Communicable Diseases, Emerging and Re-Emerging Diseases

Biology 447 - Environmental Microbiology Outline q Communicable Diseases q Nosocomial Infections (hospital-acquired) q Antibiotic Resistance q Mapping Emerging Diseases q Neglected Diseases q Emerging Diseases in the US q Diseases preventable by vaccination q Global Emerging and Re-emerging Diseases - HIV - Hepatitis - Influenza - Malaria - Herpes - Ebola - Tuberculosis - HPV - SARS - Avian Influenza - West Nile virus - Trypanosomiasis - Others q Summary

10/24/2008 2 Communicable Diseases

10/24/2008 3 Introduction

10/24/2008 4 In 2001, a review of the scientific literature identified 1415 species of infectious organisms known to be pathogenic to humans, including:

– 217 viruses and prions, – 538 bacteria and rickettsiae, – 307 fungi, – 66 protozoa and – 287 helminths.

Of these, 61% were zoonotic and 12% were associated with diseases considered to be emerging

(Taylor, Latham & Woolhouse, 2001).

10/24/2008 5 10/24/2008 6 10/24/2008 7 Communicable Diseases: Definition

• Defined as • “any condition which is transmitted directly or indirectly to a person from an infected person or animal through the agency of an intermediate animal, host, or vector, or through the inanimate environment”.

• Transmission is facilitated by the following:

– more frequent human contact due to • Increase in the volume and means of transportation (affordable international air travel), • globalization (increased trade and contact)

– Microbial adaptation and change

– Breakdown of public health capacity at various levels

– Change in human demographics and behavior

– Economic development and land use patterns

10/24/2008 8 CD- Modes of transmission

• Direct • Blood-borne or sexual – HIV, Hepatitis B,C • Inhalation – Tuberculosis, influenza, anthrax • Food-borne – E.coli, Salmonella, • Contaminated water- Cholera, rotavirus, Hepatitis A

• Indirect • Vector-borne- malaria, onchocerciasis, trypanosomiasis • Fomites

• Zoonotic diseases – animal handling and feeding practices (Mad cow disease, Avian Influenza)

• Nosocomial Infections- physician or health care worker induced diseases

10/24/2008 9 Importance of Communicable Diseases

Significant burden of disease especially in low and middle income countries

– Social impact

– Economic impact

– Potential for rapid spread

– Human security concerns – Intentional use

10/24/2008 10 Communicable Diseases account for a significant global disease burden

• In 2005, CDs accounted for about 30% of the global Burden of Disease and 60% of the BoD in Africa.

• CDs typically affect LIC and MICs disproportionately.

• Account for 40% of the disease burden in low and middle income countries

• Most communicable diseases are preventable or treatable.

10/24/2008 11 Communicable Disease Burden Varies Widely Among Continents

10/24/2008 12 Communicable Disease Burden Varies Widely Among Continents

67%

10/24/2008 13 Communicable disease burden in Europe

10/24/2008 14 Communicable disease burden in Europe 3%

10/24/2008 15 Causes of Death Vary Greatly by Country Income Level

Age distribution of death in Sierra Leone around 2005 Age distribution of death in Denm ark around 2005 Male Female Male Female

90 - 94 90 - 94

75 - 79 75 - 79

60 - 64 60 - 64

45 - 49 45 - 49 Age group 30 - 34 Age group 30 - 34

15 - 19 15 - 19

0 - 4 0 - 4 80 60 40 20 0 20 40 60 80 80 60 40 20 0 20 40 60 80 Percent of total of deaths Percent of total deaths

Sierra Leone - Age Denmark - Age distribution at death distribution at death (2005) (2005) 10/24/2008 16 CDs have a significant social impact

• Disruption of family and social networks – Child-headed households, social exclusion

• Widespread stigma and discrimination – TB, HIV/AIDS, Leprosy – Discrimination in employment, schools, migration policies

• Orphans and vulnerable children – Loss of primary care givers – Susceptibility to exploitation and trafficking

• Interventions such as quarantine measures may aggravate the social disruption

10/24/2008 17 CDs have a significant economic impact in affected countries

• At the macro level

– Reduction in revenue for the country (e.g. tourism) • Estimated cost of SARS epidemic to Asian countries: $20 billion (2003) or $2 million per case. • Drop in international travel to affected countries by 50-70% • Malaria causes an average loss of 1.3% annual GDP in countries with intense transmission • The plague outbreak in India cost the economy over $1 billion from travel restrictions and embargoes

• At the household level • Poorer households are disproportionately affected • Substantial loss in productivity and income for the infirmed and caregiver • Catastrophic costs of treating illness

10/24/2008 18 International boundaries are disappearing

• Borders are not very effective at stopping communicable diseases

• With increasing globalization • interdependence of countries – more trade and human/animal interactions

• The rise in international traffic and commerce makes challenges even more daunting

• Other global issues affect or are affected by communicable diseases. • climate change • migration • Change in biodiversity

10/24/2008 19 10/24/2008 20 Human Security concerns

• Potential magnitude and rapid spread of outbreaks/pandemics. e.g. SARS outbreak – No country or region can contain a full blown outbreak of Avian influenza

• Bioterrorism and intentional outbreaks – Anthrax, Small pox

• New and re-emerging diseases – Ebola, TB (MDR-TB and XDR-TB), Hantavirus, etc

10/24/2008 21 Nosocomial Infections

10/24/2008 22 Nosocomial Infection

Any infection that is acquired from being in a hospital or other healthcare institution (e.g., nursing home)

Nosocomial: Originating or taking place in a hospital, acquired in a hospital, especially in reference to an infection.

The term "nosocomial" comes from two Greek words: "nosus" meaning "disease" + "komeion" meaning "to take care of." Hence, "nosocomial" should apply to any disease contracted by a patient while under medical care. However, "nosocomial" has been whittled down over the years and now just refers to hospitals -- it is now synonymous with hospital-acquired.

10/24/2008 23 • 44,000 - 98,000 preventable deaths occur in U.S. hospitals every year

• 17-29 billion healthcare dollars “wasted” because of medical errors

10/24/2008 24 Burden of Nosocomial Infection in U.S. Hospitals

• 1.7 - 2 million nosocomial infections/year

• Results in 80,000-100,000 deaths/year – Medication errors cause ~7,000 deaths

• Cost: 5-6 billion dollars/year

10/24/2008 25 Nosocomial infection in Canada

Every year, 250,000 Canadians pick up infections while they are in hospitals being treated for something else.

That's one out of every nine Canadians who are admitted to hospital.

Every year, those infections kill more than 8,000 people.

That's more than will die of breast cancer, AIDS and car accidents combined.

Many of those deaths can be prevented - by simple hand washing.

10/24/2008 26 Hand washing compliance by physicians in Australia

% of appropriate occasions

Self reported compliance = 74%

Actual (measured) compliance = 8%

Canadian compliance rates are steadily rising since the onset of Clostridium difficile and other outbreaks in hospitals. They are now estimated to be over 50% - 60%

10/24/2008 27 Epidemiology and Cholera

Cholera is still a problem in some parts of the world

10/24/2008 28 10/24/2008 29 What is cholera?

...all is darkness and confusion, vague theory, and a vain speculation. Is it a fungus, an insect, a miasma, an electrical disturbance, a deficiency of ozone, a morbid off-scouring from the intestinal canal?

We know nothing; we are at sea in a whirlpool of conjecture.

- Wakley T. The Lancet II, 393, 1853

10/24/2008 30 English physician and a leader in the adoption of anaesthesia and medical hygiene.

He is considered to be one of the fathers of epidemiology, because of his work in tracing the source of a cholera outbreak in Soho, England, in 1854.

Wikipedia

http://www.ph.ucla.edu/epi/ snow.html#BROAD

10/24/2008 31 Original Snow map of Soho, England during the 1854 cholera outbreak showing the individual cases of cholera 10/24/2008 32 During the next three days, 127 people living in or around Broad Street died. Few families, rich or poor, were spared the loss of at least one member. Within a week, three-quarters of the residents had fled from their homes, leaving their shops shuttered, their houses locked and the streets deserted. Only those who could not afford to leave remained there. It was like the Great Plague all over again.

By 10 September, the number of fatal attacks had reached 500 and the death rate of the St Anne's, Berwick Street and Golden Square subdivisions of the parish had risen to 12.8 per cent -- more than double that for the rest of London.

From Judith Summers in her history of the Soho neighborhood of London. 10/24/2008 33 He traced the outbreak in South London to contaminated water supplied by the Vauxhall Water Company -- a theory that the authorities and the water company itself were, not surprisingly, reluctant to believe.

Now he saw his chance to prove his theories once and for all, by linking the Soho outbreak to a single source of polluted water.

His research led him to a pump on the corner of Broad Street and Cambridge Street, at the epicenter of the epidemic.

"I found," he wrote afterwards, "that nearly all the deaths had taken place within a short distance of the pump." In fact, in houses much nearer another pump, there had only been 10 deaths -- and of those, five victims had always drunk the water from the Broad Street pump, and three were schoolchildren who had probably drunk from the pump on their way to school.

From Judith Summers in her history of the Soho neighborhood of London.

10/24/2008 34 Lambeth Water Company (water obtained upstream from London) – 5 per 100,000

Southwark and Vauxhall Water Company (water obtained from London) – 70 per 100,000

10/24/2008 35 He took his findings to the Board of Guardians of St James's Parish, in whose parish the pump fell.

Though they were reluctant to believe him, they agreed to remove the pump handle as an experiment. When they did so, the spread of cholera dramatically stopped. [actually the outbreak had already lessened for several days]

There were several unexplained deaths from cholera that did not at first appear to be linked to the Broad Street pump water -- notably, a widow living in West End, Hampstead, who had died of cholera on 2 September, and her niece, who lived in Islington, who had succumbed with the same symptoms the following day. Since neither of these women had been near Soho for a long time, Dr Snow rode up to Hampstead to interview the widow's son. He discovered from him that the widow had once lived in Broad Street, and that she had liked the taste of the well-water there so much that she had sent her servant down to Soho every day to bring back a large bottle of it for her by cart. The last bottle of water -- which her niece had also drunk from -- had been fetched on 31 August, at the very start of the Soho epidemic.

10/24/2008 From Judith Summers in her history of the Soho neighborhood of London. 36 So what had caused the cholera outbreak?

The Reverend Henry Whitehead, vicar of St Luke's church, Berwick Street, believed that it had been caused by divine intervention, and he undertook his own report on the epidemic in order to prove his point. However, his findings merely confirmed what Snow had claimed, a fact that he was honest enough to own up to.

Furthermore, Whitehead helped Snow to isolate a single probable cause of the whole infection: just before the Soho epidemic had occurred, a child living at number 40 Broad Street had been taken ill with cholera symptoms, and its nappies (diapers) had been steeped in water which was subsequently tipped into a leaking cesspool situated only three feet from the Broad Street well.

From Judith Summers in her history of the Soho neighborhood of London.

10/24/2008 37 Gro Harlem Brundtland, M.D., M.P.H. former Director-General, World Health Organization Geneva, Switzerland

In Washington, D.C., 28 October 1998

"In historic terms the marriage between science and health is a relatively recent event. Not long ago superstition, magic and astrology were the only weapons our ancestors had to fight diseases and epidemics that haunted the world. They were seen as divine punishments or unfavorable influence of the heavenly bodies."

"We owe that marriage to the creators of modern bacteriology, epidemiology and therapeutics - to scientists such as Louis Pasteur, Robert Koch, John Snow, Alexander Fleming and Paul Erlich - and their discoveries that shaped modern medicine and public health policies. They helped rescue our civilization from the dark ages of the unknown - and the unknown had names such as plagues, cholera or syphilis."

10/24/2008 38 Cholera is still here

10/24/2008 39 10/24/2008 40 10/24/2008 41 Cholera

David A Sack, R Bradley Sack, G Balakrish Nair, A K Siddique

Intestinal infection with Vibrio cholerae results in the loss of large volumes of watery stool, leading to severe and rapidly progressing dehydration and shock. Without adequate and appropriate rehydration therapy, severe cholera kills about half of affected individuals. Cholera toxin, a potent stimulator of adenylate cyclase, causes the intestine to secrete watery fluid rich in sodium, bicarbonate, and potassium, in volumes far exceeding the intestinal absorptive capacity.

Cholera has spread from the Indian subcontinent where it is endemic to involve nearly the whole world seven times during the past 185 years. V cholerae serogroup O1, biotype El Tor, has moved from Asia to cause pandemic disease in Africa and South America duringToday? the past 35 years. A new serogroup, O139, appeared in south Asia in 1992, has become endemic there, and threatens to start the next pandemic. Research on case management of cholera led to the development of rehydration therapy for dehydrating diarrhoea in general, including the proper use of intravenous and oral rehydration solutions.

Appropriate case management has reduced deaths from diarrhoeal disease by an estimated 3 million per year compared with 20 years ago. Vaccination was thought to have no role for cholera, but new oral vaccines are showing great promise.

10/24/2008 42 Epidemiology

10/24/2008 43 Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems.

Principles of Epidemiology in Public Health Practice Third Edition An Introduction to Applied Epidemiology and Biostatistics

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Office of Workforce and Career Development Atlanta, GA 30333

http://wvlc.uwaterloo.ca/biology447/emergingdiseases/principlesofepidemiology.pdf

10/24/2008 44

Key features and applications of descriptive and analytic epidemiology

• Summarizing Data: Calculation and interpretation of mean, median, mode, ranges, variance, standard deviation, and confidence interval

• Measures of Risk: Calculation and interpretation of ratios, proportions, incidence rates, mortality rates, prevalence, and years of potential life lost

• Displaying Public Health Data: Preparation and application of tables, graphs, and charts such as arithmetic-scale line, histograms, pie chart, and box plot

• Public Health Surveillance: Processes, uses, and evaluation of public health surveillance in the United States

• Investigating an Outbreak: Steps of an outbreak investigation

10/24/2008 45 Mapping Emerging Diseases

10/24/2008 46 Emerging diseases on the Rise

• An international research team has provided the first scientific evidence that deadly emerging diseases have risen steeply across the world, and has mapped the outbreaks' main sources.

• They say new diseases originating from wild animals in poor nations are the greatest threat to humans.

• Expansion of humans into shrinking pockets of biodiversity and resulting contacts with wildlife are the reason, they say. Meanwhile, richer nations are nursing other outbreaks, including multidrug-resistant pathogen strains, through overuse of antibiotics, centralised food processing and other technologies.

10/24/2008 47 • The study appears in the Feb. 21 2008 issue of the leading scientific journal Nature. Emerging diseases-defined as newly identified pathogens, or old ones moving to new regions--have caused devastating outbreaks already.

• The HIV/AIDS pandemic, thought to have started from human contact with chimps, has led to over 65 million infections; recent outbreaks of SARS originating in Chinese bats have cost up to $100 billion. Outbreaks like the exotic African Ebola virus have been small, but deadly.

10/24/2008 48 • Despite three decades of research, previous attempts to explain these seemingly random emergences were unsuccessful.

• In the new study, researchers from four institutions analysed 335 emerging diseases from 1940 to 2004, then converted the results into maps correlated with human population density, population changes, latitude, rainfall and wildlife biodiversity.

• They showed that disease emergences have roughly quadrupled over the past 50 years. Some 60% of the diseases travelled from animals to humans (such diseases are called zoonoses) and the majority of those came from wild creatures.

• With data corrected for lesser surveillance done in poorer countries, "hot spots" jump out in areas spanning sub-Saharan Africa, India and China; smaller spots appear in Europe, and North and South America. 10/24/2008 49 Emerging diseases on rise

• "We are crowding wildlife into ever-smaller areas, and human population is increasing. The meeting of these two things is a recipe for something crossing over." Marc Levy, a global- change expert at the Center for International Earth Science Information Network (CIESIN), an affiliate of Columbia University's Earth Institute

• The main sources are mammals.

• Some pathogens may be picked up by hunting or accidental contact; others, such as Malaysia's Nipah virus, go from wildlife to livestock, then to people.

• Humans have evolved no resistance to zoonoses, so the diseases can be extraordinarily lethal. The scientists say that the more wild species in an area, the more pathogen varieties they may harbour.

• About 20 percent of known emergences are multidrug- resistant strains of previously known pathogens, including tuberculosis.

• Increasing use and reliance on modern antibiotics has helped 10/24/2008 breed such dangerous strains 50 Emerging diseases on rise

• More diseases emerged in the 1980s than any other decade- likely due to the HIV/AIDS pandemic, which led to other new diseases in immune-compromised victims.

• In the 1990s, insect-transmitted diseases saw a peak, possibly in reaction to rapid climate changes that started taking hold then.

• "The world's public-health resources are misallocated. Most are focused on richer countries that can afford surveillance, but most of the hotspots are in developing countries. If you look at the high-impact diseases of the future, we're missing the point."

• "We need to start finding pathogens before they emerge," said Daszak.

10/24/2008 51 • Emerging infectious diseases (EIDs) are a significant burden on global economies and public health. Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors, but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs.

• Here we analyse a database of 335 EID 'events' (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic.

• EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time.

10/24/2008 52 • We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database.

• Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease 'hotspots').

• They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low.

• We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.

10/24/2008 53 Nature 451, 990-993 (21 February 2008) | doi:10.1038/nature06536; Received 2 August 2007; Accepted 11 December 2007 Global trends in emerging infectious diseases

Kate E. Jones1, Nikkita G. Patel2, Marc A. Levy3, Adam Storeygard3,5, Deborah Balk3,5, John L. Gittleman4 & Peter Daszak2 Institute of Zoology, Zoological Society of London, Regents Park, London NW1 4RY, UK Consortium for Conservation Medicine, Wildlife Trust, 460 West 34th Street, 17th Floor, New York, New York 10001, USA Center for International Earth Science Information Network, Earth Institute, Columbia University, 61 Route 9W, Palisades, New York 10964, USA Odum School of Ecology, University of Georgia, Athens, Georgia 30602, USA Present addresses: Department of Economics, Brown University, Providence, Rhode Island 02912, USA (A.S.); School of Public Affairs, Baruch College, City University of New York, 1 Bernard Baruch Way, Box D-0901, New York, New York 10010, USA (D.B.).

10/24/2008 54 Global distribution of relative risk of an EID event

Caption: Maps are derived for EID events caused by (a) zoonotic pathogens from wildlife, (b) zoonotic pathogens from nonwildlife, (c) drug-resistant pathogens, and (d) vector-borne.

The relative risk is calculated from regression coefficients and variable values in Table 1 (omitting the variable measuring reporting effort), categorized by standard deviations from the mean and mapped on a linear scale from green (lower values) to red (higher values). Credit: Jones et. al., Nature 2008

10/24/2008 55 Neglected Diseases

10/24/2008 56 Neglected diseases

• Cause over 500,000 deaths and 57 million DALYs annually.

• Include the following

– Helminthic infections • Hookworm (Ascaris, trichuris), lymphatic filariasis, onchocerciasis, schistosomiasis, dracunculiasis

– Protozoan infections • Leishmaniasis, African trypanosomiasis, Chagas disease

– Bacterial infections • Leprosy, trachoma, buruli ulcer

10/24/2008 57 Emerging Diseases in the United States

10/24/2008 58 Emerging and re-emerging Diseases in the USA

Chlamydia Measles * Diphtheria * Meningococcus Encephalitis MRSA West Nile Pertussis * St. Louis Poliomyelitis * E. coli Rabies N gonorrhea Rocky Mountain Spotted Fever H. Influenzae Rubella * Hantavirus SARS (Severe Acute Respiratory Syndrome) Hepatitis A-G (A and B*) Salmonellosis Human herpes viruses Shigellosis HHV 1-8 S. pneumoniae HIV/AIDS Syphilis Human papilloma viruses * Tetanus * Influenza * Emerging strains Toxic-Shock Syndrome Legionella pneumophila Tuberculosis * Lyme Disease *

* Vaccination possible

10/24/2008 59 Emerging / Re-emerging - Diseases

• HIV/AIDS/Opportunistic infections • Hepatitis A-G, Other ? • Herpes, Flu, Other viral diseases • Candiaiasis, Other fungal diseases • Bacterial/Drug resistant bacterial: – E. coli 015.7:H7

– Other food/H2O-borne – S. pneumonia, MRSA, VRSA – Vancomycin resistant Enterococcus (VRE) – Multiple-drug resistant TB (MDRTB) – Bio-engineered agents Malaria – drug-resistant

10/24/2008 60 Why are these mainly “older” diseases “re-emerging” in the USA ?

• Change in vaccination patterns and percentage coverage • Lack of herd immunity • New strains of organisms • Faster transmission • Hygiene and general health? • Overuse of antibiotics (in humans and animals) • Immuno-compromised individuals (AIDS, cancer treatment patients, children, etc) • Breakdown in public health or control • Human demographics, behaviour • Ecological changes

10/24/2008 61 Diseases in the USA preventable by vaccination

10/24/2008 62 Vaccine Preventable Diseases Adults • Mumps* • Pneumococcus** • Polio • Rubella* • Tetanus** • Varicella* • Diphtheria** • Hepatitis A • Hepatitis B • Influenza** • Lyme Disease • Measles* • Haemophilis influenza type B (Hib)

www.cdc.gov, 2/4/2002 10/24/2008 63 Vaccine Preventable Diseases - Adults

• Diphtheria** • Hepatitis A • Hepatitis B • Influenza** • Lyme Disease • Measles* • Haemophilis influenza type B (Hib) • Mumps* • Pneumococcus** • Polio • Rubella* • Tetanus** • Varicella*

10/24/2008 64 Vaccine Preventable Diseases of children

• Diphtheria • Hepatitis A • Hepatitis B • Pertussis • Measles* • Haemophilis influenza type B (Hib)

10/24/2008 65 Antibiotic Resistance in Pathogenic Organisms:

Emerging Drug Resistance in Bacteria

• MRSA = Methicillin-Resistant Staphylococcus aureus

• VRE = Vancomycin-resistant enterococcus

• 3CRKP = Klebsiella pneumoniae resistant to 3rd generation cephalosporins

• FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones

• Clostridium difficile (NAP1) resistant to fluoroquinolones

10/24/2008 67 MRSA

• Any strain of Staphylococcus aureus that is resistant to the antibiotic group known as the beta-lactams which include penicillins and cephalosporins • Patients in hospitals are at higher risk for MRSA infection due to the transfer of bacteria between individuals in a confined area • Two types of MRSA infection can occur – Community acquired (CA-MRSA) – Health-care associated (HA-MRSA) MRSA

• In 2007 880,000 individuals were infected with Methicillin- Resistant Staphylococcus aureus. • 85% of these cases were contracted by individuals residing in hospitals for an unspecified amount of time (institutionally accquired MRSA) • The remaining 15% of these infections were community associated cases Proportion of Staphylococcus aureus isolates reported as methicillin-resistant in the US and Canada

Sources: US Centers for Disease Control and Prevention (CDC) data and Canadian Nosocomial Infection Surveillance Program (CNISP) data. Methicillin-Resistant Staphylococcus aureus (MRSA)

• Staphylococcus aureus is commonly carried on the skin or in the nose of healthy people. Approximately 25% to 30% of the population is colonized (when bacteria are present, but not causing an infection) in the nose.

• It is one of the most common causes of skin infections but most of are minor (such as pimples and boils) and can be treated without antibiotics. It also can cause serious infections (such as surgical wound infections, bloodstream infections, and pneumonia).

Who is susceptible to MRSA infection? • MRSA usually infects hospital patients who are elderly or very ill. You may be at more risk if you have had frequent, long-term, or intensive use of antibiotics. Intravenous drug users and persons with long-term illnesses or who are immuno-suppressed are also at increased risk. • The infection can develop in an open wound such as a bedsore or when there is a tube such as a urinary catheter that enters the body. MRSA rarely infects healthy people.

10/24/2008 71 Methicillin-Resistant Staphylococcus aureus (MRSA)

10/24/2008 72 Modes of MRSA Infection

• Within 48 hours of initial symptoms MRSA progress substantially. After 72 hours, tissues can become resistant to treatment. • About 75 percent of CA-MRSA infections are localized to skin and soft tissue and usually can be treated effectively. • Vancomycin and teicoplanin are antibiotics used to treat MRSA infections. Teicoplanin is similar in structure and activity to vancomycin but a longer half-life • Although they have been successful in the treatment of MRSA, increasing incidence of resistance has become an issue of great concern Note: • Staphylococcus aureus and MRSA can also cause illness in persons outside of hospitals and healthcare facilities.

• MRSA infections that are acquired by persons who have not been recently (within the past year) hospitalized or had a medical procedure (such as dialysis, surgery, catheters) are know as Community- Acquired-MRSA infections (CA-MRSA

• Data from a prospective study in 2003, suggests that 12% of clinical MRSA infections are community-associated, but this varies by geographic region and population.

• CDC has investigated clusters of CA-MRSA skin infections among athletes, military recruits, children, Pacific Islanders, Alaskan Natives, Native Americans, men who have sex with men, and prisoners. Factors that have been associated with the spread of MRSA skin infections include: close skin-to-skin contact, openings in the skin such as cuts or abrasions, contaminated items and surfaces, crowded living conditions, and poor hygiene.

10/24/2008 74 Vancomycin-resistant enterococci

• Enteroccocci are bacteria that are normally present in the human intestines and in the female genital tract and are often found in the environment. These bacteria can sometimes cause infections.

• Vancomycin is an antibiotic that is often used to treat infections caused by enterococci. In some instances, enterococci have become resistant to this drug and thus are called vancomycin-resistant enterococci (VRE). Most VRE infections occur in hospitals.

• In the last decade enterococci have become recognized as leading causes of nosocomial bacteremia, surgical wound infection, and urinary tract infection

• Enterococci are readily recovered outdoors from vegetation and surface water, probably because of contamination by animal excrement or untreated sewage. In humans, typical concentrations of enterococci in stool are up to 108 CFU per gram

10/24/2008 75 Vancomycin-resistant enterococci

• Enteroccocci are bacteria that are normally present in the human intestines and in the female genital tract and are often found in the environment. These bacteria can sometimes cause infections.

• In the last decade enterococci have become recognized as leading causes of nosocomial bacteremia, surgical wound infection, and urinary tract infection

10/24/2008 76 • Among several phenotypes for vancomycin-resistant enterococci, VanA (resistance to vancomycin and teicoplanin) and VanB (resistance to vancomycin alone) are most common.

• In the United States, VanA and VanB account for approximately 60% and 40% of vancomycin-resistant enterococci (VRE) isolates, respectively.

• Enterococci are intrinsically resistant to many antibiotics. Unlike acquired resistance and virulence traits, which are usually transposon or plasmid encoded, intrinsic resistance is based in chromosomal genes, which typically are nontransferrable

10/24/2008 77 VRE

• Form of the bacteria enterococcus which has become resistant to treatments of infection • Present in the digestive and urinary tract • People who have been on vancomycin for long periods of time show increased susceptibility of VRE infection • Transferred from one person to another through indirect contact through the touching of contaminated material, especially prevalent in hospital settings • Grows well on hands and can survive for weeks upon inanimate objects like toilet seats and door handles VRE Mechanisms of Resistance

• There are six different types of vancomycin resistance (VanA-VanF) • VanA-C are the most commonly reported types of VRE associated with infection in humans • They show varying resistance to vancomycin and tectoplanin • Treated with Linezolid and Chloramphenicol but resistance is developing Clostridium difficile

• Clostridium difficlile is a bacterium that causes diarrhea and intestinal colitis that is most commonly found in long term care facilities and hospitals. • C. difficile can be found in feces and similar to VRE can be transmitted through contaminated surfaces and the fecal-oral route • Increased incidence in the past few years, especially in hospitals • Large outbreak in Quebec in 2003 brought nationwide attention to the increasing problem Annual Incidence (per 100,000 Population) of C. difficile Infection in Sherbrooke, Quebec, 1991–2003

Data from Ciarán P. Kelly, M.D., and J. Thomas LaMont, M.D C. difficile and Antibiotics

• Using antibiotics increases the chance of developing C.difficile diarrhea due to the alteration of the good bacteria within the intestines and colon. • When C.difficile colonizes the gut, toxins are released which cause bloating, constipation, and diarrhea • In vitro studies indicate that toxin expression may be enhanced by stressors • Often infections can be halted by discontinuing antibiotic use • If not, metronidazole and vancomycin are used Implications of Antibiotic Resistance

• In addition to being more difficult to treat, resistant bacteria are also more expensive • In 2001, the annual overall costs to the Canadian health system were estimated to be $200 million • In the US, this figure was estimated to be as high as $10 billion • New antibiotics are expensive and have greater toxicity • Costs are rising CDC’s National Nosocomial Infection Surveillance (NNIS) System, 1989 - 2004

MRSA VRE 3CRKP FQRPA 70

MRSA = methicillin-resistant Staphylococcus aureus 60

40 FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones

VRE = vancomycin-resistant enterococcus

Proportion of Proportion Resistant of (%) Isolates 3CRKP = Klebsiella pneumoniae resistant to 3rd generation cephalosporins 0 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 Year

10/24/2008 85 Global Diseases

10/24/2008 86 10/24/2008 87 10/24/2008 88 HIV/AIDS

10/24/2008 89 Emerging viral diseases

AIDS • First reported 6/5/81 by CDC

Epidemiologic Notes and Reports

• Pneumocystis Pneumonia --- Los Angeles

• In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died. All 5 patients had laboratory-confirmed previous or current cytomegalovirus (CMV) infection and candidal mucosal infection.

10/24/2008 90 1982: Term AIDS replaces GRID

1983: Universal precautions introduced 0 MMWR 1983;32:101

• The virus that causes AIDS identified 0 Gallo- HTLV III; Montagnier-LAV 0 Name changed to human immunodeficiency virus (HIV)

1985: First serologic test for HIV licensed by FDA

• Rock Hudson died of AIDS on 10/2/85

1986: AZT approved by FDA 0 Record approval time of 6 months

10/24/2008 91 HIV

• Very dynamic virus • 109 viral particles/day • Loss of 108-109 CD4 cells/day • Replicate every two days • 680,000 viral particles produced and cleared daily • 95% of virus produced from newly infected cells

CD4 - A glycoprotein on the surface of helper T cells that serves as a receptor for HIV. CD4 A type of protein molecule in human blood that is present on the surface of 65% of human T cells. CD4 is a receptor for the HIV virus. When the HIV virus infects cells with CD4 surface proteins, it depletes the number of T cells, B cells, natural killer cells, and monocytes in the patient's blood. Most of the damage to an AIDS patient's immune system is done by the virus' destruction of CD4+ lymphocytes. CD4 is sometimes called the T4 antigen.

10/24/2008 92 1989: U.S. AIDS cases reported at 100,000 1991: Estimated HIV infected in USA 1.5 million • Magic Johnson announces he is HIV positive 1993: Multiple drugs fail in clinical trials • Period of extreme pessimism for HIV infected 1995: First protease inhibitor approved: 0 Inverase,saquinivir • HIV kinetics reported at 10 billion virions/day

10/24/2008 93 1996: • HIV viral load testing – Becomes major method to assess ART • Mellors J; Ann Intern Med 1997;126:946 • ACTG 076 shows benefit of AZT in reducing perinatal transmission • NEJM 1996;335:1621 • Initial reports of benefit of HAART (highly active antiretroviral therapy ) – Ritonavir and indinavir approved – Fisrt NNRTI, nevirapine approved – First triple combination HAART study • Eradication of HIV might be possible with HAART – Dr. David Ho Time “Man of the Year”

10/24/2008 94 1997: 13% decrease in AIDS deaths – 60-80% reduction in new AIDS-defining conditions, hospitalizations and deaths • Palella et al, NEJM 1998;338:853, • Mocroft at al, Lancet 1998;352:1725 1999: HIV spread to humans from chimpanzees – Occurred in Africa decades before recognition (maybe even longer) 2000: AIDS pandemic raging in “Third World” – 36.1 million people infected with HIV – 21.8 million deaths – 14,000-16,000 new infections/day 2001: Two distinct epidemics

10/24/2008 95 HIV Natural History

• Clinical Latent Period: Asymptomatic - May have PGL; Viral set point at 6 month: Equilibrium between immune system and HIV; Persists for years; Gradual, relentless degradation of immune function • Early Symptomatic HIV Infection: CD4 < 500; Opportunistic Infection(s) • AIDS: CD4 < 200; AIDS Defining Illness(s) • Advanced HIV Infection: CD4 < 50; Serious opportunistic Infection(s); Death

10/24/2008 96 How Is HIV Spread?

Routes of Transmission: – Sexual – Intravenous Drug Use h Inhalation drug abuse

– Exposure to blood/blood products h Occupational exposure

– Mother to child h Breast feeding

10/24/2008 97 Mother-to-Child Transmission Global Situation

• Estimated 2.4 million HIV-positive women give birth annually to 600,000 HIV-positive babies – 1800 new infections each day 0 90% in sub-Saharan Africa 0 <1% (1000) in USA and Europe • Transmission rates 0 USA/Europe: 13–30% without ART, approaching 1–3% with ART 0 Developing countries: 20–43% without ART, lower rates with ART, even with short-course therapy • Breast feeding for 6 months 0 Additional 5–10% infections, with the highest rates of transmission occurring in the first and second months post- partum

Wiktor SZ, et al. XIIIth IAC, Durban, 2000. Abstract 354

10/24/2008 98 HIV Co-infections

• Impact of TB on HIV – TB considerably shortens the survival of people with HIV/AIDS. – TB kills up to half of all AIDS patients worldwide. – TB bacteria accelerate the progress of AIDS infection in the patient

• HIV and Malaria – Diseases of poverty – HIV infected adults are at risk of developing severe malaria – Acute malaria episodes temporarily increase HIV viral load – Adults with low CD4 count more susceptible to treatment failure

10/24/2008 99 Global HIV Burden

10/24/2008 100 10/24/2008 101 HIV/AIDS

• Interventions depend on – Epidemiology – mode of transmission, age group – Stage of epidemic –concentrated vs. generalized

• Elements of an effective intervention • Strong political support and enabling environment. • Linking prevention to care and access to care and treatment • Integrate it into poverty reduction and address gender inequality • Effective monitoring and evaluation • Strengthening the health system and Multisectoral approaches

• Challenges in prevention and scaling up treatment globally include • Constraints to access to care and treatment • Stigma and discrimination • Inadequate prevention measures. • Co-infections (TB, Malaria)

10/24/2008 102 Malaria

10/24/2008 103 Malaria

• Every year, 500 million people become severely ill with malaria • causes 30% of Low birth weight in newborns globally.

• >1 million people die of malaria every year. One child dies from it every 30 seconds

• 40% of the world’s population is at risk of malaria. Most cases and deaths occur in SSA.

• Malaria is the 9th leading cause of death in LICs and MICs • 11% of childhood deaths worldwide attributable to malaria • SSA children account for 82% of malaria deaths worldwide

10/24/2008 104 Annual Reported Malaria Cases by Country (WHO 2003)

10/24/2008 105 Global malaria prevalence

10/24/2008 106 Malaria Control

• Malaria control – Early diagnosis and prompt treatment to cure patients and reduce parasite reservoir – Vector control: • Indoor residual spraying • Long lasting Insecticide treated bed nets – Intermittent preventive treatment of pregnant women

• Challenges in malaria control – Widespread resistance to conventional anti-malaria drugs – Malaria and HIV – Health Systems Constraints • Access to services • Coverage of prevention interventions

10/24/2008 107 Hepatitis

10/24/2008 108 Hepatitis and Liver Disease

• 500-1000 therapeutic agents implicated in hepatitis

• 15-20 million Americans are alcoholics

• Tenth leading cause of death in USA

– 25,000 deaths/year

– 1% of all deaths

• 40 % of chronic liver disease HCV-related

– 8-10,000 deaths/year.

– HCV associated end stage liver disease is the most frequent indication for liver transplant

– As HCV population ages incidence of chronic liver disease could increase substantially

10/24/2008 109 Hepatitis

• Asymptomatic - anicteric • Mild symptomatic - anicteric • Classic icteric infection (pertaining to or affected with jaundice) • Fulminant hepatitis (sudden, flaring up type) • Chronic hepatitis

10/24/2008 110

Viral Hepatitis - Overview

Type of Hepatitis A B C D E Source of feces blood/ blood-derived/body fluids feces virus

Route of transmission fecal-oral Percutaneous/permucosal fecal-oral

Chronic infection no yes yes yes no ensure safe Prevention pre/post- pre/post- blood donor pre/post- exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

10/24/2008 111 Viral Hepatitis

VIRAL GENOME SPREAD INCUBATION CHRONICITY CLASS HAV Picoravirus RNA Enteric 15-45 Days None

HBV Hepadana DNA Parenteral 40-120 Days 5-10 %

HCV Flavivirus RNA Parenteral 15-90 Days > 85 %

HDV Satellite RNA Parenteral 25-75 Days 2-70 %

HEV Calci-Like RNA Enteric 20-80 Days None

HGV Flavivirus RNA Parenteral Unknown Probable

10/24/2008 112 Human Herpesviruses

• Alpha Herpesviruses: – Herpes Simplex Virus Type 1 (HSV-1) – Herpes Simplex Virus Type 2 (HSV-2) – Varicella Zoster Virus (HZV) The Herpes Simplex Virus type 1 (HSV1), which is • Beta Herpesviruses: the cause of cold sores, has an icosahedral – Cytomegalovirus (CMV) capsid shown here at 13 Å resolution. – Human Herpesvirus Type 6 (HHV-6) – Human Herpesvirus Type 7 (HHV-7) • Gamma Herpesviruses: – Epstein-barr Virus (EBV) – Human Herpesvirus Type 8 (HHV-8)

• Kaposi’s Sarcoma Asso. Herpesvirus

10/24/2008 113 Viruses - Herpes; HSV-1 & 2 • HSV-1: – Oral/genital/mucocutaneous lesions; – Acute gingivostomatitis; – Pharyngitis; – Herpes labialis; – Keratoconjunctivitis; – Encephalitis; – Herpetic Whitlow; • HSV-2: – Oral/genital/mucocutaneous lesions; – At least 1:4 persons > 12 y.o. infected; – 70-90% asymptomatic shedding; – Only about 20% of HSV-2 Ab+ know they are infected

10/24/2008 114 Herpes Viruses

• EBV: Epstein-Barr virus (EBV) occurs world-wide and infects most people – Infects > 85% of population; at some point in their lives. Children are largely immune to its effects, but infection in older people can cause a – Agent of infectious mononucleosis condition called infectious mononucleosis. – Cause of oral hairy leukoplakia; Long-term infection is, in very rare cases, linked to the development of – Oncogenic: Burkitt’s Lymphoma; some forms of cancer. – Linked to Hodgkin’s Disease/ other malignancies • CMV: – Problematic in immumocomp. pts; Retinitis, enteritis; – Linked to vasculopathies, CAD? – Role in organ transplant rejection; – Other graft/host involvement

10/24/2008 115 Varicella-Zoster (VZV)

• Chickenpox: Ubiquitous infection of childhood – Primary infection results in the characteristic disseminated cutaneous lesions. – The virus then establishes lifelong latency in dorsal root ganglia from whence it may reactivate to cause localized cutaneous eruptions known as herpes zoster or shingles. • Herpes zoster usually occurs later in life as a consequence of immunosuppressive illness or immunosuppressive medical therapy. • Declining VZV-specific immunity later in life is associated with an increased risk of herpes zoster.

10/24/2008 116 Human Papillomavirus

• Most common viral STD – Infects about 1/3 of sexually active population in USA – >60 strains have been identified – 25 strains associated with genital tract infections/cancer • Strongly associated with: – Cervical cancer • Causative agent – Oral cancer – Peri-anal/testicular cancer – Especially severe in HIV infected

10/24/2008 117 Papilloma; Focal Epithelial Hyperplasia (FEH)

• Etiological agent: – Human papilloma virus (HPV) – “Wart” • Clinical appearance: – Flat (FEH) – Siky – Cauliflower-like

10/24/2008 118 Influenza

10/24/2008 119 Influenza

Influenza virus particle

Image from: www.drugdevelopment-technology.com

10/24/2008 120 Influenza

• Acute, febrile illness, usually self limited – Headache, malaise, myalgias – Fever - 104oF-106oF (days 1-3) – URI symptoms • Nasal discharge, sore throat, cough (days 2-7) • Cervical adenopathy (children > adults) and rhonchi • Attack rate: 10 - 40% – Viral shedding: 0 One day before - until 10 days after symptom onset 0 Peak day 3-4 0 Shedding is prolonged in young children • Transmission: 0 Person to person via small particle aerosols 0 Virus is relatively stable and favors low humidity and cool temperatures

10/24/2008 121 Influenza virus

Cold virus 10/24/2008 122 • Influenza (flu) is a serious disease – Flu is not a cold! • It is far more dangerous than a bad cold – The virus infects the lungs. • It can lead to pneumonia/other sequellae. • Every year in the USA approximately: – 114,000 people are hospitalized – 20,000 people die because of the flu. • Most who die are over 65 years old. But small children less than 2 years old are as likely as those over 65 to have to go to the hospital because of the flu.

http://www.cdc.gov/nip/Flu/Public.htm#Facts

10/24/2008 123 H1N1 influenza • Influenza (the flu) is a contagious respiratory illness caused by influenza viruses. It can cause mild to severe illness, and at times can lead to death. The best way to prevent seasonal flu is by getting a seasonal flu vaccination each year.

• Each year in the United States on average, 5% to 20% of the population gets the flu; on average, more than 200,000 people are hospitalized from flu-related complications, and; about 36,000 people die from flu-related causes.

• Some people, such as older people, young children, and people with certain health conditions, are at high risk for serious flu complications. This flu season could be worse. There is a new and very different flu virus spreading worldwide among people called 2009 H1N1 flu.

• CDC – Atlanta 2009

10/24/2008 124 Avian Influenza

10/24/2008 125 Avian Influenza

• Seasonal influenza causes severe illness in 3-5 million people and 250000 – 500000 deaths yearly

• 1st H5N1 avian influenza case in Hong Kong in 1997.

• By October 2007 – 331 human cases, 202 deaths.

10/24/2008 126 Avian Influenza

• Control depends on the phase of the epidemic

– Pre-Pandemic Phase • Reduce opportunity for human infection • Strengthen early warning system

– Emergence of Pandemic virus • Contain and/or delay the spread at source

– Pandemic Declared • Reduce mortality, morbidity and social disruption • Conduct research to guide response measures

• Antiviral medications – Oseltamivir, Amantadine

• Vaccine – still experimental under development. • Can only be produced in significant quantity after an outbreak

10/24/2008 127 Confirmed human cases Avian Influenza

10/24/2008 128 Migratory pathway for birds and Avian influenza

10/24/2008 129 The Spread of Avian Flu -- Status as of the Summer 2008

10/24/2008 130 West Nile Virus

10/24/2008 131 WNV In USA

12/11/02

10/24/2008 132 • Spread by mosquitoes, which transmit it from infected birds. Mosquito species does make some difference.

• -Alligators have WNV titers as high as birds, thus they can serve as a reservoir too.

• -Certain titers need to be reached in order to infect mosquitoes. Horses and humans do not have high titers.

• -300 captive alligators that died in 2002 in Florida, necropsies showed the alligators had high viral loads of WNV.

10/24/2008 133 West Nile Virus Clinical Presentation

• Incubation period 3 - 14 days – 20% develop “West Nile fever” – 1 in 150 develop meningoencephalitis – Advanced age primary risk factor for severe neurological disease and death • Mild dengue-like illness of sudden onset – Duration 3 - 6 days – Fever, lymphadenopathy, headache, abdominal pain, vomiting, rash, conjunctivitis, eye pain, anorexia – Symptoms of West Nile fever in contemporary outbreaks not fully studied

10/24/2008 134 • Suspect WNV when: – Symptoms consistent with WNV – Unexplained bird or horse deaths – Mosquito season – Age > 50 years • Symptoms: – Most cases asymptomatic or mild dengue-like illness • Incubation period usually 5 (3) to 15 days 0 Fever, lymphadenopathy, headache 0 Abdominal pain, vomiting, rash, conjunctivitis – Muscle weakness and /or flaccid paralysis, hyporeflexia – EMG/NCV showing axonal neuropathy – Lymphocytopenia – MRI: • Shows enhancement of leptomeninges and/or periventricular area – CNS involvement and death in minority of cases

10/24/2008 135 West Nile Virus Human Cases in the US

1999 -62 cases with 7 deaths in New York only

1999 -21 cases with 2 deaths in 12 states

2000 -66 cases with 9 deaths in 10 states

2001 -4156 cases with 284 deaths in 40 states

2002 -9862 cases with 264 deaths in 46 states

2004 -2539 cases with 100 deaths in 42 states

2005 -3000 cases with 119 deaths in 44 states

2006 -4269 cases with 177 deaths in 44 states

2007 -3630 cases with 124 deaths in 43 states

10/24/2008 136 10/24/2008 137 U.S. cases of West Nile for 2002

10/24/2008 138 U.S. cases of West Nile for 2004

10/24/2008 139 U.S. cases of West Nile for 2005

10/24/2008 140 U.S. cases of West Nile for 2007

10/24/2008 141 SARS (Severe Acute Respiratory Syndrome)

10/24/2008 142 10/24/2008 143 Severe Acute Respiratory Syndrome (SARS)

The Initial Epidemic • Outbreak of atypical pneumonia in Hong Kong in March 2003 – Between 03/11/03 and 03/25/03 156 patients were hospitalized with SARS – 138 were identified as secondary or tertiary cases as a result of exposure to index case(s) • 112 secondary cases • 26 tertiary cases – Includes 69 HCWs • 20 MDs • 34 Nurses • 15 Allied HCWs – 54 patients on ward or visitors • 16 medical students • 32 of the 138 patients (23.2%) had severe respiratory failure – 5 patients died (3.6%) • All had been hospitalized with a major medical condition

10/24/2008 144 Severe Acute Respiratory Syndrome (SARS)

The Clinical Presentation- Initial 138 Cases • Incubation period was 2-10 days from initial exposure to onset of fever – Median incubation period was 6 days • The most common clinical symptoms were: – Fever (100%) > 100.50 – Chills, rigors or both (73.2%) – Myalgia (60.9%) – Cough (57.3%) – Headache (55.8%) – Dizziness (42.8%) • Less common symptoms included: – Sore throat, sputum production, coryza (cold symptoms), nausea, vomiting, and diarrhea

10/24/2008 145 Routes of Transmission:

• The principal way SARS appears to be spread is through droplet transmission – Namely, when a SARS patient coughs or sneezes droplets into the air and someone else breathes them in. • It is possible that SARS can be transmitted through the air or from objects that have become contaminated. • People at risk: – Direct close contact with an infected person – Sharing a household with a SARS patient – HCWs who did not use infection control procedures while caring for a SARS patient. • In the United States, there is no indication of community transmission at this time.

10/24/2008 146 Spread of SARS

From New York Times

10/24/2008 147 10/24/2008 148 Severe Acute Respiratory Syndrome (SARS) Cause of SARS • Scientists at CDC and other laboratories have detected a previously unrecognized coronavirus in patients with SARS.1-4

– Confirmed as causative agent by WHO on 04/16/03

– Virus a member of the coronavirus family, never before seen in humans

1. http://www.cdc.gov/ncidod/sars/casedefinition.htm 2. Peiris J et al, Lancet 2003 http://image.thelancet.com/extras/03art3477web.pdf 3. Drosten C et al. NEJM 2003 www.nejm.org 4. Ksiazek T et al. NEJM 2003 www.nejm.org

10/24/2008 149 • http://en.wikipedia.org/wiki/SARS

SARS is a novel coronavirus. An art model of CoV, modified from Dr. Kathryn. V. Holmes [N Engl J Med. 2003; 348(20):1948-51] by Prof. Yi Xue LI and Ye CHEN of Bioinformation Center, Shanghai Institutes for Biological Sciences, CAS.

10/24/2008 150 Hantavirus

10/24/2008 151 Hantavirus Pulmonary Syndrome (HPS)

• An outbreak of unexplained illness occurred in May 1993 an area of the Southwest shared by NM, AZ, CO, and UT (Four Corners). – A number of previously healthy young adults suddenly developed acute respiratory symptoms; about half soon died. – A hantavirus, which is transmitted by rodents, was suspected. – The virus named Sin Nombre virus (SNV) and its principal carrier, the deer mouse were positively identified. • A "bumper crop" of rodents there, due to heavy rains during the spring of 1993. • Determined that person to person transmission of SNV was unlikely. • SNV had actually been present, but unrecognized, at least as early as 1959. • Since the discovery in 1993, hantavirus pulmonary syndrome (HPS) has been identified in over half of the states of the U.S.

10/24/2008 152 10/24/2008 153 Ebola Virus • Ebola hemorrhagic fever (Ebola HF) is a severe, often-fatal disease in humans and nonhuman primates (monkeys, gorillas, and chimpanzees) that has appeared sporadically since its initial recognition in 1976. • The disease is caused by infection with Ebola virus, named after a river in the Democratic Republic of the Congo (formerly Zaire) in Africa, where it was first recognized. The virus is one of two members of a family of RNA viruses called the Filoviridae. • There are five identified subtypes of Ebola virus. Four of the five have caused disease in humans: Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast and Ebola-Bundibugyo. The fifth, Ebola-Reston, has caused disease in nonhuman primates, but not in humans.

The incubation period for Ebola HF ranges from 2 to 21 days. The onset of illness is abrupt and is characterized by fever, headache, joint and muscle aches, sore throat, and weakness, followed by diarrhea, vomiting, and stomach pain. A rash, red eyes, hiccups and internal and external bleeding may be seen in some patients.

10/24/2008 154 Nipah Virus

• Nipah virus, also a member of the family Paramyxoviridae, is related but not identical to Hendra virus. Nipah virus was initially isolated in 1999 upon examining samples from an outbreak of encephalitis and respiratory illness among adult men in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Penninsula where pig farmers became ill with encephalitis.

• 265 patients with viral encephalitis, 105 died (40% case fatality rate)

• From bat reservoir: – 1994 – Hendra virus – 1997 – Australian Lyssavirus – 1997 – Menangle virus – 1999 – Nipah virus – 2004 – SARS-like CoV

10/24/2008 155 Hendra Virus • Hendra virus (formerly called equine morbillivirus) is a member of the family Paramyxoviridae. The virus was first isolated in 1994 from specimens obtained during an outbreak of respiratory and neurologic disease in horses and humans in Hendra, a suburb of Brisbane, Australia.

• The natural reservoir for Hendra virus is thought to be flying foxes (bats of the genus Pteropus) found in Australia. The natural reservoir for Nipah virus is still under investigation, but preliminary data suggest that bats of the genus Pteropus are also the reservoirs for Nipah virus in Malaysia.

• In Australia, humans became ill after exposure to body fluids and excretions of horses infected with Hendra virus. In Malaysia and Singapore, humans were infected with Nipah virus through close contact with infected pigs.

10/24/2008 156 African Trypanosomiasis

10/24/2008 157 African Trypanosomiasis

• Called Sleeping Sickness, vector is the tsetse fly

• Classical example of an emerging infection, 1890-1930

• Leading public health problem in Africa during that time, colonialism brought it to new areas

• Nearly eliminated by 1960 using population screening, case treatment, chemoprophylaxis

• Re-emerging infection in central Africa

10/24/2008 158 African Trypanosomiasis, cont.

West African East African

Agent: T. brucei gambiense T. brucei rhodesiense Vector: riverine tsetse fly savanna tsetse fly Distribution: west/central Africa east/south Africa Reservoir: human antelope/cattle Disease: chronic (years) rapid progression: 1-4 weeks Mortality: 100% 100% At risk: rural persons rural, visitors to game reserves

10/24/2008 159 10/24/2008 160 10/24/2008 161 Problems Estimating Disease Burden

• 60 million people at risk, but <2 million screened

• No health facilities in many areas at risk

• Conflict or insecurity in epidemic foci

• Outbreaks in 2004 reported in DRC, Angola

• Clinical diagnosis is difficult until late in disease -intermittent fever -lymph node swelling -headaches and sleep disturbance -weight lose (they look like AIDS) -lab diagnosis is hard (antigenic variation)

10/24/2008 162 Prevalence of trypanosomiasis

• In 1986, WHO est. that 70 million people lived in transmission areas. • • In 1998, 40,000 cases were reported, but it was estimated that 300,000 to 500,000 cases were undiagnosed.

• Villages in the Congo, Angola, and Sudan, prevalence has reached 50%.

• By 2005, surveillance had been reinforced and new cases dropped.

• 1998-2004 cases fell from 40,000 to 18,000.

• The estimated cases is currently between 50,000 and 70,000.

10/24/2008 163 Management of Trypanosomias

Disease management in three steps:

1) Screening for potential infection. Serological tests and/or checking for swollen cervical glands.

2) Diagnosis shows whether the parasite is present.

3) Staging to determine the disease progression. Examination of cerebro-spinal fluid by lumbar puncture

10/24/2008 164 Treatments for Trypanosomias

First stage treatments:

Pentamidine: discovered in 1941, used against T.b. gambiense. Despite a few undesirable effects, it is well tolerated by patients.

Suramin: discovered in 1921, used against T.b. rhodesiense. Effects in the urinary tract and allergic reactions.

Second stage treatments:

Melarsoprol: discovered in 1949, used against both forms. Arsenic derivative with many side effects. Fatal encephalopathy (3% to 10%). 1997 resistance up to 30%.

Eflornithine: was registered in 1990. Only effective against T.b. gambiense. Less toxic alternative to melarsoprol, but the

10/24/2008regimen is strict and difficult to apply. 165 Tuberculosis

10/24/2008 166 Tuberculosis (TB)

TB is not on the decline. One third of the world's population is infected with TB – In 1999 TB caused 8,000 deaths/day – 7- 8 million people become infected with TB/year – 5-10 % of these people will develop active TB – Between 1993 and 1996, TB increased 13 % – TB accounts for more than 1/4 of all preventable adult deaths the developing world. Someone is newly infected with TB every second ! – TB is the leading killer of women – TB outranks all causes of maternal mortality – TB creates more orphans than any other infectious disease – TB is the leading cause of death among HIV-positive individuals

10/24/2008 167 Global Prevalence of TB cases (WHO)

10/24/2008 168 Tuberculosis

10/24/2008 169 10/24/2008 170

Tuberculosis Control

• Challenges for tuberculosis control – MDR-TB - In most countries. About 450000 new cases annually. – XDR-TB cases confirmed in South Africa. – Weak health systems – TB and HIV

• The Global Plan to Stop TB 2006-2015. – an investment of US$ 56 billion, a three-fold increase from 2005. The estimated funding gap is US$ 31 billion. – Six step strategy: Expanding treatment; Health Systems Strengthening; Engaging all care providers; Empowering patients and communities; Addressing MDR TB, Supporting research

10/24/2008 171 Tuberculosis Transmission

• Caused by Mycobacterium tuberculosis

• Spread by: - Airborne route - Droplet nuclei • Affected by: – Infectiousness of patient – Environmental conditions – Duration of exposure

• Most persons exposed do not become infected

10/24/2008 172 First-Line Treatment of Tuberculosis for Drug-Sensitive TB

10/24/2008 173 Pathogenesis - Latent M.tuberculosis Infection

• Inhaled droplet nuclei with M. tuberculosis : - Reach alveoli - Are taken up by alveolar macrophages - Reach regional lymph nodes - Enter bloodstream and disseminate

• Chest radiograph may have transient abnormalities

• Specific cell-mediated immune response controls further spread

10/24/2008 174 Summary

10/24/2008 175 • Why do there seem to be more emerging and re-emerging diseases in the past few decades?

• One reason is certainly better detection, monitoring and surveillance systems….

• Another set of reasons may be the changes that have happened in the recent past………….

10/24/2008 176 Why are there more emerging or re-emerging diseases?

1. Human demographics and behavior 2. Technology and Industry 3. Economic development and land use 4. International travel and commerce 5. Microbial adaptation and change 6. Breakdown of public health measures 7. Human vulnerability 8. Climate and weather 9. Changing ecosystems 10. Poverty and social inequality 11. War and famine 12. Lack of political will 13. Intent to harm

10/24/2008 177 1. Human demographics and behavior

• More people, more crowding an aging population in many parts of the world (high AIDS infections rates change that age distribution) • Changing sexual mores (HIV, STDs) • Injection drug use (HIV, Hepatitis C) • Changing eating habits: out more, more produce (food-borne infections) • More populations with weakened immune system: elderly, HIV/ AIDS, cancer patients and survivors, persons taking antibiotics and other drugs • More children in daycare (infection spread)

10/24/2008 178 2. Technology and Industry

• Mass food production (Campylobacter, E.coli O157:H7, etc…)

• Use of antibiotics in food animals (antibiotic-resistant bacteria)

• More organ transplants and blood transfusions (Hepatitis C, WNV,…)

• New drugs for humans (prolonging immuno-suppression)

• People live longer but then have weakened immune systems

• Water and food supply systems larger and more complex and prone to “single site of failure”

• Industrial pollution (TB)

10/24/2008 179 3. Economic development and land use

• Changing ecology influencing waterborne, disease transmission (e.g. dams, deforestation)

• Contamination of watershed areas by cattle (Cryptosporidium)

• More exposure to wild animals and vectors (Lyme disease, erhlichiosis, babesiosis, HPS,…)

• Logging in rain forest exposes workers to new vectors

• New standing water from construction (mosquito and other vectors increase)

• Some developments (Aswan High dam in Egypt) lead to higher infection rates (Schistosomiasis) – reforestation in the US has led to increase in Lyme disease

10/24/2008 180 4. International travel and commerce

• Persons infected with an exotic disease anywhere in the world can be into major US city within hours (SARS)

• 400 million people a year travel internationally. Circumnavigation of the world used to take 365 days, now 36 hours – quarantine of travellers is not feasible.

• Foods from other countries imported routinely into other countries (Cyclospora,….)

• Cruise ship travel (single source epidemics)

• Transportation of food products very widespread and facilitates spread of vectors and carriers. Vectors hitchhiking on imported products (Asian tiger mosquitoes on lucky bamboos,….)

10/24/2008 181 Speed of Global Travel in Relation to World Population Growth

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10/24/2008 182 5. Microbial adaptation and change

• Increased antibiotic resistance with increased use of antibiotics in humans and food animals (VRE, VRSA, penicillin- and macrolide- resistant Strep pneumonia, multidrug-resistant Salmonella,….)

• Many patients making antibiotics do NOT complete the full course of treatment – leads to resistant microorganisms

• In the US it is estimated that 30% of antibiotic prescriptions are for diseases that are viral or willl not respond to anti-bacterial antibiotics (Why do doctors still prescribe them?)

• Increased virulence (Group A Strep?)

• Jumping species from animals to humans (avian influenza, HIV?, SARS?)

• New (or previously unknown) organisms can be produced by contacts between microorganisms

10/24/2008 CDC From: Murphy and Nathanson. Semin. Virol. 5, 87, 1994 183 EmergingEmerging Vancomycin-resistant Vancomycin-resistant Enterococcal Enterococcal Infections* Infections*

25 ICU 20 Non-ICU

Resistant 10 % 5

0 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

* in U.S. NNIS Hospitals 10/24/2008 CDC184 6. Breakdown of public health measures

• Lack of basic hygienic infrastructure (safe water, safe foods, etc..)

• Inadequate vaccinations (measles, diphtheria)

• Discontinued mosquito control efforts (dengue, malaria)

• Lack of monitoring and reporting (SARS)

• Lack of basic medical facilities in many parts of the world (the Ebola outbreak in Kitwit continued with high mortality for weeks or months before anyone outside heard about it – many victims were medical personnel)

10/24/2008 185 7. Human vulnerability Increased vulnerability with malnutrition or water shortages

Decreased immunity with many other infections (eg AIDS)

Increased number of immuno-compromised and elderly patients

10/24/2008 186 8. Climate and Weather

• With increased global temperature (global warming or global climate change) there will be increased rainfall that will:

» increase breeding grounds for mosquitoes » increase vegetation and rodent numbers » increase runoff into reservoirs (with contamination a likely result)

• Higher ocean temperatures may stimulate growth of Vibrio spp.

• And many other possibilities……………………..

10/24/2008 187 9. Changing ecosystems

• Ecological or ecosystem changes can alter the pattern of distribution of both pathogens and vectors (of the 10 emerging diseases targeted by the WHO, 7 have arthropod vectors)---- Malaria in Canada?

• It can also alter human or animal distribution as populations migrate

• Destruction of rainforest can increase humidity

• Urban development can increase particulate matter and temperatures in the area.

10/24/2008 188 10. Poverty and social inequality

• Mortality from infectious diseases is very closely linked with income level

• Lower income levels correlate with: • Lack of clean water and sanitation • Poor housing • Lack of access to medical treatment • Lack of transportation • Exposure to higher pollutant levels (often, but not always in rural environments)

• The lowest income group is increasing the fastest

10/24/2008 189 11. War and famine

• About 1% of the worlds population are war refugees • They are exposed to new, often poor conditions and microorganisms and disease vectors. • Famine and war are often closely linked (of 16 food emergencies in 2001, 9 were linked to civil unrest)

10/24/2008 190 12. Lack of political will

• A global political commitment is difficult to achieve – but the Millenium Declaration of the countries of the UN is a start.

• Long-term commitments (10 to 20 years) required to solve many of these problems are difficult for most governments with a 3 to 5 year lifetime before elections.

• Also needs long-term commitment from donors, governments, health care professionals and patients.

• Development of new treatments and antibiotics for the most common developing world diseases (AIDS, malaria, etc) is not as profitable as for developed world “diseases” such as heart conditions, depression and cancer.

10/24/2008 191 13. Intent to harm

• Bioterrorism: mailings of “weaponized” Anthrax in US 2001

• Bio-Crimes: Salmonella in OR, Shigella in TX (deliberate contamination of food)

• Potential agents: Smallpox, Anthrax. Botulism toxin, Plague, Tularemia, and others ….

Aum Shinrikyo (responsible for the Sarin nerve gas attack on the Tokyo subway) had tried botulinum toxin, anthrax and had sent people to Zaire to get Ebola virus.

10/24/2008 192 Prevention of Emerging Infectious Diseases Will Require Action in Each of These Areas

§ Surveillance and Response

Detect, investigate, and monitor emerging, the diseases they cause, and the

factors influencing their emergence, and respond to problems as they are

identified.

§ Applied Research

Integrate laboratory science and epidemiology to increase the effectiveness

of public health practice.

CDC

10/24/2008 193 § Infrastructure and Training

§ Strengthen public health infrastructures to support

surveillance, response, and research and to implement

prevention and control programs

§ Provide the public health work force with the knowledge

and tools it needs.

§ Prevention and Control

§ Ensure prompt implementation of prevention strategies

and enhance communication of public health information

about emerging diseases

10/24/2008 194 Sources of Information and slides:

• Center for Disease Control – www.cdc.gov • Louis G. DePaola, DDS, MS Dental School, University of Maryland • Duc J. Vugia, M.D., M.P.H. Division of Communicable Disease Control, California Department of Health Services • WHO – http://www.who.int/en/

10/24/2008 195 Other Effects of Emerging Diseases:

Example –

The decline of Gyps species vultures in India feeding on cattle carcasses Avian Flu and the consequent increase in feral dog populations.

10/24/2008 196 10/24/2008 197 1992

10/24/2008 1992

10/24/2008 1990 2001

10/24/2008 2000 2001

10/24/2008 201 The End

10/24/2008 202 10/24/2008 203 Appendix

Potential Bioterrorism Agents

10/24/2008 204 Complete List of Potential Bioterrorism Agents from the Center for Disease Control, Atlanta, Georgia, USA From: http://emergency.cdc.gov/agent/agentlist.asp

• Anthrax (Bacillus anthracis) • Arenaviruses • Bacillus anthracis (anthrax) • Botulism (Clostridium botulinum toxin) • Brucella species (brucellosis) • Brucellosis (Brucella species) • Burkholderia mallei (glanders) • Burkholderia pseudomallei (melioidosis) • Chlamydia psittaci (psittacosis) • Cholera (Vibrio cholerae) • Clostridium botulinum toxin (botulism) • Clostridium perfringens (Epsilon toxin) • Coxiella burnetii (Q fever) • Ebola virus hemorrhagic fever • E. coli O157:H7 (Escherichia coli) • Emerging infectious diseases such as Nipah virus and hantavirus • Epsilon toxin of Clostridium perfringens 10/24/2008 205 Complete List of Potential Bioterrorism Agents from the CDC

• Escherichia coli O157:H7 (E. coli) • Food safety threats (e.g., Salmonella species, Escherichia coli O157:H7, Shigella) • Francisella tularensis (tularemia) • Glanders (Burkholderia mallei) • Lassa fever • Marburg virus hemorrhagic fever • Melioidosis (Burkholderia pseudomallei) • Plague (Yersinia pestis) • Psittacosis (Chlamydia psittaci) • Q fever (Coxiella burnetii) • Ricin toxin from Ricinus communis (castor beans) • Rickettsia prowazekii (typhus fever) • Salmonella species (salmonellosis) • Salmonella Typhi (typhoid fever) • Salmonellosis (Salmonella species)

10/24/2008 206 Complete List of Potential Bioterrorism Agents from the CDC

• Shigella (shigellosis) • Shigellosis (Shigella) • Smallpox (variola major) • Staphylococcal enterotoxin B • Tularemia (Francisella tularensis) • Typhoid fever (Salmonella Typhi) • Typhus fever (Rickettsia prowazekii) • Variola major (smallpox) • Vibrio cholerae (cholera) • Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]) • Viral hemorrhagic fevers (filoviruses [e.g., Ebola, Marburg] and arenaviruses [e.g., Lassa, Machupo]) • Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum) • Yersinia pestis (plague)

10/24/2008 207