ABSTRACT

Objective

This study aimed to analyze the spatial distribution of leprosy and disabilities in children under 15 years of age in Cuiabá.

Methods

Ecological study carried out in the city of Cuiabá, Mato Grosso, Brazil. The study population consisted of leprosy cases in children under 15 years old notified in the Notifiable Diseases Information System, between 2008 and 2018. Based on residential addresses, cases were georeferenced. In the analysis of the spatial distribution of the cases, the estimation of the Kernel density was used and, later, the statistics of spatial, spatio-temporal and Spatial Variation in Temporal Trends were applied.

Results

514 cases of leprosy were reported in children under 15 years of age in Cuiabá, with a percentage of 10.1% of cases with degree of physical disability 1 and 2.3% with degree of physical disability 2 at the time of diagnosis. With the techniques of spatial and spatio-temporal scanning, clusters of risk for leprosy were identified in the North, West, East and South regions of Cuiabá, and with the technique of Spatial Variation in Temporal Trends, a cluster was identified in the West region of Cuiabá.

Conclusion

In Cuiabá, cases of leprosy in children under 15 years of age with disabilities were distributed throughout the urban area of the city, with the highest density of cases in the North and West regions, followed by the East region. The clusters with the highest Relative Risk were identified in the East and West regions, characterized by having low and medium income levels

Keywords:
Leprosy; Child health; Social vulnerability; Spatial analysis

INTRODUCTION

Leprosy is a chronic infectious disease with slow evolution, characterized by high infectivity and low pathogenicity, resulting in severe neuropathies, disability grading (DG), and deformities¹1. World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy [Internet]. Genebra: World Health Organization; 2018 [acessado em 10 out. 2022]. Disponível em: https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
https://apps.who.int/iris/bitstream/hand...

2. Ploemacher T, Faber WR, Menke H, Rutten V, Pieters T. Reservoirs and transmission routes of leprosy: a systematic review. PLoS Negl Trop Dis 2020; 14(4): e0008276. https://doi.org/10.1371/journal.pntd.0008276.
https://doi.org/10.1371/journal.pntd.000... -³3. Sanchez MN, Nery JS, Pescarini JM, Mendes AA, Ichihara MY, Teixeira CSS, et al. Physical disabilities caused by leprosy in 100 million cohort in Brazil. BMC Infect Dis 2021; 21(1): 290. https://doi.org/10.1186/s12879-021-05846-w
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Among the main international strategies and commitments of the 21^st century regarding diseases considered “neglected”, the Sustainable Development Goals (SDG) of the 2030 Agenda of the United Nations (UN)⁴4. United Nations Development Programme. Sustainable Development Goals Integration [Internet]. New York: United Nations Organization; 2022 [acessado em 10 out. 2022]. Disponível em: https://www.undp.org/sustainable-development-goals
https://www.undp.org/sustainable-develop... and the “Global Leprosy Strategy 2021– 2030 — Towards zero leprosy”, strategies that aim to eradicate the disease, reduce the number of children and adolescents diagnosed with leprosy, increase early diagnosis, and the non-occurrence of disabilities and/or deformities, in addition to combating stigma and ensuring that human rights are respected⁴4. United Nations Development Programme. Sustainable Development Goals Integration [Internet]. New York: United Nations Organization; 2022 [acessado em 10 out. 2022]. Disponível em: https://www.undp.org/sustainable-development-goals
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5. Black MM, Walker SP, Fernald LCH, Andersen CT, DiGirolamo AM, Lu C, et al. Early childhood development coming of age: science through the life course. Lancet 2017; 389(10064): 77-90. https://doi.org/10.1016/S0140-6736(16)31389-7
https://doi.org/10.1016/S0140-6736(16)31... -⁶6. World Health Organization. Towards zero leprosy. Global leprosy (Hansen’s Disease) strategy 2021–2030 [Internet]. 2021 [acessado em 10 out. 2022.] Disponível em: https://www.who.int/publications/i/item/9789290228509
https://www.who.int/publications/i/item/... .

The occurrence of leprosy in children under 15 years of age suggests the existence of bacilliferous household/family index cases, with strong indications of continuous and active transmission of the bacillus at home and in the community⁷7. Pradhan S, Nayak BP, Dash G. Childhood leprosy: a review. Indian Journal of Paediatric Dermatology 2019; 20(2): 112-6. https://doi.org/10.4103/ijpd.IJPD_47_18
https://doi.org/10.4103/ijpd.IJPD_47_18... ,⁸8. Jha R, Marahatta S. Profiles of pediatric leprosy: a report from a University Hospital of Nepal in the post-elimination era. Am J Trop Med Hyg 2021; 104(1): 219-22. https://doi.org/10.4269/ajtmh.20-1135
https://doi.org/10.4269/ajtmh.20-1135... . Often, patients and family members are unaware of any contact they have had with the disease, as well as the existence of cases of leprosy in the family or in the vicinities⁹9. Pedrosa VL, Dias LC, Galban E, Leturiondo A, Palheta J Jr, Santos M, et al. Leprosy among schoolchildren in the Amazon region: a cross-sectional study of active search and possible source of infection by contact tracing. PLoS Negl Trop Dis 2018; 12(2): e0006261. https://doi.org/10.1371/journal.pntd.0006261
https://doi.org/10.1371/journal.pntd.000... . Often, index cases are not identified early by health services, and close and prolonged contact causes the disease to affect children and adolescents, perpetuating the disease transmission chain and making it rather difficult to be eliminated⁷7. Pradhan S, Nayak BP, Dash G. Childhood leprosy: a review. Indian Journal of Paediatric Dermatology 2019; 20(2): 112-6. https://doi.org/10.4103/ijpd.IJPD_47_18
https://doi.org/10.4103/ijpd.IJPD_47_18...

8. Jha R, Marahatta S. Profiles of pediatric leprosy: a report from a University Hospital of Nepal in the post-elimination era. Am J Trop Med Hyg 2021; 104(1): 219-22. https://doi.org/10.4269/ajtmh.20-1135
https://doi.org/10.4269/ajtmh.20-1135...

9. Pedrosa VL, Dias LC, Galban E, Leturiondo A, Palheta J Jr, Santos M, et al. Leprosy among schoolchildren in the Amazon region: a cross-sectional study of active search and possible source of infection by contact tracing. PLoS Negl Trop Dis 2018; 12(2): e0006261. https://doi.org/10.1371/journal.pntd.0006261
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10. Darlong J, Govindasamy K, Daniel A. Characteristics of children with leprosy: factors associated with delay in disease diagnosis. Indian J Dermatol Venereol Leprol 2022; 88(3): 337-41. https://doi.org/10.25259/IJDVL_1382_20
https://doi.org/10.25259/IJDVL_1382_20... -¹¹11. Prakoeswa FRS, Maharani F, Fitriah M, Nugraha J, Soebono H, Prasetyo B, et al. Comparison of IL-17 and FOXP3+ levels in maternal and children leprosy patients in endemic and nonendemic areas. Interdiscip Perspect Infect Dis 2021; 2021: 8879809. https://doi.org/10.1155/2021/8879809
https://doi.org/10.1155/2021/8879809... .

Leprosy in children under 15 years of age in Brazil is a serious public health problem, with a high occurrence of cases¹²12. Vieira MCA, Nery JS, Paixão ES, Andrade KVF, Penna GO, Teixeira MG. Leprosy in children under 15 years of age in Brazil: a systematic review of the literature. PLoS Negl Trop Dis 2018; 12(10): e0006788. https://doi.org/10.1371/journal.pntd.0006788
https://doi.org/10.1371/journal.pntd.000... . In 2019, 27,864 new cases of leprosy were reported in Brazil, of which 1,545 (5.5%) were reported in children under 15 years of age and 2,351 (9.9%) presented DG at the time of diagnosis¹³13. Brasil. Secretaria de Vigilância em Saúde. Ministério da Saúde. Hanseníase 2022 [Internet]. Boletim Epidemiológico; 2022 [acessado em 10 out. 2022]. Disponível em: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/especiais/2022/boletim-epidemiologico-de-hanseniase-_-25-01-2022.pdf
https://www.gov.br/saude/pt-br/centrais-... ,¹⁴14. Brasil. Ministério da Saúde. Departamento de Informática do SUS. DATASUS. Acompanhamento dos dados de hanseníase – Brasil (2000-2017); 2019. [acessado em 4 de nov. de 2022] Disponível em: http://tabnet.datasus.gov.br/cgi/dhdat.exe?hanseniase/hantfma17.def
http://tabnet.datasus.gov.br/cgi/dhdat.e... .

Through a search in the literature, it was possible to identify few studies that proposed to analyze the occurrence of leprosy in children under 15 years of age in the Brazilian context. Thus, the objective of the study was to analyze the spatial distribution of leprosy and disabilities in children under 15 years of age in Cuiabá.

METHODS

This is an ecological study¹⁵15. Morgenstern H. Ecologic studies in epidemiology: concepts, principles, and methods. Annu Rev Public Health 1995; 16: 61-81. https://doi.org/10.1146/annurev.pu.16.050195.000425
https://doi.org/10.1146/annurev.pu.16.05... , using spatial and space-time analysis techniques, developed in the city of Cuiabá, capital of the state of Mato Grosso, Center-West Region of Brazil¹⁶16. Prefeitura de Cuiabá. Secretária Municipal de Saúde. Unidades Básicas de Saúde [Internet]. Cuiabá; 2019. [acessado em 10 out. 2022] Disponível em: https://www.cuiaba.mt.gov.br/secretarias/saude/atencao-basica/
https://www.cuiaba.mt.gov.br/secretarias...

17. Brasil. Instituto Brasileiro de Geografia e Estatística. Cidades. Cuiabá. Panorama [Internet] 2021. [acessado em 10 out. 2022] Disponível em: https://cidades.ibge.gov.br/brasil/mt/cuiaba/panorama
https://cidades.ibge.gov.br/brasil/mt/cu... -¹⁸18. Prefeitura de Cuiabá. Instituto de Planejamento e Desenvolvimento Urbano. Diretoria de Pesquisa e Informação. Perfil socioeconômico de Cuiabá, volume IV [Internet]. Cuiabá: Central de Texto, 2010. [acessado em 10 out. 2022] Disponível em: https://www.cuiaba.mt.gov.br/upload/arquivo/perfil_socioeconomico_de_cuiaba_Vol_IV.pdf
https://www.cuiaba.mt.gov.br/upload/arqu... . For the study, the 140 urban Human Development Units (HDU) in Cuiabá were considered as the ecological analysis unit¹⁹19. Atlas do Desenvolvimento Humano. Perfil. Mato Grosso, Centro-Oeste [Internet]. [acessado em 01 nov. 2022]. Disponível em: http://www.atlasbrasil.org.br/perfil/uf/51
http://www.atlasbrasil.org.br/perfil/uf/... .

Cuiabá has a territorial area of 3,266.538 km²2. Ploemacher T, Faber WR, Menke H, Rutten V, Pieters T. Reservoirs and transmission routes of leprosy: a systematic review. PLoS Negl Trop Dis 2020; 14(4): e0008276. https://doi.org/10.1371/journal.pntd.0008276.
https://doi.org/10.1371/journal.pntd.000... and an estimated population of 623,614 people in 2021¹⁷17. Brasil. Instituto Brasileiro de Geografia e Estatística. Cidades. Cuiabá. Panorama [Internet] 2021. [acessado em 10 out. 2022] Disponível em: https://cidades.ibge.gov.br/brasil/mt/cuiaba/panorama
https://cidades.ibge.gov.br/brasil/mt/cu... ,¹⁸18. Prefeitura de Cuiabá. Instituto de Planejamento e Desenvolvimento Urbano. Diretoria de Pesquisa e Informação. Perfil socioeconômico de Cuiabá, volume IV [Internet]. Cuiabá: Central de Texto, 2010. [acessado em 10 out. 2022] Disponível em: https://www.cuiaba.mt.gov.br/upload/arquivo/perfil_socioeconomico_de_cuiaba_Vol_IV.pdf
https://www.cuiaba.mt.gov.br/upload/arqu... . As socioeconomic indicators, the municipality has a percentage of people without schooling of 4.56% for women and 4.79% for men, Human Development Index (HDI) of 0.785 and Gini Index of 0.59. It should be noted that only 53.52% of its territory has a sewage system¹⁷17. Brasil. Instituto Brasileiro de Geografia e Estatística. Cidades. Cuiabá. Panorama [Internet] 2021. [acessado em 10 out. 2022] Disponível em: https://cidades.ibge.gov.br/brasil/mt/cuiaba/panorama
https://cidades.ibge.gov.br/brasil/mt/cu... ,¹⁸18. Prefeitura de Cuiabá. Instituto de Planejamento e Desenvolvimento Urbano. Diretoria de Pesquisa e Informação. Perfil socioeconômico de Cuiabá, volume IV [Internet]. Cuiabá: Central de Texto, 2010. [acessado em 10 out. 2022] Disponível em: https://www.cuiaba.mt.gov.br/upload/arquivo/perfil_socioeconomico_de_cuiaba_Vol_IV.pdf
https://www.cuiaba.mt.gov.br/upload/arqu... .

Regarding the health system, the city has 63 Family Health Programs (FHP), distributed in four administrative regions: North, with 13 FHP and 10 Family Health Strategies (FHS) teams; South, with 21 FHP and 20 FHS; East: with 15 FHP and 10 FHS; West, with 11 FHP and 8 FHS¹⁶16. Prefeitura de Cuiabá. Secretária Municipal de Saúde. Unidades Básicas de Saúde [Internet]. Cuiabá; 2019. [acessado em 10 out. 2022] Disponível em: https://www.cuiaba.mt.gov.br/secretarias/saude/atencao-basica/
https://www.cuiaba.mt.gov.br/secretarias... . As a study population, all new cases of leprosy in children under 15 reported in the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação – SINAN) in the period from 2008 to 2018 were considered²⁰20. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Sistema de Informação de Agravos de Notificação (SINAN) Hanseníase [Internet]. SINAN; 2022. [acessado em 03 nov. 2022]. Disponível em: http://portalsinan.saude.gov.br/hanseniase
http://portalsinan.saude.gov.br/hansenia... .

The study data included clinical and sociodemographic information of the notified cases, such as date of notification, date of birth, gender (male and female), education, operational classification (paucibacillary (PB); multibacillary (MB)), clinical form, evaluation of the DG at the time of diagnosis (DG 0, DG 1, and DG 2), and residence address. Access to the SINAN database was obtained through authorization from the Sanitary Surveillance Service of the Regional Health Management of Cuiabá, in November 2019.

After analyzing the consistency of the database, a descriptive analysis was performed with the aim of characterizing the profile of leprosy cases in children under 15 years of age.

In the spatial analysis stage, cases of leprosy in children under 15 years of age were georeferenced based on the geographic coordinates (latitude and longitude) of the residential addresses, using the QGIS 3.14 software. For this stage, cases whose addresses were not available (blank and/or incomplete) were excluded, also opting for the exclusion of cases from rural areas, due to the inaccuracy of location of geographic coordinates in these areas.

After georeferencing, the leprosy cases were spatially distributed through the digital mesh of urban HDU, made available at the Social Vulnerability Atlas of the Institute for Applied Economic Research (Atlas da Vulnerabilidade Social do Instituto de Pesquisa Econômica Aplicada – IVS – IPEA)²¹21. Instituto de Pesquisa Econômica Aplicada. Atlas da vulnerabilidade social nos municípios brasileiros [Internet]. Brasília: IPEA; 2015 [acessado em 10 out. 2022]. Disponível em: http://ivs.ipea.gov.br/images/publicacoes/Ivs/publicacao_atlas_ivs.pdf
http://ivs.ipea.gov.br/images/publicacoe... .

In order to verify the places with the highest occurrence of leprosy in children under 15 years of age with disabilities (higher density of cases), according to the HDU, the Kernel density estimate was used, which consists of an exploratory interpolation method based on the definition of circular areas around points of occurrence of a phenomenon (cases), so that it generates a density surface for the identification of clusters²²22. Silverman, BW. Density estimation for statistics and data analysis. Monographs on Statistics and Applied Probability [Internet]. London: Chapman and Hall; 1986 [acessado em 10 out. 2022]. Disponível em: https://ned.ipac.caltech.edu/level5/March02/Silverman/paper.pdf
https://ned.ipac.caltech.edu/level5/Marc... .

It is noteworthy that the search radius (bandwidth) used was the standard of the Esri® ArcGis™ Desktop 10.8 software, based on the Silverman bandwidth estimation formula, a non-parametric measure to estimate the probability density function of a random variable²²22. Silverman, BW. Density estimation for statistics and data analysis. Monographs on Statistics and Applied Probability [Internet]. London: Chapman and Hall; 1986 [acessado em 10 out. 2022]. Disponível em: https://ned.ipac.caltech.edu/level5/March02/Silverman/paper.pdf
https://ned.ipac.caltech.edu/level5/Marc... .

In order to identify clusters in space and space-time, the sweep statistics technique was applied²³23. Kulldorff M, Nagarwalla N. Spatial disease clusters: detection and inference. Stat Med 1995; 14(8): 799-810. https://doi.org/10.1002/sim.4780140809
https://doi.org/10.1002/sim.4780140809... whose hypotheses are: H₀: there are no clusters of leprosy cases in the HDU; H₁: there are clusters of leprosy cases in the HDU.

With a view to identifying purely spatial clusters²³23. Kulldorff M, Nagarwalla N. Spatial disease clusters: detection and inference. Stat Med 1995; 14(8): 799-810. https://doi.org/10.1002/sim.4780140809
https://doi.org/10.1002/sim.4780140809... , in which the distribution is heterogeneous and events are rare in relation to the general population, the discrete Poisson model was considered; no geographic overlapping of clusters; clusters with a maximum size equal to 50% of the exposed population; cluster with circular shape and 999 Monte Carlo replications. In addition, the spatial scanning technique was processed by controlling the occurrence of leprosy cases in children under 15 years of age by the size of the HDU population (population of children under 15 years of age) and attempts to detect clusters of high and low relative risks (RR). Type I error set at less than 5% was adopted as statistically significant (p<0.05).

For the space-time scan²³23. Kulldorff M, Nagarwalla N. Spatial disease clusters: detection and inference. Stat Med 1995; 14(8): 799-810. https://doi.org/10.1002/sim.4780140809
https://doi.org/10.1002/sim.4780140809... , the same parameters mentioned above were used, and the maximum size of the temporal cluster equal to 50% of the study period was added, with precision in years, in the period from 2008 to 2018.

Finally, the analysis of spatial variations in temporal trends (SVTT) was carried out, with the aim of detecting geographic regions that present differences in relation to their temporal trends. The method uses the period in a fixed way, which, in this case, was considered the year unit, and gradually searches, through spatial windows of different sizes, the temporal trend inside and outside each one of these, having as hypotheses: H₀, there are no differences between the temporal trends inside and outside the spatial windows; H₁, time trends are different inside and outside the spatial windows²⁴24. Anselin L. Local indicators os spatial association – LISA. Geographical Analysis 1995; 27(2): 93-115. https://doi.org/10.1111/j.1538-4632.1995.tb00338.x
https://doi.org/10.1111/j.1538-4632.1995... ,²⁵25. Moraga P, Kulldorf M. Detection of spatial variations in temporal trends with a quadratic function. Stat Methods Med Res 2016; 25(4): 1422-37. https://doi.org/10.1177/0962280213485312
https://doi.org/10.1177/0962280213485312... .

The SVTT analysis was performed considering a linear temporal trend from Poisson distribution: Y_ij~P₀(E_ij × θ_ij), where Y_ij and E_ij are, respectively, the observed and expected number of cases or events in a given area i and a period j, and θ_ij the relative risk in area i and period j²⁵25. Moraga P, Kulldorf M. Detection of spatial variations in temporal trends with a quadratic function. Stat Methods Med Res 2016; 25(4): 1422-37. https://doi.org/10.1177/0962280213485312
https://doi.org/10.1177/0962280213485312... .

For the model in question, the expected number of cases in each area was calculated using indirect standardization: Ec=p×CP, where E_c is the expected number of cases within the window under H₀; p is the population at the place of interest; C and P are the total number of cases and inhabitants, respectively.

The temporal trend was estimated using Poisson regression, considering time (in years) as an independent variable. Based on the count of occurrences of leprosy in children under 15 years of age, a maximum likelihood calculation was performed on all possible analysis windows. This maximum likelihood was compared with that of a large set of random data, derived from a Monte Carlo simulation, enabling statistical inference in the analyses²⁵25. Moraga P, Kulldorf M. Detection of spatial variations in temporal trends with a quadratic function. Stat Methods Med Res 2016; 25(4): 1422-37. https://doi.org/10.1177/0962280213485312
https://doi.org/10.1177/0962280213485312... .

It is important to highlight that the clusters identified in these analyses do not indicate that the number of cases is high or low in relation to the rest of the HDU, but only identifies their temporal trend in comparison to the rest of the study units²⁵25. Moraga P, Kulldorf M. Detection of spatial variations in temporal trends with a quadratic function. Stat Methods Med Res 2016; 25(4): 1422-37. https://doi.org/10.1177/0962280213485312
https://doi.org/10.1177/0962280213485312... .

The following parameters for the SVTT analysis were specified: type I error set at less than 5% (p<0.05), maximum spatial window size of the risk area of 50% of the study population; circular shape of the spatial window; maximum of 999 replications in Monte Carlo simulation; no geographic overlapping to report hierarchical clusters. Choosing the maximum size of the geographic cluster for 50% of the population was the usual recommendation for this type of analysis.

It should be noted that, for the spatial, space-time, and VETT analysis, the population of each HDU in Cuiabá (population of children under 15 years of age) was considered as the reference population (denominator) according to the last Demographic Census¹⁷17. Brasil. Instituto Brasileiro de Geografia e Estatística. Cidades. Cuiabá. Panorama [Internet] 2021. [acessado em 10 out. 2022] Disponível em: https://cidades.ibge.gov.br/brasil/mt/cuiaba/panorama
https://cidades.ibge.gov.br/brasil/mt/cu... .

For the analyses, the SaTScan software, version 9, was used, with choropleth maps (maps prepared with quantitative data using colors to establish a relationship between what is shown on the map and the caption), through the software Esri® ArcGis™ Desktop 10.8 and QGIS 3.14.

RESULTS

Between 2008 and 2018, there were variations in the detection rates of leprosy in children under 15 years of age in Cuiabá, with rates ranging from one to eight cases per 100,000 inhabitants in the period.

With the exclusion of duplicate notifications, 514 cases of leprosy were reported in children under 15 years of age in Cuiabá. Most cases were females (50.9%), mostly MB (52.5%), with dimorphic clinical form (46.3%). As for DG, 52 cases (10.1%) had DG 1, 12 (2.3%) had DG 2, and 148 cases (28.8%) were not evaluated at the time of diagnosis. Table 1 brings the main characteristics of the cases in the investigated period.

For the georeferencing stage of the cases, from the total (514) three notifications whose addresses belonged to the rural area of Cuiabá and three that had a blank and/or incomplete address were excluded, making a total of 508 remaining cases. Of the 508 cases, 462 were georeferenced, with a total of 90.9% of georeferencing.

Figure 1 shows the spatial distribution of the density of leprosy cases in children under 15 years of age in the HDU of Cuiabá, where it was found that the highest densities of cases are found in the northeast region of the municipality. Regarding cases with DG 0 (276 cases), the highest density of cases was identified in the central, north, and south areas of the municipality, while for cases with DG 1 (40 cases), the areas with the highest density were identified in the north and south, while the highest densities of DG 2 (10 cases) were located in the north region. Finally, regarding the cases not assessed for DG at the time of diagnosis (136 cases), a higher density of cases was found in the north, central, and south areas.

Using purely spatial scanning, four risk clusters were identified, cluster 1 with RR=15.71 (95%CI 11.90–20.74), cluster 2 with RR=2.47 (95%CI 2.03–3.00), cluster 3 with RR=8.28 (95%CI 4.43–14.56), and cluster 4 with RR=2.19 (95%CI 1.64–2.91).

With the space-time scan, the conformation of three high-risk clusters can be observed, being cluster 1 with RR=36.08 (95%CI 24.14–53.92) in the period between 2015 and 2016, cluster 2 with RR=3.36 (95%CI 2.55–4.42) in the period between 2014 and 2016, and cluster 3 with RR=87.74 (95%CI 32.91–233.87) in 2012.

Finally, with the application of SVTT, a cluster with an internal temporal trend of -30.86%/year and an external temporal trend of -2.28%/year was identified. The internal temporal trend represents the degree of growth or reduction in the number of leprosy cases over the years within the cluster, being compared with the external trend, that is, the trend throughout the city of Cuiabá not belonging to the same cluster. It was possible to observe that, in the identified cluster, the internal trend of reduction was more intense than the external trend, expressing a greater reduction in the number of leprosy cases, compared to the rest of the municipality.

Table 2 shows the clusters identified through purely spatial, spatio-temporal, and SVTT scanning techniques.

In Figure 2, it is evident that, with the results of applying the purely spatial scan, the cluster with the highest RR was located in the west and east regions (15.71), followed by a cluster located in portions of the west and north regions (8.28), with the cluster with the lowest RR located in the north and south regions (2.47 and 2.19) of the city. The same figure also shows the clusters identified through the space-time scan, with the cluster with the highest RR located in the southern region (87.74), followed by a cluster located in the western region (composed of a HDU with 36.08), and the cluster with the lowest RR located in the north and west regions (3.36). Finally, with the application of SVTT, a cluster located in the western region of Cuiabá was identified.

DISCUSSION

In Cuiabá, the spatial distribution of leprosy in children under 15 years of age is heterogeneous, with regions that have a higher concentration of cases and clusters of risk. Leprosy cases with physical disabilities were distributed across practically the entire urban area of Cuiabá, while the highest risk clusters were located in regions characterized by low socioeconomic indicators. The spatial analysis indicated the regions with the highest occurrence of leprosy in Cuiabá, bringing evidence that the municipality faces operational difficulties in controlling the disease, especially in early diagnosis.

Leprosy in children under 15 years of age in Cuiabá classifies the municipality as a scenario of very high endemicity for the disease, being one of the Brazilian cities that most notified the disease in the period from 2008 to 2018²⁶26. Martoreli Júnior JF, Ramos ACV, Alves JD, Crispim JA, Alves LS, Berra TZ, et al. Inequality of gender, age and disabilities due to leprosy and trends in a hyperendemic metropolis: evidence from an eleven-year time series study in Central-West Brazil. PLoS Negl Trop Dis 2021; 15(11): e0009941. https://doi.org/10.1371/journal.pntd.0009941
https://doi.org/10.1371/journal.pntd.000... .

Most cases were classified as MB and with a dimorphic clinical form. Studies indicate that people affected by the MB forms of the disease are more likely to develop physical disabilities, especially the involvement of hands and feet, impairing self-care and the functionality of the affected limb³3. Sanchez MN, Nery JS, Pescarini JM, Mendes AA, Ichihara MY, Teixeira CSS, et al. Physical disabilities caused by leprosy in 100 million cohort in Brazil. BMC Infect Dis 2021; 21(1): 290. https://doi.org/10.1186/s12879-021-05846-w
https://doi.org/10.1186/s12879-021-05846... ,²⁷27. Costa RMPG, Mendes LCB. Qualidade de vida dos sujeitos com sequelas pela hanseníase e autocuidado: uma revisão integrativa. Cienc Cuid Saude 2020; 19: e45649. https://doi.org/10.4025/ciencuidsaude.v19i0.45649
https://doi.org/10.4025/ciencuidsaude.v1... _.

As for DG, in Cuiabá, 10.1% had DG 1; and 2.3% had DG 2 at the time of diagnosis, so that the percentage of disabilities was 12.4%. Comparing with Brazil, in the period from 2009 to 2018, the observed proportion of DG 1 was 3.1%, whereas, for DG 2, the observed proportion was 2.7%²⁸28. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Hanseníase no Brasil: caracterização das incapacidades físicas [Internet]. Brasília: Ministério da Saúde; 2020 [acessado em 10 out. 2022]. Disponível em: https://bvsms.saude.gov.br/bvs/publicacoes/hanseniase_brasil_caracterizacao_incapacidades_fisicas.pdf
https://bvsms.saude.gov.br/bvs/publicaco... . These epidemiological data confirm that Cuiabá has a percentage of DG higher than the national average, especially DG 1, suggesting deficiencies in the early diagnosis of leprosy in the population studied²⁸28. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Hanseníase no Brasil: caracterização das incapacidades físicas [Internet]. Brasília: Ministério da Saúde; 2020 [acessado em 10 out. 2022]. Disponível em: https://bvsms.saude.gov.br/bvs/publicacoes/hanseniase_brasil_caracterizacao_incapacidades_fisicas.pdf
https://bvsms.saude.gov.br/bvs/publicaco... .

The proportion of new cases of leprosy diagnosed with DG, especially DG 2, is an important indicator of late diagnosis, especially in children under 15 years of age, indicating that this population, from an early age, already has contact with Mycobacterium leprae²⁷27. Costa RMPG, Mendes LCB. Qualidade de vida dos sujeitos com sequelas pela hanseníase e autocuidado: uma revisão integrativa. Cienc Cuid Saude 2020; 19: e45649. https://doi.org/10.4025/ciencuidsaude.v19i0.45649
https://doi.org/10.4025/ciencuidsaude.v1... ,²⁸28. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Hanseníase no Brasil: caracterização das incapacidades físicas [Internet]. Brasília: Ministério da Saúde; 2020 [acessado em 10 out. 2022]. Disponível em: https://bvsms.saude.gov.br/bvs/publicacoes/hanseniase_brasil_caracterizacao_incapacidades_fisicas.pdf
https://bvsms.saude.gov.br/bvs/publicaco... .

It is also noteworthy that a large portion did not present disabilities at the time of diagnosis (58.8%), but 30.7% were not evaluated, results that suggest fragility in health services as well as in the performance and qualification of health professionals, which may be linked to the management of the disease, and non-existence or non-adherence to protocols.

With the Kernel density estimator, it was possible to verify that the cases of leprosy with disabilities were distributed in practically the entire urban area of Cuiabá, however, areas with a higher concentration of cases were identified in the north and west administrative regions, followed by the east region.

Through spatial scanning, the highest RR were identified in the east and west regions with 15.71 and 8.28, respectively. It is worth mentioning that, in these regions, income varies between low, medium-low, and medium, with the fact that the highest rates related to demographic density are also found in these regions, suggesting a relationship between the occurrence of leprosy in children under 15 years of age and social vulnerability²⁹29. Castillo RR, Gascón LCH, Ruiz-Fuentes JL, Fundora FMP, Albajés CRR, Henao-Martínez AF, et al. Leprosy in children in Cuba: epidemiological and clinical description of 50 cases from 2012-2019. PLoS Negl Trop Dis 2021; 15(10): e0009910. https://doi.org/10.1371/journal.pntd.0009910
https://doi.org/10.1371/journal.pntd.000... ,³⁰30. Venkatakrishnan Y, Thangaraju P, Jeganathan S, Sankaran SK, Kannan R. Nutritional status and morbidity profile of children with leprosy contact in a rural community. Trop Doct 2020; 50(4): 311-7. https://doi.org/10.1177/0049475520932193
https://doi.org/10.1177/0049475520932193... .

Social vulnerabilities are an important aspect in leprosy, and the difficulty of accessing health services, the gaps in knowledge about the disease, often explained by the low quality and time of education/literacy, and the participation of people in society strongly generate the maintenance of the disease chain²⁹29. Castillo RR, Gascón LCH, Ruiz-Fuentes JL, Fundora FMP, Albajés CRR, Henao-Martínez AF, et al. Leprosy in children in Cuba: epidemiological and clinical description of 50 cases from 2012-2019. PLoS Negl Trop Dis 2021; 15(10): e0009910. https://doi.org/10.1371/journal.pntd.0009910
https://doi.org/10.1371/journal.pntd.000... . Malnutrition and incomplete immunization show risks for acquiring the disease³⁰30. Venkatakrishnan Y, Thangaraju P, Jeganathan S, Sankaran SK, Kannan R. Nutritional status and morbidity profile of children with leprosy contact in a rural community. Trop Doct 2020; 50(4): 311-7. https://doi.org/10.1177/0049475520932193
https://doi.org/10.1177/0049475520932193... .

With the space-time scan, three clusters of risk for leprosy were identified, involving the years 2012 to 2016. In Cuiabá, in 2015, local health services were mobilized to carry out actions related to active search for cases, focusing on schoolchildren aged 5 to 14 years, with campaigns to examine and treat this population and their possible contacts³¹31. Prefeitura de Cuiabá. Cuiabá é Destaque nas campanhas de busca e tratamento aos casos de hanseníase [Internet]. 2016 [acessado em 10 de out. 2022]. Disponível em: https://www.cuiaba.mt.gov.br/saude/cuiaba-e-destaque-nas-campanhas-de-busca-e-tratamento-aos-casos-de-hanseniase/12668
https://www.cuiaba.mt.gov.br/saude/cuiab... ,³²32. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de vigilância em Doenças Transmissíveis. Plano Integrado de ações estratégicas de eliminação da hanseníase, filariose, esquistossomose e oncocercose como problema de saúde pública, tracoma como causa de cegueira e controle das geohelmintíases: palno de ação 2011-2015 [Internet]. Brasília: Ministério da Saúde; 2013 [acessado em 10 out. 2022]. Disponível em: https://bvsms.saude.gov.br/bvs/publicacoes/plano_integrado_acoes_estrategicas_hanseniase.pdf
https://bvsms.saude.gov.br/bvs/publicaco... . The aforementioned campaign may have had an impact on the studied region, however, during the previous or subsequent years, no other strategy linked to the active detection of leprosy was found in public archives.

Based on the SVTT analysis, a cluster with an internal temporal trend of -30.86%/year and an external temporal trend of -2.28%/year was identified, located in the western region of Cuiabá. This result indicates that, within the agglomeration, the internal trend of reduction was more intense than the external trend, expressing a greater reduction in the number of leprosy cases, compared to the rest of the municipality.

It is noteworthy that the western region of Cuiabá has the lowest number of family health units in the municipality, so it is questionable whether the active search for cases is being carried out effectively, as well as whether this decreasing temporal trend is real or rather a reflection of underreporting/underdiagnosis of cases.

One can hypothesize that the municipality faces difficulties in the early diagnosis of the disease and, consequently, to prevent its continuous transmission. Studies carried out with leprosy cases in the same age group have already identified that early exposure to the pathogen led to a late diagnosis³³33. Lima RSK, Oliveira LBP, Gama RS, Ferreira JAG, Grossi MAF, Fairley JK, et al. A importância da busca ativa como estratégia de controle da hanseníase em territórios endêmicos. Hansen Int 2016; 41(1-2): 55-63.,³⁴34. Ruiz-Fuentes JL, Castillo RR, Gascón LCH, Pastrana F. Leprosy in children: a Cuban experience on leprosy control. BMJ Paediatr Open 2019; 3(1): e000500. https://doi.org/10.1136/bmjpo-2019-000500
https://doi.org/10.1136/bmjpo-2019-00050... .

The fact that there is DG 2 in children and adolescents is worrying, showing that it is far below the goal of reaching zero status of the disease³⁵35. Xavier MB, Tavares NCS, Corrêa SC, Gonçalves BK, Ramos MMAB, Macedo GMM. Correlation between the clinical forms of leprosy and the degree of neurological incapacity. Rev Para Med 2014; 28(2): 15-21.,³⁶36. World Health Organization. Leprosy/Hansen disease: contact tracing and post-exposure prophylaxis [Internet]. 2020 [acessado em 10 out. 2022]. Disponível em: https://www.who.int/publications/i/item/9789290228073
https://www.who.int/publications/i/item/... . Leprosy is highly disabling when not properly treated, especially in this population, which can influence school performance and cause problems related to social limitations, discrimination, self-esteem, and stigma³⁷37. Balata ILB. Incapacidade física em menores de 15 anos com diagnóstico de hanseníase [trabalho de conclusão de curso]. São Luís: Universidade Federal do Maranhão, Centro de Ciências Biológicas e da Saúde; 2018.. Classically, the presence of the disease is also related to stigma, especially when deformities occur¹1. World Health Organization. Guidelines for the diagnosis, treatment and prevention of leprosy [Internet]. Genebra: World Health Organization; 2018 [acessado em 10 out. 2022]. Disponível em: https://apps.who.int/iris/bitstream/handle/10665/274127/9789290226383-eng.pdf
https://apps.who.int/iris/bitstream/hand... . A comprehensive assessment of children under 15 years of age needs to be increased within the scope of Primary Health Care (PHC)³⁸38. Carneiro VCCB, Oliveira PTR, Carneiro SR, Maciel MC, Pedroso JS. Impact of expansion of primary care in child health: a population-based panel study in municipalities in the Brazilian Amazon. BMJ Open 2022; 12(3): e048897. https://doi.org/10.1136/bmjopen-2021-048897
https://doi.org/10.1136/bmjopen-2021-048... .

Effective actions to overcome leprosy involve more investments in health and the development of different intervention strategies in the community, both in research and surveillance in the community or critical territories and in the provision of individual care to children, adolescents and their families³⁹39. Khanna D, Wildt G, Duarte Filho LAMS, Bajaj M, Lai JF, Gardiner E, et al. Improving treatment outcomes for leprosy in Pernambuco, Brazil: a qualitative study exploring the experiences and perceptions of retreatment patients and their carers. BMC Infect Dis 2021; 21(1): 282. https://doi.org/10.1186/s12879-021-05980-5
https://doi.org/10.1186/s12879-021-05980... . Education and communication in health with the community is fundamental for the mobilization, awareness, and empowerment of people, especially in the age group of children under 15 and adolescents⁴⁰40. Oliveira JDCP, Marinus MWLC, Monteiro EMLM. Práticas de atenção à saúde de crianças e adolescentes com hanseníase: discursos de profissionais. Rev Gaúcha Enferm 2020; 41: e20190412. https://doi.org/10.1590/1983-1447.2020.20190412
https://doi.org/10.1590/1983-1447.2020.2...

41. Van’t Noordende AT, Kuipers P, Pereira ZBS. Strengthening personal and family resilience: a literature review for the leprosy context. Lepr Rev 2019; 90: 88-104.-⁴²42. Nasir A, Yusuf A, Listiawan MY, Makhfudli M. The lfe experience of leprosy families in maintaining interacton patterns in the family to support healing in leprosy patients in Indonesian society. A phenomenological qualitative study. PLoS Negl Trop Dis 2022; 16(4): e0010264. https://doi.org/10.1371/journal.pntd.0010264
https://doi.org/10.1371/journal.pntd.001... .

An ally in the fight against leprosy is chemoprophylaxis. According to World Health Organization (WHO) guidelines, single-dose rifampicin (SDR) as post-exposure prophylaxis (PEP) can be used in children and adolescents³⁶36. World Health Organization. Leprosy/Hansen disease: contact tracing and post-exposure prophylaxis [Internet]. 2020 [acessado em 10 out. 2022]. Disponível em: https://www.who.int/publications/i/item/9789290228073
https://www.who.int/publications/i/item/... . SDR-PEP can be studied by policy makers and/or health managers based on WHO recommendations and effectiveness and feasibility³⁶36. World Health Organization. Leprosy/Hansen disease: contact tracing and post-exposure prophylaxis [Internet]. 2020 [acessado em 10 out. 2022]. Disponível em: https://www.who.int/publications/i/item/9789290228073
https://www.who.int/publications/i/item/... ,⁴³43. Bandeira SS, Pires CA, Quaresma JAS. Leprosy reactions in childhood: a prospective cohort study in the Brazilian Amazon. Infect Drug Resist 2019; 12: 3249-57. https://doi.org/10.2147/IDR.S217181
https://doi.org/10.2147/IDR.S217181... ,⁴⁴44. Richardus JH, Tiwari A, Barth-Jaeggi T, Arif MA, Banstola NL, Baskota R, et al. Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme. Lancet Glob Health 2021; 9(1): e81-e90. 10.1016/S2214- https://doi.org/10.106/S2214-109X(20)30396-X
https://doi.org/10.106/S2214-109X(20)303... .

One of the limitations in this study was related to the database used, with secondary data, which may contain inconsistent information regarding quantity and quality, with the presence of ignored and/or incomplete data. Another limitation involves georeferencing, which allows identifying a certain number of locations in urban areas and is not accurate for rural areas. Finally, it should be noted that the analyses were processed by year, so that oscillations in case detection considering smaller units (months, days) could not be captured.

As a conclusion of the study, in Cuiabá, through the spatial analysis used, it was identified that leprosy in children under 15 years of age presents heterogeneous spatial behavior, located mainly in territories with social vulnerability and lack of health services. Based on the present study, a critical situation of leprosy in children under 15 years of age and the occurrence of disabilities can be observed, suggesting that the disease in the analyzed scenario constitutes a public health problem still far from being solved.

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