Emerging & Re-emerging Infectious Diseases Dr. Garba Iliyasu MBBS,FMCP(Infectious Diseases) Outline Of Presentation Infectious diseases- trends Definition of emerging & re-emerging diseases Factors contributing to emergence Examples Public health response Infectious Disease- Trends Receded in Western countries 20th century Urban sanitation, improved housing, personal hygiene, antisepsis & vaccination Antibiotics further suppressed morbidity & mortality The leading cause of morbidity and mortality in developing countries Infectious Disease- Trends Since last quarter of 20th century- New & Resurgent infectious diseases Definition Emerging infectious disease Newly identified & previously unknown infectious agents that cause public health problems either locally or internationally Definition Re-emerging infectious disease Infectious agents that have been known for some time, had fallen to such low levels that they were no longer considered public health problems & are now showing upward trends in incidence or prevalence worldwide Emerging Infections in the World since 1973 1973 1976 1977 1977 1977 1977 1980 1981 1982 1982 1982 Rotavirus Cryptosporidium Ebola virus Legionella Hantaan virus Campylobacter HTLV-1 Toxin prod. S.aureus E.coli 0157:H7 HTLV-II Borrelia burgdorferi Enteritis/Diarrhea Enteritis/Diarrhea VHF Legionnaire’s dz VHF w/ renal flr Enteritis/Diarrhea Lymphoma Toxic Shock Synd. HUS Leukemia Lyme disease Emerging Infections in the World and US since 1973 1983 1983 1988 1988 1989 1989 1990 1991 1992 1992 HIV Helicobacter pylori Hepatitis E HHV 6 Hepatitis C Ehrlichia chaffeensis Guanarito virus Encephalitozoon Vibrio cholerae O139 Bartonella henselae AIDS Peptic ulcer dz Hepatitis Exanthema subitum Hepatitis Human ehrlichiosis VHF Disseminated dz Cholera Cat scratch dz Emerging Infections in the World and US since 1973 1993 1994 1994 1995 1995 1996 1997 1999 1999 2001 2003 2003 2007 Sin Nombre virus Sabia virus Hendra virus Hepatitis G H Herpesvirus-8 vCJD prion Avian influenza (H5N1) Nipah virus West Nile virus BT Bacillus anthracis Monkeypox SARS-CoV New strains of Ebola Hanta Pulm. Synd. VHF Respiratory dz Hepatitis Kaposi sarcoma Variant CJD Influenza Encephalitis Encephalitis Anthrax Pox SARS VHF Examples of Re-Emerging Infectious Diseases Diphtheria- Early 1990s epidemic in Eastern Europe(1980- 1% cases; 1994- 90% cases) Cholera- 100% increase worldwide in 1998 (new strain eltor, 0139) Human Plague- India (1994) after 15-30 years absence. Dengue/ DHF- Over past 40 years, 20-fold increase to nearly 0.5 million (between 1990-98) GLOBAL EXAMPLES OF EMERGING AND RE-EMERGING INFECTIOUS DISEASES AS Fauci After great advances in medical research and antimicrobial drug discovery, technology development, improvement in sanitation.. WHY are microbes still posing such a problem? Emergence of infectious disease are the results from dynamic interactions between rapidly evolving infectious agents and changes in the environment and in host behaviour that provide such agents with favourable new ecological niches Factors Contributing To Emergence AGENT Evolution of pathogenic infectious agents (microbial adaptation & change) Development of resistance to drugs Resistance of vectors to pesticides Factors Contributing To Emergence HOST Human demographic change (inhabiting new areas) Human behaviour (sexual & drug use) Human susceptibility to infection (Immunosuppression) Poverty & social inequality Factors Contributing To Emergence ENVIRONMENT Climate & changing ecosystems Economic development & Land use (urbanization, deforestation) Technology & industry (food processing & handling) CONTD. International travel & commerce Breakdown of public health measure (war, unrest, overcrowding) Deterioration in surveillance systems (lack of political will) INTERNATIONAL TRAVEL International travel and Commerce. 365 days to circumnavigate the globe…now it takes 36 hours -used to quarantine ships, but 36 h faster than disease incubation International travel -Travel and HIV/AIDS. -Silk route and plague. -Slaves trade and yellow fever. -Migration to new world and smallpox. -Cholera and Hajj. Transmission of Infectious Agent from Animals to Humans >2/3rd emerging infections originate from animals- wild & domestic Emerging Influenza infections in Humans associated with Geese, Chickens & Pigs Animal displacement in search of food after deforestation/ climate change (Lassa fever) Humans themselves penetrate/ modify unpopulated regions- come closer to animal reservoirs/ vectors (Yellow fever, Malaria) Emerging Zoonoses: Humananimal interface Avian influenza virus Borrelia burgdorferi: Lyme Bats: Nipah virus Deer tick (Ixodes scapularis) Ebola virus Marburg virus Hantavirus Pulmonary Syndrome Mostomys rodent: Lassa fever Emerging Infectious Diseases of the 21st century 1. SARS No infectious disease has spread so fast and far as SARS did in 2003 SARS Cases 19 February to 5 July 2003 Total: 8,439 cases, 812 deaths, 30 countries in 7-8 months Europe: 10 countries (38) Canada (243) Russian Fed. (1) Mongolia (9) China (5326) USA (72) Kuwait (1) India (3) Colombia (1) Hong Kong (1755) Korea Rep. (3) Macao (1) Taiwan (698) Malaysia (5) Viet Nam (63) Singapore (206) Brazil (3) Indonesia (2) Philippines (14) Thailand (9) South Africa (1) ( Australia (5) New Zealand (1) Source: www.who.int.csr/sars SARS Mid November 2002 Guangdong Province, China “ outbreak of atypical pneumonia” 11 February 2003 WHO informed 305 cases (5 deaths) 30% in health care workers July 2003 8,437 probable cases from 32 countries major foci in China, SE Asia and Toronto SARS CoV - infectivity (MMWR 2003:52 (18): 405-11) ANIMAL ORIGIN OF SARS-CoV? - IgG seroprevalence: animal traders (13.0%); HCW (2.9%); Guangdong CDC workers (1.6%); Healthy adults (1.3%) - RR (95%CI) for IgG by animal trade: masked palm civet 7.9 (5.0 – 12.6) wild boar 6.2 (3.8 – 10.3) muntjac deer 6.1 (3.4 – 10.9) hare 5.0 (2.5 – 10.2) Others- cat, fowl, pheasant, snakes (not significant) - Martina B et al 2003 demonstrated ease of infection & transmssion in and between cats and ferrets - Guan Y et al 2003 isolated SARS-CoV from Himalayan civet cat, raccoons, and animal traders in southern China…all the animal strains retain the 29 nucleotides missing in human isolates 2003 Guan Y et al 2003; Martina B et al 2003; MMWR 2. Influenza A Was known as endemic gastrointestinal viruses of wild waterfowl, now has jump species into domestic fowl, farm animals and humans Antigenic changes in haemagglutinin and neurominidase glycoproteins – ‘shifts’ (major antigenic changes in HA or NA) Deadly pandemics has occurred in 1888, 1918, 1957 and 1968 Dr. KANUPRIYA CHATURVEDI FIGURE 6. Documented human infections with avian influenza viruses, 1997–2004. Highly Pathogenic Avian Influenza (H5N1) In 2003, avian influenza H5N1 in birds affected 60 countries across Asia, Europe, Middle-East & Africa >220 million birds killed by AI virus or culled to prevent further spread Majority of human H5N1 infection due to direct contact with birds infected with virus Novel Swine (H1N1)-2009 Swine flu causes respiratory disease in pigs – high level of illness, low death rates Occasional human swine infection reported Swine Flu Influenza A (H1N1) March 18 2009 – outbreak reported in Mexico April 15th CDC identifies H1N1 (swine flu) April 25th WHO declares public health emergency April 27th Pandemic alert raised to phase 4 April 29th Pandemic alert raised to phase 5 Influenza A (H1N1) By May 5th more than 1000 cases confirmed in 21 countries Worldwide- 162,380 cases 1154 deaths Screening at airports for flu like symptoms (especially passengers coming from affected area 3. MERS Cov Middle east respiratory corona virus Novel virus Identified in 2013 in Saudi Arabia Links to camels Dr. KANUPRIYA CHATURVEDI 3. Lassa fever 12 Jan 1969- 1st recognized case an American missionary nurse in Lassa, NE- Nigeria 25 Jan 1969- Air lifted to Evangel. Hospital Jos, N. Nigeria 26 Jan 1969- Pt was cared by two american nurses but died that day One of the two caring nurses fell sick after an 8d IP and died after an illness lasting 11d 20 Feb 1969- Head Nurse of the hospital where autopsy for 1st case was done fell sick Pt evacuated to USA by air on a commercial Boeing 707, separated with curtain only Pt recovered after severe protracted illness at ICU of Columbia University NY Lassa fever A virus was isolated and later named Lassa at Yale Arbovirus Research (YAR) Unit 9 Jun 1969- One of YAR virologists fell ill and survived only as a result of an immune plasma transfusion donated by the surviving third case 30 Nov 1969- A Laboratory technician at YAR fell ill and died Jan-Feb 1970- a devastating hospital outbreak at Vom and Jos: Outbreak affected 28 patients with 12 deaths, including the American doctor who first identified the disease and did autopsies Epidemiology Endemic in areas of West Africa, including Nigeria, Liberia, Sierra Leone, and Guinea Estimated 300,000-500,000 infections/year, with 5000 deaths Rodent-to-human transmission (the “multimammate rat”, Mastomys species-complex) Secondary human-to-human transmission with the potential for nosocomial outbreaks with high casefatality Transmission Rodent-to-human: Inhalation of aerosolized virus Ingestion of food or materials contaminated by infected rodent excreta Catching and preparing Mastomys as a food source Transmission Human-to-human: Direct contact with blood, tissues, secretions or excretions of infected humans Needle stick or cut Inhalation of aerosolized virus 4. Ebola virus infection 1976- First Major Outbreak 1976- Sudan & Zaire Occur concurrently Ebola Zaire & Sudan Ebola History 1989 and 1992: Ebola Reston USA and Italy Imported macaques from Philippines 1994: Ebola Côte d'Ivoire Center for Food Security and Public Health Iowa State University - 2004 Ebola Response Update for 16 July 2014 Distribution of EVD Outbreaks Majority of outbreaks are due to Ebola virus (species Zaire ebolavirus) 7 745 4 5 44 16 July 2014 Ebola Response Update for 16 July 2014 Current West African outbreak -as of 8th Sept 2014 Guinea Sierra Leone Liberia Nigeria Senegal EBOLA ZAIRE Total – 4293 Mortality 2296 including 8 in Nigeria PCF=53% http://www.cdc.gov/vhf/ebola/outbreaks/guinea/index.html 45 21 July 2014 Overview cont. Arenavirida Bunyaviridae Filovirida e e Flaviviridae Junin CrimeanCongo H.F. Ebola Kyasanur Forest Disease Machupo Hantavirus Marburg Omsk H.F. Sabia Rift Valley fever Guanarito Lassa Yellow Fever Dengue Ebola out break link to primates The link between human infection by the Ebola virus and their proximity to primates is clear. -Outbreaks occurred in countries with large population of wild gorilla and chimpanzee. - The outbreaks coincided with the outbreaks in wild animals. - The same distinct viral strains were isolated in animal carcasses and in the bodies of those who handled those carcasses. - These outbreaks were preceded by an abnormally large death in wild Gorilla populations. Where does Ebola hide? 2002- Fruit Bats Antibodies against Ebola (Pourrut et al. 2005) Ebola Gene sequences in liver and spleen (Leroy et al. 2005) Fruit bats do not show any symptoms Best candidate to be the reservoir Ebola Response Update for 16 July 2014 Ebola virus ecology 49 16 July 2014 Transmission. Person to person transmission occurs by direct contact with infected body fluids such as blood, sweat, saliva, semen, vaginal fluids, urine, sputum direct inoculation by contaminated instruments such as needles, pins, razor blades Care givers in the home Funeral practices Health care workers Virology Pleomorphic negative-sense RNA virus Viral genome is 19kb long encoding: (1)Structural protiens- glycoprotien(GP), nuclear protien (NP), matrix protien(VP24 & VP40) (2) Non structural protiens-VP30 & VP35 (3)Viral polymerase Pathogenesis Glycoprotiens(GP) plays a major role in pathogenesis -Attaches the virus to epithelial cells, cells lining the blood vessel, hepatocytes, neutrophils, monocytes - Inhibit early steps of neutrophil activation Release of cytokines associated with inflammation, fever, damage to the vascular integrity, viral cytopathic effect on cells Clinical Presentation Incubation period: 2-21days Phase A: Influenza like symptoms- fever, body weakness, head ache, arthralgia, myalgia, sore throat, nausea, vomitting Phase B: Persistent fever, head ache, intense fatigue, diarrhea, abdominal pain, anorexia, vomitting (1-6) Phase C: Pseudo-remission, some may recover (7-8) Phase D: Aggravation with sudden deterioration, respiratory distress, bleeding, neuro-psychiatric manifestation, petaechiae rashes, cardiovascular collapse. Mortality almost 100% (Ndambi et al., 1999) Diagnosis. Diagnosis is by ELISA for specific IgG antibody (presence of IgM antibody indicates recent infection); ELISA antigen detection in blood, serum or organ homogenates PCR Postmortem diagnosis is through immunohistochemical examination of formalin –fixed skin biopsy specimens Treatment - No approved treatment or vaccine for Ebola Treatment is primarily supportive Fluid and electrolytes management Control of bleeding Oxygen therapy Pain management Antibiotics for secondary bacterial Experimental therapy Drugs: Zmapp Favipiravir Estrogen receptor drugs e.g clomiphene Amiodarone TKM-Ebola Vaccines: DNA vaccines, Adenovirus-based vaccine, VSIV vaccine 5. MDR TB estimated cases Africa low HIV incidence, 10,449 Established Market Economies, 1,681 Central Europe, 1,462 Latin America, 11,301 Eastern Mediterranean Region, 18,330 Africa high HIV incidence, 48,141 Eastern Europe, 65,853 Western Pacific Region, 152,018 Global burden: 424,203 cases South-east Asia, 114,967 Zignol M. et al. J Infect Dis. 2006;194:479-85. Total number of MDR-TB cases estimated to have occurred in Africa in 2004 is 58,590 (95% CLs: 48,835-118,089) RESISTANCE IN NIGERIA Fawcett et al (1976) [naïve] INH res 7% SM res 2% Kolo (1991) INH res 19% SM res 13% PZA res 29% Idigbe et al 92 (1992) [treated] Overall res 56% INH res 38% Rif res 2% ≤ 500 501-999 1000-4999 Abdullahi (2006) INH res 29% SM res 14% PZA res 24% ≥ 5000 Lawson et al (2007) unpublished [naïve] MDR TB 12.5% The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved XDR-TB Extensively drug-resistant TB (XDR TB) defined as: MDR TB with further resistance to at least three of the six major classes of second line drugs Source: MMWR March 24, 2006 / Vol 55 / No. 11, 301-305 Resistance to: • At least rifampicin and isoniazid (MDR-TB) • A fluoroquinolone • One or more of the following injectable drugs: kanamycin, amikacin, capreomycin Source: Global XDR-TB Task Force, 7-8 October, 2006 Is malaria an “emerging” disease? YES !!! [At least drug-resistant malaria is an emerging disaster] Bioterrorism Possible deliberate release of infectious agents by dissident individuals or terrorist groups Biological agents are attractive instruments of terror- easy to produce, mass casualties, difficult to detect, widespread panic & civil disruption CONTD. Highest potential- B. anthracis, C. botulinum toxin, F. tularensis, Y. pestis, Variola virus, Viral haemorrhagic fever viruses Likeliest route- aerosol dissemination Key Tasks in Dealing with Emerging Diseases Surveillance at national, regional, global level epidemiological, laboratory ecological anthropological Investigation and early control measures Implement prevention measures behavioural, political, environmental Monitoring, evaluation Key tasks - carried out by whom? Global Regional Synergy National Dr. KANUPRIYA CHATURVEDI What skills are needed? Infectious diseases Epidemiology Public Health Telecom. & Informatics International field experience Laboratory Information management Multiple expertise needed ! Lesson learnt An infectious disease in one country is a threat to all Important role of air travel in international spread Tremendous negative economic impact on trade, travel and tourism, estimated loss of $ 30 to $150 billion during SIRS THANKS FOR LISTENING