Primary Series and Booster Coronavirus Disease 2019 Vaccine Effectiveness in a Cohort of Healthcare Workers in Albania During a BA.1 and BA.2 Variant Period, January-May 2022.

Background: Healthcare workers (HCWs) have experienced high rates of coronavirus disease 2019 (COVID-19) morbidity and mortality. We estimated COVID-19 2-dose primary series and monovalent booster vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (BA.1 and BA.2) infection among HCWs in 3 Albanian hospitals during January-May 2022. Methods: Study participants completed weekly symptom questionnaires, underwent polymerase chain reaction (PCR) testing when symptomatic, and provided quarterly blood samples for serology. We estimated VE using Cox regression models (1 - hazard ratio), with vaccination status as the time-varying exposure and unvaccinated HCWs as the reference group, adjusting for potential confounders: age, sex, prior SARS-CoV-2 infection (detected by PCR, rapid antigen test, or serology), and household size. Results: At the start of the analysis period, 76% of 1462 HCWs had received a primary series, 10% had received a booster dose, and 9% were unvaccinated; 1307 (89%) HCWs had evidence of prior infection. Overall, 86% of primary series and 98% of booster doses received were BNT162b2. The median time interval from the second dose and the booster dose to the start of the analysis period was 289 (interquartile range [IQR], 210-292) days and 30 (IQR, 22-46) days, respectively. VE against symptomatic PCR-confirmed infection was 34% (95% confidence interval [CI], -36% to 68%) for the primary series and 88% (95% CI, 39%-98%) for the booster. Conclusions: Among Albanian HCWs, most of whom had been previously infected, COVID-19 booster dose offered improved VE during a period of Omicron BA.1 and BA.2 circulation. Our findings support promoting booster dose uptake among Albanian HCWs, which, as of January 2023, was only 20%. Clinical Trials Registration. NCT04811391.

Primary series COVID-19 vaccine effectiveness among healthcare workers in Albania, February-December 2021.

Background: Healthcare workers have experienced high rates of morbidity and mortality from coronavirus disease 2019 (COVID-19). Methods: A prospective cohort study was conducted in three Albanian hospitals between 19 February and 14 December 2021. All participants underwent polymerase chain reaction (PCR) and serological testing at enrolment, regular serology throughout, and PCR testing when symptomatic.Vaccine effectiveness (VE) against COVID-19 and against all severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections (symptomatic or asymptomatic) was estimated. VE was estimated using a Cox regression model, with vaccination status as a time-varying variable. Findings: In total, 1504 HCWs were enrolled in this study; 70% had evidence of prior SARS-CoV-2 infection. VE was 65.1% [95% confidence interval (CI) 37.7-80.5] against COVID-19, 58.2% (95% CI 15.7-79.3) among participants without prior SARS-CoV-2 infection, and 73.6% (95% CI 24.3-90.8) among participants with prior SARS-CoV-2 infection. For BNT162b2 alone, VE was 69.5% (95% CI 44.5-83.2). During the period when the Delta variant was predominant, VE was 67.1% (95% CI 38.3-82.5). VE against SARS-CoV-2 infection for the full study period was 36.9% (95% CI 15.8-52.7). Interpretation: This study found moderate primary series VE against COVID-19 among healthcare workers in Albania. These results support the continued promotion of COVID-19 vaccination in Albania, and highlight the benefits of vaccination in populations with high levels of prior infection.

Factors associated with receipt of COVID-19 vaccination and SARS-CoV-2 seropositivity among healthcare workers in Albania (February 2021-June 2022): secondary analysis of a prospective cohort study.

Background: Healthcare workers (HCWs) have been disproportionally affected by COVID-19. We investigated factors associated with two- and three-dose COVID-19 vaccine uptake and SARS-CoV-2 seropositivity among 1504 HCWs enrolled (19 February-7 May 2021) in a prospective COVID-19 vaccine effectiveness cohort in Albania through a secondary analysis. Methods: We collected sociodemographic, occupational, health, prior SARS-CoV-2 infection, and COVID-19 vaccination data from all HCWs at enrollment. Vaccination status was assessed weekly through June 2022. A serum sample was collected from all participants at enrollment and tested for anti-spike SARS-CoV-2 antibodies. We analyzed HCWs characteristics and outcomes using multivariable logistic regression. Findings: By 11 June 2022, 1337 (88.9%) HCWs had received two COVID-19 vaccine doses, of whom 255 (19.1%) received a booster. Factors significantly associated with receiving three doses (adjusted odds ratio (aOR), 95% CIs) were being ≥35 years (35-44 years: 1.76 (1.05-2.97); 45-54 years: 3.11 (1.92-5.05); ≥55 years: 3.38 (2.04-5.59)) and vaccinated against influenza (1.78; 1.20-2.64). Booster dose receipt was lower among females (0.58; 0.41-0.81), previously infected (0.67; 0.48-0.93), nurses and midwives (0.31; 0.22-0.45), and support staff (0.19; 0.11-0.32). Overall 1076 (72%) were SARS-CoV-2 seropositive at enrollment. Nurses and midwifes (1.45; 1.05-2.02), support staff (1.57; 1.03-2.41), and HCWs performing aerosol-generating procedures (AGPs) (1.40; 1.01-1.94) had higher odds of being seropositive, while smokers had reduced odds (0.55; 0.40-0.75). Interpretation: In a large cohort of Albanian HCWs, COVID-19 vaccine booster dose uptake was very low, particularly among younger, female, and non-physician HCWs, despite evidence demonstrating the added benefit of boosters in preventing infection and severe disease. Reasons behind these disparities should be explored to develop targeted strategies in order to promote uptake in this critical population. SARS-CoV-2 seroprevalence was higher among non-physicians and HCWs performing APGs. A better understanding of the factors contributing to these differences is needed to inform interventions that could reduce infections in the future. Funding: This study was funded by the Task Force for Global Health (US Centers for Disease Control (CDC) cooperative agreement # NU51IP000873) and the World Health Organization, Regional Office for Europe.

Retrospective Analysis of Six Years of Acute Flaccid Paralysis Surveillance and Polio Vaccine Coverage Reported by Italy, Serbia, Bosnia and Herzegovina, Montenegro, Bulgaria, Kosovo, Albania, North Macedonia, Malta, and Greece.

Here we analyzed six years of acute flaccid paralysis (AFP) surveillance, from 2015 to 2020, of 10 countries linked to the WHO Regional Reference Laboratory, at the Istituto Superiore di Sanità, Italy. The analysis also comprises the polio vaccine coverage available (2015-2019) and enterovirus (EV) identification and typing data. Centralized Information System for Infectious Diseases and Laboratory Data Management System databases were used to obtain data on AFP indicators and laboratory performance and countries' vaccine coverage from 2015 to 2019. EV isolation, identification, and typing were performed by each country according to WHO protocols. Overall, a general AFP underreporting was observed. Non-Polio Enterovirus (NPEV) typing showed a high heterogeneity: over the years, several genotypes of coxsackievirus and echovirus have been identified. The polio vaccine coverage, for the data available, differs among countries. This evaluation allows for the collection, for the first time, of data from the countries of the Balkan area regarding AFP surveillance and polio vaccine coverage. The need, for some countries, to enhance the surveillance systems and to promote the polio vaccine uptake, in order to maintain the polio-free status, is evident.

Detection of a Novel Phlebovirus (Drin Virus) from Sand Flies in Albania.

Phlebotomine sand flies are generalist vectors with significant implications for public health. They are able to transmit phleboviruses that cause sand fly fever, headaches, or meningitis in humans. Albania is a country in Southeast Europe with a typical Mediterranean climate which provides convenient conditions for the presence of sand flies. Hence, the circulation of phleboviruses, such as the Toscana and Balkan viruses, has been recently described in the country. We followed a virus discovery approach on sand fly samples collected in 2015 and 2016 in seven regions of Albania, with the aim to investigate and characterize potentially circulating phleboviruses in phlebotomine sand flies. A presumed novel phlebovirus was detected in a pool consisting of 24 Phlebotomus neglectus males. The virus was provisionally named the Drin virus after a river near the locality of Kukës, where the infected sand flies were trapped. Genetic and phylogenetic analysis revealed that the Drin virus is closely related to the Corfou (CFUV) virus, isolated in the 1980s from Phlebotomus major sand flies on the eponymous island of Greece, and may also be involved in human infections because of its similarity to the sand fly fever Sicilian virus. The latter justifies further studies to specifically address this concern. Together with recent findings, this study confirms that Albania and the Balkan peninsula are hot spots for phleboviruses.

Crimean-Congo hemorrhagic fever with hepatic impairment and vaginal hemorrhage: a case report.

BACKGROUND: Crimean-Congo hemorrhagic fever is a tick-borne disease described in more than 30 countries in Europe, Asia, and Africa. Albania is located in the southwestern part of the Balkan Peninsula. In 1986, the first case of Crimean-Congo hemorrhagic fever was registered, and cases of patients with hemorrhagic fever are rising, and most of them present in a serious condition, when the mortality rate is very high. In districts like Mirdite, Lezhe, Gjirokaster, Skrapar, Erseke, and Kukes, there is delineated human-to-human transmission. CASE PRESENTATION: We report the case of a 32 year-old Albanian woman from a rural area of Albania. She was hospitalized at the Infectious Diseases Service, for a severe influenza-like illness of 4 days duration. Our patient had been bitten by a tick while working in her garden. She presented with nausea, vomiting, headache and muscle pain. A physical examination found a high fever of 40 °C, an enlarged liver, petechia, and vaginal bleeding; flapping tremor and fetor hepaticus were found as a sign for hepatic encephalopathy; and confusion and disorientation were observed in her neurological examination. Her platelet and white blood cell counts were very low, while her aspartate aminotransferase and alanine aminotransferase levels were very high. She was transferred to the intensive care unit because of her worsening condition. Serological and C-reactive protein test results for Crimean-Congo hemorrhagic fever were positive. She was treated with oral ribavirin and discharged with normal parameters. CONCLUSIONS: People in high-risk professions in the endemic areas should be informed and trained on the risk of Crimean-Congo hemorrhagic fever as a matter of urgency. Vaginal bleeding is not always a gynecological problem. In Albania, these places are the mountainous areas, so people who have traveled to these areas and who have symptoms after a tick bite are advised to contact their doctors.

Crimean-Congo hemorrhagic fever virus in ticks collected from livestock in Albania.

Albania is a Balkan country endemic for Crimean-Congo hemorrhagic fever (CCHF). It was shown previously that CCHF virus (CCHFV) sequences from Albanian patients cluster into Europe 1 clade. Aim of the present study was to test for CCHFV ticks collected in several regions of Albania, and to determine the genetic lineage(s) of the CCHFV strains in relation with their geographic distribution. A total of 726 ticks (366 Hyalomma marginatum, 349 Rhipicephalus bursa and 11 Rhipicephalus sanguineus) collected from livestock during 2007-2014 were included in the study. Thirty of 215 (13.9%) tick pools were positive for CCHFV. Lineage Europe 1 was detected in H. marginatum ticks collected in the endemic region of Albania, while lineage Europe 2 was detected mainly in R. bursa ticks in various regions of the country. Both genetic lineages were detected in the CCHF endemic area (northeastern Albania), while only Europe 2 lineage was detected in the south of the country. A higher genetic diversity was seen among Europe 2 than Europe 1 Albanian sequences (mean distance 3.7% versus 1%), suggesting a longer evolution of AP92-like strains (Europe 2) in their tick hosts. The present study shows that besides CCHFV lineage Europe 1, lineage Europe 2 is also present in Albania. Combined with results from recent studies, it is concluded that lineage Europe 2 is widely spread in the Balkans and Turkey, and is associated mainly with R. bursa ticks (at least in this region). Its pathogenicity and impact to the public health remain to be elucidated.

Hemorrhagic fever with renal syndrome in Albania. Focus on predictors of acute kidney injury in HFRS.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent borne zoonosis, caused by the members of the family Bunyaviridae, genus Hantavirus. The main clinical features of the infection by this virus family are fever, thrombocytopenia and acute kidney injury. OBJECTIVE: The aim of our study was to identify, for the first time, characteristic features of HFRS in the Albanian population. STUDY DESIGN: The study comprised 33 consecutive patients admitted with suspected HFRS from April 2011-April 2016 at one center. Clinical diagnosis was confirmed by ELISA and real-time PCR. Statistical analysis was performed to identify prognostic markers and indicators of disease severity. RESULTS: The virus strain causing HFRS was Dobrava type in all 33 cases. The disease outbreaks occurred during the period June-July. Mean hospital stay was 15.7±6.9days. 29 (88%) of the patients were male. The mean age was 39.7±14.1. 16 (48.5%) patients were from Northeast Albania. 8 (24.2%) patients required dialysis. The strongest correlation was the inverse relationship of nadir platelet count with urea and creatinine, p<0.0001, p<0.0079 respectively. Creatinine and hyponatremia were inversely correlated p=0.0007, whereas hyponatremia and nadir platelet count had the highest sensitivity and specificity for development of severe AKI, 92.6%, 100%; 88.9%, 83.3% respectively. Mortality rate was 9.09%. CONCLUSION: HFRS is a severe viral disease in Albania caused by Dobrava strain. It is associated with high mortality, 9.09% in our cohort. In our study, thrombocytopenia, urinary volume, hyponatremia were indicators of more severe disease.

Surveillance of Arthropod-Borne Viruses and Their Vectors in the Mediterranean and Black Sea Regions Within the MediLabSecure Network.

PURPOSE OF REVIEW: Arboviruses, viruses transmitted by arthropods such as mosquitoes, ticks, sandflies, and fleas are a significant threat to public health because of their epidemic and zoonotic potential. The geographical distribution of mosquito-borne diseases such as West Nile (WN), Rift Valley fever (RVF), Dengue, Chikungunya, and Zika has expanded over the last decades. Countries of the Mediterranean and Black Sea regions are not spared. Outbreaks of WN are repeatedly reported in the Mediterranean basin. Human cases of RVF were reported at the southern borders of the Maghreb region. For this reason, establishing the basis for the research to understand the potential for the future emergence of these and other arboviruses and their expansion into new geographic areas became a public health priority. In this context, the European network "MediLabSecure" gathering laboratories in 19 non-EU countries from the Mediterranean and Black Sea regions seeks to improve the surveillance (of animals, humans, and vectors) by reinforcing capacity building and harmonizing national surveillance systems to address this important human and veterinary health issue. The aim of this review is to give an exhaustive overview of arboviruses and their vectors in the region. RECENT FINDINGS: The data presented underline the importance of surveillance in the implementation of more adapted control strategies to combat vector-borne diseases. Partner laboratories within the MediLabSecure network present a wide range of infrastructures and have benefited from different training programs. SUMMARY: Although reporting of arboviral presence is not carried out in a systematic manner, the expansion of the area where arboviruses are present cannot be disputed. This reinforces the need for increasing surveillance capacity building in this region to prevent future emergences.

Detection of Leishmania infantum and a Novel Phlebovirus (Balkan Virus) from Sand Flies in Albania.

OBJECTIVE: To organize entomological campaigns to trap sand flies in selected regions of Albania and to test them for the presence of existing or new phleboviruses and for leishmania DNA. METHODS: Sand flies were collected in 14 locations from May to October 2014 using three different types of traps. Pools with a maximum of 30 individuals were prepared according to gender, trapping site, and trapping date; they were tested for the presence of (1) phlebovirus RNA with three different PCR systems (2) and Leishmania DNA using two different real-time PCR assays. RESULTS: A total of 972 sand flies (568 females, 404 males) were aliquoted to 55 pools. Three pools (in two different regions) were positive for Leishmania infantum. Two pools (Kruje region) were positive for phlebovirus RNA and a 575-nucleotide (nt) colinearized sequence of a novel virus most closely related to but clearly distinct from Tehran virus (16% and 3% divergence at nt and amino acid levels). Next generation sequencing analysis indicated that this virus might be transmitted by either Phlebotomus neglectus, Phlebotomus tobbi, or both vectors. CONCLUSIONS: Visceral leishmaniasis has been clinically recognized in Albania for at least 80 years; however, this is the first time that L. infantum, detected by molecular means, has been reported in sand flies in Albania. At the outset of this study, only Adria virus (Salehabad species) was recognized in Albania. A novel virus, Balkan virus, was identified and genetic analysis revealed that it belongs to the Sandfly fever Naples virus group containing human pathogens.

Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis.

BACKGROUND: Vaccine-associated paralytic poliomyelitis (VAPP) and immunodeficient long-term polio excretors constitute a significant public health burden and are a major concern for the WHO global polio eradication endgame. CASE PRESENTATION: Poliovirus type 3 characterized as Sabin-like was isolated from a 5-month-old Albanian child with X-linked agammaglobulinemia and VAPP after oral polio vaccine administration. Diagnostic workup and treatment were performed in Italy. Poliovirus replicated in the gut for 7 months. The 5' non coding region (NCR), VP1, VP3 capsid proteins and the 3D polymerase genomic regions of sequential isolates were sequenced. Increasing accumulation of nucleotide mutations in the VP1 region was detected over time, reaching 1.0 % of genome variation with respect to the Sabin reference strain, which is the threshold that defines a vaccine-derived poliovirus (VDPV). We identified mutations in the 5'NCR and VP3 regions that are associated with reversion to neurovirulence. Despite this, all isolates were characterized as Sabin-like. Several amino acid mutations were identified in the VP1 region, probably involved in growth adaptation and viral persistence in the human gut. Intertypic recombination with Sabin type 2 polio in the 3D polymerase region, possibly associated with increased virus transmissibility, was found in all isolates. Gamma-globulin replacement therapy led to viral clearance and neurological improvement, preventing the occurrence of persistent immunodeficiency-related VDPV. CONCLUSIONS: This is the first case of VAPP in an immunodeficient child detected in Albania through the Acute Flaccid Paralysis surveillance system and the first investigated case of vaccine associated poliomyelitis in Italy since the introduction of an all-Salk schedule in 2002. We discuss over the biological and clinical implications in the context of the Global Polio Eradication Program and emphasize on the importance of the Acute Flaccid Paralysis surveillance.

Genital human papillomavirus infection and genotype prevalence among Albanian women: a cross-sectional study.

"High risk" HPV types have different geographical distribution and evidence suggests their respective prevalence may vary in different areas and regions. An accurate description of high-risk HPV circulation is a key feature for the rational design of prevention and screening campaigns. A cross-sectional, virological study was conducted on adult Albanian women living either in the Tirana area or in the Duress prefecture. Clinical and gynecological evaluations were performed according to current standard criteria. HPV detection and typing were carried out by a combined MY09/MY11 and GP5+/GP6+ PCR followed by direct sequencing of generated amplicons. Virological data were obtained from 402 out of 452 patients enrolled between January 2004 and December 2007. Sixty-one patients (15.1% of the cohort) were found to be infected with a genital HPV. As expected, viral prevalence was higher among women younger than 30 years of age (25.2%) in comparison to those aged 30 or older (13.6%). HPV 16 was found to be the most frequent type (41% of cases), followed by HPV 53 (7.2%), HPV 31 (5.8%), and HPV 18 (4.3%). HPV 81 and HPV 84 were the most prevalent low-risk types detected with prevalences of 11.6% and 5.8%, respectively. No differences were noted in any type-specific prevalence between young and mature women. The circulation of HPV types is far more complex than assumed generally. Detailed knowledge of HPV type circulating patterns in specific local geographical areas is essential for appropriate implementation of screening, prevention, and surveillance campaigns.

Ecology of the Crimean-Congo hemorrhagic fever endemic area in Albania.

Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Albania. Ticks collected from cattle grazing in the endemic areas of Albania were tested for presence of CCHFV RNA, while serum samples collected from goats, cattle, hares, and birds were tested for the presence of specific IgG antibodies to CCHFV. One of the 31 pools prepared, consisting of four female Hyalomma spp. ticks, was found to carry CCHFV RNA with 99.2-100% homology to sequences detected in patients from the same region. Antibodies were not detected in cattle, hares, and birds, but 2/10 goats presented high titers of IgG antibodies. The shepherd of that flock was a member of a family affected by CCHF 10 days before the collection of goats' sera, and he presented a mild form of the disease.

Report of a serological study of Coxiella burnetii in domestic animals in Albania.

The prevalence of Coxiella burnetii antibodies in domestic ruminants in Albania has been investigated. A total of 1656 serum samples taken from sheep, goats, and cattle housed on farms located in 20 different districts were tested by ELISA for the presence of specific antibodies to C. burnetii phase I and II antigens. Specific IgG antibodies were detected in 9.1% of the animals from both lowland and mountainous areas. In total, a slightly higher percentage of antibodies was detected in sheep and goats (9.8%) than in cattle (7.9%).

Cytokine levels in Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) virus causes severe disease in humans with a mortality reaching 30%. A CCHF outbreak took place in Albania in 2003. As in other viral hemorrhagic fevers cytokines may be involved and play a role in the pathogenesis and outcome of the disease. OBJECTIVES: To investigate the levels of TNF-alpha, sTNF-R, IL-6 and IL-10 in serum samples obtained from laboratory confirmed CCHF cases and relate them to the severity of the disease. STUDY DESIGN: A study population of 51 was divided into three groups: group A, consisting of PCR-positive cases; group B, consisting of PCR-negative and serology-positive cases; group C, consisting of doubly negative cases. Concentrations of serum TNF-alpha, sTNF-R, IL-6 and IL-10 were measured during the illness. RESULTS: High levels of all cytokines tested were present in one fatal case. Statistically significant differences between the groups were obtained for TNF-alpha and IL-6: TNF-alpha was detected in 3 cases in group A, and in none of the other groups, while IL-6 was elevated in 10/16 patients in group A, 4/9 in group B, and 4/26 in group C. sTNF-R was not significantly different for the three groups. High concentration of IL-10 was detected only in the fatal case. CONCLUSIONS: TNF-alpha and IL-6 are the cytokines most often detected during a CCHF viral infection. TNF-alpha was associated with the severe form of CCHF, while IL-6 was elevated in both severe and mild cases.