Epidemiology of Visceral Leishmaniasis in Georgia

This study investigated the transmission and prevalence of Leishmania parasite infection of humans in two foci of Visceral Leishmaniasis (VL) in Georgia, the well known focus in Tbilisi in the East, and in Kutaisi, a new focus in the West of the country. The seroprevalence of canine leishmaniasis was investigated in order to understand the zoonotic transmission. Blood samples of 1575 dogs (stray and pet) and 77 wild canids were tested for VL by Kalazar Detect rK39 rapid diagnostic tests. Three districts were investigated in Tbilisi and one in Kutaisi. The highest proportions of seropositive pet dogs were present in District #2 (28.1%, 82/292) and District #1 (26.9%, 24/89) in Tbilisi, compared to 17.3% (26/150) of pet dogs in Kutaisi. The percentage of seropositive stray dogs was also twice as high in Tbilisi (16.1%, n = 670) than in Kutaisi (8%, n = 50); only 2/58 wild animals screened were seropositive (2. 6%). A total of 873 Phlebotomine sand flies were collected, with 5 different species identified in Tbilisi and 3 species in Kutaisi; 2.3% of the females were positive for Leishmania parasites. The Leishmanin Skin Test (LST) was performed on 981 human subjects in VL foci in urban areas in Tbilisi and Kutaisi. A particularly high prevalence of LST positives was observed in Tbilisi District #1 (22.2%, 37.5% and 19.5% for ages 5–9, 15–24 and 25–59, respectively); lower prevalence was observed in Kutaisi (0%, 3.2% and 5.2%, respectively; P<0.05). This study shows that Tbilisi is an active focus for leishmaniasis and that the infection prevalence is very high in dogs and in humans. Although exposure is as yet not as high in Kutaisi, this is a new VL focus. The overall situation in the country is alarming and new control measures are urgently needed

Seroepidemiology and molecular diversity of Leishmania donovani complex in Georgia

Background Leishmaniasis includes multiple clinical syndromes, most notably visceral, cutaneous, and mucosal forms. Visceral leishmaniasis (VL), also known as kala-azar, is a potentially fatal disease endemic to large parts of Africa and Asia, and in South-Eastern Europe (Greece, Turkey, Georgia). Visceral leishmaniasis is a parasitic zoonosis caused by species of the L. donovani complex. In the classical epidemiological model the main reservoir for VL are canines. Methods The study included a cohort of 513 individuals of both genders (190 males and 323 females) from the ages of 1 to 70 years that were screened in ten villages across two districts in Kakheti using the Kalazar Detect™ rK39 rapid diagnostic test. The phylogenetic diversity patterns of local strains, based on the rDNA internal transcribed spacer (ITS) sequences, were assessed for samples obtained from patients with suspected L. donovani infection, from canine reservoirs and from Phlebotomus sand flies obtained from different geographical areas of Georgia and from Azerbaijan. Results Out of a total of 600 domestic dog blood samples 95 (15.8 %) were positive by rK39 rapid diagnostic tests. For symptomatic domestic dogs, the testing of conjunctival swabs or bone marrow aspirates revealed a higher VL incidence in Kvareli District (Kvareli; 19.4 %, n = 329) compared with that observed for Sagarejo District (Sagarejo; 11.4 %, n = 271). A total of 231 sand flies of both genders were collected during the 2-month period; of the 114 females, 1.75 % were PCR positive for the presence of Leishmania spp. Conclusions VL infection rates remain high in both canines and humans in Georgia, with disease in several known natural foci. The genetic relationships derived from rDNA internal transcribed spacer (ITS) sequence comparisons identified genetic subgroups, revealing preliminary insights into the genetic structure of L. donovani complex members currently circulating in the South Caucasus and demonstrates the utility of ITS-based genotyping in the resource-limited country of Georgia

Incrimination of Phlebotomus kandelakii and Phlebotomus balcanicus as Vectors of Leishmania infantum in Tbilisi, Georgia

A survey of potential vector sand flies was conducted in the neighboring suburban communities of Vake and Mtatsminda districts in an active focus of visceral Leishmaniasis (VL) in Tbilisi, Georgia. Using light and sticky-paper traps, 1,266 male and 1,179 female sand flies were collected during 2006–2008. Five Phlebotomus species of three subgenera were collected: Phlebotomus balcanicus Theodor and Phlebotomus halepensis Theodor of the subgenus Adlerius; Phlebotomus kandelakii Shchurenkova and Phlebotomus wenyoni Adler and Theodor of the subgenus Larroussius; Phlebotomus sergenti Perfil'ev of the subgenus Paraphlebotomus. Phlebotomus sergenti (35.1%) predominated in Vake, followed by P. kandelakii (33.5%), P. balcanicus (18.9%), P. halepensis (12.2%), and P. wenyoni (0.3%). In Mtatsminda, P. kandelakii (76.8%) comprised over three fourths of collected sand flies, followed by P. sergenti (12.6%), P. balcanicus (5.8%), P. halepensis (3.7%), and P. wenyoni (1.1%). The sand fly season in Georgia is exceptionally short beginning in early June, peaking in July and August, then declining to zero in early September. Of 659 female sand flies examined for Leishmania, 12 (1.8%) specimens without traces of blood were infected including 10 of 535 P. kandelakii (1.9%) and two of 40 P. balcanicus (5.0%). Six isolates were successfully cultured and characterized as Leishmania by PCR. Three isolates from P. kandelakii (2) and P. balcanicus (1) were further identified as L. infantum using sequence alignment of the 70 kDa heat-shock protein gene. Importantly, the sand fly isolates showed a high percent identity (99.8%–99.9%) to human and dog isolates from the same focus, incriminating the two sand fly species as vectors. Blood meal analysis showed that P. kandelakii preferentially feeds on dogs (76%) but also feeds on humans. The abundance, infection rate and feeding behavior of P. kandelakii and the infection rate in P. balcanicus establish these species as vectors in the Tbilisi VL focus

Implementation of the One Health approach to fight arbovirus infections in the Mediterranean and Black Sea Region: Assessing integrated surveillance in Serbia, Tunisia and Georgia

Background In the Mediterranean and Black Sea Region, arbovirus infections are emerging infectious diseases. Their surveillance can benefit from one health inter-sectoral collaboration; however, no standardized methodology exists to study One Health surveillance. Methods We designed a situation analysis study to document how integration of laboratory/clinical human, animal and entomological surveillance of arboviruses was being implemented in the Region. We applied a framework designed to assess three levels of integration: policy/institutional, data collection/data analysis and dissemination. We tested the use of Business Process Modelling Notation (BPMN) to graphically present evidence of inter-sectoral integration. Results Serbia, Tunisia and Georgia participated in the study. West Nile Virus surveillance was analysed in Serbia and Tunisia, Crimea-Congo Haemorrhagic Fever surveillance in Georgia. Our framework enabled a standardized analysis of One Health surveillance integration, and BPMN was easily understandable and conducive to detailed discussions among different actors/institutions. In all countries, we observed integration across sectors and levels except in data collection and data analysis. Data collection was interoperable only in Georgia without integrated analysis. In all countries, surveillance was mainly oriented towards outbreak response, triggered by an index human case. Discussion The three surveillance systems we observed prove that integrated surveillance can be operationalized with a diverse spectrum of options. However, in all countries, the integrated use of data for early warning and inter-sectoral priority setting is pioneeristic. We also noted that early warning before human case occurrence is recurrently not operationally prioritized

Epidemiology of visceral leishmaniasis in Georgia

ObjectiveThe purpose of this study was to describe the epidemiology ofvisceral leishmaniasis in Georgia and to define new control measures.IntroductionVisceral leishmaniasis (VL) is a zoonotic, protozoal infection thatis endemic in Georgia, which commonly affects young children.In recent years, the incidence of VL has increased sharply and thegeographic distribution has increased. Recently, VL moved to highlypopulated areas as new foci appeared from 2010-2015, during which,610 laboratory confirmed cases of VL were registered in Georgia.The majority of cases were found in East Georgia (94.2%) and 5.8%of cases in West Georgia (representing new foci of VL in Georgia).MethodsBlood samples from 2,100 individuals suspected to have VL weretested using the rk39 based VL rapid diagnostic test, an enzyme-linkedimmunosorbent assay (ELISA). Also, 1,575 randomly selected dogs(stray and pet) and 77 wild canids were tested for VL using the sameELISA. Confirmed human cases were followed up for 9-12 months.ResultsThe most affected age group was 0-5 years (72.2%). Of thepatients, 13.9% were HIV positive and lethal outcomes were observedin 2.1%of patients. Mortality was associated with delayed diagnosisand HIV co-infection. Relapse developed in 6.4% of cases. AmongHIV positive patients, secondary prophylaxis was conducted withliposomal amphotericin B, which decreased the number of relapses by76% in 12-24 month follow-ups. A high incidence of VL in humanswas associated with a high prevalence of leishmaniasis in stray anddomestic dogs. Leishmania antibodies were found in 23.7% of strayand domestic dogs and 2.6% of wild animals screened in Tbilisi.ConclusionsOverall, the VL situation in Georgia is concerning and new controlmeasures are needed. Our study revealed a high prevalence of VLin humans and dogs in East Georgia. Early and accurate diagnosis/treatment and effective control measures should be conductedregularly to prevent the spread of VL in Georgia. In addition,secondary prophylaxis in HIV infected patients is also recommended

Epidemiology of visceral leishmaniasis in Georgia

ObjectiveThe purpose of this study was to describe the epidemiology ofvisceral leishmaniasis in Georgia and to define new control measures.IntroductionVisceral leishmaniasis (VL) is a zoonotic, protozoal infection thatis endemic in Georgia, which commonly affects young children.In recent years, the incidence of VL has increased sharply and thegeographic distribution has increased. Recently, VL moved to highlypopulated areas as new foci appeared from 2010-2015, during which,610 laboratory confirmed cases of VL were registered in Georgia.The majority of cases were found in East Georgia (94.2%) and 5.8%of cases in West Georgia (representing new foci of VL in Georgia).MethodsBlood samples from 2,100 individuals suspected to have VL weretested using the rk39 based VL rapid diagnostic test, an enzyme-linkedimmunosorbent assay (ELISA). Also, 1,575 randomly selected dogs(stray and pet) and 77 wild canids were tested for VL using the sameELISA. Confirmed human cases were followed up for 9-12 months.ResultsThe most affected age group was 0-5 years (72.2%). Of thepatients, 13.9% were HIV positive and lethal outcomes were observedin 2.1%of patients. Mortality was associated with delayed diagnosisand HIV co-infection. Relapse developed in 6.4% of cases. AmongHIV positive patients, secondary prophylaxis was conducted withliposomal amphotericin B, which decreased the number of relapses by76% in 12-24 month follow-ups. A high incidence of VL in humanswas associated with a high prevalence of leishmaniasis in stray anddomestic dogs. Leishmania antibodies were found in 23.7% of strayand domestic dogs and 2.6% of wild animals screened in Tbilisi.ConclusionsOverall, the VL situation in Georgia is concerning and new controlmeasures are needed. Our study revealed a high prevalence of VLin humans and dogs in East Georgia. Early and accurate diagnosis/treatment and effective control measures should be conductedregularly to prevent the spread of VL in Georgia. In addition,secondary prophylaxis in HIV infected patients is also recommended

Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern

One year since the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China, several variants of concern (VOC) have appeared around the world, with some variants seeming to pose a greater thread to public health due to enhanced transmissibility or infectivity. This study provides a framework for molecular characterization of novel VOC and investigates the effect of mutations on the binding affinity of the receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2) using in silico approach. Notable nonsynonymous mutations in RBD of VOC include the E484K and K417N/T that can be seen in South African and Brazilian variants, and N501Y and D614G that can be seen in all VOC. Phylogenetic analyses demonstrated that although the UK-VOC and the BR-VOC fell in the clade GR, they have different mutation signatures, implying an independent evolutionary pathway. The same is true about SA-VOC and COH-VOC felling in clade GH, but different mutation signatures. Combining molecular interaction modeling and the free energy of binding (FEB) calculations for VOC, it can be assumed that the mutation N501Y has the highest binding affinity in RBD for all VOC, followed by E484K (only for BR-VOC), which favors the formation of a stable complex. However, mutations at the residue K417N/T are shown to reduce the binding affinity. Once vaccination has started, there will be selective pressure that would be in favor of the emergence of novel variants capable of escaping the immune system. Therefore, genomic surveillance should be enhanced to find and monitor new emerging SARS-CoV-2 variants before they become a public health concern

Correction: Spread of the Invasive Mosquitoes Aedes aegypti and Aedes albopictus in the Black Sea Region Increases Risk of Chikungunya, Dengue, and Zika Outbreaks in Europe.

[This corrects the article DOI: 10.1371/journal.pntd.0004664.]