1. Presented By Humaira Hussain PhD Scholar-BCH 10-Arid-1763
Recent Advances In Micro/Nanotechnologies For Global Control Of Hepatitis B Infection
Presented By Humaira Hussain PhD Scholar-BCH Arid-1763

2. Contents General Concepts Signs and symptoms Types Hepatitis B Virus
HBV : Structure
Properties of HBV
Replication of HBV
Global Patterns of Chronic HBV Infection
Concentration of Hepatitis B Virus in Various Body Fluids
Pathogenesis & Immunity
Possible Outcomes of HBV Infection
Epidemiology
Conventional methods for the treatment of Hepatitis B

3. Nanotechnology
Introduction to nanotechnology
Recent advances in nanotechnology for
i. Diagnosis of Hepatitis B
ii.Treatment of Hepatitis B
Biosensors
Electrochemical biosensing strategies
Methodolgy
Electrochemical DNA biosensor
Conclusion
Future perspectives

4. General Concepts Hepatitis = 'inflammation of the liver'.
six medically important viruses are commonly described as “hepatitis viruses”:
HAV,HBV,HCV,HDV,HEV,HGV.

5. Signs and symptoms
Many people with hepatitis go undiagnosed, because the disease is mistaken for the flu or because there are no symptoms at all.
The most common symptoms of hepatitis are:
Loss of appetite
Fatigue
Mild fever
Muscle or joint aches
Nausea and vomiting
Abdominal pain

7. Conti….. Less common symptoms include: Dark urine Light-colored stools
Jaundice (yellowing of the skin and whites of the eyes)
Generalized itching
Altered mental state, stupor, or coma
Internal bleeding

8. Types
Hepatitis can be
Acute (inflammation of the liver that lasts less than six months)
Chronic (inflammation of the liver that lasts more than six months)

9. Hepatitis B Virus

10. HBV : Structure

11. Properties of HBV A member of the hepadnavirus group
Circular partially double-stranded DNA viruses
Replication involves a reverse transcriptase.
Endemic in the human population and Hyperendemic in many parts of the world.
A number of variants
It has not yet been possible to propogate the virus in cell culture

12. Replication of HBV

13. Concentration of Hepatitis B Virus
in Various Body Fluids
Low/Not
High
Moderate
Detectable
blood
semen
urine
serum
vaginal fluid
feces
wound exudates
saliva
sweat
tears
breastmilk 1 1 1

14. High-risk groups for HBV infection
People from endemic regions
Babies of mothers with chronic HBV
Intravenous drug abusers
People with multiple sex partners
Hemophiliacs and other patients requiting blood and blood product treatments
Health care personnel who have contact with blood
Residents and staff members of institutions for the mentally retarded

15. Pathogenesis & Immunity
Virus enters hepatocytes via blood
Immune response (cytotoxic T cell) to viral antigens expressed on hepatocyte cell surface responsible for clinical syndrome
5 % become chronic carriers (HBsAg> 6 months)
Higher rate of hepatocellular ca in chronic carriers, especially those who are “e” antigen positive
Hepatitis B surface antibody likely confers lifelong immunity (IgG anti-HBs)
Hepatitis B e Ab indicates low transmissibility

16. Epidemiology
Human body is a sole reservoir for HBV. However, the high replication activity of HBV leads to production of high concentration of viral particles circulating in blood and body fluids of infected person, and therefore makes hepatitis B extremely transmissible.
Most people become chronically infected at childbirth when the mother is a hepatitis B carrier (vertical transmission), while others become infected by close personal contact or by injections (medical and dental instruments or intravenous drug use) (horizontal transmission).
The horizontal transmission risk of chronic of HBV infection incidence is 30% to 50% for the age group between birth and 5 years of age, decreases dramatically to 7–10% by aging

17. Possible Outcomes of HBV Infection
Acute hepatitis B infection
3-5% of adult-acquired infections
95% of infant-acquired infections
Chronic HBV infection
Chronic hepatitis
12-25% in 5 years
Cirrhosis
6-15% in 5 years
20-23% in 5 years
Hepatocellular carcinoma
Liver failure
Death
Liver transplant
Death

18. Global Patterns of Chronic HBV Infection
High (>8%): 45% of global population
lifetime risk of infection >60%
Early childhood infections common
Intermediate (2%-7%): 43% of global population
lifetime risk of infection 20%-60%
Infections occur in all age groups
Low (<2%): 12% of global population
lifetime risk of infection <20%
Most infections occur in adult risk groups 35

20. Current Treatment Options
Interferon alfa (Intron A)
Response rate is 30 to 40%.
Lamivudine (Epivir HBV)
(relapse ,drug resistance)
Adefovir dipivoxil (Hepsera)

21. Other Methods Vaccination Highly effective recombinant vaccines
Hepatitis B Immunoglobulin (HBIG)
Exposed within 48 hours of the incident/ neonates whose mothers are HBsAg and HBeAg positive.
Other measures
Screening of blood donors, blood and body fluid precautions.

22. The control of hepatitis B virus (HBV) infection is a challenging task, specifically in developing countries where there is limited access to diagnostics and antiviral treatment mainly due to high costs and insufficient healthcare infrastructure.
Advances in micro/nanotechnology are pioneering the development of new generation methodologies in diagnosis and screening of HBV.
Owing to combination of nanomaterials (metal/inorganic nanoparticles, carbon nanotubes, etc.) with microfabrication technologies, utilization of miniaturized sensors detecting HBV and other viruses from ultra-low volume of blood, serum and plasma is realized.

24. What is Nanotechnology?
The science of manipulating materials on an atomic or molecular scale especially to build microscopic devices.

25. Recent advances in nanotechnological tools for diagnosis of HBV and HBV co-infections
Advances in nanotechnology and microfluidic platforms rapidly enable significant developments of biosensing technologies and medical diagnostics.
Advances in micro-nanofabrication technologies allow for developing rapid, user-friendly, accurate and specific diagnostic methods, which achieve low detection limits of the target analytes/cells.

26. Biosensors:
A biosensor is an analytical device used for the detection of an analyte that combines a biological component with a physicochemical detector
It consists of three parts:
i. The sensitive biological element
ii.The transducer or the detector element
iii. Biosensor reader device

28. Electrochemical biosensing strategies
Electrochemical-based sensing technologies have been one of the most studied platforms in the detection of HBV biomarkers such as nucleic acids, capsid proteins or other components.
In this detection platform, specific recognition elements are immobilized on a sensor surface or freely present in the sensing solution, conductivity/resistivity are monitored upon the recognition and capture of target molecules.
A recent study demonstrated that simultaneous detection of 5-type HBV antigens (i.e., hepatitis A, B, C, D, E) is facilitated by an electrochemical immunosensor array.

29. Methodolgy
The described assay is based on following simple methodology; 5-type HBV antibodies were immobilized onto a self-made electrochemical sensor array using gold nanoparticles and protein A as matrices, and the immunosensor array is then used to capture their corresponding antigens from sample solution . It is shown that described electrochemical assay has produced similar results with respect to ELISA method.

30. Electrochemical DNA biosensors
Electrochemical DNA biosensors hold a great promise to develop biosensors for HBV diagnosis. These biosensors have demonstrated a broad range of application by utilizing DNA hybridization,
Mismatch analysis,
Direct DNA analysis-based on guanine signal, and
PCR-based approaches
In the perspective of DNA hybridization approaches, sensor surface is chemically modified with single stranded DNA molecules, which are complementary to HBV specific DNA sequences.

31. Conti….
In one of the latest study, electrochemically deposited Au nanoparticles on single walled carbon nanotube (SWCNT) arrays were utilized, to self-assemble of single-stranded probe DNA on the SWCNT/Au platform for HBV specific DNA sequences detection.

32. Conclusion
Advances in micro/nanotechnology are pioneering the development of new generation methodologies in diagnosis and screening of HBV.
The potential, capability and promising applications of nanomaterials together with microfabricated and nano-assembled technologies that serve as a sensory system for detection of viral infections.

33. Future perspectives
Although the current diagnostic technologies can reliably detect HBV, they are relatively laborious, impractical and expensive for resource-limited settings.
To achieve effective viral detection, the sensing system needs to have high sensitivity and selectivity, signal amplification and label-free detection capabilities.
Moreover, the ideal sensor must be cost-effective, user-friendly.

34. Refrences
Yildiz, UH., F Inci , S Wang , M Toy , HC Tekin , A Javaid , DT Lau and U Demirci Plant-derived epigenetic modulators for cancer treatment and prevention. Biotechnology Advances, 32: