An investigation of polymorphisms in innate and adaptive immune response genes in canine leishmaniosis

The outcome of infection with Leishmania infantum in dogs is variable, which is thought to be due to the nature of the immune response mounted by the host. As a consequence, the clinical signs and severity of canine leishmaniosis vary between individual dogs. Host immunogenetic factors might play an important role in determining the outcome of infection. The aim of this study was to examine polymorphisms in innate and adaptive immune response genes, to determine whether any of these were associated with susceptibility or resistance to L. infantum infection. Genomic DNA was obtained from two groups: pet dogs in endemic regions of Europe and a group of Beagles exposed to sand fly infection as part of a vaccine study. Genotyping was performed using a SNP (single nucleotide polymorphism) array for selected immune response genes. The first part of the study compared 62 clinical cases with 101 clinically unaffected dogs that were seronegative for Leishmania antibodies. One SNP in the CIITA gene demonstrated a significantly higher minor allele frequency in the case group, compared with the control group at the individual SNP level after permutation, but was not significant after correction for multiple testing. The second part of the study examined 48 Beagle dogs exposed to L. infantum over two transmission seasons. Twenty-seven dogs with a resistant phenotype (no evidence of clinical disease, seronegative at the end of the study period, negative on lymph node culture and only transiently PCR positive in bone marrow) were compared with 21 dogs demonstrating a susceptible phenotype (clinical disease, seropositive, positive lymph node culture and consistently PCR positive in bone marrow). Three SNPs in TLR3, two SNPs in PTPN22 and one SNP in TLR4 and IL1A were associated with the susceptible phenotype in the Beagle group at the individual SNP level after permutation analysis, but were not significant after correction for multiple testing. Further validation of these SNPs is required in a larger cohort of dogs, ideally with extreme phenotypes to confirm an association with the outcome of L. infantum infection

First detection of Leishmania major in dogs living in an endemic area of zoonotic cutaneous leishmaniasis in Tunisia

Background: Dogs are considered the main domestic animals that may be a reservoir for Leishmania infantum, the agent of zoonotic visceral leishmaniasis (ZVL) in several countries of the world. The dog may host other Leishmania species, but its epidemiological role in the maintenance and spreading of these parasites is not completely elucidated. Zoonotic cutaneous leishmaniasis (ZCL), caused by Leishmania major, affects thousands of people every year and is particularly diffused in many countries of North Africa and Middle East Asia. In ZCL endemic countries, few reports of L. major-positive dogs have been reported, probably because most human cases occur in poor rural areas where the social role of the dog and its medical management is not well considered. The aim of the present study is to better understand the possible involvement of domestic dogs in the epidemiology of ZCL. Methods: Our research focused on a well-established endemic focus of ZCL, in the area of Echrarda, Kairouan Governorate, central Tunisia. A total of 51 dogs with no or mild clinical signs of vector borne diseases were selected in small villages where human cases of ZCL are yearly present. All dogs were sampled for the Leishmania spp. diagnosis, by using the following procedures: blood sample for serology and buffy coat quantitative polymerase chain reaction (qPCR), popliteal fine needle aspiration, and cutaneous biopsy punch for lymph node and skin qPCR. Results: The results demonstrated a high percentage (21.6%) of dogs positive at least at one or more test; the most sensitive technique was the lymph node qPCR that detected 8/11 positive dogs. Nine, out of the eleven positive dogs, resulted as infected by Leishmania infantum; ITS1-PCR-sequencing allowed Leishmania major identification in the remaining two cases, both from the popliteal lymph node samples, which can suggest a possible visceral spread of a cutaneous Leishmania species in the dog. Interestingly, one of the two L. major-positive dogs was living in the same house where 6-year-old children showed cutaneous lesions referred to as ZCL. Conclusions: To our knowledge, this is the first report of L. major-positive dogs in Tunisia, the epidemiological role of which remains under investigation

Seropositivity rates for agents of canine vector-borne diseases in Spain : a multicentre study

Background: Controlling canine vector-borne diseases (CVBD) is a major concern, since some of these diseases are serious zoonoses. This study was designed to determine seropositivity rates in Spain for agents causing the following five CVBD: leishmaniosis (Leishmania infantum: Li), heartworm (Dirofilaria immitis: Di), ehrlichiosis (Ehrlichia canis: Ec), anaplasmosis (Anaplasma phagocytophilum/Anaplasma platys: An) and Lyme disease (Borrelia burgdorferi: Bb). Methods: Anti-An, -Bb, and -Ec antibodies and the Di antigen were determined using the 4DX SNAP® Test (IDEXX Laboratories) and anti-L. infantum (Li) antibodies using the Leishmania SNAP® Test (IDEXX Laboratories) in blood and/or serum samples. Results: Among 1100 dogs examined, overall seropositivity rates were: Li (15.7%), Ec (5%), An (3.1%), Di (1.25%) and Bb (0.4%). While seropositivity towards Bb and Di was similar in all geographic regions, rates were significantly higher in the east of Spain (8.3%) for An, significantly higher in the north (20%) for Ec, and significantly higher in the Southeast (46.6%) and South (27.4%), and significantly lower in the north (0%) for Li. No statistical associations were observed between sex and the CVBD analyzed (p ≥ 0.05) while the following associations with other variables were detected: a higher seropositivity to Ec (40%) and Bb (6.7%) in dogs under one year of age compared with adults (p < 0.05); and a higher seropositivity to An and Li in dogs that lived outdoors versus indoors (p = 0.01; p < 0.001, respectively). Seropositivity rates of 2.1%, 0%, 1.7%, 0.5% and 4.2% were recorded respectively for An, Bb, Ec, Di and Li in dogs with no clinical signs (n = 556) versus 3.8%, 0.6%, 7.5%, 1.8% and 25.9% for those with signs (n = 507) suggestive of a CVBD. Conclusion: The data obtained indicate a risk for dogs in Spain of acquiring any of the five CVBD examined. Veterinarians in the different regions should include these diseases in their differential diagnoses and recommend the use of repellents and other prophylactic measures to prevent disease transmission by arthropod vectors. Public health authorities also need to become more involved in the problem, since some of the CVBD examined here also affect humans

Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE

: Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping

LeishVet guidelines for the practical management of canine leishmaniosis

The LeishVet group has formed recommendations designed primarily to help the veterinary clinician in the management of canine leishmaniosis. The complexity of this zoonotic infection and the wide range of its clinical manifestations, from inapparent infection to severe disease, make the management of canine leishmaniosis challenging. The recommendations were constructed by combining a comprehensive review of evidence-based studies, extensive clinical experience and critical consensus opinion discussions. The guidelines presented here in a short version with graphical topic displays suggest standardized and rational approaches to the diagnosis, treatment, follow-up, control and prevention of canine leishmaniosis. A staging system that divides the disease into four stages is aimed at assisting the clinician in determining the appropriate therapy, forecasting prognosis, and implementing follow-up steps required for the management of the leishmaniosis patient

Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data from the PRESTIGIO Registry

Background: Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population. Methods: This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death. Results: Among 148 PWH followed for a median (interquartile range) of 47 (32-84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85-11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%-13%), and that of ≥1 event or death was 22% (95% CI, 16%-31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65-1.02). Conclusions: PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio

Sand fly synthetic sex-aggregation pheromone co-located with insecticide reduces the incidence of infection in the canine reservoir of visceral leishmaniasis: a stratified cluster randomised trial

The predominant sand fly vector of the intracellular parasite Leishmania infantum, that causes human and canine visceral leishmaniasis in the Americas, is Lutzomyia longipalpis. Dogs are the proven reservoir. Vector control tools to reduce transmission suited to this predominantly exophilic vector are lacking. Insecticide-impregnated dog collars protect dogs against infectious bites from sand fly vectors, and result in reductions of new infections in both dogs and humans. However, collars are costly for endemic communities, and alternative approaches are needed. Recently the bulk synthesised sex-aggregation pheromone of male Lu. longipalpis was shown to attract large numbers of conspecific females to lethal pyrethroid insecticides, indicating the potential for use in a vector control application. This study, conducted in Brazil, evaluated the efficacy of this novel lure-and-kill approach to reduce seroconversion and infection incidence with L. infantum in the canine reservoir, in addition to measuring its impact on household abundance of Lu. longipalpis. Deployed in 14 stratified clusters, the outcomes were compared to those attributed to insecticide impregnated collars fitted to dogs in another 14 clusters; each intervention was compared to 14 clusters that received placebo treatments. The beneficial effects of the lure-and-kill method were most noticeable on confirmed infection incidence and clinical parasite loads, and in reducing sand fly abundance. The overall effect of the two interventions were not statistically dissimilar, though the confidence intervals were broad. We conclude that the novel low-cost lure-and-kill approach should be added to the vector control toolbox against visceral leishmaniasis in the Americas