Nosocomial Infections in U.S.

Result of treatment in a hospital or a healthcare service unit, but secondary to the patient's original condition

Centers for Disease Control and Prevention (CDC) projections for 2007
1 of 22 patients would get a nosocomial infection 1.7 million cases a year 99,000 would die

59th Annual Clinical Laboratory Science Convention May 8 10, 2007

Emerging Infectious Diseases

Edward S. Balkovic, Ph.D.
QC Microbiology Technical Support Genzyme Corporation Framingham, MA ed.balkovic@genzyme.com

Objectives
Historical Overview Factors for disease emergence Specific Examples

Key References
Armies of Pestilence
Author: R. S. Bray Barnes & Noble Book, New York, NY (1996)

Man and Microbes: Disease and Plagues in History & Modern Times
Author: Arno Karlen G.P. Putnam Books, New York, NY (1995)

Plagues and Peoples

Author: William H. Neill Doubleday, New York, NY (1976)

Infections in the Pre-antibiotic Era

Infections were the major cause of death and disabilities in the U.S. until mid-20th century Smallpox, tuberculosis, diphtheria, cholera, plague, polio, mumps, measles, typhoid, scarlet, and rheumatic fever Life expectancy in the U.S. with birth in 1900: - 45 years male - 47 years female
Elderly population (65+) was 3-4% of the total population

Factors in the Reduction of Mortality due to Infectious Diseases Antisepsis

Antibiotics Immunization Sanitation Public Health

Impact
Reduced childhood mortality

Life expectancy in the U.S. with birth in 2000:

- 74 years male - 79 years female Elderly population (65+) - 13% of the population (36 million) Life expectancy at 65+ and 75+ males females 65+ 15 yrs 19 yrs 75+ 9 yrs 14 yrs

Current Top Causes for Death in U.S.

1) Heart Disease 2) Cancer 3) Stroke

4) Pneumonia

Are We Making Progress to Eliminate Infectious Microbes?

Antimicrobials
Control symptoms Destroy organisms Eradicate diseases

Weve prematurely claimed victory before

Its time to close the book on infectious diseases, declare the war against pestilence won, and shift national resources to such chronic problems as cancer and heart disease. Surgeon General William H. Stewart
1967
Sources: World Health Organization. WHO Report on Global Surveillance of Epidemic-prone Infectious Disease. Geneva: WHO, 2003. Emerging Crisis in Infectious Diseases: Challenges for the 21st Century. The Pfizer Journal. 2004;5:2.

Five Distinct Threats Have Emerged and Infectious Diseases Remain a Dominant Cause of Death
1. Resurgence of endemic diseases (developing world) 4. New/emerging infections 5. Threat of bioterrorism

2.
3.

Growing link between microbes and chronic diseases Drug-resistant microbes

Infectious Diseases Caused 26% of Global Deaths in 2002

Respiratory infections HIV/AIDS Diarrhea Tuberculosis Malaria 4.0 million 2.8 million 1.8 million 1.6 million 1.3 million

Source: Emerging Crisis in Infectious Diseases: Challenges for the 21st Century. The Pfizer Journal. 2004;5:2.

Costs of Infectious Diseases in the US

Costs of common infectious diseases can be broken into: - direct costs such as treatment - indirect costs like lost work due to death or disability Disease
Intestinal infections Food Borne diseases S.T.Ds. (excluding AIDS) Influenza

Estimated Costs
$23 billion total $5-6 billion total $5 billion in direct costs $5 billion in direct costs + $12 billion in indirect costs $ 4 billion in direct costs

Antibiotic Resistant bacteria

Infectious Disease Mortality in the United States, 1980-1996

80 70

Crude ID Mortality Rate Deaths per 100,000 population

60 50 40

30
20 10 0

Year
Source: JAMA 1996;275:189-193 and unpublished CDC data

Definition of Emerging Infections:

New, re-emerging, or drug resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future. - Institute of Medicine, 1992

Why are we concerned about Emerging Infectious Diseases?

Pose a threat to all persons regardless of age, sex, lifestyle, ethnic background, or socioeconomic status
Cause suffering and death Impose a financial burden on society

Factors of Emergence
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Microbial adaptation and change Human Demographics and Behavior International Travel and Commerce Economic Development and Land Use Technology and Industry Breakdown of public health measures Human susceptibility to infection Climate and Weather Changing Ecosystems Poverty and Social Inequality War and Famine Lack of Political Will Intent to Harm

Board on Global Health (BGH) and the Institute of Medicine (IOM)

1. Microbial Adaptation and Change

Number of microbes utilizing different genetic mechanisms - genome sequences show that lateral transfer is common - high mutation rates in RNA viruses-rapid adaptation - quick reproduction so rare mutations build up rapidly Antimicrobials for livestock growth enhancement and over prescription of antimicrobials by Drs. (convenience) - evolve modifying enzymes and drug pumps Superbugs Streptococcus - penicillin Staphylococcus - vancomycin Tuberculosis - isoniazid Malaria - chloroquine

2. Human Demographics and Behavior

Increases in the human population, even in the U.S. Increased movements Urbanization - more people concentrated in cities - often without adequate infrastructure

Increases in the elderly populations

Increases in children in daycare - working woman with kids under 5: 30% in 1970 75% in 2000 Fast paced Lifestyles - increase in convenience items and more stress High-risk behavior - Drug use and unprotected sex

Migration

FROM: Martin Cetron - EID Conference 2002

3. International Travel and Commerce

365 days to circumnavigate the globenow it takes 36 hrs - used to quarantine ships, but 36 h faster than disease incubation 400 million people per year travel internationally increased incidence of both Tuberculosis and Influenza transmission on long flights Transportation of products is an increased concern - rapid transport of disease harboring fresh produce - transport of livestock facilitates movements of viruses and arthropods (especially ticks) Increases in Cruise ship travel

4. Economic Development and Land Use

Consumption of natural resources, deforestation, and dam building Logging in the rain forest has exposed people to new viruses Historic example - emergence of Yellow Fever when humans entered the Central American jungle to build the Panama Canal New standing water from dam building, canalization, and irrigation

Historic example - Aswan dam increases rates of Schistosomiasis in Egypt

Reforestation in some parts of North America has caused the emergence of Lyme disease in those areas

5. Technology and Industry

Advances in Technology - most changes are positive but Medical technology - people living longer, but have weaker immune systems - blood transfusions and organ transplants save lives, but can cause infections - implanting parts causes biofilm growth Transportation technology - ability to rapidly move people and goods Industrial Changes - mass production of food now we all get our water and food from the same sources Industrial Pollution - increases incidence of TB

6. Breakdown of Public Health

Late 1970s- IMF and World Bank forced reductions in public sector investment, especially in Latin America and Africa

Debate over whether this had a negative impact on public health - bank has shown that these countries are economically better off - other side says, the reduction in public health sector caused immunization levels, nutrition, and medical supplies to drop
Similar reduction in public health funding occurred in the US. - reduction in programs for disease prevention and surveillance Lack of diagnosis and treatment in many areas of the world -In Democratic Republic of the Congo, Ebola outbreak high mortality before there help sent

7. Human Susceptibility to Infection

Impaired Host Immunity - AIDS - Increases in the older population Genetic Polymorphisms
Malnutrition - host susceptibility is aggravated

8. Climate and Weather

Global warming? - climatologists project temps to increase up to 5.8C by 2100 Elevated rainfall - creates new breeding habitats for mosquitoes - decreases salinity which can increase toxic bacteria - increases vegetation which increases rodents (1993 Hanta virus outbreak) - increases runoff into drinking reservoirs (1993 Cryptosporidiosis outbreak)

Higher ocean temps increase Vibrio parahaemolyticus (shellfish)

Some soil pathogens carried by dry dusty winds (Coccidiodes)

9. Changing Ecosystems
Ecological changes can increase the risk of infection by altering human exposure or pathogen distribution Rainforest destruction - forests reduce while cropping increases humidity Urban development increases atmospheric particles and increases air temperatures Of the 10 EID targeted by WHO, 7 have arthropod vectors

10. Poverty and Social Inequality

Mortality from infectious diseases more closely than ever correlates with income - developing and former communist bloc countries Factors: malnutrition, lack of clean water and sanitation, poor housing, ignorance of risky behaviors (including absence of social agencies to teach), lack of transportation, lack of funds for out-of-pocket expenses Population of the poorest is increasing the fastest

11. War and Famine

War refugees are a full 1% of the global population

War refuges are forced onto new areas where they are exposed to new microbes from vectors and people War and famine are closely linked
In 2001, tracking 16 countries with food emergencies, showed that 9 were because of civil unrest Famine is also caused by social, economic, and political forces

12. Lack of Political Will

A global political commitment is rather vague

- Who will be the parties in a global social contract? - How is their will determined? - How can the liberties of individual countries be balanced against collective responsibility? - Is there collective responsibility?
Must have commitment from 4 groups: donors, health care professionals, country authorities, and patients Do developing world diseases matter to politicians here?

13. Intent to Harm - Bioterrorism

Even before 2001, some recognized the threat

1972 - Biological Weapons Convention (BWC) treaty prohibited the possession, stockpiling, and use, BUTit had nothing for monitoring, inspection, or enforcement
U.S. abandoned its biological warfare program in 1969, BUT Soviet Union kept its program up after signing the BWC, U.S. did not find this out until the mid-1990s Aum Shinrikyo (Japanese cult) had also experimented with botulin, anthrax, and sent teams to Zaire for Ebola

Examples of Emerging & Re-emerging Infectious Diseases

Avian Flu

AS Fauci NIAID / NIH

The Big Three for ID

Disease
Malaria
Tuberculosis

Microbe
Plasmodium
M. tuberculosis

Cases (Annual) 300-500 million 8 million 5 million

Cases (Total) 300-500 million 2 billion

Deaths (Annual) 1 million 2 million

AIDS

HIV

40 million 3.1 million

Role of Infectious Diseases in the Creation of Chronic Diseases Is Becoming Clearer

Stomach Cancer: 555,000 new cases per year due to Helicobacter pylori Cervical Cancer: increased risk due to human papilloma virus

Liver Cancer: 8 in 10 cases due to Hepatitis B or C

Hodgkins Disease: can be caused by Epstein-Barr virus Atherosclerosis: Chlamydia pneumoniae may contribute to its progression
Sources: American Society for Microbiology. New and Reemerging Infectious Diseases: A Global Crisis and Immediate Threat to the Nations Health, The Role of Research. Washington, D.C.: ASM, 1997. Cited in Emerging Crisis in Infectious Diseases. Volume 70: Epstein-Barr virus and Kaposis sarcoma herpesvirus/human herpesvirus 8. IARC monographs on the Evaluation of Carcinogenic Risks to Humans. 1997. Cited in Emerging Crisis in Infectious Diseases. Bahrmand AR, Bahadori M, et al. Chlamydia pneumonia DNA is more frequent in advanced than in mild atherosclerosis lesions. Scand J Infect Dis. 2004;36:119-123. Cited in Emerging Crisis in Infectious Diseases.

Examples of Human Pathogens Emerging via Species Jump

Pathogen Ebola virus Escherichia coli O157:H7 Borrelia burgdorferi HIV-1 HIV-2 Hendra virus vCJD Australian bat lyssavirus Original host Bats(?) Cattle Rodents(?) Chimpanzees Primates Bats Cattle Bats Year reported 1977 1982 1982 1983 1986 1994 1996 1996

H5N1 influenza A virus Nipah virus SARS coronavirus

Chickens Bats Palm civets(?)

1997 1999 2003

FROM: Mark E. J. Woolhouse - ASM Microbe Magazine / November 2006

Accumulation of Newly Reported Human Pathogens since 1980

FROM: Mark E. J. Woolhouse - ASM Microbe Magazine / November 2006

Emerging Infectious Diseases in the News

Specific Agents

The Next Influenza Pandemic?

Avian FLU

Timeline of Emergence of Influenza A Viruses in Humans

Asian Influenza Spanish Influenza

Hong Kong Influenza

H1

Russian Influenza

H3 H2
1998/9
1957 1968 1977 1997 2003

H1
1918

Flu Pandemics Worldwide Epidemics

Potential for Future Influenza Pandemics

H1,H2,H3

Timeline of Emergence of Influenza Viruses in Humans

Avian Influenza

H9 H5
Russian Influenza

H7 H5

Asian Influenza Spanish Influenza

Hong Kong Influenza

H1

H3

H1
1918

H2
1998/9 1957 1968 1977 1997 2003

Regular vaccines

Pandemic vaccines

Cycle of Avian Influenza Viruses in Animals & Humans

Direct bird to human transmission also possible

Domestic birds

Natural avian influenza cycle

Shore birds Waterfowl

Pandemic disease cycle

Mammals (primarily swine)

Humans

WHO confirmed Human Cases (H5N1) thru 4/11/2007

Total Cases: 291 Deaths: 172 (59%)

From: Washington Post 08/30/06

Influenza Pandemic of 1918-1919

Results of 1918 Influenza Pandemic

Died 500,000 in United States / ~20 million U. S. cases
Total U.S. population in 1918: ~100 million (2005: ~300 million)

Estimated 20 - 40 million people died worldwide Up to 100 million died?

Almost 1 billion ill (1/2 of worlds population)

Now you can see why your mother told you to cover your mouth and nose when you sneeze or cough

Sneeze - millions of tiny droplets of water & mucus expelled ~200 miles / hr. Sneeze with your mouth uncovered - aerosols (with mucus, saliva and virus) can float around in the air ~10 meters in distance.

Medium-Scale Flu Pandemic ??

(without vaccine or drugs)

United States 20 - 50 million cases 300 700 K serious cases

Worldwide

20 50% of pop. affected

2 50 million deaths
Source: WHO

90 200 K deaths
Source: CDC

Annual Impact of Influenza in U.S.

(~42K auto deaths / ~16K murders) 36,000 deaths 200,000 or more hospitalizations 17 - 50 million people infected 70 million missed work days 38 million missed school days $3 - 15 billion in direct & indirect costs
Sources: CDC, NTSB, FBI

Treatment & Prevention

2006

1918

Treatment
Binding to neuraminidase

Tamiflu

Relenza

2006 2007 Influenza Vaccine Formulation

One virus from last years vaccine: A/New Caledonia/20/99 (H1N1)-like

Two new viruses:

A/Wisconsin/67/2005 (H3N2)-like virus B/Malaysia/2506/2004-like virus

Sanofi Pasteur

Chiron

MedImmune

GSK

2007 2008 Influenza Vaccine Formulation

Two viruses from 2006 -2007 vaccine: A/Wisconsin/67/2005 (H3N2)-like virus B/Malaysia/2506/2004-like virus One new virus: A/Solomon Islands/3/2006 (H1N1)-like
Sanofi Pasteur

Chiron

MedImmune

GSK

FDA Licenses First Avian Flu Vaccine for Humans 4/17/07

Not for public sale

Vaccine purchased by federal government for inclusion within the National Stockpile for distribution by public health officials, if needed

Monovalent Avian Influenza Virus Vaccine

WHO Stages of Pandemic Influenza

Stages of Pandemic Influenza We are currently in Stage 3
Inter-pandemic phase New virus in animals, no human cases
Low risk of human cases

1 2 3

Higher risk of human cases No or very limited human-to-human transmission Evidence of increased human-to-human transmission Evidence of sustained human-to-human transmission Efficient and sustained human-to-human transmission

Pandemic alert
Pandemic alert

4
5 6

NewNew virus causes human cases virus causes human cases

Pandemic

Bird Flu Fears are Overblown

I have a bunch of patients coming in here who are more worried about bird flu than they are about heart disease. The fear is out of proportion to the current risk
Marc Siegel, MD Internist & Assoc Prof, NYU School of Medicine

One migratory bird does not a pandemic make

Anthony Fauci, MD - Director National Institute Allergies & Infectious Diseases / NIH

Pandemic Preparedness
"The pandemic clock is ticking;
we just dont know what time it is."
Edgar Marcuse, MD

Chairman, National Vaccine Advisory Committee 1994-1998

1918

BREAK - TIME

We will start again in 15 minutes

Whooping cough outbreak at hospital waning No new cases discovered at St. Vincent after Sept. 30
Lee Hammel TELEGRAM & GAZETTE STAFF - Oct 19, 2006 Stephen Smith, Boston Globe Staff & CBS4Boston.com | November 2006

St. Vincent Hospital in Worcester, an outbreak in September infected 30 staff members Officials believe a gastrointestinal surgeon who is a military reservist contracted the disease while on duty in California and unknowingly carried it into the hospital While doctors are required to report whooping cough to officials promptly, the city has no record of the cases at St. Vincent Hospital being reported until Sept. 28, three weeks after the hospital confirmed them UMass Memorial Health Care diagnoses two cases in a typical month at its Memorial and University campuses Canadian study had shown that healthcare workers are 1.7 times more likely than the general public to suffer from whooping cough, increase attributed to contact with infected patients

Whooping cough outbreak strikes 25 at Children's

Stephen Smith, Boston Globe Staff & CBS4Boston.com | November 2006

At least one young patient and 25 staff members at Children's Hospital Boston have been diagnosed with whooping cough Sixty other staff members at Children's have symptoms of the bacterial illness and are undergoing blood tests Workers sent home until finish a five-day course of the antibiotic azithromycin 19-month-old boy admitted Sept. 21 with a fever, cough, and wheezing. Initially diagnosed with respiratory syncytial virus, but because of worsening symptoms, he was sent to intensive care and subsequently diagnosed with whooping cough Outbreak radiated outward, infecting nurses, clinical assistants, and administrative staff members Child recovered - none of hospital workers seriously ill

Pertussis a.k.a. Whooping Cough

Highly communicable respiratory disease >90% susceptible household contacts may contract it Significant morbidity in all ages
Most severe effects in infants Human adolescents and adults are reservoir

PertussisUnited States, 1940-2005*

250000 200000 150000 100000 50000 0 1940

Cases

1950

1960

1970

1980

1990

2000

Year

PertussisUnited States, 1980-2005*

30000 25000 20000

Cases

15000 10000 5000 0 1980

1985

1990

1995

2000

2005

Year

Pertussis US Age Demographics

Age Groups (Years) <1 1-4 5-9 10-19 >15 >20 United States (1978-81) 53.5 26.5 8.2 5.4 6.5 United States (1997-2000) 29.4 11.1 9.8 29.4
20.4

Reported Pertussis by Age Group 1980-2004*

No. of Reported Cases
20000 15000 10000 5000
< 11 yrs 19 yrs

1118 yrs

0 1990

1995

2000

Year

Pertussis Whats going On?

The Problem Immunity following pertussis infection or vaccination is not lasting Immunity wanes after 5-10 years Low level prevalence of pertussis in community Revaccination of adolescents and adults with aP not recommended
Severe side effects

The Solution

Provisional ACIP Recommendations for Tdap Vaccines

Adolescents 11-18 years of age should receive a single dose of Tdap instead of Td, preferably at 11-12 years of age* Adults should receive a single dose of Tdap to replace a single dose of Td* Adults who have or who anticipate having close contact with an infant 12 months of age or younger (e.g., parents, child care providers, healthcare providers) should receive a single dose of Tdap* Any woman who might become pregnant is encouraged to receive a single dose of Tdap
*if the person has completed the recommended childhood DTaP/DTP vaccination series

E. coli O157:H7

E. coli O157:H7 in bagged Spinach

California cow

Sept. 2006

E. coli O157:H7
4 recognized classes of enterovirulent E. coli (collectively referred to as EEC group) that cause gastroenteritis in humans enterohemorrhagic (EHEC) strain designated E. coli O157:H7 E. coli serotype O157:H7 - rare variety of E. coli produces large quantities of one or more related, potent toxins that cause severe damage to the lining of the intestine Toxins [verotoxin (VT), shiga-like toxin] are closely related or identical to the toxin produced by Shigella dysenteriae

E. coli O157:H7
Hemorrhagic colitis acute disease
severe cramping (abdominal pain) and diarrhea which is initially watery but becomes grossly bloody. Occasionally vomiting occurs. Fever is either low-grade or absent. Illness is usually self-limited and lasts for an average of 8 days Some individuals exhibit watery diarrhea only. Infective dose -- Unknown, may be similar to that of Shigella spp. (as few as 10 organisms)

Hemolytic uremic syndrome (HUS)

particularly in very young renal failure and hemolytic anemia 0 to 15% of hemorrhagic colitis victims may develop HUS can lead to permanent loss of kidney function In elderly, HUS, plus two other symptoms, fever and neurologic symptoms, constitutes thrombotic thrombocytopenic purpura (TTP) Can have mortality rate in the elderly as high as 50%

Hemorrhagic colitis associated with a rare Escherichia coli serotype

LW Riley, RS Remis, SD Helgerson, HB McGee, JG Wells, BR Davis, RJ Hebert, ES Olcott, LM Johnson, NT Hargrett, PA Blake, and ML Cohen New England Journal of Medicine Volume 308:681-685 March 24, 1983

Abstract

We investigated two outbreaks of an unusual gastrointestinal illness that affected at least 47 people in Oregon and Michigan in February through March and May through June 1982. The illness was characterized by severe crampy abdominal pain, initially watery diarrhea followed by grossly bloody diarrhea, and little or no fever. It was associated with eating at restaurants belonging to the same fast-food restaurant chain in Oregon (P < 0.005) and Michigan (P = 0.0005) and with eating any of three sandwiches containing three ingredients in common (beef patty, rehydrated onions, and pickles). Stool cultures did not yield previously recognized pathogens. However, a rare Escherichia coli serotype, 0157:H7, that was not invasive or toxigenic by standard tests was isolated from 9 of 12 stools collected within four days of onset of illness in both outbreaks combined, and from a beef patty from a suspected lot of meat in Michigan. The only known previous isolation of this serotype was from a sporadic case of hemorrhagic colitis in 1975. This report describes a clinically distinctive gastrointestinal illness associated with E. coli 0157:H7, apparently transmitted by undercooked meat.

Scientists Look to Vaccines in the War on E. Coli

By Andrew Pollack New York Times - 5/2/07

Vaccines for people and for cattle are just two approaches under development to prevent or treat food poisoning by the strain E. coli O157:H7 Current approach - try to prevent contamination through careful handling, rigorous inspections and government regulation Type III Secreted Protein (TTSP) vaccine for cattle approved in 12/06 for controlled distribution in Canada. Can reduce but not eliminate the E. coli shed into manure Other methods being tested include: cattle antibiotics (neomycin), an industrial chemical (sodium chlorate), bacterial-killing viruses (phages) and friendly bacteria (lactobacillus) Potential barrier - ranchers & feedlots have little incentive to pay
do not make the cows grow faster do not they keep cows healthy - O157 does not sicken the cows

Scientists Look to Vaccines in the War on E. Coli

By Andrew Pollack New York Times - 5/2/07

Efforts to develop drugs and vaccines for people also face barriers Outbreaks are rare and sporadic
difficult to test such treatments in clinical trials

Hard to diagnose the infection in time to intervene medically Treatment would have to be very safe, because it would be given to children and because most people improve without any intervention E. coli O157:H7 causes 75,000 cases of infection and 61 deaths in the United States each year, 1999 CDC estimate Antibiotics only make things worse - kill bacteria / release more toxin Intravenous fluids shown to reduce severity of kidney problems Monoclonal antibodies to latch onto toxin and neutralize it Vaccine made of complex sugar on the surface of the bacteria, the Otype polysaccharide being tested in early human safety trials

Norovirus

Cruise Ships

Sick cruise ship docks in Florida for cleaning

November 20, 2006

FORT LAUDERDALE, Fla. - A thorough scrubbing of the Carnival Liberty began Sunday as the ship docked after a virus sickened nearly 700 passengers on a trans-Atlantic cruise. Fourteen guests and five crew remained ill and in isolation when the ship arrived at Port Everglades, according to a statement released by Carnival Cruise Lines, a brand of Carnival Corp. Some passengers were escorted off the ship in wheelchairs by crew wearing blue gloves. Preliminary tests identified the source of the outbreak as the highly contagious norovirus, which had struck several guests just before they boarded the cruise Nov. 3 in Rome, Carnival officials said. More than 530 guests and 140 crew reported to the ship's infirmary with similar symptoms during the 16-day voyage.
Passengers: 2,974 (~18%) Crew: 1,160 (~12%)

Multi-Drug Resistant Acinetobactor

Multi-drug resistant bacteria increases in hospital settings

- November 2006

SAN FRANCISCO Acinetobacter is about four times more resistant to standard antibiotics than it was almost a decade ago, and incidence rates have dramatically increased in hospitals, according to research presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, held here. In 1995, multi-drug resistant (MDR) strains of Acinetobacter caused 4.5% of infections. By 2004, the rate increased to 16.7%, and the strain was resistant to three drug types in one in four cases, according to a CDC study. Hospitals with more than 500 beds reported the majority of infections (55%), followed by those with 200 to 500 beds (45%). Hospitals located in the Northeast region of the United States had the highest cases of drug-resistant Acinetobacter. Although only 26% of all cases came from the Northeast, 74% of all drug-resistant cases came from that region.

Spread of disease tied to US combat deployments

Stateside doctors are left grappling
BY John Donnelly, Boston Globe Staff | May 7, 2007

A parasitic disease rarely seen in United States but common in the Middle East has infected an estimated 2,500 US troops in the last four years because of massive deployments to remote combat zones in Iraq and Afghanistan, military officials said. Leishmaniasis, which is transmitted through the bite of the tiny sand fly, usually shows up in the form of reddish skin ulcers on the face, hands, arms, or legs. But a more virulent form of the disease also attacks organs and can be fatal if left untreated. In some US hospitals in Iraq, the disease has become so commonplace that troops call it the "Baghdad boil." Family doctors have had difficulty figuring out the cause in civilian contractors who went to Iraq.

Delonte West

Paul Pierce

Delonte West

Paul Pierce

More than half of athletic trainers report treating MRSA

Nosocomial Infections by Kirsten H. Ellis Infectious Diseases News Staff Writer May 2007 More than half of athletic trainers have treated athletes for skin infections caused by an antibiotic-resistant superbug, according to study results presented at the 17th Annual Scientific Sessions of the Society for Healthcare Epidemiology of America, held recently in Baltimore. Methicillin-resistant Staphylococcus aureus was once a concern only among hospitalized patients and immunocompromised patients. During the past 10 years, however, incidences of MRSA have increased among otherwise healthy people. All health care providers who treat athletes should be concerned about MRSA, Kristin Brinsley-Rainisch, MPH, a health scientist at the CDC, told Infectious Disease News. Brinsley-Rainisch presented results from the study conducted by CDC researchers. If an athlete presents with a purulent skin infection, health care providers should consider MRSA as the cause. Its also important to provide athletes with information on appropriate wound care to prevent transmission, Brinsley-Rainisch said. Increased risk Athletes are at an increased risk because the bacteria can be spread through skin-to-skin contact in sports and from shared clothing, sports gear or other items such as towels. Increased likeliness of athletes to have open sores from sports injuries also multiplies their susceptibility to MRSA. MRSA in otherwise healthy people was first widely recognized as a problem in the late 1990s. Although the infections are not considered life-threatening, MRSA skin abscesses may require surgical draining. Another concern is the bacterias resistance to first-line antibiotics. In rare cases, MRSA can cause potentially fatal conditions, including pneumonia, blood stream infections and necrotizing fasciitis, also known as a flesh-eating disease. There are reported deaths of athletes associated with MRSA infection. Trainers questioned Through a web-based survey, researchers questioned certified athletic trainers (n=364) regarding experience with skin infections. Respondents had a median of nine years experience. More than half of trainers surveyed (56%), worked with high school athletes, whereas 35% worked with college athletes. The remainder worked with professional teams or in clinical settings. Fifty-three percent of respondents reported treating MRSA. Of those who reported treating MRSA, 86% said they had treated MRSA in male athletes, and 35% reported treating MRSA in female athletes. Ninety-two percent of the trainers surveyed reported treating an athlete for skin infections caused by any organism. The average number of infection treatments in the past year was 7.5 per trainer. Infections typically occurred on the lower leg (38%), forearm (31%) or knee (29%). In infections suspected to be caused by MRSA, trainers reported applying a bandage (97%) or a warm compress (84%) and cleaning the

Celtics clean house

Mark Murphy / Boston Herald / October 27th, 2006

Team medical staff yesterday determined that an ingrown toenail infection that sidelined Delonte West two weeks ago and the infected paper cut on Paul Pierces middle finger, which forced the Celtics captain to miss the last two exhibition games, were fueled by the same bacteria type - known as staphylococcus aureus, a methicillin-resistant strain, for all of you pre-med types. Or you can call it MRSA for short. Locker room and shower areas, in the meantime, were sanitized by a cleaning crew, though there was no way of telling whether the infection actually started in one of those areas. Trainer Ed Lacerte and team physician Dr. Brian McKeon briefed the players on the issue.

Staphylococcus aureus (Staph)

- Common bacteria

- Acquired mainly through direct contact (individuals and objects) - Asymptomatic carriers - Found in nose, armpit, groin, and other similar areas - Causes soft tissue infections such as boils and impetigo - Can cause pneumonia and bloodstream infections - Treatable with antibiotics

Methicillin-resistant Staphylococcus aureus (MRSA)

Healthcare-associated MRSA
- First detected in Britain in 1961 - Cannot be treated with common penicillin-like antibiotics - Acquired a gene that produces a mutated version of transpeptidase, neither penicillin nor methicillin can bind - In the past confined to patients in hospitals, nursing homes, long-term care facilities, dialysis centers; who have weakened immune systems - 1974 - MRSA infections accounted for 2% of staph infections 1995 - 22% 2004 - 63%

Methicillin-resistant Staphylococcus aureus (MRSA)

Community-Associated MRSA

- Movement into the community in the 1980's

- Persons with CA-MRSA infections are typically younger and healthier than persons with healthcare-associated MRSA - Outbreaks in prisons, athletic teams, military camps, child-care settings - Possibility for longer lasting or more severe infections, if the initial antibiotic prescribed is not capable of killing the bacteria - virulence factors to cause disease in normal hosts?

Evolution of Antimicrobial Resistance

Penicillin Methicillin Penicillin-resistant Methicillin-resistant S. aureus [1950s] [1960s] S. aureus (MRSA) S. aureus
[1997] Vancomycin

[1990s]

Vancomycin (glycopeptide) [ 2002 ] intermediate resistant S. aureus

Vancomycin-resistant enterococcus (VRE)

History of Staph & MRSA in Athletes

1984 - rugby team in London

1986 - outbreak of boils in football and basketball - Kentucky

1993 - 1st case of MRSA in a wrestling team in Vermont

2002 - 03 MRSA boom!!! -Los Angeles county: athletes & county jail -Colorado, Indiana, and Pennsylvania fencers, football, & wrestlers
2004 - 06 high school, college, professional football and basketball

CA-MRSA in Sports 2003 - 2006

Professional football teams
St. Louis Rams San Francisco 49ers Miami Dolphins Cleveland Browns Houston Texans Tampa Bay Buccaneers

College football teams

USC
11 in one year- 6 hospitalizations

Georgia

Texans find out skin infection is a stubborn opponent Leigh Hopper, Houston Chronicle - Oct. 31, 2003
To fight the stubborn bug, the team spent $6,000 buying $50 tubes of Bactroban to distribute to players and staff. Twice a day, for five days, everyone used Q-Tips to swab their noses with the antibacterial ointment. The idea, Bastin said, was to eliminate MRSA harmlessly colonizing unsuspecting nostrils. The team is supplying special, numbered towels for the weight room, so no one mistakenly uses a towel that's not his own, Bastin said. Equipment managers are taking extra care to wipe out helmets. Bastin said the team has always practiced good hygiene but has been told "to take it up another notch." Players are urged to wash their hands frequently and to let a trainer or team doctor examine any wounds or unusual-looking spots on the skin.

Gamecock athletics go high-tech in staph prevention

11-15-2006 COLUMBIA, S.C. -- The University of South Carolina has become the first athletic program in the Southeastern Conference to apply high tech, proactive measures like SportsAide(TM) in its fight against the spread of staph infections throughout its athletic complex. SportsAide, provided by SportCoatings(TM) of Rochester Hills, Mich., uses a patented, non-leaching microtechnology that creates a durable bond on sports surfaces and controls the growth of a wide array of bacteria, mold, fungi and algae. "The University of South Carolina is very concerned about the health and well-being of our student-athletes," said Athletics Director Eric Hyman. "We've adopted a policy to use the most advanced technology available, like SportsAide, to provide the safest environment possible for our student athletes." The unique 24/7 protection of the Sports Antimicrobial System (SportsAide, TurfAide(TM) and SportsAide(TM) fabric conditioner) is the reason it is protecting the locker rooms, training rooms, equipment and fields of the Washington Redskins, Miami Heat, Virginia Tech Hokies and teams across the country.

Bug Killing

Spraying the Minnesota Viking locker room

Football equipment in Virginia Tech's locker room receive an "antimicrobial" coating to kill bacteria and other microbes

CleenFreek Product Overview

Originator of the SportsHygiene category Patent pending performance products in the Sporting Good Industry Manufacturing performance equipment such as sport towels, yoga and exercise mats, head and wristbands, and sport sandals that prevent growth of bacteria, fungus, mold, mildew, and are odor resistant Recently introduced patented sport wipes for hands, feet, equipment and surfaces, along with a hand sanitizing gel that have an FDA and EPA MRSA kill claim Towels with Triclosan inhibit the growth of bacteria, fungi, mold, mildew, and are odor resistant

Recommendations
Don't share towels or wipe your face with a towel you use on equipment Don't ignore skin infections that won't heal

Shower after a workout

Use liquid soap, not bars Wash your hands well
To kill germs you must wash under nails and rub thoroughly for 20-30 seconds FROM: Athletic Trainers Workshop

Deadly tropical disease arrives on U.S. shores

Scientists say West Nile threat pales by comparison
BY AMY ELLIS NUTT / Star-Ledger Staff / 11/19/06

Chikungunya, severe and sometimes deadly infectious disease that devastated islands of Indian Ocean, arrived in US Colorado, Louisiana, Maryland, Minnesota & at least 6 other states have reported cases of travelers returning from visits to Asia and East Africa sick with the mosquito-borne virus, according to CDC Fever, nausea, crippling joint pain and even neurological damage Usually not fatlal - lasts for 3 to 7 days International travel has dramatically increased global reach France - 850 cases, UK - 93 and U.S. - > 12 "chikungunya" Swahili for "that which bends up," refers to stooped posture of patients afflicted with the severe joint pain associated with disease

Vaccine Appears to Prevent Cervical Cancer

By DENISE GRADY New York Times - November 21, 2002 Scientists are reporting today that they have created the first vaccine that appears able to prevent cervical cancer. The vaccine works by making people immune to a sexually transmitted virus that causes many cases of the disease. The vaccine is experimental and will not be available to the public for several years. A successful vaccine could sharply reduce rates of cervical cancer, which affects 470,000 women a year worldwide and kills 225,000. In the United States, there are 13,000 cases a year and 4,100 deaths. In a study of 2,392 young women, half of them vaccinated and half given placebo shots, the vaccine was 100 percent effective. Followed for 17 to 27 months, no vaccinated women developed infections or precancerous growths from the virus, whereas 41 nonvaccinated women did become infected, including 9 with precancerous cervical growths. A report on the study is being published today in The New England Journal of Medicine.

Human Papillomavirus (HPV)

Human Papillomavirus vaccine

June 2006 - Gardasil (tetravalent VLP vaccine formulation - Merck) was approved by FDA (VLP = virus-like particle) Prevent cervical cancer and other diseases in females caused by certain types of genital HPV Protects against four HPV types (6,11,16, 18), which are responsible for 70% of cervical cancers and 90% of genital warts CDCs Advisory Committee on Immunization Practices (ACIP) recommended for 11-12 year-old girls, but can be administered to girls as young as 9 years of age. Also is recommended for 13-26 year-old females who have not yet received or completed vaccine series Tested in >11,000 females (9-26 years of age) in many countries around the world, including U.S Vaccine was safe & caused no serious side effects. Adverse events were mainly injection site pain. Reaction was common, but mild.

Human Papillomavirus vaccine

Efficacy mainly been studied in young women (16-26 years of age) who previously had not been exposed to any of the four HPV types in the vaccine Clinical trials demonstrated 100% efficacy in preventing cervical precancers caused by the targeted HPV types, and nearly 100% efficacy in preventing vulvar and vaginal pre-cancers and genital warts caused by the targeted HPV types No therapeutic effect on HPV-related disease If a girl or woman is already infected with one of the HPV types in the vaccine, the vaccine will not prevent disease from that type. Duration of vaccine protection is unclear. Current studies (with five-year follow-up) indicate that the vaccine is effective for at least five years.

Human Papillomavirus vaccine

ACIP recommendation for vaccine use in girls as young as 9 years of age is based on 'bridging' immunogenicity and safety studies, which were conducted in about 1,100 females, 9-to-15 years of age. These studies demonstrated that over 99% of study participants developed antibodies after vaccination; titers were higher for young girls than for older females participating in the efficacy trials. Delivered through a series of 3 intra-muscular injections over a six-month period. The second and third doses should be given 2 and 6 months after the first dose. Can be administered at the same visit as other age-appropriate vaccines, such as Tdap, Td, MCV4, and hepatitis B vaccines. Cost: $360 series of three shots

Cancer-virus vaccine targets wrong age group

By Gregory Lopes and Christopher M. Dolan THE WASHINGTON TIMES 02/21/07

Middle-school girls inoculated with breakthrough vaccine will be no older than 18 when they pass Gardasil's five-year window of proven effectiveness -- more than a decade before the typical cancer patient contracts the sexually transmitted HPV Infectious disease specialists and cancer pathologists say the incubation period for HPV becoming cancer is 10 to 15 years -- meaning the average cervical cancer patient, who is 47, contracted the virus in her 30s and would not be protected by Gardasil taken as a teen Merck is working on a booster shot to extend Gardasil's five years of protection None of the HPV vaccine legislation being considered addresses the potential for booster inoculations that could fall outside the enforcement mechanism -- rules that bar students from school unless they have the required shots.

Cancer-virus vaccine targets wrong age group

By Gregory Lopes and Christopher M. Dolan THE WASHINGTON TIMES 02/21/07

"The point in vaccinating kids 9 to 12 is not to reduce number of cases found in that age group, but to vaccinate prior to beginning sexual activity," said CDC spokesman Curtis Allen. "The benefits of the vaccine decrease as women age because they are more likely to have already been infected by one of the HPV strains." 70% of females are sexually active by age 18, according to CDC But based on cancer statistics, cervical cancer incubation periods, and the five-year life-span of Gardasil, state lawmakers -- who have billed the inoculations as a cure to cervical cancer -- would have a much greater effect on cervical cancer rates by mandating its use later Cervical cancer rates are less than one per 100,000 women until age 20 and then begin to pick up in the late 20s and early 30s Thus, women who likely contracted HPV in their early 20s could be protected by Gardasil taken at 17 or 18

Cancer-virus vaccine targets wrong age group

By Gregory Lopes and Christopher M. Dolan THE WASHINGTON TIMES 02/21/07

Potential risks that short-term studies used for federal approval don't detect Dr. Clayton Young, OB-GYN in Texas - "My concern is that we are pushing ourselves into something worse than we already have," Dr. Young said. "Vaccinating for only two strains may lead to an increase in infection with other and possibly more aggressive strains." Gardasil is effective against two of 10 carcinogenic HPV strains. Ttwo strains dominate the current statistics, estimated to have caused 6,800 new cervical cancer cases in 2006, while the other eight strains combined affected 2,900 women. Clinical trials for vaccine effectiveness to prevent cervical cancer did not include the age group of girls for whom the vaccine is being recommended by federal regulators.
measured ab responses against HPV as a proxy for cervical cancer

Prevnar - pneumococcal conjugate vaccine

4/24/07

Heptavalent pneumococcal conjugate vaccine or PCV7 Active immunization of infants and toddlers against invasive disease caused by Streptococcus pneumoniae due to capsular serotypes included in the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F). Routine schedule is 2, 4, 6, and 12 to 15 months of age. Introduced in 2000 All but eradicated common causes of pneumonia, meningitis and ear infections in children Doctors have been waiting for arrival of replacement bacteria CDC Researchers noted increase in rates of bacterial infections not covered by the current pneumococcal vaccine among native children in Alaska
Since 2004, 140 percent increase compared to pre-vaccine period

(1994)

CDC Strategy Report addressing Emerging Infectious Diseases (1994)

Surveillance and Response
detect, promptly investigate, & monitor emerging diseases & factors that influence them

Applied Research
integrate lab science and epidemiology

Prevention & Control

enhance communication of public health information and ensure prompt implementation of prevention strategies

Infrastructure
strengthen local state, and federal public health infrastructures to support surveillance and implement prevention and control programs

Six Priority Areas of the CDC

1) International Outbreak Assistance (emergency response, epidemiology)

2) Global Approach to Disease Surveillance (global early warning networks)

3) Applied Research on Diseases of Global Importance (lots into flu now) 4) Application of Proven Public Health Tools (bed nets, vaccines, etc) 5) Global Initiatives for Disease Control (the big three and vaccines) 6) Public Health Training and Capacity Building (International Emerging Infections Programs)

Questions???