Emerging vector-borne diseases in the United States: What s next and are we prepared?

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Emerging vector-borne diseases in the United States: What s next and are we prepared? Lyle R. Petersen, MD, MPH Director Division of Vector-Borne Diseases Centers for Disease Control and Prevention IOM Forum on Microbial Threats September 16, 2014 National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-Borne Diseases Bacterial Diseases Branch

Emerging Infectious Disease as Defined by Wikipedia Incidence increased in last 35 years or could increase in future* Caused by Newly identified strains that may have involved from a known infection or spread to a new population or area undergoing ecologic transformation or Remerging infections * IOM report 1992: new, reemerging, or drug-resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future.

Simplified Patterns of Vector-Borne Disease Transmission Scenario one: People are incidental hosts Scenario two: People are primary hosts National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-Borne Diseases Bacterial Diseases Branch

Vector-Borne Disease Emergence in the United States Humans incidental hosts YES NO Mosquitoes Arboviruses Arboviruses Ticks Arboviruses Bacteria Parasites Not currently important

Vector-Borne Disease Transmission: Humans as Incidental Hosts Common features Incredibly complex transmission cycle High turnover in many animal reservoirs herd immunity temporary Human immunity not important to transmission cycle Mosquito-borne Amplifies quickly Influenced by factors not easily measured or predicted far in advance Stochastic process subject to substantial random variability Unpredictable outbreaks garner public attention Tick-borne Amplifies slowly in comparison More predictable Long-term trends garner less public attention

Vector-Borne Disease Emergence in the United States Humans incidental hosts YES NO Mosquitoes Arboviruses Arboviruses Ticks Arboviruses Bacteria Parasites Not currently important

West Nile Virus Flavivirus Birds are vertebrate hosts; Culex mosquitoes vectors Introduced into New York City area in 1999 No means of natural transport to Western Hemisphere Emergence during a heat wave Genetics suggests separate introductions in Europe and USA of lineage 1 WNV from Africa At least two sequential genetic mutation events of consequence NY99 strain: NS3 T249P mutation increases viremia and mortality in birds WN02 strain: E-V159A mutation changes viral transmission dynamics in birds and mosquitoes Continued co-evolution: Birds becoming less susceptible to illness and death, but viruses creating higher viremia

WNV Neuroinvasive Disease Incidence, by County, US, 1999-2007

Estimated Number of West Nile Infections and Illnesses, 1999-2013 17,460 neuroinvasive disease cases reported For every reported neuroinvasive disease case, 30-70 non-neuroinvasive disease cases 524,000-1.2 million non-neuroinvasive disease cases 150-300 infections 2.6-5.2 million infections Economic cost of hospitalized patients through 2012: $778 million

Average annual incidence of WNV neuroinvasive disease United States, 1999 2013 1.20 1.00 Incidecne per 100,000 population 0.80 0.60 0.40 0.20 0.00 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Year

Average annual incidence of WNV severe neurological disease by county United States, 1999 2013

Average annual number of WNV neuroinvasive disease cases by county United States, 1999-2013

Vector-Borne Disease Emergence in the United States Humans incidental hosts YES NO Mosquitoes Arboviruses Arboviruses Ticks Arboviruses Bacteria Parasites Not currently important

Distribution of Key Tick-Borne Diseases, 2012 Diseases reported to CDC by state health departments. Each dot represents one case. The county where the disease was diagnosed is not necessarily the county where the disease was acquired.

Notifiable Tick-Borne Diseases in the U.S. Ixodes scapularis (Blacklegged tick) Anaplasmosis Lyme disease Babesiosis Powassan (deer tick virus) infection Amblyomma americanum (Lone star tick) Ehrlichiosis Multiple tick species Rocky Mountain spotted fever

Ixodes scapularis: A Growing Concern Increased frequency and distribution Reforestation Habitat fragmentation Increased deer populations Climate change Increased exposure to tick habitat Suburbanization Deer populations in CT

Reported Tick-Borne Diseases in the United States, 2004-2013 5000 4500 4000 3500 3000 2500 2000 1500 1000 500 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Eh/An tot RMSF Babesia *Includes HGA, HME, and other or unspecified ehrlichiosis Babesiosis became nationally notifiable in 2010

Reported Cases of Lyme Disease by Year, United States, 1996-2013 45,000 40,000 35,000 Probable cases* Confirmed cases Cases 30,000 25,000 20,000 15,000 10,000 5,000 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 *National Surveillance case definition revised in 2008 to include probable cases; details at http://www.cdc.gov/ncphi/disss/nndss/casedef/lyme_disease_2008.htm

Lyme Disease U.S. Case Distribution 17-Year Trend 1996 2012 http://www.cdc.gov/lyme/stats/maps/interactivemaps.html

Lyme Disease Incidence Exceeds 300,000 Three independent approaches: Cases Annually The number of people who tested positive, based on data from a survey of clinical laboratories The number of people diagnosed, based on medical claims information (ICD9 codes) Survey data to estimate the number of people who report that they ve been diagnosed with Lyme disease in the previous year

Recently Recognized Tick-Borne Pathogens in the United States Heartland virus (Amblyomma americanum) Borrelia miyamotoi and other novel borrelia (Ixodes scapularis) 364D rickettsiosis (Dermacentor occidentalis) Rickettsia parkeri (Amblyomma maculatum) Ehrlichia muris-like organism

Heartland Virus N ENGL J MED 367;9 NEJM.838 ORG AUGUST 30, 2012 Two Missouri patients suspected of having ehrlichiosis positive for a novel phlebovirus related to SFTS virus Common features at presentation: Fever, fatigue, headache, nausea, myalgia, arthralgia, thrombocytopenia, and leukopenia. Seven additional cases have now been reported, in Missouri, Oklahoma, Tennessee* Five hospitalized, two died Amblyomma americanum suspected tick vector** Serological evidence indicates widespread exposure to wildlife * MMWR 2014;63:270-1, Clin Infect Dis (on line) ** Am J Trop Med Hyg 2013;89:445-452

Vector-Borne Disease Emergence in the United States Humans only incidental hosts YES NO Mosquitoes Arboviruses Arboviruses Ticks Arboviruses Bacteria Parasites Not currently important

Dengue Caused by four flaviviruses No known important animal reservoir Causes fever, rash, severe pain ( break bone fever ), shock, hemorrhage Subsequent infections increase likelihood of severe disease 400 million infections per year globally Transmitted by Aedes aegypti mosquitoes Have resurged in the Americas since control efforts stopped in 1970s Aedes albopictus can also sustain transmission Introduced to the Americas in 1985

Dengue Incidence is Rapidly Increasing in the Americas 2500000 2000000 Number Cases 1500000 1000000 500000 0 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 Year Source: Pan American Health Organization (PAHO)

Can Dengue Reemerge in Temperate Climates? Dengue in the Continental USA Dengue epidemics until first half of the 1900s 807 returning travelers with dengue reported in 2013 8 outbreaks in Texas since 1980 2 outbreaks in Florida since 2009 Aedes aegypti Aedes albopictus 26

Environmental Parameters Limit Dengue Transmission in the Contiguous States Example: Dengue Outbreak on the US-Mexico Border 8 times more infections in Matamoros 4% infected in Brownsville 32% in Matamoros Substantial Aedes aegypti infestations in both locations Different environmental conditions 85% homes air conditioned in Brownsville; 29% in Matamoros Lot size 3 times greater in Brownsville No air conditioning increased dengue risk 7 fold in Matamoros Smaller lot size increased dengue risk 15 fold in Brownsville Am J Trop Med Hyg 2008;78: 364-9 27

Chikungunya Virus Makonde language: to dry up or become contorted Alphavirus Like dengue Man-mosquito-man transmission cycle Aedes aegypti is the traditional urban vector Also spread by Aedes albopictus Most infected persons symptomatic (76%-97%) Fever (76-100%) and joint pain (71-100%) most common symptoms Outbreak in Americas began in late 2013 in St. Martin

Chikungunya in the Americas* Number countries 35 30 25 20 15 10 5 706,093 reported cases 113 reported deaths 700 600 500 400 300 200 100 Number cases (thousands) 0 Nov Dec Jan Feb Mar Apr May Jun Jul Aug 2013-2014 * Reported to PAHO as of Sept 12 0

Chikungunya in the Western Hemisphere Countries and territories in the Americas where autochthonous chikungunya cases have been reported (as of September 9, 2014).

Chikungunya in the Contiguous United States* Historically, from 2006 2013: An average 28 people/year with positive tests for recent CHIKV infection (Range 5 65 per year) Current Outbreak 43 states reporting cases 934 travel-associated cases 202 (22%) NY 184 (20%) FL 8 locally-acquired cases (FL) * As of Sept 9, 2014; includes HI and AK http://www.cdc.gov/chikungunya/geo/index.html

What s Next? West Nile virus will continue to cause focal and regional outbreaks Dengue and chikungunya virus will remain significant problems in US territories (chikungunya at least for the short-run) Tick-borne diseases will continue to increase in incidence and distribution Discovery of novel tick-borne pathogens, some of public health significance Importation and emergence of pathogens not currently endemic to the US

Are we prepared? ArboNET surveillance system National in scope Human, animal, vector data Flexible Capacity eroding Tick-borne disease surveillance Surveillance present, but incomplete and overwhelmed Advanced molecular detection: Greatly improved capacity for detection of imported and novel agents Communication capacity greatly improved

Are we prepared? Increasing knowledge of ecologic parameters of pathogen transmission Developing vector-borne disease modeling capacity Surveillance can indicate impending WNV outbreaks (at least for the shortrun) and aggressive measures can stop them, but Many localities aren t prepared to respond quickly Lack of adequate surveillance Lack adequate mosquito control Political controversy Pesticide resistance

Are we prepared? Have good treatment regimens for bacterial vector-borne diseases, but Delayed recognition and improper treatment increases morbidity and mortality Lack sensitive diagnostics for early diagnosis of rickettsial diseases and Lyme disease Blood donor screening has almost eliminated the risk of WNV and Chagas disease But at considerable expense Doesn t cover other pathogens, such as dengue, babesia, chikungunya, ehrlichiosis, anaplasmosis Promising late-stage development of dengue vaccines

Are we prepared? Safe and likely effective WNV vaccine constructs exist But no regulatory pathway to bring them to market and may not be sufficiently profitable New and effective public health pesticides are in development But unclear if any will be marketed New non-pesticide vector control tools in development Unclear which will be operationalized

Are we prepared? No effective, scalable vector control method for Ixodes scapularis or Aedes aegypti No Lyme disease vaccine No arboviral therapeutics No regulatory pathway to market Entomologic and ecologic research and training capacity disappearing rapidly

The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the Centers for Disease Control and Prevention