A systematic review of neurological manifestations of SARS-CoV-2 infection: the devil is hidden in the details.

BACKGROUND AND PURPOSE: We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system. METHODS: We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. RESULTS: We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barré syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards. CONCLUSIONS: This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.

Tularemia transmission to humans: a multifaceted surveillance approach.

Tularemia has sustained seroprevalence in Eurasia, with estimates as high as 15% in endemic regions. The purpose of this report is to characterise the current epidemiology of Francisella tularensis subspecies holarctica in Georgia. Three surveillance activities are summarised: (1) acute infections captured in Georgia's notifiable disease surveillance system, (2) infectious disease seroprevalence study of military volunteers, and (3) a study of seroprevalence and risk factors in endemic regions. Descriptive analyses of demographic, exposure and clinical factors were conducted for the surveillance studies; bivariate analyses were computed to identify risk factors of seropositivity using likelihood ratio χ2 tests or Fisher's exact tests. Of the 19 incident cases reported between 2014 and August 2017, 10 were confirmed and nine met the presumptive definition; the estimated annual incidence was 0.12/100 000. The first cases of tularemia in Western Georgia were reported. Seroprevalences of antibodies for F. tularensis were 2.0% for military volunteers and 5.0% for residents in endemic regions. Exposures correlated with seropositivity included work with hay and contact with multiple types of animals. Seroprevalence studies conducted periodically may enhance our understanding of tularemia in countries with dramatically underestimated incidence rates.

First description of a cefixime- and ciprofloxacin-resistant Neisseria gonorrhoeae isolate with mutations in key antimicrobial susceptibility-determining genes from the country of Georgia.

Antimicrobial resistance in Neisseria gonorrhoeae is a global health problem. Enhanced international collaborative surveillance and disease control are needed to reduce the global burden of this important pathogen. Currently the antimicrobial resistance properties and molecular mechanisms of multidrug-resistant N. gonorrhoeae in the Republic of Georgia represent a significant knowledge gap. Here we report the isolation of a strain of N. gonorrhoeae exhibiting resistance to cefixime and ciprofloxacin with reduced susceptibility to penicillin and tetracycline from a patient being treated at a Georgian medical centre. Notably, this isolate was found to contain a mosaic penA allele and to harbour mutations in genes conferring susceptibility to the ß-lactam, cephalosporin, fluoroquinolone, macrolide and penicillin classes of antibiotic. To our knowledge, this is the first report to describe the key mutations conferring the antimicrobial resistance properties of an isolate of N. gonorrhoeae from Georgia.

CONFLICT IN EASTERN UKRAINE: STRATEGY FOR TUBERCULOSIS.

This root cause analysis concerns the conflict in the Eastern Ukraine and its impact on healthcare delivery in the context of treating internally displaced persons (IDPs). Inadequate treatment of tuberculosis (TB) was selected as a major topic for intervention planning in conflict areas in Ukraine. With respect to treating TB among IDPs, rapid diagnosis and adequate nutrition and shelter are important components of care and disease control. The DOT, supported by trained primary healthcare providers equipped with rapid MDR TB diagnostic capacities, need to provide appropriate shelter and nutrition to IDPs. In addition to active disease management, this paper discusses the important role of ongoing project monitoring and communicating evaluation findings with all the major stakeholders shaping the national TB strategy in Ukraine. A comprehensive strategy is essential for successful transitioning and re-structuring of TB healthcare delivery both during after conflict resolution.

IMPORTANT ASPECT OF HEALTH CARE ASSOCIATED INFECTIONS IN GEORGIA WITH THE FOCUS ON VENTILATOR-ASSOCIATED PNEUMONIA (REVIEW).

Health care associated infections are the most frequent adverse event accompanying healthcare delivery worldwide. Of these, respiratory tract infections, including ventilator-associated pneumonia (VAP), have been recognized as the most common infections in acute hospitals. Sparse anecdotal and epidemiologic data from intensive care units (ICU) and infectious diseases physicians, as well as several publications in this field, suggest that the etiology of VAP in Georgia is most likely Klebsiella pneumoniae. This review article discusses the challenges of infection control in the Georgian health care system, with a focus on VAP. We present the most significant risk factors as well as potential strategies to remediate infection control practices and reduce the prevalence of VAP.

Comparison of total antibody and interferon-γ T-cell responses in patients following infection with brucellosis in Georgia.

Brucellosis is an ancient disease that still remains a significant threat to humans and is typically linked to exposure to infected animals and/or consumption of unpasteurized animal products. Despite this history, we have a relatively limited understanding of the host characteristics of this disease; consequently, further research is necessary. In this study, we examined the humoral immune response in 43 Georgian individuals that had been diagnosed with brucellosis 3-12 months before enrollment in the study, many of whom still had symptoms after the completion of antibiotic therapy. In total, 35 of 43 (83%) of the patients had antibodies that bound to Brucella lipopolysaccharide (LPS) by COMPELISA, and 34 of 38 (89%) patients had demonstrable specific antibodies to Brucellergene™ antigens; the results from the two ELISAs were highly correlated (p=0.031, r=0.851). We also studied the cellular immune responses in 15 patients. All of the patients generated interferon (IFN)-γ in response to ex vivo stimulation with Brucella protein antigens, and the majority of the patients maintained measurable humoral responses to both LPS and protein antigens. From this initial study, we conclude that measurement of antibody and of cellular (IFN-γ) responses to brucellergene OCB protein epitopes may be worthy of further investigation as an alternative or adjunct to current diagnostics.

Als-like syndrome in the patient with chronic hepatitis C.

Amyotrophic lateral sclerosis (ALS) is the most common and most severe form of the motor neuron disease. The etiology of ALS is unknown. Several underlying causes are proposed, including viral infection. There is clinical evidence suggesting that ALS may be associated with Human Immunodeficiency Virus. Besides, enterovirus RNA sequences have been detected in a spinal cord of patients with ALS. We describe a patient with a 9 year history of hepatitis C, with a progressive weakness and atrophy of the right arm. Neurologic examination revealed bilateral hypotrophy and fasciculations of brachial girdle muscles more expressed on the right. No sensory or sphincter deficit was present. Nerve conduction studies and EMG were performed. Local EMG of the right deltoid muscle revealed a 4-5th stage lesion of peripheral neuromotor system, characteristic to neurogenic disease. Viruses can be one of the triggering factors of ALS. HV has never been associated with ALS. However, we found it interesting to describe this case of ALS-syndrome developed on the background of the chronic hepatitis C to draw attention of specialists on the possible role of HCV in ALS.

The role of imaging studies in CNS infections.

Recent advances in nervous system imaging techniques have greatly improved the diagnosis and treatment of central nervous system infections. Nowadays, the most useful imaging modalities are harmless to the patient and widely available. Whereas Analysis of CSF, biopsy, and laboratory analysis remain the gold standard to identify the infectious agent for instance in meningitis, neuroimaging is crucial in clearly depicting inflammatory lesions of brain and spine. Notably, in opportunistic disease neuroimaging has a pivotal role not only in diagnosis but also in monitoring therapeutic response. The present review discusses imaging characteristics of bacterial, viral, fungal and prion infections of the central nervous system.

Prion diseases--mysterious persistent infections.

The group of persistent viral infections includes latent, chronic and slow infections. The latter can be caused by: conventional viruses (e.g. polyomavirus JC - causative agent of the Progressive Multifocal Leucoencephalopathy (PML)); defective forms of conventional viruses (e.g. defective measles virus, causing Subacute Sclerosing Panencephalitis (SSPE)) and non-conventional infectious agents - prions (proteinaceous infectious particles), causative agents of transmissible spongiform encephalopathies of humans and different animal species. Prion Diseases are unique in that the same pathologic substrate may cause infectious , genetic and sporadic disease. The primary signs of prion diseases are cognitive impairment and ataxia. On histologic analysis of tissue, spongiform degeneration of the brain accompanied by activated astrocytes and microglia is observed. Prion diseases are the least frequent of all persistent infections. However, there is a big scientific interest in these diseases aimed to solve many open questions related to these mysterious diseases. Emergence of the variant Creutzfeldt-Jakob disease in 1996 in Europe manifested a new threat - prions may cross a species barrier, humans may get infection from diseased animals. According to some authors, the list of prion diseases may grow to include several neurodegenerative disorders. The present review discusses current scientific concepts and peculiarities of prion diseases.