Advances in Antimicrobial Strategies

Introduction

Module Information Module Coordinators: A/Prof Vincent Chow and A/Prof Kevin Tan Email: micctk@nus.edu.sg; mictank@nus.edu.sg Tel: 6516-3691; 6516-6780 LECTURES: WEDNESDAYS TIME:1400 1600 hrs VENUE:LT 20 PRACTICALS: FRIDAYS TIME:1000 1400 hrs VENUE:LS Lab 9 @MD4 Lecturers: A/Prof. Vincent Chow (VC) A/Prof. Kevin Tan (KT) Lectures: 16 hrs A/Prof .Sylvie Alonso (SA) Team Presentations: 8 hrs A/Prof. Gamini K. (GK) Practicals / Tutorials: 28 hrs A/Prof. Tan Yee Joo (TYJ) A/Prof. Thomas Dick (TD) Total 50 hrs

WK

MONTH LECTURES/ TEAM PRESENTATIONS WEDNESDAYS

PRACTICALS / TUTORIALS FRIDAYS

0 * *

1 Introduction (VC) Lab Methods (GK)

P1 (Diagnostic Microbiology) (SA/GK)

2 Lab Methods (GK)

3 Antibiotic Resistance (GK) P2 (Diagnostic Microbiology) (SA/GK)

4 Microbial Pathogenesis (TYJ) P3 (Diagnostic Microbiology) (SA/GK)

5 *

6 Immunology & Infection (SA) *

7 Mid-Semester Break

8 Immunization (SA) P4 (Immunological Methods) (KT/VC)

9 Opportunistic Infections P5 (Molecular Techniques) (VC/TYJ)

10 New and New Infections (VC)

P6 (Molecular Techniques) (VC/TYJ)

11 Team Presentations

12 Team Presentations P7 (Molecular Techniques) (VC)

13 Team Presentations *

14 Team Presentations

Objectives LSM 4223 is an advanced course in the study of human infectious

diseases with emphasis on new and emerging infections as well as those of major clinical/economic importance Students are expected to have basic knowledge of infectious diseases

Understanding the principles and practice of Medical Microbiology Microbial pathogenesis Host immune response and vaccines Nature and emergence of antimicrobial resistance Changing epidemiology of infections Classical diagnostic techniques and current molecular approaches

Seminars will be conducted as team presentations to explore current topics on infectious diseases & recent advances in antimicrobial strategies in depth

Reference Texts Fundamentals of Microbiology (Alcamo)

Jones & Bartlett

Medical Microbiology (Jawetz, Melnick & Adelberg) McGraw Hill, Appleton and Lange

Medical Microbiology (Baron S) http://gsbs.utmb.edu/microbook/

Microbial Biotechnology (Lee)

World Scientific

Reference Textbooks for Immunology Background Reading

Caution about Websites

Good websites: From authoritative sources

WHO www.who.int CDC www.cdc.gov

From good Universities

Bad websites: Those not from academic or authoritative sources

Your Lecturers

A/Prof Vincent Chow MD, PhD, FRCPath Associate Professor Molecular Virologist Department of Microbiology

Tel: 65 6516 6200 Email: micctk@nus.edu.sg

Research area - Emerging Viral Diseases - Molecular genetics and infectomics

Your Lecturers Dr. Kevin SW Tan BSc (Hons) PhD Associate Professor Molecular Parasitologist Laboratory of Molecular and Cellular Parasitology

Department of Microbiology Level 5, Block MD4 Tel: 6516 6780 Email: mictank@nus.edu.sg

Research area

Cell and molecular biology of the malaria parasite Plasmodium falciparum Clinical aspects of the protozoan parasite Blastocystis hominis

Your Lecturers A/Prof. Gamini Kumarasinghe MBBS, DPath, FRCPath, FRCPA Senior Consultant Division of Microbiology, National University Hospital Clinical Microbiologist Department of Laboratory Medicine Main Building, Level 3

National University Hospital Email: GaminiK@nuh.com.sg

Main responsibilities Supervision of the clinical microbiology laboratory, clinical

liaison and consultation Infection control policy formulation

Your Lecturers A/Prof. Sylvie Alonso PhD Associate Professor Bacteriologist / Immunologist

Department of Microbiology Tel: 65 6516 3541 Email: micas@nus.edu.sg

Research area Host-pathogen Interactions Development of live bacterial vaccines

Your Lecturers

A/Prof. Tan Yee Joo Associate Professor, Microbiology, NUS Virologist Email: mictyj@nus.edu.sg Research areas

Understanding how RNA viruses make use of host cell machineries for their own benefits

SARS coronavirus, avian influenza virus, hepatitis C virus

Your Lecturers A/Prof. Thomas Dick Associate Professor, Microbiology, NUS Molecular Bacteriologist Email: micdickt@nus.edu.sg Research areas

Resistance and persistence of bacterial infections

Antibacterial drug discovery

Assessment

Assessment

Team presentation 10% Written report (CA) 20% Lab reports 20% Final exam 50% Total 100%

Team Presentations Broad Topics

Critical Discussion on Diagnostic Lab Methods Microbial Pathogenesis and Host Defence Evolution of Microbial Pathogens / Emerging

Diseases Infections of Immunocompromised/ Vaccines

Typically: 8 group presentations Team reports = CA

~ 7-8 students per group Full details on IVLE

Relevance and Impact of Infectious Diseases

Lectures Lab methods of Diagnosis Antibiotic/ Drug Resistance Microbial Pathogenesis Immunology and Infection Vaccines Opportunistic Infections Emerging Infections

http://www.cia.gov/nic/special_globalinfectious.html

http://www.cia.gov/nic/special_globalinfectious.html

http://www.cia.gov/nic/special_globalinfectious.html

http://www.cia.gov/nic/special_globalinfectious.html

Swine Flu Genes in this new virus very similar to influenza

viruses in pigs in North America. Genes from swine flu viruses in Europe and Asia. Genes from avian and human flu viruses. Quadruple reassortant" virus. Reinforces the importance of pigs as mixing

vessels for reassortment events.

Novel H1N1-2009 virus

Highly contagious among humans. Transmission similar to seasonal influenza

coughing, sneezing, via infected surfaces and objects.

Symptoms fever, cough, sore throat, runny or blocked nose, headache, body aches, lethargy. Also diarrhea and vomiting.

Clinical severity

Mild to severe. Most infected individuals recover without treatment.

However, hospitalizations and deaths may occur especially in high-risk groups (70%), i.e. asthma, heart disease, renal disease, diabetes, immunosuppressed, pregnancy.

Unlike seasonal influenza, adults over 65 years are not at increased risk of flu complications. One third have cross-reactive neutralizing antibodies.

WHO activities in avian influenza and pandemic influenza preparedness I. Reduce human exposure to the H5N1 virus II. Strengthen the early warning systems III. Intensify rapid containment operations IV. Build capacity to cope with a pandemic V. Coordinate global scientific research and development

H5N1 Airborne Spread?

Two separate groups, led by Y. Kawaoka (Wisconsin-Madison), and Ron Fouchier (Rotterdam).

Passaged the virus from one ferret to another several times, to mimic natural evolution. After several generations, the virus had acquired the ability of airborne transmission.

H5N1 Controversy in 2011

Transmissible strain had 5 mutations in 2 genes. Each mutation already exists in nature: but only in separate strains, and so far not together in a single strain.

Potential for this H5N1 strain to be abused as a bioterrorist agent or for biological warfare.

Current H5N1 fatality rate of ~60%.

http://www.cia.gov/nic/special_globalinfectious.html

http://www.cia.gov/nic/special_globalinfectious.html

Impact of Infectious Diseases on Trade Cholera in Peru. The outbreak of cholera in 1991 cost the Peruvian fishing industry an

estimated $775 million in lost tourism and trade because of a temporary ban on seafood exports.

Avian flu in Hong Kong. The avian influenza outbreak in 1997 cost the former colony hundreds of millions of dollars in lost poultry production, commerce, and tourism, with airport arrivals in November of that year alone down by 22 percent from the preceding year.

BSE and nvCJD in Britain. The outbreak of BSE and new variant Creutzfeldt-Jakob disease in the United Kingdom in 1995 prompted a mass slaughter of cattle, drastically cut beef consumption, and led to the imposition of a three-year EU embargo against British beef. The losses to the British economy were estimated by the WHO at $5.75 billion, including $2 billion in lost beef exports.

Foot and mouth disease in Taiwan. In 1997 an outbreak of foot and mouth disease (FMD) devastated Taiwan's pork industry--one of the largest in the world--shutting down exports for a full year.

Nipah in Malaysia. In 1999, the Nipah virus caused the shutdown of over half of the country's pig farms and an embargo against pork exports.

Cyclospora in Guatemalan raspberries. The outbreak of cyclospora-related illness in the United States and Canada associated with raspberries from Guatemala led to curbs in imports that cost Guatemala several million dollars in lost revenue.

http://www.cia.gov/nic/special_globalinfectious.html

Projected Outcomes (2020) by National Intelligence Council, CIA, USA Steady Progress

Aging of global populations and declining fertility rates, socioeconomic advances, and improvements in health care and medical breakthroughs

Non-infectious diseases as heart disease and cancer would replace infectious diseases as the overarching global health challenge

Unlikely because it gives inadequate emphasis to persistent demographic and socioeconomic challenges in the developing countries, to increasing microbial resistance to existing antibiotics

Projected Outcomes (2020) Progress Stymied

Little or no progress in countering infectious diseases over the duration of this estimate

HIV/AIDS reaches catastrophic proportions as the virus spreads throughout the vast populations of India, China, the former Soviet Union, and Latin America

Multidrug treatments encounter microbial resistance and remain prohibitively expensive for developing countries

Multidrug resistant strains of TB, malaria, and other infectious diseases appear at a faster pace than new drugs and vaccines, wreaking havoc on world health

Although more likely than the "steady progress" scenario, this scenario also is unlikely to prevail because it underestimates the prospects for socioeconomic development, international collaboration, and medical and health care advances

Projected Outcomes (2020) Deterioration, Then Limited Improvement

Worsens during the first half of time frame Decreases after that, owing to better prevention and control efforts, new drugs and

vaccines, and socioeconomic improvements In the previous decade, under this scenario, negative demographic and social

conditions in developing countries, such as continued urbanization, poor health care capacity, and natural disasters remain conducive to the spread of infectious diseases

During this decade, more positive demographic changes such as reduced fertility and aging populations; gradual socioeconomic improvement in most countries; medical advances against childhood and vaccine-preventable killers such as diarrheal diseases, neonatal tetanus, and measles; expanded international surveillance and response systems; and improvements in national health care capacities take hold in all but the least developed countries

Barring the appearance of a deadly and highly infectious new disease, a catastrophic upward lurch by HIV/AIDS, or the release of a highly contagious biological agent capable of rapid and wide-scale secondary spread, these developments produce at least limited gains against the overall infectious disease threat

Most likely scenario

Salient Points Globally, infectious diseases are a leading cause of

death Infectious diseases influence social, economic and

political aspects of countries Human behavior and mutations in pathogens lead

to spread of infectious diseases New and reemerging infectious diseases will pose a

rising global health threat Need novel strategies to detect, treat and prevent

emerging and existing infectious threats

LSM 4223Module InformationSlide Number 3ObjectivesReference TextsSlide Number 6Caution about WebsitesYour LecturersYour LecturersYour LecturersYour LecturersYour LecturersYour LecturersAssessmentAssessmentTeam PresentationsRelevance and Impact of Infectious DiseasesSlide Number 18Slide Number 19Slide Number 20Slide Number 21Swine Flu Novel H1N1-2009 virus Clinical severitySlide Number 25H5N1 Airborne Spread?H5N1 Controversy in 2011Slide Number 28Slide Number 29Impact of Infectious Diseases on TradeProjected Outcomes (2020) byNational Intelligence Council, CIA, USAProjected Outcomes (2020)Projected Outcomes (2020)Salient Points