Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.
TL;DR: Current knowledge of CCHFV is summarized, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range, including an extensive discussion of C CHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees.
About: This article is published in Antiviral Research.The article was published on 2013-10-01 and is currently open access. It has received 572 citations till now. The article focuses on the topics: Crimean–Congo hemorrhagic fever & Tick.
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TL;DR: Various circumstances contributed to suicides among persons with and without known mental health conditions, including relationship problems/loss, life stressors, and recent/impending crises were common across groups.
Abstract: INTRODUCTION Suicide rates in the United States have risen nearly 30% since 1999, and mental health conditions are one of several factors contributing to suicide. Examining state-level trends in suicide and the multiple circumstances contributing to it can inform comprehensive state suicide prevention planning. METHODS Trends in age-adjusted suicide rates among persons aged ≥10 years, by state and sex, across six consecutive 3-year periods (1999-2016), were assessed using data from the National Vital Statistics System for 50 states and the District of Columbia. Data from the National Violent Death Reporting System, covering 27 states in 2015, were used to examine contributing circumstances among decedents with and without known mental health conditions. RESULTS During 1999-2016, suicide rates increased significantly in 44 states, with 25 states experiencing increases >30%. Rates increased significantly among males and females in 34 and 43 states, respectively. Fifty-four percent of decedents in 27 states in 2015 did not have a known mental health condition. Among decedents with available information, several circumstances were significantly more likely among those without known mental health conditions than among those with mental health conditions, including relationship problems/loss (45.1% versus 39.6%), life stressors (50.5% versus 47.2%), and recent/impending crises (32.9% versus 26.0%), but these circumstances were common across groups. CONCLUSIONS Suicide rates increased significantly across most states during 1999-2016. Various circumstances contributed to suicides among persons with and without known mental health conditions. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE States can use a comprehensive evidence-based public health approach to prevent suicide risk before it occurs, identify and support persons at risk, prevent reattempts, and help friends and family members in the aftermath of a suicide.
509 citations
TL;DR: Basic information is provided needed for microbiologists to understand the many factors that affect the geographic range and population density of ticks and the risk of human exposure to infected ticks.
230 citations
TL;DR: The most significant pathogens that infect humans as well as the epidemiology, clinical features, diagnosis, and treatment of diseases that they cause are emphasized.
Abstract: Increases in tick-borne disease prevalence and transmission are important public health issues. Efforts to control these emerging diseases are frustrated by the struggle to control tick populations and to detect and treat infections caused by the pathogens that they transmit. This review covers tick-borne infectious diseases of nonrickettsial bacterial, parasitic, and viral origins. While tick surveillance and tracking inform our understanding of the importance of the spread and ecology of ticks and help identify areas of risk for disease transmission, the vectors are not the focus of this document. Here, we emphasize the most significant pathogens that infect humans as well as the epidemiology, clinical features, diagnosis, and treatment of diseases that they cause. Although detection via molecular or immunological methods has improved, tick-borne diseases continue to remain underdiagnosed, making the scope of the problem difficult to assess. Our current understanding of the incidence of tick-borne diseases is discussed in this review. An awareness of the diseases that can be transmitted by ticks in specific locations is key to detection and selection of appropriate treatment. As tick-transmitted pathogens are discovered and emerge in new geographic regions, our ability to detect, describe, and understand the growing public health threat must also grow to meet the challenge.
193 citations
Cites background from "Crimean-Congo hemorrhagic fever: hi..."
...Like most arboviral infections, CCHFV infections initially present as nonspecific febrile illness (238); it has been estimated that 88% of infections are subclinical (254)....
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...Relapse of infection has not been observed (238, 239)....
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...agent of the most widespread tick-borne viral infection of humans, causing severe viral hemorrhagic fever outbreaks with a case fatality rate of 5 to 30% (238, 239)....
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TL;DR: The concept of an epidemic calendar is explored, which is the idea that seasonality is a unifying feature of epidemic-prone diseases and, in the absence of control measures, the local calendar can be marked by epidemics, and a holistic view of hypothesized drivers of seasonality for each disease is presented.
Abstract: Seasonal cyclicity is a ubiquitous feature of acute infectious diseases [1] and may be a ubiquitous feature of human infectious diseases in general, as illustrated in Tables Tables11–4. Each acute infectious disease has its own seasonal window of occurrence, which, importantly, may vary among geographic locations and differ from other diseases within the same location. Here we explore the concept of an epidemic calendar, which is the idea that seasonality is a unifying feature of epidemic-prone diseases and, in the absence of control measures, the local calendar can be marked by epidemics (Fig 1). A well-known example of a calendar marked by epidemics is that of the Northern Hemisphere, where influenza outbreaks occur each winter [2, 3] (hence the colloquial reference to winter as "the flu season"). In contrast, chickenpox outbreaks peak each spring [4, 5], and polio transmission historically occurred each summer [6].
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Fig 1
Epidemic calendar.
The concept of an epidemic calendar is illustrated in the top panel. Infectious diseases are seasonal, especially the occurrence of acute and epidemic-prone diseases. In any given population, infectious diseases are distributed throughout the year. Annual cycles of infectious disease are a ubiquitous feature of infection (Tables (Tables11–4). The illustration depicts the wintertime seasonality of flu, springtime peaks of varicella (i.e., chickenpox), and the summertime occurrence of gonorrhea and polio, in the Northern Hemisphere. The bottom panel is a SIR schematic for the transmission of human infectious diseases, which include acute and chronic diseases, those that are vector-borne, and those that are zoonotic with animal reservoirs. The vector, human, and reservoir hosts populations are partitioned into individuals who are susceptible to infection, infected, and recovered and immune. Seasonality may enter into any of the eight key elements of the system: (1) susceptible recruitment via reproduction, (2) transmission, (3) acquired immunity and recovery, (4) waning immunity, (5) natural mortality, (6) symptomatology and pathology (which may be acute or chronic, depending on the disease), (7) disease-induced mortality, and (8) cross-species transmission. Disease illustrations reproduced from Google Medical Information. I, infected; R, recovered and immune; S, susceptible.
156 citations
TL;DR: Current knowledge of the role of ticks in CCHFV maintenance and transmission is summarized, and guidance for how to fill the knowledge gaps is provided and earlier reports that used unreliable methods and perceptions to ascribe a vector role to some species of ticks are identified.
135 citations
References
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TL;DR: Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries, and it has the most extensive geographic distribution of the medically important tickborne viral diseases, closely approximating the known global distribution of Hyalomma spp ticks.
Abstract: Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries, and it has the most extensive geographic distribution of the medically important tickborne viral diseases, closely approximating the known global distribution of Hyalomma spp ticks. Human beings become infected through tick bites, by crushing infected ticks, after contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viraemic livestock. Clinical features commonly show a dramatic progression characterised by haemorrhage, myalgia, and fever. The levels of liver enzymes, creatinine phosphokinase, and lactate dehydrogenase are raised, and bleeding markers are prolonged. Infection of the endothelium has a major pathogenic role. Besides direct infection of the endothelium, indirect damage by viral factors or virus-mediated host-derived soluble factors that cause endothelial activations and dysfunction are thought to occur. In diagnosis, enzyme-linked immunoassay and real-time reverse transcriptase PCR are used. Early diagnosis is critical for patient therapy and prevention of potential nosocomial infections. Supportive therapy is the most essential part of case management. Recent studies suggest that ribavirin is effective against CCHF, although definitive studies are not available. Health-care workers have a serious risk of infection, particularly during care of patients with haemorrhages from the nose, mouth, gums, vagina, and injection sites. Simple barrier precautions have been reported to be effective.
982 citations
TL;DR: It was only in 1967, when Soviet workers first used the generally accepted newborn white mouse inoculation technique for CCHF virus isolation and study, that the etiologic agent could be characterized antigenically, physiochemically, and morphologically.
Abstract: Crimean-Congo hemorrhagic fever (CCHF) came to modern medical attention in 1944–1945, when about 200 Soviet military personnel were infected while assisting peasants in war-devastated Crimea (Ukrainian SSR). Subsequent epidemics occurred in Astrakhan (1953–1968) and Rostov Oblasts (1963–1971) of USSR and in Bulgaria (1953–1973). There have been numerous lesser outbreaks in southern USSR and, in 1976, outbreaks in Pakistan. However, it was only in 1967, when Soviet workers first used the generally accepted newborn white mouse (NWM) inoculation technique for CCHF virus isolation and study, that the etiologic agent could be characterized antigenically, physiochemically, and morphologically. Collaboration in 1968 between the Soviet and American experts M. P. Chumakov and Jordi Casals demonstrated the serologically identical properties of virus strains from human CCHF patients and corpses, lower mammals, and ticks from Asian and European areas of the USSR and from Bulgaria, Congo (Zaire), Nigeria, and Pakistan. These results, confirmed and broadened in subsequent studies, enabled serological and other research tools to be developed for producing identifiable antibodies and antigens required in experimental procedures and seroepidemiological surveys and obtaining scientific evidence to demonstrate vector and reservoir species and virus dynamics in nature. CCHF virus, a member (without generic assignment) of the family Bunyaviridae, is the prototype of the CCHF serogroup, which also includes Hazara virus (from Ixodes redikorzevi parasitizing alpine voles in Pakistan). CCHF virus is enzootic in the Palearctic, Oriental, and Ethiopian Faunal Regions, chiefly in steppe, savanna, semidesert, and foothill biotopes where 1 or 2 Hyalomma species are the predominant ticks parasitizing domestic and wild animals. Presence of the virus has been demonstrated by isolations from humans, other mammals, and/or ticks, or by seroepidemiological survey results, in western and southern India, Pakistan, Afghanistan, Iran, Soviet Middle Asia (Turkmen, Uzbek, Kazakh, Kirgiz, and Tadzhik SSR), Transcaucasia (Armenian and Azerbaijan SSR), European USSR (Ukrainian and Moldavian SSR, Kalmyk and Daghestan ASSR, Astrakhan and Rostov Oblasts, and Krasnodar and Stavropol Regions of RSFSR), Bulgaria, Yugoslavia, Greece, Hungary, France, Senegal, Nigeria, Central African Empire, Zaire, Uganda, Kenya, Ethiopia, Tanzania, and Egypt. The ecologically atypical CCHF foci in Moldavian deciduous forest habitats of Ixodes ritinus and Dermatentor and Rhipicephalus species may represent a spillover phenomenon associated with environmental changes created by humans. CCHF virus is a true tick-associated arbovirus; it survives transstadially (from larva to nymph to adult) and interseasonally in several tick species and is transmitted transovarially to the F1 generation (in some cases to F2) in Hyalomma m. marginatum, H. marginatum rufipes, Dermacentor marginatus , and Rhipicephalus rossicus . Twenty-five tick species and subspecies have been reported to be CCHF virus reservoirs/vectors (the single record from an argasid, the birdparasitizing Argas persicus, remains to be confirmed). One-host ticks, Boophilus annulatus, B. microplus, B. decoloratus (and probably B. geigyi ), appear to maintain intense virus interaction for many weeks or months between several tick species infesting artiodactyls (especially cattle). The 2-host vectors are Hyalomma m. marginatum, H. mmginatum turanicum and H. marginatum rufipes (and probably H. marginatum isaaci ); they feed as immatures on birds, hares, or hedgehogs and, as adults, chiefly on artiodactyls (often also on humans). Other 2-host vectors, H. anatolicum anatolicum, H. detritum , and Rhipicephalus bursa , feed both as immatures and adults on artiodactyls. The H. marginatum complex, and H. a. anatolicum , are especially important in causing epidemics and outbreaks of human CCHF owing to their great numbers during certain periods and to their aggressiveness in seeking human hosts. Others, including 13 species of 3-host ticks [ Haemaphysalis punctata, Amblyomma variegatum, Dermacentor (2 spp.), Hyalomma (5 spp.), and Rhipicephalus (4 spp.)], which generally seek human hosts less aggressively than the cited hyalommas, serve chiefly to maintain enzootic foci of CCHF virus circulation between ticks and wild and domestic mammals. Ground-feeding birds are often hosts of CCHF virus-infected ticks but birds apparently do not become viremic; the epidemiological role of these birds is to support populations of certain vector species and to disseminate these species intracontinentally and/or intercontinentally. CCHF epidemics have developed on a background of favorable climatic factors and environmental changes beneficial for survival of large numbers of hyalommas and of the hosts of both their immature and adult stages. The environmental changes have been wartime neglect of agricultural lands, introduction of susceptible military personnel or new settlers into infected foci, widescale collectivization of agriculture, changing pasture patterns, converting floodplains and marshy deltas to farmland and pastures, flood control, etc. Unusually severe winter-spring weather, resulting in decimation of Hyalomma populations and also of hosts of immature stages, appears to have been largely responsible for virus circulation to revert from epizootic (epidemic) to enzootic intensity. Humans become infected when bitten by infected ticks, or when crushing these ticks in their bare hands or shearing tick-infested sheep. Household and nosocomial cases resulting from contamination by bloody discharges from CCHF patients have been especially numerous and severe, often with great mortality, in villages and hospitals where the disease was unrecognized. Other cases have occurred from laboratory accidents and from handling infected animal carcasses. Mild, moderate, and severe disease courses are described. A certain number of human infections may be clinically inapparent. Mortality rates in CCHF patients have ranged from 15 to 40% or more. Despite the absence of specific drugs for treating CCHF, the Leshchinskaya regimen of hospital care has resulted in appreciable reduction in mortality rates. There are no scientific data to indicate that the virus is less virulent in Africa than in Eurasia. An apparently effective vaccine has been developed to prevent infections in persons in high-risk situations. Various measures applied to prevent human illness have had mixed success. The sensitivity of serological tests for CCHF antibodies needs to be improved to obtain more reliable survey results and to determine whether there are significant differences between CCHF virus strains. The fluorescent antibody technique (FAT) is useful for determining the presence of antibodies to the virus in vertebrate tissues and in ticks (but the dynamics of the virus in ticks has not been investigated). The indirect FAT is an important candidate for research in relation to epidemiological surveys. Most CCHF strains yield no agglutinating antigens (unlike all other arboviruses causing significant human disease, except Colorado tick fever virus); CCHF virus also replicates poorly or not at all in most cell cultures and no visible cytopathogenic effect has been described.
Addendum . In 1978, while this manuscript was in press, CCHF isolates were reported from Hyalomma dromedarii in Turkmenia and Rhipicephalus appendiculatus in Uganda. Thus, 27 tick taxa have been associated with CCHF virus.
877 citations
"Crimean-Congo hemorrhagic fever: hi..." refers background or methods or result in this paper
...A severe hemorrhagic illness attributed to the bite of a tick or louse was described in Tadjikistan in the 12th century, and similar diseases were known in other parts of Central Asia (Hoogstraal, 1979)....
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...…savannah, steppe and lightly wooded areas, and the ability of their aggressively questing larvae and nymphs to feed on a variety of hosts, including hedgehogs, hares and ground-feeding birds, while the adults actively seek out sheep, cattle and other large animals (reviewed in Hoogstraal (1979))....
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...The three decades following the identification of CHF in 1944 saw a remarkable effort, principally by Soviet and Bulgarian scientists, to identify tick vectors and vertebrate hosts of the virus in the Soviet Union and neighboring countries (Hoogstraal, 1979)....
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...…outbreak of CCHF took place in the summer of 1944, when Soviet troops re-occupying areas of the Crimean peninsula that had been under German occupation developed an acute febrile illness with a high incidence of bleeding and shock (Grashchenkov, 1945; Chumakov 1965, 1974; Hoogstraal, 1979)....
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...Many such reports appeared in the Russian-language literature in the period 1945–1978, and most are available in translation from the AFPMB web site cited above; they are reviewed in detail by Hoogstraal (1979), and some are summarized by Nalca and Whitehouse (2007)....
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TL;DR: Data on the vector tick Ixodes ricinus suggest that an extension of its northern and altitude range has been accompanied by an increased prevalence of tick-borne encephalitis, and climate change may also be partly responsible for the change in distribution of Dermacentor reticulatus.
Abstract: Zoonotic tick-borne diseases are an increasing health burden in Europe and there is speculation that this is partly due to climate change affecting vector biology and disease transmission. Data on the vector tick Ixodes ricinus suggest that an extension of its northern and altitude range has been accompanied by an increased prevalence of tick-borne encephalitis. Climate change may also be partly responsible for the change in distribution of Dermacentor reticulatus. Increased winter activity of I. ricinus is probably due to warmer winters and a retrospective study suggests that hotter summers will change the dynamics and pattern of seasonal activity, resulting in the bulk of the tick population becoming active in the latter part of the year. Climate suitability models predict that eight important tick species are likely to establish more northern permanent populations in a climate-warming scenario. However, the complex ecology and epidemiology of such tick-borne diseases as Lyme borreliosis and tick-borne encephalitis make it difficult to implicate climate change as the main cause of their increasing prevalence. Climate change models are required that take account of the dynamic biological processes involved in vector abundance and pathogen transmission in order to predict future tick-borne disease scenarios.
601 citations
TL;DR: This review will address the vertebrate mechanisms of these barriers as a guide to identify the possible targets of these large numbers of known salivary proteins with unknown function.
Abstract: When attempting to feed on their hosts, ticks face the problem of host hemostasis (the vertebrate mechanisms that prevent blood loss), inflammation (that can produce itching or pain and thus initiate defensive behavior on their hosts) and adaptive immunity (by way of both cellular and humoral responses). Against these barriers, ticks evolved a complex and sophisticated pharmacological armamentarium, consisting of bioactive lipids and proteins, to assist blood feeding. Recent progress in transcriptome research has uncovered that hard ticks have hundreds of different proteins expressed in their salivary glands, the majority of which have no known function, and include many novel protein families (e.g., their primary structure is unique to ticks). This review will address the vertebrate mechanisms of these barriers as a guide to identify the possible targets of these large numbers of known salivary proteins with unknown function. We additionally provide a supplemental Table that catalogues over 3,500 putative salivary proteins from various tick species, which might assist the scientific community in the process of functional identification of these unique proteins. This supplemental file is accessble fromhttp://exon.niaid.nih.gov/transcriptome/tick_review/Sup-Table-1.xls.gz.
490 citations
"Crimean-Congo hemorrhagic fever: hi..." refers background in this paper
...It is facilitated by the presence in tick saliva of anticoagulants and immunomodulatory proteins, which may facilitate virus infection and elicit a specific immune response in the host, making it partially resistant to further infestation (Francischetti et al., 2009; Willadsen, 2004)....
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