Features of the course of acute decompensated ischemic heart failure and/or ongoing adverse left ventricular remodeling in patients with identified human herpes virus type 6

Objective. To determine serum levels of immunoglobulin M (IgM) and G (IgG) antibodies to human herpes virus type 6 (HHV-6) (anti-HHV-6) and features of clinical and morphological portrait in patients with acute decompensated heart failure (ADHF) of ischemic genesis and/or adverse left ventricular (LV) remodeling.Material and Methods. This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials. gov (#NCT02649517) and comprised 25 patients (84% men) with ADHF and LV ejection fraction (EF) ≤ 40%. All patients underwent endomyocardial biopsy (EMB) with immunohistochemistry (IHC) analysis for the presence of HHV-6, compliment C1q, major histocompatibility complex of class II (MHC II), and B-lymphocyte antigen (CD19) as the markers of autoimmune reaction as well as the serum levels of anti-HHV-6 IgM and IgG. Serum levels of IgM and IgG were measured using enzymelinked immunosorbent assay (ELISA) with the calculation of positivity coefficient (PC) according to manufacturer instructions. The test results were interpreted as positive when PC value was greater than 0.8.Results. The endomyocardial biopsy study detected HHV-6 antigen expression in 15 (60%) out of 25 enrolled patients including 10 cases with diagnosed HHV-6-positive myocarditis and five patients with carriage of viruses. According to IHC, the autoimmune HHV-6 myocarditis was confirmed in three cases (30%). The data of ELISA (n = 18) detected anti-HHV-6 IgM in 5 patients (28%) and anti-HHV-6 IgG in 11 cases (61%). The simultaneous presence of both anti-HHV-6 IgM and IgG was detected in two patients (11%). In addition, anti-HHV-6 IgM and IgG were absent in two (11%) cases. Eight patients (44%) with HHV-6-positive myocarditis included three patients (17%) tested positive for serum anti-HHV-6 IgM, three patients (17%) tested positive for serum anti-HHV-6 IgG, and two patients (11%) who had nether anti-HHV-6 IgM nor anti-HHV-6 IgG in blood serum. Among virus carriers, one patient (20%) was tested positive for anti-HHV-6 IgM and four patients (80%) were tested positive for anti-HHV-6 IgG. The patients without HHV-6 antigen expression (n = 5, 28%) included one patient (5.6%) tested positive for anti-HHV-6 IgM and two patients (11%) tested positive for anti-HHV-6 IgG. The entire sample of patients was divided into two groups depending on the serum level of anti-HHV-6 IgM: group 1 comprised patients tested positive for anti-HHV-6 IgM (n = 5); group 2 comprised patients (n = 13) tested negative for anti-HHV-6 IgM. Clinical and instrumental parameters differed only in the duration of CHF history, which was greater in group 1 than in group 2 (11.0 [8.0; 12.0] vs. 22.5 [14.5; 75.5] months, respectively (p = 0.045). The groups did not significantly differ in the studied markers in myocardial tissue according to the results of IHC analysis. No associations were found between the severity of HHV-6 antigen expression and serum levels of anti-HHV-6 IgM and IgG.Conclusion. Patients with ADHF and/or adverse LV remodeling after complete myocardial revascularization had higher percentage of HHV-6 antigen expression whose severity was not associated with the serum levels of anti-HHV-6 IgM and IgG.

The role of viruses and bacteria in the development of cancer

Recently, there have been some scientific studies proving the role of viruses and bacteria in the development of cancer. Among them are eighteen types of pathogens (Helicobacter pylori, hepatitis B virus (HBV), hepatitis C virus (HCV), Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium, human papillomavirus (HPV), Barr (EBV) virus, Ephthia virus-human cell 1 (HTLV-1), human herpes virus type 8 (HHV-8) and human immunodeficiency virus type 1 (HIV-1), belong to group 1 carcinogens. Further study of the role of viruses and bacteria in the development of cancer is of great importance for the early prevention of cancer. Key words: cancer, viruses, bacteria

CLINICAL CASES OF DETECTION OF CHROMOSOMALLY INTEGRATED HUMAN HERPESVIRUS TYPE 6 IN TWO CHILDREN

The article describes two clinical observations of the detection of chromosomally integrated human herpes virus type 6 (HHV-6). In both cases, the children were referred to an immunologist with a diagnosis of chronic infection caused by the human herpesvirus type 6, in order to exclude an immunodeficiency state and determine the strategies of treating this infection. However, during the molecular biological examination of children, a chromosomal integration of HHV-6 was determined, which led to a revision of the diagnostic search and abandoning massive antiviral therapy.

Cellular composition of macrophage infiltration in patients with acute decompensation of ischemic HFrEF depending on the diagnosed human herpes virus type 6

Funding Acknowledgements Type of funding sources: None. Objective To determine the cellular composition of macrophage infiltration in patients with acute decompensation of ischemic heart failure (ADHF) depending on the diagnosed human herpes virus type 6 (HHV6) antigen expressions in myocardial tissue. Methods This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials.gov (#NCT02649517) and included 25 patients (84% men, LVEF of 29.17 ± 9.4%) with ADHF. Inclusion criteria were ADHF, not earlier than 6 months after optimal surgery (PCI or/and CABG) and optimal drug treatment for HF according to ESC guidelines. Invasive coronary angiography was performed in all patients to exclude the progression of coronary atherosclerosis. All patients underwent endomyocardial biopsy with immunohistochemically analysis (IHC) for presence of HHV6. Immunohistochemical criteria of myocarditis were at least 14 leukocytes per sq. mm in the myocardium including up to 4 monocytes and 7 or more CD3+ T lymphocytes per sq. mm. Macrophage infiltration in the heart was assessed by double immunofluorescence. CD68 was a marker for the cells of the macrophage lineage, CD80 was considered as M1-like macrophage and CD163, CD206, stabilin-1 were as M2-like macrophage biomarkers. Each area was evaluated in 5 random fields. The 1 patient who did not have IHC was excluded from the analysis. Results After IHC, HHV6 antigen expression were detected in 63% (n = 15). There were HHV6-positive myocarditis in 42% (n = 10) and HHV6-positive patients without myocarditis - 21% (n = 5). HHV6-negative myocarditis was identified in 25% (n = 6) cases. HHV6-negative patients without myocarditis were founded in 12% (n = 3). Group with HHV6-positive myocarditis had a greater number of CD 45 (19.5 [14.0;31.0] & 14.0 [12.0;21.0], p = 0.446) and CD 68 (18.0 [14.0;30.0] & 12.0 [9.0;15.0], p = 0.075) cells than group with HHV6-negative myocarditis. The number of CD 68 (18.0 [14.0;30.0] & 12.0 [8.0; 14.0], p = 0.049) and CD 45 (19.5 [14.0;31.0] & 8.0 [7.0;8.0], p = 0.003) significantly were differed between groups with HHV6-positive myocarditis and with HHV6-positive patients without myocarditis. The analysis of macrophage infiltrate in the groups showed differences between groups with HHV6-positive myocarditis and HHV6-negative myocarditis only in the number of CD68-/CD80+ macrophages (57.0 [33.0;68.0] & 85.0 [75.5;110.0], p = 0.009). Cellular composition of macrophage infiltration is presented in pic. 1. Conclusions The incidence of myocardial HHV6 antigen expression was 63% in patients with ADHF. There were HHV6-positive myocarditis in 42% and carriage of HHV6 in 21% in this study. HHV6-positive myocarditis has been associated with a lot of number of CD 45 and CD 68 in myocardial tissue. The predominance of M2-like macrophages was observed in patients with HHV6-positive myocarditis and carriage of HHV6. There were the largest number of CD 68-/CD 80+ macrophages (M1) were detected in patients with HHV6-negative myocarditis. Abstract Figure.

ENCEFALITIS POR VIRUS HERPES HUMANO TIPO 6 EN UNA ADOLESCENTE CON LUPUS ERITEMATOSO SISTÉMICO. PRIMER CASO REPORTADO EN EL ECUADOR.

The case of a fourteen-year-old patient with Systemic Lupus Erythematosus with severe activity index and immunosuppressive treatment is described. He went to the Pediatric Emergency Department of the Carlos Andrade Marín Specialty Hospital, for presenting fever, headache, nausea, auditory hallucinations and paresis in the lower extremities. Cerebrospinal fluid was studied by Polymerase Chain Reaction, in which the presence of Human Herpes Virus type 6 or also called Roseolovirus was detected. Ganciclovir was started with a favorable clinical response in 72 hours. Conclusions: The presence of HHV-6 encephalitis should be considered in immunocompromised patients with encephalopathy and use of ganciclovir as directed therapy.

Human Herpes Virus Type 6 is Associated with CNS Infections in Children in Sudan

Objective HHV-6 is increasingly recognized as febrile agent in children, however, less is known in sub-Saharan African countries. In here, we aimed to investigate the involvement of HHV-6 in pediatric CNS infections in Khartoum, Sudan. This report is part of a larger study on the microbial aetiologies of CNS infections in this population. Results Out of 503, 13 (2.6%) CSF specimens were positive for HHV-6 DNA which constituted 33% (13/40) of cases with proven infectious meningitis. Median Ct for all HHV-6 positive specimens was 38 with range of 31.9 to 40.8. Median virus copy was 281.3/PCR run (1x105 virus copies/ml CSF) with range of 30 to 44x103 copies/PCR run (12x103 and 18x106 virus copies/ml CSF). All positive patients presented with fever, vomiting and 86% with seizures. Male to female ratio was 1:1; 50% were toddlers, 42% infants and 8% teenagers. Most (83%) were admitted in the dry season and 17% in the rainy season. CSF leukocytosis was seen in 33%. Normal and low CSF glucose levels were seen in 86% and 14%, respectively. CSF proteins levels were low in 14% and high in 43%. In conclusion, HHV-6 is common in CNS infections in children in Sudan.

The case of inherited chromosomal integrated human herpes virus type 6b in child with recurrent respiratory tract infections

The five years old boy with recurrent respiratory tract infections was under observation of infectiologist due to high levels of human herpes virus type 6 (HHV-6), found in patient’s blood and saliva during a few years. The patient got the medicines against the HHV-6, without any effect. We investigated the patient’s and his mom’s nails and found the HHV-6 type B, so it was inherited chromosomal integrated HHV-6. Thus, to avoid the unnecessary treatment, in case of repeated high level of HHV-6, we need to exclude chromosomal integrated HHV-6.

Marshall’s syndrome in the practice of infection disease doctor and pediatrician (сlinical case)

On the basis of literary sources, modern ideas about Marshall syndrome in children are given, as well as the main clinical and laboratory criteria for the diagnosis of this syndrome. A clinical case of Marshall syndrome in a boy 3 years 6 months infected with human herpes virus type 6 is described. Differential diagnostic criteria of Marshall syndrome and active herpesvirus infections in children are presented on the example of a clinical case.

Sarcoma de Kaposi lingual. Rara variante en paciente VIH positivo. A propósito de un caso.

Kaposi's sarcoma is a vascular lesion of intermediate-grade malignant potential affecting skin, mucosa, lymph nodes, and viscera. Four clinical variants have been recognized: classic, African Kaposi sarcoma, immunosuppression-associated Kaposi sarcoma and AIDS-associated Kaposi sarcoma. Human herpes virus type 8 is implicated as the etiological agent in all of them. We present a 39-year-old man with a history of pulmonary tuberculosis under treatment, and two months of evolution HIV / AIDS, with a lympangiomatous Kaposi sarcoma in an atypical location. Keywords: Kaposi's sarcoma; HIV; HHV-8; vascular neoplasia; lymphangioma-like Kaposi sarcoma.

Acute Fulminant Cerebral Edema: A Newly Recognized Phenotype in Children With Suspected Encephalitis

Background Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted. Methods All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases. Results Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1–18 years) and 8.0 years (0.5–18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen. Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described. Conclusions AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition.