2 = 12.34; p = 0.002). Seventy-one per cent of the cases were among males; the mean age was 43 years. No differences in the percentages of registrations were observed between the healthcare units with regard to clinical form, operational classifi cation or degree of physical incapacity. Out of the total number of municipalities in the state, 64.7% presented recurrences and these accounted for 6 to 20% of all registrations. CONCLUSIONS: The new registrations of cases of recurrence in Mato Grosso were infl uenced by the diagnoses made at PHUs, thus suggesting that there is a defi ciency within the healthcare services in recognizing cases of recurrence.


INTRODUCTION
Leprosy control began at the end of the 1940s, 4 with the introduction of sulfones to treat the disease.After some time, given the ineffi ciency of this therapy, studies on resistance to sulfone monotherapy began. 8The existence of this resistance was proven experimentally by Pettit & Rees in 1964, 15 by means of the technique of inoculation of Mycobacterium leprae, as standardized by Shepard. 17From the 1980s onwards, the World Health Organization (WHO) started to recommend the use of polychemotherapy regimens.This has resulted in treatment and cure for more than 11 million leprosy patients.a Polychemotherapy has been decisive in shortening the duration of treatments, thereby leading to an inversion in the fl ow of cases coming into and leaving the registers of active leprosy cases and a decline in the coeffi cient of prevalence in most endemic countries.c Recurrences are the most important indicator of treatment effectiveness, a even if leprosy recurrences may be caused by strains that are monoresistant or multiresistant to chemotherapy. 4,7,12,13,15cording to the Brazilian Ministry of Health, d the clinical criteria for diagnosing recurrence should be based on the operational classifi cation, when the possibility of a reaction state has been ruled out.Paucibacillary patients are considered to be cases of recurrence when, after discharge because cure was achieved, they present impaired neural function, new areas with abnormal sensitivity, new lesions and/or exacerbation of previous lesions that do not respond to corticosteroid treatment within a 90-day period.For multibacillary patients, it is when they present the same dermatological-neurological abnormalities as described for paucibacillary patients, with the addition of results from bacilloscopic and/or histopathological examinations that are compatible with the active forms of the disease, and when they do not respond to treatment with corticosteroids and/or thalidomide.Confi rmation of such recurrence should be discussed with specialists at reference centers, according to the criteria for diagnostic suspicion and confi rmation.c At the start of 2007, there were 2,270 cases of recurrence around the world, of which 1,584 (69.8%) were registered in Brazil.b According to the Brazilian Ministry of Health, the cumulative risk of recurrence after polychemotherapy was adopted was 0.7% for cases subjected to a multibacillary regimen and 1.1% for paucibacillary cases.e Furthermore, there are important differences in the records of recurrence in Brazilian regions where there is high prevalence of the disease, such as the borders of the Statutory Amazon Region.The states of Mato Grosso, Acre, Amazonas, São Paulo, Paraná and Santa Catarina register the highest rates in Brazil: between 4% and 8% of the cases of recurrence among all the registrations in 2006.f Studies that identify factors relating to recurrence are essential for better accuracy to be obtained in relation to the clinical, epidemiological and therapeutic diagnoses, thereby avoiding increased morbidity, persistence of bacteria, resistance to medications and physical incapacity.Through these high numbers of recorded cases of recurrence in Mato Grosso, the present study had the objective of comparing the records of leprosy cases diagnosed at primary healthcare units and specialized units in the state of Mato Grosso.

METHODS
This was a cross-sectional study using the registrations caused by leprosy recurrence that were notifi ed in the state of Mato Grosso, Central-West Brazil, between 2004 and 2006.These were obtained from the notifi able diseases information system (SINAN/MT).The cases selected were patients living in the municipalities of Cuiabá, Cáceres, Diamantino, Rondonópolis or Várzea Grande, between 2004 and 2006.These municipalities were selected because they had diagnostic and leprosy study support units: polyclinics, medical specialty centers and the medium and high complexity reference center (CERMAC).These municipalities have 1,032,523 inhabitants, i.e. 36.2% of the total population of the state, which is estimated to be 2,854,462 inhabitants.g The comparative analysis included the cases diagnosed as recurrence at specialized units, the individuals living in the fi ve municipalities selected and those diagnosed in primary healthcare units in the other municipalities of the state.The cases were compared with regard to sex, age, clinical-laboratory characteristics and geographical distribution among the municipalities of the state.
All registrations of recurrence (n = 344) were included according to the municipality of residence.From this total, 21 registrations were excluded because of diagnostic error, double data entries and transfers to other states, and thus 323 cases registered over the study period were evaluated.To validate the data relating to the three cases of double data entry, the treatment units were consulted.For this study, the diagnostic unit and its municipality were used.In selecting the cases of recurrence, the date and year of diagnosis were used.In most cases, these coincided with the date and year of treatment.When there was disagreement or failure to fi ll in the date and year fi eld in the medical records, it was sought to validate the data by means of the annotations in the medical fi les.The cases were classifi ed according to the operational classification (paucibacillary or multibacillary), which was obtained through confi rmation of the diagnosis of recurrence that was made at the diagnostic unit.No registrations of recurrence that presented changes in operational classifi cation after the start of the retreatment were observed.
The following variables were selected for analysis: sex, age, municipality of residence, clinical form, operational classifi cation, degree of physical incapacity evaluated at the start of the treatment and bacilloscopy at the time of diagnosing the recurrence.
The indicator of the percentage of leprosy recurrence corresponded to the percentage of registrations of recurrence.This was defi ned as the number of recurrences during the years investigated, divided by all the registrations for leprosy treatment during the same year, multiplied by 100.For the denominator, the registrations with diagnostic error, double data entries and transfers to other states were also removed.The percentage recurrence was calculated for all the municipalities, taking into consideration the operational classifi cation of the set of registrations for each locality.
The municipalities were aggregated according to the type of healthcare unit, in order to compare the clinicallaboratory criteria used in the units for diagnosing the recurrence.
To compare the total numbers of cases of recurrence between the primary healthcare units (PHU) and the specialized units (SU), according to the operational classifi cation, the ratio of the percentages of cases of recurrence [(PHU/SU)-1)*100] was calculated using an electronic spreadsheet.
To compare and calculate the proportions according to the relative frequencies of the variables, the chisquare test was used in Epi-Info, version 3.

RESULTS
The 323 cases of recurrence of leprosy registered in Mato Grosso between 2004 and 2006 represented a mean of 107.6 cases/year.
Table 1 presents a comparison of percentages of registrations due to recurrence that were diagnosed in the primary healthcare units and specialized units, according to the variables of sex, age, clinical form, operational classifi cation and degree of physical incapacity at diagnosis.No statistically signifi cant difference in percentages was seen between the healthcare units according to sex.The majority (71%, n = 229) of the patients with recurrence were male; the mean age was 42.6 years (SD = 15.8;minimum 12 years and maximum 84 years).The fi ve children with recurrence were diagnosed in primary healthcare units.The municipality of Cuiabá presented the highest percentage (13%; n = 43).Out of all the records of recurrence, 20.1% were diagnosed in specialized units and 79.9% in primary healthcare units.In general, the dimorphous form accounted for 48% (n = 156) of the registrations; 82% (n = 266) were multibacillary and 56% (n = 182) did not have any physical incapacity.There were no differences in the percentages of registrations between the units according to the clinical form, operational classifi cation or degree of physical incapacity.
There was a statistically signifi cant difference in the percentage of cases of recurrence between the diagnostic units, according to the bacilloscopy results [χ 2 = 5.86 (p = 0.053)] (Table 2).Among the cases of multibacillary recurrence, 37% (n = 76) were diagnosed with a negative bacilloscopy result in primary healthcare units [χ 2 = 12.34 (p = 0.002)].
In Table 3, it can be seen that the difference in the percentages of diagnoses of recurrence among all the registrations for leprosy treatment, between those at primary healthcare units and those at specialized units was 116%.For the category of cases of paucibacillary recurrence, this difference reached 150%.
The Figure presents the geographical distribution of registrations of cases of leprosy recurrence according to municipality of residence, in the categories of total number of cases of recurrence (A), cases of multibacillary recurrence (B) and cases of paucibacillary recurrence (C).Out of the 141 municipalities in Mato Grosso, 139 presented notifi cations of leprosy cases.Among this total, 64.7% (n = 90) registered cases of recurrence, among which 14% (n = 13) presented more than fi ve cases, with percentages of 6% to 20% of all the registrations.Multibacillary cases accounted for most of the registrations and there was no difference in this respect between geographical areas of the state.Total of more than fi ve paucibacillary cases were registered in the municipalities of Cuiabá and Araputanga.

DISCUSSION
The results obtained showed that a larger percentage of the registrations of recurrence were diagnosed at primary healthcare units.Most of these cases were confi rmed, even if the bacilloscopy results were negative.Such results suggest that there were defi ciencies relating to operational factors, including the capacity of the healthcare service network to diagnose cases of recurrence.
According to the Brazilian Ministry of Health ( 2006), h the criteria for certifying healthcare units as reference centers for leprosy include: a multidisciplinary team with up-to-date training for healthcare relating to leprosy; provision of healthcare at specialized level, to clarify diagnoses, recurrences and intercurrences relating to episodes of reaction and neural lesions of leprosy, among others.The patients diagnosed in Mato Grosso presented epidemiological characteristics similar to those of patients undergoing treatment in Brazilian cities in other states. 2The cases were predominantly among males, at economically productive ages, and in the multibacillary form.
Occurrences of cases among children are an important epidemiological indicator, and analysis of such cases broadens the discussion regarding operational problems within the healthcare network. 1,10The records of cases of recurrence at primary healthcare units among the present study population corroborate this refl ection, because of diffi culty in differential approaches in relation to other dermatological or neurological diseases and diffi culty in diagnostic management for confi rming the case of recurrence.
c Through the introduction of the basic operational standards (1996), i it was envisaged that patients' access to basic and specialized healthcare services would be improved.In Mato Grosso, specialized attendance for leprosy is concentrated in municipalities with medium and large-sized populations (Cuiabá, Cáceres, Rondonópolis and Várzea Grande).In the remaining municipalities in this state, access to diagnoses of greater accuracy for cases of recurrences is more diffi cult.
Among other factors, the weaknesses of primary healthcare units in terms of case resolution have been indicated as one of the problems for maintaining the strategy of changes to the care model, 5 especially regarding the hierarchical fl ow for attendance.The lack of mechanisms for regulating the municipalities' responsibilities may explain the defi ciency in the quality of care. 14Other studies 16,19 have indicated that there are higher percentages of recurrence among paucibacillary patients than among multibacillary patients, thus differing from the percentages found in this study (greater percentages for recurrence in the multibacillary cases).These results may suggest that healthcare professionals fi nd it easier to confi rm the diagnosis in multibacillary cases.19]21 Although bacilloscopic index results were not analyzed in the present study, given that this indicator was not available within SINAN during the study period, the higher percentage of negative bacilloscopy results obtained at primary healthcare units also suggests that there is a greater likelihood of diagnostic errors in distinguishing between reactional states and recurrence.
Reactional states or leprosy reactions are reactions of the patient's immune system to M. leprae.The clinical signs, which are called infl ammatory episodes, may affect both paucibacillary and multibacillary cases, and when they appear following chemotherapy, they may be confounded with cases of recurrence. 3,9,11,20cording to Ximenes et al (2007) 21 and Shetty et al (2005), 18 patients who present reactional episodes are more likely to be treated as cases of recurrence.This indicates that there is a need for greater attention to the differential diagnosis between these two conditions.Among paucibacillary patients, recurrence can be confounded with a late reverse reaction, considering that M. leprae cannot be isolated in these cases. 9cording to Gallo & Oliveira, 9 in addition to the diffi culty of characterizing patients with recurrence, there is no consensus regarding established parameters that might guide healthcare services towards diagnostic confi rmation.There is therefore a need to conduct studies that might direct healthcare professionals towards such confi rmation, with greater precision.
The paucibacillary cases registered as recurrences in municipalities with populations of fewer than 20,000 inhabitants (Araputanga, Castanheira, Guiratinga, Nova Bandeirantes, Salto do Céu and Terra Nova do Norte) stood out.These municipalities had lower capacity for diagnosing cases of recurrence and did not have reference centers to ensure the accuracy of diagnoses.
The Brazilian National Health System (SUS) j recommends that municipalities should organize primary healthcare service, while the State should impose standards, perform assessments, provide technical advice and reorganize the referral and counter-referral system.
Within this context, effective attendance for leprosy depends on improvement of the leprosy indicators agreed at managerial levels within SUS. k This study presents the limitations inherent to crosssectional studies conducted using secondary data.It is known that healthcare professionals who are well-qualifi ed in diagnosing and treating leprosy, with professional experience obtained because of the high prevalence of this disease, may be allocated to primary healthcare units in Mato Grosso, away from the state capital. 6However, the technological diffi culties in meeting the diagnostic criteria for recurrence of leprosy at these units reduces the importance of the points made above regarding the limitations of the study, to some extent.
It is concluded that the numbers of new cases of recurrence registered in Mato Grosso are infl uenced by the diagnoses made in primary healthcare centers, thus suggesting that there are defi ciencies within the healthcare services, with regard to recognizing cases of recurrence.

Figure .
Figure.Geographical distribution of registrations of leprosy cases in the municipalities of residence, according to (A) total number of cases of recurrence, (B) cases of multibacillary recurrence and (C) cases of paucibacillary recurrence.State of Mato Grosso, Central-West Brazil, 2004-2006.Source: Notifiable Diseases Information System (SINAN/leprosy).State Health Department of Mato Grosso (SES/MT), 2004-2006.

Table 1 .
2.1.The geographical distribution of the records of percentage recurrence was performed by means of the Terraview software, version 3.2.0.Comparison of the percentages of leprosy registrations due to recurrence, diagnosed at primary healthcare units and specialized units, according to selected variables.State of Mato Grosso, Central-WestBrazil, 2004-2006.
Source: Notifi able Diseases Information System (SINAN/leprosy).State Health Department of Mato Grosso (SES/MT), 2004-2006.a percentage calculated on the line

Table 2 .
Comparison of the percentages of leprosy registrations due to recurrence, diagnosed at primary healthcare units and specialized units, according to the bacilloscopy result for the diagnosis and operational classifi cation.State of Mato Grosso, Central-WestBrazil, 2004-2006.

Table 3 .
Ratio of percentages of recurrence of leprosy in primary healthcare units and specialized units, according to operational classifi cation.State of Mato Grosso, Central-WestBrazil, 2004-2006.