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Association between feline immunodeficiency virus and Leishmania infantum infections in cats: a retrospective matched case-control study

Abstract

Background

Feline leishmaniosis caused by Leishmania infantum is often associated with feline immunodeficiency virus (FIV) infection; however, the role and clinical significance of this coinfection remain unknown. This study aimed to assess whether FIV is associated with L. infantum infection in cats from canine leishmaniosis endemic areas and to report the clinical signs and hematological alterations associated with coinfection.

Methods

A retrospective matched case-control study (ratio 1:2) was conducted. Data of clinical examination and complete blood count (CBC) were selected from a cohort of 705 cats examined for epidemiological studies on feline leishmaniosis conducted between 2012 and 2019. Ninety-one FIV seropositive cases and 182 FIV seronegative control cats were selected. Matching was done according to age, sex, lifestyle and geographic provenience of case cats. Rapid ELISA devices were mainly used to detect anti-FIV antibodies. Anti-Leishmania IgG antibodies were detected by indirect-immunofluorescence test (IFAT). Leishmania DNA was searched in blood, oral and conjunctival swabs by quantitative real-time PCR.

Results

Feline immunodeficiency virus seropositive cats had no hematological abnormalities suggestive of an advanced stage of FIV infection and were statistically more frequently IFAT positive, and their risk of being L. infantum antibody positive was 2.8 greater than in the FIV seronegatives. The association of FIV seropositivity with L. infantum antibody positivity was confirmed in the univariable model of logistic regression. A multivariate model found FIV infection and L. infantum PCR positivity as predictors of a positive L. infantum IFAT result. Male outdoor cats from rural or suburban areas were at risk for FIV and L. infantum antibody positivity. Clinical signs more frequently associated with the coinfection were oral lesions, pale mucous membranes and low body condition score (BCS).

Conclusions

This study documents that FIV seropositive cats with no hematological abnormalities suggestive of an advanced stage of FIV infection are more prone to be L. infantum seroreactive by IFAT in endemic areas. Therefore, FIV seropositive cats should be tested for L. infantum antibodies and treated for preventing sand fly bites. Pale mucous membranes, low BCS and oral lesions but no CBC abnormalities were significantly associated with the coinfection.

Graphical abstract

Background

Leishmaniosis is a vector-borne disease caused by protozoa of the Leishmania genus transmitted by sand fly bites. Leishmania infantum is the most widespread species and is of zoonotic concern, with dogs considered the main domestic reservoir in endemic areas. However, other domestic and wild animals are reported to be infectious to sand flies [1]. In recent years, an increasing number of case reports of feline leishmaniosis (FeL) and subclinical infections caused by L. infantum were documented in endemic areas of the Mediterranean basin [2], and FeL is considered an emerging feline disease [3].

Many studies have confirmed that feline L. infantum infection is not negligible in areas where canine leishmaniosis is endemic [2]. However, different levels of endemicity and type of population under study or differences in diagnostic methodologies may be responsible for the high variability in antibody or molecular prevalences reported in published studies [2]. Investigations have been performed on L. infantum prevalence in cats in Southern Italy for a long time, reporting an antibody prevalence between 6.9 and 59% [4,5,6,7,8,9,10] and a molecular prevalence between 1.3 and 61% [5, 7,8,9, 11, 12]. In Spain, the antibody prevalence reported ranges between 3.2 and 4.8% in the Madrid area [13,14,15,16], between 2.2 and 16% in the northeast [17,18,19] and 28.3% in the south of the country [20]. The molecular prevalence reported ranges between 0 and 0.43% in the Madrid area [13,14,15,16], between 3 and 26% in the northeast [6, 17,18,19, 21] and 25.7% in the south of the country [20].

Feline immunodeficiency virus (FIV) is a retrovirus distributed in feline populations worldwide and associated with adult, male and free-roaming cats because the main transmission path is via biting [22]. Prevalence rates of FIV positivity are therefore influenced by the characteristics of populations under study, and surveys reporting FIV prevalence in the same area of South Italy investigated in the present study found a wide range of positivity, between 7.6 and 37% [6, 8, 23]. FIV prevalence studies available from various regions of Spain reported ranges between 5.1 and 20.9% [13,14,15, 17, 19, 24, 25].

Among risk factors for feline L. infantum infection, co-infection with feline immunodeficiency virus is the most investigated. Many studies found a significant association between FIV and L. infantum positivity in cats [5, 9, 10, 12, 19, 26,27,28]. However, other studies did not document this association [8, 14, 17, 20, 29,30,31,32]. Therefore, the association between FIV and L. infantum infection in cats remains unclear. The aims of the present study were to assess whether FIV and L. infantum infections are associated in cats living in canine leishmaniosis endemic areas of South Italy (Calabria and Sicily) and Spain (Catalonia and Andalusia) and to investigate clinical signs and hematological abnormalities associated with this coinfection.

Methods

Study design, cat characteristics and selection

A retrospective matched case–control study was carried out. Feline immunodeficiency virus seropositive (cases) and FIV seronegative (controls) cats were selected from our research database if they were evaluated by physical examination and tested for FIV as well as for L. infantum by IFAT and PCR in blood, conjunctival and oral swabs with the same methodology. A population of 705 cats studied between 2012 and 2019 was examined. The assumptions were: alpha < 5%, power ≥ 80%, two controls per case, L. infantum positivity 17.3% (prevalence of the population where cases and controls were extracted from) and expected odds ratio (OR) of 2.5. The target sample size was 92 cases and 184 controls. Cases and controls were matched according to age (> 6 months and exposed to sand flies for at least one transmission season), sex (male/female), lifestyle (indoor/outdoor) and geographical provenience (Sicily, Calabria, Catalonia, Andalusia) (Table 1). Cats were enrolled after their owners provided informed consent and in compliance with the requirements of ethics committees from the authors' academic institutions. The “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) recommendations were followed to describe the study methods [33].

Table 1 Signalment and history data of 91 feline immunodeficiency virus (FIV)-positive cases and 182 FIV-negative controls, with description of number (N) and percentage (%) of cats recorded for each variable

Diagnosis of feline retroviral infections

Different diagnostic tests were used in the period of time considered for the retrospective selection of matched cases and controls (2012–2019). In particular, anti-FIV antibodies were investigated with commercial kits (SNAP Combo Plus FeLV antigen and FIV antibody test, Idexx Laboratories, Westbrook, ME, USA; Pet Check FIV antibody test kit, IDEXX Laboratories, Westbrook, ME, USA; INgezim FIV, Ingenasa, Madrid, Spain). The FeLV positivity was assessed by a rapid ELISA test detecting p27 antigenemia (SNAP Combo Plus FeLV antigen and FIV antibody test, Idexx Laboratories, Westbrook, ME, USA) or by blood real-time PCR (U3 region LTR-genesig® Advanced kit, Rownhams, UK). All tests were performed according to the manufacturer’s protocol.

Leishmania infantum

IFAT

Antigen slides were produced by C.Re.Na.L (Centro di Referenza Nazionale per la Leishmaniosi, Palermo, Italy) using L. infantum strain MHOM/IT/80/IPT1. A fluoresceinated anti-cat immunoglobulin G (IgG) antibody [working anti-feline IgG (H + L)-FITC, Fuller Laboratories, Fullerton, CA, USA] was used according to Persichetti et al. (2016), and the endpoint titer of positive samples was determined preparing serial two-fold dilutions of serum starting from 1:20. The cutoff value for positivity was set at 1:80 [34, 35]. Fluorescence microscope readings were done by a unique operator (MM).

PCR

The EDTA blood and swab DNA was extracted using the PureLink Genomic DNA kit (Invitrogen, Life Technologies Waltham, MA, USA). Blood from a clinically healthy non-infected cat was always used as a negative control. The quantitative real-time polymerase chain reaction (RT-PCR) was carried out in a CFX96 Real-time System (Bio-Rad Laboratories s.r.l., Hercules, CA, USA) using TaqMan Master Mix (Applied Biosystems by ThermoFisher, Waltham, MA, USA) and performed as previously described [36].

Complete blood count

Complete blood count (CBC) was performed using a laser hematology analyzer (IDEXX ProCyte Dx Hematology Analyzer, IDEXX laboratories, Westbrook, ME, USA). Reference intervals of statistically analyzed CBC parameters are listed in Additional file 1: Table S1. Blood smears were stained by May Grünwald-Giemsa staining and examined for morphological abnormalities and platelet concentration estimate.

Variables

Data extracted from the database and included in the statistical analysis were: (1) FIV and L. infantum diagnostic test results: anti-FIV antibodies (positive/negative); IFAT anti-L. infantum antibodies (titer ≥ 1:80/≤ 1:40); L. infantum PCR assay (positive/negative PCR test from blood and/or swabs); L. infantum IFAT and PCR tests (positive/negative at both tests); (2) potential risk factors for FIV and L. infantum positivity from signalment and history data set: sex (male/female), age (months), age group [two different cutoff values for age group setting were analyzed as they influence the exposure of cats to a different number of transmission seasons: 24 months (≤ 24 months/> 24 months) and 36 months (≤ 36 months/> 36 months)], hair (shorthaired, medium-longhaired, longhaired), lifestyle and origin (indoor/outdoor; single-cat/multi-cat household; stray/owned), provenience (Sicily, Calabria, Catalonia, Andalusia), environment (rural and suburban/ urban); (3) clinical abnormalities more frequently detected in the 273 cats (8–37% of them): poor body condition score (BCS) (< 3.5/5: underweight, ≥ 3.5/5 normal and overweight), cutaneous (presence/absence of at least one of the following: ulcers, papules, nodules, crusts, scales and alopecia), oral (presence/absence of at least one of the following: gingivitis, stomatitis) and ocular (presence/absence of at least one of the following: blepharitis, conjunctivitis, keratitis, uveitis and panophthalmitis) lesions, enlarged lymph nodes (presence/absence), pale mucous membranes (pale/ normal); (4) CBC abnormalities: anemia (and anemia severity: low, moderate or severe), neutrophilia, neutropenia, monocytosis, lymphocytosis, lymphopenia, eosinophilia, eosinopenia, basophilia, thrombocytopenia.

Statistical analysis

Statistical analyses were performed using Stata 16 (StataCorp LP, College Station, TX).

Data set was evaluated for normal distribution by skewness and kurtosis test. T-test was used in case of normal distribution and Mann-Whitney U test when data were not normally distributed to make comparisons. According to FIV and Leishmania status, differences between groups were evaluated, and the IFAT titers between cases and controls were also compared. Odds ratios (OR) and 95% confidence intervals (CI) of Leishmania and FIV positivity were calculated and stratified according to the other variables studied. We used a univariate logistic regression model adjusted for all variables studied, and only the statistically significant ones were reported (P ≤ 0.05). Multivariable models were computed using statistically significant univariate models (P ≤ 0.05) considering two different categories: (1) risk factors; (2) clinical signs and CBC changes. Overall, 13 sets of multivariable logistic regression were constructed. Statistical analyses of L. infantum tests were carried out separately for IFAT, PCR and positivity to both tests. P-value was considered significant for values ≤ 0.05.

Results

Description and analysis of clinical characteristics of cases and controls

A total of 273 cats were selected with a 1:2 case/control ratio. The 273 sera were tested for anti-FIV antibodies, and 264 of them were also tested for FeLV and found negative. In particular, 144 sera were tested with SNAP Combo Plus FeLV antigen and FIV antibody rapid test (Idexx Laboratories, Westbrook, ME, USA). One hundred twenty cats were tested for anti-FIV antibodies by Pet Check FIV antibody test kit (IDEXX Laboratories. Westbrook, ME, USA) and by blood PCR for FeLV (U3 region LTR-genesig® Advanced kit, Rownhams, UK). Nine sera were tested for anti-FIV antibodies by ELISA (INgezim FIV, Ingenasa, Madrid, Spain).

The 182 controls were matched to 91 cases, and the differences between the two groups according to the matched variables were not statistically significant (Fisher’s exact test). Signalment and history data of both case and control cats are reported in Table 1. The age of cats was the unique normally distributed variable (range 7–204 months; mean 66.1 months ± 48), and the difference of mean ages (cases: 67.2 months ± 47.4; controls: 64.9 months ± 48.1) of the two groups was not statistically significant (t-test). The two different cutoff values used for age group settings did not yield different results, and we reported results obtained with age group cutoff set at 24 months. No statistically significant differences were found in the other clinical characteristics of the two groups of cats examined in addition to the ones used to match cases and controls (Fisher’s exact test and chi-square test). The clinical features considered in the selected cats are listed in Table 2. The proportion of cats with enlarged lymph nodes and skin lesions was higher among FIV-seropositive cats than the FIV seronegatives [Fisher’s exact test: P = 0.025 (OR = 1.765; 95% CI 1.05–2.944) and P = 0.023 (OR = 1.978; 95% CI 1.081–3.562), respectively] (Table 2). Additionally, the ratios of neutrophilia and monocytosis were higher among cases than controls [Fisher’s exact test, respectively: P = 0.002 (OR = 2.513; 95% CI 1.337–4.513) and P < 0.001 (OR = 3.661; 95% CI 1.851–7.108), respectively] (Table 3).

Table 2 Clinical findings considered in the 91 feline immunodeficiency virus (FIV)-positive cases and 182 FIV-negative controls, with description of number (N) and percentage (%) of cats recorded for each variable
Table 3 Statistically significant hematological changes in 91 feline immunodeficiency virus (FIV)-positive cases compared to 182 FIV-negative controls, with description of number (N) and percentage (%) of cats recorded for each variable

Leishmania infantum and FIV positivity association

Leishmania infantum IFAT and PCR results are displayed in Table 4. Cases were statistically more frequently IFAT positive than controls [Fisher’s exact test: P = 0.001 (OR = 2.765; 95% CI 1.482–5.249)], but the difference was not significant when considering the PCR test results or both tests (Fisher’s exact test). Feline immunodeficiency virus infection was associated only with an increased risk of L. infantum antibody positivity detected by IFAT, and the ORs of strata for selected covariates in FIV and IFAT L. infantum-positive cats are summarized in Table 5.

Table 4 Positivity to L. infantum tests of 91 feline immunodeficiency virus (FIV)-positive cases and 182 FIV-negative controls, with description of number (N) and percentage (%) of cats recorded for each variable
Table 5 Odds ratios (OR), 95% confidence intervals (CI) and P-values for feline immunodeficiency virus (FIV) and IFAT L. infantum positivity (IFAT/FIV) according to the selected covariates

Medians of IFAT titers of positive cases and controls were not statistically different (Mann-Whitney U-test).

The results of univariable and multivariable analyses of significant risk factors and clinical abnormalities are listed in Table 6. In the univariable models, L. infantum antibody positivity was significantly associated with FIV antibody positivity, but this association was not found with PCR positivity (logistic regression: P = 0.002). A unique multivariable model yielding significant associations was obtained, and it was with L. infantum antibody positivity, anti-FIV antibody positivity and L. infantum PCR (logistic regression: P < 0.0001). Logistic regression models did not find significant associations of risk factors and clinical abnormalities considered for L. infantum and FIV-positive cats.

Table 6 Univariate and multivariate analyses of significant risk factors and clinical abnormalities according to L. infantum positivity

Discussion

Clinical characteristics of cases and controls

Feline immunodeficiency virus is a RNA virus belonging to the family Retroviridae, subfamily Lentiviridae, a group of viruses known to cause life-long infections with protracted incubation periods [22]. Immunosuppression is determined in FIV-positive cats by a progressive decline in CD4+ T cells number, reduction in the CD4+/CD8+ ratio, generalized lymphoid depletion, reduced ability to respond to antigenic stimulation and dysregulation of cytokine production [22]. Immunosuppression contributes to secondary and opportunistic infections but FIV-positive cats remain clinically healthy for years, depending on the infecting isolate [22]. The FIV seropositive case cats of this study differed from controls regarding clinical abnormalities observed in the 273 studied cats. In particular, FIV seropositive cats more frequently showed enlarged lymph nodes and skin lesions. Peripheral lymphadenomegaly is reported in both early and more advanced stages of FIV infection and is directly caused by the virus as well as by secondary infections, immune-mediated and neoplastic conditions observed in FIV-positive individuals [22]. Miscellaneous skin diseases are described in FIV-positive cats, and they are mainly caused by secondary and opportunistic infections that may have a more severe and prolonged course compared to FIV negative cats [37]. Additionally, cutaneous neoplasms (particularly carcinomas) are reported with high rates in FIV-positive cats [37]. In the present study, FIV seropositive cats had hematological abnormalities related only to increased neutrophil and monocyte concentration. In agreement with the present results, neutrophilia [38] and monocytosis [38, 39] were the most common hematological abnormalities seen at the time of the first diagnosis in cats with naturally occurring FIV infection in previous studies [39, 40]. During the asymptomatic phase of FIV infection, the number of granulocyte/macrophage and erythroid progenitors is unchanged [40], and cats have a normal hematological response to concurrent diseases [38]. Conversely, in advanced stages of FIV infection cytopenia (anemia, leukopenia, neutropenia, and lymphopenia) is more common [40]. In this study, the stage of FIV infection was not assessed with immunological markers, and this is a limitation shared with all field studies that have so far investigated the association between FIV and L. infantum infections. Based on hematological findings, we assume that many of these cats were not in terminal stages of the disease. FIV-induced immunosuppression could have facilitated a secondary or opportunistic infection, to which an appropriate inflammatory response (neutrophilic and monocytic) was made [38]. However, it is important to highlight that neutrophilia is also compatible with stress leukogram, immune-mediated disorders, neoplasia and tissue necrosis and that monocytosis may also occur in many of these conditions [41].

Leishmania infantum and FIV positivity association

We found that FIV antibody positivity was associated with IFAT antibody positivity to L. infantum in cats from areas endemic for both infections. In particular, FIV seropositive cats had a 2.8 times higher risk to be L. infantum antibody positive. Similarly to a previous study, we did not find differences in the antibody titer among the two groups [6]. Additionally, this association was confirmed by the logistic regression analysis performed in the univariable model and in the significant multivariable model constructed. Previous studies evaluating risk factors for L. infantum positivity, such as FIV seropositivity, were prevalence studies that analyzed cross-sectional data [5, 9, 10, 12, 19, 26,27,28, 30, 42]. Large cross-sectional studies are often based on routinely collected samples and history, and clinical findings data can be incomplete and do not provide information on some confounding factors [5]. We designed a specific case-control study to test the hypothesis that FIV seropositivity was associated with L. infantum positivity in endemic areas, and we were able to match cases and controls for confounding factors such as age, sex, lifestyle and geographic area. The study was retrospective, but data were obtained from a selected population of 705 cats homogeneous for systematic recording of clinical data and L. infantum and CBC assays. Unfortunately, methods used for testing retroviral infections were inhomogeneous, and this is a limitation of the study. However, all the different tests we used have high sensitivity and specificity and are widely used in relevant studies about feline pathogens [43,44,45].

As well as cross-sectional studies, case-control studies are not able to prove which of the associated variables has a causative role. This question is answered by longitudinal field investigations which unfortunately are not easily performed in veterinary medicine.

We did not find associations of FIV seropositivity with L. infantum PCR positivity. We performed PCR assays on three different tissues preferring non-invasive samples (swabs) and residual EDTA blood, and the number of PCR-positive cats was low when the sample size was calculated according to IFAT positivity. Consequently, results concerning PCR should be interpreted with caution, and a larger sample size should be assessed. However, in the multivariate model, PCR positivity was also a FIV seropositivity predictor for L. infantum antibody positivity. Since 1998, a significant association between FIV infection and anti-L. infantum antibodies was reported [10], and subsequently many other studies have confirmed this association with L. infantum antibody [12, 19, 26, 27], PCR [28, 42], antibody and/or PCR [5, 9] positivity. However, sample size and FIV prevalence were variable in these studies as well as diagnostic techniques used to evaluate both FIV and L. infantum positivity, and this is a limitation to compare results from different studies or make a meta-analysis. The role of FIV coinfection in L. infantum-positive cats could therefore be better investigated by evaluating markers useful to assay the cat immunocompetence. In L. infantum-infected dogs, susceptibility to the development of clinical disease is due to reduced cellular immune response and high antibody level [46]. Adaptive humoral and cell-mediated immune response is elicited by L. infantum feline infection, but no difference was found in FIV seropositive cats in a study evaluating the ex vivo blood production of L. infantum-specific IFN-γ [6].

The selected cohort of 273 cats included only cats > 6 months in order to examine cats exposed to sand flies for at least one transmission season, and we analyzed two different cutoff values for setting age groups to compare cats exposed to two or three transmission seasons with cats exposed to four or more sand fly seasons. In fact, age was often found to be a risk factor for cat L. infantum positivity in previous studies. In particular, cats > 12 [13, 47], 24 [7] or 36 months [9, 28, 48] were more frequently found infected. However, we did not find significant differences in L. infantum positivity among age groups of case and control cats, similarly to other studies comparing L. infantum positivity in cats of various age groups [26, 27] and where age analysis did not include age grouping [30]. Higher antibody titers in dogs are associated with the progression of infection to disease, but a longitudinal clinical, serological and parasitological evaluation of cats is needed to correctly analyze these data [46]. However, age can also influence host susceptibility to diseases in case of kittens or senior age [49, 50], but we did not set age groups with this aim. Iatta et al. [5] compared cats aged between 19 and 72 months (adults) with younger and older cats. Curiously, these adult cats had the highest risk for L. infantum positivity compared to the other age groups [5].

Akhtardanesh and others (2020) evidenced by a multivariate logistic regression analysis that L. infantum infection was more frequent in adult (particularly cats > 3 years old) and FIV seropositive cats [28]. Differently, when we stratified results of IFAT L. infantum and FIV seropositive cats according to selected covariates (Table 5), we found higher odds in males compared to females, in outdoor compared to indoor cats and in cats from rural and sub-urban areas compared to those from urban areas. Interestingly, males were always the sex category more frequently found positive in other studies detecting a significant sex difference in L. infantum positivity of cats [13, 26, 51]. Concerning lifestyle and housing, other studies found a significantly higher L. infantum positivity in cats from multi-cat compared to single-cat households [48], from rural compared to urban areas [51] and from colonies compared to catteries [47].

Concerning clinical findings (Table 5), the higher odds were for pale mucous membranes, low BCS and oral lesions. These latter findings are reported in feline leishmaniosis, and oral lesions are among the most frequent clinical signs observed in clinical cases [3]. Unfortunately, the clinicopathological data available from all 273 selected cats included only CBC, and no other clinicopathological abnormalities could be analyzed in the matched cats. This is a limitation of the study, and we are able to provide information only about CBC abnormalities that were not significantly associated with positivity to both pathogens.

Conclusions

This case-control study documents that FIV seropositive cats with no hematological abnormalities suggestive of an advanced stage of FIV infection are more prone to be L. infantum seroreactive by IFAT in endemic areas. Therefore, FIV seropositive cats should be tested for L. infantum antibodies and treated to prevent sand fly bites. Pale mucous membranes, low BCS and oral lesions but no CBC abnormalities were significantly associated with the coinfection.

Availability of data and materials

Data supporting the conclusions of this article are included in the report. Raw data are available from the corresponding author upon reasonable request.

References

  1. Cardoso L, Schallig H, Persichetti MF, Pennisi MG. New epidemiological aspects of animal leishmaniosis in Europe: the role of vertebrate hosts other than dogs. Pathogens. 2021;10:307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pennisi MG. Leishmaniosis of companion animals in Europe: an update. Vet Parasitol. 2015;208:35–47.

    Article  PubMed  Google Scholar 

  3. Pennisi MG, Persichetti MF. Feline leishmaniosis: is the cat a small dog? Vet Parasitol. 2018;251:131–7.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Iatta R, Mendoza-Roldan JA, Latrofa MS, Cascio A, Brianti E, Pombi M, et al. Leishmania tarentolae and Leishmania infantum in humans, dogs and cats in the Pelagie archipelago, southern Italy. Plos Neglect Trop D. 2021;15:e0009817.

    Article  Google Scholar 

  5. Iatta R, Furlanello T, Colella V, Tarallo VD, Latrofa MS, Brianti E, et al. A nationwide survey of Leishmania infantum infection in cats and associated risk factors in Italy. Plos Neglect Trop D. 2019;13:e0007594.

    Article  CAS  Google Scholar 

  6. Priolo V, Martínez-Orellana P, Pennisi MG, Masucci M, Prandi D, Ippolito D, et al. Leishmania infantum-specific IFN-γ production in stimulated blood from cats living in areas where canine leishmaniosis is endemic. Parasit Vector. 2019;12:133.

    Article  Google Scholar 

  7. Otranto D, Napoli E, Latrofa MS, Annoscia G, Tarallo VD, Greco G, et al. Feline and canine leishmaniosis and other vector-borne diseases in the Aeolian Islands: pathogen and vector circulation in a confined environment. Vet Parasitol. 2017;236:144–51.

    Article  PubMed  Google Scholar 

  8. Persichetti MF, Pennisi MG, Vullo A, Masucci M, Migliazzo A, Solano-Gallego L. Clinical evaluation of outdoor cats exposed to ectoparasites and associated risk for vector-borne infections in southern Italy. Parasit Vector. 2018;11:136.

    Article  Google Scholar 

  9. Pennisi MG, Lupo T, Malara D, Masucci M, Migliazzo A, Lombardo G. Serological and molecular prevalence of Leishmania infantum infection in cats from Southern Italy. J Feline Med Surg. 2012;14:656–7.

    Google Scholar 

  10. Pennisi MG, Masucci M, Catarsini O. Presenza di anticorpi anti-Leishmania in gatti FIV+ che vivono in zona endemica. Atti LII Convegno Società Italiana Scienze Veterinarie. 1998;52:265–6.

    Google Scholar 

  11. Latrofa MS, Iatta R, Toniolo F, Furlanello T, Ravagnan S, Capelli G, et al. A molecular survey of vector-borne pathogens and haemoplasmas in owned cats across Italy. Parasit Vectors. 2020;13:116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pennisi MG. A high prevalence of feline leishmaniasis in southern Italy. Proceedings of the second international canine leishmaniasis forum, Sevilla, Spain. 2002. p. 39–48.

  13. Montoya A, García M, Gálvez R, Checa R, Marino V, Sarquis J, et al. Implications of zoonotic and vector-borne parasites to free-roaming cats in central Spain. Vet Parasitol. 2018;251:125–30.

    Article  CAS  PubMed  Google Scholar 

  14. Miró G, Rupérez C, Checa R, Gálvez R, Hernández L, García M, et al. Current status of L. infantum infection in stray cats in the Madrid region (Spain): implications for the recent outbreak of human leishmaniosis? Parasit Vector. 2014;7:112.

    Article  Google Scholar 

  15. Ayllón T, Diniz PPVP, Breitschwerdt EB, Villaescusa A, Rodríguez-Franco F, Sainz A. Vector-borne diseases in client-owned and stray cats from Madrid, Spain. Vector Borne Zoonot. 2012;12:143–50.

    Article  Google Scholar 

  16. Ayllon T, Tesouro MA, Amusategui I, Villaescusa A, Rodriguez-Franco F, Sainz A. Serologic and molecular evaluation of Leishmania infantum in cats from Central Spain. Ann N Y Acad Sci. 2008;1149:361–4.

    Article  CAS  PubMed  Google Scholar 

  17. Sherry K, Miró G, Trotta M, Miranda C, Montoya A, Espinosa C, et al. A serological and molecular study of Leishmania infantum infection in cats from the Island of Ibiza (Spain). Vector Borne Zoonot. 2011;11:239–45.

    Article  Google Scholar 

  18. Millán J, Zanet S, Gomis M, Trisciuoglio A, Negre N, Ferroglio E. An investigation into alternative reservoirs of canine leishmaniasis on the endemic Island of Mallorca (Spain): reservoirs of Leishmania infantum in Mallorca island. Transbound Emerg Dis. 2011;58:352–7.

    Article  PubMed  Google Scholar 

  19. Alcover MM, Basurco A, Fernandez A, Riera C, Fisa R, Gonzalez A, et al. A cross-sectional study of Leishmania infantum infection in stray cats in the city of Zaragoza (Spain) using serology and PCR. Parasit Vector. 2021;14:178.

    Article  CAS  Google Scholar 

  20. Martin Sanchez J, Acedo C, Munozperez M, Pesson B, Marchal O, Morillasmarquez F. Infection by Leishmania infantum in cats: epidemiological study in Spain. Vet Parasitol. 2007;145:267–73.

    Article  CAS  PubMed  Google Scholar 

  21. Tabar M-D, Altet L, Francino O, Sánchez A, Ferrer L, Roura X. Vector-borne infections in cats: molecular study in Barcelona area (Spain). Vet Parasitol. 2008;151:332–6.

    Article  CAS  PubMed  Google Scholar 

  22. Hosie MJ, Addie D, Belák S, Boucraut-Baralon C, Egberink H, Frymus T, et al. Feline immunodeficiency. ABCD guidelines on prevention and management. J Feline Med Surg. 2009;11:575–84.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Donato G, Masucci M, De Luca E, Alibrandi A, De Majo M, Berjaoui S, et al. Feline morbillivirus in Southern Italy: epidemiology, clinico-pathological features and phylogenetic analysis in cats. Viruses. 2021;13:1449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Iniesta L, Rodríguez-Cortés A, Pastor J, Quintana J, Espada Y, Alberola J, et al. Cross-sectional serosurvey of feline leishmaniasis in ecoregions around the northwestern Mediterranean. Am J Trop Med Hyg. 2007;76:676–80.

    Article  PubMed  Google Scholar 

  25. Solano-Gallego L, Hegarty B, Espada Y, Llull J, Breitschwerdt E. Serological and molecular evidence of exposure to arthropod-borne organisms in cats from northeastern Spain. Vet Microbiol. 2006;118:274–7.

    Article  CAS  PubMed  Google Scholar 

  26. Sobrinho LSV, Rossi CN, Vides JP, Braga ET, Gomes AAD, de Lima VMF, et al. Coinfection of Leishmania chagasi with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in cats from an endemic area of zoonotic visceral leishmaniasis. Vet Parasitol. 2012;187:302–6.

    Article  PubMed  Google Scholar 

  27. Spada E, Proverbio D, Migliazzo A, Della Pepa A, Perego R, De Giorgi GB. Serological and molecular evaluation of Leishmania infantum infection in stray cats in a nonendemic area in Northern Italy. ISRN Parasitol. 2013;2013:1–6.

    Article  Google Scholar 

  28. Akhtardanesh B, Moeini E, Sharifi I, Saberi M, Sadeghi B, Ebrahimi M, et al. Leishmania infection in cats positive for immunodeficiency virus and feline leukemia virus in an endemic region of Iran. Vet Parasitol Reg Stud Rep. 2020;20:100387.

    CAS  Google Scholar 

  29. Bezerra JAB, de Medeiros Oliveira IVP, Yamakawa AC, Nilsson MG, Tomaz KLR, de Oliveira KDS, et al. Serological and molecular investigation of Leishmania spp. infection in cats from an area endemic for canine and human leishmaniasis in Northeast Brazil. Rev Bras Parasitol Vet. 2019;28:790–6.

    Article  CAS  PubMed  Google Scholar 

  30. Attipa C, Papasouliotis K, Solano-Gallego L, Baneth G, Nachum-Biala Y, Sarvani E, et al. Prevalence study and risk factor analysis of selected bacterial, protozoal and viral, including vector-borne, pathogens in cats from Cyprus. Parasit Vector. 2017;10:130.

    Article  Google Scholar 

  31. Chatzis MK, Leontides L, Athanasiou LV, Papadopoulos E, Kasabalis D, Mylonakis M, et al. Evaluation of indirect immunofluorescence antibody test and enzyme-linked immunosorbent assay for the diagnosis of infection by Leishmania infantum in clinically normal and sick cats. Exp Parasitol. 2014;147:54–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Solano-Gallego L, Rodriguez-Cortes A, Iniesta L, Quintana J, Pastor J, Espada Y, et al. Cross-sectional serosurvey of feline leishmaniasis in ecoregions around the Northwestern Mediterranean. Am J Trop med Hyg. 2007;76:676–80.

    Article  CAS  PubMed  Google Scholar 

  33. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Plos Med. 2007;4:e296.

    Article  Google Scholar 

  34. Persichetti MF, Solano-Gallego L, Vullo A, Masucci M, Marty P, Delaunay P, et al. Diagnostic performance of ELISA, IFAT and Western blot for the detection of anti-Leishmania infantum antibodies in cats using a Bayesian analysis without a gold standard. Parasit Vector. 2017;10:119.

    Article  Google Scholar 

  35. Persichetti M-F, Solano-Gallego L, Serrano L, Altet L, Reale S, Masucci M, et al. Detection of vector-borne pathogens in cats and their ectoparasites in southern Italy. Parasit Vector. 2016;9:247.

    Article  Google Scholar 

  36. Vitale F, Reale S, Vitale M, Petrotta E, Torina A, Caracappa S. TaqMan-based detection of Leishmania infantum DNA using canine samples. Ann N Y Acad Sci. 2004;1026:139–43.

    Article  CAS  PubMed  Google Scholar 

  37. Backel K, Cain C. Skin as a marker of general feline health: cutaneous manifestations of infectious disease. J Feline Med Surg. 2017;19:1149–65.

    Article  PubMed  Google Scholar 

  38. Sparkes AH, Hopper CD, Millard WG, Gruffydd-Jones TJ, Harbour DA. Feline immunodeficiency virus infection. Clinicopathologic findings in 90 naturally occurring cases. JVIM. 1993;7:85–90.

    CAS  Google Scholar 

  39. Hopper CD, Sparkes AH, Gruffydd-Jones TJ, Crispin SM, Muir P, Harbour DA, et al. Clinical and laboratory findings in cats infected with feline immunodeficiency virus. Vet Rec. 1989;125:341–6.

    Article  CAS  PubMed  Google Scholar 

  40. Lutz H, Hosie M. Shalm’s veterianry hematology. 6th ed. Hoboken: Wiley; 2010.

    Google Scholar 

  41. Wong V, Hoff B, Tox D. Veterinary hematology: a diagnostic guide and color atlas. Can Vet J. 2013;54:609.

    PubMed Central  Google Scholar 

  42. Elmahallawy EK, Zanet S, Poggi M, Alsharif KF, Agil A, Trisciuoglio A, et al. Feline leishmaniosis in Northwestern Italy: current status and zoonotic implications. Vet Sci. 2021;8:215.

    Article  PubMed  PubMed Central  Google Scholar 

  43. De Luca E, Crisi PE, Marcacci M, Malatesta D, Di Sabatino D, Cito F, et al. Epidemiology, pathological aspects and genome heterogeneity of feline morbillivirus in Italy. Vet Microbiol. 2020;240:108484.

    Article  PubMed  Google Scholar 

  44. Hartmann K, Griessmayr P, Schulz B, Greene CE, Vidyashankar AN, Jarrett O, et al. Quality of different in-clinic test systems for feline immunodeficiency virus and feline leukaemia virus infection. J Feline Med Surg. 2007;9:439–45.

    Article  PubMed  Google Scholar 

  45. Rivas AK, Alcover M, Martínez-Orellana P, Montserrat-Sangrà S, Nachum-Biala Y, Bardagí M, et al. Clinical and diagnostic aspects of feline cutaneous leishmaniosis in Venezuela. Parasit Vector. 2018;11:141.

    Article  Google Scholar 

  46. Solano-Gallego L, Koutinas A, Miró G, Cardoso L, Pennisi MG, Ferrer L, et al. Directions for the diagnosis, clinical staging, treatment and prevention of canine leishmaniosis. Vet Parasitol. 2009;165:1–18.

    Article  CAS  PubMed  Google Scholar 

  47. Morganti G, Veronesi F, Stefanetti V, Di Muccio T, Fiorentino E, Diaferia M, et al. Emerging feline vector-borne pathogens in Italy. Parasit Vector. 2019;12:193.

    Article  Google Scholar 

  48. Mosallanejad B, Avizeh R, RaziJalali MH, Pourmehdi M. Antibody detection against Leishmania infantum in sera of companion cats in Ahvaz, south west of Iran. Arch Razi Inst. 2013;68:165–71.

    Google Scholar 

  49. Ray M, Carney HC, Boynton B, Quimby J, Robertson S, St Denis K, et al. 2021 AAFP feline senior care guidelines. J Feline Med Surg. 2021;23:613–38.

    Article  PubMed  Google Scholar 

  50. Pedersen NC. An update on feline infectious peritonitis: virology and immunopathogenesis. Vet J. 2014;201:123–32.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Cardoso L, Lopes AP, Sherry K, Schallig H, Solano-Gallego L. Low seroprevalence of Leishmania infantum infection in cats from northern Portugal based on DAT and ELISA. Vet Parasitol. 2010;174:37–42.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Sara Montserrat‐Sangrà, (Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, Spain), Angela Burrascano, (Dipartimento di Scienze Veterinarie, Università degli Studi di Messina), Istituto Maimònides de Investigaciòn Biomèdica de Cordoba (Cordoba, Spain), and Centro de Sanidad y Bienestar Animal (SBA) de Sadeco (Cordoba, Spain) for technical collaboration. The paper has been sponsored by Elanco Animal Health in the framework of the 16th CVBD® World Forum Symposium.

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Authors and Affiliations

Authors

Contributions

VP conceived the research study. VP, MFP and GD collected samples and carried out laboratory work with the supervision and/or collaboration of MM, MGP, LSG, PMO, ARB and FV. VP, MFP, MGP and GD selected data. VP and MM performed the statistical analysis. VP, MGP and MM interpreted the results. VP, MGP and GD wrote the first draft of the manuscript. MGP, MM, GD and LSG revised the manuscript. All authors agreed to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved and the resolution documented in the literature. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maria Grazia Pennisi.

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Ethics approval and consent to participate

Cats were sampled during the annual health check, elective surgery or trap‐neuter‐release programs and always after the signature of informed consent by the owner. Residual blood samples were mainly used for cats from Catalonia. Colony stray cats from Cordoba were sampled after approval by Centro de Sanidad y Bienestar Animal (SBA) de SADECO.

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The authors declare that they have no competing interests.

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Supplementary Information

Additional file 1

: Table S1. Reference values of complete blood count (CBC) parameters statistically evaluated. RV: reference values.

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Priolo, V., Masucci, M., Donato, G. et al. Association between feline immunodeficiency virus and Leishmania infantum infections in cats: a retrospective matched case-control study. Parasites Vectors 15, 107 (2022). https://doi.org/10.1186/s13071-022-05230-w

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