Human-Pathogenic Kasokero Virus in Field-Collected Ticks.
Schuh Amy J,Amman Brian R,Patel Ketan,Sealy Tara K,Swanepoel Robert,Towner Jonathan S
Emerging infectious diseases
Kasokero virus (KASV; genus Orthonairovirus) was first isolated in 1977 at Uganda Virus Research Institute from serum collected from Rousettus aegyptiacus bats captured at Kasokero Cave, Uganda. During virus characterization studies at the institute, 4 laboratory-associated infections resulted in mild to severe disease. Although orthonairoviruses are typically associated with vertebrate and tick hosts, a tick vector of KASV never has been reported. We tested 786 Ornithodoros (Reticulinasus) faini tick pools (3,930 ticks) for KASV. The ticks were collected from a large R. aegyptiacus bat roosting site in western Uganda. We detected KASV RNA in 43 tick pools and recovered 2 infectious isolates, 1 of which was derived from host blood-depleted ticks. Our findings suggest that KASV is maintained in an enzootic transmission cycle involving O. (R.) faini ticks and R. aegyptiacus bats and has the potential for incidental virus spillover to humans.
Nairobi Sheep Disease Virus: A Historical and Epidemiological Perspective.
Krasteva Stephanie,Jara Manuel,Frias-De-Diego Alba,Machado Gustavo
Frontiers in veterinary science
Nairobi Sheep Disease virus (NSDv) is a zoonotic and tick-borne disease that can cause over 90% mortality in small ruminants. NSDv has historically circulated in East Africa and has recently emerged in the Asian continent. Despite efforts to control the disease, some regions, mostly in warmer climates, persistently report disease outbreaks. Consequently, it is necessary to understand how environmental tolerances and factors that influence transmission may shed light on its possible emergence in other regions. In this study, we quantified the available literature of NSDv from which occurrence data was extracted. In total, 308 locations from Uganda, Kenya, Tanzania, Somalia, India, Sri Lanka and China were coupled with landscape conditions to reconstruct the ecological conditions for NSDv circulation and identify areas of potential disease transmission risk. Our results identified areas suitable for NSDv in Ethiopia, Malawi, Zimbabwe, Southeastern China, Taiwan, and Vietnam. Unsuitable areas included Democratic Republic of Congo, Zambia, and Southern Somalia. In summary, soil moisture, livestock density, and precipitation predispose certain areas to NSDv circulation. It is critical to investigate the epidemiology of NSDv in order to promote better allocation of resources to control its spread in regions that are more at risk. This will help reduce disease impact worldwide as climate change will favor emergence of such vector-borne diseases in areas with dense small ruminant populations.
Detection of a novel putative phlebovirus and first isolation of Dugbe virus from ticks in Accra, Ghana.
Kobayashi Daisuke,Ohashi Mitsuko,Osei Joseph H N,Agbosu Esinam,Opoku Millicent,Agbekudzi Alfred,Joannides Joannitta,Fujita Ryosuke,Sasaki Toshinori,Bonney J H Kofi,Dadzie Samuel,Isawa Haruhiko,Sawabe Kyoko,Ohta Nobuo
Ticks and tick-borne diseases
Ticks are ectoparasites that transmit various types of human and animal pathogens. In particular, emerging and re-emerging diseases caused by tick-borne viruses are public health concerns around the world. However, in many countries of the sub-Saharan African region, epidemiological information on tick-borne viral infections is limited, and their prevalence and distribution remain largely unknown. In this study, we conducted surveillance on ticks to detect medically important tick-borne bunyaviruses in three study sites in and near to Accra, the capital city of Ghana, in 2015. Domestic dogs and cattle were surveyed and were found to be infested with various tick species belonging to the genera Rhipicephalus, Amblyomma and Haemaphysalis. Importantly, we detected a novel putative phlebovirus in Rhipicephalus ticks, and successfully isolated a new strain of Dugbe virus from Am. variegatum ticks. To our knowledge, this is the first report of tick-associated viruses in Ghana other than Crimean-Congo hemorrhagic fever virus.
Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo.
Fajs Luka,Humolli Isme,Saksida Ana,Knap Nataša,Jelovšek Mateja,Korva Miša,Dedushaj Isuf,Avšič-Županc Tatjana
Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick borne disease often associated with hemorrhagic presentations and high case fatality rate. Kosovo is a highly endemic area for CCHF, with a significant case fatality rate. The aim of our study was to determine the prevalence of CCHF in Kosovo. We tested 1105 serum samples from healthy population in both endemic and non-endemic areas in the country. Our results revealed a seroprevalence of 4.0% (range 0-9.3%) which is comparable to the seroprevalence in other countries. We show that seroprevalence is correlated to the disease incidence in each studied municipality. We also tested 401 animal sera (353 cow, 30 sheep, 10 goat and 8 chicken) in four endemic municipalities in Kosovo. We detected specific antibodies in all animals except in chicken. Seroprevalence in cows is comparable to other endemic areas and correlates to the seroprevalence in humans. No CCHF RNA could be detected in 105 tick samples obtained in 2012 and 2013. Sequencing of CCHFV positive ticks from 2001 revealed that the virus is most closely related to viral strains that were detected in CCHF patients from Kosovo. Results suggest that mild CCHF cases are most probably underdiagnosed and consequently that the burden of disease is higher than reported. Our study provides key information for CCHF surveillance and raises awareness for possible imported cases in CCHF non-endemic countries.
Kupe virus, a new virus in the family bunyaviridae, genus nairovirus, kenya.
Crabtree Mary B,Sang Rosemary,Miller Barry R
Emerging infectious diseases
We have previously described isolation and preliminary identification of a virus related to Dugbe virus (DUGV), family Bunyaviridae, genus Nairovirus. Six isolates of the virus were obtained from pools of Amblyomma gemma and Rhipicephalus pulchellus ticks collected from hides of cattle in Nairobi, Kenya, in October 1999. We report results of further characterization of this virus, including growth kinetics in cell culture and full-length genome sequencing and genetic characterization, which show it to be distinct from DUGV. We suggest that this is a new virus in the family Bunyaviridae, genus Nairovirus, and we propose that it be designated Kupe virus.
Molecular detection of Crimean-Congo haemorrhagic fever virus in ticks collected from infested livestock populations in a New Endemic Area, South of Iran.
Farhadpour F,Telmadarraiy Z,Chinikar S,Akbarzadeh K,Moemenbellah-Fard M D,Faghihi F,Fakoorziba M R,Jalali T,Mostafavi E,Shahhosseini N,Mohammadian M
Tropical medicine & international health : TM & IH
OBJECTIVE:Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with potentially fatal systemic effects on man. We aimed to determine the presence of CCHF virus among collected ticks from domestic livestock from October 2012 to September 2013. METHODS:A total of 1245 hard and soft ticks were collected from naturally infested ruminants in Marvdasht County, Fars Province, south of Iran. Nine tick species and one unidentified species in four disparate genera were detected. A total of 200 ticks were randomly selected and analysed by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of CCHF virus genome. RESULTS:The viral genome was detected in 4.5% (9 samples) of the studied tick population. The infected ticks belonged to the species of Hyalomma marginatum' Hyalomma anatolicum and Rhipicephalus sanguineus. The viruses detected in these three tick species were clustered in the same lineage as Matin and SR3 strains in Pakistan and some other Iranian strains. These results indicate that the ticks were wildly infected with a genetically closely related CCHF virus in the region. CONCLUSION:Regular controls and monitoring of livestock to reduce the dispersion of ticks and providing information to those involved in high-risk occupations are urgently required.
Crimean-Congo hemorrhagic fever in European part of Turkey: genetic analysis of the virus strains from ticks and a seroepidemiological study in humans.
Gargili Aysen,Midilli Kenan,Ergonul Onder,Ergin Sevgi,Alp Hatice G,Vatansever Zati,Iyisan Selma,Cerit Cigdem,Yilmaz Gulden,Altas Kemal,Estrada-Peña Agustin
Vector borne and zoonotic diseases (Larchmont, N.Y.)
A survey of ticks from domestic ruminants, together with a serosurvey in humans was conducted in Thrace (northwestern Turkey) to evaluate the prevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) in ticks and humans. More prevalent ticks were Hyalomma marginatum, Hyalomma aegyptium, Rhipicephalus bursa, and Rhipicephalus (Boophilus) annulatus, with low numbers of Dermacentor marginatus, Rhipicephalus sanguineus group, and Ixodes ricinus. No differences in the tick faunal composition were found among surveyed provinces. CCHFV was detected using specific primers for strains belonging to both Europe 1 and Europe 2 clades in a total of 15 pools of ticks collected in nine localities. The maximum likelihood estimate of infection rate was calculated as 0.72/100 ticks (95% CI = 0.42-1.16). Viral RNA was observed only in H. marginatum, R.(B.) annulatus, and R. bursa with overall maximum likelihood estimate infection rates being 0.93 (95% CI = 0.35-2.05), 0.74 (95% CI = 0.24-1.78), and 1.67 (95% CI = 0.69-3.46), respectively. The surveyed region is the only place where both viral strains are circulating together in nature in Turkey. Results from serosurvey on 193 samples from three localities in the region showed that immunoglobulin M and immunoglobulin G rates are compatible with an epidemiological situation in which the virus has been present for a long time and is not the result of a recent invasive event from the main epidemic center in Anatolia (north-central Turkey). Seropositivity rates cannot be compared against the tick faunal composition, because of the homogeneity in the results about tick surveys. The high rate of seropositivity, and the prevalence of CCHFV in both Europe 1 and 2 clades among the ticks, but few clinical cases suggest that the circulation of both viral strains may confer protection against the CCHFV infection.
Tick-borne pathogens, including Crimean-Congo haemorrhagic fever virus, at livestock markets and slaughterhouses in western Kenya.
Chiuya Tatenda,Masiga Daniel K,Falzon Laura C,Bastos Armanda D S,Fèvre Eric M,Villinger Jandouwe
Transboundary and emerging diseases
Vectors of emerging infectious diseases have expanded their distributional ranges in recent decades due to increased global travel, trade connectivity and climate change. Transboundary range shifts, arising from the continuous movement of humans and livestock across borders, are of particular disease control concern. Several tick-borne diseases are known to circulate between eastern Uganda and the western counties of Kenya, with one fatal case of Crimean-Congo haemorrhagic fever (CCHF) reported in 2000 in western Kenya. Recent reports of CCHF in Uganda have highlighted the risk of cross-border disease translocation and the importance of establishing inter-epidemic, early warning systems to detect possible outbreaks. We therefore carried out surveillance of tick-borne zoonotic pathogens at livestock markets and slaughterhouses in three counties of western Kenya that neighbour Uganda. Ticks and other ectoparasites were collected from livestock and identified using morphological keys. The two most frequently sampled tick species were Rhipicephalus decoloratus (35%) and Amblyomma variegatum (30%); Ctenocephalides felis fleas and Haematopinus suis lice were also present. In total, 486 ticks, lice and fleas were screened for pathogen presence using established molecular workflows incorporating high-resolution melting analysis and identified through sequencing of PCR products. We detected CCHF virus in Rh. decoloratus and Rhipicephalus sp. cattle ticks, and 82 of 96 pools of Am. variegatum were positive for Rickettsia africae. Apicomplexan protozoa and bacteria of veterinary importance, such as Theileria parva, Babesia bigemina and Anaplasma marginale, were primarily detected in rhipicephaline ticks. Our findings show the presence of several pathogens of public health and veterinary importance in ticks from livestock at livestock markets and slaughterhouses in western Kenya. Confirmation of CCHF virus, a Nairovirus that causes haemorrhagic fever with a high case fatality rate in humans, highlights the risk of under-diagnosed zoonotic diseases and calls for continuous surveillance and the development of preventative measures.
The high genetic variation of viruses of the genus Nairovirus reflects the diversity of their predominant tick hosts.
Honig Jessica E,Osborne Jane C,Nichol Stuart T
The genus Nairovirus (family Bunyaviridae) contains seven serogroups consisting of 34 predominantly tick-borne viruses, including several associated with severe human and livestock diseases [e.g., Crimean Congo hemorrhagic fever (CCHF) and Nairobi sheep disease (NSD), respectively]. Before this report, no comparative genetic studies or molecular detection assays had been developed for this virus genus. To characterize at least one representative from each of the seven serogroups, reverse transcriptase-polymerase chain reaction (RT-PCR) primers targeting the L polymerase-encoding region of the RNA genome of these viruses were successfully designed based on conserved amino acid motifs present in the predicted catalytic core region. Sequence analysis showed the nairoviruses to be a highly diverse group, exhibiting up to 39.4% and 46.0% nucleotide and amino acid identity differences, respectively. Virus genetic relationships correlated well with serologic groupings and with tick host associations. Hosts of these viruses include both the hard (family Ixodidae) and soft (family Argasidae) ticks. Virus phylogenetic analysis reveals two major monophyletic groups: hard tick and soft tick-vectored viruses. In addition, viruses vectored by Ornithodoros, Carios, and Argas genera ticks also form three separate monophyletic lineages. The striking similarities between tick and nairovirus phylogenies are consistent with possible coevolution of the viruses and their tick hosts. Fossil and phylogenetic data placing the hard tick-soft tick divergence between 120 and 92 million years ago suggest an ancient origin for viruses of the genus Nairovirus.
Crimean-Congo hemorrhagic fever virus in ticks in Turkey: A broad range tick surveillance study.
Orkun Ömer,Karaer Zafer,Çakmak Ayşe,Nalbantoğlu Serpil
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
In Turkey, Crimean-Congo hemorrhagic fever (CCHF) outbreaks started in northern regions in 2002. Human cases still continue to increase and the disease spreads in many other provinces of Turkey. The ecological role of the vector tick species occurring in Turkey is not certain exactly. Therefore, we planned a broad range tick study in three different ecological and geographical areas extending from the West Black Sea regions down to the Central Anatolia. The aim of this study was to determine and characterize CCHFV molecularly in feeding-ticks collected from various wild and domestic animals and from humans as well as in questing and unfed ticks. In this study, 4283 tick samples derived from 21 tick species were collected from 76 villages and 10 central districts in total. All tick pools were screened for the presence of CCHFV RNA by two nested RT-PCRs. PCR assays were positive for 27 (3.6%) of 736 pools. CCHFV was detected in Hyalomma marginatum, Dermacentor marginatus, Rhipicephalus bursa, Rhipicephalus turanicus, Hyalomma excavatum and Haemaphysalis parva pools. As a result of the phylogenetic analysis, it was determined that the obtained CCHFV sequences are clustered into Europe 1 clade. CCHFV was detected among ticks obtained from cattle, goats, wild boar, hare, and the ground. The presence of CCHFV in ticks obtained from various domestic and wild hosts and the nature, and thereby the distribution patterns of the virus in different ecological areas were presented in this study. Furthermore, CCHFV was also detected in unusual tick species. Consequently, these results indicate that tick surveillance studies in large-scale and wide varieties contribute to the ecology and epidemiology of CCHF in that region, and can be used as an early-warning system.
Prevalence and Phylogenetic Analysis of Crimean-Congo Hemorrhagic Fever Virus in Ticks from Different Ecosystems in Xinjiang, China.
Moming Abulimiti,Yue Xihong,Shen Shu,Chang Chenchen,Wang Cheng,Luo Tao,Zhang Yanfang,Guo Rong,Hu Zhihong,Zhang Yujiang,Deng Fei,Sun Surong
The Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Orthonairovirus and family Nairoviridae, is transmitted by ticks and causes severe hemorrhagic disease in humans. To study the epidemiology of CCHFV in different ecosystems in Xinjiang, China, a total of 58,932 ticks were collected from Tarim Basin, Junggar Basin, Tianshan Mountain, and Altai Mountain from 2014 to 2017. Hyalomma asiaticum asiaticum was the dominant tick species in Tarim and Junggar basins, whereas Dermacentor nuttalli and Hyalomma detritum were found in Tianshan Mountain and Altai Mountain, respectively. Reverse transcription-polymerase chain reaction of the CCHFV small (S) genome segment was used for the molecular detection. The CCHFV-positive percentage was 5.26%, 6.85%, 1.94%, and 5.56% in Tarim Basin, Junggar Basin, Tianshan Mountain, and Altai Mountain, respectively. Sequences of the S segment were used for phylogenetic analysis and the results showed that the newly identified CCHFV strains belonged to two clades. Our study confirms that H. asiaticum asiaticum is the major vector of CCHFV in desert habitats which is consistent with previous studies, and also suggests that H. detritum and D. nuttalli are emerging vectors for CCHFV in Xinjiang. Moreover, this study reports the presence of CCHFV in the mountain habitat of Xinjiang for the first time, suggesting that future surveillance of CCHFV should also include mountainous areas.
The emerging tick-borne Crimean-Congo haemorrhagic fever virus: A narrative review.
Serretiello Enrica,Astorri Roberta,Chianese Annalisa,Stelitano Debora,Zannella Carla,Folliero Veronica,Santella Biagio,Galdiero Marilena,Franci Gianluigi,Galdiero Massimiliano
Travel medicine and infectious disease
Crimean-Congo Haemorrhagic Fever (CCHF) is an increasingly relevant viral zoonosis caused by the negative-sense single-stranded (ss) RNA Crimean-Congo Haemorrhagic Fever Orthonairovirus (CCHFV) (Nairoviridae family, Bunyavirales order). The viral genome is divided into three segments (L-M-S) of distinct size and functions. The infection is generally mediated by a tick vector, in particular belonging to the Hyalomma genus, and the transmission follows a tick-vertebrate-tick ecologic cycle, with asymptomatic infected animals functioning as reservoirs and amplifiers for CCHFV. Human hosts could be infected primarily through infected ticks or by contact with infected hosts or their body fluids and tissues, also in a nosocomial way and in occupational contexts. Infected symptomatic patients generally manifest a nonspecific illness, which progresses across four stages, with possibly lethal outcomes. Disease outbreaks show a widespread geographic diffusion and a highly variable mortality rate, dramatically peaking in untreated patients. The lack of an adequate animal model and the elevated virus biological risk (only manageable under biosafety level 4 conditions) represent strongly limiting factors for a better characterization of the disease and for the development of specific therapies and vaccines. The present review discusses updated information on CCHFV-related disease, including details about the virus (taxonomy, structure, life cycle, transmission modalities) and considering CCHF pathogenesis, epidemiology and current strategies (diagnostic, therapeutic and preventive).
Serologic survey of the Crimean-Congo haemorrhagic fever virus infection among wild rodents in Hungary.
Földes Fanni,Madai Mónika,Németh Viktória,Zana Brigitta,Papp Henrietta,Kemenesi Gábor,Bock-Marquette Ildikó,Horváth Győző,Herczeg Róbert,Jakab Ferenc
Ticks and tick-borne diseases
Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne pathogen, which causes an increasing number of severe infections in many parts of Africa, Asia and in Europe. The virus is primarily transmitted by ticks, however, the spectrum of natural hosts regarding CCHFV includes a wide variety of domestic and wild animals. Although the presence of CCHFV was hypothesized in Hungary, data in support of CCHFV prevalence has thus far, proven insufficient. In the present study, rodents belonging to four species, the yellow-necked mouse (Apodemus flavicollis), the striped field mouse (A. agrarius), the wood mouse (A. sylvaticus) and the bank vole (Myodes glareolus), were all systematically trapped in the Mecsek Mountain region (Southwest Hungary), from 2011 through 2013. Rodent sera were collected and screened for CCHFV antibodies with dot-blot pre-screening and immunofluorescence assay. Among the 2085 tested rodents, 20 (0.96%) were positive for IgG antibody against CCHFV. Seroprevalence was the highest (1.25%) in A. flavicollis serum samples. Distinctly, we now provide the first data regarding CCHFV occurrence and seroprevalence among wild rodents in Hungary. This observation represents a need for large-scale surveillance to effectively assess the enzootic background and the potential public health risk of CCHFV in Hungary.
Crimean-Congo hemorrhagic fever.
Whitehouse Chris A
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV), which is a member of the Nairovirus genus (family Bunyaviridae). CCHF was first recognized during a large outbreak among agricultural workers in the mid-1940s in the Crimean peninsula. The disease now occurs sporadically throughout much of Africa, Asia, and Europe and results in an approximately 30% fatality rate. After a short incubation period, CCHF is characterized by a sudden onset of high fever, chills, severe headache, dizziness, back, and abdominal pains. Additional symptoms can include nausea, vomiting, diarrhea, neuropsychiatric, and cardiovascular changes. In severe cases, hemorrhagic manifestations, ranging from petechiae to large areas of ecchymosis, develop. Numerous genera of ixodid ticks serve both as vector and reservoir for CCHFV; however, ticks in the genus Hyalomma are particularly important to the ecology of this virus. In fact, occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. Therefore, exposure to these ticks represents a major risk factor for contracting disease; however, other important risk factors are known and are discussed in this review. In recent years, major advances in the molecular detection of CCHFV, particularly the use of real-time reverse transcription-polymerase chain reaction (RT-PCR), in clinical and tick samples have allowed for both rapid diagnosis of disease and molecular epidemiology studies. Treatment options for CCHF are limited. Immunotherapy and ribavirin have been tried with varying degrees of success during sporadic outbreaks of disease, but no case-controlled trials have been conducted. Consequently, there is currently no antiviral treatment for CCHF approved by the U.S. Food and Drug Administration (FDA). However, renewed interested in CCHFV, as well as increased knowledge of its basic biology, may lead to improved therapies in the future. This article reviews the history, epidemiology, ecology, clinical features, pathogenesis, diagnosis, and treatment of CCHF. In addition, recent advances in the molecular biology of CCHFV are presented, and issues related to its possible use as a bioterrorism agent are discussed.
Molecular (ticks) and serological (humans) study of Crimean-Congo hemorrhagic fever virus in the Iberian Peninsula, 2013-2015.
Palomar Ana M,Portillo Aránzazu,Santibáñez Sonia,García-Álvarez Lara,Muñoz-Sanz Agustín,Márquez Francisco J,Romero Lourdes,Eiros José M,Oteo José A
Enfermedades infecciosas y microbiologia clinica
INTRODUCTION:Crimean-Congo hemorrhagic fever (CCHF) is a viral disease, mainly transmitted through tick bite, of great importance in Public Health. In Spain, Crimean-Congo hemorrhagic fever virus (CCHFV) was detected for the first time in 2010 in Hyalomma lusitanicum ticks collected from deer in Cáceres. The aim of this study was to investigate the presence of CCHFV in ticks from Cáceres, and from other Spanish areas, and to evaluate the presence of antibodies against the virus in individuals exposed to tick bites. METHODS:A total of 2053 ticks (1333 Hyalomma marginatum, 680 H. lusitanicum and 40 Rhipicephalus bursa) were analyzed using molecular biology techniques (PCR) for CCHFV detection. The determination of specific IgG antibodies against CCHFV in 228 serum samples from humans with regular contact with ticks (at risk of acquiring the infection) was performed by indirect immunofluorescence assay. RESULTS:The CCHFV was not amplified in ticks, nor were antibodies against the virus found in the serum samples analyzed. CONCLUSION:The absence of the CCHFV in the ticks studied and the lack of antibodies against the virus in individuals exposed to tick bites would seem to suggest a low risk of acquisition of human infection by CCHFV in Spain.
[The isolation of Dhori viruses (Orthomyxoviridae, Thogotovirus) and Crimean-Congo hemorrhagic fever virus (Bunyaviridae, Nairovirus) from the hare (Lepus europaeus) and its ticks Hyalomma marginatum in the middle zone of the Volga delta, Astrakhan region, 2001].
L'vov D N,Dzharkenov A F,Aristova V A,Kovtunov A I,Gromashevskiĭ V L,Vyshemirskiĭ O I,Galkina I V,Larichev V F,Butenko A M,L'vov D K
In August, 2001, in the middle zone of the delta of the Volga River, the Astrakhan region, during investigation of the natural foci of West Nile fever and Crimean--Congo hemorrhagic fever (CCHF), the material from the hare (Lepus europaeus, Pallas, 1778 (Lagomorpha, Leporidae) and collected from it the ticks Hyalomna marginatum Koch 1844, was obtained. 4 strains of Dhori virus (Orthomyxoviridae, Thogotovirus) and 2 strains of CCHF virus (Bunyaviridae, Nairovirus) were isolated. This is the first isolation of Thogotovirus genus virus from the wild vertebrates. Considering the overlap of the Dhori virus and CCHF virus areas, similar ecology and the isolation both viruses from the same pool of the ticks, the necessity for the use of the test-system for indication of the viruses, differential diagnosis and accumulation of the data concerning the role of Dhori virus in the human and farm animals pathology is discussed.
[Results of investigation of ticks in Volga river delta (Astrakhan region, 2017) for Crimean-Congo hemorrhagic fever virus (Nairoviridae, Orthonairovirus, CCHFV) and other tick-borne arboviruses.]
Vakalova E V,Butenko A M,Vishnevskaya T V,Dorofeeva T E,Gitelman A K,Kulikova L N,Lvov D K,Alkhovsky S V
INTRODUCTION:There are natural foci of Crimean-Congo hemorrhagic fever (CCHF) that vectored by Hyalomma marginatum ticks in Volga river delta (Astrakhan region, South of Russia). The circulation of Dhori virus (DHOV) (Thogotovirus: Orthomyxoviridae) has been also shown here. We hypothesized that other tick-borne arboviruses are also likely to circulate in the region. In particular, Bhanja virus (Phlebovirus: Phenuiviridae), Wad Medani virus (Orbivirus: Reoviridae), and Tamdy virus (Orthonairovirus: Nairoviridae), which were found to circulate in neighboring regions and are vectored by Haemaphysalis spp., Dermacenter spp., and Hyalomma spp. ticks. OBJECTIVES:The aim of the study was to examine ixodid ticks in Volga river delta for the presence of CCHFV, DHOV, Bhanja virus, Wad Medani virus, and Tamdy virus. MATERIAL AND METHODS:Ticks were collected in Volga river delta in 2017. We used molecular genetic methods for the detection and analysis of nucleic acids (PCR, sequencing, phylogenetic analysis). RESULTS:We detect CCHFV and DHOV RNA in H. marginatum ticks. The rate of infected H. marginatum ticks was 1.98% for CCHFV and 0.4% for DHOV. The results of genetic analysis showed that found DHOV strains are almost identical (99-100% in the M gene) and forms a separate genetic lineage alongside of Batken virus from Central Asia. At the same time, Bhanja virus, Wad Medani virus, and Tamdy virus were not found in ticks, collected in this region. CONCLUSIONS:DHOV is circulating in the natural foci of CCHF in the Volga river delta. The ratio of infection of H. marginatum with CCHFV and DHOV was determined for the first time.
Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.
Bente Dennis A,Forrester Naomi L,Watts Douglas M,McAuley Alexander J,Whitehouse Chris A,Bray Mike
Crimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank.
Phylogeny of tick-derived Crimean-Congo hemorrhagic fever virus strains in Iran.
Biglari Peyvand,Chinikar Sadegh,Belqeiszadeh Hamid,Telmadarraiy Zakkyeh,Mostafavi Ehsan,Ghaffari Masoud,Javaherizadeh Siavash,Nowotny Norbert,Fooks Anthony R,Shahhosseini Nariman
Ticks and tick-borne diseases
The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was assessed by collecting ticks from Golpayegan, Isfahan Province. Real time RT-PCR was used to detect the CCHFV RNA in the tick population and the origins of the viral sequences were determined. The CCHFV RNA was detected in 5.2% of 492 ticks collected from livestock in different regions of Golpayegan. The tick species that tested positive for the presence of CCHFV RNA included Hyalomma, Rhipicephalus and Haemaphysalis species. Phylogenetic analysis using the partial S-segment indicated that eight sequences clustered in clade IV (Asia-1) and three other sequences aligned within clade VI (Europe) with other CCHFV strains from Kosovo (Kosova1917) and Russia (Kashmanov).
Genetic Diversity of Crimean Congo Hemorrhagic Fever Virus Strains from Iran.
Chinikar Sadegh,Bouzari Saeid,Shokrgozar Mohammad Ali,Mostafavi Ehsan,Jalali Tahmineh,Khakifirouz Sahar,Nowotny Norbert,Fooks Anthony R,Shah-Hosseini Nariman
Journal of arthropod-borne diseases
BACKGROUND:Crimean Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. It has a negative-sense, single stranded RNA genome approximately 19.2 kb, containing the Small, Medium, and Large segments. CCHFVs are relatively divergent in their genome sequence and grouped in seven distinct clades based on S-segment sequence analysis and six clades based on M-segment sequences. Our aim was to obtain new insights into the molecular epidemiology of CCHFV in Iran. METHODS:We analyzed partial and complete nucleotide sequences of the S and M segments derived from 50 Iranian patients. The extracted RNA was amplified using one-step RT-PCR and then sequenced. The sequences were analyzed using Mega5 software. RESULTS:Phylogenetic analysis of partial S segment sequences demonstrated that clade IV-(Asia 1), clade IV-(Asia 2) and clade V-(Europe) accounted for 80 %, 4 % and 14 % of the circulating genomic variants of CCHFV in Iran respectively. However, one of the Iranian strains (Iran-Kerman/22) was associated with none of other sequences and formed a new clade (VII). The phylogenetic analysis of complete S-segment nucleotide sequences from selected Iranian CCHFV strains complemented with representative strains from GenBank revealed similar topology as partial sequences with eight major clusters. A partial M segment phylogeny positioned the Iranian strains in either association with clade III (Asia-Africa) or clade V (Europe). CONCLUSION:The phylogenetic analysis revealed subtle links between distant geographic locations, which we propose might originate either from international livestock trade or from long-distance carriage of CCHFV by infected ticks via bird migration.
Crimean-Congo hemorrhagic fever cases in the North of Iran have three distinct origins.
Shahhosseini Nariman,Chinikar Sadegh,Shams Elnaz,Nowotny Norbert,Fooks Anthony R
An on-going surveillance program on Crimean-Congo haemorrhagic fever virus (CCHFV) in Iran has been launched since 2000. An outbreak of CCHF occurred in northern Iran between June and July 2015. Three cases were involved in this outbreak. One patient died after admission to hospital, and the others were treated successfully. Phylogenetic analysis showed that three sequences obtained from Iranian patients grouped within clade IV (Asia-1), clade V (Europe) and clade VI (Greece). The partial sequence of the strain Noshahr59 (KT588642) showed the highest similarity with other strains isolated from Russia, Kosovo and Turkey (Clade V, Europe). The genome sequence of the strain Chalous65 (KT588640) showed 100% homology to the strain AP29 isolated from Greece (DQ211638). The genome sequence of the strain Noshahr43 (KT588641) showed 88% similarity to the Pakistani and previously reported Iranian strains (AF527810, AJ538198, AY366379 and AY366373). These data support previous studies, which showed a distinct similarity between Iranian S segments of CCHFV strains with other strains within clade IV (Asia-1) and clade V (Europe). In addition, clade VI was detected for the first time in Iran. Moreover, strain Chalous65 with similar genetic characteristics to strain AP29 from Greece was isolated from a fatal human case.
Genomic characterisation of three Mapputta group viruses, a serogroup of Australian and Papua New Guinean bunyaviruses associated with human disease.
Gauci Penelope J,McAllister Jane,Mitchell Ian R,Boyle David B,Bulach Dieter M,Weir Richard P,Melville Lorna F,Gubala Aneta J
The Mapputta serogroup tentatively contains the mosquito-associated viruses Mapputta, Maprik, Trubanaman and Gan Gan. Interestingly, this serogroup has previously been associated with an acute epidemic polyarthritis-like illness in humans; however, there has been no ensuing genetic characterisation. Here we report the complete genome sequences of Mapputta and Maprik viruses, and a new Mapputta group candidate, Buffalo Creek virus, previously isolated from mosquitoes and detected by serology in a hospitalised patient. Phylogenetic analyses indicate that the group is one of the earliest diverged groups within the genus Orthobunyavirus of the family Bunyaviridae. Analyses show that these three viruses are related to the recently sequenced Australian bunyaviruses from mosquitoes, Salt Ash and Murrumbidgee. A notable feature of the Mapputta group viruses is the absence of the NSs (non-structural) ORF commonly found on the S segment of other orthobunyaviruses. Viruses of the Mapputta group have been isolated from geographically diverse regions ranging from tropical Papua New Guinea to the semi-arid climate of south-eastern Australia. The relevance of this group to human health in the region merits further investigation.
Apodemus agrarius is a potential natural host of severe fever with thrombocytopenia syndrome (SFTS)-causing novel bunyavirus.
Ni Hongxia,Yang Fan,Li Yongdong,Liu Wenbin,Jiao Suli,Li Zixiong,Yi Bo,Chen Yi,Hou Xiaomei,Hu Fengjiao,Ding Yibo,Bian Guolin,Du Yan,Xu Guozhang,Cao Guangwen
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
BACKGROUND:Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne, novel bunyavirus-caused emerging infectious disease. It becomes a threat to public health due to its high fatality rate. OBJECTIVE:To clarify the epidemiological characteristics of SFTS and natural host(s) of SFTS-causing virus (SFTSV) in East China. STUDY DESIGN:Serum antibody against SFTSV in 496 healthy villagers was examined by ELISA. SFTSV in acute sera of SFTS cases and lung tissues of house and field mouse/rats were identified using quantitative RT-PCR, cell culture, and sequencing. RESULTS:A total of 22 laboratory-confirmed SFTS cases were diagnosed between 2012 and 2014, of which 5 (22.7%) reported a history of tick-bites. The seroprevalance of SFTSV antibody was 10.5% in healthy villagers. SFTSV genomic RNAs were identified in 2 of 8 Apodemus agrarius but not in Rattus norvegicus (n=40) and Rattus losea (n=4). The 3 segments of SFTSV from 11 SFTS cases and 2 A. agrarius were successfully sequenced. Phylogenetic analyses indicated that at least 3 different SFTSV strains (inland-type, Ningbo-native-type, and their reassortant-type) were present in Ningbo. The 3 segments of the 2 SFTSV isolates from A. agrarius shared great sequence homologies to those isolated from the patients living in nearby villages. CONCLUSION:The present study indicated that A. agrarius might be a natural host of SFTSV in East China.
Phylogenetic analysis of Bunyamwera and Ngari viruses (family Bunyaviridae, genus Orthobunyavirus) isolated in Kenya.
Odhiambo C,Venter M,Lwande O,Swanepoel R,Sang R
Epidemiology and infection
Orthobunyaviruses, tri-segmented, negative-sense RNA viruses, have long been associated with mild to severe human disease in Africa, but not haemorrhagic fever. However, during a Rift Valley fever outbreak in East Africa in 1997-1998, Ngari virus was isolated from two patients and antibody detected in several others with haemorrhagic fever. The isolates were used to identify Ngari virus as a natural Orthobunyavirus reassortant. Despite their potential to reassort and cause severe human disease, characterization of orthobunyaviruses is hampered by paucity of genetic sequences. Our objective was to obtain complete gene sequences of two Bunyamwera virus and three Ngari virus isolates from recent surveys in Kenya and to determine their phylogenetic positioning within the Bunyamwera serogroup. Newly sequenced Kenyan Bunyamwera virus isolates clustered closest to a Bunyamwera virus isolate from the same locality and a Central African Republic isolate indicating that similar strains may be circulating regionally. Recent Kenyan Ngari isolates were closest to the Ngari isolates associated with the 1997-1998 haemorrhagic fever outbreak. We observed a temporal/geographical relationship among Ngari isolates in all three gene segments suggesting a geographical/temporal association with genetic diversity. These sequences in addition to earlier sequences can be used for future analyses of this neglected but potentially deadly group of viruses.
Epidemiological and genetic investigation of a cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus.
Mao Lingling,Deng Baocheng,Liang Yuhong,Liu Yun,Wang Zijiang,Zhang Jie,Wu Wei,Yu Lei,Yao Wenqing
BMC infectious diseases
BACKGROUND:To analyze and discuss the transmission route of a cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). METHOD:We performed an epidemiological investigation and a genetic analysis of patients with severe fever with thrombocytopenia syndrome (SFTS) caused by SFTSV, their close contacts and the surrounding population. RESULTS:We found that all patients had contact with the blood of the first patient. The comparison of gene sequences in the three isolated SFTSV strains showed that the strains were closely related. Six close contacts and nine individuals in the surrounding population were positive for SFTSV IgM antibody. CONCLUSION:We suspect that the cluster outbreak was transmitted via blood and that the natural reservoir host of SFTSV exists in the patients' environment.
Spontaneous Acute Subdural Hemorrhage in a Patient with a Tick Borne Bunyavirus-Induced Severe Fever with Thrombocytopenia Syndrome.
Yoo Jihwan,Oh Ji Woong,Jang Chang Gi,Moon Ju Hyung,Kim Eui-Hyun,Chang Jong Hee,Kim Sun Ho,Kang Seok-Gu
Korean journal of neurotrauma
We report the first case of severe fever with thrombocytopenia syndrome (SFTS) and a spontaneous acute subdural hematoma (SDH) in Korea. A 79-year-old male presented with fever and thrombocytopenia. On the third day of hospitalization, his mental changed from drowsy to semi-coma. Brain computed tomography indicated an acute subdural hemorrhage on the right convexity. He was given early decompressive craniectomy, but did not survive. Real-time reverse transcription polymerase chain reaction analysis of a blood sample indicated the presence of SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage and SFTS. This case report describes our treatment of a patient with acute SDH and an infection from a tick-borne species of Bunyaviridae.
Maguari Virus Associated with Human Disease.
Groseth Allison,Vine Veronica,Weisend Carla,Guevara Carolina,Watts Douglas,Russell Brandy,Tesh Robert B,Ebihara Hideki
Emerging infectious diseases
Despite the lack of evidence for symptomatic human infection with Maguari virus (MAGV), its close relation to Cache Valley virus (CVV), which does infect humans, remains a concern. We sequenced the complete genome of a MAGV-like isolate (OBS6657) obtained from a febrile patient in Pucallpa, Ucayali, Peru, in 1998. To facilitate its classification, we generated additional full-length sequences for the MAGV prototype strain, 3 additional MAGV-like isolates, and the closely related CVV (7 strains), Tlacotalpan (1 strain), Playas (3 strains), and Fort Sherman (1 strain) viruses. The OBS6657 isolate is similar to the MAGV prototype, whereas 2 of the other MAGV-like isolates are located on a distinct branch and most likely warrant classification as a separate virus species and 1 is, in fact, a misclassified CVV strain. Our findings provide clear evidence that MAGV can cause human disease.
A cluster of cases of human-to-human transmission caused by severe fever with thrombocytopenia syndrome bunyavirus.
Chen Hongbin,Hu Ke,Zou Jinjing,Xiao Jinxiu
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in six epidemic provinces of China and was identified to be caused by a novel bunyavirus in 2009. It is progressive in nature and potentially fatal. SFTS usually occurs as sporadic cases and is considered a tick-transmitted disease. Here we present a group of three patients with proven SFTS and one with probable SFTS, for whom the epidemiological data show person-to-person transmission characteristics. The index patient and two secondary patients died. None reported a tick bite.
Identification of Umbre Orthobunyavirus as a Novel Zoonotic Virus Responsible for Lethal Encephalitis in 2 French Patients with Hypogammaglobulinemia.
Pérot Philippe,Bielle Franck,Bigot Thomas,Foulongne Vincent,Bolloré Karine,Chrétien Delphine,Gil Patricia,Gutiérrez Serafín,L'Ambert Grégory,Mokhtari Karima,Hellert Jan,Flamand Marie,Tamietti Carole,Coulpier Muriel,Huard de Verneuil Anne,Temmam Sarah,Couderc Thérèse,De Sousa Cunha Edouard,Boluda Susana,Plu Isabelle,Delisle Marie Bernadette,Bonneville Fabrice,Brassat David,Fieschi Claire,Malphettes Marion,Duyckaerts Charles,Mathon Bertrand,Demeret Sophie,Seilhean Danielle,Eloit Marc
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Human encephalitis represents a medical challenge from a diagnostic and therapeutic point of view. We investigated the cause of 2 fatal cases of encephalitis of unknown origin in immunocompromised patients. METHODS:Untargeted metatranscriptomics was applied on the brain tissue of 2 patients to search for pathogens (viruses, bacteria, fungi, or protozoans) without a prior hypothesis. RESULTS:Umbre arbovirus, an orthobunyavirus never previously identified in humans, was found in 2 patients. In situ hybridization and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) showed that Umbre virus infected neurons and replicated at high titers. The virus was not detected in cerebrospinal fluid by RT-qPCR. Viral sequences related to Koongol virus, another orthobunyavirus close to Umbre virus, were found in Culex pipiens mosquitoes captured in the south of France where the patients had spent some time before the onset of symptoms, demonstrating the presence of the same clade of arboviruses in Europe and their potential public health impact. A serological survey conducted in the same area did not identify individuals positive for Umbre virus. The absence of seropositivity in the population may not reflect the actual risk of disease transmission in immunocompromised individuals. CONCLUSIONS:Umbre arbovirus can cause encephalitis in immunocompromised humans and is present in Europe.
Hemorrhagic fever caused by a novel tick-borne Bunyavirus in Huaiyangshan, China.
Zhang Yong-Zhen,Zhou Dun-Jin,Xiong Yanwen,Chen Xiao-Ping,He Yong-Wen,Sun Qiangzheng,Yu Bin,Li Juan,Dai Yong-An,Tian Jun-Hua,Qin Xin-Cheng,Jin Dong,Cui Zhigang,Luo Xue-Lian,Li Wei,Lu Shan,Wang Wen,Peng Jin-Song,Guo Wen-Ping,Li Ming-Hui,Li Zhen-Jun,Zhang Shaomin,Chen Chen,Wang Yan,de Jong Menno D,Xu Jianguo
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
BACKGROUND:From April to July in 2009 and 2010, unexplained severe hemorrhagic fever-like illnesses occurred in farmers from the Huaiyangshan mountains range. METHODS:Clinical specimens (blood, urine, feces, and throat swabs) from suspected patients were obtained and stored. Mosquitoes and ticks in affected regions were collected. Virus was isolated from 2 patients and characterized by whole genome sequencing. Virus detection in additional patients and arthropods was done by virus-specific reverse transcription (RT) PCR. Clinical and epidemiological data of RT-PCR confirmed patients were analyzed. RESULTS:An unknown virus was isolated from blood of two patients and from Haemaphysalis ticks collected from dogs. Whole genome sequence analysis identified the virus as a novel member of the family Bunyaviridae, most closely related to the viruses of the genus Phlebovirus within which it forms a separate lineage. Subsequently, infection was confirmed by RT-PCR in 33 of 58 suspected patients. The illness in these patients was characterized by fever, severe malaise, nausea, vomiting, and diarrhea. Prominent laboratory findings included low white cell- and platelet counts, coagulation disturbances, and elevation of liver enzymes. Hemorrhagic complications were observed in 3 cases, 5 (15%) patients died. CONCLUSIONS:A novel tick-borne Bunyavirus causing life-threatening hemorrhagic fever in humans has emerged in the Huaiyangshan mountain areas of China. Further studies are needed to determine the epidemiology, geographic distribution and vertebrate animal ecology of this virus.
Identification of Oropouche Orthobunyavirus in the cerebrospinal fluid of three patients in the Amazonas, Brazil.
Bastos Michele de Souza,Figueiredo Luiz Tadeu Moraes,Naveca Felipe Gomes,Monte Rossicleia Lins,Lessa Natália,Pinto de Figueiredo Regina Maria,Gimaque João Bosco de Lima,Pivoto João Guilherme,Ramasawmy Rajendranath,Mourão Maria Paula Gomes
The American journal of tropical medicine and hygiene
Oropouche fever is the second most frequent arboviral infection in Brazil, surpassed only by dengue. Oropouche virus (OROV) causes large and explosive outbreaks of acute febrile illness in cities and villages in the Amazon and Central-Plateau regions. Cerebrospinal fluid (CSF) samples from 110 meningoencephalitis patients were analyzed. The RNA extracted from fluid was submitted to reverse transcription-polymerase chain reaction and sequencing to identify OROV. Three CSF samples showed the presence of OROV causing infection in the central nervous system (CNS). These patients are adults. Two of the patients had other diseases affecting CNS and immune systems: neurocysticercosis and acquired immunodeficiency syndrome, respectively. Nucleotide sequence analysis showed that the OROV from the CSF of these patients belonged to genotype I. We show here that severe Oropouche disease is occurring during outbreaks of this virus in Brazil.
Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome.
Zhang Yong-Zhen,He Yong-Wen,Dai Yong-An,Xiong Yanwen,Zheng Han,Zhou Dun-Jin,Li Juan,Sun Qiangzheng,Luo Xue-Lian,Cheng Yu-Li,Qin Xin-Cheng,Tian Jun-Hua,Chen Xiao-Ping,Yu Bin,Jin Dong,Guo Wen-Ping,Li Wei,Wang Wen,Peng Jin-Song,Zhang Guo-Bin,Zhang Shaomin,Chen Xiao-Min,Wang Yan,Li Ming-Hui,Li Zhenjun,Lu Shan,Ye Changyun,de Jong Menno D,Xu Jianguo
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND: Hemorrhagic fever-like illness caused by a novel Bunyavirus, Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently been described in China. METHODS: Patients with laboratory-confirmed HYSV infection who were admitted to Union Hospital or Zhongnan Hospital between April 2010 and October 2010 were included in this study. Clinical and routine laboratory data were collected and blood, throat swab, urine, or feces were obtained when possible. Viral RNA was quantified by real-time reverse-transcriptase polymerase chain reaction. Blood levels of a range of cytokines, chemokines, and acute phase proteins were assayed. RESULTS: A total of 49 patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients died. A fatal outcome was associated with high viral RNA load in blood at admission, as well as higher serum liver transaminase levels, more pronounced coagulation disturbances (activated partial thromboplastin time, thrombin time), and higher levels of acute phase proteins (phospholipase A, fibrinogen, hepcidin), cytokines (interleukin [IL]-6, IL-10, interferon-γ), and chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein 1b). The levels of these host parameters correlated with viral RNA levels. Blood viral RNA levels gradually declined over 3-4 weeks after illness onset, accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was also detectable in throat, urine, and fecal specimens of a substantial proportion of patients, including all fatal cases assayed. CONCLUSIONS. Viral replication and host immune responses play an important role in determining the severity and clinical outcome in patients with infection by HYSV.
Fever with thrombocytopenia associated with a novel bunyavirus in China.
Yu Xue-Jie,Liang Mi-Fang,Zhang Shou-Yin,Liu Yan,Li Jian-Dong,Sun Yu-Lan,Zhang Lihong,Zhang Quan-Fu,Popov Vsevolod L,Li Chuan,Qu Jing,Li Qun,Zhang Yan-Ping,Hai Rong,Wu Wei,Wang Qin,Zhan Fa-Xian,Wang Xian-Jun,Kan Biao,Wang Shi-Wen,Wan Kang-Lin,Jing Huai-Qi,Lu Jin-Xin,Yin Wen-Wu,Zhou Hang,Guan Xu-Hua,Liu Jia-Fa,Bi Zhen-Qiang,Liu Guo-Hua,Ren Jun,Wang Hua,Zhao Zhuo,Song Jing-Dong,He Jin-Rong,Wan Tao,Zhang Jing-Shan,Fu Xiu-Ping,Sun Li-Na,Dong Xiao-Ping,Feng Zi-Jian,Yang Wei-Zhong,Hong Tao,Zhang Yu,Walker David H,Wang Yu,Li De-Xin
The New England journal of medicine
BACKGROUND:Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing. METHODS:We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples. RESULTS:We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness. CONCLUSIONS:A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission.
Bao Chang-jun,Guo Xi-ling,Qi Xian,Hu Jian-li,Zhou Ming-hao,Varma Jay K,Cui Lun-biao,Yang Hai-tao,Jiao Yong-jun,Klena John D,Li Lu-xun,Tao Wen-yuan,Li Xian,Chen Yin,Zhu Zheng,Xu Ke,Shen Ai-hua,Wu Tao,Peng Hai-yan,Li Zhi-feng,Shan Jun,Shi Zhi-yang,Wang Hua
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus [SFTSV]) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. METHODS:We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). RESULTS:An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. CONCLUSIONS:Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.
A rare fatal case of a novel bunyavirus-associated hemophagocytic lymphohistiocytosis.
Lin Ling,Xu You-Zu,Wu Xiao-Mai,Ge Hong-Fei,Feng Jia-Xi,Chen Mei-Fang,Lv Dong-Qing,Li Bo-Li,Lin Jian
Journal of infection in developing countries
Herein we describe a rare fatal case of a novel bunyavirus-associated hemophagocytic lymphohistiocytosis (HLH) in a 62-year-old female patient. The novel bunyavirus infects patients with or without HLH who have similar clinical features such as fever, thrombocytopenia, and leukocytopenia. Therefore, the diagnosis of HLH can be easily missed. When HLH occurs, the disease worsens and the fatality rate rises. Our finding highlights the importance of bone marrow biopsy performed as soon as possible for patients suspected of having a novel bunyavirus infection and showing marked cytopenia in three cell lines.