Incidence of human visceral leishmaniasis : the importance of municipal socio-economic indicators in the state of Pernambuco , Brazil

Objective: To analyze the main municipal socioeconomic factors associated with the incidence of HVL in the state of Pernambuco, northeastern Brazil. Methods: It is a analytical cross-sectional study. Data on the incidence of HVL and socioeconomic factors were collected from 954 cases notified by the SINAN (National System of Notifiable Diseases) and SIM (Mortality Information System). The cases considered were reported by municipalities in the state of Pernambuco, Brazil, from 2005 to 2014. Statistical differences were analyzed by Research, Society and Development, v. 9, n. 12, e47091211368, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i12.11368 2 Pearson's correlation test, followed by multiple regression analysis. Significant differences were considered when p <0.05. Results: The FIRJAN Municipal Development Index was the variable that showed the most remarkable statistical robustness and strong negative association with the incidence of HVL. The municipal spending on health and residing in the metropolitan region also influenced its mean incidence rates. Conclusion: The indicators that had an influence on the performance of the incidence of LVH were the FIRJAN Municipal Development Index, health expenditure and residing in the metropolitan region.


Introduction
Leishmaniasis is part of the group of neglected infectious diseases; it frequently occurs in poorer countries and affects the most vulnerable populations that face difficulties in accessing health services (OPAS, 2019). This zoonosis is associated with numerous factors, such as malnutrition, poor housing, changes in the immune system, financial resources, and environmental changes (WHO, 2020). Furthermore, they occur mainly in remote rural areas with precarious housing with little or no access to modern health installations (Okwor & Uzonna).
Human Visceral Leishmaniasis (HVL) is also known as kala-azar; it is the most severe form of the disease, with the potential for outbreak and mortality. It can be fatal in more than 95% of cases when left untreated (WHO, 2020). It is a zoonosis caused mostly by the intracellular parasite called Leishmania infantum (Dantas-Torres, 2006) e Leishmania donovani (Ready, 2014). It is transmitted through the bite of infected female sandflies; the clinical picture is characterized by irregular fevers, weight loss, enlarged spleen and liver, and anemia (WHO, 2020).
Early diagnosis and treatment are essential to minimize the impacts of the disease.
However, there is a time gap between symptom onset and the diagnosis of Leishmaniasis. On average, the individual visits seven healthcare services until the diagnosis is confirmed.
Although Brazil has the Visceral Leishmaniasis Surveillance and Control Program, which has guidelines focused on reducing disease morbidity and lethality, with reservoir and vector control and health education, the disease has expanded in the country (Zuben & Donalísio, 2016). More than 51 thousand HVL cases were reported in Brazil from 2003 to 2018, with an average lethality of 7.2%. It is emphasized that most cases of the disease in the country are concentrated in the northeast region (Albuquerque e Silva et al., 2019).
The epidemiological aspects of Leishmaniasis in northeastern Brazil have changed in recent years. Although the incidence of the disease has decreased in children, there has been an increase in adults (Lima et al., 2018). The high numbers of cases in the Northeast region indicate that studies are still needed to provide results and create guidelines of future intervention strategies developed from the knowledge of factors associated with HVL in priority areas.
In this way, the objectives of the Pan American Health Organization and the World Health Organization, regarding the consolidation of actions to reduce the morbidity and mortality of Visceral Leishmaniasis in the Americas, will be achieved soon (PAHO, 2020).
Therefore, this study's objective was to analyze the main socioeconomic factors associated with the incidence of Human Visceral Leishmaniasis in Pernambuco's municipalities in the northeast region of Brazil.

Method
An analytical cross-sectional study was conducted in a historical series containing information on HVL from 184 municipalities in the state of Pernambuco, Brazil. System (SUS -Sistema Único de Saúde). The municipality of residence for each case was used as a filter. Duplicate cases were excluded. Research, Society andDevelopment, v. 9, n. 12, e47091211368, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i12.11368 The sample consisted of 954 reported cases (924 records at SINAN and 30 records notified by SIM).
First, the data were described on means (± Standard Deviation). Subsequently, the incidence of HVL per 100 thousand inhabitants was transformed to a logarithmic scale. The Neperian logarithm was used to reduce the dependent variable's spreading degree and minimize the asymmetry problem generated by the high proportion of zeros in the analysis (Fletcher, MacKenzie & Villouta, 2005).
Through the Pearson Test, we performed the correlation of the average effects of the independent variables on the Neperian logarithm of the incidence of HVL per 100 thousand inhabitants.
Afterward, the significance and magnitude of the impact of each independent variable (estimated by the parameters β1, β2, β3, β4, β5, and β6) on the incidence of HVL in the municipalities were verified through Multiple Regression Analysis by Ordinary Least Squares (OLS), according to the equation described in Figure 1. The incidence of HVL per 100 thousand inhabitants was the dependent variable; the independent variables were those that refer to the municipality's socioeconomic characteristics  The validation of the significance of the coefficients obtained from the primary analysis was carried out as described by Angrist & Pischke (2008). We adopted the model with a linear trend (through a variable that, in increasing order from 1 to 10, represents the years studied in this work) followed by a model with a quadratic trend (through the variable constructed in the linear squared analysis). The analyzes were performed using the Stata/SE 13 for Windows program (StataCorp LP, College Station, TX, USA). Significant differences were considered when p <0.05. Research, Society and Development, v. 9, n. 12, e47091211368, 2020 (CC BY 4.

Results
Table I presents the descriptive analysis of the average incidence per 100 thousand inhabitants and socioeconomic variables associated with HVL in Pernambuco's state in the initial (2005) and final year (2014) study period.
The average incidence of HVL was 1.78 cases per 100 thousand inhabitants in 2005.
After ten years, an average of 3.63 cases per 100 thousand inhabitants was observed. The highest municipal socioeconomic indicators were observed in 2014. The results were expressed as mean ± standard deviation. Source: Research data.
The temporal evolution of the incidence in Neperian logarithm (ln) of HVL per 100 thousand inhabitants for the state of Pernambuco was described in Figure 3. The lowest incidence of the disease was described in 2010 (ln = 51/100 thousand inhabitants), and, in 2014, there was an express increase in the incidence of HVL in the region (ln = 110/100 thousand inhabitants).

Discussion
HVL is a significant public health problem that is difficult to reduce its incidence rates in endemic regions. In the state of Pernambuco, in a 10-year temporal analysis (2005 to 2014), there were variations in the disease incidence rates, with a higher value (3.63 cases per 100 thousand inhabitants) at the end of the studied period.
The incidence verified in 2014 was higher than the national average incidence ( The rapid test's greater availability contributed to improving the disease cases detection (WHO, 2020), reflecting on the increased incidence observed in 2014s. The spread of HVL is a multifactorial issue that involves the environmental context, such as deforestation and climate change. It also includes other factors such as immunosuppression, drug resistance, human mobility, and animals. However, low socioeconomic levels stand out as contributing to the spread of the disease (Oryan & Akbari, 2016).
In the state of Pernambuco, the municipal socioeconomic indicators were higher in the year 2014. However, The Pearson test indicated a negative correlation between primary care coverage and the Firjan Health index. The multiple regression analysis showed that the average health level of the municipalities (Firjan Health Index) was the variable that had the most significant association with the incidence of HVL. Even with the Metropolitan Region variable's inclusion in the model, it showed a negative and significant association at the 5% level, revealing its robustness.
Although the percentage of people attended by basic health units was not associated with significant direct effects on the incidence of HVL in the state of Pernambuco, it is highlighted that these services are essential for the population. Advancing coverage of primary health care services contributes to improving the monitoring of chronic diseases, improving diagnosis, and greater access to medicines (Pinto & Giovanella, 2018).
Furthermore, the expansion of primary care coverage does not necessarily guarantee efficiency in the service provided. In this sense, the Firjan index of municipal development in health and essential sanitation services is positively associated with efficiency in the services provided by Primary Care in a municipality (Silva et al., 2018). This fact can contribute to more significant detection of new cases of the disease.
Investment in urban infrastructure is also of fundamental contribution to the fight against Visceral Leishmaniasis, given that this disease is found frequently in areas lacking urban infrastructure, with no garbage and sewage collection; except cases of HIV co-infection that are associated with higher levels of education and evidence of higher socioeconomic status (Lima et al., 2018).
The investment in development improvements in the municipality's health and infrastructure, such as adequate basic sanitation, are essential points for applying resources.
Thus, it is possible to promote primary health care services' efficiency and reduce unnecessary public spending (Silva et al., 2018).
In this study, through multiple regression analysis, it was observed that Municipal Health Expenditure was also associated with the incidence of HVL (p <0.05 In Brazil, Leishmaniasis is among the diseases characterized as a priority health problem, and treatment is offered free of charge by the SUS (Albuquer e Silva at al, 2019).
Even with free treatment access, the costs arising from HVL for patients and their families are elevated (Uranw et al., 2013). These low-income families' costs can contribute to further impoverishment and reinforce the vicious cycle of disease and poverty. For this reason, public investment in treatment and control contributes to alleviating poverty and the impacts of the disease (Alvar, Yactayo & Bern, 2006).
In Brazil, the resources allocated to states and municipalities to promote their services are limited, so it is essential to invest and manage resources in a planned way (Silva et al., 2018). Despite the limitations associated with the use of secondary data and underreporting of cases, it can be inferred that investing in health development in the municipalities of Pernambuco State is a central point to reduce the incidence of HVL in that region. To contribute to the understanding of the factors associated with HVL in this state, future studies that consider individual factors, both biotic and abiotic, are necessary.

Conclusion
The mean incidence of HVL in the municipalities of the state of Pernambuco, in a temporal analysis from 2005 to 2014, presented a negative correlation with the percentage of Primary Care Coverage and the FIRJAN Municipal Development Index. However, in a multifactorial regression analysis, the FIRJAN Municipal Development Index was the variable with the most remarkable statistical robustness, indicating a strong negative association with this disease's incidence.
Strategic investments in health in the municipalities of the state of Pernambuco are indispensable to obtain reductions in the incidence of HVL, mainly those that contribute to an increase in the FIRJAN Municipal Development Index.