Sun-Whan Park

Severe Fever with Thrombocytopenia Syndrome Virus in Ticks Collected from Humans, South Korea, 2013

We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May–October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea.

Haemaphysalis longicornis a vector that harbors severe fever with thrombocytopenia syndrome virus (SFTSV) is a major species of tick in South Korea. To investigate the existence and prevalence of SFTSV in Korea, we collected ticks from nine provinces in South Korea for detecting SFTSV. In all, we collected 13,053 ticks, and H. longicornis (90.8%, 11,856/13,053) was the most abundant among them. The minimum infection rate (MIR) of SFTSV in H. longicornis was 0.46% (55 pools). SFTSV was detected in ticks during all the developmental stages, showing MIR in larvae (2/350, 0.57%), nymphs (38/10,436, 0.36%), males (2/221, 0.90%), and females (13/849, 1.53%), respectively. Viruses were detected in ticks collected between April and September. A higher MIR was detected in ticks from the southern part of the country. We amplified the M and S segment partial genes from a sample and analyzed the nucleotide sequence. The results showed a 93-98% homology to Chinese and Japanese strains registered in Genbank. In this study, we confirmed the existence of SFTSV for the first time in South Korea. The SFTSV prevalence data from the studies are essential for raising the awareness of SFTS in South Korea.

Nosocomial Transmission of Severe Fever With Thrombocytopenia Syndrome in Korea

Of the 27 healthcare workers (HCWs) who had contact with a fatally ill patient with severe thrombocytopenia syndrome in Korea (SFTS), 4 who were involved in cardiopulmonary resuscitation complained of fever and were diagnosed with SFTS via seroconversion. Exposure to respiratory secretions, blood, or gowns soiled by body fluids was significantly associated with infection of HCWs.

Severe fever with thrombocytopenia syndrome virus, South Korea, 2013.

During 2013, severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in South Korea. Environmental temperature probably affected the monthly and regional distribution of case-patients within the country. Phylogenetic analysis indicated that the isolates from Korea were closely related to isolates from China and Japan.

Use of Plasma Therapy for Severe Fever with Thrombocytopenia Syndrome Encephalopathy.

To the Editor: The central nervous system (CNS) manifestations of severe fever with thrombocytopenia syndrome (SFTS) include apathy, seizure, muscular tremor, and coma (1,2); however, the mechanism underlying CNS manifestations in SFTS is not clear. Deng et al. reported that illness of 15 (13%) of 115 patients with SFTS met the case definition for suspected encephalitis (1). However, they did not present any straightforward evidence of CNS invasion by STFS virus (SFTSV). Cui et al. similarly reported that encephalitis developed in one fifth of 538 patients with SFTS (2). They found evidence of SFTSV by isolating the virus from the cerebrospinal fluid (CSF) in 1 of 2 patients with SFTS whose CSF was obtained, but they did not mention CSF pleocytosis (2). We report a case of SFTS-associated encephalopathy, without pleocytosis and with normal CSF protein and glucose levels, that was confirmed by real-time reverse transcription PCR of the CSF. The patient was treated with experimental plasma exchange followed by convalescent plasma therapy. During 2015, a 62-year-old woman who had a history of treated tuberculous meningitis 10 years earlier was admitted to a tertiary hospital in Seoul, South Korea (Republic of Korea), with a 5-day fever, myalgia, and headache. On hospital day (HD) 2, CSF examination revealed 1 leukocyte/mm3, protein 35 mg/dL (reference 9–58 mg/dL), glucose 74 mg/dL (reference 45–80 mg/dL), and CSF/blood glucose ratio 0.66 (reference 0.50–0.80). No bacteria or fungi were isolated from CSF. On HD 4, her headache worsened, and she displayed confused verbal responses and lacked orientation of time and place. No focal neurologic signs were observed. On HD 5, magnetic resonance imaging of the brain indicated no additional abnormalities of the parenchyma and extra-axial structures except for a focal parenchymal defect in the right midbrain that had been discovered as a sequelae of tuberculous meningitis 10 years earlier. On HD 7, follow-up CSF examination revealed no leukocytes, protein 57 mg/dL, glucose 209 mg/dL, and CSF/blood glucose ratio 0.62. SFTSV was detected by real-time reverse transcription PCR (Technical Appendix) in plasma and CSF (Figure). On HD 8, the patient became comatose and had no eye, verbal, and motor responses to noxious stimuli (Glasgow coma scale 3). Bilateral exotropia was noted with spared light and corneal reflexes and oculocephalic responses. Experimental plasma exchange was performed, and her viral load declined slightly; however, consciousness and platelet count did not change. An ABO-identical nurse who had recovered from SFTS in September 2014 agreed to donate plasma; her indirect immunofluorescence antibody assay (IFA) for SFTSV IgG had been 1:1,024 in October 2014. On HD 17, the patient’s titer of SFTSV IgG was 1:64 before the plasma therapy. We obtained ≈400 mL of convalescent plasma (IFA assay for SFTSV IgG 1:256 at the time of donation) from the donor and transfused it into the patient on HD 17. The viral load in the blood decreased steeply by a factor of 10 (6 × 102 to 6 × 101 copies/mL) during the first 7 hours (4–11 pm on HD 17); it then gradually decreased from 3 × 101 at 7 am on HD 18 to 6 × 100 copies/mL on HD 20, by which time the patient’s mental status had fully recovered (Figure). Figure Changes in viral RNA load and immunofluorescence antibody titer and timing of therapies for a 62-year-old woman with SFTSV-associated encephalopathy in response to plasma exchange followed by convalescent plasma therapy, South Korea, 2015. CSF, cerebrospinal ... This case is unique in that SFTS was detected in CSF in the absence of pleocytosis and with normal CSF protein and glucose levels, as in previous reports on influenza-associated acute encephalopathy (3). Although headache and encephalitis can occur in patients with SFTS (1,2), the pathophysiology of CNS manifestations in SFTS is unknown. As with influenza-associated acute encephalopathy, a possible hypothesis is direct invasion of SFTSV into the CNS; another hypothesis is that elevated cytokine levels or renal and hepatic dysfunction are associated with SFTS encephalopathy. We are aware of 1 report of a favorable outcome of plasma exchange and ribavirin in 2 patients with SFTS and multiorgan failure in South Korea (4). However, the patients’ clinical condition did not substantially improve despite the 5-day plasma exchange therapy and viral load only slightly decreased. Use of convalescent plasma therapy in severe acute respiratory syndrome, influenza A(H1N1) and A(H5N1), and Ebola virus disease has been reported (5–7), but little evidence exists to support its use. However, given the lack of conclusive data, these potential experimental treatments for emerging infectious diseases warrant further study in a clinical trial. Response was favorable in a mouse model of SFTS treated postexposure with antiserum from a patient who had recovered from SFTS (8). We do not know whether the convalescent plasma therapy given to the patient described here actually had a positive effect because her IFA titer was already increasing around the time she received the plasma therapy. At the time of this writing, 2 patients with SFTS who were treated with intravenous immunoglobulin and corticosteroid had been reported (9). Cautious interpretation of these experimental therapies is necessary because these therapies may not have had anything to do with the patients’ recovery. Technical Appendix: Performance of real-time reverse transcription PCR to detect severe fever with thrombocytopenia syndrome virus RNA. Click here to view.(82K, pdf)

Molecular genomic characterization of tick- and human-derived severe fever with thrombocytopenia syndrome virus isolates from South Korea

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. Methodology/Principal findings In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV. Conclusions/Significance Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia.

One-Step Reverse Transcription-Polymerase Chain Reaction for Ebola and Marburg Viruses

Objectives Ebola and Marburg viruses (EBOVs and MARVs, respectively) are causative agents of severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. In 2014, there was a major Ebola outbreak in various countries in West Africa, including Guinea, Liberia, Republic of Sierra Leone, and Nigeria. EBOV and MARV are clinically difficult to diagnose and distinguish from other African epidemic diseases. Therefore, in this study, we aimed to develop a method for rapid identification of the virus to prevent the spread of infection. Methods We established a conventional one-step reverse transcription-polymerase chain reaction (RT-PCR) assay for these pathogens based on the Superscript Reverse Transcriptase-Platinum Taq polymerase enzyme mixture. All assays were thoroughly optimized using in vitro-transcribed RNA. Results We designed seven primer sets of nucleocapsid protein (NP) genes based on sequences from seven filoviruses, including five EBOVs and two MARVs. To evaluate the sensitivity of the RT-PCR assay for each filovirus, 10-fold serial dilutions of synthetic viral RNA transcripts of EBOV or MARV NP genes were used to assess detection limits of viral RNA copies. The potential for these primers to cross react with other filoviruses was also examined. The results showed that the primers were specific for individual genotype detection in the examined filoviruses. Conclusion The assay established in this study may facilitate rapid, reliable laboratory diagnosis in suspected cases of Ebola and Marburg hemorrhagic fevers.

Full-Genome Sequences of Severe Fever with Thrombocytopenia Syndrome Virus, Isolated from South Korea in 2014

ABSTRACT Here, we present the full-length genome sequencing of severe fever with thrombocytopenia syndrome (SFTS) virus, isolated from South Korea in 2014. The five Korean strains were compared by phylogenetic analysis with full SFTS genome sequences of two neighboring nations, China and Japan.

Severe Fever with Thrombocytopenia Syndrome Presenting with Hemophagocytic Lymphohistiocytosis

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the newly discovered SFTS Bunyavirus, and there have been no case reports of SFTS patients presenting with hemophagocytic lymphohistiocytosis (HLH) in the English literature. We report a case of SFTS presenting with HLH in a 73-year-old immunocompetent male farmer. Although the patient had poor prognostic factors for SFTS, such as old age and central nervous system symptoms, he recovered fully with supportive care.

Needle-Stick Injury Caused by a Patient With Severe Fever With Thrombocytopenia Syndrome in Korea

To the Editor—Several studies have identified clusters of severe fever with thrombocytopenic syndrome (SFTS) infections among family members and that appear to have been transmitted by human contact. In addition, possible transmission from the index patient with SFTS to healthcare workers (HCWs) has been reported. Blood and body fluids were suggested as the possible transmission route. Therefore, strict adherence to routine blood and body fluid precautions is required when HCWs come into contact with any patient, especially anyone with suspected viral hemorrhagic fever or a tick-borne rickettsial disease. Herein we report the result of needle-stick injury to an HCW caused by a patient with a high viral load of SFTS. A 62-year-old woman was admitted to Asan Medical Center with a 5-day fever, myalgia, and a headache (July 1, 2015). On her hospital day (HD) 6, her blood pressure decreased to 80/45 mm Hg and her condition rapidly declined, causing a need for mechanical ventilation. The patient was admitted to the intensive care unit. On HD 7, SFTS-associated encephalopathy was diagnosed from detection of SFTS virus (SFTSV) by real-time polymerase chain reaction assay (RT-PCR) from plasma and cerebrospinal fluid. On HD 12, a nurse who took care of the patient experienced needle-stick injury on her finger during blood sampling. The needle was filled with the patient’s blood. The needle penetrated her left third finger skin with a notable amount of bleeding. The viral load of the patient was 1 × 10 on HD 13. Four days later (July 16, 2015), we checked her blood for SFTSV by RT-PCR and immunofluorescence assay titer for evaluation of possible SFTSV transmission, despite no development of symptoms, because there was a previous report of subclinical infection in 1 HCW who had contacted an index patient. SFTSV was not found by RT-PCR and the total immunoglobulin G level for SFTSV immunofluorescence assay was less than 1:32. The HCW had not developed any symptoms 6 weeks after the needle-stick injury. Her convalescent serum drawn 1 month after the injury recheck (August 13, 2015) revealed SFTSV was not detected by RT-PCR and the total immunoglobulin G level for SFTSV immunofluorescence assay was less than 1:32. Recently, viral hemorrhagic fevers, such as Ebola virus disease, have attracted renewed attention owing to the large Ebola virus disease outbreak in West Africa. Therefore, nosocomial transmission to HCWs from patients with suspected viral hemorrhagic fever is of paramount importance. SFTSV is a third group within the genus phlebovirus, family Bunyaviridae, one of the 5 families causing viral hemorrhagic fever. Interestingly, the overall transmission rate of SFTS in a previous study by our group was 15%, which is comparable to the household transmission rate (16%) of Ebola virus disease in the absence of personal protective devices. Therefore, it is theoretically possible that direct inoculation of blood that contains sufficient volumes of infectious SFTS can cause infection via needle-stick injury. Fortunately, SFTSV was not transmitted in our case despite the high viral load in the index patient’s blood. However, the possible effects of needle-stick injury, such as Ebola virus disease transmission, deserve further scrutiny.