Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia.

Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).

[ZIKA FEVER: CLINICAL, EPIDEMIOLOGICAL, LABORATORY, AND DIAGNOSTIC ASPECTS].

The authors overview data on the prevalence of Zika fever with reference to biological properties of the causative agent, epidemiological process, pathogenesis, and clinical symptoms of the disease. Special attention is given to the identification of the virus in pregnant women, microcephaly in the babies born by Zika-infected women, algorithm of laboratory diagnostics, and measures needed to prevent and control mosquitoes that spread viruses.

[Zika virus infection: clinical and diagnostic aspects and organization of preventive measures].

The article presents modem data about Zika virus outbreak, the biological characteristics of the pathogen, vectors, the nature of the epidemic process, pathogenesis and diagnosis of infection. This infection has a high potential for epidemic spread because vectors are widely represented in the fauna of many climatic and geographic zones. It presents information on the main clinical manifestations of the disease. Particular attention is paid to the problem of congenital maiformations of the nervous system (microcephaly and others) detected in infants born to women infected with Zika virus. The basis of therapy in this disease constitute a pathogenic agent. The'package of, measures for the prevention of disease caused by Zika virus, including early identification and treatment of patients, as well as measures for the destruction of the virus vectors.

[Evacuation of contagious patients in the modern system of medical support].

Evacuation of contagious patients in the modern system. of medical support. The main problematic issues of organizing and conducting the evacuation of contagious patients are defined. A peculiarity of evacuation and healthcare delivery to contagious patients is the need for permanent complex of sanitary and anti-epidemic (preventive) measures aimed at preventing the spread of infectious diseases. Set out fundamental approaches to triage of infectious patients at different stages of medical evacuation, defined sorting group. The attention is focused on the clinical-and-syndrome principle infectious pathology diagnostics. The experience of the medical evacuation of infectious diseases in Afghanistan is analysed. The necessity of protecting the accompanying medical staff is showed. The possibilities, the benefits and how to use for the isolation of infectious patients and the evacuation of mobile autonomous units - the transport of insulating boxes are studied.

[EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

[Meningococcal disease: early clinical diagnosis and emergency care].

Late diagnosis of meningococcal disease leads to high mortality. Early diagnosis of its generalized forms plays a crucial role in the pre-hospital phase and mainly based on the clinical picture of the disease. In most cases, pre-hospital typical mistake is late diagnosis of meningococcal disease: We propose an algorithm of early diagnosis of generalized forms of the disease in order to reduce the number of diagnostic errors. Proper and timely diagnosis will enable the physician pre-hospital fully implement measures to provide emergency and urgent care in generalized meningococcal infection, leading to. a more.favourable course and a significant improvement in the outcomes of the disease in the course of further hospital treatment.

[Treatment of Ebola virus disease].

Treatment of Ebola virus disease. The article presents data on the etiology, pathogenesis, clinical presentation, diagnosis and modern approaches to the treatment of Ebola haemorrhagic fever. This serious infectious disease with a high fatality rate is characterized by intoxication, severe haemorrhages, disseminated intravascular coagulation, and multiple organ failure with the development of severe shock. It is emphasized that the treatment of patients with Ebola should be conducted under strict anti-epidemic regime. Since there is currently no effective drugs against Ebola virus, the basis of modern treatment of this disease are pathogenic and symptomatic treatments. The main activities should be aimed at correcting violations homeostasis, blood volume deficiency, disorders of water and electrolyte balance, acid-base status osmolar and oncotic pressure shortfall of clotting factors and blood components. The treatment program should be drawn up taking into account the stage of the disease, the severity of the course and comorbidity.

[EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.

[Ebola virus disease: clinical and diagnostic aspects and organization of treatment-and-prophylactic measures].

The article presents data about world spread of Ebola virus disease, biological characteristics of the pathogen, the laws of the epidemic process in this disease, its pathogenesis, clinical manifestations and diagnosis. Pointed out that the current anti-viral agents, effective for the Ebola virus, have not been developed. Timely performed pathogenetic therapy improves the prognosis of the disease. The basis of this therapy is infusion-detoxification activities and replenishment of losses, of electrolytes, as well as anti-inflammatory and anti-emetic drugs. The Armed Forces of the Russian Federation received the guidelines for preventive measure that can reduce Ebola virus disease transmission. Recommendations for emergency anti-epidemic commission consisted of representatives of the command, specialists and medical services and logistics, are given. Fundamentally important condition for the effective anti-epidemic measures is not only the constant readiness of medical personnel in the detection of disease EVD, but also the appropriate level of equipment of medical institutions of medical supplies and equipment.

[Perspective applications of multi-species probiotics in the prevention of antibiotic-associated diarrhea].

The problem of antibiotic-associated conditions is one of the most actual problems of clinical practice. The antibiotic-associated diarrhea is a multidisciplinary problem. Investigations of the small intestine microecological status and assessment of microflora at the patients receiving antibiotics testifies to dysbiosis existence. In article results of open-label investigation of a multispecies probiotic RioFlora Balance using for antibiotic-associated diarrhea prophylaxis in patients used antibacterial therapy are presented.

[Delivery of healthcare to patients with infectious diseases during the pre-hospital stage].

In the field infectious military hospital work with double-triple overcharge. It leads to reduction of health care to patients, requires the additional hospital departments or evacuation of contagious patients to other hospitals. That is why the pre-hospital care is of prime importance. According to modem concept the number of interim stages is minimal--1 stage--on site of definition of contagious patients (isolator of medical station of military unit) and 2 stage--infectious military hospital. Main measures of health care to contagious patients during the pre-hospital stage are early active detection of patients or suspected of having infection, early clinical diagnosis, medical sorting, delivery of emergency care, treatment in isolators in case of delay of evacuation and evacuation in infectious military hospital.

[Intestinal dysbiosis in liver cirrhosis].

Intestinal dysbiosis is revealed in 28.5% of patients with liver cirrhosis, mainly in classes B and C by Child-Pugh by the results of hydrogen breath test. It is established that revealed intestinal dysbiosis in patients with liver cirrhosis of viral etiology aggravates the course of the disease.

[Infection agents and irritable bowel syndrome].

The discussion concerns onset and pathogenesis of functional intestinal diseases. Current data are presented on association of functional intestinal diseases with different infectious agents with illustration on the model of postinfectious irritable colon syndrome (ICS). ICS-like conditions in patients who had previously intestinal infections are considered.

[The treatment of acute intestinal diarrheal infections]. / Lechenie ostrykh kishechnykh diareinykh infektsii.

The article presents a short characteristic of the general therapeutic principles in intestinal diarrheal infections, the main of which are the following: early beginning, individual approach and complex therapy. Therapeutic schemes of the most frequent diseases are given. Special attention is paid to the great importance of rational bacterio-therapy in current treatment of acute intestinal diarrheal infections. Individual approach considers determination or supposition of disease etiology and clinical form before treatment, as well as evaluation of state pathogenesis taking into account the body physiologic specificity, severity and period of disease, possible complications and concomitant disease. Complex therapy supposes simultaneous effect on disease agent, several links of its pathogenesis, struggle with intoxication, restoration of the disturbed functions of organs and systems, increase in body defense, treatment of concomitant diseases.