Tick-borne Diseases, an Emerging Health Threat to US Forces Korea Terry A. Klein, COL (Ret), PhD Vector-borne Disease Program Manager FHP&PM,
AGENDA Objectives, Concept, Organization Mite-, Tick, and Flea-borne Diseases Scrub Typhus (mite-borne) SFG Rickettsia (mite-, flea-, tick-borne) Anaplasmosis/ Ehrlichiosis (tick-borne) SFTS virus (tick-borne, nosocomial) TBE (tick-borne) Babesiosis (tick-borne) Bartonellosis (flee-, tick-borne) 2
Concept Vector-borne Disease Surveillance Establish comprehensive vector-borne disease (VBD) surveillance programs in collaboration with US Army, Air Force, and Navy, GEIS partners, US agencies, and ROK military and KCDC/KNIH. Program components: Mosquito-, tick-, flea-, mite- and rodent-borne pathogens of medical and veterinary importance that includes: epidemiological investigations; mapping vector and VBD distributions; geographical, seasonal, and risk assessments; outbreak response; and vector/host and disease control. Provide up-to-date febrile vector-borne disease information to the medical community
Disease Murine typhus (flea-borne) Scrub typhus mite-borne Ehrlichiosis/ Anaplasmosis Tick-, Mite, and Flea-borne Health Threats in the ROK Risk* Low Intermediate Intermediate Typical Risk Period Typical Severity Potential attack rates/month (in the absence of countermeasures for personnel in field conditions) Mild to Rare cases, risk varies by exposure Year-round Severe and vector populations Seasonal < %, 6,000 Korean cases; under Moderate (Apr-Dec) diagnosed in US personnel Risk present, KCDC un-reportable, Seasonal (Mar-Nov) Very Severe level unknown; Positive ticks at US training sites Mode of Transmission Infected flea feces that enter the bite wound Larval chigger mites Ticks Lyme disease Intermediate Seasonal (Mar-Oct) Moderate to Severe Risk present, level unknown; Symptoms differ from US form Ticks Rickettsioses, tick-borne (SFG, and others)** Tick-borne encephalitis (TBE) Severe fever w/ thrombocytopenia syndrome (SFTS) Intermediate Intermediate Intermediate Seasonal (Mar-Nov) Seasonal (Mar-Nov) Seasonal (Mar-Nov) Moderate to Severe Risk present, 2% of US soldiers seropositive, under reported, level unknown Risk present, KCDC un-reportable, Moderate to level unknown; Positive ticks on Very Severe Jeju Island Moderate to Very Severe Risk present, level unknown; KCDC positive ticks; Common at US military training sites Fleas, Mites, Ticks Ticks Ticks, nosocomial (blood of infected patients) *National Center for Medical Intelligence Assessment, 200; **SFG rickettsiae are not reportable diseases (KCDC)
Scrub Typhus: A Hidden Disease (A War-Stopper) Leptotrombidium pallidum Leptotrombidium scutellare Mite-borne zoonoses, Leptotrombidium spp., transmitted by bite of larval mite and maintained only through transovarial transmission Causitive Agent: Orientia tsutsugamushi (Many serotypes) Eschar with maculopapular rash Serologically difficult to diagnose Distribution: Central, eastern, and southeastern Asia Explosive epidemics: poverty, rats/mice, disasters, wars Incubation period: 6-2 days, usually 0-2 days Although 5 US Soldiers seroconverted for scrub typhus in 995 while deployed to Korea, no cases were reported 5
Percent Seroconversion Annual No. of Scrub Typhus Cases SFG Rickettsia and Scrub Typhus 2.5 2.5 (8/898) No cases reported while in Korea!! Ticks on Tick Drag 0.5 0 (0/929) (5/935) Spotted Fever Group Typhus Group Scrub Typhus Group 2000 0000 8000 6000 000 Eschar Before Fever 2000 0 9 95 96 97 98 99 00 0 02 03 0 05 06 07 08 09 0 2 3 5 6 From 995 pre- and post-deployment sera for US Soldiers deployed to Korea. Rash appears on the trunk about 7 days After Fever UNTIL 202 (ONE UNCONFIRMED CASE), THERE WERE NO CASES REPORTED FROM US SOLDIERS WHILE STATIONED IN KOREA, EVEN WHEN TYPICAL ESCHARS WERE OBSERVED
Number of Scrub Typhus Cases, 2003-203 Cumulative Weekly Incidence of Scrub Typhus Cases in ROK Populations 2003-20 Most of cases reported in the southern half of the ROK Two primary vectors, L. scutelare (south), L. pallidum (north) Most cases are reported during the fall; >8,000 cases from 202-205 Empirically, cases are similar to SFG Rickettsia Two cases reported during 202 and 203 among US personnel,000 0,000 9,000 8,000 7,000 6,000 5,000,000 3,000 2,000,000 0 20 203 202 20 200 2009 2008 2007 2006 2005 200 2003 3 5 7 9 3 5 7 9 2 23 25 27 29 3 33 35 37 39 3 5 7 9 5 203 202 20 2005 2006 2007, 2008 200 2009, 20 200 2003 7
Tick-borne Disease Surveillance Collect ticks from vegetation, mammals, reptiles, and birds to determine their geographical and host distributions Identify ticks; determine their relative abundance and identify new records and species Determine tick habitats suitable for the collection of large numbers of ticks Curate ticks and provide them to GEIS and KNIH partners to be assayed for tick-borne pathogens Determine the distribution of tick-borne pathogens Access tick-borne disease risks among US and ROK populations Collecting ticks from vegetation by tick drag Ticks feeding on a lizard Tick feeding on a rodent Tick feeding on a bird Tick Bite 8
Ecology of Tick-borne Diseases in Korea Following Japanese occupation, WWII, and Korean War, hills and mountains mostly devoid of forests 960 s Tree planting policy instituted Effects of reforestation on birds, small/large mammal, and reptile populations unknown Comprehensive tick-borne zoonoses surveillance lacking Incidence/prevalence of diseases unknown; Some non-reportable (KCDC); Mortality rates 2-30% Early detection & treatment critical Potential serious health threat to US Forces Korean War Burial Mound Present 9
SFG Rickettsia and Other Pathogens There were a total of 906/,0 pools (62.9%) of all ticks collected during 20 positive for Rickettsia spp. A total of 592/026 (57.7%) H. longicornis pools were positive for RHIAgent Rickettsia spp. primers A total of 82/,026 (8.0%) H. longicornis pools were positive for Rickettsia spp. A total of 3/2 (2.%) Ixodes nipponensis pools were positive for R. monacensis A total of 223/285 (9.8%) of H. flava pools were positive for Rickettsia spp. Borrelia spp. close to B. afzelii and B. garinii; B. burgdorferi s.s., not in Korea *During 203, pool each of H. longicornis also positive for A. phagocytophilum and E. chaffeensis Tick Species # Tick pools Rickettsia spp. (genus-specific) Rickettsia spp. Rickettsia spp. (HlR) Rickettsia monacensis* Anaplasma phagocytophilum Bartonella Ehrlichia chaffeensis spp. (genusspecific) Borrelia spp. Borrelia spp. (genus-specific) Amblyomma testudinarium 0 0 na na 0 0 0 0 0 Haemaphysalis flava 285 223 ( 78.2%) na na 0 0 0 5 (5.3%) 0 Haemaphysalis longicornis Borrelia s.l. Group,026 67 (65.7%) 592 (57.7%) na 0* 0* 0 (.3%) 0 Haemaphysalis phasiana 3 0 na na 0 0 0 0 0 Ixodes nipponensis 2 9 na 3 (2.%) 2 (/6%) 0 0 30 (2.2%) 3 (0.5%) Ixodes turdus 0 na na 0 0 0 0 0 Total,0 906 (62.9%) 592 (.%) 3 (2.%) 2 (0.%) 0 0 89 (6.2%) 3 (0.9%) * Only I. nipponensis assayed for R. monacensis.
Spotted Fever Group Rickettsiae SFG rickettsiae consist of a number of rickettsial agents, mostly transmitted by ticks Exceptions are R. typhi and R. felis (murine typhus; fleas) and R. akari (rickettsialpox; mites) Incubation period is usually 5- days; many infections result in an eschar at the bite site before the onset of fever; a maculopapular rash appears on the extremities 3-5 days after the onset of fever that may move to the trunk Rickettsial agents are often classified as non-pathogenic until patients are diagnosed with disease There are at least 5 SFG rickettsiae strains/species in the ROK; they are currently being characterized; one () has been identified (R. monacensis, a known pathogen); two (2) are close to R. heilongiensis and R. japonica (both known pathogens; two (2) are have not been characterized At least 2 patients with symptoms of SFG Rickettsia and negative for scrub typhus have presented at the Brian Allgood Army Community Hospital SFG richettsiae are not reportable diseases in Korea; may be confused with scrub typhus All stages of ticks (transovariol transmission) are infective
Annual Number Cases Lyme Disease Lyme Disease Borrelia burgdorferi is the causative agent of Lyme disease in the US and transmitted by Ixodes spp. Borellia afzelii, B. burgdorferi s.l. and B. garinii detected in I. persulcatus, I. nipponensis, Haemaphysalis longicornis, and H. flava. First case reported by KCDC in 200. Early diagnosis and treatment important; patients may develop severe joint pain and neurological and cardiac symptoms. Treatment with doxycycline, amoxicillin, or cefuroxime axetil; In severe cases, IV treatment with ceftriazone or penicillin. 6 2 0 8 6 2 0 Only reportable since 202 202 203 20 205 Year Bulls Eye at Bite Site not always present in Korea
SFTS Epidemiology and Prevention Transmission: By bite of infected tick (Haemaphysalis longicornis, H. flava, Ixodes nipponensis, Amblyomma testudinarium) Nosocomial transmission: Blood contact Incubation Period: 6- days Environmental: Rural areas, grasses, forests Seasonal: March-November Zoonotic/Domestic Hosts: Mammals, including: goats, sheep, cattle, pigs, monkeys, dogs, cats, deer, rodents Transovarial transmission: All stages infective Prevention: No vaccine. Use personal protective measures; repellents, proper clothing, habitat avoidance Tick Removal: Do not burn or use other methods as this may enhance infection Collecting ticks from vegetation by tick drag Engorged H. flava Unfed H. longicornis 3
SFTS Current Distribution China/Japan China 2009: first emergence of an SFTS in central China(Hubei, Henan) 200: 53 cases (deaths 8, 5.%) 20: 6 cases (6 deaths, 0%) 203: 676 cases (8 deaths, 7.%) Annual downward trend in mortality as cases are recognized Japan 203 203: 7 cases, 9 deaths (52.9%) Map of China and Japan showing the geographic distribution of SFTS patients. Fan Ding et al. Epidemiologic Features of SFTS in China. 20-202. CID(Online first) Mar.3,203. Korea 203 First case (retrospective) 202 203: 36 cases, 7 deaths (.%) 20: 5 cases, 6 deaths (3.%) 205: 78 cases, 2 deaths (26.9%) Based on mortality rates in China, non-hospitalized mildmoderate cases not reported
Chungcheongbuk Geographical Distribution of SFTS Patients in the ROK, 203 and 20 Incheon Seoul Gyeonggi Gangwon 3 Incheon 2 Seoul 7 Gangwon 2 2 2 Daejeon 7 Daejeon 9 Jeollabuk Gwangju 5 Jeollanam 5 Daegu Gyeongsangnam 2 Ulsan Busan Gwangju Jeollabuk Jeollanam Daegu Gyeongsangnam Ulsan Busan 6 Jeju Isalnd 36 cases, 7 deaths (7.2% mortality) Jeju Isalnd 7 5 cases, 6 deaths (3.% mortality) SFTS Survival SFTS Death US Installation
Chungcheongbuk Geographical Distribution of SFTS Patients during 205 through June 206 Incheon 2 Seoul 7 Gangwon Incheon Seoul 7 Gangwon 2 Daejeon 2 9 0 Daejeon 8 Gyeongsangbuk Gwangju Jeollabuk Jeollanam Daegu Gyeongsangnam Ulsan Busan Jeollabuk 0 Gwangju Jeollanam Daegu Gyeongsangnam Busan 50 cases, 6 deaths (32.0% mortality) 78 cases, 2 deaths SFTS Survival (26.9% mortality) 36 cases, 5 deaths SFTS Death (3.9% mortality) US Installation Jeju Isalnd 7
Chungcheongbuk Geographical Distribution of SFTS Positive Ticks Collected from Vegetation during 20 Incheon Seoul Gangwon Daejeon Jeollabuk Daegu Ulsan Gwangju Jeollanam Busan Jeju Isalnd SFTSV Positive Ticks
Number SFTS Cases, by Age Number SFTS Cases, by Gender Distribution of SFTS patient survival and deaths based on patient age and gender in the ROK, 203-20 30 25 20 5 0 5 0 <0 0-9 20-29 30-39 0-9 50-59 60-69 70-79 80-89 >90 Male Female 0 35 30 25 20 5 0 5 0 <0 0-9 20-29 30-39 0-9 50-59 60-69 70-79 80-89 >90 Survive Death
Distribution of SFTS patients by age and gender in China Based on studies by Liu et al. (Scientific Reports, 205), the age and gender of Chinese populations follow a similar pattern as that shown for Korea Similarly, in Korea the composition of males and females positive for SFTS virus is similar
Number SFTS Cases/year Number of SFTS Cases, by Month Monthly distribution of SFTS patients, including survival and deaths, in the ROK, 203-205 0 35 30 25.7% 38.2% 37.9% 33.3% 7.2% 20 5 37.5% 0 5 0 20.0% Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Survive Death 00 80 60 26.9% 0 20 7.2% 32.0% 0 203* 20 205 Survive Death China, epidemic peak is from May-July (>67% of all cases) Korea, epidemic peak extends from June-October (86.7%), while only.8% of the cases are reported from May-July.
What we know: Understanding the Epidemiology Rickettsia monacensis recently identified (manuscript published) Haemaphysalis longicornis, H. flava, and Ixodes nipponensis are the primary ticks More than 95% of all ticks collected from rodents are Ixodes nipponensis species of ticks positive for SFTS virus. Are they vectors? What we suspect: R. japnonica and R. heilongiensis may be present (identified, but not confirmed) Reforestation results in the potential for increasing tick-borne disease threats Deer, wild pig, feral dog and other small-large mammals increasingly present Rodents are one of the reservoirs for R. monacensis What we don t know: What is the distribution of wild/feral animals; affect on tick population distributions? What is the geographical and seasonal distributions of ticks? Are Soldiers being bitten by ticks? What are the annual transmission rates among US Soldiers to predict risk? What are the vectors of rickettsial? Ticks, mites, and/or fleas? What tick species are the primary vectors of SFTS and TBE viruses?
Sunset over the Demilitarized Zone QUESTIONS Collaborators: Dr. Heung-Chul Kim, CPT Jaree Johnson (5 th MED DET, 65 th MED BDE) LTC Hengmo McCall, Ms. Suk-Hee Yi (FHP&PM, ) Dr. Jin-Won Song and others (Korea University) Dr. Joon-Sook Chae, Seoul Natl University Dr. Won-Jang Jong (Konkuk University) Dr. Won-Ja Lee (Korea NIH) Dr. Allen Richards, and others (NMRC) Dr. Michael Wiley, Dr. Gustavo Palacios, and others (USAMRIID) LTC Richard Jarman, Dr. Jun Hang, and others (WRAIR) North Korea Funding provided by the Global Emerging Infections Surveillance and Response System (GEIS), Armed Forces Health Surveillance Branch (AFHSB) and the National Center for Medical Intelligence (NCMI), Korea Centers for Disease Control and Prevention. South Korea