EMERGING AND RE-EMERGING INFECTIOUS DISEASES Detels - 10 Oct 2011

Learning Objective To able to define and give example of emerging and reemerging infectious disease (ERID). Able to discuss what is the factors contributed to ERID List current pathogens classified as ERID Explain what steps is used to lower the threat of ERID Have understanding of Influenza and dengue as ERID cases

IMPACT OF INFECTIOUS DISEASES Emerging Infectious Diseases IMPACT OF INFECTIOUS DISEASES 14th century - Europe - plague kills 20-45% of the world’s population 1831 - Cairo - 13% of population succumbs to cholera 1854-56 - Crimean war – deaths due to dysentery were 10 times higher than deaths due to casualties 1899-1902 - Boer War – deaths due to dysentery were 5 times higher than deaths due to casualties Detels - 10 Oct 2011

Emerging Infectious Diseases Direct economic impact of selected infectious disease outbreaks, 1990-2003 Heymann DL. Emerging and re-emerging infections. In Oxford Textbook of Public Health, 5th ed, 2009, p1267. Detels - 10 Oct 2011

Emerging Infectious Diseases Forum on Microbial Threats. The impact of globalization on infectious disease emergence and control. Institute of Medicine of the National Academies, Washington DC, 2006, p. 5. Emerging Infectious Diseases Detels - 10 Oct 2011

Definition Emerging infectious disease (EID): Infectious disease whose incidence has increased in the past 20 years and threatens to increase in the near future Include Newly recognized agents (SARS, acinetobacter) Mutation of zoonotic agents that cause human disease (e.g., H5N1, H1N1) Resurgence of endemic diseases (malaria, tuberculosis)

Re-emerging infectious disease: re-emergence of microbes that had been successfully controlled. E.g: Dengue Enterovirus 71 Clostridium difficile Mumps virus Streptococcus, Group A Staphylococcus aureus

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (1) Human demographic change Human move to new area and are exposed to new environmental sources of infectious agents, insects and animals Unsustainable urbanization causes breakdowns of sanitary and other public health measures in overcrowded cities (e.g., slums) Multiple factors contribute to the emergence of new or re-emergence of previously known diseases (Lederberg et al. 1992; Centers for Disease Control and Prevention 1994; Murphy 1994), including the following: - Human demographic change by which persons begin to live in previously uninhabited remote areas of the world and are exposed to new environmental sources of infectious agents, insects and animals. - Breakdowns of sanitary and other public health measures in overcrowded cities and in situations of civil unrest and war. - Economic development and changes in the use of land, including deforestation, reforestation, and urbanization. - Other human behaviors, such as increased use of child-care facilities, sexual and drug use behaviors, and patterns of outdoor recreation. - International travel and commerce that quickly transport people and goods vast distances. - Changes in food processing and handling, including foods prepared from many different individual animals and transported great distances. - Evolution of pathogenic infectious agents by which they may infect new hosts, produce toxins, or adapt by responding to changes in the host immunity. - Development of resistance of infectious agents such as Mycobacterium tuberculosis and Neisseria gonorrhoeae to chemoprophylactic or chemotherapeutic medicines. Resistance of the vectors of vector-borne infectious diseases to pesticides. - Immunosuppression of persons due to medical treatments or new diseases that result in infectious diseases caused by agents not usually pathogenic in healthy hosts. - Deterioration in surveillance systems for infectious diseases, including laboratory support, to detect new or emerging disease problems at an early stage. Examples of emerging infectious disease threats include the following: - Toxic shock syndrome, due to the infectious toxin-producing strains of Staphylococcus aureus, illustrates how a new technology yielding a new product, super-absorbent tampons, can create the circumstances favoring the emergence of a new infectious disease threat. - Lyme disease, due to the infectious spirochete Borrelia burgdorferi, illustrates how changes in the ecology, including reforestation, increasing deer populations, and suburban migration of the population, can result in the emergence of a new microbial threat that has now become the most prevalent vector-borne disease in the United States. - Shigellosis, giardiasis, and hepatitis A are examples of emerging diseases that have become threats to staff and children in child-care centers as the use of such centers has increased due to changes in the work patterns of societies. - Opportunistic infections, such as pneumocystis pneumonia caused by Pneumocystis carinii, chronic cryptosporidiosis caused by Cryptosporidium species, and disseminated cytomegalovirus infections, illustrate emerging disease threats to the increasing number of persons who are immunosuppressed because of cancer chemotherapy, organ transplantation, or HIV infection. - Foodborne infections such as diarrhea caused by the enterohemorrhagic strain 0157:H7 of Escherichia coli and waterborne infections such as gastrointestinal disease due to Cryptosporidium species are examples of emerging disease threats that have arisen due to such factors as changes in diet, food processing, globalization of the food supply and contamination of municipal water supplies. Hantavirus pulmonary syndrome first detected in the USA in 1993 and caused by a previously unrecognized hantavirus illustrates how exposure to certain kinds of infected rodents can result in an emerging infectious disease. Nipah virus disease first detected in Malaysia in 1999 and caused by a previously unrecognised Hendra-like virus demonstrates how close contact with pigs can result in an emerging infectious disease. Emergence of the new toxigenic Vibrio cholerae O139 strain of cholera in Asia is an example of a new strain of an infectious agent for which there is no protection from prior infection with other strains or with current vaccines and for which standard diagnostic tests are ineffective. Detels - 10 Oct 2011

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (2) Economic development and changes in the use of land including deforestation, reforestation, and urbanization Global warming changes in geographical distribution of agents and vectors Changing human behaviours increased use of child-care facilities, sexual and drug use behaviours, and patterns of outdoor recreation Social inequality Detels - 10 Oct 2011

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (3) International travel and commerce that quickly transport people and goods vast distances Changes in food processing and handling including foods prepared from many different individual animals and countries, and transported great distances Detels - 10 Oct 2011

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (4) Evolution of pathogenic infectious agents by which they may infect new hosts, produce toxins, or adapt by responding to changes in the host immunity.(e.g. influenza, HIV) Development of resistance by infectious agents such as Mycobacterium tuberculosis and Neisseria gonorrhoeae to chemoprophylactic or chemotherapeutic medicines. Detels - 10 Oct 2011

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (5) Resistance of the vectors of vector-borne infectious diseases to pesticides. Immunosuppression of persons due to medical treatments result in infectious diseases caused by agents not usually pathogenic in healthy hosts.(e.g. leukemia patients) Detels - 10 Oct 2011

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (6) Deterioration in surveillance systems for infectious diseases, including laboratory support, to detect new or emerging disease problems at an early stage (e.g. Indonesian resistance to “scientific colonialism”) Illiteracy limits knowledge and implementation of prevention strategies Lack of political will – corruption, other priorities Antimicrobial drug resistance as a major factor in the emergence and re-emergence of infectious diseases deserves special attention. Although significant reductions in infectious disease mortality have occurred since the introduction antimicrobials for general use in the 1940s, antimicrobial drug resistance has emerged because of their widespread use in humans. Drugs that once seemed invincible are losing their effectiveness for a wide range of community-acquired infections, including tuberculosis, gonorrhea, pneumococcal infections (a leading cause of otitis media, pneumonia, and meningitis), and for hospital-acquired enterococcal and staphylococcal infections. Resistance to antiviral (e.g. amantadine-resistant influenza virus and acyclovir-resistant herpes simplex), anti-fungal (e.g. azole-resistant Candida species), and anti-protozoal (e.g., metronidazole-resistant Trichomonas vaginalis) drugs is also emerging. Drug-resistant malaria has spread to nearly all areas of the world where malaria occurs. Concern has also arisen over strains of HIV resistant to antiviral drugs. Increased microbial resistance has resulted in prolonged hospitalizations and higher death rates from infections; has required much more expensive, and often more toxic, drugs or drug combinations (even for common infections); and has resulted in higher health care costs (Centers for Disease Control and Prevention 1994). Antimicrobial drug resistance has also emerged because of the use of antimicrobials in domesticated animals. For example, the use of fluoroquinolones in poultry has created a reservoir of quinolone-resistant Campylobacter jejuni that has now been isolated in humans. An aggressive public health response to these new, emerging and re-emerging infectious disease threats must be made to characterize them better and to mount an effective response for their control. For example, the 1999 outbreak of West Nile fever in New York City and surrounding areas demonstrates how a viral encephalitis, initially classified as St. Louis encephalitis and later confirmed to be due to West Nile-like virus, can reach far beyond its normal setting. The WHO (WHO 1995a) has outlined the following high priority areas: (a) strengthen global surveillance of infectious diseases; (b) establish national and international infrastructures to recognize, report and respond to new disease threats; (c) further develop applied research on diagnosis, epidemiology, and control of emerging infectious diseases; and (d) strengthen the international capacity for infectious disease prevention and control. Another unfortunate source of a new or emerging disease threat is the spectre of biological warfare or bioterrorism, especially in an age where terrorist acts are frequent events (Christopher et al, 1997). Several countries are developing rapid response capability to deal with such contingencies. Detels - 10 Oct 2011

Emerging Infectious Diseases FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (7) Biowarfare/bioterrorism: potential source of new or emerging disease threats (e.g. anthrax and letters) War, civil unrest creates refugees, food and housing shortages, increased density of living, etc. Famine causing reduced immune capacity, etc. Manufacturing strategies; e.g., pooling of plasma, etc. Detels - 10 Oct 2011

NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (1) Emerging Infectious Diseases NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (1) Year Disease or Pathogen 1993 Hantavirus pulmonary syndrome (Sin Nombre virus) 1992 Vibrio cholerae O139 1991 Guanarito virus 1989 Hepatitis C 1988 Hepatitis E; human herpesvirus 6 1983 HIV 1982 Escherichia coli O157:H7; Lyme borreliosis; human T-lymphotropic virus type 2 1980 Human T-lymphotropic virus Source: Workshop presentation by David Heymann, World Health Organization, 1999 Detels - 10 Oct 2011

NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (2) Emerging Infectious Diseases NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (2) Year Disease or Pathogen 2009 H1N1 2004 Avian influenza (human cases) 2003 SARS 1999 Nipah virus 1997 H5N1 (avian influenza A virus) 1996 New variant Creutzfelt-Jacob disease; Australian bat lyssavirus 1995 Human herpesvirus 8 (Kaposi’s sarcoma virus) 1994 Savia virus; Hendra virus Source: Workshop presentation by David Heymann, World Health Organization, 1999 Detels - 10 Oct 2011

STRATEGIES TO REDUCE THREATS (1) Emerging Infectious Diseases STRATEGIES TO REDUCE THREATS (1) DEVELOP POLITICAL WILL AND FUNDING IMPROVE GLOBAL EARLY RESPONSE CAPACITY WHO National Disease Control Units (e.g. USCDC, CCDC) Training programs Detels - 10 Oct 2011

STRATEGIES TO REDUCE THREATS (2) Emerging Infectious Diseases IMPROVE GLOBAL SURVEILLANCE Improve diagnostic capacity (training, regulations) Improve communication systems (web, e-mail etc.) and sharing of surveillance data Rapid data analysis Develop innovative surveillance and analysis strategies Detels - 10 Oct 2011

STRATEGIES TO REDUCE THREATS (3) Emerging Infectious Diseases 3. IMPROVE GLOBAL SURVEILLANCE (continued) Utilize geographical information systems Utilize global positioning systems Utilize the Global Atlas of Infectious Diseases (WHO) Increase and improve laboratory capacity Coordinate human and animal surveillance Detels - 10 Oct 2011

Emerging Infectious Diseases Detels - 10 Oct 2011

STRATEGIES TO REDUCE THREATS (4) Emerging Infectious Diseases STRATEGIES TO REDUCE THREATS (4) 4. USE OF VACCINES Increase coverage and acceptability (e.g., oral) New strategies for delivery (e.g., nasal spray administration) Develop new vaccines Decrease cost Decrease dependency on “cold chain” 5. NEW DRUG DEVELOPMENT Detels - 10 Oct 2011

STRATEGIES TO REDUCE THREATS (5) Emerging Infectious Diseases STRATEGIES TO REDUCE THREATS (5) 6. DECREASE INAPPROPRIATE DRUG USE Improve education of clinicians and public Decrease antimicrobial use in agriculture and food production 7. IMPROVE VECTOR AND ZOONOTIC CONTROL Develop new safe insecticides Develop more non-chemical strategies e.g. organic strategies 8. BETTER AND MORE WIDESPREAD HEALTH EDUCATION (e.g., west Nile virus; bed nets, mosquito repellent) Detels - 10 Oct 2011

STRATEGIES TO REDUCE THREATS (5) Emerging Infectious Diseases STRATEGIES TO REDUCE THREATS (5) 9. Develop new strategies requiring low-cost technology 10. Social and political mobilization of communities 11. Greater support for research 12. Reduce poverty and inequality Detels - 10 Oct 2011

Emerging Infectious Diseases EPIDEMIOLOGY AND BIOLOGY OF INFLUENZA Detels - 10 Oct 2011

Clinical Outcomes of Influenza Infection Emerging Infectious Diseases Clinical Outcomes of Influenza Infection Asymptomatic Symptomatic Respiratory syndrome - mild to severe Gastrointestinal symptoms Involvement of major organs - brain, heart, etc. Death Detels - 10 Oct 2011

Emerging Infectious Diseases Virology of Influenza Subtypes: A - Causes outbreak B - Causes outbreaks C - Does not cause outbreaks Detels - 10 Oct 2011

Immunogenic Components of the Influenza Virus Emerging Infectious Diseases Immunogenic Components of the Influenza Virus Surface glycoproteins, 15 hemagglutinin (H1-H15), nine neurominidases (N1-N9) H1-H3 and N1N2 established in humans Influenza characterized by combination of H and N glycoproteins 1917 pandemic - H1N1 2004 avian influenza - H5N1 2009 H1N1 Antigenic mix determines severity of disease Human response specific to hemagglutinin and neurominidase glycoproteins Detels - 10 Oct 2011

Emerging Infectious Diseases Figure 1. Natural hosts of influenza viruses Nicholson et al. Influenza. Lancet 362:1734, 2003 Detels - 10 Oct 2011

Emerging Infectious Diseases The H1N1 Epidemic Detels - 10 Oct 2011

Emerging Infectious Diseases Detels - 10 Oct 2011

Emerging Infectious Diseases Detels - 10 Oct 2011

Factors Influencing the Response to Influenza Emerging Infectious Diseases Factors Influencing the Response to Influenza Age Pre-existing immunity (some crossover) Smoking Concurrent other health conditions Immunosuppression Pregnancy Detels - 10 Oct 2011

Emerging Infectious Diseases Kaplan K. How the new virus came to be. LA Times, 14 Sept, 2009; latimes.com/health Detels - 10 Oct 2011

Emerging Infectious Diseases EPIDEMIOLOGY AND BIOLOGY OF H5N1 INFLUENZA Detels - 10 Oct 2011

Characteristics of H5N1 Avian Influenza Emerging Infectious Diseases Characteristics of H5N1 Avian Influenza 1. Highly infectious and pathogenic for domestic poultry 2. Wild fowl, ducks asymptomatic reservoir 3. Now endemic in poultry in Southeast Asia 4. Proportion of humans with subclinical infection unknown 5. Case fatality in humans is >50% Detels - 10 Oct 2011

Spread of H5N1 Avian Influenza Emerging Infectious Diseases Spread of H5N1 Avian Influenza 12 14 16 18 20 22 24 26 28 30 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 2 December, 2003 January Feb 2005-6 2006-7 2004 South Korea China & Laos Resurgence in Thailand, Vietnam, Cambodia and Indonesia Cambodia Indonesia Thailand Vietnam Europe, Africa Japan Detels - 10 Oct 2011

Intervention Strategies (H5N1) Emerging Infectious Diseases Intervention Strategies (H5N1) Culling (killing of infected flocks) Innovative surveillance strategies - Identification and analysis of human to human clusters - Characterization of strains * Necessity for vaccine development (Science 304:968-9, 5/2004) Vaccination of bird handlers (vaccine being developed) Vaccination of commercial bird flocks Detels - 10 Oct 2011

Emerging Infectious Diseases Barriers to H5N1 Control Reservoir in wild birds and ducks Economic impact of culling of poultry stocks Popularity of “wet markets” promotes transmission within poultry and to other species (e.g., pigs) Resistance to antivirals and vaccines Mistrust of rich nations Detels - 10 Oct 2011

Emerging Infectious Diseases Don’t get the flu vaccine! Detels - 10 Oct 2011

Emerging Infectious Diseases RECOMMENDATIONS TO PREVENT FLU Detels - 10 Oct 2011

STRATEGIES TO PREVENT FLU (1) Emerging Infectious Diseases STRATEGIES TO PREVENT FLU (1) COVER MOUTH AND NOSE WHEN SNEEZING WASH HANDS FREQUENTLY WITH SOAP AND WATER OR ALCOHOL AVOID TOUCHING EYES, NOSE AND MOUTH AVOID CONTACT WITH SICK PEOPLE AVOID CROWDED CONGESTED ENVIRONMENTS Detels - 10 Oct 2011