SPACIALITY OF HUMAN VISCERAL LEISHMANIASIS IN THE STATE OF MARANHÃO, BRAZIL

Objective: the study analyzed the spatio-temporal and epidemiological behavior of HVL in the state of Maranhão, between 2010 and 2020. Theoretical framework: In Brazil, HVL is one of several diseases with compulsory notification, and is registered in 21 Federation Units, establishing itself in the five Brazilian regions. The Northeast region has the highest number of recorded cases, considered a focus of transmission of the disease, with Maranhão being one of the states with the highest occurrence. Method: the study used secondary data from the Notifiable Diseases Information System. The incidence rate, lethality rate, mortality rate, Odds Ratio and Annual Increment Rate were calculated. Results and conclusions : pointed to an endemic scenario of the disease. The predominant profile was male, aged between 1 and 9 years old, brown color/race, primary education and urban residence area. It is necessary to monitor the environment where vectors are present to control them and reduce the possibility of illness. Implications: the study is relevant as it contributes with epidemiological data and health indicators from an endemic region, so that health authorities can implement surveillance actions, health education and carry out public health interventions respecting socioeconomic differences and local environmental. Novelty: the identification of areas at risk for the disease in a given region allows us to know their spatiality, the population's chances of becoming ill and the rate of increase in the disease


INTRODUCTION
Visceral Leishmaniasis (VL) is a disease of global relevance, endemic in 76 countries.It is considered a compulsorily notifiable zoonosis, classified as Neglected Tropical Disease (NTD).In the Americas, LV remains a challenge for national and regional surveillance and control programs, due to its high incidence and wide geographical distribution (BRAZIL, 2021a;PAHO, 2021).This is the most serious form of leishmaniasis, with a high lethality and mortality rate (PAHO, 2021).
Public health policies are necessary for the monitoring and prevention of neglected diseases.Through them, the Federal Government regulates the ways for the control and reduction of cases.In this context, for the LV, the Department of Epidemiological Surveillance of the Ministry of Health, in 2006, established the Visceral Leishmaniasis Surveillance and Control Program (PVC-LV), which aims actions to identify cases of the disease, facilitate access to diagnosis and appropriate treatment, as well as, train professionals and raise awareness among the population (BRAZIL, 2021a).Among the strategies of PVC-LV are prevention measures directed towards the human population, canine, combating the vetora, spraying insecticides and environmental management.However, due to the epidemiological characteristics and the still insufficient knowledge about the transmission of VL, these control strategies are still not very effective.In this context, health education actions must be prioritized and able to mobilize the population in order to prevent the spread of the disease and its social and economic impacts (BRAZIL, 2019).To strengthen surveillance and control of Leishmaniasis in the Americas, the Pan American Health Organization (PAHO, 2017) has instituted an action plan to carry out technical cooperation, missions, consultancies and training.In Brazil, Technical Note No. 5/2021-CGZV/DEIDT/SVS/MS proposes the incorporation of insecticide-impregnated collars for the control of VL in priority municipalities, classified as high, intense and very intense transmission (BRASIL, 2021b).
In Brazil, the disease has a high incidence and has been related to urbanization and rural exodus, inadequate basic sanitation conditions associated with socioeconomic characteristics becoming a public health and geographical expansion problem (RODRIGUES et al., 2017).The Northeast region has the highest number of cases of VL, considered a focus of disease transmission, Maranhão being one of the states with the highest case record (LIMA et al., 2021).

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The municipalities that concentrated about 80% of the new cases of LV are to be found in the states of Bahia (54), Ceará (48) and Maranhão (45) (IPEA, 2016).
VL is considered a disease whose conditions of transmission depend mainly on local factors.An intervention program will be more effective when targeted at higher risk groups and specific control measures to which it will be implemented (WERNECK 2014).This study analyzed the spatio-temporal and epidemiological behavior of VL in the state of Maranhão, between 2010 and 2020.

THEORETICAL FRAME
Neglected Tropical Diseases (NTDs) are a set of diseases prioritized by the World Health Organization (WHO), caused by infectious agents or parasites, that are intrinsically related to public health, especially in densely populated and/or impoverished tropical areas.(BODIMEADE; MARKS; MABEY, 2019; ENGELS; ZHOU, 2020).The greatest burden of NTDs has occurred in countries with the lowest Human Development Index (HDI) (MACHADO DE ASSIS; RABELLO; COTA, 2021).According to the World Health Organization (WHO, 2022a), NTDs are prevalent in 149 tropical and subtropical countries, with a high morbidity and mortality rate.
DTNs are distributed mainly in areas where there is a shortage of health services, basic sanitation and inadequate drinking water coverage (BODIMEADE; MARKS; MABEY, 2019; ENGELS; ZHOU, 2020).In addition, factors such as deforestation, lack of control over the use of natural resources and low educational level make it possible to maintain poverty (MACHADO DE ASSIS; RABELLO; COTA, 2021).The challenges for its containment include prevention and treatment, the negative impact on social conditions and the high capacity for geographical expansion (PAHO, 2017).This disease was considered to be rural, but with urbanization and migratory flow, the problem became a public health problem (BATISTA et al., 2021).
Among NTDs, Visceral Leishmaniasis (VL), caused by protist Leishmania chagasi, is included among the 10 WHO absolute priority endemics worldwide (BRAZIL, 2019).It is endemic in 13 countries in America, with approximately 97% of reported cases occurring in Brazil, and with a record also in Argentina, Bolivia, Colombia, Guatemala, Honduras, Mexico, Paraguay, Venezuela and Uruguay (PAHO 2020).LV has a major economic impact and is representative as a social problem.This disease, when not treated, can lead to death.
The control of VL is linked to strategies and actions that aim to reduce incidence, mortality, lethality and morbidity, starting from the diagnosis and early treatment of cases.These strategies and actions include home visits, health education activities, canine surveys, treatment of sick dogs, entomological surveys (catching and identifying phlebotomus) and spraying in risk areas.Understanding the dynamics of vector populations is relevant to establish effective control strategies and interrupt the transmission chain between hosts and reservoirs (BRAZIL, 2014).
The Flebotomíneos, previously restricted to rural regions, have expanded to different habitats of urban and peri-urban areas and are found distributed throughout Brazilian territory.The study by Capucci et al., 2023 identified that increasing environmental changes and deforestation make possible the risk of generating ecological imbalance and increasing cases of leishmaniasis, indicating the relevance of the need to have prevention and control strategies.
The planning and implementation of public policies for the control of VL should take into account, that Brazil is one of the countries with the greatest discrepancy in terms of wealth distribution (RIBEIRO et al., 2021) and, in this sense, there is need to decrease social inequalities, as well as perform early diagnosis, along with effective patient management and social awareness.Furthermore, actions to expand basic sanitation, access to education and health services are necessary to improve the living conditions of vulnerable populations, avoiding an increase in the prevalence of LV in Brazil.The epidemiology of the disease is directly linked to social vulnerability, infrastructure and influence of environmental factors.(WIJERATHNA et al., 2017;WHO, 2021).
In 1913, the first case of visceral leishmaniasis (VL) was recorded in Brazilian territory (state of Mato Grosso, Central-West region), and from 1980, with the intensification of the expansion and urbanization of the cities, epidemics have been observed.A study carried out in the states of the Midwest region found that the occurrence of VL is related to the epidemiological characteristics that included: climatic variables (temperature and precipitation); socioeconomic factors (with prevalence in low-income populations; individuals living in the urban zone and male sex; age from zero to 14 years; deaths from the age of 40 and highlighting from the age of 60); vulnerability of urban infrastructure (areas with population agglomerations, migratory flow, environmental degradation, inadequate hygienic-sanitary conditions; anthropic disorders); presence of the vetora, dogs and other animals.Studies related to the regional aspects of VL epidemiology can help in the adoption of strategies for better effectiveness in its control (ÀVILA, et al, 2023).
In Brazil, despite the efforts for early diagnosis and adequate treatment for VL, 5-10% of the cases still show a fatal outcome.The state of Mato Grosso is endemic to the disease and from 2007 to 2018, of the 377 cases registered, 46 (12.2%) evolved to death by LV.Late diagnosis was the cause of fatal VL outcomes.In this context, it is necessary to strengthen primary care services for the early recognition and treatment of the disease (CARVALHO et al., 2022).

METHODOLOGY
It is an ecological study with a time series analysis, descriptive and quantitative.It made use of secondary data from the Information System of Agravos and Notifications (SINAN), available in the TABNET program of the IT department of the Brazilian Unified Health System (DATASUS), referring to the total number of human cases of VL in Maranhão, per year of notification (2010 to 2020), as well as population data.
The variables analyzed were sex, age group, color/race, schooling, zone of residence and evolution (cure and death).Ignored or blank fields refer to information not being filled in.In the variable of schooling there was the sum of the categories of incomplete and complete education, as well as of the ignored (Ig), blank (Br) and not applicable (NA).
The Generalized Linear Model (GLM) with Poisson distribution was used to understand the association of VL with epidemiological factors.For the variables sex, age, schooling, color/race and zone of residence, the Odds Ratio (odds ratio) and Confidence Interval (95% CI) were calculated.
The incidence rate was calculated according to Brazil ( 2014) and the mortality rate was calculated according to Almeida et al. (2020).The analysis of the Annual Increment Rate (TIA) used the Prais-Winsten regression to understand the dynamics of the disease by variable over the years.In this manner, it was possible to understand if the disease showed tendencies for growth, diminution or stability during the period.The calculation was based on the study by Antunes (2005) and applied by Böhm et al. (2016), which calculated the TIA from the regression data: TIA= [-1+(10b)]*100, where b is the slope coefficient of the line in the Prais-Winsten regression.The trends were considered significant when the p-values of regression showed α ≤ 0.05.Otherwise, the trends were found to be stable.The analyzes were elaborated in the PAST 4.10 Statistical Program.
The spatial analysis of human LV (LVH) was performed in the state of Maranhão which has 217 municipalities and an estimated area of 332 thousand km² (Figure 1).The maps were  It should be noted that there was no need for submission to the Research Ethics Committee, since it is a study on official secondary data in the public domain, without the identification of the subjects.This survey meets CONEP Resolution No. 466/2012.

RESULTS AND DISCUSSION
In Brazil, between 2010 and 2020, 38,634 cases of VHL were registered and of these 13.79% (5,329 cases) were reported in Maranhão, being the most prevalent in the Northeast region.It can be observed that between 2016 and 2018, the prevalence of VHL in Maranhão was above 10% (Figure 2).Of the 217 municipalities that make up the State, 136 (62.7%) had at least one confirmed case of LVH.The municipality of São Luís do Maranhão presented the 6 highest prevalence of cases notified (40.68%), followed by Imperatriz (12.01%) and Caxias (5.48%), which together represent 58.17% of the total of cases of the state.LV is constantly expanding worldwide.In Brazil, its distribution is recorded in all regions.The Northeast region stands out with higher prevalence of cases (53.9%) in the period from 2017 to 2019 (SILVA et al., 2021) and between 2010 and 2019 (LIMA et al., 2021) when compared to the other regions.The increase of 28.5% of LV in Brazil in 2017 justified the increase of 26.4% in the Americas (PAHO, 2019).
The concentration of municipalities with LV notification, in the triennium from 2009 to 2011, were registered in the Northeast region, in the state of Pará (North region), in the north of Minas Gerais (Southeast region) and in the state of Mato Grosso do Sul (Center-West region).And in this same period, Maranhão concentrated 85.7% of the cases of the disease reported in 45 municipalities (IPEA, 2016).In this context, the municipality of São Luís (MA) presented higher prevalence of notified cases.This municipality, in the period from 2014 to 2017 was pointed out as an intense transmission area of LV (COIMBRA et al., 2019).
Regarding the epidemiological profile, of the total of 5329 individuals affected by LV, 63.9% (3404) were male and 36.1% (1925) female.Comparing the prevalence of VL between sex and age group, the 1 to 9 year age group was predominant in females (55%) and males (34.9%).In schooling, the masculine was predominant at all levels of education.In the profile of those affected by the disease, there was a higher frequency of confirmed cases in the male sex (63.9%), age group between 1 and 9 years (42.3%),color/brown race (74.3%), elementary school (27.4%) and urban residence area (62.1%) (Table 1).In Maranhão, more than 50% of the individuals affected by LVH, in all age groups, are males.This data corroborates with studies conducted in Pernambuco (62.35%) (BUARQUE et al., 2021), in Fortaleza (65.1%) (RODRIGUES et al., 2017), in Tocantins (59.96%) (MARTINS et al., 2020), in Rio Grande do Norte (67%) (LIMA et al., 2018) and in Morocco (KAHIME et al., 2017).This greater susceptibility of the male sex is not yet fully understood, but it may be related to a cultural issue, not caring about pathology (MARTINS et al., 2020).Differently in the study carried out in Aldeia Altas municipality was observed higher incidence of VL in females (LIMA et al., 2020).
Children are more affected by LVH (MARTINS et al., 2020;PEZENTE, 2020;BATISTA et al., 2021;BENEDETTI;BUARQUE et al., 2021;).The immaturity of the immune system, the higher exposure to the vector in the peridomycilium and the nutritional status can justify this higher prevalence (BRAZIL, 2014).In addition to this age group, high prevalence was recorded in the 20 to 29 years (BENEDETTI; PEZENTE, 2020) and in the 20 to 39 years (BATISTA et al., 2021;BUARQUE et al., 2021;MARTINS et al., 202220).
The brown race was the most affected in Maranhão and this data corroborates with the research carried out in Fortaleza (ALMEIDA et al., 2020), in Piauí (BATISTA et al., 2021) and in Pernambuco (SOUSA et al., 2018).However, in Roraima, the predominant race was indigenous in 50.0% of cases (BENEDETTI; PEZENTE, 2020).This difference may be related to the distinct racial characteristics between the populations of each locality (ALMEIDA et al., 2020).
Schooling was defined as a proxy variable, whose frequency is related to low socioeconomic conditions and vulnerabilities of individuals affected by the disease (ALMEIDA et al., 2020).In this study, the disease affected, more often, individuals with low schooling.Similar data were found in research carried out in Fortaleza, between 2007and 2017(ALMEIDA et al., 2020).
The urban zone is the one that concentrates the largest number of individuals with LV, as also observed by Silva et al. (2021) and Batista et al. (2021).Meanwhile, in Roraima was the rural area (BENEDETTI; PEZENTE, 2020), as well as in Morocco (KAHIME et al., 2017).There is a change in the pattern of transmission, since the disease ceases to have its predominance in the rural zone by the process of urbanization.This can be mainly explained by the migration of people from the countryside to the cities, deforestation and the construction of environmental impact works (REIS et al, 2019).
In relation to the evolution of the disease, a total of 79.3% of cure and 8.6% of deaths were observed.In the historical series, an oscillation in the lethality and mortality rate due to LV was identified.The highest mortality rate was 11.63/100 thousand inhabitants (2020), while the mortality rate was 1.05/100 thousand inhabitants (2017) (Table 2).When analyzing the evolution of the problem in relation to sex, the male showed a higher rate for cure (64.3%), abandonment (65.8%) and death by LV (66.5%).In the age group, it was observed that the evolution of cases with discharge for cure was greater among children (01 to 09 years).There is a tendency for less cure in people over 60 years of age and a higher percentage of deaths.The lethality rate was predominant in the age group of 70+, but the mortality rate is significant from the age of 60.The brown race showed a higher percentage of cure, abandonment, death and mortality rate due to LV, however the indigenous race showed a higher lethality rate (13.5%).The individuals with elementary schooling showed a higher rate for cure (28.7%), abandonment (34.1%), death (35.4%) and mortality rate (2.3%) for LV.
Illiterates have the highest mortality rate (14.8%).The urban residence area remains predominant also for the evolution of LV and mortality rate (3.7%), but the lethality rate was more prevalent in rural (7.3%) (Table 3).The percentage of cure in Maranhão, in the period studied, was similar to the percentage in the Americas (64.3%) (PAHO, 2021).The lethality of 6.8% in the period 2010 to 2020 was lower than the national average (7.2%) in the period 2003 to 2018 (BRAZIL, 2019).In the American continent, the lethality rate has been increasing gradually, from 3.1% (2000) to 9.5% (2020) (BRAZIL, 2022;PAHO, 2021).The proportion of deaths in males was higher as evidenced in the state of Tocantins (MARTINS et al., 2020).One of the factors influencing lethality is late diagnosis (BENEDETTI; PEZETTI, 2020).Early identification of patients is important, and appropriate prophylactic and therapeutic measures are needed (RODRIGUES et al., 2017).There was also a trend of lower cure, higher mortality rate and lethality in elderly individuals, which may be related to the immune system of these individuals (BRAZIL, 2014).
LVH, in the state of Maranhão, was registered with high incidence in some municipalities, in all the years of the history series, with the exception of 2012.Of the municipalities with the occurrence of the aggravation, the incidence was 1 up to 33.04 cases/100,000 inhabitants.In this scenario we observed two municipalities with very intense incidence (Porto Franco and Presidente Dutra), 14 with intense stratification and 41 with high incidence.In the American continent, between 2001 and 2020, the average incidence coefficient was 2.0 cases/100,000 inhabitants.(BRAZIL, 2022;PAHO, 2021).The social and environmental determinants of health are related to the higher incidence rates of VL (IPEA, 2016).It was also observed the advance of the presence of VHL in municipalities that were  Climate and environmental factors, intense urban expansion and deforestation are favorable to the vector and the transmission process (REIS et al., 2019).The temperature of approximately 20ºC and humidity above 90% are ideal environmental conditions for vector development (FIOCRUZ, 2022).Maranhão has a hot climate with an average of over 18ºC in every month, which favors this scenario (IBGE, 2002).Incidence rates increase in proportion to temperature and precipitation elevation indicating this relationship with the number of cases of VL (MENDES et al., 2016).
A study in an area endemic for VHL, in Maranhão, revealed that 76% of the population does not have access to information about the illness through Community Health Agents (CHAs).And 95% did not attend lectures or had access to other means of publicizing the disease (LOPES et al., 2019).
The trend analysis showed stability for incidence of cases in both sexes and in all color/race categories.It was observed that the ages of 20 to 69 years showed a tendency to growth.With regard to the time of study, there was a tendency for growth among individuals with elementary and middle schooling.The zone of peri-urban residence showed a tendency to decline (Table 4).In Rio Grande do Norte, an increase in cases from 20 years of age and a decrease in the age group from 0 to 9 years of age was observed, which suggests a relationship with nutritional status and childhood immunizations (LIMA et al., 2018).The chances of individuals getting infection with LVH, in Maranhão, according to the epidemiological profile and the reference category (Table 5) are: male sex (55 times more); age group from 1 to 9 years (7.8 times more) and from 20 to 39 years (1.6 times more), but people over 60 years old, have 50% less chances; elementary education (5.3 times more); brown individuals with 99% more chances and those who have a rural residence zone present 71 times more chance of being infected with LVH while in the urban zone it is 5 times (2)

CONCLUSIONS
The epidemiological profile of VHL in Maranhão allowed to observe that its expansion may be related to sex, age range, schooling and urbanization of the vetora.The growth of unplanned cities, socio-environmental changes, migration of human and canine populations originating from endemic areas, the abandonment of treatment by sick individuals and the lack of information about the disease are opportunistic for the expansion of the parasite into new environments and create an adequate scenario for the dissemination of LVH.
The spatial-temporal analysis of VHL in the state, in 10 years, has changed, which also reveals an inefficiency of public health policies for containing the disease.This reinforces the concept of negligence of this problem.
In the absence of vaccines against VHL, the measures for the prevention and reduction of the disease must be guided in environmental monitoring and control of vectors and reservoirs, in education in the health of the population, in individual protection, in the qualification of doctors and nurses for the early diagnosis and treatment of the patients.To this end, it is essential to implement efficient government strategies, services and actions, as well as the development of new public health policies to reduce the disease, especially in endemic areas.

Figure 2 .
Figure 2. Total number of cases and prevalence of HVL reported in the state of Maranhão, between 2010 and 2020 Source: authors (2023).
___________________________________________________________________________ Rev. Gest.Soc.Ambient.| Miami | v.18.n.2 | p.1-16 | e04501 | 2024.10 initially identified as silent and in the course of the years began to register the notification of cases of the disease.

Figure 3 .
Figure 3. Incidence of HVL cases in the municipalities of Maranhão State, from 2010 to 2020.Note:The numbering used to identify the highlighted municipalities is the same as in Figure1.Source: authors(2023).

Table 2 .
Evolution of LV in the State of Maranhão, from 2010 to 2020

Table 3 .
Evolution, lethality rate and mortality due to HVL in the state of Maranhão, from 2010 to 2020, according to the sociodemographic profile.

Table 4 .
Rate of Annual LVH Increment, in the state of Maranhão, from 2010 to 2020, considering the incidence by the variables of the epidemiological profile.

Table 5 .
Association of HVL with sociodemographic factors of those affected, inMaranhão, Brazil, between 2010  and 2020.