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Communicable Diseases, Nosocomial Diseases, Emerging and Re-Emerging Diseases Biology 447 - Environmental Microbiology 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 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 7 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 • Formites • Zoonotic diseases – animal handling and feeding practices (Mad cow disease, Avian Influenza) • Nosocomial Infections- physician or health care worker induced diseases 10/24/2008 8 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 9 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 10 Communicable Disease Burden Varies Widely Among Continents 10/24/2008 11 Communicable Disease Burden Varies Widely Among Continents 67% 10/24/2008 12 Communicable disease burden in Europe 10/24/2008 13 Communicable disease burden in Europe 3% 10/24/2008 14 Nosocomial Infections 10/24/2008 20 Nosocomial Infection Any infection that is acquired from being in a hospital or other healthcare institution (e.g., nursing home) 10/24/2008 21 • 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 22 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 23 Emerging Drug Resistance in Bacteria • MRSA = Methicillin-Resistant Staphylococcus aureus • VRE = Vancomycin-resistant enterococcus • 3CRKP = Klebsiella pneumoniae resistant to 3rd generation cepalosporins • FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones • Clostridium difficile (NAP1) resistant to fluoroquinolones 10/24/2008 24 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 25 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 26 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 CommunityAcquired-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 27 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 CommunityAcquired-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 28 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 30 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 31 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 32 • 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 33 CDC’s National Nosocomial Infection Surveillance (NNIS) System, 1989 - 2004 MRSA VRE 3CRKP FQRPA Proportion of Resistant Isolates (%) 70 MRSA = methicillin-resistant Staphylococcus aureus 60 50 FQRPA = Pseudomonas aeruginosa resistant to fluoroquinolones 40 30 VRE = vancomycin-resistant enterococcus 20 10 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 34 3CRKP and FQRPA 10/24/2008 35 Clostridium difficile (NAP1) 10/24/2008 36 Potential Bioterrorism Agents 10/24/2008 37 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 38 Complete List of Potential Bioterrorism Agents from the CDC • • • • • • • • • • • • • • • 10/24/2008 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) 39 Complete List of Potential Bioterrorism Agents from the CDC • • • • • • • • • • • • • 10/24/2008 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) 40 Complete list of potential bioterrorism agents (CDC) • Anthrax (Bacillus anthracis) Arenavirues Bacillus anthracis (anthrax) Botulism (Clostridium botulinum toxin) Brucella species (brucellosis) – Plague (Yersinia pestis) – Psittacosis (Chlamydia psittaci) – Q fever (Coxiella burnetii) – Ricin toxin from Ricinus communis (castor beans) Brucellosis (Brucella species) – Rickettsia prowazekii (typhus fever) Burkholderia mallei (glanders) – Salmonella species (salmonellosis) Burkholderia pseudomallei (melioidosis) – Salmonella Typhi (typhoid fever) Chlamydia psittaci (psittacosis) – Salmonellosis (Salmonella species) Cholera (Vibrio cholerae) – Shigella (shigellosis) Clostridium botulinum toxin (botulism) – Shigellosis (Shigella) Clostridium perfringens (Epsilon toxin) – Smallpox (variola major) Coxiella burnetii (Q fever) – Staphylococcal enterotoxin Ebola virus hemorrhagic fever – Tularemia (Francisella tularensis) E. coli O157:H7 (Escherichia coli) – Typhoid fever (Salmonella Typhi) Emerging infectious diseases such as Nipah virus and hantavirus – 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) Epsilon toxin of Clostridium perfringens Escherichia coli O157:H7 (E. coli) Food safety threats (e.g., Salmonella species,scherichia coli O157:H7, Shigella) Francisella tularensis (tularemia) Glanders (Burkholderia mallei) Lassa fever • Marburg virus hemorrhagic fever • Melioidosis (Burkholderia pseudomallei) 10/24/2008 41 Neglected Diseases 10/24/2008 42 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 43 Mapping Emerging Diseases 10/24/2008 44 Emerging diseases on rise Date: 21/02/2008 • 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 multidrugresistant pathogen strains, through overuse of antibiotics, centralised food processing and other technologies. • 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 45 Emerging diseases on rise Date: 21/02/2008 • 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 multidrugresistant pathogen strains, through overuse of antibiotics, centralised food processing and other technologies. • 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 46 • 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 47 • 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 48 Emerging diseases on rise - Date: 21/02/2008 • "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) • 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 breed such dangerous strains 10/24/2008 49 Emerging diseases on rise - Date: 21/02/2008 • "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) • 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 breed such dangerous strains 10/24/2008 50 Emerging diseases on rise Date: 21/02/2008 • 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 highimpact 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 diseases on rise Date: 21/02/2008 • 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 highimpact diseases of the future, we're missing the point." • "We need to start finding pathogens before they emerge," said Daszak. 10/24/2008 52 Nature 451, 990-993 (21 February 2008) Global trends in emerging infectious diseases Kate E. Jones, Nikkita G. Patel, Marc A. Levy, Adam Storeygard, Deborah Balk, John L. Gittleman & 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 53 Nature 451, 990-993 (21 February 2008) Summary: 1. 2. 3. 4. 5. 6. 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. 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 54 Global distribution of relative risk of an EID event A B C D Caption: Global distribution of relative risk of an EID event. 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 pathogens. 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 10/24/2008 55 Geographic Origins of EID events from 1940 to 2004 Caption: Global richness map the geographicorigins origins of 2004. The map is is derived for for EID Caption: Global richness map of of the geographic of EID EID events eventsfrom from1940 1940toto 2004. The map derived EID events caused by all pathogen types. Circles represent one degree grid cells, and the area of the circle is events caused by all pathogen types. Circles represent one degree grid cells, and the area of the circle is proportional proportional to events the number ofcell. events in the Jones cell. Credit: to the number of in the Credit: et. al.,Jones Natureet. al., Nature 10/24/2008 56 Emerging Diseases in the United States 10/24/2008 57 Emerging and re-emerging Diseases in the USA Chlamydia Diphtheria * Encephalitis West Nile St. Louis E. coli N gonorrhea H. Influenzae Hantavirus Hepatitis A-G (A and B*) Human herpes viruses HHV 1-8 HIV/AIDS Human papilloma viruses * Influenza * Emerging strains Legionella pneumophila Lyme Disease * Measles * Meningococcus MRSA Pertussis * Poliomyelitis * Rabies Rocky Mountain Spotted Fever Rubella * SARS (Severe Acute Respiratory Syndrome) Salmonellosis Shigellosis S. pneumoniae Syphilis Tetanus * Toxic-Shock Syndrome Tuberculosis * * Vaccination possible 10/24/2008 58 Emerging / Re-emerging – Diseases - Continued • • • • • 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 59 Why are these mainly “older” diseases “re-emerging” in the USA ? • Change in vaccination patterns and percentage coverage of population • 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 60 Why are these mainly “older” diseases “re-emerging” in the USA ? • Change in vaccination patterns and percentage coverage of population • 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 Why are these mainly “older” diseases “re-emerging” in the USA ? • Change in vaccination patterns and percentage coverage of population • 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 62 Diseases in the USA preventable by vaccination 10/24/2008 63 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 64 Vaccine Preventable Diseases - Adults - Continued • • • • • • • • • • • • • 10/24/2008 Diphtheria** Hepatitis A Hepatitis B Influenza** Lyme Disease Measles* Haemophilis influenza type B (Hib) Mumps* Pneumococcus** Polio Rubella* Tetanus** Varicella* 65 Vaccine Preventable Diseases of children • • • • • • 10/24/2008 Diphtheria Hepatitis A Hepatitis B Pertussis Measles* Haemophilis influenza type B (Hib) 66 Vaccines for Potential Bioterrorism Agents • Anthrax – Cell-free culture of an avirulent, non-encapsulated, derivative of a bovine isolate-V770 • 2-dose efficacy in monkeys • Estimated > 90% effective against cutaneous anthrax • Botulism – Pentavalent toxoid (A-E) • 3 doses 100% effacicious in primates • Tuleraemia – Live attenuated vaccine - 80% protection • Plague – Suspension of killed Yersinia pestis - Questionable immunity • Smallpox – Vaccinia vaccine; Effective in one dose; Side effects • Viral Hemorrhagic Fevers – No vaccine available 10/24/2008 67 Increasing Antibiotic Resistance 10/24/2008 68 Global Emerging and Re-emerging Diseases 10/24/2008 69 Enlarged View on next 2 pages 10/24/2008 70 10/24/2008 71 Continued: From: WHO – Emerging Issues in Water and Infectious disease ISBN 92 4 159082 3 (LC/NLM classification: QW 80) ISSN 1728-2160 10/24/2008 72 10/24/2008 73 Global Diseases 10/24/2008 74 10/24/2008 75 10/24/2008 76 HIV/AIDS 10/24/2008 77 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 78 1982: Term AIDS replaces GRID 1983: Universal precautions introduced MMWR 1983;32:101 The virus that causes AIDS identified Gallo- HTLV III; Montagnier-LAV 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 Record approval time of 6 months 10/24/2008 79 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 80 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: Inverase,saquinivir HIV kinetics reported at 10 billion virions/day 10/24/2008 81 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 82 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 83 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 84 How Is HIV Spread? Routes of Transmission: – Sexual – Intravenous Drug Use Inhalation drug abuse – Exposure to blood/blood products Occupational exposure – Mother to child Breast feeding 10/24/2008 85 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 90% in sub-Saharan Africa <1% (1000) in USA and Europe • Transmission rates USA/Europe: 13–30% without ART, approaching 1–3% with ART Developing countries: 20–43% without ART, lower rates with ART, even with short-course therapy • Breast feeding for 6 months Additional 5–10% infections, with the highest rates of transmission occurring in the first and second months postpartum Wiktor SZ, et al. XIIIth IAC, Durban, 2000. Abstract 354 10/24/2008 86 HIV/AIDS • In 2005, 38.6 million people worldwide were living with HIV, of which 24.7 million (two-thirds) lived in SSA – 4.1 million people worldwide became newly infected – 2.8 million people lost their lives to AIDS • New infections occur predominantly among the 15-24 age group. • Previously unknown about 25 years ago. Has affected over 60 million people so far. 10/24/2008 87 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 88 Global HIV Burden 10/24/2008 89 Adults and Children With HIV/AIDS, 12/31/02 Eastern Europe & Central \Asia North America Western Europe 980,000 570,000 Caribbean 440,000 1,200,000 North Africa & Middle East 550,000 Latin America Sub Saharan Africa 1,500,000 29,400,000 East Asia & Pacific 1,200,000 South & South-East Asia 6,000,000 Australia & New Zealand 15,000 People living with HIV/AIDS .......................... 42 million New HIV infections in 2002 ........................... 5 million Deaths due to HIV/AIDS in 2002 .................... 10/24/2008 3.1 million 90 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 • • • • 10/24/2008 Constraints to access to care and treatment Stigma and discrimination Inadequate prevention measures. Co-infections (TB, Malaria) 91 Malaria 10/24/2008 92 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 93 Annual Reported Malaria Cases by Country (WHO 2003) 10/24/2008 94 Global malaria prevalence 10/24/2008 95 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 96 Hepatitis 10/24/2008 97 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 – – – 10/24/2008 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 98 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 99 Viral Hepatitis - Overview Type of Hepatitis A Source of virus Route of transmission Chronic infection Prevention 10/24/2008 feces fecal-oral no B C D blood/ blood-derived/body fluids Percutaneous/permucosal yes yes E feces fecal-oral yes no ensure safe pre/postpre/postblood donor pre/postexposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification 100 Viral Hepatitis GENOME HAV VIRAL CLASS Picoravirus RNA Enteric 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 10/24/2008 SPREAD INCUBATION 15-45 Days CHRONICITY None Probable 101 Human Herpesviruses • Alpha Herpesviruses: – Herpes Simplex Virus Type 1 (HSV-1) – Herpes Simplex Virus Type 2 (HSV-2) – Varicella Zoster Virus (HZV) • Beta Herpesviruses: – Cytomegalovirus (CMV) – Human Herpesvirus Type 6 (HHV-6) – Human Herpesvirus Type 7 (HHV-7) The Herpes Simplex Virus type 1 (HSV1), which is the cause of cold sores, has an icosahedral capsid shown here at 13 Å resolution. • Gamma Herpesviruses: – Epstein-barr Virus (EBV) – Human Herpesvirus Type 8 (HHV-8) • Kaposi’s Sarcoma Asso. Herpesvirus 10/24/2008 102 Viruses - Herpes; HSV-1 & 2 • HSV-1: – – – – – – – Oral/genital/mucocutaneous lesions; Acute gingivostomatitis; Pharyngitis; Herpes labialis; Keratoconjunctivitis; Encephalitis; Herpetic Whitlow; • HSV-2: – – – – 10/24/2008 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 103 Herpes Viruses • EBV: – – – – – Epstein-Barr virus (EBV) occurs world-wide and infects most people at some point in their lives. Children are largely immune to its effects, but infection in older people can cause a condition called infectious mononucleosis. Long-term infection is, in very rare cases, linked to the development of some forms of cancer. Infects > 85% of population; Agent of infectious mononucleosis Cause of oral hairy leukoplakia; Oncogenic: Burkitt’s Lymphoma; 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 104 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 105 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 106 Papilloma; Focal Epithelial Hyperplasia (FEH) • Etiological agent: – Human papilloma virus (HPV) – “Wart” • Clinical appearance: – Flat (FEH) – Siky – Cauliflower-like 10/24/2008 107 Avian Influenza 10/24/2008 108 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 109 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 110 Confirmed human cases Avian Influenza 10/24/2008 111 Migratory pathway for birds and Avian influenza 10/24/2008 112 The Spread of Avian Flu -- Status as of the Summer 2008 10/24/2008 113 West Nile Virus 10/24/2008 114 WNV In USA 12/11/02 10/24/2008 115 • 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 116 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 117 • 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 – – – – Fever, lymphadenopathy, headache 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 118 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 119 10/24/2008 120 U.S. cases of West Nile for 2002 10/24/2008 121 U.S. cases of West Nile for 2004 10/24/2008 122 U.S. cases of West Nile for 2005 10/24/2008 123 U.S. cases of West Nile for 2007 10/24/2008 124 African Trypanosomiasis 10/24/2008 125 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 126 African Trypanosomiasis, cont. West African Agent: Vector: Distribution: Reservoir: Disease: Mortality: At risk: 10/24/2008 T. brucei gambiense riverine tsetse fly west/central Africa human chronic (years) 100% rural persons East African T. brucei rhodesiense savanna tsetse fly east/south Africa antelope/cattle rapid progression: 1-4 weeks 100% rural, visitors to game reserves 127 10/24/2008 128 10/24/2008 129 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 130 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 131 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 132 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 regimen is strict and difficult to apply. 10/24/2008 133 SARS (Severe Acute Respiratory Syndrome) 10/24/2008 134 10/24/2008 135 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 136 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 137 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 138 Spread of SARS From New York Times 10/24/2008 139 10/24/2008 140 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 141 • 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 142 Hantavirus 10/24/2008 143 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 144 10/24/2008 145 Influenza 10/24/2008 146 Influenza Influenza virus particle Image from: www.drugdevelopment-technology.com 10/24/2008 147 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: One day before - until 10 days after symptom onset Peak day 3-4 Shedding is prolonged in young children Transmission: Person to person via small particle aerosols Virus is relatively stable and favors low humidity and cool temperatures 10/24/2008 148 Influenza virus 10/24/2008 Cold virus 149 • 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 150 Tuberculosis 10/24/2008 151 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 ! – – – – 10/24/2008 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 152 Global Prevalence of TB cases (WHO) 10/24/2008 153 Tuberculosis 10/24/2008 154 10/24/2008 155 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. – – 10/24/2008 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 156 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 157 First-Line Treatment of Tuberculosis for DrugSensitive TB 10/24/2008 158 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 159 Ebola Virus 10/24/2008 160 Nipah Virus • 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 161 Hendra Virus 10/24/2008 162 Summary 10/24/2008 163 • 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 164 Why are there more emerging or re-emerging diseases? 1. 2. 1. 4. 5. 1. 7. 1. 2. 3. 4. 5. 6. Human demographics and behavior Technology and Industry Economic development and land use International travel and commerce Microbial adaptation and change Breakdown of public health measures Human vulnerability Climate and weather Changing ecosystems Poverty and social inequality War and famine Lack of political will Intent to harm 10/24/2008 165 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 166 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 167 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 168 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 169 6 Days to Circumnavigate ( the Globe 350 5 300 4 250 200 3 150 2 100 50 1 0 0 1850 10/24/2008 ) 400 1900 Year 1950 World Population in billions ( ) Speed of Global Travel in Relation to World Population Growth 2000 170 5. Microbial adaptation and change • Increased antibiotic resistance with increased use of antibiotics in humans and food animals (VRE, VRSA, penicillin- and macrolideresistant 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 From: Murphy and Nathanson. Semin. Virol. 5, 87, 1994 CDC 171 Emerging Vancomycin-resistant Enterococcal Infections* % Resistant Emerging Vancomycin-resistant Enterococcal Infections* * in U.S. NNIS Hospitals 10/24/2008 CDC 172 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 173 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 174 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 175 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 176 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 177 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 178 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 179 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 180 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 181 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 182 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 183 10/24/2008 184 10/24/2008 185 10/24/2008 186 10/24/2008 187 10/24/2008 188 The End 10/24/2008 189 10/24/2008 190