Pathogens transmitted to humans by phlebotomine sand flies are neglected, as they cause infectious diseases that are not on the priority list of national and international public health systems. ...However, the infections caused by protozoa of the Leishmania genus and viruses belonging to the Phlebovirus genus (family Phenuiviridae)-the most significant group of viruses transmitted by sand flies-have a relevant role for human pathology. These infections are emerging in the Mediterranean region and will likely spread in forthcoming decades, posing a complex threat to human health. Four species and 2 hybrid strains of Leishmania are pathogenic for humans in the Mediterranean Basin, with an estimated annual incidence of 239,500-393,600 cases of cutaneous leishmaniasis and 1,200-2,000 cases of visceral leishmaniasis. Among the phleboviruses, Toscana virus can cause neuroinvasive infections, while other phleboviruses are responsible for a typical "3-day fever"; the actual incidence of Phlebovirus infections in the Mediterranean area is unknown, although at least 250 million people are exposed. Here, we reviewed the current literature on epidemiology of sand fly-borne infections in the Mediterranean Basin, with a focus on humans. Our analysis indicates the need for increased public health activities directed to determine the disease burden of these infections as well as to improve their surveillance. Among the emerging challenges concerning sand fly-borne pathogens, the relationships between sand fly-borne protozoa and viruses should be considered in future studies, including epidemiological links between Leishmania and phleboviruses as well as the conditional capacity for these pathogens to be involved in interactions that may evolve towards increased virulence.
Testicular Dirofilaria repens infection was identified and confirmed by sequence analysis in a child in northeastern Italy. Because human dirofilariasis is emerging in southern and eastern Europe, ...this parasitic infection should be considered in the differential diagnosis of scrotal swelling in disease-endemic countries to avoid unnecessary interventions, such as orchiectomy.
Background
Most people infected with
Leishmania
remain asymptomatic, which is a common element that may promote the resurgence of clinically evident leishmaniasis in individuals with impaired ...cell-mediated immune responses. Unfortunately, there is no universally accepted assay to identify asymptomatic infection. This cross-sectional study focuses on the employment of three methods targeting different features of the parasitic infection to be used in combination for the screening of latent leishmaniasis in a newly endemic area of northeastern Italy.
Methodology/principal findings
The selected methods included highly sensitive Real-Time PCR for detection of parasitic kinetoplast (k)DNA in peripheral blood, Western Blot (WB) for detection of specific IgG, and Whole Blood stimulation Assay (WBA) to evaluate the anti-leishmanial T-cell response by quantifying the production of IL-2 after stimulation of patients’ blood with
Leishmania
specific antigens. Among 145 individuals living in a municipality of the Bologna province, northeastern Italy, recruited and screened for
Leishmania
infection, 23 subjects tested positive (15.9%) to one or more tests. Positive serology was the most common marker of latent leishmaniasis (15/145, 10%), followed by the detection of specific cell-mediated response (12/145, 8%), while only few individuals (6/145, 4%) harbored parasitic DNA in the blood.
Conclusions/significance
Combining different tests substantially increased the yield of positivity in detecting latent
Leishmania
infection. The test combination that we employed in this study appears to be effective to accurately identify latent leishmaniasis in an endemic area.
Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus (DENV) concurrent infection is possible and often ...under-recognized in geographical areas where these infections are both endemic.
Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014.
Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated; the treatment of dengue was symptomatic.
Outcomes: The patients were discharged in good general condition.
Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection.
In immunocompromised patients, asymptomatic Leishmania infection can reactivate, and evolve to severe disease. To date, no test is considered the gold standard for the identification of asymptomatic ...Leishmania infection. A combination of methods was employed to screen for Leishmania infection in patients undergoing kidney transplant (KT).
We employed polymerase chain reaction for the detection of parasitic DNA in peripheral blood, Western blot to identify serum immunoglobulin G and whole blood assay to detect cytokines/chemokines after stimulation of whole blood with parasitic antigen.
One-hundred twenty patients residing in Italy were included in the study at the time of KT. Each patient that tested positive to at least one test was considered as Leishmania positive. Fifty out of 120 patients (42%) tested positive for one or more tests. The detection of specific cell-mediated response (32/111, 29%) was the most common marker of Leishmania infection, followed by a positive serology (24/120, 20%). Four patients (3%) harbored parasitic DNA in the blood.
Our findings underline the high prevalence of asymptomatic Leishmania infection in patients undergoing KT in Italy, who are potentially at-risk for parasite reactivation and can benefit from an increased vigilance. Understanding the clinical relevance of these findings deserves further studies.
Visceral leishmaniasis (VL) caused by Leishmania infantum is an ongoing health problem in southern Europe, where dogs are considered the main reservoirs of the disease. Current data point to a ...northward spread of VL and canine leishmaniasis (CanL) in Italy, with new foci in northern regions previously regarded as non-endemic.
Multilocus microsatellite typing (MLMT) was performed to investigate genetic diversity and population structure of L. infantum on 55 samples from infected humans, dogs and sand flies of the E-R region between 2013 and 2017. E-R samples were compared with 10 L. infantum samples from VL cases in other Italian regions (extra E-R) and with 52 strains within the L. donovani complex. Data displayed significant microsatellite polymorphisms with low allelic heterozygosity. Forty-one unique and eight repeated MLMT profiles were recognized among the L. infantum samples from E-R, and ten unique MLMT profiles were assigned to the extra E-R samples. Bayesian analysis assigned E-R samples to two distinct populations, with further sub-structuring within each of them; all CanL samples belonged to one population, genetically related to Mediterranean MON-1 strains, while all but one VL cases as well as the isolate from the sand fly Phlebotomus perfiliewi fell under the second population. Conversely, VL samples from other Italian regions proved to be genetically similar to strains circulating in dogs.
A peculiar epidemiological situation was observed in northeastern Italy, with the co-circulation of two distinct populations of L. infantum; one population mainly detected in dogs and the other population detected in humans and in a sand fly. While the classical cycle of CanL in Italy fits well into the data obtained for the first population, the population found in infected humans exhibits a different cycle, probably not involving a canine reservoir. This study can contribute to a better understanding of the population structure of L. infantum circulating in northeastern Italy, thus providing useful epidemiologic information for public health authorities.
•Cases caused by Leishmania major were mostly infected when visiting friends and relatives.•Most cases caused by Leishmania tropica occurred in migrants.•Pentavalent antimony had an overall cure rate ...of 76%, in line with previous studies.•The cure rate for intralesional pentavalent antimony was higher (86%) than that for systemic (67%).•Liposomal amphotericin B had a cure rate of 44% for cases caused by L. tropica.
Cutaneous leishmaniasis (CL) in Asia, Northern, and Sub-Saharan Africa is mainly caused by Leishmania major and Leishmania tropica. We describe and evaluate the treatment outcome of CL among travelers and migrants in Europe.
We conducted a retrospective study of parasitological confirmed CL cases caused by L. major and L. tropica during 2013-2019 in Europe. Data were collected from medical records and databases within the LeishMan network.
Of 206 included cases of CL, 75 were identified as L. major and 131 as L. tropica. Of patients with L. tropica infection, 80% were migrants, whereas 53% of patients with L. major infection had been visiting friends and relatives. Among patients with L. tropica, 48% were younger than 15 years. Pentavalent antimony cured 73% (L. major) and 78% (L. tropica) of patients. The cure rate for intralesional administration was 86% and 67% for systemic, on L. tropica. Liposomal amphotericin B had a cure rate of 44-63%.
L. major infections were mostly found in individuals visiting friends and relatives, whereas L. tropica were mainly identified in migrants. No patients with L. major relapsed. Pentavalent antimony, liposomal amphotericin B, and cryotherapy had cure rates in accordance with previous studies.
The diagnosis of visceral leishmaniasis (VL) remains challenging, due to the limited sensitivity of microscopy, the poor performance of serological methods in immunocompromised patients and the lack ...of standardization of molecular tests. The aim of this study was to implement a combined diagnostic workflow by integrating serological and molecular tests with standardized clinical criteria. Between July 2013 and June 2015, the proposed workflow was applied to specimens obtained from 94 in-patients with clinical suspicion of VL in the Emilia-Romagna region, Northern Italy. Serological tests and molecular techniques were employed. Twenty-one adult patients (22%) had a confirmed diagnosis of VL by clinical criteria, serology and/or real-time polymerase chain reaction; 4 of these patients were HIV-positive. Molecular tests exhibited higher sensitivity than serological tests for the diagnosis of VL. In our experience, the rK39 immunochromatographic test was insufficiently sensitive for use as a screening test for the diagnosis of VL caused by L. infantum in Italy. However, as molecular tests are yet not standardized, further studies are required to identify an optimal screening test for Mediterranean VL.
PDF
