The document provides information about Hepatitis B virus (HBV). It discusses the history of HBV discovery, morphology and structure of the virus, epidemiology, transmission routes, clinical outcomes, and laboratory diagnosis. Key points include that HBV is a partially double-stranded DNA virus that infects hepatocytes and can lead to both acute and chronic liver disease. It remains a major global health problem with 350 million chronic carriers worldwide.
Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation
In the United States, an estimated 1.2 million Americans are living with chronic Hepatitis B and 3.2 are living with chronic Hepatitis C
Many do not know they are infected
Each year an estimated 21,000 persons become infected with Hepatitis A; 35,000 with Hepatitis B, and 17,000 with Hepatitis C
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual intercourse)
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral
*causes short-term disease and is not a chronic carrier state
Viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation
In the United States, an estimated 1.2 million Americans are living with chronic Hepatitis B and 3.2 are living with chronic Hepatitis C
Many do not know they are infected
Each year an estimated 21,000 persons become infected with Hepatitis A; 35,000 with Hepatitis B, and 17,000 with Hepatitis C
Hepatitis A – fecal/oral, contaminated food, vaccine available
Hepatitis B – blood, semen, vertical (mother-child), vaccine available
Hepatitis C – blood (IV drug use, transfusion, organ donation, unsterile injecting equipment, sexual intercourse)
Hepatitis D – survives only in cells co-infected with hepatitis B
Hepatitis E* – contaminated food or water, fecal/oral
*causes short-term disease and is not a chronic carrier state
Covid-19 Brief Review | A holistic review at pandemic Akhtar Hussain
Presentation holistically and briefly covers the technical aspects of global pandemic. To put things in perspective a comparison woth recent pandemics is also included.
I have tried to make the presentation as rational and unbiased. Though with the ever coming developments daily some things might become redundant even in 10 days only. would love to get suggestions for improvement.
To Assess the Severity and Mortality among Covid 19 Patients after Having Vac...YogeshIJTSRD
The severity and mortality of COVID 19 cases has been associated with the Three category such as vaccination status, severity of disease and outcome. Objective presently study was aimed to assess the severity and mortality among covid 19 patients. Methods Using simple lottery random method 100 samples were selected. From these 100 patients, 50 patients were randomly assigned to case group and 50 patients in control group after informed consents of relative obtained. Patients in the case group who being died after got COVID 19 whereas 50 patients in the control group participated who were survive after got infected from COVID 19 patients. Result It has three categories such as a Vaccination status For the vaccination status we have seen 59 patients were not vaccinated and 41 patients was vaccinated out of 100. b Incidence There were 41 patients were vaccinated whereas 59 patients were not vaccinated. c Severity In the case of mortality we selected 50 patients who were died from the Corona and I got to know that out of 50 patients there were 12 24 patients were vaccinated whereas 38 76 patients were non vaccinated. Although for the 50 control survival group total 29 58 patients were vaccinated and 21 42 patients was not vaccinated all graph start. Conclusion we have find out that those people who got vaccinated were less infected and mortality rate very low. Prof. (Dr) Binod Kumar Singh | Dr. Saroj Kumar | Ms. Anuradha Sharma "To Assess the Severity and Mortality among Covid-19 Patients after Having Vaccinated: A Retrospective Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd45065.pdf Paper URL: https://www.ijtsrd.com/other-scientific-research-area/other/45065/to-assess-the-severity-and-mortality-among-covid19-patients-after-having-vaccinated-a-retrospective-study/prof-dr-binod-kumar-singh
Oral Manifestation of HIV. In detail history of the origin of HIV, the Virus pathology, Classification of HIV.
Systematic manifestation and Oral Manifestation of HIV.
The various tests available for HIV testing and Drug regimens for HIV, Immuno-compromised, pregnant and PCP'S
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Couples presenting to the infertility clinic- Do they really have infertility...
Hepatitis B virus
1. Hepatitis B
By: Sunil Pandey
Nobel College: Medical Microbiology
Email- pandeysunil347@gmail.com
6/29/201
4
Sunil Pandey- Medical Microbiology 1
2. History
Ancient disease- described in 5th century B.C.
Earliest recognized blood-borne outbreak of hepatitis–
Germany in 1883 after receiving smallpox vaccine.
In 1947 MacCallum and Bauer introduce the term Hepatitis
A for infectious and Hepatitis B for serum hepatitis
This terminology was adopted by WHO in 1973
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Sunil Pandey- Medical Microbiology 2
3. Contd…
1965 Baruch Samuel Blumberg
NIH
discovered hepatitis B surface
antigen (HBs Ag) Australia Ag,
nowadays known as hepatitis
surface antigen
1970, Dane Cameron and Briggs
visualized the hepatitis B virus
(HBV) virion-Dane particle.
Maginus & Espmark
HBe Ag
Baruch Samuel Blumberg
Received nobel prize in 1976
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Sunil Pandey- Medical Microbiology 3
5. General introduction of virus
Hepadnavirus, partially double stranded DNA virus.
Composed of a 27nm nucleocapsid core(HBcAg)
Surrounded by an outer lipoprotein coat also called envelop
containing the surface antigen (HBsAg)
Contain DNA –dependent polymerase which can repair the
gap in DNA template and have reverse transcriptase activity.
Infected hepatocyte contain an excess of noninfectious viral
lipoprotein particles composed of envelop protein.
Persistent infections display pronounced hepatotropism.
Fail to propagate in cell culture.
Intracellular HBV is non-cytopathic and causes little or no
damage to the cell. 6/29/201
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Sunil Pandey- Medical Microbiology 5
6. Morphology of virus
Ultra structure shows three distinct morphology
1. Small, spherical, noninfectious particles, containing HBsAg
that measures 17 to 25nm in diameter. Concentrations of 1013
particles per ml.
2. Tubular, filamentous form of various length. They also
contain HBsAg polypeptides.
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Sunil Pandey- Medical Microbiology 6
7. 3. Complex, spherical, double shelled particle of 42nm
which is the Hepatitis B virion.
-consist of an outer envelop containing host- derived lipids
and all S gene polypeptides, the large(L), middle(M) and
small(S) surface proteins also known as preS1, preS2 and
HBsAg.
-Within the sphere nucleocapsid of 27nm which contain core
protein HBcAg, 3.2kb circular partially double stranded
viral DNA genome, an endogenous DNA polymerase
enzyme and protein kinase activity.
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Sunil Pandey- Medical Microbiology 7
10. A
A
A
A
A
A
A
A
A
A
A
A
2.1kb RNA
2.4kb RNA
3.5kb RNA
0.7kb RNA
Pre-S1 Pre-S2
ORF-S
ORF-P
ORF-X
ORF-C DR1
5’
5’
+strand
-strand
Pre-C
DR2
Hepatitis B Virus RNAs
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Sunil Pandey- Medical Microbiology 10
11. S gene/ pre S gene
Large - S domain+ Pre S
domain (pre S1+preS2)
Middle - S domain + pre S2
Small ( major ) –S domain
Pre core/ core gene
HBc Ag
HBe Ag
X gene
HBxAg
P gene
DNA polymerase( DNA
dependent DNA
poymerase/RNA dep RT)
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Sunil Pandey- Medical Microbiology 11
12. Antigen of Hepatitis B
HBs antigen
Longer t1/2 1-3 days
Proportion of HBs protein is different in 3 morphological forms
HBsAg is heterogeneous antigenically, with a common antigen a and two pair of mutally
exclusive antigens d&y and w&r
Therefore, 4 major subtype adw, ayw, adr and ayr.
HBc antigen
Derived from envelop that encloses the viral DNA
Not detectable in the blood stream
Marker of infectious viral material and accurate index of viral replication
HBe antigen
Found in highly productive HBV carriers
Important in survival & spread of infection
HB x antigen
Alters host in a way that it is more permissive for viral
replication
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Sunil Pandey- Medical Microbiology 12
15. Stability of virus
Not destroyed
Ether
Acid (pH 2.4 for at least 6hr)
Heat (98 C for 1min, 60 C for 10hr)
30 C to 32 C for at least 6 months.
Frozen at -15 C for 15 years
HBV present in blood withstand
drying on a surface for at least a
week.
Destroyed
Na hypochlorite for 10min
2% aqueous glutaraldehyde at RT for
5 min.
Heat at 98oC for 2min.
Formaldehyde at 18.5g/l.
70%isopropylalcohol.
80%ethyl alcohol at 11oC for 2min.
Wescodyne (Iodophor disinfectant)
Diluted 1:213or combined β-
propriolactone &UV irradiation.
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Sunil Pandey- Medical Microbiology 15
16. Epidemiology
Incidence
Is a ubiquitous virus with global distribution.
Is most common and serious infectious disease.
More than one third of the world’s population has been
infected.
About 5% of the population are chronic carrier, 350 million
people.
25% percent of chronic carrier develop serious disease
Causes more than 1 million death every year.
HBsAg carrier rate varies from 0.1 to 20%.
In endemic area of Africa and Asia infant and children are
more affected than adult, while in low endemic area it’s
reverse. 6/29/201
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Sunil Pandey- Medical Microbiology 16
18. Prevalence of chronic HBV infection
Early in life Adolescent /young
adult
Adults, welldefined
risk groups
Asia, Middle East,
Pacific islands,
Africa
India, Japan US, Canada
6/29/2014 Sunil Pandey- Medical Microbiology 18
19. Modes of Transmission
Percutaneous
Injecting drug use
Occupational, household (needle stick, non-intact skin)
(Needle stick 33%)
Therapeutic (contaminated equip, unsafe injections)
Transfusions and transplants from infectious donors
Permucosal
Sex with infected partner
Birth to infected mother (perinatal)
Household (exposure to infected contact)
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Sunil Pandey- Medical Microbiology 19
20. Heterosexual*
(41%)
Homosexual Activity (9%)
Household Contact (2%)
Health Care Employment (1%)
Others (1%)
Unknown (31%)
Injecting
Drug Use
(15%)
Modes of Transmission
6/29/2014 Sunil Pandey- Medical Microbiology 20
21. Pathology & Pathogenesis
Sexual Percutaneous Perinatal
? Haematopoetic
cell
Envelope protein Vs.
hepatocyte receptor
Virus specific
Immune complex injury
MGN
Vasculitis
Pancreatitis
neuropathies
Monocyte
Lymphocyte
Fibroblast
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Sunil Pandey- Medical Microbiology 21
22. Four stages in the disease
The first stage is immune tolerance.
The duration of this stage for healthy adults is approximately
2-4 weeks and coincide with the incubation period. For
newborns, the duration of this period often is decades.
Active viral replication is known to continue despite little or
no elevation in the aminotransferase levels and no symptoms
of illness.
In the second stage, an inflammatory reaction with a
cytopathic effect occurs.
HBeAg can be identified in the sera and a decline of the levels
of HBV DNA is seen.
The duration of this stage for patients with acute infection is
approximately 3-4 weeks (symptomatic period).
For patients with chronic infection, 10 years or more may
elapse before cirrhosis develops. 6/29/201
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Sunil Pandey- Medical Microbiology 22
23. In the third stage, the host can target the infected hepatocytes
and the HBV Viral replication no longer occurs.
HBeAb can be detected. The HBV DNA levels are lower or
undetectable, and aminotransferase levels are within the
reference range.
In this stage, an integration of the viral genome into the host's
hepatocyte genome takes place.
HBsAg still is present.
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Sunil Pandey- Medical Microbiology 23
24. In the fourth stage, the virus cannot be detected and
antibodies to various viral antigens have been produced.
Different factors have been postulated to influence the
evolution of these stages, including age, sex,
immunosuppression, and co-infection with other viruses.
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Sunil Pandey- Medical Microbiology 24
25. Carriers
Who don’t progress to stage I and II are the chronic carriers.
It may be of two types
Super carrier-high titer of HBsAg, HBeAg, DNA polymerase
with elevated ALT.
Simple carrier-low titer of HBsAg with negative HBeAg, DNA
polymerase.
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Sunil Pandey- Medical Microbiology 25
26. Acute
Infection
Chronic
Carrier
Resolution
30 ~ 50 years
Chronic
Hepatitis
Stabilization
Progression
Cirrhosis
Compensated
Cirrhosis
Liver
Cancer Death
Feitelson, Lab Invest, 1994
Decompensated
Cirrhosis
(Death)
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Sunil Pandey- Medical Microbiology 26
27. Clinical outcomes of Hepatitis B infections
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Sunil Pandey- Medical Microbiology 27
28. Acute Hepatitis B
Incubation period- 45to 120 days average 60 to 90 days.
Phases of disease
1. Preicteric
2. Icteric
3. Convalescent
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Sunil Pandey- Medical Microbiology 28
29. Clinical features
Preicteric
a. Tiredness
b. Anorexia
c. Vague abdominal discomfort
d. Nausea & Vomiting
e. Sometime arthralgias & rash
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Sunil Pandey- Medical Microbiology 29
30. Icteric
a. Within 10days of initial symptoms
b. Dark urine Pale stool Yellowish discoloration of mucous
membranes.
c. Total bilirubin- exceeds 20 to 40 mg/l
d. Hepatospleenomegaly
e. After disappearance of jundice-Anti HBs.
Convalescent
a. Anti HBc IgM to IgG type
b. Transient presence of HBsAg, HBeAg and viral DNA (<6 months)
c. Seroconversion to anti HBsAg and anti HBeAg
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Sunil Pandey- Medical Microbiology 30
32. Chronic Hepatitis B
After acute infection virus remain in 5 to 10% cases of
adult, even more higher among children upto 70 to 90%.
350 million of person worldwide are chronic carriers.
Among them 100 million in China.
Among the persistent carrier 70% will develop Chronic
persistent hepatitis and remaining 30% will develop
Chronic active hepatitis.
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Sunil Pandey- Medical Microbiology 32
33. Phases of viral replication in
chronic Hepatitis B
High-replicative(super carrier)
HBsAg, HBeAg and HBV DNA present and detectable in
sera.
ALT may increase
Moderate inflammatory activity
Histologically apparent
Risk of developing cirrhosis is high.
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Sunil Pandey- Medical Microbiology 33
34. Low-replicative
Loss of HBeAg
Decreased HBV DNA concentration
Appearance of Anti HBeAg
Decreased inflammatory activity
Non-replicative
Viral markers are absent or below detectable level.
Diminished inflammatory activity
If cirrhrosis already then persist indefinitely.
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Sunil Pandey- Medical Microbiology 34
36. Hepatocellular carcinoma
Only 5% patient with cirrhosis develop HCC.
HCC is responsible for 90% of primary malignant tumor
of liver.
Worldwide 7th most common cancer in male while 9th in
female.
Causes >500000 deaths annually with male & female
ratio 4:1.
Appears after a mean duration of about 35 years of HBV
infection.
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38. Fulminant Hepatitis
Rare condition, develop in about 1% cases.
It is due to massive necrosis of liver substance.
Usually fatal
Survival in adult is uncommon.
Genetic heterogeneity, co-infection, host immunological
factors are responsible.
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39. Extra-hepatic manifestations
Mediated by circulating immune comlpexes
Both acute hepatitis & chronic hepatitis
Acute hepatitis –10-20%
Serum sickness like illness
fever,rash,artralgia,PAN.
Gainotti- Crosti syndrome
papular acrodermatits (children)
Glomerular disease
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40. Laboratory diagnosis
1. SEROLOGICAL METHODS
2. MOLECULAR METHODS
a. Detection in window period
b. Fulminant hepatitis
c. Biochemical/histological suggestive of HBV but HBsAg –ve
d. Pts with chronic HBV to see response
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41. Serological Methods
Three clinically useful antigen-antibody systems have been
identified for Hepatitis B
1. Hepatitis surface antigen(HBsAg) and antibody to it
(anti-HBsAg)
2. Antibody (anti-HBc IgM and anti-HBc IgG)to core
antigen (HBcAg)
3. Hepatitis e antigen (HBeAg) and antibody to it (anti-
HBeAg)
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44. Molecular Methods
PCR
Can detect levels as low as 0.001pg(200to 400 genomic
equivalents)
Dot Blot Hybridization
Can detect 0.1 to 1.0 pg (28,000 to 280000 genomic
equivalents)
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45. Immune prophylaxis
Introduce in 1974 as HBIG, containg high titer of human hepatitis B IG.
It protect as passive immunization, if give soon after or shortly before exposure of
HBV. But it lasts only 3to 6 months.
Maternal-neonatal transmission of HBV and subsequent development of chronic
hepatitis reduced drastically when given in conjugation with HB vaccine. Given
within 24hr after birth, 85 to 95% effective.
In case of adult given within 48 hour of HBV exposure
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47. 1965 Discovery of Australian antigen
1973 Successful HBV infection of chimpanzees
1981 Licensure of plasma-derived vaccine
1986 Licensure of recombinant vaccine
1991 Universal infant vaccination
1996 Universal adolescent vaccination
Hepatitis B Vaccine
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48. Types of Hepatitis B vaccines
Plasma-derived
consists of highly purified, formalin-inactivated, alum-absorbed, hepatitis
B subvirion particles (22nm) of HBsAg free of detectable nucleic acid.
Recombinant
S gene cloned IsolationInserted into an expression plasmid
Introduce to yeast or Chinese hamster ovary Expressed protein into 22nm
antigenic particle.
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49. Immunogenicity of vaccines
3 dose course : protective levels
- >95% in healthy infants and children.
- >90% healthy adults <40 yrs
- <90% healthy adults >40 yrs
- 65-75% by age 60 yrs
Factors for decreased vaccine response:
- Smoking
- Obesity
- HIV infection
- Imunocompromised patients
-Haemodialysis
- Prematurity
- Genetic factors
- Chronic disease.
- Subcutaneous injection
- Freezing of vaccine
- Accelerated schedule
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51. Dose
Primary 1
Primary 2
Primary 3
Minimum
Interval
- - -
4 weeks
8 weeks*
Usual
Interval
---
1 month
5 months
Hepatitis B Vaccine
Adolescent and Adult Schedule
*third dose must be separated from
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53. Recommended Dose of Hepatitis
B Vaccine
Infants and children
<11 years of age
Adolescents 11-19
years
Adults >20 years
Recombivax HB
Dose (mcg)
0.5 mL (5)
0.5 mL (5)
1.0 mL (10)
Engerix-B
Dose (mcg)
0.5 mL (10)
0.5 mL (10)
1.0 mL (20)
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55. Recommendation for pre exposure
immunization with Hepatitis B
1. Infants (Universal immunization)
2. Infants and adolescents not vaccinated previously (catch-up vaccination)
3. Person with occupational risk
4. Haemodialysis patients
5. Recipients of blood and blood products
6. Susceptible drug abusers.
7. Sexually active men or women
8. Susceptible inmates who have a history of high risk behavior
9. Household contacts and sex partners of HBV carriers
10. Population with a high incidence of disease
11. International traveller to area of high HBV endemicity
12. Transplant candidates.
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56. Treatment
Acute hepatitis B
currently, no definitive treatment only symptomatic.
Chronic hepatitis B
Two classes of treatment
a. Antiviral-to destroying HBV
b. Immunemodulators-enhance immune system to mount defense against
the virus
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58. References
1. Manual of Clinical Microbiology, Patrick R Murray 9th edition.
2. Topely and Wilson’s, Virology volume-1 ,9th edition.
3. Mandell’s, Principle and Practice of Infectious Diseases, 5th edition
4. Documents on Hepatitis A-E published by WHO, Department of
Communicable Diseases Surveillance and Response
5. Textbook of Microbiology, Ananthanarayan and Paniker,7th ediition
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