Rabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to ...prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure.
The study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose.
Age emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45–60 and 75–92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG.
This study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.
Tick-borne encephalitis (TBE) is an emerging vector-borne and food-borne disease caused by the tick-borne encephalitis virus (TBEV;
), with a distribution spanning the Eurasian continent. Despite its ...significant public health impact in various European regions, TBE remains largely underdiagnosed in Serbia due to limited awareness and diagnostic challenges. In response to this, our study aimed to comprehensively assess TBEV exposure in individuals infested with ticks and to identify potential TBEV foci within Serbia.
From 2019 to 2021, we conducted an observational study involving 450 patients who reported tick infestations.
Our demographic analysis revealed a median age of 38 years, with a slight male predominance among the participants. We documented tick infestations in 38 municipalities across 14 districts of Serbia, with a notable concentration in proximity to Fruška Gora Mountain. The ticks most frequently removed were
, with nymphs and adult females being the predominant stages. On average, nymphs were removed after about 27.1 hours of feeding, while adult females remained attached for approximately 44.4 hours. Notably, we found age as a significant predictor of infestation time for both nymphs and adult females. Furthermore, we detected TBEV-neutralizing antibodies in 0.66% of the serum samples, shedding light on potential TBEV foci, particularly in Fruška Gora Mountain and other regions of Serbia.
Our study emphasizes the urgent need for active TBE surveillance programs, especially in areas suspected of hosting TBEV foci, in order to assess the true TBE burden, identify at-risk populations, and implement effective preventive measures.
Ticks carry numerous pathogens that, if transmitted, can cause disease in susceptible humans and animals. The present study describes our approach on how to investigate clinical presentations ...following tick bites in humans. To this aim, the occurrence of major tick-borne pathogens (TBPs) in human blood samples (
= 85) and the ticks collected (
= 93) from the same individuals were tested using an unbiased high-throughput pathogen detection microfluidic system. The clinical symptoms were characterized in enrolled patients. In patients with suspected TBP infection, serological assays were conducted to test for the presence of antibodies against specific TBPs. A field study based on One Health tenets was further designed to identify components of a potential chain of infection resulting in
infection in one of the patients. Ticks species infesting humans were identified as
,
sensu lato (s.l.),
, and
. Five patients developed local skin lesions at the site of the tick bite including erythema migrans, local non-specific reactions, and cutaneous hypersensitivity reaction. Although
s.l.,
,
, and
Cryptoplasma sp. DNAs were detected in tick samples, different
species were the most common TBPs identified in the ticks. The presence of TBPs such as
,
,
,
,
,
, and
in ticks was further confirmed by DNA sequencing. Two of the patients with local skin lesions had IgG reactive against spotted fever group rickettsiae, while IgM specific to
,
, and
were detected in the patient with erythema migrans. Although
infection was detected in one human blood sample, none of the components of the potential chain of infection considered in this study tested positive to this pathogen either using direct pathogen detection in domestic dogs or xenodiagnosis in ticks collected from domestic cats. The combination of high-throughput screening of TBPs and One Health approaches might help characterize chains of infection leading to human infection by TBPs, as well as prevalence of emerging rickettsial pathogens in the Balkan region.
Tick-borne encephalitis (TBE) is vaccine-preventable neglected zoonotic neuroinvasive disease, caused by tick-borne encephalitis virus (TBEV). Many of the Central and Eastern European countries are ...affected by TBE, which is often poorly perceived by tourists visiting endemic territories. Here we are reporting a fatal case of imported TBE in Serbian resident who was exposed to a tick bite during a visit to Switzerland.
Mediterranean spotted fever-like illness (MSF-like illness) is a tick-borne disease caused by
Rickettsia sibirica mongolitimonae
first reported in France more than 25 years ago. Until today, more ...than 50 cases of MSF-like illness have been reported in different regions of Europe and Africa, highlighting variable clinical manifestation. Here we report a case of MSF-like illness following a bite from a
Hyalomma
tick in the Skopje region of North Macedonia.
•Tick-borne pathogens (TBPs) detection in platelet fraction and whole blood differs in the same patient.•Most common TBPs detected in platelet fraction were Borrelia spielmanii and Rickettsia sp., ...followed by Borrelia afzelii and Anaplasma phagocytophilum.•Most common TBPs detected in while blood were Anaplasma spp. and Anaplasma phagocytophilum, followed by Rickettsia spp. and Borrelia afzelii.
The tick-borne pathogens (TBPs) with adhesive phenotype can use platelets for dissemination and colonization of distant tissues and organs, and it has been shown that they can be found concentrated in the platelet fraction of blood. This study shows the differential presence of TBPs in samples of human platelet fraction (n = 68), whole blood samples (n = 68) and ticks collected (n = 76) from the same individuals, using an unbiased high-throughput pathogen detection microfluidic system. The clinical symptoms were characterized in enrolled patients. In patients with suspected TBP infection, serological assays were conducted to test for the presence of antibodies against specific TBPs. Tick species infesting humans were identified as Ixodes ricinus, Dermacentor reticulatus, and Haemaphysalis punctata. Eight patients developed local skin lesions at the site of the tick bite including non-specific lesions, itching sensation at the lesion site, and eschar. Most common TBPs detected in platelet fraction were Borrelia spielmanii and Rickettsia sp., followed by Borrelia afzelii and Anaplasma phagocytophilum. Multiple infections with three TBPs were detected in platelet fraction. In whole blood, most common TBPs detected were Anaplasma spp. and A. phagocytophilum, followed by Rickettsia spp. and B. afzelii. In ticks, the most common TBP detected was Rickettsia spp., followed by Borrelia spp. and Anaplasma spp. Overall, nine different pathogens with variable prevalence were identified using species-specific primers, and the most common was Rickettsia helvetica. In three patients, there were no coincidences between the TBPs detected in whole blood and tick samples. Only in one patient was detected A. phagocytophilum in both, whole blood and tick samples. These results suggest the unequal detection of TBPs in whole blood, platelet fraction and ticks collected, from the same individual. The results justify the use of both whole blood and platelet fraction for molecular diagnosis of TBPs in patients.
Tick-borne pathogens (TBPs) have complex life cycles involving tick vectors and vertebrate hosts. However, there is limited empirical evidence on the zoonotic circulation of TBPs. In this study, we ...used a One Health approach to study the possible circulation of TBPs in ticks, animals and humans within a rural household in the foothills of the Fruška Gora mountain, northern Serbia. The presence of TBP DNA was assessed using microfluidic PCR (25 bacterial species, 7 parasite species, 5 bacterial genera, 3 parasite genera) in animal, human and tick samples and the presence of tick-borne encephalitis virus (TBEV) RNA was screened for using RT-qPCR on tick samples. In addition, Lyme borreliosis serology was assessed in patients sera. Rhipicephalus sanguineus and Ixodes ricinus ticks were identified on dogs and Haemaphysalis punctata was identified on house walls. Rickettsia helvetica was the most common pathogen detected in pooled R. sanguineus and I. ricinus tick samples, followed by Hepatozoon canis. None of the H. punctata tick samples tested positive for the presence of TBPs. Anaplasma phagocytophilum and Rickettsia monacensis were the most frequent pathogens detected in dogs, followed by Rickettsia felis, whereas Anaplasma bovis was the only pathogen found in one of the goats tested. None of the human blood samples collected from family members tested positive for the presence of TBPs. Although microfluidic PCR did not detect Borrelia sp. in any of the tested tick or blood samples, a family member with a history of Lyme disease was seropositive for Borrelia burgdorferi sensu lato (s.l.). We conclude that, despite the presence of TBPs in tick and vertebrate reservoirs, there is no evidence of infection with TBPs across various components of the epidemiological chain in a rural Fruška Gora household.
Tick-borne pathogens (TBPs) pose a major threat to human health in Europe and the whole northern hemisphere. Despite a high prevalence of TBPs in Ixodes ricinus ticks, knowledge on the incidence of ...tick-borne diseases in humans infested by this tick species is limited. This study was conducted in the year 2019 on patients who presented themselves to the Pasteur Institute Novi Sad with tick infestations. Ticks (n = 31) feeding on human (n = 30) and blood samples from the same individuals were collected by physicians and a microfluidic real-time high-throughput PCR system was used to test the genomic DNA of the samples for the presence of 27 bacterial and eight parasitic microorganisms in Serbia. Except for one Rhipicephalus sanguineus s.l. adult male tick, all ticks infesting humans were morphologically identified as I. ricinus. A high proportion of ticks (74 %, 23/31) were infected with at least one of the tested TB microorganisms, being Rickettsia helvetica (54 %, 17/31) the most common pathogen, but Borrelia afzelii (9 %, 3/31), Anaplasma phagocytophilum (6 %, 2/31), Borrelia miyamotoi (6 %, 2/31), and Francisella like-endosymbiont (6 %, 2/31), Borrelia valaisiana (3 %, 1/31), Borrelia lusitaniae (3 %, 1/31), Rickettsia felis (3 %, 1/31) and Rickettsia aeschlimannii (3 %, 1/31) were also identified. Despite the high infection rate of TBPs in ticks, only two human blood samples (6 %, 2/30) tested positive for the presence of TBPs, one patient (code H12, 67 years old female) was diagnosed with Borrelia spp. and the other patient was diagnosed (code H17, 71 years old female) with R. felis infection. The tick infesting patient H12 tested positive for B. afzelii, and R. helvetica and the tick infesting patient H17 tested positive for R. felis. Upon clinical examination, both patients were diagnosed with erythema migrans. No additional discomfort was reported by the patient and no additional pathology was observed by the physician. We concluded that humans bitten by I. ricinus in Serbia are exposed to a diverse array of TBPs with clinical impact in the Serbian cohort studied.
Lyme borreliosis (LB) and tick-borne encephalitis (TBE) are important tick-borne diseases in Europe. This study aimed to investigate the seroreactivity against
and TBE virus (TBEV) in tick-infested ...individuals in North Macedonia and Serbia. Serum samples were collected from tick-infested individuals and from healthy individuals in the same regions. Samples were tested for anti-
IgG reactivity and TBEV-neutralizing antibodies. Results showed higher seroreactivity against
antigens in patients and healthy donors from Novi Sad compared to those from the Skopje region. However, there was no statistically significant difference between tick-infested patients and healthy donors within each region. No TBEV-neutralizing antibodies were detected in participants from Novi Sad or in the control groups, except for one person from North Macedonia who had a moderate TBEV-neutralizing reaction. The study highlights the need for improved surveillance and diagnostic capabilities for LB and TBE in these regions. It also suggests the potential existence of TBEV foci in North Macedonia. The findings provide a complementary understanding of the LB and TBE epidemiology in the studied regions; however, further research is needed to investigate the presence and distribution of
spp. and TBEV in ticks to assess the significance of detected seroreactivity.
Passive immunotherapy with convalescent COVID-19 plasma (CCP) is used as a therapeutic procedure in many countries, including Serbia. In this study, we analyzed the association between demographic ...factors, COVID-19 severity and the reactivity of anti-SARS-CoV-2 antibodies (Abs) in Serbian CCP donors. Individuals (
= 468) recovered from confirmed SARS-CoV-2 infection, and who were willing to donate their plasma for passive immunization of COVID-19 patients were enrolled in the study. Plasma samples were tested for the presence of IgG reactive to SARS-CoV-2 spike glycoprotein (S1) and nucleocapsid antigens. Individuals were characterized according to age, gender, comorbidities, COVID-19 severity, ABO blood type and RhD factor. Total of 420 candidates (420/468; 89.74%) reached the levels of anti-SARS-CoV-2 IgG that qualified them for inclusion in CCP donation program. Further statistical analysis showed that male individuals (
= 0.034), older age groups (
< 0.001), existence of hypertension (
= 0.008), and severe COVID-19 (
= 0.000) are linked with higher levels of anti-SARS-CoV-2 Abs. These findings will guide the selection of CCP donors in Serbia. Further studies need to be conducted to assess the neutralization potency and clinical efficiency of CCP collected from Serbian donors with high anti-SARS-CoV-2 IgG reactivity.
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