Jan Richter

Extraparenchymal neurocysticercosis, caused by Taenia solium, is an uncommon form of neurocysticercosis involving the subarachnoid space and ventricular system. Clinical manifestations are heterogeneous, including seizures, meningitis, and intracranial hypertension, and are often associated with worse outcomes. Diagnosis remains challenging, as cysts may be difficult to detect on conventional imaging due to signal characteristics similar to cerebrospinal fluid, frequently leading to inconclusive results. We describe a patient presenting with a six-month history of focal seizures in whom the diagnosis was established following surgical excision of a cystic lesion, with definitive confirmation provided by positive PCR detection of T. solium nuclear ribosomal DNA in the excised tissue. The patient received 14 days of dual antiparasitic therapy and remained free of neurological symptoms during 12 months of follow-up. This case highlights the potential limitations of noninvasive diagnostic modalities and the challenges that physicians might encounter when evaluating infectious diseases that are not endemic to their country of practice. It also underscores the value of a structured diagnostic approach, as recommended by several international health bodies, complemented by advanced molecular techniques such as PCR. Overall, it provides a clinically relevant illustration of key diagnostic challenges and decision-making steps in the evaluation of this complex condition.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by immune-mediated demyelination and neurodegeneration. Although the exact cause of MS remains unclear, accumulating epidemiological and immunological evidence strongly implicates Epstein–Barr virus (EBV) infection as a major environmental factor associated with disease development. Nearly all individuals with MS are EBV seropositive, and longitudinal studies have demonstrated that EBV infection precedes MS onset, supporting a causal relationship. EBV establishes lifelong latency in B cells and can profoundly influence host immune responses, providing several potential mechanisms through which it may contribute to autoimmunity. In this review, we summarize current knowledge of EBV biology and discuss epidemiological findings linking EBV infection with MS risk. We then examine alterations in EBV-specific immune responses observed in MS, including dysregulated humoral and cellular immunity. Particular attention is given to molecular mimicry involving the Epstein–Barr nuclear antigen 1 (EBNA1) and central nervous system proteins, which may promote cross-reactive autoimmune responses. Finally, we discuss evidence for the presence and potential role of EBV-infected immune cells within the MS brain and highlight key unanswered questions that remain critical for understanding EBV-driven neuroinflammation.

West Nile virus (WNV) causes human disease with variable severity. Toll-like receptor 3 (TLR3) is essential for innate immune responses to viral infections, including WNV. The non-synonymous single-nucleotide polymorphism (SNP) rs3775291 (C/T), which alters TLR3 function, has been linked to susceptibility to several viral pathogens, but its role in WNV infection is unclear. This study investigates the association between rs3775291 and WNV infection in hospitalized patients. A case–control study was conducted in Cyprus, including 20 hospitalized WNV patients and 22 healthy controls (HCs). Genotyping was performed using a TaqMan allelic discrimination assay. The C/T genotype was significantly more frequent in WNV patients (65%) than in HCs (27.3%) (p = 0.0217; OR = 0.1648, 95% CI: 0.04073–0.6731). C/T and T/T genotypes combined were more common in patients (75%) versus HCs (36.4%) (p = 0.0157; OR = 0.1905, 95% CI: 0.05017–0.7232). The T allele was more frequent in patients, but not statistically significant (p = 0.0640). The results indicate that the C/T genotype is associated with increased susceptibility to WNV infection and the likelihood of hospitalization. Further studies in larger, independent cohorts and across diverse populations and age groups are warranted to validate these findings.

The COVID-19 pandemic has had a profound impact on healthcare systems worldwide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens in SARS-CoV-2-positive individuals may exacerbate symptom severity and lead to poorer clinical outcomes. Background/Objectives: This study is the first to investigate the prevalence of viral and bacterial co-infections in SARS-CoV-2-positive individuals in Cyprus. Methods: A total of 1111 SARS-CoV-2-positive nasopharyngeal swab samples collected from non-hospitalized patients were analyzed for the presence of 18 viral and 3 bacterial respiratory pathogens. Results: Of these, 51 samples (4.6%) were found to have at least one additional respiratory pathogen. The most frequently detected viruses were rhinovirus/enterovirus (n = 28; 2.5%) and adenovirus (n = 8; 0.7%), while the bacterial pathogens identified were Legionella pneumophila (n = 1; 0.1%) and Bordetella pertussis (n = 1; 0.1%). The highest proportion of co-infections was observed in the youngest age group (<10 years), where 52.9% of co-infections were identified, followed by the 30–39 age group, which accounted for 15.7% of cases. Among single respiratory virus co-infections, rhinovirus/enterovirus (27.5%) and adenovirus (13.7%) were the most frequently detected in the <10 age group, followed by RSV (3.9%), bocavirus, influenza B, HMPV A + B, and coronavirus NL63 (each at 2%). Conclusions: The current study underscores the importance of simultaneous testing for SARS-CoV-2 and other respiratory pathogens, as this may have significant implications for both individual patient care and healthcare services.

The COVID-19 pandemic has had a profound impact on healthcare systems world-wide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens in SARS-CoV-2-positive individuals may exacerbate symptom severity and lead to poorer clinical outcomes. Background/Objectives: This study is the first to investigate the prevalence of viral and bacterial co-infections in SARS-CoV-2-positive individuals in Cyprus. Methods: A total of 1,111 SARS-CoV-2-positive nasopharyngeal swab samples were analysed for the presence of 18 viral and 3 bacterial respiratory pathogens. Re-sults: Of these, 51 samples (4.6%) were found to have at least one additional respira-tory pathogen. The most frequently detected viruses were Rhinovirus/Enterovirus (n = 28; 2.5%) and Adenovirus (n = 8; 0.7%), while the bacterial pathogens identified were Legionella pneumophila (n = 1; 0.1%) and Bordetella pertussis (n = 1; 0.1%). The highest proportion of co-infections was observed in the youngest age group (<10 years), where 52.9% of co-infections were identified, followed by the 30–39 age group, which ac-counted for 15.7% of cases. Among single respiratory virus co-infections, Rhinovi-rus/Enterovirus (27.5%) and Adenovirus (13.7%) were the most frequently detected in the <10 age group, followed by RSV (3.9%), Bocavirus, Influenza B, HMPV A+B, and Coronavirus NL63 (each at 2%). Conclusions: The current study underscores the im-portance of detecting co-infections in SARS-CoV-2-positive individuals, as this could have significant implications for therapeutic management. Early identification of coinfecting pathogens may guide targeted treatment strategies, reduce complications, and improve overall clinical outcomes.

Community-acquired pneumonia (CAP) remains the leading cause of hospitalization among infectious disease in Europe, and a major cause of morbidity and mortality. In order to determine and characterize the aetiology of CAP in hospitalized adults in Cyprus, respiratory and blood samples were obtained from hospitalized patients with CAP, and analyzed using Multiplex Real-Time PCR/RT-PCR, and ID/AMR enrichment panel (RPIP) analysis. Probe-based allelic discrimination was used to investigate genetic host factors in patients. The aetiology could be established in 87% of patients. The most prevalent viral pathogens detected were influenza A, SARS-CoV-2, and human rhinovirus. The most common bacterial pathogens detected were Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Antimicrobial resistance genes were identified in 23 patients. S. aureus was the most common AMR correlated strain in our study. A positive correlation was detected between bacterial infections and the NOS3 rs1799983 G allele and the FCGR2A rs1801274 G allele. A positive correlation was also detected between the TNF-α rs1800629 A allele and sepsis, while a negative correlation was detected with the ACE rs1799752 insertion genotype and the severity of pneumonia. In conclusion, the targeted NGS panel approach applied provides highly sensitive, comprehensive pathogen detection, in combination with antimicrobial resistance AMR insights that can guide treatment choices. In addition, several host factors have been identified that impact the disease progression and outcome.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 resulted in the coronavirus disease 2019 (COVID-19) pandemic, which has had devastating repercussions for public health. Over the course of this pandemic, the virus has continuously been evolving, resulting in new, more infectious variants that have frequently led to surges of new SARS-CoV-2 infections. In the present study, we performed detailed genetic, phylogenetic, phylodynamic and phylogeographic analyses to examine the SARS-CoV-2 epidemic in Cyprus using 2352 SARS-CoV-2 sequences from infected individuals in Cyprus during November 2020 to October 2021. During this period, a total of 61 different lineages and sublineages were identified, with most falling into three groups: B.1.258 & sublineages, Alpha (B.1.1.7 & Q. sublineages), and Delta (B.1.617.2 & AY. sublineages), each encompassing a set of S gene mutations that primarily confer increased transmissibility as well as immune evasion. Specifically, these lineages were coupled with surges of new infections in Cyprus, resulting in the following: the second wave of SARS-CoV-2 infections in Cyprus, comprising B.1.258 & sublineages, during late autumn 2020/beginning of winter 2021; the third wave, comprising Alpha (B.1.1.7 & Q. sublineages), during spring 2021; and the fourth wave, comprising Delta (B.1.617.2 & AY. sublineages) during summer 2021. Additionally, it was identified that these lineages were primarily imported from and exported to the UK, Greece, and Sweden; many other migration links were also identified, including Switzerland, Denmark, Russia, and Germany. Taken together, the results of this study indicate that the SARS-CoV-2 epidemic in Cyprus was characterized by successive introduction of new lineages from a plethora of countries, resulting in the generation of waves of infection. Overall, this study highlights the importance of investigating the spatiotemporal evolution of the SARS-CoV-2 epidemic in the context of Cyprus, as well as the impact of protective measures placed to mitigate transmission of the virus, providing necessary information to safeguard public health.

The aim of this study was to investigate and obtain insights into the appearance, spread and impact of the Omicron variants and their sub-lineages in Cyprus by analyzing 611 high-coverage full-genome sequences for the period from November 2021 until April 2022. All viruses sequenced were identified to belong to either Delta (B.1.617.2) or Omicron (lineage BA.1 and BA.2, respectively), with a variety of different sub-lineages. A detailed analysis of the mutational profile is presented and discussed. The Omicron variant BA.1 was shortly followed by BA.2; despite emerging against a background of high vaccination (81% of adult population) and pre-existing natural immunity, they gave rise to the largest waves of infection, with daily numbers rising dramatically, highlighting their increased ability for immune evasion. Within a period of only five months, the percentage of the Cypriot population with a confirmed infection increased from ~15% of the total population to >57%. Despite unprecedented case numbers, a significant reduction in hospital burden and mortality was observed. Our findings highlight the role of the importation of new variants through travel and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures.

Charcot-Marie-Tooth disease type 1A (CMT1A), the most common inherited demyelinating peripheral neuropathy, is caused by PMP22 gene duplication. Overexpression of WT PMP22 in Schwann cells destabilizes the myelin sheath, leading to demyelination and ultimately to secondary axonal loss and disability. No treatments currently exist that modify the disease course. The most direct route to CMT1A therapy will involve reducing PMP22 to normal levels. To accomplish this, we developed a gene therapy strategy to reduce PMP22 using artificial miRNAs targeting human PMP22 and mouse Pmp22 mRNAs. Our lead therapeutic miRNA, miR871, was packaged into an adeno-associated virus 9 (AAV9) vector and delivered by lumbar intrathecal injection into C61-het mice, a model of CMT1A. AAV9-miR871 efficiently transduced Schwann cells in C61-het peripheral nerves and reduced human and mouse PMP22 mRNA and protein levels. Treatment at early and late stages of the disease significantly improved multiple functional outcome measures and nerve conduction velocities. Furthermore, myelin pathology in lumbar roots and femoral motor nerves was ameliorated. The treated mice also showed reductions in circulating biomarkers of CMT1A. Taken together, our data demonstrate that AAV9-miR871–driven silencing of PMP22 rescues a CMT1A model and provides proof of principle for treating CMT1A using a translatable gene therapy approach.