MICR 454L

Emerging and Re-Emerging

Infectious Diseases

Lecture 1: Identifying the Problem

Dr. Nancy McQueen & Dr. Edith Porter

Overview – the course

Course requirements and challenge for the students Quizzes Midterm Research paper presentation and discussions Hot topics presentations Case studies Comprehensive final exam

The Problem:

Emerging and Re-emerging Infectious diseases

Overview – the problem

Identifying the problem Factors responsible for emerging infections

World population growth Urbanization Ecological disturbances Technological advances Microbial evolution and adaptation Human behavior and attitudes

The problem of emerging infections

The problem is a worldwide challenge by microbes whose survival is linked to ours The vast majority of microbes are beneficial The small minority of microbes that produce disease are called

pathogens. History of the problem

From the 1950’s through the 1970’s microbial diseases appeared to be on their way out Vaccinations Antibiotics and other antimicrobics Improved world economy and decreased poverty

However, from 1980 to 1992 the CDC reported a 22% increase (excluding AIDS) in infectious diseases

The problem of emerging infections

In 1996, published data indicated that since 1980 there was a greater than 50% increase in deaths caused by microbes in the United States.

Emerging infections are defined as those infections whose incidence in humans has increased in the past two decades or will increase in the future.

Emerging infections can be defined as New Reemerging Drug resistant infections

Emergence is a two step process Introduction of the infectious agent into a new population. The agent

may be: Already present Located within another species A variant of an existing pathogen

Dissemination of the infectious agent What are some of these emerging infections?

Emerging and Re-emerging Infectious Diseases

Red names are newly emerging infectious diseases; Blue names are re-emerging infectious diseases; Black names are emerging bioterrorism infectious diseases; Names circled in green are RNA viruses

Adapted from Morens, D. M., et al. 2004. The Challenge of Emerging and Re-emerging Infectious Diseases. Nature 430: 242-249

avian

Recent outbreaks of infectious diseases

Leading causes of deathLeading causes of death

25%

31%13%

11%

5%

9%

6%Infectious diseases

Cardiovascular diseases

Cancers

Injuries

Maternal complications

Respiratory and Digestivediseases

Other

Leading causes of death,1998. There were 53.9 million deaths world-wide in 1998. Cancers, cardiovascular, and respiratory and digestive diseases can also be caused by infections. Thus , the percentage of deaths due to infectious diseases may be even higher than shown. (Source: WHO report, 1999.)

Leading causes of death in Africa versus the Americas

Causes of death in the Americas and Africa, 2002, by percentage of cause.There were 10.7 million deaths in Africa, 6.7 million due to infectious diseases. There were 6 million deaths in the Americas, 623,000 due to infectious diseases. Intentional deaths include murder suicide, and war.

Africa 2002: 10.7 million deaths

63%10%

4%

7%

7%

2%

2% 5%

Infections

Cardiovascular

Cancers

Injuries

Maternal and perinatal

Respiratory

Intentional

Other

Leading infections disease killers

Leading infectious disease killers

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0.5

1

1.5

2

2.5

3

3.5

4

Acuterespiratoryinfection

AIDS Diarrhealdiseases

Tuberculosis Malaria Measles

Death

s in m

illions

Over age 5

Under age 5

Leading infectious killers. The graph shows millions of deaths world-wide in 1998 for persons of all ages. Pneumonia and influenza are included in acute respiratory infections. Deaths among HIV-positive individuals with tuberculosis are included under AIDS. (Source: WHO report, 1999.

Factors responsible for emerging diseases World population growth – most important Urbanization (changes in demographics) Ecological disturbances

Deforestation – disturbances to natural habitat Climate changes Natural disasters (drought, flooding)

Technical advances Air travel Unsafe blood supplies

Human behavior and attitudes Complacency Migration Societal factors

Microbial evolution and adaptation Antimicrobial resistance Evasive strategies

World population growthWorld Population Growth

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1945

1955

1965

1975

1985

1995

2005

2015

2025

2035

2045

Year

Po

pu

lati

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(in

bil

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World population, 1950 to 2050. Projections are based on an estimated annual growth rate of 1.25%. (Source: U.S. Census Bureau, International Dada Base, May 10, 2000.

World population growth is central to the issue

Population growth

Technological advances Ecological

disturbancesIncreased urbanization

Advances in biology and medicine

Changes in human behavior and activities

Increased transmission

How does increased population result in an increase of infectious diseases?

Increased transmission Population density

Person to person transmission is facilitated by population density increases

Distribution of the population The elderly are more susceptible to disease and can serve

as a source of infection Other potential effects:

Greater likelihood of global warming Larger numbers of travelers More frequent wars Increased numbers of refugees and internally displaced

persons

How does increased population result in an increase of infectious diseases?

Increased hunger and malnutrition More crowded living in urban slums Increased numbers of people living in poverty Inadequate potable water supply More large dam construction and irrigation

projects

Urbanization In the past 50 years, about 25% of the

population have left their rural environment for the cities

By 2030, more than 75% of the world’s population will live in cities

Urbanization

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20

30

40

50

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1900 1950 1995 2030

Year

Perc

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f w

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Progressive urbanization of out planet. The different colors for 2030 indicate proportions of urban population that are projected to live in developed countries (20%) and underdeveloped countries (80%)

240 million

750 million

2.5 billion

5 billion

Urbanization and poverty

Drain on natural Decreased public Malnutrition resources and health infrastructure and decreased and increased pollution *Sanitation health services

*Rodent increase *Immunization

Increased infectious diseases

Urbanization The magnitude of the effect of urbanization

on infectious diseases depends upon: Economy of the country Public health infrastructure necessary to cope

with the increasing population density

Slums and shanty towns. Poverty is associated with a lack of sanitary facilities, an increase in rodent populations, a lack of safe drinking water, and other circumstances that contribute to infectious diseases

Urbanization

Emergence of diseases due to urbanization Dengue fever – is caused by a flavivirus

Causes Dengue fever and Dengue hemorrhagic fever Is transmitted by Aedes mosquitoes that are unable to fly

long distances House–to-house infestation of the mosquito occurs in

cramped urban living conditions Disease has moved into the U.S. as the virus infects a

different species of Aedes mosquito West Nile virus – is also caused by a flavivirus

Is also transmitted by a mosquito vector First identified in the U.S. in New York City in 1999.

Spread of WNV in the United States

Even in developed countries urbanization often leads to poverty and disease

Ecological disturbances

Deforestation

Deforestation. As people move into and/or develop agriculture in areas that were formerly forests, there is increased contact with animals, including insects, that harbor infectious microbes. In search of food, the displaced animals return to neighborhoods that were once their lands.

Ecological disturbances Deforestation

Eastern U.S. Raccoons foraging for food rabies (zoonotic disease - transmitted from

animal to human) Lyme, Connecticut in 1970’s

Intersection of humans with rodent-deer life cycle of B. burgdorferi infected ticks emergence of Lyme disease

Guanarito region of central Venezuela Humans in contact with excretions of infected rodents Venezuelan

hemorrhagic fever Central railroad in Brazil

Indigenous mammals displaced Kissing bugs feeding on humans Chagas disease

Aswan High Dam in Egypt New snail habitat schistosomiasis

Aswan High Dam in Egypt Flood lands Mosquitoes Rift valley fever

Ecological disturbances - Deforestation

Leishmania

A village with a high incidence of leishmaniasis. Leishmaniasis is a protozoan infection transmitted by infected sand flies. Sand flies are poor fliers, but they can traverse the short distance from their forest habitat.

HIV

Deforestation

The interspecies leap. AIDS, which originated in Africa, is presumed to have jumped the species barrier from infected monkeys to humans.

Ecological disturbances Climatic changes including global warming may

favor the outbreak of many infectious diseases: Vibrio parahaemolyticus - ocean borne Malaria - mosquitoes Rift Valley fever - mosquitoes Hantavirus - mice Cholera - waterborne Hepatitis - waterborne Lyme disease - ticks Dengue fever - mosquitoes Cryptosporidosis - waterborne

Ecological disturbances Climatic changes are likely to particularly effect vector-

borne diseases (diseases carried to humans by arthropods) May effect the vector May effect the microbe

Disease Population at risk, millions

Prevalence of infection Present distribution Possible change of distribution as a result of climatic change

Malaria 2,100 270 million Tropics, subtropics Highly likely

Lymphatic filariasis 900 90.2 million Tropics, subtropics Likely

Onchocersiasis 90 17.8 million Africa, Latin America Likely

Schistosomiasis 600 200 million Tropics, subtropics Very likely

African trypanosomiasis

50 25,000 new cases per year Tropical Africa Likely

Leishmaniasis 350 12 million infected + 400,000 new cases per year

Asia, Southern Europe, Africa, South America

Not known

Dracunculiasis 63 1 million Tropics (Africa, Asia) Unlikely

Arboviral diseases

Dengue NA NA Tropics, subtropics Very likely

Yellow fever NA NA Africa, Latin America Likely

Japanese encephalitis NA NA East and Southeast Asia

Likely

Other arboviral diseases

NA NA Tropical to temperate zones

Likely

Ecological disturbances

Natural disasters Flooding malaria and cholera in Africa Drought famine disease in Africa Increased humidity crop of pine needles

mouse deer populationemerging Hantavirus infections in Four Corners area of U.S.

Technological advances International travel – SARS, penicillin-resistant

gonorrhea, monkeypox

It’s a small world after all. In a span of a couple of days, President Bill Clinton demonstrated the truth of this cliché. He flew from Washington to New York and back. Then he flew to Cincinnati, Denver, and Aspen. After briefly returning to Washington again, he flew to Morocco. From there he returned to Washington one more time. All that travel took place in one weekend.

Approximate flying time from New York City

Sydney, Australia: 22 hours (1 stop)

Tokyo, Japan: 14 hours (nonstop)

Tel Aviv, Israel: 10 hours (nonstop)

Nairobi, Kenya: 16 hours (1 stop)

Incubation period for selected diseases

Whooping cough: 7-10 days

Gonorrhea: 2-6 days

Salmonella food poisoning: 8-48 hours

Ebola fever: 4-16 days

Measles: 12-32 days

Chicken pox: 10-23 days

Technological advances Blood transfusions - hepatitis, HIV, malaria,

trypanosomiasis, syphilis, Chaga’s disease. Organ transplants and immunosuppressive

drugs - CMV,

mad cow disease

Microbial evolution and adaptation

Antimicrobic resistance In the last 50 years antibiotics and antimicrobics

have saved the lives of innumerable individuals with infections

However now the microbes are becomimg resistant to antimicrobics - why? GROSS MISUSE of antimicrobics

Microbial evolution and adaptation

• Development of antimicrobic resistance:

Developing countries

Insufficient use of antimicrobics

Too expensive

Save it for a rainy day

Failure to complete dose

Developed countries

Overuse of antimicrobics

Available virtually on demand

Used when not necessary

Failure to complete dose

Antimicrobic resistance

Emergence of antimicrobial drug resistant bacteria

Increasing resistance of selected pathogens

Methicillin resistant Staphylococcus aureus

Microbial evolution and adaptation

Bacterial disease Viral disease Protozoan diseaseTyphoid fever HIV infection Malaria

Tuberculosis Hepatitis B Visceral leishmaniasis

Gonorrhea

Staphylococcal infection

Shigellosis

Pneumococcal infection

Enterococcal infection

Examples of drug-resistant diseases:

Microbial evolution and adaptation

Microbes change their surface structures to evade host defenses – Vibrio cholera

Changing one’s coat. Trypanosomes and other microorganiams can form new surface antigens not recognized by antibodies. This is an important evasion strategy.

Antibody can bind to antigen

Antibody can’t bind to antigen

Microbial evolution and adaptation Acquisition of new proteins introduced by lysogenic

bacteriophages Toxins produced by Streptococcus pyogenes that lead to

necrotizing fasciitis (flesh eating bacteria). Mutations and evolution of viruses.

Mainly RNA viruses Include Ebola virus, SARS virus, Hantavirus, Avian

influenza virus More on this later

Adaptation of insect vectors Mosquitoes become resistant to DTT

Malaria ? West Nile virus

Human behavior and attitudes

Complacency - “it can’t happen to me” Return to risky sexual behavior and AIDS and

gonorrhea Failure to immunize your children - measles Failure to get immunizations when traveling to

foreign countries - yellow fever and malaria

Human behavior and attitudes Human migration -wars and conflicts resulting

from political differences result in refugees or internally displaced persons who move from one part of the country to another

A refuge camp. Refuge camps are hotbeds of infection. Crowding and lack of hygiene and sanitation favor the incidence and transmission of disease

Human behavior and attitudes Societal factors

Increased numbers of women workers in child care centers Intestinal parasites Diarrhea Middle ear infections Meningitis

Increased longevitynursing homes, day care centers for adults, and assisted living environments

Food production and dietary habits lead to food-borne diseases Centralized food processing –E. coli from spinach Fast food and take-out restaurants Import of agricultural produce - hepatitis A from

strawberries and onions from Mexico, Cyclospora from Guatamalan raspberries

Human behavior and attitudes Tattooing and body piercing and

Staphylococcus aureus infections:

Tattooing and skin piercing. Tattooing and skin piercing are a risky part of popular culture. The skin is invaded, potentially resulting in serious infection because of he use of unclean instruments

Take Home Message Infectious disease deaths decreased from the 1950s

through the 1970s. Infectious disease deaths started to rise again in the

1980s. New, emerging, and reemerging infections are a major

health problem today. The world population growth is central to the issue of

emerging infections. Other contributing factors include: Urbanization Ecological disturbances Technological advances Microbial evolution and adaptation Human behavior and attitudes

Resources The Microbial Challenge, by Krasner, ASM Press,

Washington DC, 2002. Brock Biology of Microorganisms, by Madigan and

Martinko, Pearson Prentice Hall, Upper Saddle River, NJ, 11th ed, 2006.

Microbiology: An Introduction, by Tortora, Funke and Case; Pearson Prentice Hall; 9th ed, 2007.

Emerging Infectious Diseases. Michael A. Palladino, series editor; Benjamin Cummings speical topics in biology, 2006.