[Unspecified encephalitis in HIV-infected patients: clinical and postmortem evaluation].

BACKGROUND: The search for an aetiology of central nervous system (CNS) lesions In HIV patients can be extremely challenging. AIM: To establish the nature and character of CNS lesion according to the data of pathological examination of deceased HIV-patients who had an antemortem clinical diagnosis of unspecified encephalitis. MATERIALS AND METHODS: We analysed clinical and laboratory data of 225 HIV-patients admitted to the ICU at the Infectious Clinical Hospital №2 (Moscow, 2018). The principal diagnosis was unspecified encephalitis characterized by cerebral oedema. Had died 183 (67.9%) patients. We conducted pathological examination in 43 (23.5%). RESULTS: CNS lesions occurred in 331 patients (58.8% of 563 ICU). The antemortem diagnosis established were as follows: 12.1% toxoplasmosis; 6.6% HIV-encephalitis; 5.1% CNS lymphoma; 3.6% cryptococcal meningoencephalitis; 3.0% cytomegaloviral diseases; 2.1% progressive multifocal leukoencephalopathy. The cause of the pathology remained unidentified in 225 patients (68% with CNS lesions). Majority of patients were ART-naive. Post-mortem verification was conducted in 29 (67.4%) deceased patients, of which HIV-encephalitis 34.5%, toxoplasmosis 10.3%, progressive multifocal leukoencephalopathy 3.4%. The nature of brain damage in the remaining 20.7% cases was not established even after post-mortem investigation. Productive lepto-meningitis 8 (27.6%), indicating a prolonged duration of the inflammatory process. In the brain 48.1% patients with subacute and productive changes, had a pre-hospital time of more than 30 days, in contrast to 11.1% of patients who had acute pathological processes in the CNS (p0.05). Autopsy didnt reveal any inflammatory changes in the brain in 14 (32.6%) patients, though cerebral oedema 93.3%, haemorrhagic syndrome 60% cases. CONCLUSION: Accurate retrospective identification of the aetiology of CNS lesions combined with assessing in vivo characterisation of the pathological process plays an essential role in subsequent formation of diagnostic approaches in pathologies of the CNS in HIV-patients.

[Cutaneous and visceral leishmaniasis in patients with HIV infection in Russia. Case report].

The article contains information on the problem of the combined course of HIV infection and leishmaniasis: a number of statistical and overview data in the world. It also presents a brief description of known cases of HIV patients with leishmaniasis in the Russian Federation. In all cases the diagnostics of leishmaniasis was difficult due to the lack of alertness of physicians to this illness, as well as poor knowledge of epidemiological situation of leishmaniasis. All patients with visceral leishmaniasis but one caught it during their stay in Crimea. Cutaneous leishmaniasis was described in HIV infection in the Russian Federation for the second time and is associated with the patient's residence in the Chechen Republic.

Opportunistic diseases in patients with HIV infection in the intensive care unit.

AIM: The aim of the study was to analyze the incidence and prevalence of opportunistic diseases and comorbidities in patients admitted in the intensive care unit. MATERIALS AND METHODS: A specialized intensive care unit (ICU) for patients with severe HIV infection was set up in 2014 at the infectious diseases 2nd state hospital Moscow. It provides intensive care and treatments for HIV patients with severe co-morbidities and opportunistic infections. Retrospective analysis of medical records from 2014-2016 was carried out. Also carried out was a comparative study of the most common presentation of secondary diseases with available data of HIV patients in Russia from 1993-1997. RESULTS: The number of patients treated increased from 455 to 852, and the death rate in the department decreased from 64.8 to 50.2% since it began operating. The opportunistic infections noted were cytomegalovirus, pneumocystis pneumonia, esophageal candidiasis, tuberculosis and toxoplasmosis of the brain. The most common comorbidities were chronic hepatitis C and mixed form of chronic hepatitis with cirrhosis complications. Despite the vast diagnostic possibilities, bacterial pneumonia and encephalitis of unknown origin significantly occurred. Comparative study of secondary disease since the early 1990s revealed a significant increase in cerebral toxoplasmosis (from 1.7 to 10.4%), pneumocystis pneumonia (from 5.2 to 16.0%) and encephalitis of unspecified etiology (from 13.8 to 39.4%). CONCLUSION: Disease severity among HIV patients is increasing. CMV and pneumocystis pneumonia were predominant opportunistic diseases. There were significant changes in the presentation of secondary diseases compared to data from 1993-1997.

Development of opportunistic lesions in patients with HIV infection in the absence of pronounced immunodeficiency.

AIM: Statistical data concerning patients with opportunistic infections depending on parameters of immunity and the description of a number of clinical cases of development of opportunistic lesions in patients with HIV infection in the absence of the expressed immunodeficiency. MATERIALS AND METHODS: Medical records of the patients with HIV infection hospitalized in 2012-2015 in the Infectious Diseases Clinical Hospital No. 2 of Moscow, and the clinical cases of patients with development of opportunistic lesions with satisfactory indicators of the immune status. RESULTS: The distribution of patients with HIV infection who had opportunistic infections, depending on the number of CD4+ lymphocytes at the time of development of the disease revealed a significant group of patients with a sufficiently large number of CD4+ cells. Statistical data on the development of various opportunistic lesions with different parameters of the immune status are presented. The authors describe a number of relevant clinical cases. The possible causes of the development of opportunistic diseases and their recurrence in patients with HIV infection with a satisfactory amount of CD4+ lymphocytes are discussed. In the pathogenesis of this phenomenon are important not only quantitative but also qualitative parameters of immunity, as well as the characteristics of the causative agents of opportunistic lesions.

[Clinical and epidemiological features of visceral leishmaniasis in the Republic of Crimea]. / Kliniko-épidemiologicheskie osobennosti vistseral'nogo leishmanioza v Respublike Krym.

The paper analyzes official statistical data, as well as visceral leishmaniasis (VL) cases who have visited the Clinical Center, I.M. Sechenov First Moscow State Medical University, and the results of parasitological studies of the materials submitted to the Reference Center for Monitoring of Leishmaniasis, E.I. Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases. Account is taken of the observations made by the Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare, and of the literature data available in Russian and foreign (Ukraine) scientific journals and monographs. During the period of 1932 to 2015, a total of 14 VL cases acquired in the Crimea were notified, of which there were 4 cases of VL concurrent with HIV infection. The majority of infections occurred in the eastern part of the peninsula. Given that many areas of Crimea have the status of recreation and annually receive millions of vacationists, it is necessary to conduct a more in-depth study of all aspects of this infection.

[Intrauterine Pneumocystis infection]. / Vnutriutrobnaya pnevmotsistnaya infektsiya.

Pneumocystosis is well known as an opportunistic infection that is presently most frequently registered in patients with HIV infection and in those with other immunodeficiency states. Earlier, after the Second World War, Pneumocystis pneumonia was most commonly detected in debilitated and premature children; nosocomial outbreaks of pneumocystosis were studied in detail in the 1960s and 1970s. The pathogen is transmitted through the air, but a number of references indicate that it can be transmitted through the placenta. Despite the increasing number of publications on pneumocystosis in pediatrics, physicians remain unfamiliar with this disease. The paper provides evidence that Pneumocystis jiroveci can infect the fetus in utero. If unrecognized, the disease can lead to a child's death due to severe respiratory failure. The authors describe their case of generalized pneumocystosis that has developed in a child with evidence of intrauterine infection (detection of the pathogen in the autopsy material and placenta and identification of serological markers in his/her parents). The issues that are associated with intrafamilial infection and a risk for in utero transmission of P. jiroveci are discussed.

[Follow-up study of HIV-infected patients with prior cerebral toxoplasmosis].

AIM: To assess follow-up study results in human immunodeficiency virus (HIV)-infected patients with prior cerebral toxoplasmosis (CT). SUBJECT AND METHODS: Follow-up study results were assessed in HIV-infected patients with prior CT. RESULTS: The fate of only 97 out of 137 (66% of the hospitalized) patients discharged from hospital is known, as 40 convalescents have been lost to follow up. Thereafter, relapses developed in 19 patients, of whom 6 died. Eleven more patients with HIV infection died due to its progression and development of other secondary lesions. Five more patients died from narcotic overdose, staphylococcal sepsis, and acute pancreatic necrosis. The main peak of fatal outcomes was within the first 2 years after discharge. 3.5-year survival rates after TC were 75%. The causes of recurrent and progressive HIV infection were non-compliance with secondary prevention of CT and low adherence to an antiretroviral therapy regimen, the blame of which fell not only on the patients, but also their attending physicians and specialists who had advised how to enhance treatment motivation. CONCLUSION: Further follow-up of convalescent CT patients calls for closer attention to the possible development of recurrences within the first three years after discharge in particular, regardless of CD4 cell counts.

[Secondary diseases and Burkitt's lymphoma in HIV-infected patients].

The authors give the clinical data of 110 human immunodeficiency virus (HIV)-infected patients who stayed in a correctional facility during 2014. Of the examinees, there were almost 50% of the patients with advanced stages (IVA-IVB) with different secondary/opportunistic diseases, among which was Burkitt's lymphoma, a rather rare malignant disease that developed in obvious immunodeficiency in the absence of antiretroviral therapy.

[Location of foci in cerebral toxoplasmosis in HIV-infected patients].

AIM: To analyze the data of magnetic resonance imaging (MRI) of the brain in its toxoplasmosis in HIV-infected patients. SUBJECT AND METHODS: The clinical picture of cerebral toxoplasmosis was studied in 207 patients aged 18-76 years with Stage 4B HIV infection concurrent with the disease. Brain MRI using an Obraz-1 low-field (0.12 T) MRI scanner (Russia) was carried out in 115 (55.5%) patients. This investigation was conducted in 74 (65%) treated patients over time. RESULTS: Brain T2-weighted and FLAR MRI scans most frequently revealed higher-signal polymorphic foci and T1-weighted MRI scans showed lower-signal ones predominantly involving the white matter or white-grey matter border. Perifocal edema was often recorded. Intravenous gadolinium contrast study indicated that these foci accumulated the contrast agent around the periphery following the target patterns. Sixty-four (86.5%) patients were observed to have significant positive changes: reductions in the number and sizes of foci and the area of perifocal edema; in 29 patients, the inflammatory foci changed into cysts as a favorable outcome of necrotizing encephalitis. The foci resolved completely only in 7% of the patients. CONCLUSION: MRI is of great importance in intensive care, neurology, or neurosurgery units where patients with cerebral toxoplasmosis mimicking an acute cerebrovascular accident or a brain tumor are particularly frequently admitted to.

[Cerebral toxoplasmosis in the pattern of secondary CNS involvements in HIV-infected patients in the Russian federation: clinical and diagnostic features].

The incidence of cerebral toxoplasmosis (CT) among all brain involvements was determined in patients with Stage 4B HIV infection (AIDS) in 2003-2009. Clinical and laboratory parameters were estimated in 156 patients to reveal diagnostic criteria. As a result, CT was shown to be a leading cause of neurologic diseases in patients with late-stage HIV infection (34.7% of cases of brain involvement). In 11.5%, it took place as a generalized process. CT concurrent with cytomegalovirus infection, tuberculosis, or other secondary lesions was frequently diagnosed. Of importance in the diagnosis of CT are magnetic resonance imaging results in addition to basic, clinical data that can assume this diagnosis. The high and moderate serum concentrations of T.gondii IgG are of diagnostic value, which may be used as an auxiliary method to verify the diagnosis.

[Pneumocystis pneumonia and generalized tuberculosis in HIV-infected patients].

The paper describes a clinical case of pneumocystis pneumonia in the presence of generalized tuberculosis in a female patient with HIV infection. The lack of prevention of pneumocystosis and its late diagnosis and treatment resulted in a fatal outcome. The problem of early clinical diagnosis in the concurrent course of secondary involvements is discussed.

[Current course of pneumocystic pneumonia in HIV-infected patients].

AIM: To describe clinical and laboratory characteristics of pneumocystic pneumonia (PP) in patients with HIV-infection for improvement of diagnosis quality. MATERIAL AND METHODS: Detailed examination was performed in 111 HIV-infected patients with suggested diagnosis of PP. The following investigations were made: clinical, x-ray examinations, total count and biochemical blood tests, enzyme immunoassay, indirect immunofluorescence reaction (II-FR) for Pneumocystis jiroveci antigens in bronchoalveolar lavage fluid (BALF) or induced sputum. For diagnosis of other secondary diseases PCR was used for investigation of BALF and bronchial biopsy to detect DNA of Mycobacterium tuberculosis complex, Candida albicans, Cytomegalovirus, Toxoplasma gondii, Mycoplasma spa., Herpes simplex I, II. DNA of cytomegalovirus in blood was detected with PCR. Microscopic tests of the sputum were conducted for detection of acid-resistant mycobacteria. RESULTS: PP was associated with other secondary diseases in 59% patients (pulmonary tuberculosis ---16%, CMV pneumonia--31%, combination of all the lesions--5%). PP diagnosis was cancelled and pulmonary tuberculosis was diagnosed in 12 patients. In combination of PP with other pathology dominant were symptoms observed in PP monoinfection and only effective anti-pneumocystic treatment revealed signs of comorbid pathology. Tuberculosis patients had weaker signs of respiratory failure, symmetric bilateral interstitial or small-focal alterations were detected less frequently. CONCLUSION: Current PP course characteristics in HIV infection are identified. In clinical diagnosis of PP special attention should be paid to data complex especially to increasing respiratory failure, high ESR, elevated lactate dehydrogenase, low blood pO2, fast response to ex juvantibus therapy. The most effective method of the diagnosis verification--BALF IIFR.

[The pattern of central nervous system lesions in HIV-infected patients of the specialized unit in infectious disease hospital].

AIM: To define the incidence and features of brain lesion (BL) in HIV-infected inpatients. SUBJECTS AND METHODS: Four hundred and fifty-eight patients with Stage 4B HIV infection (AIDS) and central nervous system (CNS) lesion admitted to Infectious Diseases Hospital Two, Moscow, were followed up in 2003-2009. The authors used cerebrospinal fluid (CSF) microscopic and bacteriological assays for DNA of T. gondii, M. tuberculosis, herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), HSV type 6, and varicella-zoster virus, Cr. neoformans, C. albicans, C. glabrata, and C. krusei. Blood and CSF were tested for IgM and IgG T. gondii antibodies; brain magnetic resonance imaging was carried out. RESULTS: In patients with late-stage HIV infection, the principal cause of neurological diseases was cerebral toxoplasmosis (34.7% of BL cases) and a generalized process involving the brain, lung, heart, liver, and eyes in 11.5%. There was commonly cerebral toxoplasmosis concurrent with CMV infection with clinical manifestations. 16-32% of the inpatients developed tuberculosis meningoencephalitis that was a manifestation of hematogenous disseminated tuberculosis involving the lung. There was a rise in the incidence of cancers (brain lymphomas, astrocytomas) running with CNS lesion. Mental disorders progressing to dementia were a distinctive property of CMV ventriculoencephalitis, one of the leading factors in the development of AIDS dementia complex. Molecular diagnostic techniques are needed to ascertain the etiology of BL in HIV infection. CONCLUSION: The CSF test for DNA of causative agents is a specific and most sensitive method for diagnosing a relevant CNS lesion.

[Cerebral toxoplasmosis in HIV-infected patients].

AIM: To detect clinical characteristics of cerebral toxoplasmosis in HIV-infected patients, to clarify diagnostic role of detection of DNA and antibodies to Toxoplasma gondii in the cerebrospinal fluid (CSF) and blood. MATERIAL AND METHODS: Diagnostic procedures were performed in 156 patients with HIV infection at the stage IVB (AIDS) in 2003-2006. All the patients suffered from diseases of the central nervous system (CNS). Toxoplasmosis was diagnosed in 57 (36%) cases. Lumbar puncture, MR imaging of the brain, reaction of indirect immunofluorescence, polymerase chain reaction and enzyme immunoassay were made to identify IgM and IgG to T. gondii. RESULTS: Typical for HIV-infected patients with cerebral toxoplasmosis were focal symptoms of CNS affection, hemipareses, adynamia, mental disorders, intoxication symptoms. CONCLUSION: MR imaging data are very important. Toxoplastosis is characterized by multiple destructive foci in the hemispheres and cerebellum with great amount of the parasites along the periphery of brain tissue necrosis. Detection of the infective agent DNA and specific IgG antibodies in cerebrospinal fluid confirms the presence of toxoplasmosis but sensitivity of the markers is low. IgG antibodies to T. gondii have diagnostic implications if they occur in high and moderate titers.

[Secondary diseases in patients with HIV infection: 15-year follow-up]. / Vtorichnye zabolevaniia u bol'nykh c VICh-infektsiei - 15-letnee nabliudenie.

AIM: To analyse the results of a 15-year study of opportunistic diseases in AIDS patients. MATERIAL AND METHODS: The spectrum of opportunistic diseases were made in AIDS patients in respect to clinical, laboratory and autopsy data for the periods: 1987-1992 (n = 27, 25 deaths--92.6%), 1993-1997 (n = 95, 58 deaths--61.8%), 1998-1999 (n = 70, 28 deaths--40%), 2000-2001 (n = 126, 31 deaths--24.6%), 2002 (n = 80, 32 deaths--40%). RESULTS: The spectrum of opportunistic diseases in AIDS patients was determined for the above time periods and causes underlying these diseases have been determined. CONCLUSION: Among opportunistic diseases associated with HIV infections most prevalent were the following: tuberculosis, cytomegaloviral infections, cerebral toxoplasmosis. Leading modern trends were identified: increasing morbidity of AIDS, tuberculosis, new AIDS cases at late stages with severe opportunistic diseases (2/3 of deaths).

Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent.

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA(+) type I, and CagA(-) type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10(7) CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10(4)-10(5) CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a > or =100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2-3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.

Oral immunization with recombinant Helicobacter pylori urease confers long-lasting immunity against Helicobacter felis infection.

Recombinant Helicobacter pylori urease (rUre) has been shown to confer protection against challenge with Helicobacter felis in mice. The purpose of the present study was to examine duration of the immune response and long-term protective efficacy of immunization with rUre. Swiss Webster mice were orally immunized four times at weekly intervals with 100 microg rUre plus 5 microg heat-labile enterotoxin of Escherichia coli (LT) adjuvant, or with LT only. At 4, 10, 20 or 40 weeks post immunization, 25 rUre-immunized mice and control mice were challenged with H. felis and sacrificed at 2 or 10 weeks post-challenge. H. felis infection was assessed by gastric urease assay and by histology. Anti-H. pylori urease specific antibody levels were measured in serum and saliva both pre- and post-challenge. Over the 40 week time period, the infection rates in rUre-immunized mice were significantly lower than those in controls (p < 0.05) as assessed by gastric urease activity. Protection ranged from 79 100% at 2 weeks post-challenge and 63-78% at 10 weeks post-challenge. Gastric bacterial density in rUre-immunized mice was significantly lower than that of controls (p < 0.03) as determined by histologic assessment. Anti-urease antibody levels remained elevated in the serum and mucosal compartments at 39 weeks following immunization. This study shows that immunization with rUre plus LT results in long-lasting protective immunity against challenge with H. felis.