Disease Emergence and Re-emergence

Disease Emergence and Re-emergence

INFECTIOUS DISEASES IMPACT OF INFECTIOUS DISEASES 14th century 1831 1854-56 1899-1902

- Europe - plague kills 20-45% of the worlds population - Cairo - 13% of population succumbs to cholera - Crimean war deaths due to dysentery were 10 times higher than deaths due to casualties - Boer War deaths due to

dysentery were 5 times higher than deaths due to casualties CNN, 4 Oct 2007 LA Times, 31 August 2010 Govt wakes up to superbug

Durgesh Nandan JhaDurgesh Nandan Jha, TNN | Oct 6, 2011, 04.36AM IST New Delhi: A day after TOI reported the findings of a private hospital that confirmed the prevalence of the NDM1 superbug in hospital settings, the state health department has been jolted into action. It has called an emergency meeting of all stakeholders to analyse the report and find

a solution to the danger . Delhi Health Minister A K Walia said the meeting will be held on Friday and representatives from Ganga Ram hospital, which has conducted the study, Indian Council of Medical Research (ICMR), National Centre for Disease Control (NCDC) and pathologists from Lok Nayak hospital among others are expected to

attend. Infectious disease is one of the few genuine adventures left in the world. The dragons are all dead and the lance grows rusty in the chimney corner . . . About the only sporting proposition that remains unimpaired by the relentless domestication of a once free-living human species is the war against those ferocious little fellow creatures, which

lurk in the dark corners and stalk us in the bodies of rats, mice and all kinds of domestic animals; which fly and crawl with the insects, and waylay us in our food and drink and even in our love. - (Hans Zinsser,1934 quoted in Murphy 1994) EMERGING INFECTIOUS DISEASES Microbes and vectors swim in the evolutionary

stream, and they swim faster than we do. Bacteria reproduce every 30 minutes. For them, a millennium is compressed into a fortnight. They are fleet afoot, and the pace of our research must keep up with them, or they will overtake us. Microbes were here on earth 2 billion years before humans arrived, learning every trick for survival, and it is likely that they will be here 2 billion years after we depart

(Krause 1998). 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. MICROBIAL THREATS (1) Newly recognized agents (SARS,

acinetobacter) Mutation of zoonotic agents that cause human disease (e.g., H5N1, H1N1) Resurgence of endemic diseases (malaria, tuberculosis) MICROBIAL THREATS (2) Development of drug-resistant agents (tuberculosis, gonorrhea)

Recognition of etiologic role in chronic diseases (chlamydia causing respiratory and heart disease) Use of infectious agents for terrorism and warfare (anthrax) 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.

Selected emerging and re-emerging infectious diseases, 1996-2004 Heymann DL. Emerging and re-emerging infections. In Oxford Textbook of Public Health, 5th ed, 2009, p1266. Multidrug resistant National Academies Press

http://www.nap.edu/books/0309071844/html/13.html Preventing Emerging Infectious Diseases: A Strategy for the 21 st century. The CDC Plan, p. 26, 1998. Enserink M. Old drugs losing effectiveness against flu; could statins fill gap? Science 309:177, 2005. NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (1) Year

Disease or Pathogen 1993 Hantavirus pulmonary syndrome (Sin Nombre virus) Vibrio cholerae O139 Guanarito virus

Hepatitis C Hepatitis E; human herpesvirus 6 HIV Escherichia coli O157:H7; Lyme borreliosis; human T-lymphotropic virus type 2 Human T-lymphotropic virus 1992 1991

1989 1988 1983 1982 1980 Source: Workshop presentation by David Heymann, World Health Organization, 1999 NEWLY IDENTIFIED INFECTIOUS

DISEASES AND PATHOGENS (2) Year Disease or Pathogen 2009 2004 2003 1999

1997 1996 H1N1 Avian influenza (human cases) SARS Nipah virus H5N1 (avian influenza A virus) New variant Creutzfelt-Jacob disease;

Australian bat lyssavirus Human herpesvirus 8 (Kaposis sarcoma virus) Savia virus; Hendra virus 1995 1994 Source: Workshop presentation by David Heymann, World Health Organization, 1999

NIAID List of Emerging and Re-emerging Infectious Diseases (1) Malaria Tuberculosis NIAID List of Emerging and Re-emerging Infectious Diseases (2)

NIAID List of Emerging and Re-emerging Infectious Diseases (3) Group III Agents with Bioterrorism Potential (continued) NIAID List of Emerging and Re-emerging Infectious Diseases (4) Group III Agents with Bioterrorism Potential (continued) Category B (continued)

NIAID List of Emerging and Re-emerging Infectious Diseases (5) Group III Agents with Bioterrorism Potential (continued) Category C DISEASE EMERGENCE AND RE-EMERGENCE: CAUSES GENETIC/BIOLOGIC FACTORS

Host and agent mutations Increased survival of susceptibles HUMAN BEHAVIOR POLITICAL SOCIAL ECONOMIC PHYSICAL ENVIRONMENTAL FACTORS

ECOLOGIC FACTORS Climatic changes Deforestation Etc. FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (1) 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 Unsustainable urbanization causes breakdowns of sanitary and other public health measures in overcrowded cities (e.g., slums) 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 - climate changes cause changes in geographical distribution of agents and vectors Changing human behaviours, such as increased use of child-care facilities, sexual and drug use

behaviours, and patterns of outdoor recreation Social inequality 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 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. 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 or new diseases that result in infectious diseases caused by agents not usually pathogenic in healthy hosts.(e.g. leukemia patients)

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 FACTORS CONTRIBUTING TO EMERGENCE OR RE-EMERGENCE OF INFECTIOUS DISEASES (7) Biowarfare/bioterrorism: An unfortunate 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. 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 STRATEGIES TO REDUCE THREATS (2)

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 STRATEGIES TO REDUCE THREATS (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

STRATEGIES TO REDUCE THREATS (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

NEW DRUG DEVELOPMENT STRATEGIES TO REDUCE THREATS (5) DECREASE INAPPROPRIATE DRUG USE Improve education of clinicians and public Decrease antimicrobial use in agriculture and food production

IMPROVE VECTOR AND ZOONOTIC CONTROL Develop new safe insecticides Develop more non-chemical strategies e.g. organic strategies BETTER AND MORE WIDESPREAD HEALTH EDUCATION (e.g., west Nile virus; bed nets, mosquito repellent)

STRATEGIES TO REDUCE THREATS (6) DEVELOPMENT OF PREDICTIVE MODELS BASED ON: Epidemiologic data

Climate change surveillance Human behavior ESTABLISH

PRIORITIES The risk of disease The magnitude of disease burden Morbidity/disability Mortality Economic cost REDUCE POTENTIAL FOR RAPID SPREAD

DEVELOP MORE FEASIBLE CONTROL STRATEGIES Ford TE et al. Using satellite images of environmental changes to predict infectious disease outbreaks. Emerging Infect Dis 15(9):1345, 2009. STRATEGIES TO REDUCE THREATS (5) Develop new strategies requiring low-cost technology

Social and political mobilization of communities Greater support for research Reduce poverty and inequality ESSENTIAL FACTORS FOR DISEASE ERADICATION Knowledge of its epidemiology and transmission patterns/mode Availability of effective tools for diagnosis,

treatment and prevention Knowledge of local cultural and political characteristics Community acceptance and mobilization Political will and leadership Adequate and sustained funding ROLE OF THE PUBLIC HEALTH PROFESSIONAL (1)

Establish surveillance for: Unusual diseases Drug resistant agents Assure laboratory capacity to investigate new agents (e.g., high-throughput labs) Develop plans for handling outbreaks of unknown agents Inform physicians about responsible

antimicrobial use ROLE OF THE PUBLIC HEALTH PROFESSIONAL (2) Educate public about Responsible drug compliance Emergence of new agents Infection sources Vector control

Malaria prophylaxis Be aware of potential adverse effects of intervention strategies Anticipate future health problems Promote health and maximize human functional ability EPIDEMIOLOGY AND

BIOLOGY OF INFLUENZA The figure shows peak influenza activity for the United States by month for the 1976-77 through 2008-09 influenza seasons. The month with the highest percentage of cases (nearly 50%) was February, followed by January with 20% and March and December, with approximately 15% of all cases. Prevention and control of seasonal influenze with vaccines. MMWR 58(RR-8):5, 2009

Clinical Outcomes of Influenza Infection Asymptomatic Symptomatic Respiratory syndrome - mild to severe Gastrointestinal symptoms Involvement of major organs - brain, heart, etc. Death

Virology of Influenza Subtypes: A - Causes outbreak B - Causes outbreaks C - Does not cause outbreaks 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 Figure 1. Natural hosts of influenza viruses Nicholson et al. Influenza. Lancet 362:1734, 2003

Genetic Changes in Influenza Antigenic drift - results of errors in replication and lack of repair mechanism to correct errors Antigenic shift - reassortment of genetic materials when concurrent infection of different strains occurs in the same host Nicholson et al. Influenza. Lancet 362:1735, 2003

Figure 2. Origin of antigenic shift and pandemic influenza. The segmented nature of the influenza A genome, which has eight genes, facilitates reassortment; up to 256 gene combinations are possible during coinfection with human and non-human viruses. Antigenic shift can arise when genes encoding at least the haemagglutinin surface glycoprotein are introduced into people, by direct transmission of an avian virus from birds, as occurred with H5N1 virus, or after genetic reassortment in pigs, which support Surveillance for Flu

http://www.cdc.gov/h1n1flu/updates/us/ http://www.cdc.gov/h1n1flu/updates/us/ The H1N1 Epidemic Preparing for the flu Healy M. Vaccinate or risk it? Parents weigh choice. LA Times, 14 Sept, 2009; latimes.com/health

Factors Influencing the Response to Influenza Age Pre-existing immunity (some crossover) Smoking Concurrent other health conditions Immunosuppression Pregnancy

Kaplan K. How the new virus came to be. LA Times, 14 Sept, 2009; latimes.com/health EPIDEMIOLOGY AND BIOLOGY OF H5N1 INFLUENZA 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% December, 2003

January 2004 Feb Europe, Africa

Resurgence in Thailand, Vietnam, Cambodia and Indonesia 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 Indonesia

Thailand Cambodia China & Laos Japan Vietnam

South Korea Spread of H5N1 Avian Influenza 2005-6 2006-7 Outbreaks of Avian Influenza A (H5N1)... MMWR 53(5):102, 2004

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 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 Dont get the flu vaccine! RECOMMENDATIONS TO

PREVENT FLU 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 STRATEGIES TO PREVENT FLU (2) IF SICK STAY HOME, DONT EXPOSE OTHERS FOLLOW PUBLIC HEALTH ADVICE; e.g. school closures etc.

GET FLU SHOT(S) TAKE ANTIVIRAL DRUGS IF PHYSICIAN RECOMMENDS

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