Day 1 :
University of Oslo, Norway
Keynote: Synergy (not polarization) between Th1 and Th2 responses against Mycobacterium tuberculosis infection: Evidence from an endemic setting
Time : 10:05-10:50
Fekadu Abebe (PhD) is a senior scientist at the University of Oslo, Norway. He is an expert in infection immunity at the University of Oslo, where he is involved in teaching and supervision of PhD and MPH students. He has led several projects related to tuberculosis including studies of biomarkers of protective immunity against tuberculosis in human population in endemic setting. He has published over 50 articles in peer reviewed scientific journals (mostly as first or senior author).
At present, tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills an estimated 2 million people globally, more people than HIV/AIDS and malaria combined. The only licensed vaccine currently in use, BCG does not control Mtb transmission. Efforts to develop an efficacious vaccine against Mtb infection during the last three decades have achieved moderate success because of lack of knowledge about correlates of protective immunity and the Th1/Th2 paradigm. According to the Th1/Th2 paradigmTh1 cells protect against intracellular pathogens, whereas Th2 cells protect against extracellular pathogen. In the past, it was generally accepted that interferon-gamma (IFN-γ)-producing Th1 cells are protective against Mtb infection, whereas the role antibodies was ignored. Earlier, we have argued that antibodies may play a crucial role against TB (Abebe & Bjune, 2007) and that IFN-γ may not be the right marker for protective immunity against TB (Abebe, 2012). As a part of a major project to identify protective immune markers in Mtb endemic population, we assessed specific antibody and cytokine responses against selected Mtb antigens (LAM, Rv2031, HBHA, the 38-kDa antigen, and ESAT-6/CFP-10) in pulmonary TB patients (PTBP), their household contacts (HHCs) and community controls (CCs) longitudinally.
Our results show that the levels of IFN-γ (Th1) and IgA (Th2) against HBHA (a promising candidate vaccine) were elevated concurrently in CCs (with no history of clinical TB) compared to PTBP and HHCs (Mtb infected). On the other hand, the level of IFN-γ against ESAT-6/CFP-10 (another candidate vaccine) was elevated in PTBP but was depressed in HHCs and CCs (with no clinical TB). Results of the present study may suggest that there is a synergy between Th1 (IFN-γ) and Th2 (IgA) responses against HBHA of Mtb. These results will be discussed in line with emerging evidence for the protective role of antibodies agains Myb infection and the Th1/Th2 paradigm.
Civil-Military-Interaction-Command Royal Dutch Armed Forces, Netherlands
Keynote: Zoonotic diseases threat needs sharing of information and new diagnostic systems in less developed countries
Time : 11:10-11:55
Stef Stienstra works internationally for several medical and biotech companies as scientific advisory board member and is also an active reserve-officer of the Royal Dutch Navy in his rank as Commander (OF4). For the Dutch Armed Forces he is CBRNe specialist with focus on (micro)biological and chemical threats and medical- and environmental functional specialist within the 1st CMI (Civil Military Interaction) Battalion of the Dutch Armed Forces. For Expertise France he is now managing an EU CBRN CoE public health project in West Africa. He is visiting professor at the University of Rome Tor Vergata giving lectures for the CBRN Master study. In his civilian position he is at this moment developing with MT-Derm in Berlin (Germany) a novel interdermal vaccination technology as well as a new therapy for cutaneous leishmaniasis for which he has won a Canadian ‘Grand Challenge’ grant. With Hemanua in Dublin (Ireland) he has developed an innovative blood separation unit, which is also suitable to produce convalescent plasma for Ebola Virus Disease therapy. He has finished both his studies in Medicine and in Biochemistry in The Netherlands with a doctorate and has extensive practical experience in cell biology, immuno-hematology, infectious diseases, biodefense and transfusion medicine. His natural business acumen and negotiation competence helps to initiate new successful businesses, often generated from unexpected combinations of technologies.
Sharing public health threat information is a necessity for governments to prevent outbreaks of infectious diseases. Zoonotic diseases are the most dangerous for outbreaks running out of control, as the population does not have natural nor artificial (from vaccination) immune response to new emerging diseases. The recent Ebola Virus Disease outbreak in West Africa was such an example. New diagnostic methods, which can be performed in developing countries lacking critical infrastructure have to be developed to have an early response on (potential) outbreaks. It must be high tech with high reliability, which can be used in rural areas without proper infrastructure. The mitigation of highly infectious and deadly disease pandemics have to be recognized at the source. Sophisticated diagnostic equipment and good calibration, maintenance and interpretation of the results is essential. To identify pathogens at molecular level new technologies are under development. In developing countries military and civilian actors cooperate fruitfully in fighting potential biological threats. In this civil-military cooperation it is not only the biosafety, which has to be considered, but also the biosecurity, as misuse of extremely dangerous strains of microorganisms cannot be excluded.
Several zoonotic infectious diseases, like anthrax, small pox and also the hemorrhagic fevers like Ebola Virus Disease are listed as potential bioweapons. With this extra threat in mind, both biosafety and biosecurity have to be implemented in all mobile or fixed clinical laboratories. An information/computer network with a cloud in which essential information can be traced, helps in early detection of outbreaks of ‘new’, mostly zoonotic, infectious diseases. The same technology helps in the forensic aspects in case of a bioterror attack
Hitit University, Turkey
Keynote: The role of intestinal microbiota in the pathogenesis of non-alcoholic Steatohepatitis
Huseyin Kayadibi has completed his Degree in Medicine at the Gülhane Military Medical Academy-School of Medicine, Turkey in 2000. He is an Associate Professor in Medical Biochemistry at Hitit University School of Medicine, where he is the Head of Medical Biochemistry. He worked at Pasarow Mass Spectrometry Laboratory, University of California Los Angeles in 2012 as a Visiting Scholar. He has been a Co-Investigator on NIH and other international projects about metabolomic, proteomic and lipidomic analysis. He is the Member of EFLM Working Group test evaluation and IFCC Working Group cerebrospinal fluid proteins. He has published more than 70 papers in peer reviewed journals. His research interests are Non-Invasive Assessment of Steatohepatitis, Liver Fibrosis, Separation Techniques and Mass Spectrometry.
Non-alcoholic steatohepatitis (NASH) is determined as the fatty liver with inflammation and fibrosis that resembles the alcoholic liver disease without the history of alcohol ingestion. Genetic and environmental factors are important in the pathogenesis of NASH. However, it is still unclear why some thin individuals develop NASH, while some obese individuals do not. Intestinal microbiota may be important in these situations. Because, microorganisms have some effects on energy homeostasis, activation of pro-inflammatory mediators and metabolism of bile acids, short chain fatty acids, choline and alcohol. Intestinal barrier components, tight junction, zonula adherence, desmosome, gap junction, integrin, selectin and cell adhesion molecule have very important roles in the gut liver axis for healthy liver. Because of intestinal barrier dysfunction causes the increased transfer of toxic metabolites to the liver from gut by the gut-liver axis. Increased levels of these substances in liver induce the multiple inflammatory processes by the activation of toll like receptors and nod like receptors that may result with the hepatitis and fibrosis. Microbial imbalance called dysbiosis may cause to the development of leaky gut and then NASH. In previously published articles, it was shown that intestinal dysbiosis and NASH are related with the lower prevalence of Bacteroidetes and higher prevalence of Firmicutes. Therefore, the species of microbiota may be important for elucidation of the pathogenesis of NASH. It was also shown that diversity of the intestinal microbiota has a key role for the pathogenesis of liver diseases. In future, studies with liver biopsy proven NASH patients will elucidate the role of intestinal microbiota and related metabolic components in the pathogenesis of NASH.
- Viral Infectious Diseases | Bacterial Infectious Diseases | Infection, Immunity and Inflammation | Tropical Infectious Diseases | Histopathology | General Cytopathology & Immunocyto Chemistry | Clinical & Molecular Cytopathology
Location: Holiday Inn Rome Eur Parco dei Medici
Hitit University, Turkey
Anthony A Azenabor
University of Wisconsin, USA
Title: Plasmodium falciparum treated with artemisinin-based combined therapy exhibits enhanced mutation, heightened cortisol and TNF-α induction
Dr. Anthony Azenabor is full professor at the University of Wisconsin-Milwaukee and an expert in Infection and Immunity, he has approached his research by explaining the impact of infection on host immune system, relying on my knowledge of Molecular Biochemistry as a major tool. His current research is aimed at providing greater insights into mechanisms involved in innate immune function during stimulation by both physiologic and infectious agents. His finding have contributed to the concept that products of activation by therapeutic interventions and the infectious agents play combined roles in the activation, wholly or in part, of host defence against pathogens and other challenges.
The artemisinin-based combined therapy (ACT) post-treatment illness in Plasmodium falciparum-endemic areas is characterized by vague malaria-like symptoms. The roles of treatment modality, persistence of parasites and host proinflammatory response in disease course are unknown. We investigated the hypothesis that ACT post-treatment syndrome is driven by parasite genetic polymorphisms and proinflammatory response to persisting mutant parasites. Patients were categorized as treated, untreated and malaria-negative. Malaria positive samples were analyzed for Pfcrt, Pfmdr1, K13 kelch gene polymorphisms, while all samples were evaluated for cytokines (TNF-α, IL-12p70, IL-10, TGF-β, IFN-γ) and corticosteroids (cortisol and dexamethasone) levels. The treated patients exhibited higher levels of parasitemia, TNF-α, and cortisol, increased incidence of parasite genetic mutations, and greater number of mutant alleles per patient. In addition, corticosteroid levels declined with increasing number of mutant alleles. TGF-β levels were negatively correlated with parasitemia, while IL-10 and TGF-β were negatively correlated with increasing number of mutant alleles. However, IL-12 displayed slight positive correlation and TNF-α exhibited moderate positive correlation with increasing number of mutant alleles. Since post-treatment management ultimately results in patient recovery, the high parasite gene polymorphism may act in concert with induced cortisol and TNF-α to account for ACT post-treatment syndrome. In conclusion, the ACT-meted-syndrome consists of post-treatment malaria-like-illness, enhanced genetic polymorphism in parasite that may not be effective phenotypes, and proinflammatory conditions accompanied by regulatory cytokine impairment.
Fernanda de Freitas Anibal
Federal University of São Carlos, Brazil
Title: Hepatic fibrosis in schistosomiasis, a new treatment
Fernanda de Freitas Anibal is a Associate Professor I in Federal University of São Carlos, and Principal Investigator at Laboratory of Inflammation and Infectious Diseases, Brazil. Currently,they are working with plants and enzymes and their effects againts schistosomiasis and leishmaniasis, about the treatment of infectious diseases. Their group studies effects of plants and their isolated fractions in order to evaluate the anti-parasitic and anti-inflammatory effects for infectious disease control. She has published more than 46 papers in scientific journals.
Schistosomiasis is an important parasitic disease caused by Schistosoma mansoni, an intravascular trematode. Praziquantel (PZQ) is the only treatment for this. Thus, studies on new antischistosomal compounds are fundamental for disease control. In our model, Mentha piperita L. compounds – menthol and menthone (MM) – in association with acetylsalicylic acid (ASA) is demonstrated in the regulation of hepatic fibrosis caused by schistosomiasis granulomas. Six different groups of ice were infected with 80 cercariae (groups: infected and untreated, infected and MM treatment; infected and treatment MM with ASA, all treated during 14 daily after 35 day pos infection; and infected treated with Praziquantel (single dose). Parasitological, cytological and histological analyses were performed. The number of eosinophils in the peritoneal cavity lavage (LPC) significantly reduced in all treated groups. Groups treated with 30 mg/kg of MM presented a 62.80% reduction and groups treated with 50 mg/kg of MM + ASA presented a 64.21% in the number of eggs. In the liver´s histological analysis we observed that all MM treated groups expressed a unique cytological profile, with diffused cells around the granuloma. In the experimental group treated with 50 mg/kg of MM + ASA, it was possible to observe the formation of type III collagen fibers, a typical wound healing characteristic. Our data strongly suggests that both the hepatic fibrosis and the inflammatory process were regulated through the schistosomiasis granulomatous process after treatment with MM with ASA.
V I Petukhov
Vladimir State University, Russia
Title: Metal-ligand homeostasis of essential metals (Zn, Cu, Fe) in epidermis: Probable norm criteria
V I Petukhov was graduated from the Faculty of Therapy, 1st Leningrad Medical Institute and Post-graduation from Central Institute of Post-Diploma Education of Physicians, Moscow. His Doctor’s field of specialization: Therapeutist – Hematologist. He has published more than 180 scientific works, including four monographs. Presently, he is a Professor of the Vladimir State University, Vladimir, Russia, and Emeritus Professor of the Baltic International Academy, Riga, Latvia.
The work is dedicated to the problem of the norm in the quantitative evaluation of metal content in the epidermal cells (hair) obtained by the method of spectrometry. Authors have analyzed the hair samples for Zn, Cu, and Fe content, which were obtained from 10000 healthy subjects (5000 males and 5000 females aged 20 to 45). The definition of the norm, in the authors’ opinion, is closely related to the basic positions of the theory of self-organized criticality (SC). The observed shifts in the homeostasis of essential metals are local and therefore cannot serve as a criterion of sufficient (or insufficient) metal content throughout the body. The use of hair spectrometry for determination of metal content in epidermal cells has proven to be ineffective in diagnostics of latent ID forms. However, the spectrometric analysis may be suitable for detecting criticality (synchronization) as a normative (regulatory) criterion in the operation of membrane ATPases.
Asian Hospital and Medical Center, Philippines
Title: A case report on Listeria monocytogenes Meningoencephalitis/Cerebritis, acute disseminated encephalomyelitis, and cytomegalovirus bacteremia in an immunocompromised patient on steroid therapy
Roberto Salvino is a Physician at the Asian Hospital and Medical Center and is actively involved in the training of Internal Medicine Residents. He was a Former Member of The Board of Council of the International Society for Infectious Diseases during 2008-2014. He is a Diplomat of the American Board of Internal Medicine. He is a member of various medical societies such as the American College of Physicians, European AIDS Clinical Society, and American Society for Microbiology, Philippine Society for Microbiology and Philippine Society for Microbiology and Infectious Diseases. He is an executive with a diverse experience in the fields of academic, clinical medicine, pharmaceutical medicine and corporate governance.
Listeria monocytogenes is an opportunistic pathogen that affects immunocompromised patients and has a very high mortality rate. Central nervous system (CNS) infection and bacteremia are the foremost clinical manifestations in susceptible hosts. Infection with multiple pathogens is not common but still possible especially in the immunocompromised. Presenting a case of a 57 year old woman admitted for sepsis from meningoencephalitis: bacterial vs. fungal vs. viral etiology and pneumonia in an immunocompromised; R/O stroke; probable glomerulonephritis; pancytopenia from sepsis and blood loss; and lower gastrointestinal bleeding. She presented three months ago with persistently elevated blood creatinine and proteinuria and was diagnosed with non-biopsy proven glomerulonephritis. Treatment with oral prednisone 60 mg total per day was given for seven weeks up to day admitted. She had hematochezia days prior, and then had high grade fever and inability to speak. Physical examination was notable for pallor, negative signs of Cytomegalovirus (CMV) retinitis on funduscopy, Broca’s aphasia, nuchal rigidity and very minimal right-sided decrease in muscle tone. Blood analyses showed low hemoglobin and platelet with normal white blood cell (WBC) count, creatinine was elevated. Electroencephalogram findings show diffuse, mild encephalopathy of non-specific etiology and plain brain CT findings of small rounded density in the left frontal lobe. Non-contrast Brain MRI revealed multiple hyper intense lesions in T2/FLAIR over the deep and sub-cortical white matter of the bilateral frontal lobes, left temporal lobe and right occipital lobe and left capsule-ganglionic region, largest measuring 2.4x2.5x3 cm seen in the periventricular left frontal lobe with minimal mass effect. Cerebrospinal fluid (CSF) analysis: colorless clear fluid with red blood cells (RBC) 990 cells/ul; WBC 650 cells/ul (62% lymphocytes, 38% neutrophils); protein 3,296 mg/L; glucose 2.4 mmol/L; cryptococcal antigen latex agglutination system, TB-PCR, acid fast stain, India ink tests were all negative; viral tests for CMV, herpes simplex, varicella zoster, Dengue and Japanese encephalitis were all negative. Empiric anti-infection treatment was started with intravenous ceftriaxone, vancomycin, metronidazole and acyclovir. Prednisone oral was continued to prevent adrenal insufficiency. CSF and blood cultures were positive for Listeria monocytogenes on the third hospital day. The antimicrobial regimen was shifted to ampicillin and meropenem. Marked clinical improvement was evident for 1-2 days after anti-infectives were shifted. Blood CMV PCR was positive thus ganciclovir was started. On the 12th hospital day, there was worsening of pneumonia, meropenem was shifted to cefepime and metronidazole. On the 16th hospital day, she had recurrence of Broca’s aphasia. Non-contrast brain MRI showed decrease in size of previous multiple lesions but new tiny sub cortical white matter FLAIR hyper intense foci were seen in the right frontal area. Repeat CSF analyses were normal except for low IgG 4.91 g/L. Acute disseminated encephalomyelitis (ADEM) treatment with dexamethasone was effective and improved speech production after three days. Gastrointestinal bleeding from a jejunal angioectasia seen in enteroscopy was controlled with cauterization. On follow-up after a month, she is coherent and conversant, able to ambulate with support. The authors conclude that early detection and treatment of Listeria infection is essential for a good prognosis. Infection with multiple pathogens should be watched out for in susceptible hosts. ADEM may develop post CNS infection and should be watched for.
Sridevi Institute of Medical Sciences & Research Hospital, India
Title: A rare case report – Adenoid cystic carcinoma presenting as a vulval nodule
Nalini A R is currently the Laboratory Director of CG Laboratory and Head of Central Lab in Shridevi Medical College, Tumkur and Associate Professor of Pathology in Department of Pathology. She has completed her Anatomical and Clinical Pathology Residency from the Prestigious Madras University in year 2010 and trained in premiere institutions like JIPMER, Pondicherry and CMC, Vellore. Her primary interest is General Surgical Pathology, Cytology with special interest in Renal Pathology. She has completed the ISN certified course in Clinical Nephropathology. She is member of State Association of Pathologists and active member of Government Pilot Project which involves Cancer Screening Surveillance Program. She also is an Honorary Consultant Pathologist in various rural health centres where they are unable to access quality diagnostic care.
Adenoid cystic carcinoma of the Bartholin’s gland is a rare malignant tumor of Female genital tract. Here is a report of a case of a 33-year-old woman, who presented with a swelling on the right side of vulvar region for a month. It was diagnosed as Bartholin cyst and treated with antibiotics, with not much improvement in her clinical condition. Based on examination, a solid fixed painful nodule with intact mucosa was palpated on the right side of the vulva. Histological features were compatible with adenoid cystic carcinoma. Often, such lesions are clinically misdiagnosed as cysts or inflammation. The present case was treated as Bartholins cyst initially, the possibility of malignancy should always be considered in any female with any painful nodular lesions near the Bartholin’s glands in vulvar region.