Day 2 :
Keynote Forum
Stef Steinstra
Civil-Military-Interaction-Command Royal Dutch Armed Forces, Netherlands
Keynote: The threat of zoonotic diseases and Ebola Virus Disease specifically
Time : 10:05-10:50
Biography:
Stef Steinstra 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-haematology, 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.
Abstract:
Public health systems are not always prepared for outbreaks of infectious diseases. Although in the past several public health institutes, like the French ‘Institut Pasteur’ and the Dutch ‘Tropeninstituut‘, were prominent surveyors of infectious diseases, the investments in worldwide public health have decreased. Now more attention is given to curative healthcare compared to preventive healthcare. The recent Ebola Virus Disease outbreak in West Africa initiated a new wave of interest to invest in Worldwide Public Health to prevent outbreaks of highly contagious diseases. Zoonotic diseases are threatening as the population does not have natural nor artificial (from vaccination) immune response to new diseases like in the Ebola Virus Disease outbreak in 2014. The new strain of the Ebola Virus in West Africa was slightly less lethal, compared to other Ebola Virus strains, but the threat of spreading was far bigger as it had a longer incubation time. Most public health systems are not trained well enough to mitigate highly infectious and deadly disease outbreaks. NGO’s helping to fight the outbreak are often better trained in curative treatments and have less experience with biological (bioweapon) threats for which the military are trained for. The UNMEER mission was unique in this. It was a setting in which military and civilian actors cooperate in fighting a biological threat. Protection is essential for health workers. Smart systems have to be developed to prevent further spreading of the disease, but 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, smallpox and hemorrhagic fevers are listed as potential bioweapons. Therefore both biosafety and biosecurity have to be implemented in all measures to fight outbreaks of highly infectious diseases
Keynote Forum
Huseyin Kayadibi
Hitit University, Turkey
Keynote: Relation of serum EpCAM levels with intestinal inflammation in children with Celiac Disease
Biography:
Huseyin Kayadibi was born and raised in Istanbul, Turkey. He received a Degree in Medicine from the GATA 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 and 2017 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.
Abstract:
Celiac disease is an autoimmune, chronic, inflammatory and systemic disease that is the result of gluten exposure in the diet. Epithelial cell adhesion molecule (EpCAM) is a non-classical adhesion molecule found in epithelial cells. It is found very much in small intestines and increases in chronic inflammatory events. The aim of the study is to determine the serum EpCAM levels and the effect of gluten-free diet (GFD) compliance on serum EpCAM levels in children with celiac disease. 46 celiac patients and 38 age-sex-matched healthy children were included in the study. Patients were divided into two groups as compliant with GFD or non-compliant with GFD. Serum EpCAM level was measured by ELISA method. Serum EpCAM levels in patients compliant with GFD were 62(34-83) ng/mL, while serum EpCAM levels in healthy children were 34(16-53) ng/ mL (P=0.023). Serum EpCAM levels in patients compliant with GFD weren’t statistically different from serum EpCAM levels in healthy children [30(20-49) ng/mL and 34(16-53) ng/mL, respectively] (P=0.908). The serum EpCAM levels of children compliant with GFD were significantly lower than the serum EpCAM levels of patients non-compliant with GFD (P=0.029). Serum EpCAM level may be a sensitive marker for determining the intestinal inflammation and gluten free diet compliance.
Introduction: Celiac disease is an autoimmune, chronic, inflammatory and systemic disease resulting from the consumption of dietary gluten grains in individuals with genetic predisposition (1). Under normal conditions, harmful food or microorganism antigens entering the gastrointestinal tract are destroyed, while the harmless ones are tolerated. This condition of physiological unresponsiveness is called "oral tolerance". In celiac disease, oral tolerance to gluten is impaired, resulting in increased levels of interleukin-15 and inflammation in the intraepithelial area (2). Under the normal conditions, intestinal epithelium acts as a barrier against the molecules in the passage, and is not permeable to macromolecules such as gluten (3). However, since this permeability is impaired in celiac disease, the gluten may pass through the subepithelial area paracellularly or transcellularly, leading to prolonged intestinal inflammation (4). The epithelial cell adhesion molecule (EpCAM) is found in the intestinal epithelium. It is structurally unlike to classical cell adhesion molecules. Although other cell adhesion molecules are abundantly expressed in normal epithelium, expression of EpCAM is limited. EpCAM is up-regulated and is expressed highly in epithelial cells during and after inflammatory tissue regeneration (5). To assess the intestinal inflammation in children with celiac disease, we aimed to determine serum EpCAM levels, to compare them to healthy children and to determine the effect of gluten-free diet (GFD) on EpCAM levels.
Patients and Methods: The study included 46 celiac patients and 38 age-sex-matched healthy children. Patients were divided into two groups of gluten free diet compatible or not according to the results of anamnesis and celiac antibody. Those with a known chronic condition other than celiac disease were excluded from the study. Serum samples were stored at -80 °C for the measurement of EpCAM by ELISA. Binary groups were compared by student's t-test and Mann-Whitney U test, and more than two groups were compared by one-way ANOVA and Kruskal Wallis Variance analysis, as appropriate. Qualitative
Discussion: Celiac disease is the only autoimmune disease in which the trigger is apparent and which enters in remission when the agent is removed. Immunological response to gluten causes mucosal damage leading to intraepithelial lymphocyte increase in the small intestine, crypt hyperplasia, and finally villous atrophy (1). In chronic inflammation, the activation of leukocytes results in the production of millions of cytokines, increase of the production of adhesion molecules, which provide leukocyte migration to infiltrated tissue. Studies have shown that inflammatory cytokines and cell adhesion molecules increase both at tissue and serum as indicators of inflammation in celiac disease (6,7).
In our study, serum levels of EpCAM, a marker that is highly epithelium-specific in the small intestine, were investigated for the evaluation of intestinal inflammation in celiac disease patients. EpCAM levels were found to be the highest in patients non-compliant with GFD, while patients compliant with GFD were found to be similar results with the healthy children. Therefore, serum EPCAM levels may be a sensitive marker for determining the intestinal inflammation and gluten-free diet compliance.
Keynote Forum
Maria Lourdes Gomez Gozali
Makati Medical Center, Philippines
Keynote: Euphorbia Hirta - A Possible Game Changer In Dengue Management
Time : 11:55-12:40
Biography:
Dr. Maria Lourdes Gozali has completed her Medical degree at the University of Santo Tomas, Philippines. She finished her pediatric residency and fellowship in infectious diseases in Makati Medical Center in the Philippines. She served as a former chairman of the Department of Pediatrics of Asian Hospital and Medical Center and was also chief of the section of the Pediatric Infectious Diseases in Makati Medical Center and Asian Hopsital and Medical Center. She is an active consultant in both hospitals, as well as in St. Luke’s Medical Center Global City.
Abstract:
Dengue continues to be an increasing cause of morbidity and mortality in Asia, Africa, the Caribbean and American regions, and Portugal. About 5% of patients develop severe dengue, which manifests as severe plasma leakage, hemorrhage or organ impairment including hepatitis, myocarditis and encephalitis. The cornerstone of treatment is maintenance of adequate circulatory volume during the stage of increased vascular permeability or hemorrhage by administering fluids, plasma expanders and blood transfusion. Use of folkloric plants such Euphorbia hirta, or in the vernacular “tawa-tawa” or “gatas-gatas” is popularly used against dengue in the Philippines. Journals showing the efficacy of E. hirta against dengue will be reviewed. These include its effects in platelet augmentation, reduction of bleeding time and blooding clotting time in animals with chemically induced thrombocytopenia, platelet increases in dengue patients belonging to the 30-55 age group and marked reduction of flu like symptoms in 70% of patients, which was attributed to its anti-inflammatory properties. Phytochemicals such as phenolic compounds and flavonoids in E. hirta are known to have platelet increasing potential. Also, the ethanol extract of E. hirta under in vitro conditions showed an 85% inhibition of plaque forming capacity of dengue with serotype 1 (DENV-1) and 34.7% inhibition of virus serotype 2. E. hirta has a platelet augmentative effect and antiviral activity, which are vital in the prevention of complications. Despite the existing evidence published, more studies are needed to validate its efficacy, establish the dose needed and toxicity.
- Viral Infectious Diseases | Infection, Immunity and Inflammation | Veterinary Infectious Diseases | Neurological Infectious Diseases | Pediatric Infectious Diseases | Histopathology | Gynecological And Breast Cytopathology | Stem Cell Therapy & Anatomical Pathology | Diagnostic Cytopathology
Location: Holiday Inn Rome Eur Parco dei Medici
Chair
Maria Lourdes Gomez Gozali
Makati Medical Center, Philippines
Session Introduction
Vijaya Satchidanandam
Indian Institue of Science, India
Title: Flavivirus vaccine: Molecular basis for attenuation of Live attenuated Japanese encephalitis virus vaccine SA14-14-2
Biography:
Vijaya Satchidanandam has completed her PhD at Indian Institute of Science and Postdoctoral studies at National Institutes of Health, USA. She is a Professor in India’s leading research institution located in Bangalore. Her laboratory investigates the “Molecular biology and immunology of flaviviral infections and mycobacterium tuberculosis”. She has published 46 papers in reputed journals.
Abstract:
Diseases caused by flaviviruses including Zika, dengue, Japanese encephalitis, West Nile encephalitis and yellow fever have become increasingly frequent over the last couple of decades, aided by global warming and expanding geographies of the mosquito vector. The extremely safe and efficacious WHO-certified live attenuated vaccine for Japanese encephalitis virus (JEV) SA-14-14-2 is used worldwide. We observed impressive enhancement in human CD8+ T cell responses in vaccines relative to volunteers naturally exposed to circulating strains of JEV. Using cell lines that support JEV infection, we queried the molecular basis underlying the generation of enhanced CD8+ T cells by the live vaccine SA-14-14-2. Our studies revealed that the vaccine virus induced severe ER stress, viral protein was rapidly degraded in vaccine virus-infected cells and was differentially recognized by a panel of monoclonal antibodies. Sustained activation of the ER stress sensor PERK in vaccine virus-infected cells led to prolonged phosphorylation of eIF2α, activation of autophagy markers and upregulation of ER chaperones in SA-14-14-2-infected cells. Interestingly, we also observed active dephosphorylation of eIF2α and inhibition of end stage autophagy in WT JEV infected cells. The mutated viral proteins responsible for these effects are being investigated. Our results can guide the rational design of efficacious vaccines against both flaviviruses such as Zika virus, dengue virus and West Nile virus and other pathogenic viruses belonging to other families.
Atif A Ahmed
Children’s Mercy Hospital, USA
Title: Molecular testing in histologically benign spindle cell proliferations
Biography:
Atif A Ahmed is Professor and Director of Anatomic Pathology Division at the Department of Pathology of Children's Mercy Hospitals, Kansas City, USA. He has graduated from University of Khartoum in 1988, completed residency and fellowship training in Pathology and is certified by the American Board of Pathology. He has published more than 50 peer-reviewed articles as well as several book chapters; and is a book editor of "Anatomic and Clinical Pathology Board Review" and "Gastrointestinal Stromal Tumors in Adults and Children". He is on the editorial board of several journals.
Abstract:
Histologically low grade spindle cell tumors in children are mostly benign and easily cured. Infrequency, such tumors can be infiltrative, commonly recur and are difficult to classify and surgically excise. Molecular tests including next generation seuencing have greatly faciltated the diagnosis and the treatment of highly malignant tumors but are rarely ultized in the management of undifferentiated low grade spindle proliferations. In the last three years, we have encountered two unusual cases of histologicaly benign infiltrative spindle cell proliferation in children that were studied by whole exome sequencing. The first case was that of a 20-cm abdominal mass that extended to the pelvis in a young child. The histology revealed bland spindle cell proliferation that infiltrated skeletal muscles and adipose tissue. The CD34-positive cells did not show any immunoreactivity to any other marker. Whole exome sequencing revealed NF1 gene mutation suggesting origin from peripheral nerve sheath. The second case was that of an infant who had right a nasal tumor involving the maxillary sinus and turbinates and extending to the skull base. The recurrent tumor shows focal early osteoid formation and was negative for ALK, CTNNB1 and GNAS mutations. Exome sequencing revealed RET Glu511Lys variant. In both cases, potential benefit by several tyrosine kinase inhibitors was revealed. In conclusion, molecular sequencing for actionable mutations is valuable in the management of low grade infiltrative spindle cell lesions in children.
Taruna Arora
National Institute of Malaria Research, India
Title: Assessing the quality of antimalarial drugs from India using minilab: A field study
Biography:
Taruna Arora has completed PhD at the age of 30 years from Uttrakhand Technical University, Dehradun and Post-doctoral studies from National Institute of Malaria Research, New Delhi, India. I had published more than 14 papers in reputed Journals. She is the member of many societies like Pharmacy Council of India (PCI), Indian Pharmacological Society (IPS), Society of Biomedical Laboratory Scientists, India (SOBLI).
Abstract:
Substandard and counterfeit antimalarial medicines poses a serious threat to public health. These medicines increases the mortality by decreasing efficacy; it also increases the threat of emergence of drug resistance, adverse effect from incorrect excipients/ active ingredients which may be potentially dangerous to the patients. Owing to this, a pilot study was conducted to survey quality of drugs collected from different malaria endemic areas of India. The survey was conducted in different geographical regions on the basis of malaria endemicity i.e. Uttar Pradesh (U.P.), Mizoram, Meghalaya, Gujarat, Madhya Pradesh. A mystery shopper approach was used for collection of samples. The quality of antimalarial drugs from these areas were assessed by using Global Pharma Health Fund Minilab test kit. This includes physical/visual inspection and disintegration test, thin-layer chromatography. High performance liquid chromatography was carried out for quantitative assessment of active pharmaceutical ingredient. A total of 150 antimalarial samples were collected. These samples includes 55 (Chloroqunie), 50 (Artemether Lumefantrine), 14 (Artesunate Sulphadoxine-Pyrimethamine), 31 (Primaquine). These samples were assessed by quality using GPHF minilab lab kit. In this study 98% of the tablets passed minilab disintegration, 2% consisting did not passed disintegration test. 99% of samples passed preliminary Qualitative TLC test when compared with 100% and 80% of the standards. 96% of samples passed quantitative HPLC test, 4% of samples (contained low active pharmaceutical ingredient) did not passed this test. The substandard drugs circulating in the market causes drug resistance, treatment failure and finally leads to death. Additional analysis such as post-marketing surveillance should be done so that good quality antimalarials reached to the population.
Haroon Firozz
Herat University, Afghanistan
Title: Histopathologic evaluation and prevalence of gastric cancer in herat provnice of Afghanistan for the first time
Biography:
Haroon Firooz has completed his speciality program in field of Pathology in Goethe University Frankfurt, Germany. He is the Head of the Pathology Department in Herat Medical Faculty of Afghanistaan. He has published more than eight papers in Herat University Medical Journal.
Abstract:
Gastric cancer is one of the leading causes of cancer related death worldwide.Many patients have inoperable diseases at diagnosis or have recurrent diseases after resection with curative intent. Gastric cancer is seperated anatomically into true gastric adenocarcinoms and gastro-oesophageal junction adenocarcinomas, and histologically into diffuse and intestinal types. Gastric cancer should be treated by teams of experts from different diciplines. Surgery is the only curative treatment for locally advanced diseases. Chemotherapy is usually implemented in combination with surgery. In metastatic diseases, outcomes are poor with median survival being around one year. For the first time in Herat province of Afghanistan author decided to have a researh on gastric cancers. Since there was no pathology laboraroy in the past, no data is avaible about previlance and incidince of this diseases. Author has collected the data and related possible causes of gastric cancer in my cancer diagnostic center, in order to inform the community about this dangerous diseases. Unfortunately in our country most of patients diagnose in late stages of cancer because of lack of facilities and awaraness of diagnostic methods.
Objective: To evaluate the histopathologic types of gastric cancer and related risk factors in Herat city.
Methods: This research is a descriptive study (based on existing data) or cross sectional study. The study population is consist of 152 gastric biopsies from the patients who were suffering form gastric disorders. Endoscopiaclly mucosal resection (biopsy) is taken by endoscopists and referred to Firooz pathology laboratory for diagnosis. The research data is from 01/01/2015 to 01/01/ 2017 .
Materials: All tissues were excised by endoscopy as mucosal resections (biopsies). The diagnosis of the tissue samples were according histologic prepared and staind slides ( H&E) after standerd histotechnology.
Results: In this study, 152 biopsies were assessed. 137 patients diagnosed gastric cancer, among them 95(69.2%) were males and 42(30.7%) females. 45.26% of cancer patients aged over 60 years old. In 71.05% of biopsies revealed intestinal type adenocarcinoma, 11.8% of patients the biopsies showed diffuse type carcinoma. Dysplasia were noted in 6.57% of biopsies. Finally 2.70% of biopsies revealed atrophic gastritis and 0.65% of cases revealed lymphoma NHL. In 49.6 % of cases the tumors had proximal location and in 50.44% of cases the tumor had distal location. Low grade adenocarcinoma were seen in 22.6% of cases, moderately differentiated were seen in 19.7% of cases and poorly differentiated were seen in 57.7% of cases. In this study 41.6% of cases revealed Helicobacter pylori in gastric mucosa. Patients who diagnosed gastric cancer did not use alcohol and tabacco, most used meat in their daily diet.
Conclusion: By considering this fact that gastric cancer is a dangesrous diseases specially in undeveloped countries like Afghanistan and kills many people, it is mandatory for physician to diagnose gastric cancer in onset and early stages, in order to survive patients. Acording to our study most of referring patients (57.7%) suffered from Grade III adenocarcinoma and diagnosed poorly differentiated adenocarcinoma during there first endoscopy and histopathologic examination and the mean age for gastric cancer was 57.8, therfore it is recommended for doctors to consider abdominal discomfort and gastric disorders as a serious problem and do necessary investigative methods especially in ages above 45 years with special emphasis on early diagnosis of disease inorder to redue and decrease death rates.
Haroon Firozz
Herat University, Afghanistan
Title: Histopathologic evaluation and prevalence of gastric cancer in herat provnice of Afghanistan for the first time
Biography:
Haroon Firooz has completed his speciality program in field of Pathology in Goethe University Frankfurt, Germany. He is the Head of the Pathology Department in Herat Medical Faculty of Afghanistaan. He has published more than eight papers in Herat University Medical Journal.
Abstract:
Gastric cancer is one of the leading causes of cancer related death worldwide.Many patients have inoperable diseases at diagnosis or have recurrent diseases after resection with curative intent. Gastric cancer is seperated anatomically into true gastric adenocarcinoms and gastro-oesophageal junction adenocarcinomas, and histologically into diffuse and intestinal types. Gastric cancer should be treated by teams of experts from different diciplines. Surgery is the only curative treatment for locally advanced diseases. Chemotherapy is usually implemented in combination with surgery. In metastatic diseases, outcomes are poor with median survival being around one year. For the first time in Herat province of Afghanistan author decided to have a researh on gastric cancers. Since there was no pathology laboraroy in the past, no data is avaible about previlance and incidince of this diseases. Author has collected the data and related possible causes of gastric cancer in my cancer diagnostic center, in order to inform the community about this dangerous diseases. Unfortunately in our country most of patients diagnose in late stages of cancer because of lack of facilities and awaraness of diagnostic methods.
Objective: To evaluate the histopathologic types of gastric cancer and related risk factors in Herat city.
Methods: This research is a descriptive study (based on existing data) or cross sectional study. The study population is consist of 152 gastric biopsies from the patients who were suffering form gastric disorders. Endoscopiaclly mucosal resection (biopsy) is taken by endoscopists and referred to Firooz pathology laboratory for diagnosis. The research data is from 01/01/2015 to 01/01/ 2017 .
Materials: All tissues were excised by endoscopy as mucosal resections (biopsies). The diagnosis of the tissue samples were according histologic prepared and staind slides ( H&E) after standerd histotechnology.
Results: In this study, 152 biopsies were assessed. 137 patients diagnosed gastric cancer, among them 95(69.2%) were males and 42(30.7%) females. 45.26% of cancer patients aged over 60 years old. In 71.05% of biopsies revealed intestinal type adenocarcinoma, 11.8% of patients the biopsies showed diffuse type carcinoma. Dysplasia were noted in 6.57% of biopsies. Finally 2.70% of biopsies revealed atrophic gastritis and 0.65% of cases revealed lymphoma NHL. In 49.6 % of cases the tumors had proximal location and in 50.44% of cases the tumor had distal location. Low grade adenocarcinoma were seen in 22.6% of cases, moderately differentiated were seen in 19.7% of cases and poorly differentiated were seen in 57.7% of cases. In this study 41.6% of cases revealed Helicobacter pylori in gastric mucosa. Patients who diagnosed gastric cancer did not use alcohol and tabacco, most used meat in their daily diet.
Conclusion: By considering this fact that gastric cancer is a dangesrous diseases specially in undeveloped countries like Afghanistan and kills many people, it is mandatory for physician to diagnose gastric cancer in onset and early stages, in order to survive patients. Acording to our study most of referring patients (57.7%) suffered from Grade III adenocarcinoma and diagnosed poorly differentiated adenocarcinoma during there first endoscopy and histopathologic examination and the mean age for gastric cancer was 57.8, therfore it is recommended for doctors to consider abdominal discomfort and gastric disorders as a serious problem and do necessary investigative methods especially in ages above 45 years with special emphasis on early diagnosis of disease inorder to redue and decrease death rates.
Tayo Alex Adekiya
University of Zululand, South Africa
Title: Exploration of the impact of climate change on schistosomiasis transmission dynamics
Biography:
Tayo Alex Adekiya is currently pursuing his Postgraduate studies in the Department of Biochemistry at the University of Zululand. Presently, he is the Secretary General of postgraduate student’s association at the university. He has recently published three papers in reputed journal.
Abstract:
Climate change has been suggested to elicit significant impact on the interactions between pathogens and their hosts. Vector-borne diseases are predominantly sensitive to climatic factors because temperature variability can alter vector development rates, transmission dynamics, as well as cause alteration in their geographical distribution. Schistosomiasis, ranked the second most widespread among neglected tropical diseases is caused by flatworms belonging to the genus Schistosoma. Symptoms of the parasitic infections include acute and chronic diseases, predisposition to cancer of the bladder, as well as pulmonary and portal hypertension and in extreme cases, death. This study employs a deterministic climate-based model using differential equations to investigate the impact of rainfall and temperature on the population dynamics of schistosomes in South Africa. Numerical simulations of the system were done using mathematical models to examine the effect of climate variability on the transmission dynamics of schistosomiasis. Results showed climate variability increases reproduction number of schistosomes and snails. Hence, schistosomiasis transmission was suggested to be seasonal. Snails’ reproduction was found to peak during summer and at the minimum during spring and autumn. So, sensitivity analysis showed reproductive number of schistosomes is more sensitive to the reproduction rate of snails and the probability of infections. Finally, the model used suggested future opportunity for modification and refinement for effective prediction of climate variability on the transmission dynamics of schistosomiasis.