Objective: To analyze clinical and laboratory features to predict the outcome of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients. Materials and methods: Retrospective analysis of medical histories of HIV-infected patients with CNS lesions in 2015–2017, and dynamic monitoring of HIV patients with CNS lesions in 2018–2019, who were intensive care unit (ICU) in Infectious Clinical Hospital No. 2 of the Department of Health of Moscow. Results and discussion: A total 196 patients with encephalitis/meningoencephalitis: 124 (63%) patients with detected JCPyV in the cerebrospinal fluid (CSF) — study group (JCPyV+), 72 patients with undetectable JCPyV in CSF — comparison group (JCPyV–). Late terms of hospitalization were noted, mainly in the JCPyV+ group (mean — 58±6 days). The majority of patients had severe immunodeficiency, in the JCPyV+ group the number of patients with CD4<200 cells/μl was significantly higher than in the JCPyV– group (87.8% and 75.8%, p<0.05). Only 22% of patients received antiretroviral therapy (ART) prior to hospitalization. The main clinical manifestations of PML in the study were: paralysis and paresis of the limbs, speech impairment, cognitive disorders in combination with cerebral symptoms in the absence of meningeal signs. In 87.8% patients with positive JCPyV DNA no other pathogens were detected in the CSF; in the patients without PML the detection of infectious agents in the CSF was also rare (14.3%). The disease led to the death for 78% patients in the JCPyV+ group and 72% JCPyV– group, p>0.05. The chance of survival was 2.5 times higher for patients admitted to hospital less than 14 days after deterioration (OR=2.468 [95% CI: 1.244–4.898]). Patients with CD4<200 cells/μL were 5.5 times more chance to die than patients with higher CD4 rates (OR=5.449 [95% CI: 2.388–12.431]). There was no relationship between the concentration of JCPyV DNA and HIV RNA in the CSF and their impact for the disease outcome. Conclusion: Survival prognosis for PML during treatment in ICU was worser for patients hospitalized after 14 days from the onset of symptoms and with CD4<200 cells/μL. Early ART initiation for all HIV-positive individuals significantly reduces the number of opportunistic infections and improve life expectancy.

Progressive multifocal leukoencephalopathy (PML) is one of the most severe opportunistic diseases of the central nervous system, which leads to multiple demyelination of brain structures, neurological symptoms and frequent death or disability of the patient. The etiological factor of this disease is Human polyomavirus 2 (JCPyV).This pathogen is widespread – antibodies are found in 80% of the world›s population. However, the clinical symptoms of this infection appear only in people with a pronounced decline in cellular immunity. Until 1980 progressive multifocal leukoencephalopathy was extremely rarely diagnosed. Now days the main cause of the clinical symptoms of PML is immunodeficiency caused by HIV infection. Clinical manifestations of PML are characterized by various non-specific neurological symptoms, similar to other lesions of the central nervous system, the symptoms progress slowly over several months, and usually lead to death. Diagnosis of PML is based on laboratory and instrumental methods, such as DNA JCPyV detection in the cerebrospinal fluid, brain biopsy, and radiation diagnostic methods. There is no effective prevention and etiotropic therapy for PML. Improved parameters of cellular immunity and antiretroviral treatment in HIV positive patients significantly increase the life expectancy of patients with PML. Despite the ability of drugs to prevent the progression of the disease, pathological changes in the brain are irreversible and lead to persistent disability of patients, therefore, it is necessary to diagnose PML in the early stages of the disease.

Progressive multifocal leukoencephalopathy (PML) is one of the most severe opportunistic diseases of the central nervous system, which leads to multiple demyelination of brain structures, neurological symptoms and frequent death or disability of the patient. The etiological factor of this disease is Human polyomavirus 2 (JCPyV).This pathogen is widespread – antibodies are found in 80% of the world›s population. However, the clinical symptoms of this infection appear only in people with a pronounced decline in cellular immunity. Until 1980 progressive multifocal leukoencephalopathy was extremely rarely diagnosed. Now days the main cause of the clinical symptoms of PML is immunodeficiency caused by HIV infection. Clinical manifestations of PML are characterized by various non-specific neurological symptoms, similar to other lesions of the central nervous system, the symptoms progress slowly over several months, and usually lead to death. Diagnosis of PML is based on laboratory and instrumental methods, such as DNA JCPyV detection in the cerebrospinal fluid, brain biopsy, and radiation diagnostic methods. There is no effective prevention and etiotropic therapy for PML. Improved parameters of cellular immunity and antiretroviral treatment in HIV positive patients significantly increase the life expectancy of patients with PML. Despite the ability of drugs to prevent the progression of the disease, pathological changes in the brain are irreversible and lead to persistent disability of patients, therefore, it is necessary to diagnose PML in the early stages of the disease.

The outbreak of shigellosis caused by Shigella. flexneri 2a which affected a total of 42 persons was revealed by epidemiological analysis and microbiological testing in a nursing home for disabled children with a severe pathology of the nervous system. At the same time, four fatal cases among children were registered. The main purpose of our study was to perform an enhanced investigation to find potentially novel etiological agent among affected persons especially in cases with fatal outcome. We applied a broad range of commercial kits based on the nucleic acid amplification techniques as well as bacteriological methods for etiological diagnosis. Additionally, several S. flexneri 2a isolates and revealed bacterial pathogens were subjected to pulsed-field gel electrophoresis (PFGE) and Whole Genome Sequencing (WGS) for expanded genetic characterization as well as demonstration of their clonality and the presents/absence of unusual pathogenic determinants. Genetic relationship between viral pathogens was characterized by Sanger sequencing of phylogenetically informative regions. Epidemiological data and lab testing allowed considering the generalized herpes simplex virus type 1 infection (HSV-1) to be a possible cause of fatal cases.