Abstract

INTRODUCTION

American visceral leishmaniasis (AVL), a zoonotic infection which affects both animals and humans, is caused by the Leishmania chagasi parasite, transmitted by Lutzomyia longipalpis . Human American visceral leishmaniasis (HAVL) is characterized by causing hepatosplenomegaly, presenting fever and affecting the body’s general state of health. It has a high rate of mortality if untreated and in malnourished children, affecting immune-depressed individuals, especially HIV carriers. ^aaMinistério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de vigilância e controle da leishmaniose visceral. Brasília (DF); 2006.

In Brazil, HAVL was a common disease in rural areas until the 1970s; it is now found in urban areas. ^aaMinistério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de vigilância e controle da leishmaniose visceral. Brasília (DF); 2006. Before 1990, 90% of cases occurred in the Northeast, the disease then expanded into all other regions of the country. The Northeast ^bbMinistério da Saúde. Secretaria de Vigilância em Saúde. Casos confirmados de Leishmaniose Visceral, Brasil, Grandes Regiões e Unidades Federadas: 1990 a 2010. Brasília (DF); 2011 [cited 2012 Jun 29]. Available from: http://portal.saude.gov.br/portal/arquivos/pdf/lv_casos_05_09_11.pdf is where 51.9% of cases in Brazil were recorded in 2009; 20.9% were in the North, 18.9% in the Southeast, 8.1% in the Midwest and 0.2% in the South. The number of reported cases increased by 89.9% between 1999 and 2009 (from 1,944 to 3,693) and the rate of mortality grew from 3.2% to 6.2%, almost tripling the number of deaths from the disease. ^bbMinistério da Saúde. Secretaria de Vigilância em Saúde. Casos confirmados de Leishmaniose Visceral, Brasil, Grandes Regiões e Unidades Federadas: 1990 a 2010. Brasília (DF); 2011 [cited 2012 Jun 29]. Available from: http://portal.saude.gov.br/portal/arquivos/pdf/lv_casos_05_09_11.pdf

The expansion of AVL is linked to the urbanization of the disease and the vector, to socio-environmental changes and to the difficulties of controlling the disease in large urban centers, where problems with malnutrition and poor housing and sanitation exist. ¹¹11 . Gontijo CMF, Melo MN. Leishmaniose visceral no Brasil: quadro atual, desafios e perspectivas. Rev Bras Epidemiol. 2004;7(3):338-49. DOI:10.1590/S1415-790X2004000300011
https://doi.org/10.1590/S1415-790X200400... Human and canine immigration from endemic areas have contributed to this expansion, introducing the L. chagasi parasite into new areas. ¹⁸18 . Scandar SAS, Silva RA, Cardoso Jr RP, Oliveira FH. Ocorrência de leishmaniose visceral americana na região de São José do Rio Preto, estado de São Paulo, Brasil. Bol Epidemiol Paulista. 2011;8(88):13-22. Human factors, civil construction projects and highways, among others, should also appear in the AVL epidemiological picture. Antonialli et al ¹1 . Antonialli SAC, Torres TG, Paranhos Filho AC, Tolezano JE. Spatial analysis of American Visceral Leishmaniasis in Mato Grosso do Sul State, Central Brazil. J Infect. 2007;54(5):509-14. DOI:10.1016/j.jinf.2006.08.004
https://doi.org/10.1016/j.jinf.2006.08.0... (2007) suggested that the spread of disease in Mato Grosso do Sul, MS, Midwestern Brazil, was influenced by three large scale projects: the Novoeste railway, the Vitória-Corumbá highway, and the Bolivia-Brazil gas pipeline.

Climatic factors may also be determinants in LVA epidemiology. Thus, the link between temperature, humidity, rainfall, and the presence of the sandfly have been investigated. ¹⁶16 . Oliveira AG, Galati EAB, Fernandes CE, Dorval MEC, Brazil RP. Seasonal variation of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in endemic area of visceral leishmaniasis, Campo Grande, state of Mato Grosso do Sul, Brazil. Acta Trop. 2008;105(1):55-61. DOI:10.1016/j.actatropica.2007.09.008
https://doi.org/10.1016/j.actatropica.20... ^{, 21}21 . Viana GMC, Nascimento MDSB, Rabelo EMF, Diniz-Neto JA, Binda Jr JR, Galvão CS et al. Relationship between rainfall and temperature: observations on the cases of visceral leishmaniasis in São Luis Island, State of Maranhão, Brazil. Rev Soc Bras Med Trop. 2011;44(6):722-4. DOI:10.1590/S0037-86822011000600013
https://doi.org/10.1590/S0037-8682201100...

Until 1998, HAVL cases recorded in the state of Sao Paulo were imported from other regions of Brazil and the first autochthonous cases appeared in Araçatuba City in 1999. ⁶6 . Camargo-Neves VLF, Katz G, Rodas LAC, Poletto DW, Lage LC, Spínola RMF, et al. Utilização de ferramentas de análise espacial na vigilância epidemiológica de leishmaniose visceral americana – Araçatuba, São Paulo, Brasil, 1998-1999. Cad Saude Publica. 2001;17(5):1263-7. DOI:10.1590/S0102-311X2001000500026
https://doi.org/10.1590/S0102-311X200100... This occurred after the detection of Lu. longipalpis in urban areas in 1997, ⁹9 . Costa IAP, Casanova C, Rodas L, Galati, EAB. Atualização da distribuição geográfica e primeiro encontro de Lutzomyia longipalpis em área urbana no Estado de São Paulo, Brasil. Rev Saude Publica. 1997;31(6):632-3. DOI:10.1590/S0034-89101997000700012
https://doi.org/10.1590/S0034-8910199700... followed by detection in canines in 1998. ⁶6 . Camargo-Neves VLF, Katz G, Rodas LAC, Poletto DW, Lage LC, Spínola RMF, et al. Utilização de ferramentas de análise espacial na vigilância epidemiológica de leishmaniose visceral americana – Araçatuba, São Paulo, Brasil, 1998-1999. Cad Saude Publica. 2001;17(5):1263-7. DOI:10.1590/S0102-311X2001000500026
https://doi.org/10.1590/S0102-311X200100... Since then, the disease has expanded into municipalities in the state, ¹⁰10 . Cutolo AA, Camargo DA, Zuben CJVN. Novos registros de Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae) na região Centro-Leste do estado de São Paulo, Brasil. Rev Bras Parasitol Vet. 2009;18(1):62-5. DOI:10.4322/rbpv.01801012
https://doi.org/10.4322/rbpv.01801012... ^{, c}cCentro de Vigilância Epidemiológica Prof. Alexandre Vranjak. LVAH – Casos autóctones e óbitos por LPI. São Paulo; 2009 [cited 2012 Jan 10]. Available from: http://www.cve.saude.sp.gov.br/htm/cve_leishvis.html with 1,919 cases and 169 deaths recorded by 2011.

The aim of this study was to analyze the expansion of HAVL and identify the key municipalities for developing surveillance and control activities.

METHODS

Reported autochthonous cases and deaths from HAVL between 1999 and 2011 in the state of Sao Paulo were the data used in the study. The state of Sao Paulo has 645 municipalities and a population of 41,262,199. The State Health Department divides the state into 17 administrative areas. The units of study were the 316 municipalities belonging to the following areas, which had reported autochthonous cases of HAVL: Araçatuba, Bauru, Marília, Presidente Prudente and São José do Rio Preto ( Figure 1A ).

The data were obtained from the Sao Paulo State Health Department. Center for Epidemiological Surveillance. ^ccCentro de Vigilância Epidemiológica Prof. Alexandre Vranjak. LVAH – Casos autóctones e óbitos por LPI. São Paulo; 2009 [cited 2012 Jan 10]. Available from: http://www.cve.saude.sp.gov.br/htm/cve_leishvis.html The number of inhabitants per municipality in the years in question were used, as were the geographical coordinates of their centroids in the Lat/Long SAD-69 system.

Data on temperature and rainfall were obtained from the Center for Integrated agrometeorological information of the Agronomic Institute (CIIAGRO – Centro Integrado de Informações Agrometeorológicas of the Instituto Agronômico ), Campinas. ^ddCentro Integrado de Informações Agrometeorológicas. Dados meteorológicos. São Paulo; 2009 [cited 2011Dec 1]. Available from: http://www.ciiagro.sp.gov.br Monthly values for temperature (ºC) measured in 60 meteorological posts in the municipalities in question were used.

The georeferenced map of the municipalities in the Lat/Long SAD-69 system, the route of the Marechal Rondon highway and the Novoeste railway and the populations of the municipalities were obtained from the Brazilian Institute of Geography and Statistics (IBGE). ^eeFundação Instituto Brasileiro de Geografia e Estatística. Informações Demográficas e Geográficas. Brasília (DF); 2011 [cited 2011 Dec 1]. Available from: www.ibge.gov.br The route of the Bolivia-Brazil gas pipeline was obtained from the Transportadora Brasileira Gasoduto Bolívia-Brasil website. ^ffTransportadora Brasileira Gasoduto Bolívia-Brasil. Gasoduto Bolívia-Brasil. Rio de Janeiro; 1997 [cited 2012 Apr 1] Available from: http://www.tbg.com.br

Annual rates for incidence and mortality and the case fatality rate from HAVL were calculated. Data on the year in which the first case(s) of HAVL occurred in each municipality were used to describe its expansion, evaluated together with the routes of the Bolivia-Brazil gas pipeline, the Marechal Rondon highway and the Novoeste railway.

Crude rates of incidence and mortality from HAVL were, respectively, calculated by dividing total cases and deaths by the population of each municipality in the middle of the period in question. Local Bayesian incidence and rates of mortality for HAVL were estimated using an empirical Bayes estimator, in which the Bayesian estimates were made locally, i.e., in relation to a local mean. ⁵5 . Câmara G, Carvalho MS, Cruz OG, Correa V. Análise espacial de áreas. In: Druck S, Carvalho MS, Câmara G, Monteiro AMV. Análise Espacial de dados geográficos. Brasília: Embrapa Cerrados; 2004. p.155-209. These rates were used to correct random fluctuation in crude rates in sparsely inhabited municipalities and to estimate possible underreporting of HAVL cases and deaths, especially in municipalities with few or no cases.

Empirical Bayesian rates were obtained by constructing a neighbor matrix for the municipalities, neighboring municipalities being those with at least one common border. TerraView Program version 4.1.0 was used to carry out these procedures. Choropleth maps were used to represent incidence and mortality rates, obtained using the ArcGIS program version 10.

Monthly mean temperature and rainfall were calculated for each of the 60 meteorological posts for the entire period of the study. Semivariance was calculated for each variable and used to create semivariograms, adjusted to a mathematical model. These show the existence of the spatial variability of the data, presenting the degree of dependence among the sample points. ²2 . Bailey TC, Gatrell AC. Interactive spatial data analysis. Essex: Longman Scientific &Technical; 1995. These analysis were carried out using the GS+ for Windows 5.0.3 Beta (GS+) Program. After detecting the spatial dependence shown in the semivariogram, values for the variables in non-sampled locations were estimated using Kriging interpolation ²2 . Bailey TC, Gatrell AC. Interactive spatial data analysis. Essex: Longman Scientific &Technical; 1995. and choropleth and contour maps obtained using the Surfer 6.01 Program.

The criteria established by the Ministry of Health ^aaMinistério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de vigilância e controle da leishmaniose visceral. Brasília (DF); 2006. for classifying Brazilian municipalities with HAVL transmission covers the last five years and the categories are: “no transmission” (mean number of cases = 0), “sporadic transmission” (mean number of cases > 0 and < 2.4, with values below the 80^thpercentile), “moderate transmission” (mean number of cases ≥ 2.4 and < 4.4, values between the 80^thand 90^thpercentiles) and intense transmission (mean number of cases ≥ 4.4, values equal to or above the 90^thpercentile). These criteria were used to classify the municipalities in question with transmission between 2007 and 2011. The same percentiles as in the criteria established by the Ministry of Health were used, but rates of incidence between 2007 and 2011 were used as cutoff points, giving a different classification (low, moderate and high incidence) which was compared with that obtained from the mean number of cases.

RESULTS

Figure 1B shows how HAVL spread in the administrative area of Araçatuba, from the main town (Araçatuba) to other municipalities in the area in 1999 (Birigui); in the administrative area of Bauru, with cases recorded in Promissão in 2002; in Marília, with cases in Guarantã, in 2003; in Presidente Prudente, with cases in Dracena and Ouro Verde, in 2005; and in Sao Jose do Rio Preto, with cases detected in Jales city, in 2007. Between 1999 and 2011, there were autochthonous cases of HAVL in 73 municipalities in the state.

The spread of HAVL was along a main axis of dissemination, from Northwest to Southeast, towards the area of Bauru, following the Marechal Rondon highway, the Novoeste railway and the construction of the Bolivia-Brazil gas pipeline. There was also a secondary axis that was derived from the main axis, which runs South towards the areas of Presidente Prudente and Marília and North towards Sao Jose do Rio Preto ( Figure 1B ).

After the first cases were detected in 1999, there was a steady increase in rates of incidence, peaking in 2008 then falling. Case fatality rates varied greatly between 1996 and 2006, before stabilizing from 2007 onwards, when the profile of the rate of mortality started to reflect that of the rate of incidence ( Figure 2A ).

There was a peak in incidences in the administrative area of Araçatuba in 2003 (19.0 cases/100,000 inhabitants) and Presidente Prudente in 2007 (10.9 cases/100,000 inhabitants), followed by a decline. Incidence in Bauru and Marília peaked in 2008, then fell. The rates of incidence in the Sao Jose do Rio Preto increased, although they were lower than those in the other areas. The rates in the five regions varied between 1.3 (Sao Jose do Rio Preto) and 6.3 cases per 100,000 inhabitants (Araçatuba) in 2011 ( Figure 2B ).

There was a higher concentration of municipalities with high HAVL incidence and rates of mortality in the region of Araçatuba, followed by Presidente Prudente and Marília ( Figures 3A and 3B ). In addition to correcting random fluctuations, the Bayesian rates indicated non-zero values for HAVL incidence and mortality in municipalities with no reports of cases in humans ( Figures 3C and 3D ).

There were higher mean temperatures in the Western and Northern regions, ( Figure 4A ). Rainfall levels behaved in the opposite way to temperature, presenting lower incidence in the West and North ( Figure 4B ). Municipalities where HAVL occurred earlier and those with the highest rates of incidence were found in the regions with the highest mean temperatures and lowest mean rainfall (administrative area of Araçatuba) ( Figures 1 and 4 ).

Figure 5A shows municipalities according to Ministry of Health classification of transmission occurring between 2007 and 2011 (mean number of cases in the last five years) and Figure 5B shows them classified according to incidence. In some situations there was no correspondence between the criteria used. Five municipalities were classed as having sporadic transmission according to the Ministry of Health criteria, but had high incidence (Irapuru, Nova Guataporanga, Pauliceia, Ouro Verde and Sao Joao do Pau D’Alho), and four municipalities with intense transmission were classified as low incidence (Araçatuba, Birigui, Lins, Bauru).

DISCUSSION

This study shows the geographical spread of HAVL in the state of Sao Paulo between 1999 and 2011, first identified in Araçatuba. ⁶6 . Camargo-Neves VLF, Katz G, Rodas LAC, Poletto DW, Lage LC, Spínola RMF, et al. Utilização de ferramentas de análise espacial na vigilância epidemiológica de leishmaniose visceral americana – Araçatuba, São Paulo, Brasil, 1998-1999. Cad Saude Publica. 2001;17(5):1263-7. DOI:10.1590/S0102-311X2001000500026
https://doi.org/10.1590/S0102-311X200100... Many factors explain this phenomenon: movement of people and goods on the highways and railways linking different regions of the country and their urban centers, migration, urbanization and poor sanitation, movement of infected animals and adaptation of the vector, among others, as well as the need to structure health care teams. ¹1 . Antonialli SAC, Torres TG, Paranhos Filho AC, Tolezano JE. Spatial analysis of American Visceral Leishmaniasis in Mato Grosso do Sul State, Central Brazil. J Infect. 2007;54(5):509-14. DOI:10.1016/j.jinf.2006.08.004
https://doi.org/10.1016/j.jinf.2006.08.0... ^{, 3}3 . Barata RB. Cem anos de endemias e epidemias. Cienc Saude Coletiva. 2000;5(2):333-45. DOI:10.1590/S1413-81232000000200008
https://doi.org/10.1590/S1413-8123200000... ^{, 15}15 . Mestre GLC, Fontes CJF. A expansão da epidemia da leishmaniose visceral no estado de Mato Grosso, 1998-2005. Rev Soc Bras Med Trop. 2007;40(1):42-8. DOI:10.1590/S0037-86822007000100008
https://doi.org/10.1590/S0037-8682200700... ^{, 18}18 . Scandar SAS, Silva RA, Cardoso Jr RP, Oliveira FH. Ocorrência de leishmaniose visceral americana na região de São José do Rio Preto, estado de São Paulo, Brasil. Bol Epidemiol Paulista. 2011;8(88):13-22. ^{, 23}23 . Ximenes MFFM, Silva VPM, Queiroz PVS, Rego MM, Cortez ALM, Batista LMM, et al. Flebotomíneos (Díptera:Psychodidae) e Leishmanioses no Rio Grande do Norte, Nordeste do Brasil – Reflexos do ambiente antrópico. Neotrop entomol. 2007;36(1):128-37. DOI:10.1590/S1519-566X2007000100016
https://doi.org/10.1590/S1519-566X200700...

Barata ³3 . Barata RB. Cem anos de endemias e epidemias. Cienc Saude Coletiva. 2000;5(2):333-45. DOI:10.1590/S1413-81232000000200008
https://doi.org/10.1590/S1413-8123200000... (2000) highlights the impact of substituting breeding livestock with sugar cane plantations in the state of Sao Paulo as having an impact on the spread of HAVL. This business involves migrant labor, often from the Northeast, where the disease is endemic. The introduction of HAVL due to migration by individuals from Minas Gerais state is also plausible. A study carried out in the metropolitan area of Belo Horizonte, MG, Southeastern Brazil, showed the HAVL transmission began in 1989, increasing significantly between 1998 and 1999, when cases of HAVL were diagnosed in 15 (42%) of the 36 municipalities in the metropolitan area. ¹²12 . Luz ZMP, Pimental DN, Cabral ALLV, Fiúza VOP, Rabello A. A urbanização das leishmanioses e a baixa resolutividade diagnóstica em municípios da Região Metropolitana de Belo Horizonte. Rev Soc Bras Med Trop. 2001;34(3):249-54. DOI:10.1590/S0037-86822001000300004
https://doi.org/10.1590/S0037-8682200100... The period in which reporting and spread of the disease increased coincides with the period in which the first human and canine cases of the disease were detected in the region of Araçatuba. ⁶6 . Camargo-Neves VLF, Katz G, Rodas LAC, Poletto DW, Lage LC, Spínola RMF, et al. Utilização de ferramentas de análise espacial na vigilância epidemiológica de leishmaniose visceral americana – Araçatuba, São Paulo, Brasil, 1998-1999. Cad Saude Publica. 2001;17(5):1263-7. DOI:10.1590/S0102-311X2001000500026
https://doi.org/10.1590/S0102-311X200100...

The hypothesis that the disease originated in the state of Mato Grosso do Sul should also be considered. Cases of AVL in humans and dogs showing symptoms of the disease were observed in the municipality of Corumbá, MS, Midwestern Brazil, from 1980 onwards. HAVL spread to other municipalities from 1998. The first cases of AVL in humans in Campo Grande, MS, were diagnosed in 1999, ¹1 . Antonialli SAC, Torres TG, Paranhos Filho AC, Tolezano JE. Spatial analysis of American Visceral Leishmaniasis in Mato Grosso do Sul State, Central Brazil. J Infect. 2007;54(5):509-14. DOI:10.1016/j.jinf.2006.08.004
https://doi.org/10.1016/j.jinf.2006.08.0... the same year in which the disease was detected in Sao Paulo State. This hypothesis is reinforced by the fact that the municipalities in Araçatuba share a border with Mato Grosso do Sul, and the link between the two regions is facilitated by the Marechal Rondon highway and the Novoeste railway.

Antonialli et al ¹1 . Antonialli SAC, Torres TG, Paranhos Filho AC, Tolezano JE. Spatial analysis of American Visceral Leishmaniasis in Mato Grosso do Sul State, Central Brazil. J Infect. 2007;54(5):509-14. DOI:10.1016/j.jinf.2006.08.004
https://doi.org/10.1016/j.jinf.2006.08.0... (2007) noted that the spread of AVL in Mato Grosso do Sul followed the construction of the Bolivia-Brazil gas pipeline, both in space and time, and raised the hypothesis that this may have been a factor in the spread of the disease in this state. The same hypothesis can be considered as partially explaining the spread of the disease in Sao Paulo, where the pipeline was constructed between 1997 and 1999, linking the cities of Castilho – in the area of Araçatuba, bordering Mato Grosso do Sul – with Campinas. Construction of the pipeline involved recruiting large numbers of workers from different regions of Brazil, among them Mato Grosso do Sul, Minas Gerais and the Northeast, who were constantly moving as the gas pipeline construction advanced. ^ffTransportadora Brasileira Gasoduto Bolívia-Brasil. Gasoduto Bolívia-Brasil. Rio de Janeiro; 1997 [cited 2012 Apr 1] Available from: http://www.tbg.com.br

Transporting infected and/or ill dogs, from various regions of Brazil with AVL transmission may have contributed to the introduction and spread of the disease in other areas. ¹⁵15 . Mestre GLC, Fontes CJF. A expansão da epidemia da leishmaniose visceral no estado de Mato Grosso, 1998-2005. Rev Soc Bras Med Trop. 2007;40(1):42-8. DOI:10.1590/S0037-86822007000100008
https://doi.org/10.1590/S0037-8682200700... Scandar et al ¹⁸18 . Scandar SAS, Silva RA, Cardoso Jr RP, Oliveira FH. Ocorrência de leishmaniose visceral americana na região de São José do Rio Preto, estado de São Paulo, Brasil. Bol Epidemiol Paulista. 2011;8(88):13-22. (2011) indicate that the introduction of the parasite in regions with no transmission may have occurred by asymptomatic dogs, which were thus not put down, arriving from other areas. Circulation of people, animals and goods between municipalities in the same endemic area may have influenced the spread of the disease, as observed by Mestre & Fontes ¹⁵15 . Mestre GLC, Fontes CJF. A expansão da epidemia da leishmaniose visceral no estado de Mato Grosso, 1998-2005. Rev Soc Bras Med Trop. 2007;40(1):42-8. DOI:10.1590/S0037-86822007000100008
https://doi.org/10.1590/S0037-8682200700... (2007).

Rates of incidence peaked then fell, which may be linked to the surveillance and control activities developed and/or to the cyclical behavior of the disease, except in Sao Jose do Rio Preto, where HAVL was most recently introduced. Ximenes et al ²³23 . Ximenes MFFM, Silva VPM, Queiroz PVS, Rego MM, Cortez ALM, Batista LMM, et al. Flebotomíneos (Díptera:Psychodidae) e Leishmanioses no Rio Grande do Norte, Nordeste do Brasil – Reflexos do ambiente antrópico. Neotrop entomol. 2007;36(1):128-37. DOI:10.1590/S1519-566X2007000100016
https://doi.org/10.1590/S1519-566X200700... (2007) showed the cyclical pattern of the disease in the state of Rio Grande do Norte, Northeastern Brazil, and suggested a period of ten years per cycle. Werneck et al ²²22 . Wernek GL, Pereira TJCF, Farias GC, Silva FO, Chaves FC, Gouvêa MV, et al. Avaliação da efetividade das estratégias de controle da leishmaniose visceral na cidade de Teresina, Estado do Piauí, Brasil: resultados do inquérito inicial – 2004. Epidemiol Serv Saude. 2008;17(2):87-96. DOI:10.5123/S1679-49742008000200002
https://doi.org/10.5123/S1679-4974200800... (2008) identifies a similar pattern in Teresina, PI, Northeastern Brazil. Although the foundations of the control measures are backed up by theory, there is no evidence of their effectiveness. ²²22 . Wernek GL, Pereira TJCF, Farias GC, Silva FO, Chaves FC, Gouvêa MV, et al. Avaliação da efetividade das estratégias de controle da leishmaniose visceral na cidade de Teresina, Estado do Piauí, Brasil: resultados do inquérito inicial – 2004. Epidemiol Serv Saude. 2008;17(2):87-96. DOI:10.5123/S1679-49742008000200002
https://doi.org/10.5123/S1679-4974200800... These measures have not been effective in controlling the spread of the disease, which is spreading throughout the state of Sao Paulo, an example of what is occurring in the country as a whole. ^aaMinistério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de vigilância e controle da leishmaniose visceral. Brasília (DF); 2006.

Using local empirical Bayesian rates meant that random fluctuations in incidence and rates of mortality were reduced. ²⁰20 . Souza WV, Barcellos CC, Brito AM, Carvalho MS, Cruz OG, Albuquerque MFM, et al. Aplicação de modelo bayesiano empírico na análise espacial da ocorrência de hanseníase. Rev Saude Publica. 2001;35(5):474-80. DOI:10.1590/S0034-89102001000500011
https://doi.org/10.1590/S0034-8910200100... By indicating locations with no reports of HAVL, but with estimated incidence > 0, these rates allowed to identified the key municipalities for the development of surveillance and control activities, either for being in the neighborhood of municipalities with confirmed transmission or due a possible underreporting of HAVL cases, estimated at between 42% and 45% by Maia-Elkhoury et al ¹³13 . Maia-Elkhoury ANS, Carmo EH, Sousa-Gomes ML, Mota E. Análise dos registros de leishmaniose visceral pelo método de captura-recaptura. Rev Saude Publica. 2007;41(6):931-7. DOI:10.1590/S0034-89102007000600007
https://doi.org/10.1590/S0034-8910200700... (2007).

The vector was present in some municipalities with empirical Bayesian rates of incidence > 0 and with no reports of HAVL cases. The others are included in the list of the 363 municipalities in the state of Sao Paulo which are classified as vulnerable, due to proximity and/or movement of people and goods from areas with transmission. ⁸8 . Comitê de Leishmaniose Visceral Americana da Secretaria de Estado da Saúde de São Paulo, SP, Brasil. Classificação epidemiológica dos municípios segundo o Programa de Vigilância e Controle da Leishmaniose Visceral Americana no Estado de São Paulo, atualizado em novembro de 2011. Bol Epidemiol Paulista. 2011;8(96):32-6. Municipalities in this situation could be viewed as key for surveillance and control activities.

Municipalities with identified incidence of HAVL, with no mortality and empirical Bayesian rates > 0, need to be investigated to verify the occurrence of underreporting of deaths, estimated at between 46% and 53%. ¹³13 . Maia-Elkhoury ANS, Carmo EH, Sousa-Gomes ML, Mota E. Análise dos registros de leishmaniose visceral pelo método de captura-recaptura. Rev Saude Publica. 2007;41(6):931-7. DOI:10.1590/S0034-89102007000600007
https://doi.org/10.1590/S0034-8910200700... This should take place mainly in those with recent transmission, where neither the population nor the health care professionals are alert to the problem of the disease.

The stratification proposed by the Ministry of Health ^aaMinistério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de vigilância e controle da leishmaniose visceral. Brasília (DF); 2006. enabled those municipalities with cases reported in the last five years to be assessed and prioritized. Of the 64 municipalities with autochthonous cases between 2007 and 2011, 12 had intense transmission, seven with high rates of incidence (Dracena, Panorama, Junqueirópolis, Tupi Paulista, Pacaembu, Flórida Paulista and Adamantina). Five municipalities with high rates of incidence were classified as having sporadic transmission due to their small populations. Regional centers playing a significant part in the spread of AVL, such as Araçatuba, Birigui, Bauru and Lins, considered as having intense transmission by the Ministry of Health, were classes as having the lowest level of incidence.

Both sets of criteria have some faults. That of the Ministry of Health, as it only considers the mean number of cases and so is not sensitive in identifying municipalities with high rates of incidence, and the classification according to the incidence fails to identify epidemiologically important municipalities. Using the mean number of cases together with incidence would produce classification criteria better able to identify key municipalities for developing surveillance and control actions, especially those municipalities with a high rate of incidence and a small number of cases. ^aaMinistério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância Epidemiológica. Manual de vigilância e controle da leishmaniose visceral. Brasília (DF); 2006. These are those on the secondary axis of AVL spread, south towards the regions of Presidente Prudente and Marília (SP). Surveillance and control measures such as educational activities aimed at reporting cases, censuses of canines and environmental management need to be intensified.

The large variation in case fatality rate from HAVL between 1999 and 2006, before the figures stabilized in 2007, may be related to the learning curve of the health care professionals providing care. Oliveira et al ¹⁷17 . Oliveira JM, Fernandes AC, Dorval MEC, Alves TP, Fernandes ID, Oshiro ET, et al. Mortalidade por leishmaniose visceral: aspectos clínicos e laboratoriais. Rev Soc Bras Med Trop. 2010;43(2):188-93. DOI:10.1590/S0037-86822010000200016
https://doi.org/10.1590/S0037-8682201000... (2010) reported that early identification of certain clinical and laboratorial characteristics of HAVL is extremely important in reducing mortality, as the appropriate treatment and preventative measures are taken. These procedures are more necessary in municipalities where transmission has most recently been identified.

The occurrence of the first cases of HAVL in the region with higher mean temperatures and lower mean rainfall may reflect the preference of Lu longipalpis for the drier, hotter areas of the state. Therefore, the spread into cooler more humid regions, such as municipalities in the areas of Bauru and Marília, show how the vector has adapted to other climates. Microclimate may be more significant to the vectors survival than macroclimate, as the adults prefer to live in humid locations. ⁴4 . Brazil RP, Brazil BG. Biologia de flebotomíneos neotropicais. In: Rangel EF, Laison R, organizadores. Flebotomíneos do Brasil. Rio de Janeiro: Editora Fiocruz; 2003. p.257-74. Silva et al ¹⁹19 . Silva JGD, Werneck GL, Cruz MSP, Costa CHN, Mendonça IL. Infecção natural de Lutzomyia longipalpis por Leishmania sp. em Teresina, Piauí, Brasil. Cad Saude Publica. 2007;23(7):1715-20. DOI:10.1590/S0102-311X2007000700024
https://doi.org/10.1590/S0102-311X200700... (2007), in a yearlong study, stated that the most humid months coincide with higher frequency of the vector and with a greater number of vectors infected with Leishmania sp.

If the macroclimate in the state of Sao Paulo did not play an essential role in the spread of AVL, the factors which would determine the spread of the disease to parts previously untouched may be deemed to be the same as those which affect or affected the spread to the regions studied. This conclusion, to be verified in future studies, together with accumulated experiences of surveillance and control, may serve as the basis for structuring activities aiming to at least delay the spread of AVL in the state of Sao Paulo.

Using Geographic Information Systems (GIS) and spatial analysis aids in describing the spread of disease, enabling patterns of occurrence and probable risk factors to be identified. ⁷7 . Carvalho MS, Souza-Santos R. Análise de dados espaciais em saúde pública: métodos, problemas, perspectivas. Cad Saude Publica. 2005;21(2):361-78. DOI:/10.1590/S0102-311X2005000200003
https://doi.org/10.1590/S0102-311X200500... ^{, 14}14 . Marshall RJ. A review of methods for the statistical analysis of spatial patterns of diseases. J R Statist Soc. 1991;154(3):421-41. DOI:10.2307/2983152
https://doi.org/10.2307/2983152... Using empirical Bayesian estimator in this study meant that random variations in incidence and mortality rates were reduced and highlighted key municipalities for developing surveillance and control activities. Using geostatistics, another technique of spatial analysis, it was possible to visualize climatic variables and compare them with the behavior of HAVL.

Using secondary data and passive notification, with the likelihood of underreporting of cases, and the use of an ecological design, are some of the limitations of this study. In spite of this, the study enabled the spread of HAVL in the state of Sao Paulo to be described and indicated possible determinants. Among these, the Marechal Rondon highway, the Novoeste railway and the construction of the Bolivia-Brazil gas pipeline and the role of climatic, environmental and socio-economic variables in spreading AVL will be the target of more in-depth studies.

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