WHO-TDR PRIORITY DISEASES. EcoEpidemiology. Durland Fish, Ph.D. Yale University School of Public Health School of Forestry and Environmental Studies

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1 PRIORITY S FOR BIODEFENSE EcoEpidemiology Integrating Ecology with Infectious Disease Epidemiology Durland Fish, Ph.D. Yale University School of Public Health School of Forestry and Environmental Studies CDC NIAID OIE DOD DHHS/USDA VECTOR-BORNE ZOONOTIC NEITHER TOTAL USDA/USAMRMC Biodefense Executive Review 3-4 April 2003 GLOBAL EMERGING DISEASES* MODES OF TRANSMISSION HUMAN HUMAN HUMAN EMERGING RE-EMERGING * Modified from Morens et al Nature 430:242 ZOONOTIC VECTOR-BORNE DIRECT HUMAN TO HUMAN WHO-TDR PRIORITY DISEASES DISEASE DEATHS DALYS* AFRICAN TRYPANOSOMIASIS 50,000 1,585 DENGUE 12, LEISHMANIASIS 41,000 1,810 MALARIA 1,080,000 40,213 SCHISTOSOMIASIS 11,000 1,713 TUBERCULOSIS 1,660,000 35,792 CHAGAS DISEASE 21, LEPROSY 2, LYMPHATIC FILARIASIS 0 5,549 ONCHOCERCIASIS MODES OF TRANSMISSION ANIMAL ANIMAL ANIMAL HUMAN DIRECT ZOONOTIC Remme, et al TRENDS in Parasitology *Disability-adjusted life years x 1,000 1

2 MODES OF TRANSMISSION ANIMAL VECTOR ANIMAL VECTOR ANIMAL HUMAN VECTOR-BORNE ZOONOTIC MODES OF TRANSMISSION Doctrine of Natural Focality of Disease 1939 ANIMAL VECTOR ANIMAL VECTOR ANIMAL ENZOOTIC CYCLE HUMAN VECTOR-BORNE ZOONOTIC Eugene N. Pavlovsky DISTRIBUTION OF A ZOONOTIC Plague in Kazakhstan HUMAN CASES ENZOOTIC/VECTOR CYCLE 2

ANIMAL VECTOR ANIMAL ENZOOTIC CYCLE HUMAN VECTOR-BORNE ZOONOTIC Eugene N.

3 RESERVOIR VECTOR SPATIAL DISTRIBUTION BOOK REVIEW RESERVOIR Natural Nidality of Transmissible Diseases with Special Reference to the Landscape Epidemiology of Zooanthroponoses, by Evgeny N. Pavlovsky Academician E. N. Pavlovsky wrote this book to fulfill the author's obligation in connection with the XXII session of the Communist Party of the Soviet Union. The book is obviously and basically a political document. VECTOR John H. Whitlock 1967 The Journal of Parasitology, 53; NATURAL FOCUS OF DISEASE Ecological Niche Concept (1957) An N-dimensional hypervolume of suitable resources and conditions for existence G. Evelyn Hutchinson

4 NEW TECHNOLOGIES FOR LANDSCAPE EPIDEMIOLOGY REMOTE SENSING LANDSCAPE COMPOSITION GEOGRAPHIC INFORMATION SYSTEMS SPATIAL RELATIONSHIPS GEOSTATISTICS SPATIAL ANALYSIS BIOTECHNOLOGY DETECTION DISTRIBUTION OF IXODES SCAPULARIS Dennis et al J. Med. Entomol. 35:629 Min. Minimum Temperature DATABASE SD of Maximum Temperature Max Vapour Pressure AUTOLOGISITC MODEL Variables: -Min. Maximum Temp -Mean Maximum Temp -Min. Mean Temp -Mean Minimum Temp -SD of Vapour Pressure Likelihood ratio: p< Wald statistic: p< Accuracy=95% Ostfeld et al., TREE 2005 The natural cycle of Lyme disease, a vector-borne zoonosis RECLASSIFICATION RESERVOIR VECTOR Peromyscus leucopus Borrelia burgdorferi Ixodes scapularis Brownstein et al Environmental Health Perspectives 111:

Maximum Temp -Mean Maximum Temp -Min. Mean Temp -Mean Minimum Temp -SD of Vapour Pressure Likelihood ratio: p<0.0001 Wald statistic: p<0.0001 Accuracy=95% Ostfeld et al.

5 RATIO OF REPTILES TO TOTAL HOST SPECIES FOR Ixodes scapularis LYME DISEASE RISK REPTILES/TOTAL HOST* Hall ER Mammals of North America. Vol II. Catalogue of American Amphibians and Reptiles. April 1999 CDC, Division of Vector-Borne Infectious Disease Yale School of Medicine, Dept. EPH High Moderate Low Minimal or None States that Report Lyme Disease Cases CDC MMWR Counties with Cases in the 90th Percentile LYME DISEASE RISK April 1999 CDC, Division of Vector-Borne Infectious Disease Yale School of Medicine, Dept. EPH High Moderate Low Minimal or None 5

April 1999 CDC, Division of Vector-Borne Infectious Disease Yale School of Medicine, Dept.

6 SPATIAL DEPENDENCE OF LYME DISEASE FOREST TICK DISEASE DEER LANDSAT THEMATIC MAPPER TM IMAGE 1 KM Broadleaf Forest Conifers, Evergreen Veg Shrubs, Ecotonal Veg Open, Grassy Areas Residential/Dense Veg Residential/Lawn Residential/Sparse Veg Urban/Commercial Area Water Bodies LANDSCAPE CLASSIFICATION THE WOOD-BURBS LYME DISEASE ENDEMIC STUDY AREA WESTCHESTER CO, NY TM IMAGE AERIAL PHOTO REMOTE SENSING APPLICATIONS IN LYME DISEASE WESTCHESTER COUNTY, NY LANDSAT THEMATC MAPPER FOREST EDGE (GREEN PIXELS) (28.5 m RESOLUTION ) ACQUIRED 20 May 1991 SHADED LAWN (RED PIXELS) 6

LANDSCAPE CLASSIFICATION THE WOOD-BURBS LYME DISEASE ENDEMIC STUDY AREA WESTCHESTER CO, NY TM IMAGE AERIAL PHOTO REMOTE SENSING APPLICATIONS IN

7 ADJACENCY ANALYSIS OF RESIDENTIAL AND DECIDUOUS FOREST CLASSES DECIDUOUS FOREST EPIDEMIC OF WEST NILE VIRUS NEW YORK CITY 1999 RESIDENTIAL/DENSE VEGETATION PREVALENCE OF ANTIBODY IN CANINES WEST NILE VIRUS OUTBREAK NEW YORK CITY AUG TWO SUSPECT CASES 30 AUG EIGHT CASES IN QUEENS 2 SEPT ID - ST. LOUIS ENCEPHALITIS 3 SEPT MOSQUITO CONTROL QUEENS 9 SEPT CITY-WIDE CONTROL 23 SEPT WEST NILE VIRUS ISOLATED FALCO, et al.1993 Am. J. Publ. Health 83:1305 LYME DISEASE TRANSMISSION IS DEPENDENT UPON LANDSCAPE FEATURES IDENTIFIABLE BY SATELLITE IMAGERY SPATIAL ANAYISIS OF WNV TOOLS DATA R = 0.84 LANDSAT 7 IMAGE GIS SOFTWARE SPATIAL STATISTICS SOFTWARE NDVI CENSUS TRACT HUMAN CASES MOSQUITO TRAP Dister et al GIS Symposium, Vancouver, BC 7

LOUIS ENCEPHALITIS 3 SEPT MOSQUITO CONTROL QUEENS 9 SEPT CITY-WIDE CONTROL 23 SEPT WEST NILE VIRUS ISOLATED FALCO, et al.1993 Am. J. Publ.

8 1999 WN Virus Cases Cases Census Tracts LANDSAT LOGISTIC REGRESSION OF NDVI AND CENSUS TRACTS WITH CASES THRESHOLD = 0.22 Probability Human WNV case Kilometers Normalized Difference Vegetation Index (NDVI) 1999 WN Virus Cases Cluster Tracts 1999 WN Virus Cases High Risk Tracts Positive Mosquitoes Kilometers LANDSAT 7 RS MODEL FOR WNV RISK NEW YORK CITY 1999 IDENTIFIED 33 OF 40 CASE CENSUS TRACTS CORRECTLY (83% SENSITIVITY) VALIDATION WITH MOSQUITO LIGHT TRAP DATA (72% ACCURACY) 861 OF 2,621 CENSUS TRACTS CLASSIFIED AS HIGH RISK (33% OF TOTAL) Brownstein et al 2003 Spatial Analysis of West Nile Virus: Rapid Risk Assessment of an Introduced Vector-Borne Zoonosis. Vector Borne and Zoonotic Diseases 2:

5 Normalized Difference Vegetation Index (NDVI) 1999 WN Virus Cases Cluster Tracts 1999 WN Virus Cases High Risk Tracts Positive Mosquitoes 10 0 10 Kilometers LANDSAT 7 RS MODEL FOR WNV RISK NEW YORK

9 ECOEPIDEMIOLOGY: PREDICTING DISEASE RISK SPATIAL (LANDSCAPE) MODELS PREDICT WHERE TEMPORAL (DYNAMIC) MODELS PREDICT WHEN Reported Lyme Disease Cases by Year United States, ,000 20,000 Cases 15,000 10,000 5, Year LYMErix World's First Lyme Disease Vaccine Now Available From SmithKline Beecham PHILADELPHIA, Jan. 12, 1999 /PRNewswire/ -- LYMErix, the world's first vaccine to prevent Lyme disease, is now available. Manufactured by SmithKline Beecham Biologicals, LYMErix was proven safe and effective in the prevention of both definite Lyme disease and asymptomatic infection. LYMErix received approval from the U.S. Food and Drug Administration in December,

PHILADELPHIA, Jan. 12, 1999 /PRNewswire/ -- LYMErix, the world's first vaccine to prevent Lyme disease, is now available.

10 News Nature Medicine 8, (2002) Poor sales trigger vaccine withdrawal Emma Hitt Atlanta Poor sales have prompted GlaxoSmithKline (GSK) to withdraw its Lyme disease vaccine, LYMErix, from the United States market. Lawsuits relating to adverse effects of the vaccine have been filed since its introduction, but the US Food and Drug Administration (FDA) found no proof that LYMErix is dangerous. Importantly, the move shows that even though the global vaccine market is expected to increase by 25% within the next five years, vaccine manufacturers are not immune to financial forces, which signals a troubled future for new vaccines against rare diseases, such as West Nile virus and Ebola if they complete development. VACCINATION TARGET WHITE-FOOTED MOUSE (Peromuscus leucopus) RESERVOIR HOST FOR Borrelia burgdorferi Lymerix Lyme Disease Vaccine Side Effects Attorney Lawyer representing victims of Lymerix, lyme disease vaccine side effects. Call our attorneys now for a free lawsuit lawsuit. 1 km Las Vegas Lymerix Lawyers, Nevada Lymerix Attorneys, Bourgault... Las Vegas Lymerix Lawyers, Nevada Lymerix Attorneys, Bourgault & Harding, Serious Injury Lawyer in Las Vegas, Nevada, Las Vegas Lymerix Lawyers serving Sacramento, California. Accidents... Lymerix Lawyers - Personal Injury Attorneys serving Sacramento, California along with Tehama County, California including the cities of Red Bluff, Corning Lymerix Lawyer in Louisiana - Lymerix Attorney in Louisiana Find a Lymerix Lawyer in Louisiana. Lymerix Assistance from Attorneys in Louisiana. lymerix.legalview.com/louisiana-attorney-lawyer/ Field Study Site in North Branford, CT The natural cycle of Lyme disease, a vector-borne zoonosis RESERVOIR VECTOR Field vaccination of Peromyscus leucopus 928 mice immunized by syringe inoculation Osp A vaccine vs. GT control Peromyscus leucopus Borrelia burgdorferi Ixodes scapularis 10

Lawsuits relating to adverse effects of the vaccine have been filed since its introduction, but the US Food and Drug Administration (FDA) found no proof that LYMErix is dangerous.

11 Experimental design: Field vaccination study CON VAX 2 treatments x 3 sites Vaccinated: YRS 1, 2 CONCLUSIONS FROM MOUSE VACCINATION STUDY Overall infection prevalence reduced by 16% 100 m 1.2 ha 100 m Assayed for effect: YR 3 Response variable: Nymphal infection prevalence Mice contribute only 27-55% of the infection prevalence in nymphal ticks Alternative reservoir hosts have a greater role in maintaining pathogen prevalence than previously recognized COLLECTING HOST-SEEKING TICKS CHOOSING THE RIGHT HOST P. LEUCOPUS IS NOT INFECTING ALL OF THE TICKS Most likely alternative hosts: DRAG CLOTH METHOD Turdus migratorius Tamias striatus Procyon lotor Nymphal Infection Prevalence Results B. burgdorferi prevalence is lower on vaccinated plots (Mantel Haenszel χ 2, p = 0.017, d.f. = 1, N = 1315) THE BIOLOGICAL SCIENCES NYMPHAL INFECTION PREVALENCE (%) Con Vax I II III SITE Tsao, et al PNAS 101: BIOCHEMISTRY MOLECULAR GENETICS PHYSIOLOGY IMMUNOLOGY CELL BIOLOGY ANATOMY DEVELOPMENTAL SYSTEMATICS BEHAVIOR EVOLUTION ECOLOGY Keeton & Gould 1986 Biological Science Norton, NY 1175 pp. 11

role in maintaining pathogen prevalence than previously recognized COLLECTING HOST-SEEKING TICKS CHOOSING THE RIGHT HOST P.

12 THE BIOMEDICAL SCIENCES BIOCHEMISTRY MOLECULAR GENETICS PHYSIOLOGY IMMUNOLOGY CELL BIOLOGY ANATOMY DEVELOPMENTAL SYSTEMATICS BEHAVIOR EVOLUTION ECOLOGY YALE INSTITUTE FOR BIOSPHERIC STUDIES Epidemiology must constantly seek imaginative and ingenious teachers and scholars to create a new genre of medical ecologists who can interpret the interplay of forces which result in disease. Thomas Francis, Jr. M.D Thanks to: USDA-ARS NIH-NIAID CDC-DVBID NASA MATHERS FOUNDATION & STAFF OF THE VECTOR ECOLOGY LABORATORY 12

edu/yibs/research/cee Epidemiology must constantly seek imaginative and ingenious teachers and scholars to create a new genre of medical

TRACKS INFECTIOUS DISEASE EPIDEMIOLOGY

TRACKS INFECTIOUS DISEASE EPIDEMIOLOGY Dr. Shruti Mehta, Director The development of antibiotics, improved access to safe food, clean water, sewage disposal and vaccines has led to dramatic progress in controlling infectious diseases. Despite