ORIGINAL RESEARCH published: 26 April 2021 doi: 10.3389/fvets.2021.653999 Trends in the Epidemiology of Leishmaniasis in the City of Barcelona (1996–2019) David Palma 1,2† , Lilas Mercuriali 1† , Jordi Figuerola 2,3*, Tomás Montalvo 1,2 , Rubén Bueno-Marí 4,5 , Joan-Pau Millet 1,2 , Pere Simón 1 , Eva Masdeu 1 and Cristina Rius 1,2 1 Agència de Salut Pública de Barcelona (ASPB), Barcelona, Spain, 2 Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBER-ESP), Madrid, Spain, 3 Estación Biológica de Doñana (EBD-CSIC), Sevilla, Spain, 4 Department of Research and Development (R&D), Laboratorios Lokímica, Valencia, Spain, 5 Parasitology Area, Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia, Spain Background: Leishmaniasis is a neglected zoonosis produced by 20 different flagellated parasites of the Leishmania genus, a protozoan transmitted to humans and other Edited by: vertebrates by the bite of dipteran insects of the Phlebotominae subfamily. It is endemic in Giulio Grandi, Mediterranean countries and the number of cases is expected to increase due to climate Swedish University of Agricultural Sciences, Sweden change and migration. Prioritizing public health interventions for prevention and control Reviewed by: is essential. The objective was to characterize the epidemiology and temporal trends in Ettore Napoli, the incidence of human leishmaniasis in the city of Barcelona, between the years 1996 University of Messina, Italy Gaetano Oliva, and 2019. University of Naples Federico II, Italy Methods: A population-based, analytical observational study among residents in the *Correspondence: city of Barcelona was conducted of all the cases of leishmaniasis reported between Jordi Figuerola jordi@ebd.csic.es 1996 and 2019 to the Public Health Agency. The epidemiological survey contains clinical, † These authors have contributed diagnostic, and epidemiological data, including contact with suspicious mammals or equally to this work and share first insects. Annual incidence-rates were calculated by sex, age, and country of origin. authorship Chi-square tests were used to assess association between studied risk factors, periods of time and type of leishmaniasis. Specialty section: This article was submitted to Results: During the study period a total of 177 cases of leishmaniasis were reported Parasitology, a section of the journal in Barcelona, being 74.6% (n = 132) of the total cases in Spanish born, although Frontiers in Veterinary Science within the foreign-born population the incidence was higher. Median age was 34 years Received: 15 January 2021 (IQR = 10–48) and 121 (66.8%) were male. The main type was cutaneous (46%) followed Accepted: 29 March 2021 by visceral (35.1%). The cumulative incidence was 0.47 per 100,000 inhabitants, with the Published: 26 April 2021 highest incidence found in 2017 (1.60 per 100,000 inhabitants). A higher incidence was Citation: Palma D, Mercuriali L, Figuerola J, observed in the 0–4-year-old group (1.73 per 100,000 inhabitants), but increased during Montalvo T, Bueno-Marí R, Millet J-P, the study period for all age groups. There was an increase of foreign origin cases, and a Simón P, Masdeu E and Rius C (2021) decrease in the number of cases associated to any immunosuppression. Trends in the Epidemiology of Leishmaniasis in the City of Barcelona Conclusion: In Barcelona, leishmaniasis incidence continues to be higher in people (1996–2019). Front. Vet. Sci. 8:653999. under 5 years of age, and 25–64 years old males, but it has also increased in population doi: 10.3389/fvets.2021.653999 from foreign country of birth. There is an increase of the cases since 2016, probably Frontiers in Veterinary Science | www.frontiersin.org 1 April 2021 | Volume 8 | Article 653999 Palma et al. Epidemiology of Leishmaniasis in Barcelona, Spain (1996–2019) due to the changes in the notification system, increasing the diagnosis of cutaneous leishmaniasis. Improvements in the current surveillance system are needed. Notification of the disease, vector, and reservoir control activities are also essential for the control of the disease. Keywords: parasitology, leishmania, zoonosis, Phlebotomus, surveillance, One Health, public health surveillance, infectious disease INTRODUCTION Incidence of Leishmaniasis in Mediterranean countries and across Europe has been described on the rise (1). Autochthonous Leishmaniasis is a zoonosis produced by 20 different flagellated cases have been recently described in non-endemic areas, like parasites of the Leishmania genus, a protozoan transmitted Southern Germany (18), and the number of imported cases to humans and other vertebrates by the bite of dipteran has increased in areas such as Sweden or London (19, 20). In insects of Phlebotominae subfamily (1, 2). The parasites that Sweden, an increase in diagnoses has been observed since 2013, cause leishmaniasis are present in 98 countries around the especially in those under 18 years of age and migrants, mainly world, causing between 700,000 and 1 million new cases from Syria and Afghanistan (19). In London, most diagnoses annually, with an estimated 350 million people at risk of occurred in tourists returning from the Mediterranean region infection worldwide (1–4). There are three main clinical and soldiers returning from other territories where the pathogen forms visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), is endemic (20). and mucocutaneous leishmaniasis (ML) (1, 4). VL is the Climate change is expected to extend the geographical most serious form of leishmaniasis and causes a systemic distribution and seasonality of phlebotomine vectors (7, 21). In disease characterized by irregular episodes of fever, spleen Morocco, the increase in minimum temperatures has increased and liver enlargement, weight loss and anemia. CL is the the survival of the sandfly larvae through the winters, extending most frequent presentation and causes skin lesions that evolve their activity season. This combined with the increase in human from nodules to painless ulcers, which can leave long lasting circulation and tourism is thought to be one of the main causes scars. ML is the most uncommon form of leishmaniasis, for dissemination of cutaneous leishmaniasis (22). Spain has and leads to the destruction of nasooropharyngeal mucosa, also experienced an increase in cases, though this phenomenon usually after years of the initial skin lesions. Diagnosis is has been attributed to multiple factors, including improvements established through direct observation or molecular detection in notification, the seasonality of sandflies (16) and a growing of Leishmania parasites in tissue specimens, mainly from skin urbanization that favors the contact between reservoirs and lesions, for cutaneous leishmaniasis, or from bone marrow, humans (23). for visceral leishmaniasis, although serological tests could also Studies in different areas of Spain have reported be used in different situations (2). The wide diversity of seroprevalence varying from 4 to 35% in dogs, with a Leishmania species is associated with a difference in the clinical high proportion of them not showing any clinical signs of presentation, routes of transmission (zoonotic vs. anthroponotic) leishmaniasis (24, 25). Phlebotomus perniciosus and Phlebotomus and treatment resistance (2, 5). In this sense, VL is usually ariasi are the main vectors of Leishmania infantum in the caused by L. donovani or L. infantum, while CL can be Iberian Peninsula (23, 26). Moreover, in Spain, leishmaniasis is a caused by L. infanfum, L braziliensis, or L. tropica, between hypoendemic, mandatory notifiable disease since 1995 (27), but others (2). reporting is compulsory for every Autonomous Region (CCAA) In urban, periurban and domestic environments, dogs (Canis through the National Surveillance Network since 2015 (28). lupus familiaris) are usually considered main reservoirs of the During the 2005–2017 period, Spain had an incidence rate of parasite, although synanthropic rodents (e.g., Rattus norvegicus), 0.62 cases per 100,000 inhabitants (16, 25), with a heterogeneous wild rabbits (Oryctolagus cuniculus), hares (Lepus granatensis), distribution, mainly affecting the Mediterranean region (the and cats (Felis catus domesticus) can also play a relevant role as Valencian Community, Catalonia, the Balearic Islands and reservoir host (6–12). Andalusia), except for the Community of Madrid, where a large In endemic developing countries, leishmaniasis mainly affects community outbreak was identified in 2009 and 2010 linked people of lower socioeconomic status, in rural areas with poor to a newly identified reservoir (26). The objective of this study housing conditions, with little or no access to health services is to characterize the epidemiology and temporal trends in (1, 13). Within the risk groups, visceral leishmaniasis can present the incidence of human leishmaniasis in the city of Barcelona, non-specific symptoms in children, and can be fatal without between the years 1996 and 2019. adequate treatment (14). Although coinfection with HIV is considered a public health problem in various parts of the world (15), the introduction of highly effective antiretroviral treatment METHODOLOGY in developed countries since 1997 has helped to decrease the HIV Study Design and Population coinfection (16), so nowadays it is a pathology more common in A population-based, analytical observational study was immunosuppression non-HIV-related (17). conducted with all reported leishmaniasis cases between Frontiers in Veterinary Science | www.frontiersin.org 2 April 2021 | Volume 8 | Article 653999 Palma et al. Epidemiology of Leishmaniasis in Barcelona, Spain (1996–2019) 1996 and 2019. Data were drawn from the registry of notifiable TABLE 1 | Descriptive statistics of the leishmaniasis cases reported in Barcelona diseases of the Epidemiology Service of the Public Health Agency between 1996 and 2019 (n = 177). of Barcelona (ASPB). The registry includes cases individually n % notified to the Epidemiology Service by healthcare professionals and, since 2016, it also includes laboratory notifications to the Sex Catalan Microbiologic Notification System (SNMC) (29). Men 121 68.4% Women 55 31.1% Variables Country of origin The registry of notifiable diseases contains the information Native 132 74.6% included in the epidemiological surveys of cases carried out by Foreign 45 25.4% public health nurses from the Epidemiology Service. Type of leishmaniasis The epidemiological survey contains clinical, diagnostic, and Visceral 61 34.5% epidemiological data, among others (Annex 1). The variables Cutanous 80 45.2% of interest included: age, sex, country of birth, date of onset Mucocutaneous 4 2.3% of symptoms (onset, diagnosis, and notification data), type Missing 32 18.1% of leishmaniasis, history of immunosuppressive disease or Neighborhood’s available family income index (AFII) immunosuppressive treatment, as well as history of contact Disadvantaged (AFII <1) 109 61.6% with an infected dog or another animal suspected of infection Favored (AFII > 1) 57 32.2% and travel to an endemic country according to WHO’s current Missing 11 6.2% guidelines at the time of the survey (30). Evolution Cured without sequelae (a) 121 68.4% Inclusion and Exclusion Criteria Cured with sequelae (a) 11 6.2% All cases of leishmaniasis from patients who resided in the city Dead 3 1.7% of Barcelona and who met the case definition according to local Lost to follow up (b) 42 23.7% guidelines were included (Annex 2). Cases were excluded if the patients resided in another city than Barcelona. (a) Sequelae defined by the surveyor’s criteria. (b) Of the 42 lost cases of “Evolution,” 9 cases were identified as “lost” by the person who Analysis carried out the survey, while the rest of the cases had no information. In all the missing cases of the Type of leishmaniasis and Neighborhood, the value was not Annual incidence-rates and its confidence interval (95%) were recorded in the epidemiological survey. calculated by sex, age, and country of birth, in relation to the municipal registry of the city of Barcelona (31). The microbiological confirmation and national surveillance system were modified in 2016 (28). Consequently, to test for temporal cutaneous (45.2%, n = 80), followed by visceral (34.5%, n = changes in the influence of these variables on the incidence of 61), and only 2.3% (n = 4) was mucocutaneous. 61.6% (n = leishmaniasis, the study period was divided into three periods: 109) of the cases occurred in people who lived in disadvantaged 1996–2005 (n = 55), 2006–2015 (n = 52), and 2016–2019 municipal districts. 68.4% (n = 121) of the cases progressed to (n = 70). healing without sequel, 6.21% (n = 11) progressed with sequel, The risk factors obtained from the survey were analyzed by and 1.63% (n = 3) died (Table 1). The diagnosis were made by the three proposed periods and the clinical presentation of the biopsy in 61% of the cases (n = 108), by a serological test in 21.5% leishmaniasis. Cases were classified according to the Available (n = 38) and by culture in 19.4% (n = 21). Family Income Index of the municipal district of residence (IRFD The cumulative incidence during the study period was 0.47 for “Index renda familiar disponible”), into disadvantaged (IRFD per 100,000 inhabitants (Table 2), with the highest incidence < 1) or favored (IRFD > 1) neighborhood (32). In 2019, 62.2% found in 2017 (1.6 per 100,000 inhabitants) and the lowest in of Barcelona’s population lived in disadvantaged neighborhoods 2012 (Figure 2). Incidence was generally higher in men than (31). A chi-squared or a Fisher’s exact test were performed, as women (0.68 vs. 0.27 per 100,000 inhabitants) and in foreign- appropriate, and a p < 0.05 was considered significant. All the born over Spanish-born population (0.74 vs. 0.41 per 100,000 analyses were done using the program STATA version 15. inhabitants). Slight changes in incidence were observed between the first and second period (0.36–0.32 per 100,000), increasing RESULTS significantly to 1.08 per 100,000 after 2016. An increase of the incidence was observed in all age groups, especially in the third Between 1996 and 2019, 177 cases of leishmaniasis were period, with the higher incidence found in the 0–4-year-old reported in Barcelona (Table 1). The median age was 34 years group (1.73 per 100,000 inhabitants) (Table 2). [interquartile range (IQR): 10–48]. 66.8% (n = 121) of the During the three studied periods there was an increase of the diagnoses occurred in men. According to origin, most cases cutaneous leishmaniasis in the second and third period (0–51.9 occurred in native population (Table 1), however, a sustained to 75.7%, p < 0.001), and a decrease of the visceral leishmaniasis increase in cases from foreign-born population were observed in the final period (54.6 to 46.2% to a 10%, p < 0.001) (Table 3). since 2003 (Figure 1). The main type of leishmaniasis was Male sex accounted for over 80% of the cases in ages 25–64, Frontiers in Veterinary Science | www.frontiersin.org 3 April 2021 | Volume 8 | Article 653999 Palma et al. Epidemiology of Leishmaniasis in Barcelona, Spain (1996–2019) FIGURE 1 | Total number of cases of leishmaniasis, in Spanish born population (native) and foreigner country of birth, in Barcelona between 1996 and 2019 (n = 177 cases). TABLE 2 | Incidence of leishmaniasis per 100,000 inhabitants and confidence interval (95%), by complete study time and periods 1996–2005 (n = 55), 2006–2015 (n = 52), and 2016–2019 (n = 70), Barcelona. 1996–2005 2006–2015 2016–2019 Total Sex Female 0.14 [0.06–0.22] 0.22 [0.12–0.32] 0.73 [0.44–1.02] 0.27 [0.19–0.34] Male 0.61 [0.43–0.79] 0.41 [0.27–0.55] 1.47 [1.04–1.89] 0.68 [0.56–0.80] Age 0–4 2.00 [0.87–3.13] 1.15 [0.35–1.94] 2.59 [0.67–4.51] 1.73 [1.52–1.93] 5–14 0.17 [0.09–0.24] 0.00 1.64 [0.56–2.71] 0.37 [0.15–0.59] 15–24 0.16 [0.10–0.22] 0.14 [0.08–0.20] 1.03 [0.21–1.85] 0.28 [0.11–0.45] 25–44 0.71 [0.47–0.95] 0.44 [0.26–0.62] 0.91 [0.49–1.33] 0.62 [0.48–0.76] 45–64 0.11 [0.00–0.22] 0.35 [0.17–0.53] 0.70 [0.30–1.09] 0.31 [0.19–0.42] 65 or more 0.03 [0.01–0.05] 0.15 [0.02–0.28] 1.23 [0.65–1.81] 0.30 [0.18–0.42] Country of origin Native 0.34 [0.24–0.44] 0.28 [0.19–0.37] 0.95 [0.68–1.22] 0.41 [0.34–0.48] Foreign 0.50 [0.09–0.90] 0.48 [0.24–0.72] 1.48 [0.88–2.08] 0.74 [0.52–0.96] Total 0.36 [0.27–0.45] 0.32 [0.23–0.41] 1.08 [0.83–1.33] 0.47 [0.40–0.54] without greater differences during the studied periods. Over Even if the current epidemiological survey does not 60% of cases occurred in disadvantaged neighborhoods during systematically collect information on type of comorbidities, the three periods (p = 0.261). Leishmaniasis in foreign subjects homelessness status, species of Leishmania or the type of animals increased over time, but only accounted for a third of the total that could have acted as a reservoir, it was possible to extract some cases in the last period. A significant decrease in cases related of this information from the comments included by interviewers. to any immunosuppression (due to disease or treatment) was Regarding comorbidities, it was observed that an 18.4% (n = 35) observed (p < 0.001). of the studied population had a diagnosis of HIV and two cases All types of leishmaniasis occurred mainly in Spanish were described as Hepatitis C positive. Four cases were informed born, men, and people from disadvantaged neighborhoods to be homeless. Seven cases were characterized as Leishmania (Table 4). Visceral leishmaniasis was present in 40.9% of donovani, and one case was described as Leishmania braziliensis. the cases that referred contact with an animal and 26% of the cases that referred intravenous drug use. A 33.8% of the cases who referred travel to an endemic country DISCUSSION presented a cutaneous type of leishmaniasis (endemic country according to WHO’s current guidelines at the time of the The results of this study have shown an increase in the incidence survey). Most of the visceral leishmaniasis required a hospital of leishmaniasis in the city of Barcelona from 1996 to 2019. This admission and it was the only leishmaniasis type related to a increase only appears as statistically significant for the period fatal outcome. 2016-2019. The establishment of the Catalan Microbiologic Frontiers in Veterinary Science | www.frontiersin.org 4 April 2021 | Volume 8 | Article 653999 Palma et al. Epidemiology of Leishmaniasis in Barcelona, Spain (1996–2019) FIGURE 2 | Annual incidence of leishmaniasis per 100,000 inhabitants, by complete sample and sexes. Barcelona, 1996–2019. (n = 177 cases). TABLE 3 | Cases of leishmaniasis according to type of disease and risk factors, population and male adults. The number of foreign-born cases during the three studied periods. has increased since 2003 while the number of cases associated 1996–2005 2006–2015 2016–2019 Total p-value to immunosuppression has decreased. There is also a change in N (%) N (%) N (%) N (%) the type of leishmaniasis in the three studied periods, with an increase of cutaneous leishmaniasis. Type of leishmania <0.001 The cumulative incidence during these 24 years of observation Visceral 30 (54.6%) 24 (46.2%) 7 (10%) 61 (34.5%) was higher than previously reported in analysis of the same Cutaneous 0 27 (51.9%) 53 (75.7%) 80 (45.2%) database (0.33 per 100,000 inhabitants between 1997 and 2014) Mucocutaneus 1 (1.82) 0 3 (4.3%) 4 (2.3%) (33) but lower than the reported incidence of Spain (16, 25). After Risk factors the modification of the confirmation and surveillance system Male sex by ages (28, 29), there was a significant increase of the total incidence Male (0–4) 7 (58.3%) 4 (50%) 2 (28.6%) 13 (48.3%) 0.545 f probably due to an improved reporting, and because a possible Male (5–14) 2 (100%) 0 5 (55.6%) 7 (63.6%) 0.491 f increase in the clinical suspicion at primary care level. Male (15–24) 1 (33.3%) 1 (50%) 3 (50%) 5 (45.5%) 1f Our study has shown that men between 25 and 64 years old Male (25–44) 30 (90.9%) 16 (72.7%) 14 (77.8%) 60 (82.2%) 0.202 f present a higher incidence of leishmaniasis in all the studied Male (45–64) 4 (100%) 9 (64.3%) 11 (91.7%) 24 (80%) 0.149 f periods. Previous studies have associated this correlation with Male (65 or more) 0 2 (40%) 10 (56.6%) 12 (50%) 0.640 f the incidence of HIV in this group (33). However, the reasons Disadvantaged 31 (63.3%) 36 (75%) 42 (60.9%) 109 (65.7%) 0.261 why men of working age have a higher incidence of leishmaniasis neighborhood are diverse, and cannot be exclusively related to this comorbidity, even when the data obtained through the epidemiological survey Foreign origin 6 (10.9%) 16 (30.8%) 23 (32.9%) 45 (25.4%) <0.001 does not allow us to test for further causality. In this population, Immunosuppression 25 (45.5%) 18 (34.6%) 7 (10%) 50 (28.5%) <0.001 men accounted for 91.9% of the cases related to alcoholism, Due to disease 24 (61.5%) 17 (32.7%) 6 (8.6%) 47 (29.2%) <0.001 81.3% of cases with a history of intravenous drug use and 70% Due to treatment 12 (30.8%) 6 (11.5%) 5 (7.1%) 23 (14.3%) 0.009 of traveling to endemic countries. Studies have described a male Total cases 55 (100%) 52 (100%) 70 (100%) 177 (100%) bias in certain infectious diseases (34), including leishmaniasis (35), proposing physiological and behavioral theories. However, P-values presented with an italic f (f) when Fisher’s exact test is performed. the evidence is not conclusive, and we cannot exclude that man are more exposed to infected vectors because of their social or working activities. Notification System as a consequence of the decree 203/2015 (29), By age groups, there was a consistent high incidence in cases which requires mandatory notification of all identified cases by under 5 years of age, but also a rise in the cases over 65 years laboratories, is likely to have contributed greatly to the observed since 2001. In the younger population, the main causes are trend, together with other factors such as the improvement in associated to a lack of effective immune response (14, 33). In diagnostic tools and possibly a real change in disease burden. our sample, an 88.9% of the age group 0-4 was from native The increase is observed in all ages, being greater in the younger origin, a 66.7% presented a visceral type of leishmaniasis, and Frontiers in Veterinary Science | www.frontiersin.org 5 April 2021 | Volume 8 | Article 653999 Palma et al. Epidemiology of Leishmaniasis in Barcelona, Spain (1996–2019) TABLE 4 | Type of Leishmaniasis according to risk factors and evolution. in Europe (7), although a possible competence of P. perniciosus to L. tropica should be accounted (37–39). Improvements in the Visceral Cutaneous Muco Total P-value cutaneous registry should allow for the systematic report of the species of N (%) N (%) N (%) (a) Leishmania involved in the clinical cases. N (%) In relation to vulnerable populations, there was a decrease Risk factors in cases related to immunosuppression, due to disease or Foreign origin 12 (19.7%) 26 (32.5%) 0 45 (27.9%) 0.092 f treatment. This decrease could correspond to the improve of Male sex 43 (71.7%) 52 (65%) 4 (100%) 109 (68.1%) 0.491 the antiretroviral treatments for HIV population (16), as well as Disadvantaged 39 (69.6%) 51 (64.6%) 3 (75%) 102 (75%) 0.911 improvements in the care of immunosuppressed patients, like neighborhood transplanted, who presents a very low incidence of cases. In this Immunosuppression 31 (50.8%) 8 (10%) 1 (25%) 50 (31.1%) <0.001 f study, most of the cases occurred in disadvantaged districts of Contact with animal 25 (40.9%) 9 (11.3%) 1 (25%) 35 (21.8%) <0.001 f Barcelona, without changes in time. Homeless cases are at a Travel to endemic 8 (13.1%) 27 (33.8%) 0 35 (20.1%) <0.001 f higher risk to get lost to follow up, facing a challenge to the country prevention and surveillance strategy for years to come. Even History of transplant 1 (1.6%) 1 (1.3%) 0 2 (1.2%) * when we did not have access to information of the individual’s History of alcoholism 8 (13.1%) 3 (3.8%) 1 (25%) 12 (6.9%) <0.001 f socio-economic status, the use of the Available Family Income History of transfusion 5 (8.2%) 0 0 5 (2.9%) * Index is a good proxy to evaluate inequalities within the city (32). Leishmaniasis is the most relevant endemic zoonosis in the Intravenous drug use 16 (26.2%) 0 0 16 (9.2%) * last years in the Mediterranean basin, due to the coexistence of Evolution Leishmania protozoa; reservoirs such as hare (11, 40), rabbits Hospital admission 57 (93.4%) 1 (1.3%) 1 (25%) 62 (32.6%) (10), rodents and dogs (9, 41), and competent vectors (sandflies Cured without 51 (83.6%) 67 (83.8%) 3 (75%) 121 (68.4%) from the genus Phlebotomus). As a Mediterranean city, Barcelona sequels has the appropriate climatic characteristics for local transmission Cured with sequels 4 (6.6%) 6 (7.5%) 1 (25%) 11 (6.2%) of Leishmania sp. The presence of the two main vectors, Death 2 (3.3%) 0 0 3 (1.7%) Phlebotomus perniciosus and Phlebotomus ariasi, are known due Total 61 (34.5%) 80 (45.2%) 4 (2.3%) 177 (100%) to the monitoring of the city of Barcelona by the ASPB, the Barcelona, 1996–2019 (missing values = 32; 18.08%). P-values presented with an italic f institution responsible for the vector surveillance and control (f) when Fisher’s exact test is performed, and with an asterisk (*) when not performed due in the city (42). Furthermore, recent research indicates that to cases with very low frequency. Norway rat, a synanthropic murid that shows high abundance and deeply distribution in the sewer system of the city (6), could play a relevant role as host reservoir of Leishmaniasis (43). At 85.19% evolved to healing without sequel. Is important to notice this point, it is important to emphasize the sewers have been that there was no differences between native or foreign-born also recorded as suitable breeding site for sandflies in Barcelona population in this age group during the three studied periods (unpublished data). (Fisher’s p = 0.142). Moreover, cases in the 0-4 age group during Climate change is affecting the geographical distribution and the third studied period (2016–2019), only occurred in Spanish- seasonality of many species, including sandflies, and increased born population. In the elderly group, there was a rise in the connectivity has facilitated the expansion of different insect diagnosis of cutaneous leishmaniasis, being 64% of the total cases vectors into new geographical areas (7, 21). A climate change over 65 years of age. This group only presented a 20% history of induced expansion of vector competent species will at the same immunosuppression and a 24% foreign origin. A 76% of the cases time lead to an expansion of the risk area for leishmaniasis. The evolved to healing without sequel. The reasons for this increase expansion of the green areas across the city due to the Climate are unclear and may be related to a change in the diagnosis change action plan (44) should consider the potential risk of system and access to dermatological services from primary care, increase in competent vector distribution and reservoirs. Overall, but further investigation is required. there is a need to enforce the surveillance system of leishmaniasis. Among population from foreign country of birth, there is Therefore, we recommend undertaking surveys in the city to a persistent increase of incidence since 2003, consistent with characterize the distribution and abundance of different vectors, a rise in foreign population migrating to Barcelona (3.8% of as a strategy to establish an effective surveillance and control the total population in 1996 to 25.7% in 2019) (31), but also program to reduce the risk of transmission. to international traveling to endemic areas, due to tourism, Our results show that that autochthonous transmission is visiting relatives and work (22, 36). The difference between occurring in the city of Barcelona and consequently a more autochtonous and imported cases is difficult to establish due in-depth study of the vectors present in the city should be to the long incubation period of leishmaniasis (2 weeks to carried out, in order to know their distribution, abundance, several years), and inconsistencies in the reporting of identified and blood feeding behavior and thus have a diagnosis of the Leishmania species. Thus, our data might be overestimating the risk of transmission and spillover into humans. Epidemiological, burden of locally acquired Leishmania. The introduction risk vectorial and health surveillance must have in consideration supposed by Leishmania braziliensis imported cases is thought the high risk groups, like homeless and exposed workers, to be limited due to the reported absence of competent vectors as those who work in sewer systems, together with vector Frontiers in Veterinary Science | www.frontiersin.org 6 April 2021 | Volume 8 | Article 653999 Palma et al. Epidemiology of Leishmaniasis in Barcelona, Spain (1996–2019) control programs associated to renovation works affecting the ETHICS STATEMENT underground structure that may facilitate the movement of Phlebotomus into inhabited areas (3). Ethical review and approval was not required for the The main limitations of this study are the loss of follow up study on human participants in accordance with the of some cases, and the lack of information regarding significant local legislation and institutional requirements. Written variables. There is a regular loss of cases each year, which may be informed consent from the participants’ legal guardian/next due to cases that occurred in the homeless, or people that were in of kin was not required to participate in this study transit and the clinical history is incomplete. There is a clear need in accordance with the national legislation and the to review the current epidemiological survey to systematically institutional requirements. collect information on the detected leishmania species, the type of treatment used and its efficacy, as well as homelessness AUTHOR CONTRIBUTIONS status, to better characterize the impact of leishmaniasis on vulnerable populations. Identifying the domestic animals that act TM, J-PM, and CR worked in the conception and first design of as reservoirs and ensuring they receive the necessary treatments the work. LM, PS, and EM were in charge of the acquisition of to reduce the risk of new transmissions to humans should also the data, and organization of the database. DP performed the be a priority to reduce the risk of local outbreaks (45, 46). It statistical analysis and wrote the first draft of the manuscript. is also important to quantify the role that non-domestic animal DP, LM, and JF worked in the interpretation of data for the species may play as reservoirs associated to human infection work. DP and LM were in charge of drafting the work. RB-M, cases in the city (5, 47). Collaboration at an epidemiological JF, PS, EM, CR, and TM critically revised the manuscript. and entomological level is one of the pillars to reduce the All authors provide their final approval of the version to be risks of transmission, thus trying to work on a One Health published and agreed to be accountable for all aspects of the concept that integrates the different fields involved in the work in ensuring that questions related to the accuracy or transmission processes. integrity of any part of the work are appropriately investigated Even though leishmaniasis is an endemic disease in Spain, and resolved. the city of Barcelona will continue to be a highly transited city, with a higher migration rate and tourism, which may ACKNOWLEDGMENTS favor the occurrence of imported cases. This constitutes an entomological, clinical, and epidemiological challenge, due to To the nursing team of the ASPB, for their work in the follow-up the variety of clinical presentations and adaptation to vectors or of cases that has allowed us to carry out this study. local reservoirs. SUPPLEMENTARY MATERIAL DATA AVAILABILITY STATEMENT The Supplementary Material for this article can be found The raw data supporting the conclusions of this article will be online at: https://www.frontiersin.org/articles/10.3389/fvets. made available by the authors, without undue reservation. 2021.653999/full#supplementary-material REFERENCES Barcelona, Spain. Emerg Infect Dis. (2019) 25:1222–4. doi: 10.3201/eid2506.1 81027 1. Inceboz, T. Epidemiology and ecology of leishmaniasis. In: Rodriguez- 7. Ready PD. Leishmaniasis emergence in Europe. Euro Surveill. (2010) Morales AJ, editor. Current Topics in Neglected Tropical Diseases. 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The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the Conflict of Interest: The authors declare that the research was conducted in the copyright owner(s) are credited and that the original publication in this journal absence of any commercial or financial relationships that could be construed as a is cited, in accordance with accepted academic practice. No use, distribution or potential conflict of interest. reproduction is permitted which does not comply with these terms. Frontiers in Veterinary Science | www.frontiersin.org 9 April 2021 | Volume 8 | Article 653999