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INTRODUCTION

Leishmaniasis is a group of parasitic diseases caused by the infection of protozoa of the genus Leishmania spp., transmitted to humans through the bite of hematophagous insects, sandflies female. Its present in four clinical forms: visceral leishmaniasis (VL); post-kala azar dermal leishmaniasis (PKDL); cutaneous leishmaniasis (CL); mucocutaneous leishmaniasis (MCL)¹. VL is considered the most serious and can be fatal in humans when left untreated, especially in vulnerable groups such as malnourished children and individuals with human immunodeficiency virus (HIV) infection².

The World Health Organization (WHO) considers a disease with increasing notification in worldwide; however, more than 90% of new cases are concentrated in six countries, Bangladesh, Brazil, Ethiopia, India, Sudan, and South Sudan, with approximately 350 million people exposed to the risk of infection¹. In the Americas, its etiological agent is the protozoan Leishmania (Leishmania) infantum chagasi³. Lutzomyia longipalpis is the most relevant sandfly species in Brazil⁴.

VL are a dynamic disease with transmission in areas wild/rural and urban. In Brazil, the urbanization process of Human Visceral Leishmaniasis (HVL) can be related to different factors, namely: environmental changes caused by anthropic actions, associated with the rapid process of human occupation in peri-urban areas; the interaction between wild and urban reservoirs and the mobilization of infected animals to areas without transmission; the adaptation of the vector L. Longipalpis, with feeding eclecticism and presence in the peridomicile; and the domestic dog (Canislupus familiaris Linnaeus, 1758), considered the main urban reservoir host of L. (L.) infantum chagasi.^1,3

For infection diagnosis, the Ministry of Health (MoH) recommends the application of rapid screening tests (immunochromatographic TR-DPP-Bio-Manguinhos) and confirmatory test, which can be serological tests (Indirect Immunofluorescence Assay - IFA and Enzyme Linked Immunosorbent Assay – ELISA), direct parasitological examination (finding the parasite in bone marrow, spleen, liver or lymph node tissue), culture, PCR test or real-time PCR². When there is no possibility of diagnosis laboratory, clinical and epidemiological findings are considered for notify the cases⁵.

The clinical manifestations of HVL are considered nonspecific, and are characterized by presenting signs and symptoms of chronic disease, making clinical diagnosis difficult for early treatment. The severity of clinical manifestations can be associated with patients’ age, nutritional status and immunogenetic characteristics. In severe cases, the evolution of the clinical condition occurs for voluminous hepatosplenomegaly, persistence of fever, pallor and progressive weight loss.^2,6

Compulsory notification combined with surveillance of human and canine cases is considered essential for directing control actions. Currently, the MoH and the Ministry of Agriculture, Livestock and Food Supply (MAPA - Ministériode Agricultura, Pecuária e Abastecimento), through the State and Municipal Health Departments, conduct the Visceral Leishmaniasis Control Program (VLCP)^2,7,8

Control measures are turned at dogs and vector insects. For the dog, topical insecticides and repellents can be used, collars impregnated with 4% deltamethrin, vaccination, treatment with miltefosine for positive cases and canine euthanasia in positive cases, with the guardian’s consent.^2,9 For the insect vector, the use of chemical insecticides is still one of the most used measures. Despite continuous and intensive control campaigns, many difficulties are found throughout Brazil, such as the difficulty in obtaining a quick and effective diagnosis in epidemiological surveys, especially with regard to dogs and the population’s refusal to chemical control, which is considered ineffective due to the probable resistance of L. longipalpis to the chemical compounds used.^2,10

The Northeast Region is the one that most notifies cases of HVL throughout Brazil, corresponding 77% of cases. Notification is carried out by health surveillance departments and collected by SINAN (Disease and Notification Information System - Sistema de Informação de Agravos de Notificação)⁴. In the state of Piauí, the occurrence of HVL has been known since 1934, with the record of successive epidemic outbreaks in the capital Teresina from the 1980s onwards. Since then, it has been considered a priority area for control measures, which despite this, has not impeded its advance in urban areas and occurrence in a lot municipalities.^11,12

Therefore, the aim of this study was to analyze the reported cases of HVL in Piauí between 2007 and 2017, with identification of epidemiological aspects of the disease in the state.

METHODS

This is a retrospective epidemiological study about the occurrence of HVL cases in the state of Piauí, notified by SINAN through the virtual public domain platform Datasus provided by the MoH.

The state of Piauí is located in northeastern Brazil, has an approximate area of 251.756 km² and 224 municipalities, with an estimated population of 3.273.227 inhabitants, a demographic density of 12.40 inhabitants/km² in 2019 and more than 2 million people living in urban area, with an average nominal per capita income of R$ 827.00. The capital, Teresina, has a territorial area of 1.391.046 km² and a demographic density of 584.94 hb/km², with an estimated population of 864.845 inhabitants.¹³

The state is in areas belonging to the Caatinga (a type of desert vegetation in Brazil), Cerrado (a vast tropical savanna ecoregion of Brazil) biomes and transition areas between Caatinga/Cerrado, with an average temperature of approximately 27.6ºC and an average annual precipitation of less than 800 mm.¹⁴

The data included in this study correspond to the 2007-2017 period, obtained with TabWin 32 and tabulated in Microsoft Office Excel 2016. The mapping of notified cases was prepared using QGIS 3.10.

Variables were analyzed according to SINAN registration, number of autochthonous cases, confirmatory criterion, municipality of notification and residence of the case, death, gender, age, education, race/skin color and area of residence (urban or rural). Annual coefficients of incidence per 10,000 inhabitants and lethality per 100,000 inhabitants were calculated, by dividing the absolute number of deaths by the number of reported cases, multiplied by 100. To perform this study, it was not necessary to be submitted to an Institutional Review Board, as the data used are freely accessible.

RESULTS

Between 2007 and 2017, 2,447 cases of HVL in the state of Piauí were notified, 2,265 autochthonous cases (92.56%) and laboratory diagnosis. For confirmation, there were performed in 2,119 cases (86.6%) (Table 1).

The highest register of cases occurred in 2007, 2008 and 2014, with 253, 279 and 283 cases respectively, while 2010 was least reported cases (157), followed by 2009 and 2016, both with notification of 158 cases. Thus, 161 cases evolved to death between 2007 and 2017, with a total lethality rate of 6.64% in state. The highest numbers of death occurred in 2009 (12.5%), 2014 (14.1%) and 2017 (12.5%). Especially, 2014 was the year with the highest notification (283 cases) and the highest lethality rate (14.1%). The lower lethality rate was recorded in 2012 (4.4%) (Figure 1).

In state, cases of HVL occurred in 183 municipalities (81.7%). In relation to the municipality of residence, in Teresina, the highest number of cases was notified, 734 cases (30%), followed by municipalities of Parnaíba, 123 cases (5.02%) and Miguel Alves, 102 (4.16%), being the only municipalities that registered more than 100 cases of HVL in residents in 2007-2017 (Figure 2).

Among the municipalities with the highest number of cases, the highest concentration of notification was observed in the capital Teresina (Table 2), representing 75.97%, with incidence of 9.01/10,000 inhabitants. In the capital, the lethality rates were 8.86%, with 65 deaths of residents, representing the higher concentration of notification of deaths by HVL in the state. However, the higher incidence of cases occurred in the municipality of Miguel Alves (31.58) and the mortality coefficient of 8.82%, close to result in Teresina.

The most affected with HVL were males (66.30%). The age that prevailed among the notifications was in children under 10 years old (43.44%) and people aged between 20 to 59 years old (41.60%), the lowest incidence was observed in the elderly over 80 years old, which represented 0.86% of reported cases (Table 3).

Education was the variable that showed the most divergences in notification, 39.84% of them were classified as “not applicable”, not presenting necessary information to understand the profile of affected individuals. However, it was possible to observe the notification of 16.31% of cases for patients with incomplete elementary school and 11.97% for complete elementary school. In individuals with incomplete or complete higher education, an occurrence percentage of 0.25% and 0.45%, respectively, was observed.

Brown race/skin color had the highest incidence (88.27%), while other in this variable were below 5% of occurrence among the notified cases. The main residence area notified for HVL was the urban (67.63%), while the rural area registered 28.61%. It is worth highlighting the notification of ignored/white cases in this variable as being 3.39% (Table 3).

DISCUSSION

In this study, it was possible to verify the notification of 2,447 cases of HVL in the state of Piauí between 2007-2017, with a total lethality rate of 6.64% (161 deaths). In 2014, 283 cases were notified with a lethality rate of 14.1%, the highest number. The year 2010 was the year that least notified cases of HVL (157 cases), and in 2012 there was the lowest lethality rate.

In Piauí, 2014, had a higher lethality rate than the Northeast region (7.9%) and Brazil (8%), as well as in 2009 and 2017, when rates of 5.6% and 9.6% were registered, respectively, while for the Northeast the records were 6.9% and 8.8%, respectively.¹⁵

Mortality from VL, in most cases, is related to the absence of treatment and greater occurrence is in groups considered vulnerable and affected by other comorbidities, e.g., malnourished children, the elderly and people with HIV⁴. Another factor that can be highlighted for the occurrence of deaths in the state is the inequality in distribution of care services, leading to late diagnosis and difficulty in accessing healthcare services for less favored social groups and people living in cities in the state countryside, resulting in late treatment.¹⁶

Laboratory diagnosis was performed in 86.6% of cases in the state of Piauí and clinical and epidemiological criteria were considered for diagnosis in 13.4% of cases. It can be noted that the adoption of more accurate confirmatory methods is being used for diagnosis, e.g., direct parasitological examination and IFA, which have increased significantly in Brazil in recent years.¹⁷

As for the municipality of residence, it can be seen that HVL is well distributed in the state, occurring in 81.7% of the municipalities. About this aspect, it was possible to observe the spatial distribution of HVL, highlighting areas with a high number of cases in residents, and, therefore, a higher risk of transmission. This classification of areas is important from the point of view of epidemiological monitoring for directing control actions.¹⁸

Municipalities without notification, or even with few cases, may have underreporting, due to the difficulty in accessing diagnosis, which may happen throughout the state as a result of failures in healthcare services.¹⁹

In Teresina, there were 75.97% of notifications and 30% of cases resided in the capital, with an incidence of 9.01. This result can be associated with the greater offer of healthcare services in Teresina compared to other municipalities in the state. The number of services provided to the population in interior cities is insufficient, requiring the displacement of residents to other municipalities in search of healthcare services.¹³ Regarding the fact that 30% of cases are residents of Teresina, it can be attributed to its population density, the municipality of Teresina is one of the most populous in the state, concentrating 26.42% of the total population of Piauí, followed by the municipality of Parnaíba (4.67%), the second in relation to the number of affected residents with HVL (5.4%) in the state.

The high number of cases in Teresina, presented in this historical series, may be mainly related to the occupation of land close to forests and pastures.²⁰ In this case, the accelerated urbanization process resulted in the adaptation of the vector, sandflies, to the peridomicile and in precarious living conditions, resulting in the high occurrence of HVL in the capital.

In Piauí, the profile of affected by HVL is mostly represented by males (66.3%), patients under 10 years old (43.44%), of brown race/skin color (88.27%) and with incomplete elementary school education (16.31%), despite the classification “not applicable” being predominant in the notifications (39.84%), which may be associated with preschool children. Similar results were observed throughout Brazil in recent years.¹⁷

According to data from the IBGE Social Indicators Synthesis released in 2017, Piauí ranks 6^th, compared to other states, about the number of people living in poverty, is represented by 45.3% of the population in the state.²¹Sanitation in Teresina, assessed by Instituto Trata Brasil, through the Brazilian National Survey of Continuous Household Sample (PNAD - Pesquisa Nacional por Amostra de Domicílios Contínua), found that 76.5% of households do not have adequate sanitation with drinking water supply, garbage collection, sewage, street cleaning and rainwater management. These aspects may be high in other municipalities in the state.²² These socioeconomic and environmental data point to social groups that live in conditions of poverty, lack of basic sanitation and deprived of access to information as being those at greatest risk of contracting the infection.

Regarding the insect vector, in Teresina, its habitats are related to places close to homes with animal husbandry and accumulation of organic matter.²³ From this vector behavior, it can be inferred that L. longipalpis is found adapted to urban conditions throughout the state, mainly related by cases reported in urban residents (67.63%) and autochthonous cases (92.56%). Furthermore, more investigative studies about the conditions the establishment of L. longipalpis in the state are still needed.

The epidemiological data presented in this study may differ from reality, given the difficulty of accessing healthcare services in many municipalities, failures in diagnosis, incomplete notification and heterogeneity in the municipality’s epidemiological surveillance actions, which results in possible failures and reduction the reliability of information contained in SINAN.²³ Thus, a more serious situation than the one presented here may be occurring, requiring further analysis of the underreporting of cases in the state. The constant epidemiological surveillance of canine and human cases is one of the most used strategy when it comes to contribute to information to guide VL control, which leads to considering the importance of epidemiological studies in the area to predict future outbreaks and their territorial dissemination.²⁴

Therefore, the results of this historical series are important for providing relevant information on the epidemiological situation of HVL in the state of Piauí, such as the spatial distribution of cases, municipalities with higher incidences, difficulty in accessing diagnosis, social groups more affected and deaths, serving to direct actions to control the disease. But for these actions to be effective and efficient, it is necessary to overcome the challenges posed by barriers to accessing real information about the disease, improvements in sanitation and effective systematization of health surveillance in the state. It is also worth the importance of assessing and reviewing the actions used for diagnosis, making it timelier and more accessible, as well as sandfly control, which must be monitored frequently to prevent future outbreaks, especially in urban centers.

REFERENCES

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23. Afonso MMS, Duarte R, Miranda JC, et al. Studies on the Feeding Habits of Lutzomyia (Lutzomyia) longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) Populations from Endemic Areas of American Visceral Leishmaniasis in Northeastern Brazil. J Trop Med. 2012;2012:1–6. https://doi.org/10.1155/2012/858657.

24. Zuben APB, Donalísio MR. Difficulties in implementing the guidelines of the Brazilian Visceral Leishmaniasis Control Program in large cities. Cad saúde Pública. 2016;32(6):1–11. http://dx.doi.org/10.1590/0102-311X00087415.

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