Science.gov

Sample records for acute hemorrhagic fever

  1. Hemorrhagic fever with renal syndrome and Crimean-Congo hemorrhagic fever as causes of acute undifferentiated febrile illness in Bulgaria.

    PubMed

    Christova, Iva; Younan, Rasha; Taseva, Evgenia; Gladnishka, Teodora; Trifonova, Iva; Ivanova, Vladislava; Spik, Kristin; Schmaljohn, Connie; Mohareb, Emad

    2013-03-01

    Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are the 2 widespread viral hemorrhagic fevers occurring in Europe. HFRS is distributed throughout Europe, and CCHF has been reported mainly on the Balkan Peninsula and Russia. Both hemorrhagic fevers are endemic in Bulgaria. We investigated to what extent acute undifferentiated febrile illness in Bulgaria could be due to hantaviruses or to CCHF virus. Using enzyme-linked immunosorbent assays (ELISAs), we tested serum samples from 527 patients with acute febrile illness for antibodies against hantaviruses and CCHF virus. Immunoglobulin M (IgM) antibodies against hantaviruses were detected in 15 (2.8%) of the patients. Of the 15 hantavirus-positive patients, 8 (1.5%) were positive for Dobrava virus (DOBV), 5 (0.9%) were positive for Puumala virus (PUUV), and the remaining 2 were positive for both hantaviruses. A plaque reduction neutralization test (PRNT) confirmed 4 of the 10 DOBV-positive samples. PRNT was negative for all PUUV-positive samples. Serologic evidence of recent CCHF virus infection was found in 13 (2.5%) of the patients. Interestingly, HFRS and CCHF were not only detected in well-known endemic areas of Bulgaria but also in nonendemic regions. Our results suggested that in endemic countries, CCHF and/or HFRS might appear as a nonspecific febrile illness in a certain proportion of patients. Physicians must be aware of possible viral hemorrhagic fever cases, even if hemorrhages or renal impairment are not manifested.

  2. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  3. Viral Hemorrhagic Fevers

    MedlinePlus

    ... The CDC Cancel Submit Search The CDC Viral Hemorrhagic Fevers (VHFs) Note: Javascript is disabled or is not ... please visit this page: About CDC.gov . Viral Hemorrhagic Fevers (VHFs) Virus Families Arenaviruses Old World/New World ...

  4. Viral hemorrhagic fever cases in the country of Georgia: Acute Febrile Illness Surveillance Study results.

    PubMed

    Kuchuloria, Tinatin; Imnadze, Paata; Chokheli, Maiko; Tsertsvadze, Tengiz; Endeladze, Marina; Mshvidobadze, Ketevan; Clark, Danielle V; Bautista, Christian T; Abdel Fadeel, Moustafa; Pimentel, Guillermo; House, Brent; Hepburn, Matthew J; Wölfel, Silke; Wölfel, Roman; Rivard, Robert G

    2014-08-01

    Minimal information is available on the incidence of Crimean-Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ≥ 38°C for ≥ 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia.

  5. Hemorrhagic fever viruses.

    PubMed

    Pigott, David C

    2005-10-01

    This article reviews the epidemiology, pathophysiology, and clinical management of patients with suspected or confirmed viral hemorrhagic fever infection. The focus is on clinical management based on case series from naturally occuring outbreaks of viral hemorrhagic fever infection as well as imported cases of viral hemorrhagic fever encountered in industrialized nations. The potential risk of bioterrorism involving these agents is discussed as well as emergency department and critical care management of isolated cases or larger outbreaks. Important aspects of management, including recognition of infected patients, isolation and decontamination procedures, as well as available vaccines and therapies are emphasized.

  6. Argentine hemorrhagic fever vaccines.

    PubMed

    Ambrosio, Ana; Saavedra, Maria; Mariani, Mauricio; Gamboa, Graciela; Maiza, Andrea

    2011-06-01

    Argentine hemorrhagic fever (AHF), an acute disease caused by Junin virus (JUNV, Arenaviridae), has been an important issue to public health in Argentina since the early 1950s. The field rodent Calomys musculinus is JUNV natural reservoir and human disease is a consequence of contact with infected rodents. A steady extention of AHF endemic area is being observed since the first reports of the disease. Important achievements have been made in: (a) improvement of methods for the etiological diagnosis; (b) implementation and validation of therapeutical measures; (c) development of vaccines to protect against AHF. Reference is made to different research strategies used to obtain anti-AHF vaccines in the past and anti-arenaviral diseases in the present. Information is updated on features and field performance of Candid #1 vaccine, a live attenuted vaccine currently used to prevent AHF. This vaccine was developed through a joint international effort that envisioned it as an orphan drug. With transferred technology, Argentine government was committed to be Candid #1 manufacturer and to register this vaccine as a novel medical product under the Argentine regulatory authority. Candid #1 vaccine is the first one used to control an arenaviral hemorrhagic fever, the first live viral vaccine to be manufactured and registered in Argentina, reaching its target population through governmental effort.

  7. Simian hemorrhagic fever virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter describes the taxonomic classification of Simian hemorrhagic fever virus (SHFV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biological pro...

  8. Pathogenesis of arenavirus hemorrhagic fevers.

    PubMed

    Moraz, Marie-Laurence; Kunz, Stefan

    2011-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments.

  9. Travelers' Health: Viral Hemorrhagic Fevers

    MedlinePlus

    ... VHFs) are caused by several families of enveloped RNA viruses: filoviruses (Ebola and Marburg hemorrhagic fever), arenaviruses ( ... in hemorrhagic fever with high death rates. Old World (Eastern Hemisphere) and New World (Western Hemisphere) viruses ...

  10. Marburg Hemorrhagic Fever (Marburg HF)

    MedlinePlus

    ... The CDC Cancel Submit Search The CDC Marburg hemorrhagic fever (Marburg HF) Note: Javascript is disabled or is ... was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, ...

  11. Ebola hemorrhagic Fever.

    PubMed

    Burnett, Mark W

    2014-01-01

    Ebola hemorrhagic fever is an often-fatal disease caused by a virus of the Filoviridae family, genus Ebolavirus. Initial signs and symptoms of the disease are nonspecific, often progressing on to a severe hemorrhagic illness. Special Operations Forces Medical Providers should be aware of this disease, which occurs in sporadic outbreaks throughout Africa. Treatment at the present time is mainly supportive. Special care should be taken to prevent contact with bodily fluids of those infected, which can transmit the virus to caregivers.

  12. Korean Hemorrhagic Fever.

    DTIC Science & Technology

    1980-03-01

    AD-A<m 761 KOREA UNIV SEOUL COLL OF MEDICINE KOREAN HEM0RRHA6IC FEVER.(U) MAR 80 H W LEE UNCLASSIFIED ICFI F/6 6/5 DAM017-79-6-9<*55 NL...I» > I,,iu. •Uli ••-. SUMMARY There were 364 hospitalized cases of Korean hemorrhagic fever (KHF) in 1979 in Korea . Lee et al...STANDARDS-1963-A ?H "LEVEtf® AD <o KOREAN HEMORRHAGIC F EVER A D A 09 47 Final Report HO WANG LEE, M. D. March 1980 i MIL. IIB«I . Mm k iw

  13. Korean Hemorrhagic Fever (Hemorrhagic Fever with Renal Syndrome (HFRS)).

    DTIC Science & Technology

    1983-08-01

    RD-RI55 255 KOREAN HEMORRHAGIC FEVER (HEMORRHAGIC FEVER WITH RENAL 11 SYNDROME (HFRS))(U) KOREA UNIV SEOUL DEPT OF MICROBIOLOGY H U LEE RUG 83 DRMDi...the first time in Korea (4,13). WHO has recently adapted to call Korean hemorrhagic fever and clinically similar diseases with a different name, HFRS...AD_______ I •. KOREAN HEMORRHAGIC FEVER • (HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)) I Final Report 0 In HO WANG LEE, M.D. August 1983 Supported by U.S

  14. Korean Hemorrhagic Fever.

    DTIC Science & Technology

    Korean hemorrhagic fever (KHF) occurred for the first time in Korea , 1951, although it had previously been known to both the Japanese and Russians...After Korean war, the disease has been fixed in the areas of DMZ as an endemic one, and from 100 to 400 cases have been being reportee every year

  15. Korean Hemorrhagic Fever.

    DTIC Science & Technology

    1982-05-01

    Medicine Seoul, Korea * S 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SUM ARY Urban rats captured in Seoul and four nearby Korean cities were found to have...rattus, urban Korean cities, 1980. . . . 15 Table 2. Isolation of Hantaan virus from antigen-positive wild house rats, Korea , 1980 .... ........... .. 16...Figures Figure 1. Map of Seoul City, South Korea and metropolitan area showing locations of urban Korean hemorrhagic fever cases, andRattu s positive

  16. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever)

    DTIC Science & Technology

    1988-06-30

    53 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea devel6ped a rare hemorrhagic fever which attracted...patients in the Republic of Korea . Year Korean Korean US Total civilian soldiers soldiers 1951 ...... 627 827 1952 .... 833 833 1953 ... ... 455 455...0 RI m HEMORRHAGIC FEVER WITH RENAL SYNDROME ( KOREAN HEMORRHAGIC FEVER) ANNUAL SUMMARY REPORT HO WANG LEE, M.D. June 30, 1988 Door., Supported by U.S

  17. Korean Hemorrhagic Fever.

    DTIC Science & Technology

    Korean hemorrhagic fever (KHF) occurred for the first time in Korea , 1951, although it had previously been known to both the Japanese and Russians...After Korean war, the disease has been fixed in the areas of DMZ as an endemic one, and from 100 to 300 cases have been reported every year. The aims...but in 1971 affected the middle districts and in 1972 invaded the southern parts of South Korea . The number of patients and the areas of KHF in 1972

  18. Korean Hemorrhagic Fever (Hemorrhagic Fever with Renal Syndrome (HFRS)).

    DTIC Science & Technology

    1984-07-01

    AD-Ai55 228 KOREAN HEMORRHAGIC FEVER (HEMORRHAGIC FEVER WITH RENAL in. SYNDROME (HFRS))(U) KOREA UNIV SEOUL DEPT OF MICROBIOLOGY H W LEE JUL 84...INTRODUCTION During the Korean War, more than 2,400 United Nations troops stationed in the 38th Parallel in Korea developed a rare disease which had not... Korean hemorrhagic fever patients in urban areas of Seoul. Korean J. Virol. 10: 1-6, 1980. 8. Lee, H. W. New epidemiological findings of HFRS in Korea . J

  19. Viral Hemorrhagic Fever Diagnostics

    PubMed Central

    Racsa, Lori D.; Kraft, Colleen S.; Olinger, Gene G.; Hensley, Lisa E.

    2016-01-01

    There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968

  20. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever)

    DTIC Science & Technology

    1989-07-31

    36 DISTRIBUTION LIST. .................... 40 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea developed a rare...hemorrhagic fever, a situa- tion that attracted worldwide attention (1). Since then it has been known as Korean hemorrhagic fever (KHF) in Korea . This...Kyunggido and Kangwondo, northern parts of South Korea . All of the 97 HFRS patients among Korean soldiers occurred in Kyunggido, Kangwondo and Seoul

  1. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever)

    DTIC Science & Technology

    1990-06-29

    DISTRIBUTION LIST .............. .................... 47 5 INTRODUCTION During the Korean War more than 3,200 United Nations troops in Korea developed a...rare hemorrhagic fever, a situa- tion that attracted worldwide attention (1). Since then it has been known as Korean hemorrhagic fever (KHF) in Korea ...Chungchoongnsmdo, and Kangwendo, norLhern parts of South Korea . Almost all HFRS patients among Korean soldiers occurred in Kyunggido aind Ksngwmndo where

  2. [Viral hemorrhagic fever].

    PubMed

    Kager, P A

    1998-02-28

    Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of thousands of deaths annually outside the Netherlands. The viruses are mostly transmitted by mosquitoes, ticks or via excreta of rodents. Important to travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever there is an efficacious vaccine. Dengue is frequently observed in travellers; prevention consists in avoiding mosquito bites, the treatment is symptomatic. Lassa and Ebola fever are extremely rare among travellers; a management protocol can be obtained from the Netherlands Ministry of Health, Welfare and Sports. Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis should be aimed at treatable disorders such as malaria, typhoid fever, rickettsiosis or bacterial sepsis, because the probability of such a disease is much higher than that of Lassa or Ebola fever.

  3. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever).

    DTIC Science & Technology

    1986-07-23

    13 Table 5. Monthly incidence of HFRS among Korean in the Republic of Korea , 1966-1985 . . . . . . . 14 A Table 6. Incidence of HFRS by...GRANT SUPPORT .. ........ 57.... 5 INTRODUCTION During the Korean War more than 3,000 United Nations .00 troops in Korea developed a rare hemorrhagic...8217;.-.* * S.’ . " 10 ... Table 1. Hospitalized cases of Hemorrhagic fever with renal syndrome patients in the Republic of Korea Year US Korean Korean

  4. Crimean-Congo Hemorrhagic Fever (CCHF)

    MedlinePlus

    ... Congo Hemorrhagic Fever (CCHF) [PDF - 2 pages] Virus Ecology Viral Hemorrhagic Fever (VHF) Information for Specific Groups ... Diagnosis Treatment Prevention Outbreak Distribution Map Resources Virus Ecology File Formats Help: How do I view different ...

  5. Ebola and marburg hemorrhagic fever.

    PubMed

    Hartman, Amy L; Towner, Jonathan S; Nichol, Stuart T

    2010-03-01

    Ebola and Marburg viruses cause a severe viral hemorrhagic fever disease mainly in Sub-Saharan Africa. Although outbreaks are sporadic, there is the potential for filoviruses to spread to other continents unintentionally because of air travel or intentionally because of bioterrorism. This article discusses the natural history, epidemiology, and clinical presentation of patients infected with Ebola and Marburg viruses. Clinicians in the United States should be aware of the symptoms of these viral infections in humans and know the appropriate procedures for contacting local, state, and national reference laboratories in the event of a suspected case of filoviral hemorrhagic fever.

  6. [Clinical aspects of viral hemorrhagic fever].

    PubMed

    Saijo, Masayuki

    2005-12-01

    Viral hemorrhagic fever (VHF) is defined as virus infections that usually cause pyrexia and hemorrhagic symptoms with multiple organ failure. VHF includes following viral infections: Ebola hemorrhagic fever (EHF), Marburg hemorrhagic fever (MHF), Crimean-Congo hemorrhagic fever (CCHF) and Lassa fever. In particular, the causative agents of EHF, MHF, CCHF, and Lassa fever are Ebola, Marburg, CCHF, Lassa viruses, respectively, and regarded as biosafety level-4 pathogens because of their high virulence to humans. Recently, relatively large outbreaks of EHF and MHF have occurred in Africa, and areas of EHF- and MHF-outbreaks seem to be expanding. Although outbreaks of VHF have not been reported in Japan, there is a possibility that the deadly hemorrhagic fever viruses would be introduced to Japan in future. Therefore, preparedness for possible future outbreaks of VHF is necessary in areas without VHF outbreaks.

  7. Crimean-Congo Hemorrhagic Fever.

    PubMed

    Shayan, Sara; Bokaean, Mohammad; Shahrivar, Mona Ranjvar; Chinikar, Sadegh

    2015-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tickborne viral infection worldwide: it has been reported in many regions of Africa, the Middle East, and Asia. The geographical distribution of CCHFV corresponds most closely with the distribution of members of the tick genera, and Hyalomma ticks are the principal source of human infection. In contrast to human infection, CCHFV infection is asymptomatic in all species. Treatment options for CCHF are limited; immunotherapy and ribavirin are effective in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has not yet been proven. This article reviews the history, epidemiology, clinical symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the development of a vaccine against it.

  8. Crimean-Congo Hemorrhagic Fever.

    PubMed

    Burnett, Mark W

    2015-01-01

    In mid-September 2009, a 22-year-old critically ill Soldier was medically evacuated from a treatment facility in southern Afghanistan to Landstuhl Regional Medical Center in Germany. Despite the efforts of the team at Landstuhl, this patient died and became the US military's first known victim of Crimean-Congo hemorrhagic fever (CCHF). CCHF is caused by a virus, which bears the same name. Because a vaccine is lacking, as well as an effective antiviral treatment, prevention is key.

  9. Simian Hemorrhagic Fever (SHF) Virus. Phase 3

    DTIC Science & Technology

    1993-07-31

    tlll AD111 CONTRACT NO: DAMDI7-91-C-1006 TITLE: SIMIAN HEMORRHAGIC FEVER (SHF) VIRUS PRINCIPAL INVESTIGATOR: Margo A. Brinton, Ph.D. CONTRACTING...SUBTITLE S. FUNDING NUMBERS Simian Hemorrhagic Fever (SHF) Virus DAMD17-91-C-1006 6. AUTHOR(S) Margo A. Brinton, Ph.D. 7. PERFORMING ORGANIZATION...simian hemorrhagic fever (SHF) virus -specific hybridoma cultures, expand two clones from each clone as well as 50 ml of supernatant fluid from

  10. [Acute rheumatic fever].

    PubMed

    Maier, Alexander; Kommer, Vera

    2016-03-01

    We report on a young women with acute rheumatic fever. Acute rheumatic fever has become a rare disease in Germany, especially in adults. This carries the risk that it can be missed in the differential diagnostic considerations of acute rheumatic disorders and febrile status. If rheumatic fever is not diagnosed and treated correctly, there is a considerable risk for rheumatic valvular heart disease. In this article diagnosis, differential diagnosis and therapy of rheumatic fever are discussed extensively.

  11. Treatment of Argentine hemorrhagic fever.

    PubMed

    Enria, Delia A; Briggiler, Ana M; Sánchez, Zaida

    2008-04-01

    Argentine hemorrhagic fever (AHF) is a rodent-borne illness caused by the arenavirus Junin that is endemic to the humid pampas of Argentina. AHF has had significant morbidity since its emergence in the 1950s, with a case-fatality rate of the illness without treatment between 15% and 30%. The use of a live attenuated vaccine has markedly reduced the incidence of AHF. Present specific therapy involves the transfusion of immune plasma in defined doses of neutralizing antibodies during the prodromal phase of illness. However, alternative forms of treatment are called for due to current difficulties in early detection of AHF, related to its decrease in incidence, troubles in maintaining adequate stocks of immune plasma, and the absence of effective therapies for severely ill patients that progress to a neurologic-hemorrhagic phase. Ribavirin might be a substitute for immune plasma, provided that the supply is guaranteed. Immune immunoglobulin or monoclonal antibodies should also be considered. New therapeutic options such as those being developed for systemic inflammatory syndromes should also be valuated in severe forms of AHF.

  12. Unilateral massive hemothorax in Dengue hemorrhagic fever: a unique presentation.

    PubMed

    Karanth, Suman S; Gupta, Anurag; Prabhu, Mukhyaprana

    2012-09-01

    Dengue hemorrhagic fever is a more serious form of disease characterised by plasma leakage syndrome, thrombocytopenia and disseminated intravascular coagulation. We present a 51 year old male who presented with fever, petechiae and acute onset of breathlessness. Emergency chest rhoentogram showed a massive right sided pleural effusion. On insertion of intercostal drain, there was a sudden gush of blood tinged fluid suggestive of hemothorax. There was no history of trauma or bleeding tendencies. Laboratory investigations revealed a raised hematocrit and severe thrombocytopenia. Dengue IgM was surprisingly positive. After aggressive supportive management the patient gradually improved and was discharged. While bilateral pleural effusion is a known occurrence in dengue hemorrhagic fever, massive hemothorax is unheard of. We report the first case in literature of dengue hemorrhagic fever presenting as unilateral massive hemothorax. A suspicion of dengue must also be borne in mind in cases of non-traumatic hemothorax especially in endemic areas.

  13. Antiviral treatment of Argentine hemorrhagic fever.

    PubMed

    Enria, D A; Maiztegui, J I

    1994-01-01

    Argentine hemorrhagic fever is a systemic viral disease caused by Junin virus, with a mortality of 15-30% in untreated individuals. Current specific therapy is highly effective in reducing mortality, and consists of the early administration of immune plasma in defined doses of specific neutralizing antibodies per kg of body weight. However, several reasons suggest the need to investigate alternative therapies. Ribavirin, a broad spectrum antiviral agent, is effective in the treatment of other viral hemorrhagic fevers, and the studies done with Junin virus infections to date indicate that this drug may also have a beneficial effect in Argentine hemorrhagic fever.

  14. Lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.

    PubMed

    El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

    2015-04-01

    Viral hemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. Lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. Rodents are important reservoirs of rodent-borne zoonosis worldwide. Transmission rodents to humans occur by aerosol spread, either from the genus Mastomys rodents' excreta (multimammate rat) or through the close contact with infected patients (nosocomial infection). Other rodents of the genera Rattus, Mus, Lemniscomys, and Praomys are incriminated rodents hosts. Now one may ask do the rodents' ectoparasites play a role in Lassa virus zoonotic transmission. This paper summarized the update knowledge on LHV; hopping it might be useful to the clinicians, nursing staff, laboratories' personals as well as those concerned zoonoses from rodents and rodent control.

  15. Acute Hemorrhagic Edema of Infancy.

    PubMed

    Serra E Moura Garcia, C; Sokolova, A; Torre, M L; Amaro, C

    2016-01-01

    Acute Hemorrhagic Edema of Infancy is a small vessel leucocytoclastic vasculitis affecting young infants. It is characterized by large, target-like, macular to purpuric plaques predominantly affecting the face, ear lobes and extremities. Non-pitting edema of the distal extremities and low-grade fever may also be present. Extra-cutaneous involvement is very rare. Although the lesions have a dramatic onset in a twenty-four to forty-eight hour period, usually the child has a non-toxic appearance. In most cases there are no changes in laboratory parameters. The cutaneous biopsy reveals an inflammatory perivascular infiltrate. It is a benign and auto-limited disease, with complete resolution within two to three weeks leaving no sequelae in the majority of cases. No recurrences are described. We report a case of a 42-day old girl admitted at our hospital with Acute Hemorrhagic Edema of Infancy.

  16. Diagnosis of Crimean-Congo hemorrhagic fever.

    PubMed

    Tezer, Hasan; Polat, Meltem

    2015-05-01

    Crimean-Congo hemorrhagic fever (CCHF) virus is the most extensive tick-borne virus, it causes a severe infection, which occurs widely in Africa, Eastern Europe and Asia. In recent years, the dramatic increase in the global distribution of CCHF, with the high mortality rates, highlights the importance of improving diagnostic capacity. Clinical and epidemiological data play a crucial role for early recognition of CCHF. However, CCHF is clinically difficult to diagnose and to distinguish, a rapid and reliable laboratory confirmation is necessary. Confirmation of infection in the acute phase of the disease can be made by detection of viral nucleic acid using reverse transcription-PCR, by demonstration of viral antigen or by virus isolation. In the convalescent phase of the disease, the diagnosis is confirmed by demonstration of an antibody response. The consideration of viral replication kinetics and antiviral humoral immune responses facilitates the selection of appropriate laboratory tests and accurate interpretation of laboratory findings.

  17. Clinical aspects of Marburg hemorrhagic fever

    PubMed Central

    Mehedi, Masfique; Groseth, Allison; Feldmann, Heinz; Ebihara, Hideki

    2011-01-01

    Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention. PMID:22046196

  18. Animal models of viral hemorrhagic fever.

    PubMed

    Smith, Darci R; Holbrook, Michael R; Gowen, Brian B

    2014-12-01

    The term "viral hemorrhagic fever" (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures.

  19. Crimean-Congo hemorrhagic fever virus, Greece.

    PubMed

    Papa, Anna; Sidira, Persefoni; Larichev, Victor; Gavrilova, Ludmila; Kuzmina, Ksenia; Mousavi-Jazi, Mehrdad; Mirazimi, Ali; Ströher, Ute; Nichol, Stuart

    2014-02-01

    Seroprevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) is high in some regions of Greece, but only 1 case of disease has been reported. We used 4 methods to test 118 serum samples that were positive for CCHFV IgG by commercial ELISA and confirmed the positive results. A nonpathogenic or low-pathogenicity strain may be circulating.

  20. Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture.

    PubMed

    Jiang, Hong; Du, Hong; Wang, Li M; Wang, Ping Z; Bai, Xue F

    2016-01-01

    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed.

  1. Infection Control During Filoviral Hemorrhagic Fever Outbreaks

    PubMed Central

    Vanessa, N Raabe; Matthias, Borchert

    2012-01-01

    Breaking the human-to-human transmission cycle remains the cornerstone of infection control during filoviral (Ebola and Marburg) hemorrhagic fever outbreaks. This requires effective identification and isolation of cases, timely contact tracing and monitoring, proper usage of barrier personal protection gear by health workers, and safely conducted burials. Solely implementing these measures is insufficient for infection control; control efforts must be culturally sensitive and conducted in a transparent manner to promote the necessary trust between the community and infection control team in order to succeed. This article provides a review of the literature on infection control during filoviral hemorrhagic fever outbreaks focusing on outbreaks in a developing setting and lessons learned from previous outbreaks. The primary search database used to review the literature was PUBMED, the National Library of Medicine website. PMID:22529631

  2. Infection control during filoviral hemorrhagic Fever outbreaks.

    PubMed

    Raabea, Vanessa N; Borcherta, Matthias

    2012-01-01

    Breaking the human-to-human transmission cycle remains the cornerstone of infection control during filoviral (Ebola and Marburg) hemorrhagic fever outbreaks. This requires effective identification and isolation of cases, timely contact tracing and monitoring, proper usage of barrier personal protection gear by health workers, and safely conducted burials. Solely implementing these measures is insufficient for infection control; control efforts must be culturally sensitive and conducted in a transparent manner to promote the necessary trust between the community and infection control team in order to succeed. This article provides a review of the literature on infection control during filoviral hemorrhagic fever outbreaks focusing on outbreaks in a developing setting and lessons learned from previous outbreaks. The primary search database used to review the literature was PUBMED, the National Library of Medicine website.

  3. A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

    PubMed

    Vatter, Heather A; Donaldson, Eric F; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael K; Pecotte, Jerilyn K; Baric, Ralph S; Wong, Scott W; Brinton, Margo A

    2015-01-01

    Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques.

  4. Immunological Features Underlying Viral Hemorrhagic Fevers

    PubMed Central

    Messaoudi, Ilhem; Basler, Christopher F.

    2015-01-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. PMID:26163194

  5. Acute subarachnoid hemorrhage

    PubMed Central

    Hassan, Ali; Ahmad, Bakhtiar; Ahmed, Zahoor; Al-Quliti, Khalid W.

    2015-01-01

    Ruptured cerebral aneurysm is the most common cause of spontaneous subarachnoid hemorrhage (SAH). Rarely cerebral venous sinus thrombosis (CVST) may present initially as acute SAH, and clinically mimics aneurysmal bleed. We report 2 cases of CVST who presented with severe headache associated with neck pain and focal seizures. Non-contrast brain CT showed SAH, involving the sulci of the convexity of hemisphere (cSAH) without involving the basal cisterns. Both patients received treatment with anticoagulants and improved. Awareness of this unusual presentation of CVST is important for early diagnosis and treatment. The purpose of this paper is to emphasize the inclusion of vascular neuroimaging like MRI with venography or CT venography in the diagnostic workup of SAH, especially in a patient with strong clinical suspicion of CVST or in a patient where neuroimaging showed cSAH. PMID:25630784

  6. Viruses Causing Hemorrhagic Fever. Safety Laboratory Procedures

    PubMed Central

    Cobo, Fernando

    2016-01-01

    Viral hemorrhagic fevers are diseases caused by viruses which belong to different families, many of them causing severe diseases. These viruses may produce different symptomatology together with a severe multisystem syndrome, and the final result might be the production of hemorrhages in several sites of the body. The majority of them have no other treatment than supportive therapy, although some antiviral drugs can be used in some circumstances. Transmission of VHF has been demonstrated through contact with animal vectors or person-to-person through the contact with body fluids. No risk of transmission has been found during the incubation period, but when the viral load is high the risk of transmission is greatest. Both health care and clinical laboratory workers must safely handle patients and specimens by taking all required precautions during their management. PMID:27014378

  7. Emergence of Crimean-Congo hemorrhagic fever.

    PubMed

    Leblebicioglu, Hakan; Ozaras, Resat; Erciyas-Yavuz, Kiraz

    2015-11-01

    Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening tick-borne infection in Africa and Eurasia. Although knowledge of epidemiology is increasing, the global extent and risk of infection is not well described. A niche-modeling framework has been used to map the global distribution of risk for CCHF based on analysis of human CCHF reports. The new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF. Migratory birds travelling across continents may also introduce CCHF to new areas through attached ticks. There is an overlap between CCHF endemic areas and breeding and wintering grounds of migratory birds.

  8. Phylogeography of Crimean Congo Hemorrhagic Fever Virus

    PubMed Central

    Klimentov, Alexander S.; Dzagurova, Tamara K.; Drexler, Jan Felix; Gmyl, Anatoly P.

    2016-01-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is one of the most severe viral zoonozes. It is prevalent throughout Africa, Asia and southern Europe. Limited availability of sequence data has hindered phylogeographic studies. The complete genomic sequence of all three segments of 14 Crimean Congo hemorrhagic fever virus strains isolated from 1958–2000 in Russia, Central Asia and Africa was identified. Each genomic segment was independently subjected to continuous Bayesian phylogeographic analysis. The origin of each genomic segment was traced to Africa about 1,000–5,000 years ago. The virus was first introduced to South and Central Asia in the Middle Ages, and then spread to China, India and Russia. Reverse transfers of genomic segments from Asia to Africa were also observed. The European CCHFV genotype V was introduced to Europe via the Astrakhan region in South Russia 280–400 years ago and subsequently gradually spread westward in Russia, to Turkey and the Balkans less than 150 years ago. Only a few recombination events could be suggested in S and L genomic segments, while segment reassortment was very common. The median height of a non-reassortant phylogenetic tree node was 68–156 years. There were reassortment events within the European CCHFV lineage, but not with viruses from other locations. Therefore, CCHFV in Europe is a recently emerged zoonosis that represents a spillover from the global gene pool. PMID:27880794

  9. Lymphocyte subsets alteration in patients with argentine hemorrhagic fever.

    PubMed

    Vallejos, D A; Ambrosio, A M; Feuillade, M R; Maiztegui, J I

    1989-02-01

    Peripheral blood lymphocyte subpopulations were studied in 15 patients with Argentine Hemorrhagic Fever (AHF), during the acute period of the disease and in early convalescence. Anti-human Ig antibodies were used to identify B cells and monoclonal antibodies to assess T4 and T8 subsets. During the acute period of the disease, significant alterations were found in B, T4, and T8 lymphocytes (P less than .001), as well as in T4/T8 ratios (P less than .001). These abnormalities disappeared in early convalescence, around 30 days after the clinical onset. Diminished numbers of T4 lymphocytes are interpreted as relevant to the immunodepression that characterizes the acute phase of AHF.

  10. [Ebola and Marburg hemorrhagic fever viruses: update on filoviruses].

    PubMed

    Leroy, E; Baize, S; Gonzalez, J P

    2011-04-01

    The Ebola and Marburg viruses are the sole members of the Filoviridae family of viruses. They are characterized by a long filamentous form that is unique in the viral world. Filoviruses are among the most virulent pathogens currently known to infect humans. They cause fulminating disease characterized by acute fever followed by generalized hemorrhagic syndrome that is associated with 90% mortality in the most severe forms. Epidemic outbreaks of Marburg and Ebola viruses have taken a heavy toll on human life in Central Africa and devastated large ape populations in Gabon and Republic of Congo. Since their discovery in 1967 (Marburg) and 1976 (Ebola), more than 2,300 cases and 1,670 deaths have been reported. These numbers pale in comparison with the burden caused by malnutrition or other infectious disease scourges in Africa such as malaria, cholera, AIDS, dengue or tuberculosis. However, due to their extremely high lethality, association with multifocal hemorrhaging and specificity to the African continent, these hemorrhagic fever viruses have given rise to great interest on the part not only of the international scientific community but also of the general public because of their perceived potential as biological weapons. Much research has been performed on these viruses and major progress has been made in knowledge of their ecology, epidemiology and physiopathology and in development of vaccine candidates and therapeutic schemes. The purpose of this review is to present the main developments in these particular fields in the last decade.

  11. Crimean-Congo hemorrhagic fever virus: new outbreaks, new discoveries.

    PubMed

    Ergonul, Onder

    2012-04-01

    Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection described in Asia, Africa and Europe. Humans become infected through the bites of ticks, by contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viremic livestock. The occurrence of CCHF closely approximates the known world distribution of Hyalomma spp. ticks. The novel studies of phylogenetic analyses reveal the interesting relations between the strains from distant outbreaks. The clinical features show common dramatic progress characterized by hemorrhage, myalgia, and fever. Besides the direct infection of endothelium, indirect damage by viral or virus mediated host-derived soluble factors that cause endothelial activations and dysfunction occur. In diagnosis, enzyme linked immunoassay and real-time reverse transcription-polymerase chain reaction are used. Early diagnosis is critical for the patient and potential nosocomial infections. Supportive therapy is the essential part of the case management. Ribavirin was suggested as an effective drug in recent studies, and it was found to be beneficial. The health care workers are under serious risk of transmission of the infection, particularly during the follow-up of the patient, with hemorrhages from the nose, mouth, gums, vagina, and injection sites.

  12. Ribavirin, Interferon, and Antibody Approaches to Prophylaxis and Therapy for Viral Hemorrhagic Fevers

    DTIC Science & Technology

    1990-01-01

    Arenavirus Lassa fever virus Lassa fever High Junin virus Argentine hemorrhagic fever High Machupo virus Bolivian hemorrhagic fever High Bunyaviridae...assumes aerosol against respiratory syncytial virus was demon- its greatest importance in the case of Lassa fever (dis- strated in experimentally...hemorrhagic fevers and efficacy of various therapeutic approaches Arenavirus infections Bunyavirus infections Argentine

  13. Crimean-Congo Hemorrhagic Fever and Hemorrhagic Fever with Renal Syndrome in Greece.

    DTIC Science & Technology

    1984-12-01

    Identify by block number) Congo Crimean Homorrhagic Fever (CCHF), Hemorrhagic Fever with Renal Syndrom . * -(HFRS), CCHF virus , Hantaan virus , Gre2ce - 20...A.STRACT ("C.une do re, ri It nreuarv md Idewtf by block number) *> CCHF virus or a virus closely related to it exists in clreece, infects humans...Hantaan-li- ke virus occuring in the colntry is orobablv a;tiqenically closer to Hantaan-- J,. DO IN 14n EOiTIONor I NOV 6S IS OBSOLETE,. SECURITY

  14. Epidemiology and Pathogenesis of Bolivian Hemorrhagic Fever

    PubMed Central

    Patterson, Michael; Grant, Ashley; Paessler, Slobodan

    2014-01-01

    The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV) is reported to have a mortality rate of 25 to 35%. First identified in 1959, BHF was the cause of a localized outbreak in San Joaquin until rodent population controls were implemented in 1964. The rodent Calomys collosus was identified as the primary vector and reservoir for the virus. Multiple animal models were considered during the 1970’s with the most human-like disease identified in Rhesus macaques but minimal characterization of the pathogenesis has been published since. A reemergence of reported BHF cases has been reported in recent years, which necessitates the further study and development of a vaccine to prevent future outbreaks. PMID:24636947

  15. Ebola hemorrhagic fever in the era of bioterrorism.

    PubMed

    Polesky, Andrea; Bhatia, Gulshan

    2003-09-01

    Viral hemorrhagic fevers are among a small group of infectious diseases considered potential candidates for use as agents of bioterrorism. Ebola hemorrhagic fever, the focus of this article, has the highest mortality rate of the viral hemorrhagic fevers and has no effective treatment. It is transmitted easily to family members and health care professionals not following universal precautions. The history of this infection, its clinical presentation, and epidemiology are discussed. Attention is paid to the immunopathogenesis of the disease with a focus on pulmonary involvement. Recommendations for infection control and Ebola virus' potential as a bioterrorism agent are addressed.

  16. Ribavirin Prophylaxis and Therapy for Experimental Argentine Hemorrhagic Fever

    DTIC Science & Technology

    1988-09-01

    cessation, values began to patients with Lassa fever in Sierra Leone. where mortality increase, progressively returning toward the base line. The reductions...similar to Bo- Virus isolation and serology. Virus was recovered from all livian hemorrhagic fever than to Lassa fever in humans (18). placebo-treated...clinical re- pti- d for use in Lassa fever patient%. Trisicol. Appi. Phama- spofl5c. J Infect. Dis. 152:218-221. cl 41519 16. McKee, K. T., Jr., IL. G

  17. Vaccine Platforms to Control Arenaviral Hemorrhagic Fevers

    PubMed Central

    Carrion, Ricardo; Bredenbeek, Peter; Jiang, Xiaohong; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S.

    2013-01-01

    Arenaviruses are rodent-borne emerging human pathogens. Diseases caused by these viruses, e.g., Lassa fever (LF) in West Africa and South American hemorrhagic fevers (HFs), are serious public health problems in endemic areas. We have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups “at risk”. Our leader LF vaccine candidate, the live reassortant vaccine ML29, is safe and efficacious in all tested animal models including non-human primates. In this study we showed that treatment of fatally infected animals with ML29 two days after Lassa virus (LASV) challenge protected 80% of the treated animals. In endemic areas, where most of the target population is poor and many live far from health care facilities, a single-dose vaccination with ML29 would be ideal solution. Once there is an outbreak, a fast-acting vaccine or post-exposure prophylaxis would be best. The 2nd vaccine technology is based on Yellow Fever (YF) 17D vaccine. We designed YF17D-based recombinant viruses expressing LASV glycoproteins (GP) and showed protective efficacy of these recombinants. In the current study we developed a novel technology to clone LASV nucleocapsid within YF17D C gene. Low immunogenicity and stability of foreign inserts must be addressed to design successful LASV/YFV bivalent vaccines to control LF and YF in overlapping endemic areas of West Africa. The 3rd platform is based on the new generation of alphavirus replicon virus-like-particle vectors (VLPV). Using this technology we designed VLPV expressing LASV GP with enhanced immunogenicity and bivalent VLPV expressing cross-reactive GP of Junin virus (JUNV) and Machupo virus (MACV), causative agents of Argentinian and Bolivian HF, respectively. A prime-boost regimen required for VLPV immunization might be practical for medical providers, military, lab personnel, and visitors in endemic areas. PMID:23420494

  18. Vaccine Platforms to Control Arenaviral Hemorrhagic Fevers.

    PubMed

    Carrion, Ricardo; Bredenbeek, Peter; Jiang, Xiaohong; Tretyakova, Irina; Pushko, Peter; Lukashevich, Igor S

    2012-11-20

    Arenaviruses are rodent-borne emerging human pathogens. Diseases caused by these viruses, e.g., Lassa fever (LF) in West Africa and South American hemorrhagic fevers (HFs), are serious public health problems in endemic areas. We have employed replication-competent and replication-deficient strategies to design vaccine candidates potentially targeting different groups "at risk". Our leader LF vaccine candidate, the live reassortant vaccine ML29, is safe and efficacious in all tested animal models including non-human primates. In this study we showed that treatment of fatally infected animals with ML29 two days after Lassa virus (LASV) challenge protected 80% of the treated animals. In endemic areas, where most of the target population is poor and many live far from health care facilities, a single-dose vaccination with ML29 would be ideal solution. Once there is an outbreak, a fast-acting vaccine or post-exposure prophylaxis would be best. The 2(nd) vaccine technology is based on Yellow Fever (YF) 17D vaccine. We designed YF17D-based recombinant viruses expressing LASV glycoproteins (GP) and showed protective efficacy of these recombinants. In the current study we developed a novel technology to clone LASV nucleocapsid within YF17D C gene. Low immunogenicity and stability of foreign inserts must be addressed to design successful LASV/YFV bivalent vaccines to control LF and YF in overlapping endemic areas of West Africa. The 3(rd) platform is based on the new generation of alphavirus replicon virus-like-particle vectors (VLPV). Using this technology we designed VLPV expressing LASV GP with enhanced immunogenicity and bivalent VLPV expressing cross-reactive GP of Junin virus (JUNV) and Machupo virus (MACV), causative agents of Argentinian and Bolivian HF, respectively. A prime-boost regimen required for VLPV immunization might be practical for medical providers, military, lab personnel, and visitors in endemic areas.

  19. Cytokines as biomarkers of Crimean-Congo hemorrhagic fever.

    PubMed

    Papa, Anna; Tsergouli, Katerina; Çağlayık, Dilek Yağcı; Bino, Silvia; Como, Najada; Uyar, Yavuz; Korukluoglu, Gulay

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a potentially severe disease caused by CCHF virus. As in other viral hemorrhagic fevers, it is considered that the course and outcome of the disease depend on the viral load and the balance among the immune response mediators, and that a fatal outcome is the result of a "cytokine storm." The level of 27 cytokines was measured in serum samples taken from 29 patients during the acute phase of the disease. Two cases were fatal. Among survivors, significant differences between severe and non-severe cases were observed in the levels of IP-10, and MCP-1, while the levels of IL-1b, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IP-10, MCP-1, TNF-α, and RANTES differed significantly between fatal and non-fatal cases (P < 0.05). RANTES was negatively correlated with the outcome of the disease. A striking similarity with the cytokine patterns seen in Ebola virus disease was observed. A weak Th1 immune response was seen. The viral load was positively correlated with IL-10, IP-10, and MCP-1 levels, and negatively correlated with the ratio IL-12/IL-10. Especially IP-10 and MCP-1 were significantly associated with the viral load, the severity and outcome of the disease, and they could act as biomarkers and, probably, as potential targets for treatment strategies design.

  20. HMGB1 Is a Potential Biomarker for Severe Viral Hemorrhagic Fevers

    PubMed Central

    Resman Rus, Katarina; Fajs, Luka; Korva, Miša; Avšič-Županc, Tatjana

    2016-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. Infection with Dobrava or Puumala virus (HFRS) and Crimean-Congo hemorrhagic fever virus (CCHFV) can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. An important factor in optimizing survival rate in patients with VHF is instant recognition of the severe form of the disease for which significant biomarkers need to be elucidated. To determine the prognostic value of High Mobility Group Box 1 (HMGB1) as a biomarker for disease severity, we tested acute serum samples of patients with HFRS or CCHF. Our results showed that HMGB1 levels are increased in patients with CCHFV, DOBV or PUUV infection. Above that, concentration of HMGB1 is higher in patients with severe disease progression when compared to the mild clinical course of the disease. Our results indicate that HMGB1 could be a useful prognostic biomarker for disease severity in PUUV and CCHFV infection, where the difference between the mild and severe patients group was highly significant. Even in patients with severe DOBV infection concentrations of HMGB1 were 2.8–times higher than in the mild group, but the difference was not statistically significant. Our results indicated HMGB1 as a potential biomarker for severe hemorrhagic fevers. PMID:27348219

  1. [Countermeasure against viral hemorrhagic fever at the border in Japan].

    PubMed

    Iwasaki, Emiko

    2005-12-01

    Human have struggled against many infectious diseases such as cholera, plague, dysentery and yellow fever for a long time. And we have spent a lot of energy to control these infectious diseases and developed various tool for them. One of these efforts was Quarantine system that was established in 14th century in Europe. But during recent days, we are suffering from newly emerged diseases. These new infectious diseases are zoonosis and most of them are serious and highly infectious. Viral hemorrhagic fever such as Ebola hemorrhagic fever, Marburg hemorrhagic fever and Lassa fever are typical these emerging serious diseases, and these outbreak always have occurred in Africa and neighboring countries. Fortunately we have never experienced any case, but as these diseases are so serious, we are so nervous diseases entering in Japan. Against these serious diseases, in Japan, Quarantine Station are doing screening examination at airport and port by questionnaire and measuring body temperature, because these viral hemorrhagic fever patients show high fever. If people were suspected viral hemorrhagic fever at Quarantine Station at the border, they will be leaded to hospital for further examination and treatment as soon as possible.

  2. Investigation of Crimean-Congo Hemorrhagic Fever and Hemorrhagic Fever with Renal Syndrome in Greece

    DTIC Science & Technology

    1991-08-19

    64. SUPPIAMINTA01T1 NOTATION 𔄁 COWA’ COW1 S $IAjCT TERMS XConinWO *A ?*,*fit I nocessary #md Voriti, by biwit flume..,FIELD I GRoi .’f ;Irra:c ee...vomiting, and abdominal pain , while flushing of the face, conjunctival injection, pulmonary edema, shock and hemorrhagic manifestations were only common...signs in 20 HFRS Greek Patients. Symptoms and signs No. of Patients Fever 20 Rigors 20 Headache 20 Abdominal pain 20 Myalgia 18 Arthralgia 18

  3. Pathogenesis of Crimean-Congo hemorrhagic fever.

    PubMed

    Akıncı, Esragül; Bodur, Hürrem; Leblebicioglu, Hakan

    2013-07-01

    Although Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne disease, little is known about its pathogenesis. The interaction of the virus with host cells is most likely responsible for the pathogenesis of CCHF. The main contributors are endothelial cells (ECs) and immune cells. There are 2 theories underlying the CCHF pathogenesis: One is that the virus interacts with the ECs directly and the other that it interacts indirectly via immune cells with subsequent release of soluble mediators. ECs are activated upon infection by the upregulation of soluble molecules and proinflammatory cytokines. Probably, in severe cases, deregulation and excessive release of the cytokines accompanied by endothelial activation have toxic effects, leading to increased vascular permeability, vasodilatation, and subsequently hypotension, multiple organ failure, shock, and death. Studies indicate that CCHF virus (CCHFV) also can impair the innate immune system and cause a delay in adaptive immune response, which is critical for the clearance of CCHFV. The virus has many different ways to block the immune response, leading to uncontrolled viral replication followed by systemic spread of the virus throughout the body. Partial activation of dendritic cells and macrophages, delayed induction of interferons, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. However, there are many points waiting for clarification about the pathogenesis of CCHF. Although the high risk of contagiousness limits research, we need more studies to understand the CCHF pathogenesis better. Here we review the main characteristics of the pathogenesis of CCHF.

  4. Hemorrhagic fever with renal syndrome in Montenegro.

    PubMed

    Gledovic, Z B; Jeknic, A S; Grgurevic, A D; Rakocevic, B B; Bozovic, B R; Mugosa, B V

    2008-09-01

    The objective of the study was to analyze the epidemiological features of hemorrhagic fever with renal syndrome (HFRS) in Montenegro. The study included 169 cases of HFRS diagnosed in the period between 1995 and 2005 according to the clinical symptoms and serological confirmation. For the analysis of the demographic characteristics of the cases, as well as of the chronological and topographical features of the disease, a descriptive epidemiological method was employed. The average incidence rate in the observed period was 2.6 per 100,000. In the observed period, 8 people died; the average case fatality rate was 4.8% (range: 0.1-15%). Among the diseased persons, 116 were males and 53 were females; most of the cases were adults. The greatest number of HFRS cases occurred during the summer months. The highest incidence rates were registered in the northeastern, rural part of the country. The most frequent type of hantaviruses in Montenegro were Dobrava-Belgrade and Hantaan, carried by rodent species, i.e., the yellow-neck mouse and the striped-field mouse. It is likely that HFRS in Montenegro will become more common in the near future, unless public health control measures are taken.

  5. Emerging intracellular receptors for hemorrhagic fever viruses.

    PubMed

    Jae, Lucas T; Brummelkamp, Thijn R

    2015-07-01

    Ebola virus and Lassa virus belong to different virus families that can cause viral hemorrhagic fever, a life-threatening disease in humans with limited treatment options. To infect a target cell, Ebola and Lassa viruses engage receptors at the cell surface and are subsequently shuttled into the endosomal compartment. Upon arrival in late endosomes/lysosomes, the viruses trigger membrane fusion to release their genome into the cytoplasm. Although contact sites at the cell surface were recognized for Ebola virus and Lassa virus, it was postulated that Ebola virus requires a critical receptor inside the cell. Recent screens for host factors identified such internal receptors for both viruses: Niemann-Pick disease type C1 protein (NPC1) for Ebola virus and lysosome-associated membrane protein 1 (LAMP1) for Lassa virus. A cellular trigger is needed to permit binding of the viral envelope protein to these intracellular receptors. This 'receptor switch' represents a previously unnoticed step in virus entry with implications for host-pathogen interactions and viral tropism.

  6. Crimean-Congo hemorrhagic fever in Iran.

    PubMed

    Keshtkar-Jahromi, Maryam; Sajadi, Mohammad M; Ansari, Hossein; Mardani, Masoud; Holakouie-Naieni, Kourosh

    2013-10-01

    The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was first identified in studies of livestock sera and ticks in the 1970s, but the first human infection was not diagnosed until 1999. Since that time, the number of cases of CCHF in Iran has markedly increased. Through January 2012, articles in the published literature have reported a total of 870 confirmed cases, with 126 deaths, for a case fatality rate (CFR) of 17.6%. The disease has been seen in 26 of the country's 31 provinces, with the greatest number of cases in Sistan and Baluchestan, Isfahan, Fars, Tehran, Khorasan, and Khuzestan provinces. The increase in CCHF in Iran has paralleled that in neighboring Turkey, though the number of cases in Turkey has been much larger, with an overall CFR of around 5%. In this article, we review the features of CCHF in Iran, including its history, epidemiology, animal and tick reservoirs, current surveillance and control programs, diagnostic methods, clinical features and experience with ribavirin therapy, and consider possible explanations for the difference in the CFR of CCHF between Iran and Turkey. The emergence of CCHF in Iran calls for countermeasures at many levels to protect the population, but also provides opportunities for studying the epidemiology, diagnosis and management of the disease.

  7. Medical examiners and Crimean-Congo hemorrhagic fever contamination risk.

    PubMed

    Ozsoy, Sait; Gokmen, Asude; Ozdemir, Mehtap; Akduman, Baris; Korkusuz, Irfan; Javan, Gulnaz T

    2015-11-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is an acute zoonotic infection caused by the CCHF virus. The viruses' activity peaks during April and May with a mortality rate of 3-30%. Transmission of the virus to human occurs through tick bites or exposure to infected animals' tissues or blood. The major at-risk group includes farmers living in endemic areas. Health-care workers are the second most affected group. Virus has shown up in a diverse geographic area which includes Middle East, Asia, Africa and Eastern Europe and is considered one of the most wide-spread tick borne infections. The most recent cases are from Iran and Turkey. This article represents autopsy results of four CCHF infected cases in 2011 and 2012, in Ankara, Turkey.

  8. [Marburg and Ebola hemorrhagic fevers--pathogens, epidemiology and therapy].

    PubMed

    Stock, Ingo

    2014-09-01

    Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.

  9. Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance.

    PubMed

    Rasmussen, Angela L; Okumura, Atsushi; Ferris, Martin T; Green, Richard; Feldmann, Friederike; Kelly, Sara M; Scott, Dana P; Safronetz, David; Haddock, Elaine; LaCasse, Rachel; Thomas, Matthew J; Sova, Pavel; Carter, Victoria S; Weiss, Jeffrey M; Miller, Darla R; Shaw, Ginger D; Korth, Marcus J; Heise, Mark T; Baric, Ralph S; de Villena, Fernando Pardo-Manuel; Feldmann, Heinz; Katze, Michael G

    2014-11-21

    Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever.

  10. Crimean-Congo hemorrhagic fever (CCHF) in Southern Kordofan.

    PubMed

    Abdelhakam, Haydar Awad Abdelrazig; Taha, Mohamed Ahmed

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a disease that poses a great threat to public health owing to its high mortality rate (30-70%), mode of transmission and geographic distribution. Here, we report on a nine years-old Sudanese boy from Southern Kordofan State who presented with Jaundice, high-grade fever, severe headache, abdominal pain and a history of hematemesis. The diagnosis of CCHF was confirmed based on clinical and serological findings.

  11. Viral hemorrhagic fevers in the Tihamah region of the western Arabian Peninsula.

    PubMed

    Zakham, Fathiah; Al-Habal, Mohammed; Taher, Rola; Alaoui, Altaf; El Mzibri, Mohammed

    2017-04-01

    Viral hemorrhagic fever (VHF) refers to a group of diseases characterized by an acute febrile syndrome with hemorrhagic manifestations and high mortality rates caused by several families of viruses that affect humans and animals. These diseases are typically endemic in certain geographical regions and sometimes cause major outbreaks. The history of hemorrhagic fever in the Arabian Peninsula refers to the 19th century and most outbreaks were reported in the Tihamah region-the Red Sea coastal plain of the Arabian Peninsula in the west and southwest of Saudi Arabia and Yemen. Herein, we describe the agents that cause VHFs and their epidemiology in Tihamah, the history of the diseases, transmission, species affected, and clinical signs. Finally, we address challenges in the diagnosis and control of VHFs in this region.

  12. Crimean-Congo Hemorrhagic Fever in Dubai, United Arab Emirates, 2010: Case Report

    PubMed Central

    Mohamed AL Dabal, Laila; Rahimi Shahmirzadi, Mohmamed Reza; Baderldin, Samar; Abro, Ali; Zaki, Ali; Dessi, Zulfa; Al Eassa, Essa; Khan, Gulfaraz; Shuri, Hassan; Alwan, Abid Mustafa

    2016-01-01

    Introduction Crimean-Congo hemorrhagic fever (CCHF) is a severe infectious disease that is not endemic in the United Arab Emirates (UAE). Case Presentation We report two cases of confirmed CCHF diagnosed in Dubai, UAE, during Hajj season 2010. Both patients presented with an acute history of high-grade fever, skin rash, and hematemesis. Conclusions In spite of maximal supportive measures and intravenous ribavirin therapy, both patients died within a few days from start of illness. More than 250 health care workers came into variable degrees of contact with the index cases, and none of them developed signs or symptoms suggestive of acquiring the illness. Health care workers from nonendemic regions should be aware of zoonotic hemorrhagic fevers imported via infected cattle and ticks and be able to diagnose and properly manage suspected cases in a timely manner. In addition, proper infection-control measures should be undertaken to prevent nosocomial spread of infection. PMID:27795839

  13. Clinical Features and Patient Management of Lujo Hemorrhagic Fever

    PubMed Central

    Sewlall, Nivesh H.; Richards, Guy; Duse, Adriano; Swanepoel, Robert; Paweska, Janusz; Blumberg, Lucille; Dinh, Thu Ha; Bausch, Daniel

    2014-01-01

    Background In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. Methods and Findings We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Conclusions Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here

  14. Program for Preparation of Immune Globulin against Bolivian Hemorrhagic Fever

    DTIC Science & Technology

    hemorrhagic fever. Donors were recruited from the rural area of San Joaquin, Bolivia, where a temporary plasmapheresis unit was established, using project...funds. The collected plasma was fractionated in the United States where one half was retained for prophylactic or therapeutic use following potential

  15. Investigations of Hemorrhagic Fever with Renal Syndrome (HFRS) in Yugoslavia.

    DTIC Science & Technology

    1991-11-07

    hantaviruses . The 130 individuals possessed hantaviral antibodies. A nationwide epidemic of hemorrhagic fever with renal syndrome (HFRS) occurred in...where four types of antibody patterns were found. Two of these antibody patterns suggested the existence of hantaviruses which are antigenically distinct...endemic areas in Yugoslavia tested for IF antibodies to Hantaan and Puumala viruses and hantaviruses antigens ...... ................. 28 10. Percentage

  16. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection

    PubMed Central

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made. PMID:25709166

  17. Acute hemorrhagic encephalitis: An unusual presentation of dengue viral infection.

    PubMed

    Nadarajah, Jeyaseelan; Madhusudhan, Kumble Seetharama; Yadav, Ajay Kumar; Gupta, Arun Kumar; Vikram, Naval Kumar

    2015-01-01

    Dengue is a common viral infection worldwide with presentation varying from clinically silent infection to dengue fever, dengue hemorrhagic fever, and severe fulminant dengue shock syndrome. Neurological manifestation usually results from multisystem dysfunction secondary to vascular leak. Presentation as hemorrhagic encephalitis is very rare. Here we present the case of a 13-year-old female admitted with generalized tonic clonic seizures. Plain computed tomography (CT) scan of head revealed hypodensities in bilateral deep gray matter nuclei and right posterior parietal lobe without any hemorrhage. Cerebrospinal fluid (CSF) and serology were positive for IgM and IgG antibodies to dengue viral antigen. Contrast-enhanced magnetic resonance imaging (MRI) revealed multifocal T2 and fluid attenuated inversion recovery (FLAIR) hyperintensities in bilateral cerebral parenchyma including basal ganglia. No hemorrhage was seen. She was managed with steroids. As her clinical condition deteriorated, after being stable for 2 days, repeat MRI was done which revealed development of hemorrhage within the lesions, and diagnosis of acute hemorrhagic encephalitis of dengue viral etiology was made.

  18. [Severe hemorrhagic forms of Rift Valley fever: about 5 cases].

    PubMed

    Salem, Mohamed Lemine Ould; Baba, Sidi El Wafi Ould; Fall-Malick, Fatimetou Zahra; Boushab, Boushab Mohamed; Ghaber, Sidi Mohamed; Mokhtar, Abdelwedoud

    2016-01-01

    Rift Valley fever (RVF) is an arbovirus caused by an RNA virus belonging to family Bunyaviridae (genus phlebovirus). It is a zoonosis that primarily affects animals but it also has the capacity to infect humans, either by handling meat, runts of sick animals or, indirectly, by the bite of infected mosquitoes (Aedes sp, Anopheles sp, Culex sp). In most cases, RVF infection in humans is asymptomatic, but it can also manifest as moderate febrile syndrome with a favorable outcome. However, some patients may develop hemorrhagic syndrome and/or neurological damages with a fatal evolution. We present a case study of the development of 5 patients with RVF associated with hemorrhagic fever syndrome admitted to the internal medicine department at National Hospital Center in Nouakchott (Mauritania), in October 2015. The outcome was favorable for two of the five patients. The other 3 died, two of hemorrhagic shock and one of septic shock.

  19. Updates in diagnosis and management of Ebola hemorrhagic fever.

    PubMed

    El Sayed, Salah Mohamed; Abdelrahman, Ali A; Ozbak, Hani Adnan; Hemeg, Hassan Abdullah; Kheyami, Ali Mohammed; Rezk, Nasser; El-Ghoul, Mohamed Baioumy; Nabo, Manal Mohamed Helmy; Fathy, Yasser Mohamed

    2016-01-01

    Ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. Ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. Major concern is pilgrimage seasons with possible transmission to Middle East populations. In this review, we aim to shed light on Ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for prevention and management. We also aim to guide future research to new therapeutic perspectives to precise targets. Our methodology was to review the literature extensively to make an overall view of the biology of Ebola virus infection, its serious health effects and possible therapeutic benefits using currently available remedies and future perspectives. Key findings in Ebola patients are fever, hepatic impairment, hepatocellular necrosis, lymphopenia (for T-lymphocyte and natural killer cells) with lymphocyte apoptosis, hemorrhagic manifestations, and complications. Pathogenesis in Ebola infection includes oxidative stress, immune suppression of both cell-mediated and humoral immunities, hepatic and adrenal impairment and failure, hemorrhagic fever, activation of deleterious inflammatory pathways, for example, tumor necrosis factor-related apoptosis-inducing ligand, and factor of apoptotic signal death receptor pathways causing lymphocyte depletion. Several inflammatory mediators and cytokines are involved in pathogenesis, for example, interleukin-2, 6, 8, and 10 and others. In conclusion, Ebola hemorrhagic fever is a serious fatal viral infection that can be prevented using strict health measures and can be treated to some extent using some currently available remedies. Newer treatment lines, for example, prophetic medicine remedies as nigella sativa may be promising.

  20. Updates in diagnosis and management of Ebola hemorrhagic fever

    PubMed Central

    El Sayed, Salah Mohamed; Abdelrahman, Ali A.; Ozbak, Hani Adnan; Hemeg, Hassan Abdullah; Kheyami, Ali Mohammed; Rezk, Nasser; El-Ghoul, Mohamed Baioumy; Nabo, Manal Mohamed Helmy; Fathy, Yasser Mohamed

    2016-01-01

    Ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. Ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. Major concern is pilgrimage seasons with possible transmission to Middle East populations. In this review, we aim to shed light on Ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for prevention and management. We also aim to guide future research to new therapeutic perspectives to precise targets. Our methodology was to review the literature extensively to make an overall view of the biology of Ebola virus infection, its serious health effects and possible therapeutic benefits using currently available remedies and future perspectives. Key findings in Ebola patients are fever, hepatic impairment, hepatocellular necrosis, lymphopenia (for T-lymphocyte and natural killer cells) with lymphocyte apoptosis, hemorrhagic manifestations, and complications. Pathogenesis in Ebola infection includes oxidative stress, immune suppression of both cell-mediated and humoral immunities, hepatic and adrenal impairment and failure, hemorrhagic fever, activation of deleterious inflammatory pathways, for example, tumor necrosis factor-related apoptosis-inducing ligand, and factor of apoptotic signal death receptor pathways causing lymphocyte depletion. Several inflammatory mediators and cytokines are involved in pathogenesis, for example, interleukin-2, 6, 8, and 10 and others. In conclusion, Ebola hemorrhagic fever is a serious fatal viral infection that can be prevented using strict health measures and can be treated to some extent using some currently available remedies. Newer treatment lines, for example, prophetic medicine remedies as nigella sativa may be promising. PMID:28163730

  1. Pathogenic mechanisms involved in the hematological alterations of arenavirus-induced hemorrhagic fevers.

    PubMed

    Schattner, Mirta; Rivadeneyra, Leonardo; Pozner, Roberto G; Gómez, Ricardo M

    2013-01-21

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

  2. Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

    PubMed Central

    Schattner, Mirta; Rivadeneyra, Leonardo; Pozner, Roberto G.; Gómez, Ricardo M.

    2013-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms. PMID:23337384

  3. Adult-onset acute rheumatic fever.

    PubMed

    Nakashima, Dainari; Ueda, Kohei; Tsukuda, Kyozo; Utsu, Noriaki; Kohki, Shimazu; Fushimi, Hiroaki; Miyakoshi, Kazuho

    2012-01-01

    A 62-year-old man was hospitalized for acute rheumatic fever. He had previously suffered from rheumatic fever at 15 years of age. The rheumatic fever was complicated by carditis, which caused valve disease that required surgical treatment. The incidence of rheumatic fever has decreased in most developed countries with improvements in sanitary conditions. The low incidence of this disease makes a timely and accurate diagnosis difficult. Due to the fact that both the first occurrence and recurrence of acute rheumatic fever can occur in the elderly and adults, this potential disease should not be overlooked when making a differential diagnosis.

  4. Ebola Hemorrhagic Fever as a Public Health Emergency of International Concern; a Review Article.

    PubMed

    Safari, Saeed; Baratloo, Alireza; Rouhipour, Alaleh; Ghelichkhani, Parisa; Yousefifard, Mahmood

    2015-01-01

    Ebola hemorrhagic fever (EHF) was first reported in 1976 with two concurrent outbreaks of acute viral hemorrhagic fever centered in Yambuku (near the Ebola river), Democratic Republic of Congo, and in Nzara, Sudan. The current outbreak of the Ebola virus was started by reporting the first case in March 2014 in the forest regions of southeastern Guinea. Due to infection rates raising over 13,000% within a 6-month period, Ebola is now considered as a global public health emergency and on August 8(th), 2014 the World Health Organization (WHO) declared the epidemic to be a Public Health Emergency of International Concern. With more than 5000 involved cases and nearly 3000 deaths, this event has turned into the largest and most dangerous Ebola virus outbreak in the world. Based on the above-mentioned, the present article aimed to review the virologic characteristics, transmission, clinical manifestation, diagnosis, treatment, and prevention of Ebola virus disease.

  5. Satellite Detection of Ebola River Hemorrhagic Fever Epidemics Trigger Events

    NASA Technical Reports Server (NTRS)

    Tucker, Compton J.; Pinzon, Jorge E.

    2006-01-01

    Ebola hemorrhagic fever, named after the Ebola River in Central Africa, first appeared in June 1976, during an outbreak in Nzara and Maridi, Sudan. In September 1976, a separate outbreak was recognized in Yambuku, Democratic Republic of the Congo (DRC). One fatal case was identified in Tandala, DRC, in June 1977, followed by another outbreak in Nzara, Sudan, in July 1979. Ebola hemorrhagic fever outbreaks results in a very high mortality of patients who contract the disease: from 50 to 80% of infected people perish from this highly virulent disease. Death is gruesome, with those afflicted bleeding to death from massive hemorrhaging of organs and capillaries. The disease was not identified again until the end of 1994, when three outbreaks occurred almost simultaneously in Africa. In October, an outbreak was identified in a chimpanzee community studied by primatologists in Tal, Cote d'lvoire, with one human infection. The following month, multiple cases were reported in northeast Gabon in the gold panning camps of Mekouka, Andock, and Minkebe. Later that same month, the putative index case of the 1995 Kikwit, DRC, outbreak was exposed through an unknown mechanism while working in a charcoal pit. In Gabon, two additional outbreaks were reported in February and JuIy,1996, respectively, in Mayibout II, a village 40 km south of the original outbreak in the gold panning camps, and a logging camp between Ovan and Koumameyong, near Booue. The largest Ebola hemorrhagic fever epidemic occurred in Gulu District, Uganda from August 2000 to January 2001. In December 2001, Ebola reappeared in the Ogooue-lvindo Province, Gabon with extension into Mbomo District, The Republic of the Congo lasting until July 2002. Since 2002 there have been several outbreaks of Ebola hemorrhagic fever in Gabon and adjacent areas of Congo. Of interest is the seasonal context and occasional temporal clustering of Ebola hemorrhagic fever outbreaks. Near simultaneous appearances of Ebola epidemics in

  6. Hemorrhagic Fever with Renal Syndrome (HFRS)

    MedlinePlus

    ... acute kidney failure, which can cause severe fluid overload. The severity of the disease varies depending upon ... Dialysis may be required to correct severe fluid overload. Intravenous ribavirin, an antiviral drug, has been shown ...

  7. [EBOLA HEMORRHAGIC FEVER: DIAGNOSTICS, ETIOTROPIC AND PATHOGENETIC THERAPY, PREVENTION].

    PubMed

    Zhdanov, K V; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fisun, A Ya

    2015-01-01

    The data on diagnostics, etiotropic and pathogenetic therapy, prevention of Ebola hemorrhagic fever are presented including diagnostic algorithms for different clinical situations. Fundamentals of pathogenetic therapy are described. Various groups of medications used for antiviral therapy of conditions caused by Ebola virus are characterized. Experimental drugs at different stages of clinical studies are considered along with candidate vaccines being developed for the prevention of the disease.

  8. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus.

    PubMed

    Zivcec, Marko; Scholte, Florine E M; Spiropoulou, Christina F; Spengler, Jessica R; Bergeron, Éric

    2016-04-21

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  9. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    DOE PAGES

    Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina; ...

    2016-04-21

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  10. [The phospholipid spectrum of erythrocyte membranes in hemorrhagic fever with renal syndrome].

    PubMed

    Kuznetsov, V I; Iushchuk, N D; Morrison, V V

    2005-01-01

    The subjects of the study--patients with severe hemorrhagic fever with renal syndrome--were divided into two groups: those who were on hemodialysis, and those who were not. The study included evaluation of the phospholipid spectrum of erythrocyte membranes in the acute period and during recovery. The results revealed conformational shifts in the structure of the bilipid membrane layer, which were maximal during the acute phase of the disease, as well as less prominent and varied changes in the phospholipid spectrum during recovery. This allows determination of the terms of rehabilitation of the patients and substantiates administration of membrane stabilizers as a part of complex therapy of residual syndrome.

  11. Emerging Infections: Lessons from the Viral Hemorrhagic Fevers

    PubMed Central

    Peters, C. J

    2006-01-01

    Two Institute of Medicine reports since 1992 have emphasized the dangerous and continuing threat to the world from emerging infectious diseases. Working with viral hemorrhagic fevers provides a number of lessons related to the processes that control emergence, the pattern of disease after emergence, and how to cope with these incidents. This short paper uses two arenavirus hemorrhagic fevers to illustrate some of these principles. Argentine and Bolivian hemorrhagic fevers first came to medical attention in the 1950’s. The forces that underlie the emergence of disease in Argentina are not understood, but the Bolivian episode has a reasonably understandable train of events behind it. The Argentine disease had serious impact on the large agricultural economy, and the ecology of the rodent reservoir did not lend itself to control; a vaccine was developed by Argentina and the U.S. with the latter motivated largely by biodefense. The Bolivian disease was controlled in large part by eliminating rodents that invaded towns, and the impact was subsequently below the level needed to trigger drug or vaccine development. These two viruses were important in the recognition of a new family of viruses (Arenaviridae), and this finding of new taxons during the investigation of emerging infectious diseases continues. PMID:18528473

  12. Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.

    PubMed

    Johnson, Reed F; Dodd, Lori E; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A; Jett, Catherine; Bernbaum, John G; Ragland, Dan R; St Claire, Marisa; Byrum, Russell; Paragas, Jason; Blaney, Joseph E; Jahrling, Peter B

    2011-12-20

    Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens.

  13. Pathology of Bolivian Hemorrhagic Fever in the Rhesus Monkey

    PubMed Central

    Terrell, Timothy G.; Stookey, James L.; Eddy, Gerald A.; Kastello, Michael D.

    1973-01-01

    Gross and microscopic lesions associated with Bolivan hemorrhagic fever virus infection in the rhesus monkey were studied in 10 animals which died following inoculation. Gross lesions included skin rash, lymphadenopathy, splenomegaly, meningeal edema, hydropericardium and enlarged friable livers. Hemorrhagic manifestations of the infection were not consistently observed, but hemorrhages were present in the skin, heart, brain and nares in some monkeys. Histopathologic lesions were fairly consistent. Hepatic necrosis with the presence of acidophilic hyaline bodies, necrotizing enteritis, epithelial necrosis and adrenal cortical necrosis were present in all monkeys. Those monkeys which died after the seventeenth day of infection had nonsupurative meningoencephalitis; lymphoid necrosis was present in 3 monkeys that died after day 18. Other microscopic lesions included myocardial degeneration, lymphoid and reticuloendothelial cell hyperplasia and lymphoid depletion. Most of the histopathologic lesions described in human autopsy material were reproduced; however, the necrosis in the skin and oral mucosa, mucosa of the gastrointestinal tract and the adrenal cortex have not been described in man. Despite these apparent discrepancies the results of this investigation indicate that the rhesus monkey is a good experimental model for the study of Bolivian hemorrhagic fever infection. ImagesFig 12Fig 13Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 7Fig 8Fig 9Fig 10Fig 11 PMID:4202335

  14. Hemorrhagic Colloid Cyst Presenting with Acute Hydrocephaly

    PubMed Central

    Akhavan, Reza; Zandi, Behrouz; Pezeshki-Rad, Masoud; Farrokh, Donya

    2017-01-01

    Colloid cysts are benign slow-growing cystic lesions located on the roof of the third ventricle that usually present with symptoms related to gradual rise of intracranial pressure. They mostly remain asymptomatic and sometimes grow progressively and cause diverse symptoms associated with increased intracranial pressure such as headache, diplopia, and sixth cranial nerve palsy. Here we report a 47-year-old female who presented to the emergency department with acute severe headache and nausea/vomiting. On MRI examination acute hydrocephaly due to hemorrhagic colloid cyst was detected. Acute hemorrhage in colloid cysts is extremely rare and may present with symptoms of acute increase in the intracranial pressure. Intracystic hemorrhage is very rarely reported as a complication of colloid cyst presenting with paroxysmal symptoms of acute hydrocephaly. PMID:28210514

  15. Crimean-Congo hemorrhagic fever in Pakistan.

    PubMed

    Rai, Mohammad A; Khanani, Mohammad R; Warraich, Haider J; Hayat, Abbas; Ali, Syed H

    2008-06-01

    Crimean-Congo virus, the causative agent of Crimean-Congo Virus Fever (CCVF) is endemic in Pakistan. Cases are documented sporadically ever year, mostly at and around the time of Eid-ul-Adha, an Islamic festival, celebrated on day 10 through 13 of the 12th month of each lunar calendar year. At this time of the year in Pakistan, livestock are brought down to the urban areas from the rural parts of the country. Animals are housed in open spaces and private houses until they are slaughtered during the 3 days of Eid-ul-Adha. This allows the CCHF virus, which is carried by a tick that inhabits the animal hide, to be transmitted through unprotected contact with live animals as well as through contact with animal blood subsequent to its slaughter. In this report, a typical case of CCVF is described that was encountered in Rawalpindi, Pakistan. A number of issues pertaining to the management of recurrent outbreaks of CCVF in the country are discussed.

  16. Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus

    DTIC Science & Technology

    2010-10-01

    04-1-0876 TITLE: Diversity, replication, pathogenicity and cell biology of Crimean Congo hemorrhagic fever virus PRINCIPAL...approach to the study of a highly pathogenic emerging virus of military importance, Crimean Congo hemorrhagic fever virus (CCHFV). CCHFV causes...disease characterized by abrupt onset fever and can progress to hemorrhage, renal failure and shock. Mortality 13-50% is common. This severe disease

  17. Diagnostic criteria of acute rheumatic fever.

    PubMed

    Burke, Rebecca J; Chang, Christopher

    2014-01-01

    Acute rheumatic fever is an inflammatory sequela of Group A Streptococcal pharyngitis that affects multiple organ systems. The incidence of acute rheumatic fever has been declining even before the use of antibiotics became widespread, however the disease remains a significant cause of morbidity and mortality in children, particularly in developing countries and has been estimated to affect 19 per 100,000 children worldwide. Acute rheumatic fever is a clinical diagnosis, and therefore subject to the judgment of the clinician. Because of the variable presentation, the Jones criteria were first developed in 1944 to aid clinicians in the diagnosis of acute rheumatic fever. The Jones criteria have been modified throughout the years, most recently in 1992 to aid clinicians in the diagnosis of initial attacks of acute rheumatic fever and to minimize overdiagnosis of the disease. Diagnosis of acute rheumatic fever is based on the presence of documented preceding Group A Streptococcal infection, in addition to the presence of two major manifestations or one major and two minor manifestations of the Jones criteria. Without documentation of antecedent Group A Streptococcal infection, the diagnosis is much less likely except in a few rare scenarios. Carditis, polyarthritis and Sydenham's chorea are the most common major manifestations of acute rheumatic fever. However, despite the predominance of these major manifestations of acute rheumatic fever, there can be significant overlap with other disorders such as Lyme disease, serum sickness, drug reactions, and post-Streptococcal reactive arthritis. This overlap between disease processes has led to continued investigation of the pathophysiology as well as development of new biomarkers and laboratory studies to aid in the diagnosis of acute rheumatic fever and distinction from other disease processes.

  18. Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

    PubMed

    Bell, T M; Bunton, T E; Shaia, C I; Raymond, J W; Honnold, S P; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

    2016-01-01

    Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development.

  19. Advanced heart block in acute rheumatic fever.

    PubMed

    Hubail, Zakariya; Ebrahim, Ishaq M

    2016-04-01

    First degree heart block is considered a minor criterion for the diagnosis of this condition. The cases presented here demonstrate that higher degrees of heart block do occur in rheumatic fever. Children presenting with acquired heart block should be worked-up for rheumatic fever. Likewise, it is imperative to serially follow the electrocardiogram in patients already diagnosed with acute rheumatic fever, as the conduction abnormalities can change during the course of the disease.

  20. Recent advances in research on Crimean-Congo hemorrhagic fever.

    PubMed

    Papa, Anna; Mirazimi, Ali; Köksal, Iftihar; Estrada-Pena, Augustin; Feldmann, Heinz

    2015-03-01

    Crimean-Congo hemorrhagic fever (CCHF) is an expanding tick-borne hemorrhagic disease with increasing human and animal health impact. Immense knowledge was gained over the past 10 years mainly due to advances in molecular biology, but also driven by an increased global interest in CCHFV as an emerging/re-emerging zoonotic pathogen. In the present article, we discuss the advances in research with focus on CCHF ecology, epidemiology, pathogenesis, diagnostics, prophylaxis and treatment. Despite tremendous achievements, future activities have to concentrate on the development of vaccines and antivirals/therapeutics to combat CCHF. Vector studies need to continue for better public and animal health preparedness and response. We conclude with a roadmap for future research priorities.

  1. Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands

    PubMed Central

    Koopmans, Marion P.G.; Vossen, Ann C.T.M.; van Doornum, Gerard J.J.; Günther, Stephan; van den Berkmortel, Franchette; Verduin, Kees M.; Dittrich, Sabine; Emmerich, Petra; Osterhaus, Albert D.M.E.; van Dissel, Jaap T.; Coutinho, Roel A.

    2009-01-01

    On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who had vacationed recently in Uganda. Exposure most likely occurred in the Python Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa have been found positive for Marburg virus. A multidisciplinary response team was convened to perform a structured risk assessment, perform risk classification of contacts, issue guidelines for follow-up, provide information, and monitor the crisis response. In total, 130 contacts were identified (66 classified as high risk and 64 as low risk) and monitored for 21 days after their last possible exposure. The case raised questions specific to international travel, postexposure prophylaxis for Marburg virus, and laboratory testing of contacts with fever. We present lessons learned and results of the follow-up serosurvey of contacts and focus on factors that prevented overreaction during an event with a high public health impact. PMID:19751577

  2. Response to imported case of Marburg hemorrhagic fever, the Netherland.

    PubMed

    Timen, Aura; Koopmans, Marion P G; Vossen, Ann C T M; van Doornum, Gerard J J; Günther, Stephan; van den Berkmortel, Franchette; Verduin, Kees M; Dittrich, Sabine; Emmerich, Petra; Osterhaus, Albert D M E; van Dissel, Jaap T; Coutinho, Roel A

    2009-08-01

    On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who had vacationed recently in Uganda. Exposure most likely occurred in the Python Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa have been found positive for Marburg virus. A multidisciplinary response team was convened to perform a structured risk assessment, perform risk classification of contacts, issue guidelines for follow-up, provide information, and monitor the crisis response. In total, 130 contacts were identified (66 classified as high risk and 64 as low risk) and monitored for 21 days after their last possible exposure. The case raised questions specific to international travel, postexposure prophylaxis for Marburg virus, and laboratory testing of contacts with fever. We present lessons learned and results of the follow-up serosurvey of contacts and focus on factors that prevented overreaction during an event with a high public health impact.

  3. Vaccines for Viral Hemorrhagic Fevers – Progress and Shortcomings

    PubMed Central

    Falzarano, Darryl; Feldmann, Heinz

    2013-01-01

    With a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. In the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. The two exceptions to this are vaccines against Dengue virus and Rift Valley Fever virus, which recently have seen significant progress in putting forward new and improved vaccines, respectively. Experimental vaccines for filoviruses and Lassa virus do exist but are hindered by a lack of financial interest and only partially or ill-defined correlates/mechanisms of protection that could be assessed in clinical trials. PMID:23773330

  4. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

    2016-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research. PMID:27110812

  5. [Ebola hemorrhagic fever: its extension reflects the African sanitary disaster].

    PubMed

    Bourée, Patrice

    2014-09-01

    Ebola virus, described in 1976 in Zaire, causes severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Epidemics occurred since this time to nowadays in Sudan, Gabon, Congo and currently in Guinea, Liberia, Sierra-Leone, Nigeria and Senegal. Specific treatment and vaccine are not available. So, to prevent the virus transmission with live and dead patients, we must use strict individual and collective measures which are not always understood by local populations and make contact tracing; it is the only way to curb the epidemic.

  6. Trigger events: enviroclimatic coupling of Ebola hemorrhagic fever outbreaks

    NASA Technical Reports Server (NTRS)

    Pinzon, Jorge E.; Wilson, James M.; Tucker, Compton J.; Arthur, Ray; Jahrling, Peter B.; Formenty, Pierre

    2004-01-01

    We use spatially continuous satellite data as a correlate of precipitation within tropical Africa and show that the majority of documented Ebola hemorrhagic fever outbreaks were closely associated with sharply drier conditions at the end of the rainy season. We propose that these trigger events may enhance transmission of Ebola virus from its cryptic reservoir to humans. These findings suggest specific directions to help understand the sylvatic cycle of the virus and may provide early warning tools to detect possible future outbreaks of this enigmatic disease.

  7. Dengue hemorrhagic fever--U.S.-Mexico border, 2005.

    PubMed

    2007-08-10

    Dengue fever is a mosquito-transmitted disease caused by any of four closely related virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) of the genus Flavivirus. Infection with one of these serotypes provides lifelong immunity to the infecting serotype only. Therefore, persons can acquire a second dengue infection from a different serotype, and second infections place them at greater risk for dengue hemorrhagic fever (DHF), the more severe form of the disease. DHF is characterized by bleeding manifestations, thrombocytopenia, and increased vascular permeability that can lead to life-threatening shock. In south Texas, near the border with Mexico, sporadic, locally acquired outbreaks of dengue fever have been reported previously; however, on the Texas side of the border, these outbreaks have not included recognized cases of locally acquired DHF in persons native to the area. In July 2005, a case of DHF was reported in a resident of Brownsville, Texas. In August 2005, health authorities in the neighboring state of Tamaulipas, Mexico, reported an ongoing dengue outbreak with 1,251 cases of dengue fever, including 223 cases (17.8%) of DHF. To characterize this dengue outbreak, the Texas Department of State Health Services (TDSHS), Mexican health authorities, and CDC conducted a clinical and epidemiologic investigation. This report summarizes the results of that investigation, which determined that the percentage of DHF cases associated with dengue fever outbreaks at the Texas-Tamaulipas border has increased. Health-care providers along the U.S. border with Mexico should be vigilant for DHF and familiar with its diagnosis and management to reduce the number of severe illnesses and deaths associated with outbreaks of dengue fever.

  8. The Role of Platelets in the Pathogenesis of Viral Hemorrhagic Fevers

    PubMed Central

    Zapata, Juan C.; Cox, Dermot; Salvato, Maria S.

    2014-01-01

    Viral hemorrhagic fevers (VHF) are acute zoonotic diseases that, early on, seem to cause platelet destruction or dysfunction. Here we present the four major ways viruses affect platelet development and function and new evidence of molecular factors that are preferentially induced by the more pathogenic members of the families Flaviviridae, Bunyaviridae, Arenaviridae, and Filoviridae. A systematic search was performed through the main medical electronic databases using as parameters all current findings concerning platelets in VHF. Additionally, the review contains information from conference proceedings. PMID:24921924

  9. Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever

    PubMed Central

    Warfield, Kelly Lyn; Olinger, Gene Garrard

    2011-01-01

    Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV), and Ebola virus (EBOV), leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL) response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks. PMID:22253531

  10. Imported case of Marburg hemorrhagic fever - Colorado, 2008.

    PubMed

    2009-12-18

    Marburg hemorrhagic fever (MHF) is a rare, viral hemorrhagic fever (VHF); the causative agent is an RNA virus in the family Filoviridae, and growing evidence demonstrates that fruit bats are the natural reservoir of Marburg virus (MARV). On January 9, 2008, an infectious disease physician notified the Colorado Department of Public Health and Environment (CDPHE) of a case of unexplained febrile illness requiring hospitalization in a woman who had returned from travel in Uganda. Testing of early convalescent serum demonstrated no evidence of infection with agents that cause tropical febrile illnesses, including VHF. Six months later, in July 2008, the patient requested repeat testing after she learned of the death from MHF of a Dutch tourist who had visited the same bat-roosting cave as the patient, the Python Cave in Queen Elizabeth National Park, Uganda. The convalescent serologic testing revealed evidence of prior infection with MARV, and MARV RNA was detected in the archived early convalescent serum. A public health investigation did not identify illness consistent with secondary MHF transmission among her contacts, and no serologic evidence of infection was detected among the six tested of her eight tour companions. The patient might have acquired MARV infection through exposure to bat secretions or excretions while visiting the Python Cave. Travelers should be aware of the risk for acquiring MHF in caves or mines inhabited by bats in endemic areas in sub-Saharan Africa. Health-care providers should consider VHF among travelers returning from endemic areas who experience unexplained febrile illness.

  11. Imaging of hemorrhagic fever with renal syndrome: a potential bioterrorism agent of military significance.

    PubMed

    Bui-Mansfield, Liem T; Cressler, Dana K

    2011-11-01

    Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS.

  12. Molecular and serological findings in suspected patients with Crimean-Congo hemorrhagic fever virus in Iran.

    PubMed

    Karlberg, Helen; Sharifi-Mood, Batool; Mousavi-Jazi, Mehrdad; Dilcher, Meik; Lindegren, Gunnel; Mardani, Masoud; Bereskly, Sandor; Weidmann, Manfred; Mirazimi, Ali

    2015-04-01

    Crimean-Congo hemorrhagic fever (CCHF) is an arthropod-borne disease of humans associated with a severe clinical picture, including hemorrhagic syndrome and a high mortality rate. CCHF virus is widely distributed throughout large areas of the world. To characterize the serological status in CCHF patients, paired clinical samples were collected from suspected CCHF patients and analyzed by microbiological and other laboratory analyses with the aim of: determining the presence of neutralizing antibodies against CCHF virus; investigating the cross-reactivity of these neutralizing antibodies against virus isolated from the same outbreak and against other available laboratory strain; and studying the relationship between the isolated virus with other virus by whole genome sequencing. Patients at Boo-Ali Hospital, Zahedan, Iran, with clinical symptoms ranging from mild to severe hemorrhagic fever were included in the study. Two serum samples were taken from each patient, the first as soon as the patient matched the criteria for CCHF notification and the second when the patient was discharged from hospital (2 weeks later). Commercial and in-house assays revealed a positive IgM signal in acute serum samples from six patients. A novel finding was that CCHF patients develop neutralizing antibodies soon after infection. Interestingly these antibodies were able to neutralize other CCHF virus strains too. The complete sequence of the Zahedan 2007 isolate, including the hitherto unknown first L-segment sequence, was identified using an original clinical sample from one patient with confirmed CCHF infection.

  13. Unique small molecule entry inhibitors of hemorrhagic fever arenaviruses.

    PubMed

    Lee, Andrew M; Rojek, Jillian M; Spiropoulou, Christina F; Gundersen, Anette T; Jin, Wei; Shaginian, Alex; York, Joanne; Nunberg, Jack H; Boger, Dale L; Oldstone, Michael B A; Kunz, Stefan

    2008-07-04

    Viral hemorrhagic fevers caused by the arenaviruses Lassa virus in Africa and Machupo, Guanarito, Junin, and Sabia virus in South America are among the most devastating emerging human diseases with fatality rates of 15-35% and a limited antiviral therapeutic repertoire available. Here we used high throughput screening of synthetic combinatorial small molecule libraries to identify inhibitors of arenavirus infection using pseudotyped virion particles bearing the glycoproteins (GPs) of highly pathogenic arenaviruses. Our screening efforts resulted in the discovery of a series of novel small molecule inhibitors of viral entry that are highly active against both Old World and New World hemorrhagic arenaviruses. We observed potent inhibition of infection of human and primate cells with live hemorrhagic arenaviruses (IC(50)=500-800 nm). Investigations of the mechanism of action revealed that the candidate compounds efficiently block pH-dependent fusion by the arenavirus GPs (IC(50) of 200-350 nm). Although our lead compounds were potent against phylogenetically distant arenaviruses, they did not show activity against other enveloped viruses with class I viral fusion proteins, indicating specificity for arenavirus GP-mediated membrane fusion.

  14. Investigation of Crimean-Congo Hemorrhagic Fever and Hemorrhagic Fever with Renal Syndrome in Greece

    DTIC Science & Technology

    1988-10-12

    nasal bleeding, hematuria and gross gastrointestinal bleeding. K-- F -6- Up todate 41 HFRS cases have been serologically diagnosed in Greece. The...CCHF in Greece up until April 1987, was discussed and the conclusions drawn are reported. 4 pA. : -3- B. HORAGIC FEVER WITH RENAL SYNDROKE (HilS) B1...level. Two house rats (Rattus rattus) captured in a slaughter house in Thessaloniki were found to be seropositive (Table 2). _ _ I -9-. Todate

  15. Pathogenesis of Ebola Hemorrhagic Fever in Primate Models In Vivo and In Vitro

    DTIC Science & Technology

    2003-01-01

    by EBOV replication. These findings are in contrast with results reported for other viral hemorrhagic fevers including dengue32 and African swine fever ,33...chemokine production, complement activation, and apoptosis. J Immunol 1998, 161:6338-6346 33. Vallee I, Tait SW, Powell PP: African swine fever virus

  16. Acute Hemorrhagic Leukoencephalitis in Children: A Case Report

    PubMed Central

    Khademi, Gholam Reza; Aelami, Mohammad Hasan

    2016-01-01

    Acute hemorrhagic leukoencephalitis (AHLE) is a rare demyelinating disease characterized by an acute rapidly progressive fulminant inflammation of the white matter. In this case report, we introduce a case of AHLE in children with an interesting and lengthy process and successful treatment. A previously healthy 13-year-old girl was admitted to the hospital because of fever and loss of consciousness. After 4 days, she was referred to our pediatric intensive care unit in Mashhad, Iran. On admission, she had right-sided parotiditis. With a diagnosis of AHLE, our patient was treated with methylprednisolone, intravenous immunoglobulin, acyclovir, and plasmapheresis. AHLE is a rare and severe demyelinating disease, the mortality and morbidity of which can be decreased by early detection and treatment with steroid therapy, intravenous immunoglobulin, acyclovir, and plasmapheresis. PMID:27217610

  17. [The Omsk hemorrhagic fever: research results (1946-2013)].

    PubMed

    Yastrebov, V K; Yakimenko, V V

    2014-01-01

    The main aspects of epidemiology and epizootology of the Omsk hemorrhagic fever (OHF) are analyzed. The discovery of the virus OHF in 1947, as well as the first outbreak of new diseases in the districts of the Omsk region, is described. Comprehensive work for decryption of the etiology of the OHF by specialists from the Omsk and Moscow Institutes is carried out. Long-term dynamics of activity of natural foci of OHF contains four periods of variable intensity of epidemic and epizootic processes. The main reservoir of the virus OHF in natural foci and the source of human infection is muskrat. Metaxenosis provides maintaining of the population of the virus, which is of some significance for hosts. Independent position of the virus OHF in the group of the Flaviviruses of mammals transmitted by ticks is established. There are two aenovariants of the virus OHF.

  18. A case of brucellosis mimicking Crimean-Congo hemorrhagic fever.

    PubMed

    Metin, Ozge; Teke, Turkan A; Gayretli Aydin, Zeynep G; Kaman, Ayse; Oz, Fatma N; Bayhan, Gulsum I; Tanir, Gonul

    2015-01-01

    Brucellosis is a zoonotic disease caused by Brucella spp. that is transmitted to humans by the ingestion of unpasteurized milk and other dairy products from infected animals or through close contact with secretions. Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by a virus that is transmitted to humans by ixoid tick bites, contact with blood and tissue of infected animals or contact with infected humans. The symptoms of brucellosis are non-specific; it can mimic other diseases. In this paper, we present a case of brucellosis that was initially evaluated as CCHF. We emphasize that brucellosis should be considered in the differential diagnosis of CCHF, especially in endemic countries.

  19. [The "Black Death" : Crimean-Congo hemorrhagic fever].

    PubMed

    Wiemer, Dorothea

    2015-07-01

    The Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease that has been known for centuries. In the last years more frequent cases reflect the effects of climate change, globalization and the increasing encroachment of humans into previously unexploited areas. Humans acquire the infection by tick bites or through the slaughtering and processing of infected animals. The course of the disease can be severe and the average mortality reaches up to 30 %. It is transmissible from human to human and there is no causal treatment. Thus, CCHF meets the criteria for a highly contagious life-threatening disease. In the following current data on the virus, its vector, the distribution and transmission will be presented, as well as information on the diagnosis, the disease, the underlying pathophysiology and consequences in dealing with patients and deceased.

  20. A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

    PubMed

    Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

    2013-01-15

    Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.

  1. Basic clinical and laboratory features of filoviral hemorrhagic fever.

    PubMed

    Kortepeter, Mark G; Bausch, Daniel G; Bray, Mike

    2011-11-01

    The filoviruses Marburg and Ebola cause severe hemorrhagic fever (HF) in humans. Beginning with the 1967 Marburg outbreak, 30 epidemics, isolated cases, and accidental laboratory infections have been described in the medical literature. We reviewed those reports to determine the basic clinical and laboratory features of filoviral HF. The most detailed information was found in descriptions of patients treated in industrialized countries; except for the 2000 outbreak of Ebola Sudan HF in Uganda, reports of epidemics in central Africa provided little controlled or objective clinical data. Other than the case fatality rate, there were no clear differences in the features of the various filovirus infections. This compilation will be of value to medical workers responding to epidemics and to investigators attempting to develop animal models of filoviral HF. By identifying key unanswered questions and gaps in clinical data, it will help guide clinical research in future outbreaks.

  2. [Two cases of acute myelogenous leukemia with Bacillus cereus bacteremia resulting in fatal intracranial hemorrhage].

    PubMed

    Yoshida, H; Moriyama, Y; Tatekawa, T; Tominaga, N; Teshima, H; Hiraoka, A; Masaoka, T; Yoshinaga, T

    1993-12-01

    This manuscript reports Bacillus cereus sepsis in two cases with acute myelogenous leukemia (AML) who suffered complications of fatal intracranial hemorrhage during remission induction therapy. The first case was 43-year-old male with AML (M0) receiving first consolidation chemotherapy who developed sudden diarrhea, abdominal pain and spiking fever. Two days later, he died of intracranial hemorrhage. The second case was 15-year-old male with AML (M5b) who was receiving first induction chemotherapy. He developed headache and vomiting following spiking fever and diarrhea. He died of subarachnoid hemorrhage the next day. In both cases, Bacillus cereus was isolated from blood culture. Fatal intracranial hemorrhage due to severe bleeding tendency caused rapid to death in both cases. These bleeding tendencies might have been induced by B. cereus sepsis. In addition, we should not overlook B. cereus as contamination, but rather consider it as a potential pathogen, when isolated from blood culture.

  3. Epidemiology and Epizootiological Investigations of Hemorrhagic Fever Viruses in the Central African Republic

    DTIC Science & Technology

    1986-03-01

    virus isolations we were able to show that five hazardous haemorrhagic fever viruses : Ebola, Marburg, Lassa , Congo-Crimean and Rift-Valley- Fever , were...JOHtJSON & WILLIAMS :unpublished observations 9-IVA’JOFF & al:Hemorragic fever in GABON.I.Incidence of Lassa ,Ebola and Marburg virus in Haut Ogout...AD ...... EPIDEMIOLOGY AND EPIZOOTIOLOGICAL INVESTIGATIONS OF HEMORRHAGIC FEVER VIRUSES IN THE CENTRAL AFRICAN REPUBLIC Final Report 000 N 0A. J

  4. Outbreak of viral hemorrhagic fever caused by dengue virus type 3 in Al-Mukalla, Yemen

    PubMed Central

    2013-01-01

    Background Investigations were conducted by the authors to explore an outbreak of viral hemorrhagic fever (VHF) reported in 2010 from Al-Mukalla city, the capital of Hadramout in Yemen. Methods From 15–17 June 2010, the outbreak investigation period, specimens were obtained within 7 days after onset of illness of 18 acutely ill patients hospitalized with VHF and 15 household asymptomatic contacts of 6 acute cases. Additionally, 189 stored sera taken from acutely ill patients with suspected VHF hospitalized in the preceding 12 months were obtained from the Ministry of Health of Yemen. Thus, a total of 222 human specimens were collected; 207 specimens from acute cases and 15 specimens from contacts. All samples were tested with RT-PCR for dengue (DENV), Alkhumra (ALKV), Rift Valley Fever (RVFV), Yellow Fever (YFV), and Chikungunya (CHIKV) viruses. Samples were also tested for DENV IgM, IgG, and NS1-antigen. Medical records of patients were reviewed and demographic, clinical, and laboratory data was collected. Results Of 207 patients tested, 181 (87.4%) patients were confirmed to have acute dengue with positive dengue NS1-antigen (97 patients, 46.9%) and/or IgM (163 patients, 78.7%). Of the 181 patients with confirmed dengue, 100 (55.2%) patients were IgG-positive. DENV RNA was detected in 2 (1%) patients with acute symptoms; both samples were molecularly typed as DENV type 3. No other VHF viruses were detected. For the 15 contacts tested, RT-PCR tests for the five viruses were negative, one contact was dengue IgM positive, and another one was dengue IgG positive. Of the 181 confirmed dengue patients, 120 (66.3%) patients were males and the median age was 24 years. The most common manifestations included fever (100%), headache (94.5%), backache (93.4%), malaise (88.4%), arthralgia (85.1%), myalgia (82.3%), bone pain (77.9%), and leukopenia (76.2%). Two (1.1%) patients died. Conclusions DENV-3 was confirmed to be the cause of an outbreak of VHF in Al

  5. Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses.

    PubMed

    Mahmutovic, Selma; Clark, Lars; Levis, Silvana C; Briggiler, Ana M; Enria, Delia A; Harrison, Stephen C; Abraham, Jonathan

    2015-12-09

    In the Western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. Junín virus (JUNV) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies ("passive immunity") is an established treatment. Here, we report the structure of the JUNV surface glycoprotein receptor-binding subunit (GP1) bound to a neutralizing monoclonal antibody. The antibody engages the GP1 site that binds transferrin receptor 1 (TfR1)-the host cell surface receptor for all New World hemorrhagic fever mammarenaviruses-and mimics an important receptor contact. We show that survivor immune plasma contains antibodies that bind the same epitope. We propose that viral receptor-binding site accessibility explains the success of passive immunity against JUNV and that this functionally conserved epitope is a potential target for therapeutics and vaccines to limit infection by all New World hemorrhagic fever mammarenaviruses.

  6. Molecular basis for antibody-mediated neutralization of New World hemorrhagic fever mammarenaviruses

    PubMed Central

    Mahmutovic, Selma; Clark, Lars; Levis, Silvana C.; Briggiler, Ana M.; Enria, Delia A.; Harrison, Stephen C.; Abraham, Jonathan

    2015-01-01

    SUMMARY In the Western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. Junín virus (JUNV) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies (‘passive immunity’) is an established treatment. Here, we report the structure of the JUNV surface glycoprotein receptor-binding subunit (GP1) bound to a neutralizing monoclonal antibody. The antibody engages the GP1 site that binds transferrin receptor 1 (TfR1) – the host cell surface receptor for all New World hemorrhagic fever mammarenaviruses - and mimics an important receptor contact. We show that survivor immune plasma contains antibodies that bind the same epitope. We propose that viral receptor-binding site accessibility explains the success of passive immunity against JUNV and that this functionally conserved epitope is a potential target for therapeutics and vaccines to limit infection by all New World hemorrhagic fever mammarenaviruses. PMID:26651946

  7. Ecology and Epidemiology of Crimean-Congo Hemorrhagic Fever Virus Transmission in the Republic of Senegal.

    DTIC Science & Technology

    1992-07-01

    ecology of tick-borne Crimean-Congo hemorrhagic fever ( CCHF ) virus in the West African savannah was devoted to integration and analysis of results, and...continued surveillance at field sites. These observations of tick and virus activity in northern Senegal produced numerous new isolates of CCHF virus...epidemiology of Crimean-Congo hemorrhagic fever ( CCHF ) in West Africa, a widespread, life-threatening, tick-borne, viral zoonosis, remains poorly understood

  8. Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses

    PubMed Central

    Lauck, Michael; Alkhovsky, Sergey V.; Bào, Yīmíng; Bailey, Adam L.; Shevtsova, Zinaida V.; Shchetinin, Alexey M.; Vishnevskaya, Tatyana V.; Lackemeyer, Matthew G.; Postnikova, Elena; Mazur, Steven; Wada, Jiro; Radoshitzky, Sheli R.; Friedrich, Thomas C.; Lapin, Boris A.; Deriabin, Petr G.; Jahrling, Peter B.; Goldberg, Tony L.; O'Connor, David H.

    2015-01-01

    Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical presentation and serological diagnosis, all reported SHF outbreaks were thought to be caused by different strains of the same virus, simian hemorrhagic fever virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in 1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent arteriviruses. Our results indicate that multiple divergent simian arteriviruses can cause SHF. PMID:25972539

  9. [A case of brucellosis misdiagnosed as Crimean-Congo hemorrhagic fever].

    PubMed

    Almiş, Habip; Yakıncı, Cengiz

    2012-07-01

    Brucellosis which is a zoonotic infection, is an important public health problem in Turkey and all over the world. The disease may involve many organs and systems. Since the symptoms of brucellosis are non-specific, difficulties in differential diagnosis and misdiagnosis are frequent. In this case report we present a case of brucellosis, misdiagnosed as Crimean-Congo hemorrhagic fever (CCHF). A 13-year-old boy was referred from another medical center with preliminary diagnosis of CCHF and admitted to our clinic with fever and a history of presence of a tick on his back. His physical observation only included splenomegaly. The laboratory results on admission were anemia, thrombocytopenia, elevation of acute phase reactants and liver transaminase levels. Abdominal ultrasonography revealed splenomegaly. Since the patient had anemia, epistaxis, fever and thrombocytopenia, he was initially diagnosed as CCHF. Meantime serum sample of the patient had been sent to Refik Saydam National Public Health Agency for CCHF PCR test. The fever of the patient could not be controlled. His detailed medical history revealed stockbreeding and consumption of raw milk products. Patient's signs and symptoms were also compatible with brucellosis and standard tube agglutination test for brucellosis was positive at 1/1280 titer in serum. The patient was diagnosed as brucellosis and the treatment was started with combination of rifampicin (1 x 600 mg/day) and doxycycline (2 x 100 mg/day). Blood cultures yielded negative result. The PCR tests for CCHF was found also negative. His fever and other complaints improved with treatment which was completed in six weeks and the follow-up was without complications. Turkey is endemic both for brucellosis and CCHF. This case was reported to emphasize that the cases of brucellosis could mimic other diseases and brucellosis should also be considered in the differential diagnosis of CCHF.

  10. Acute infectious purpura fulminans due to probable spotted fever.

    PubMed

    Kundavaram, A; Francis, N R; Jude, A P J; Varghese, G N

    2014-01-01

    Purpura fulminans (PF) is associated with several infections, most notably with meningococcus, staphylococcus, and streptococcus infections. However, there are few reports of association of this entity with spotted fever from India. We report the case of a 55-year-old man who presented with fever, headache, and myalgia. On the seventh day of fever he developed nonblanching purple hemorrhagic purpura on the trunk and most prominently on the extremities consistent with purpura fulminans. Immunofluorescent assay confirmed the diagnosis of spotted fever. PF though common with rocky mountain spotted fever (RMSF) is rarely seen in association with Indian tick typhus, the usual cause of spotted fever in India.

  11. Prolonged fever and splinter hemorrhages in an immunocompetent traveler with disseminated histoplasmosis.

    PubMed

    Bitterman, Roni; Oren, Ilana; Geffen, Yuval; Sprecher, Hannah; Schwartz, Eli; Neuberger, Ami

    2013-01-01

    We present a case of progressive disseminated histoplasmosis in an immunocompetent traveler. Histoplasmosis was acquired in South America; its manifestations included prolonged fever, splinter hemorrhages, erythema multiforme, arthritis, and mediastinal lymphadenopathy. To the best of our knowledge no splinter hemorrhages had previously been reported in a patient with histoplasmosis.

  12. Crimean-Congo hemorrhagic fever: CXCL10 correlates with the viral load.

    PubMed

    Papa, Anna; Yagci Caglayık, Dilek; Christova, Iva; Tsergouli, Katerina; Korukluoglu, Gulay; Uyar, Yavuz

    2015-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a human disease with high fatality rate. Although its pathogenesis is not elucidated yet, it is considered that cytokines play a significant role in the progression and outcome of the disease. Serum CXCL10 levels were estimated in 35 patients with acute CCHF and were correlated with the viral load, and various demographic and clinical parameters. The mean CXCL10 concentration in the patients' group was higher compared to the respective value in the control group (4421.74 pg/ml vs. 28.47 pg/ml, P < 0.05). A strong positive correlation between CXCL10 and viral load was seen (rs = 0.57, P < 0.001), while the outcome of the disease was related with the viral load (rs = 0.47, P = 0.004) and the presence of hemorrhagic manifestations (P < 0.001). The study provides an insight into the strong correlation between CXCL10 and viral load in acute CCHF cases suggesting that it plays an important role in CCHF pathogenesis.

  13. Hemorrhagic fevers, with special reference to recent outbreaks in southern Africa.

    PubMed

    Gear, J H

    1979-01-01

    In considering the diagnosis of a patient admitted to the Johannesburg Hospital, suffering from an illness characterized by high fever and complicated by a hemorrhagic state from which he died, a list of possible causes of his illness was drawn up. This list included the arthropodborne viral infections prevalent in southern Africa, namely, chikungunya fever, Sindbis fever, West Nile fever, yellow fever, and Rift Valley fever; viral infections associated with rodents, such as Lassa fever; the viral infection associated with monkeys, Marburg virus disease; the rickettsial infections; tick-bite fever (the variety of spotted fever of tick typhus occurring in southern Africa) and Q fever; the bacterial infections, especially the coccal infections, plague septicemia, and meningococcal, staphylococcal, and streptococcal septicemia; and the blood protozoal infections malaria and trypanosomiasis. In addition, rubella, Gasser's syndrome, Henoch-Schönlein purpura, and viperine snakebite were briefly described in this review. All of these conditions may be complicated by the development of a hemorrhagic state. The circulation of large numbers of infecting organisms, by they viruses, rickettsiae, bacteria, or protozoa, may initiate the coagulation cascade, the formation of fibrin and its deposition in the finer blood vessels, and the aggregation and entanglement of platelets resulting in marked thrombocytopenia and bleeding. This bleeding tendency is greatly aggravated when the infection specifically involves the parenchymal cells of the liver; such a condition results in defective formation of coagulation factors such as prothrombin. The proper care of patients in whom a hemorrhagic state has developed requires urgent and accurate diagnosis followed by immediate and appropriate treatment that will combat the infection and alleviate the hemorrhagic state and liver disorder. If the hemorrhagic state is due to one of the dangerous infectious fevers, adequate protection of the

  14. The global distribution of Crimean-Congo hemorrhagic fever

    PubMed Central

    Messina, Jane P.; Pigott, David M.; Golding, Nick; Duda, Kirsten A.; Brownstein, John S.; Weiss, Daniel J.; Gibson, Harry; Robinson, Timothy P.; Gilbert, Marius; William Wint, G. R.; Nuttall, Patricia A.; Gething, Peter W.; Myers, Monica F.; George, Dylan B.; Hay, Simon I.

    2015-01-01

    Background Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterized by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described. Methods We used an exhaustive database of human CCHF occurrence records and a niche modeling framework to map the global distribution of risk for human CCHF occurrence. Results A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region. Conclusions These new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans. PMID:26142451

  15. Spatial analysis of hemorrhagic fever with renal syndrome in China

    PubMed Central

    Fang, Liqun; Yan, Lei; Liang, Song; de Vlas, Sake J; Feng, Dan; Han, Xiaona; Zhao, Wenjuan; Xu, Bing; Bian, Ling; Yang, Hong; Gong, Peng; Richardus, Jan Hendrik; Cao, Wuchun

    2006-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) is endemic in many provinces with high incidence in mainland China, although integrated intervention measures including rodent control, environment management and vaccination have been implemented for over ten years. In this study, we conducted a geographic information system (GIS)-based spatial analysis on distribution of HFRS cases for the whole country with an objective to inform priority areas for public health planning and resource allocation. Methods Annualized average incidence at a county level was calculated using HFRS cases reported during 1994–1998 in mainland China. GIS-based spatial analyses were conducted to detect spatial autocorrelation and clusters of HFRS incidence at the county level throughout the country. Results Spatial distribution of HFRS cases in mainland China from 1994 to 1998 was mapped at county level in the aspects of crude incidence, excess hazard and spatial smoothed incidence. The spatial distribution of HFRS cases was nonrandom and clustered with a Moran's I = 0.5044 (p = 0.001). Spatial cluster analyses suggested that 26 and 39 areas were at increased risks of HFRS (p < 0.01) with maximum spatial cluster sizes of ≤ 20% and ≤ 10% of the total population, respectively. Conclusion The application of GIS, together with spatial statistical techniques, provide a means to quantify explicit HFRS risks and to further identify environmental factors responsible for the increasing disease risks. We demonstrate a new perspective of integrating such spatial analysis tools into the epidemiologic study and risk assessment of HFRS. PMID:16638156

  16. Ebola hemorrhagic Fever and the current state of vaccine development.

    PubMed

    Hong, Joo Eun; Hong, Kee-Jong; Choi, Woo Young; Lee, Won-Ja; Choi, Yeon Hwa; Jeong, Chung-Hyeon; Cho, Kwang-Il

    2014-12-01

    Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus. Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment. It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

  17. Crimean-Congo hemorrhagic fever among children in Iran.

    PubMed

    Aslani, Dalileh; Salehi-Vaziri, Mostafa; Baniasadi, Vahid; Jalali, Tahmineh; Azad-Manjiri, Sanam; Mohammadi, Tahereh; Khakifirouz, Sahar; Fazlalipour, Mehdi

    2017-03-01

    Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonotic disease which is endemic in Iran. The etiological agent of CCHF is an RNA virus belonging to the genus Nairovirus of the family Bunyaviridae. CCHF virus (CCHFV) can be transmitted to humans through bites from infected ticks and direct contact with infected blood or tissues. Although the disease has been observed in different age groups, the rate of disease is lower in children and elderly. This study was designed to characterize CCHFV-infected children in Iran. Between 2000 and 2016, a total of 908 CCHF suspected cases (in children less than 19 years old) were evaluated for CCHFV infection by CCHF IgM ELISA and RT-PCR. CCHFV infection was observed in 161 (17.73%) of subjects. Most CCHF positive children were male (70.8%) and >15 years of age (65.8%). Contact with livestock was the main risk factor (35.4%). Sistan and Baluchestan provinces had the highest frequency within the infected cohort (68.3%). The overall mortality rate was 11.8%. This study also revealed a significant reduction in CCHF-fatality rates in Iranian children when compared to earlier studies in Iran. Having contact with livestock was the major risk factor and CCHF was more common in male children of an older age.

  18. Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever.

    PubMed

    Guler, Nil; Eroglu, Cafer; Yilmaz, Hava; Karadag, Adil; Alacam, Hasan; Sunbul, Mustafa; Fletcher, Tom E; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended.

  19. Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever

    PubMed Central

    Guler, Nil; Eroglu, Cafer; Yilmaz, Hava; Karadag, Adil; Alacam, Hasan; Sunbul, Mustafa; Fletcher, Tom E.; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended. PMID:27304063

  20. Chikungunya fever presenting with acute optic neuropathy.

    PubMed

    Mohite, Abhijit Anand; Agius-Fernandez, Adriana

    2015-07-28

    Chikungunya fever is a vector borne virus that typically causes a self-limiting systemic illness with fever, skin rash and joint aches 2 weeks after infection. We present the case of a 69-year-old woman presenting with an acute unilateral optic neuropathy as a delayed complication of Chikungunya virus (CHIKV) infection contracted during a recent trip to the West Indies. She presented to our ophthalmology department with acute painless visual field loss in the right eye and a recent flu-like illness. She was found to have a right relative afferent pupillary defect (RAPD) with unilateral optic disc swelling. Serology confirmed recent CHIKV infection. Treatment with intravenous methylprednisolone was delayed while awaiting MRI scans and serology results. At 5-month follow-up, there was a persistent right RAPD and marked optic atrophy with a corresponding inferior scotoma in the visual field.

  1. Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

    PubMed Central

    Guo, Xiling; Zhang, Li; Zhang, Wenshuai; Chi, Ying; Zeng, Xiaoyan; Li, Xian; Qi, Xian; Jin, Qiu; Zhang, Xiao; Huang, Mingming; Wang, Hua; Chen, Yin; Bao, Changjun; Hu, Jianli; Liang, Shuyi; Bao, Lin; Wu, Tao

    2013-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection. PMID:23863504

  2. [Present status of an arbovirus infection: yellow fever, its natural history of hemorrhagic fever, Rift Valley fever].

    PubMed

    Digoutte, J P

    1999-12-01

    . Intermediate yellow fever--a term coined to define epidemia which do not correspond exactly to urban yellow fever. The cycle involves men and monkeys through wild vectors as Aedes furcifer but also through Aedes aegypti and the mortality rate is much lower than for urban epidemics. In urban yellow fever, man is the only vertebrate host involved in the circulation of the virus, the vector being generally Aedes aegypti. This vector maintains a selective pressure, increasing the transmission of virus capable of producing high viremia in man. In the selvatic cycles, two cycles can be distinguished: one of maintenance which does not increase the quantity of virus in circulation and one of amplification which does increase this quantity. As we shall see, it develops into an epizootic form but also in an epidemic form in man. When the decrease in yellow fevers across Africa is considered, it appears that all major epidemics occur in West Africa inspite of the presence of wild cycles of the yellow fever virus in Central and East Africa. For the rare epidemics that have occurred there, the vector has never been Aedes aegypti. In a recent outbreak in Kenya, the vector was Aedes bromeliae. The examination of part of the gene encoding for envelope protein showed the presence of two geographical types corresponding to West-Africa and Central East-Africa. Clinically speaking, yellow fever is an haemorrhagic fever with hepatitis similar to other haemorrhagic fevers such as Rift Valley fever. When, in 1987, an outbreak of haemorrhagic fever occurred in southern Mauritania, for several days it was thought to be yellow fever. Four days later, the diagnosis was corrected by isolating and identifying the virus as that of Rift Valley fever (RVFV). RVFV causes several pathogenic syndromes in human beings: acute febrile illness, haemorrhagic fever, haemorrhagic fever with hepatitis, nervous syndromes or ocular disease. Mortality rate was high for haemorrhagic fever with hepatitis, reaching 36

  3. Acute hemorrhagic conjunctivitis due to enterovirus 70 in India.

    PubMed Central

    Maitreyi, R. S.; Dar, L.; Muthukumar, A.; Vajpayee, M.; Xess, I.; Vajpayee, R. B.; Seth, P.; Broor, S.

    1999-01-01

    An outbreak of acute hemorrhagic conjunctivitis occurred in Delhi, India, during August and September 1996. The etiologic agent was confirmed as enterovirus type 70 by a modified centrifugation-enhanced culture method followed by immunofluorescence and neutralization tests. After nearly a decade, this virus is reemerging as a cause of acute hemorrhagic conjunctivitis in India. PMID:10221880

  4. Presepsin Levels of Patients with Crimean-Congo Hemorrhagic Fever.

    PubMed

    Demirpençe, Özlem; Doğan, Halef Okan; Erşan, Serpil; Şahin, Mehtap; Şahin, Hasan; Bakır, Mehmet

    2016-11-22

    Levels of presepsin (a soluble cluster of differentiation subtype 14 [CD14]) are thought to increase in cases of bacterial infection. CD14 has also been found to play a role in the pathogenesis of various viral diseases. Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral infection. Our study focuses on presepsin levels as a biomarker for CCHF. Serum presepsin levels in a CCHF group (n = 59) and control group (n = 28) were compared. Patients with CCHF were classified according to severity grading score as having mild, moderate, or severe infection and were allocated to corresponding subgroups (groups 1, 2, and 3, respectively). Presepsin levels were measured in serum samples by using a commercial enzyme-linked immunosorbent assay kit. The mean presepsin levels in the CCHF group as a whole and the healthy group were found to be significantly different (1,499.46 ± 411.96 pg/ml and 430.68 ± 61.21 pg/ml, respectively). The mean presepsin levels of the CCHF subgroups (1, 2 and 3) and the healthy group were also found to be significantly different (1,204.53 ± 371.18, 1,464.21 ± 338.37, 2,007.36 ± 82.18, and 430.68 ± 61.21 pg/ml, respectively) (p < 0.05). We also found that as the severity of the disease increased, the presepsin level also increased. We postulate that the presepsin levels could be used as a supportive biomarker for diagnosis and follow-up of the disease.

  5. Vectors of Crimean Congo Hemorrhagic Fever Virus in Iran

    PubMed Central

    Telmadarraiy, Zakkyeh; Chinikar, Sadegh; Vatandoost, Hassan; Faghihi, Faezeh; Hosseini-Chegeni, Asadollah

    2015-01-01

    Background: Ticks are important vectors and reservoirs of Crimean Congo Hemorrhagic Fever (CCHF) virus. Human beings may be infected whenever the normal life cycle of the infected ticks on non-human vertebrate hosts is interrupted by the undesirable presence of humans in the cycle. A total of 26 species of Argasid and Ixodid ticks have been recorded in Iran; including nine Hyalomma, two Rhipicephalus, two Dermacentor, five Haemaphysalis, two Boophilus, one Ixodes and two Argas as well as three Ornithodoros species as blood sucking ectoparasites of livestock and poultries. The present paper reviews tick vectors of CCHF virus in Iran, focusing on the role of ticks in different provinces of Iran using reverse transcription polymerase chain reaction (RT-PCR) assay. Methods: During ten years study, 1054 tick specimens; including two species of Argasidae and 17 species of Ixodidae were examined for their infection to CCHF virus genome. The output of all studies as well as related publications were discussed in the current paper. Results: The results show that Rhipicephalus sanguineus, Hyalomma marginatum, H. anatolicum, H. asiaticum and H. dromedarii were known as the most frequent species which were positive for CCHF virus. Conclusion: The status of ticks which were positive for CCHF virus revealed that unlike the most common idea that Hyalomma species are the most important vectors of CCHF virus, other ticks including Rhipicephalus, Haemaphysalis and Dermacentor can be reservoir of this virus; thus, considering geographical distribution, type of host and environmental conditions, different tick control measurements should be carried out in areas with high incidence of CCHF disease. PMID:26623426

  6. Epidemiology and Epizootiological Investigations of Hemorrhagic Fever Viruses in Kenya

    DTIC Science & Technology

    1988-07-01

    vertebrates and/or invertebrates as reservoirs of Haemorrhagic fever viruses particularly Marburg virus . The final results of this particular investigation...Research work done in Kenya has shown that three haemorrhagic fever viruses occur in the country. These are Rift Valley Fever Virus (RVF), Crimean...members for serology and or virus isolation. 2. Virus Isolation Attempts in VRC Haemorrhagic fever viruses are hazardous to culture and handle in

  7. Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo.

    PubMed

    Fajs, Luka; Humolli, Isme; Saksida, Ana; Knap, Nataša; Jelovšek, Mateja; Korva, Miša; Dedushaj, Isuf; Avšič-Županc, Tatjana

    2014-01-01

    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.

  8. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever.

    PubMed

    Upadhaya, Bala Krishna; Sharma, Alok; Khaira, Ambar; Dinda, Amit K; Agarwal, Sanjay K; Tiwari, Suresh C

    2010-05-01

    Dengue virus infection can clinically manifest as dengue fever, dengue shock syndrome and dengue hemorrhagic fever. Acute kidney injury as a result of dengue virus infection can occur due to various reasons including hypotension, rhabdomyolysis, sepsis and rarely immune complex mediated glomerular injury. However, glomerulonephritis associated with IgA Nephropathy in dengue virus infection has not been reported previously. We report a case of 15-year-old boy who was admitted with dengue fever and dialysis dependant acute kidney injury. Urine examination showed microscopic glomerular hematuria and proteinuria. Kidney biopsy showed mesangial proliferation with mesangial IgA dominant immune complex deposits and acute tubular necrosis. A repeated kidney biopsy 6 weeks after clinical recovery showed reversal of glomerular changes as well as resolution of mesangial IgA deposits.

  9. Transmission potential and design of adequate control measures for Marburg hemorrhagic fever.

    PubMed

    Ajelli, Marco; Merler, Stefano

    2012-01-01

    Marburg hemorrhagic fever is rare yet among the most severe diseases affecting humans, with case fatality ratio even higher than 80%. By analyzing the largest documented Marburg hemorrhagic fever epidemic, which occurred in Angola in 2005 and caused 329 deaths, and data on viral load over time in non-human primates, we make an assessment of transmissibility and severity of the disease. We also give insight into the control of new Marburg hemorrhagic fever epidemics to inform appropriate health responses. We estimated the distribution of the generation time to have mean 9 days (95%CI: 8.2-10 days) and standard deviation 5.4 days (95%CI: 3.9-8.6 days), and the basic reproduction number to be R(0) = 1.59 (95%CI: 1.53-1.66). Model simulations suggest that a timely isolation of cases, starting no later than 2-3 days after symptoms onset, is sufficient to contain an outbreak. Our analysis reveals that Marburg hemorrhagic fever is characterized by a relatively small reproduction number and by a relatively long generation time. Such factors, along with the extremely high severity and fatality, support the rare occurrence of large epidemics in human populations. Our results also support the effectiveness of social distancing measures--case isolation in particular--to contain or at least to mitigate an emerging outbreak. This work represents an advance in the knowledge required to manage a potential Marburg hemorrhagic fever epidemic.

  10. Seroprevalence of Crimean Congo hemorrhagic fever virus in Ijara District, Kenya.

    PubMed

    Lwande, Olivia Wesula; Irura, Zephania; Tigoi, Caroline; Chepkorir, Edith; Orindi, Benedict; Musila, Lillian; Venter, Marietjie; Fischer, Anne; Sang, Rosemary

    2012-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease mainly affecting pastoralists who come in contact with animals infested with Hyalomma ticks, which are the key vectors of CCHF virus (CCHFV). CCHFV has been detected among these ticks in parts of North Eastern Kenya. This study aimed to identify acute cases of CCHF, and to determine the extent of previous exposure to CCHFV in an outpatient population attending Sangailu and Ijara health centers, Ijara District, North Eastern Kenya, presenting with acute febrile illnesses. A total of 517 human serum samples were collected from these patients. The samples were screened for the presence of IgM and IgG antibodies to CCHF using CCCHF-IgG and IgM ELISA test kits. A multivariable logistic regression model was used to investigate the risk factors associated with evidence of exposure to CCHFV. A single patient tested positive for anti-CCHF IgM, while 96 were positive for anti-CCHF IgG. The seroprevalence of CCHFV was 23% in Sangailu and 14% in Ijara. Most exposed persons were aged 40-49 years. The likelihood of exposure was highest among farmers (29%). Age, location, and contact with donkeys were significantly associated with exposure to CCHFV. Acute CCHFV infections could be occurring without being detected in this population. This study confirms human exposure to CCHF virus in Ijara District, Kenya, and identifies several significant risk factors associated with exposure to CCHFV.

  11. Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever.

    PubMed

    Engin, Aynur; Arslan, Serdal; Kizildag, Sibel; Oztürk, Hasret; Elaldi, Nazif; Dökmetas, Ilyas; Bakir, Mehmet

    2010-11-01

    Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever. The clinical course and outcome of the CCHF infection are different in humans. Toll-like receptors (TLRs) are a family of pathogen recognition receptors. TLR8 and TLR9 contribute to the recognition of viruses. We investigated frequency of TLR8 Met1Val, TLR8 -129C/G, TLR9 -1486T/C and TLR9 2458G/A polymorphisms in CCHF patients and healthy controls. Our study was conducted between June 1 and August 31, 2007 in Cumhuriyet University Hospital, Turkey. TLR genotypes were detected using the PCR-RFLP assay in 85 CCHF patients and 171 healthy controls. We found that heterozygous plus homozygous mutant genotypes frequency for TLR8 Met1Val and for TLR9 -1486T/C were significantly higher in CCHF patients than controls (p = 0.038 and p = 0.009, respectively). The frequency of TLR8 -129G/G genotype in the fatal CCHF patients was significantly higher than that of the non-fatal patients (p = 0.026). The frequency of TLR9 -1486C/C genotype was significantly higher in fatal CCHF patients than in healthy controls (p = 0.009) and in patients with severe disease compared to non-severe disease (p = 0.044). Our findings suggest that TLR8 Met1Val, TLR8 -129C/G, and TLR9 -1486T/C polymorphisms are important on clinical course of CCHF disease.

  12. Alterations in favipiravir (T-705) pharmacokinetics and biodistribution in a hamster model of viral hemorrhagic fever

    PubMed Central

    Gowen, Brian B.; Sefing, Eric J.; Westover, Jonna B.; Smee, Donald F.; Hagloch, Joseph; Furuta, Yousuke; Hall, Jeffery O.

    2015-01-01

    Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, including the Arenaviridae. Several members of the Arenaviridae family of viruses are significant human pathogens that cause viral hemorrhagic fever, a severe systemic syndrome where vascular leak is a cardinal feature. Because arenaviral infections are unlikely to be diagnosed and treated until the illness has progressed to a more advanced state, it is important to understand the effects of the disease state on favipiravir pharmacokinetics (PK) and biodistribution to help guide therapeutic strategy. During acute arenavirus infection in hamsters, we found reduced plasma favipiravir concentrations and altered kinetics of absorption, elimination and time to maximum drug concentration. In addition, the amounts of the favipiravir M1 primary metabolite were higher in the infected animals, suggesting that favipiravir metabolism may favor the formation of this inactive metabolite during viral infection. We also discovered differences in favipiravir and M1 PK parameters associated with arenavirus infection in a number of hamster tissues. Finally, analysis at the individual animal level demonstrated a correlation between reduced plasma favipiravir concentration with increased disease burden as reflected by weight loss and viral load. Our study is the first to show the impact of active viral infection and disease on favipiravir PK and biodistribution, highlighting the need to consider alterations in these parameters when treating individuals with viral hemorrhagic fever of arenavirus or other etiology. PMID:26186980

  13. Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control.

    PubMed

    Matua, Gerald Amandu; Van der Wal, Dirk Mostert; Locsin, Rozzano C

    2015-01-01

    Ebola hemorrhagic fever, caused by the highly virulent RNA virus of the filoviridae family, has become one of the world's most feared pathogens. The virus induces acute fever and death, often associated with hemorrhagic symptoms in up to 90% of infected patients. The known sub-types of the virus are Zaire, Sudan, Taï Forest, Bundibugyo and Reston Ebola viruses. In the past, outbreaks were limited to the East and Central African tropical belt with the exception of Ebola Reston outbreaks that occurred in animal facilities in the Philippines, USA and Italy. The on-going outbreak in West Africa that is causing numerous deaths and severe socio-economic challenges has resulted in widespread anxiety globally. This panic may be attributed to the intense media interest, the rapid spread of the virus to other countries like United States and Spain, and moreover, to the absence of an approved treatment or vaccine. Informed by this widespread fear and anxiety, we analyzed the commonly used strategies to manage and control Ebola outbreaks and proposed new approaches that could improve epidemic management and control during future outbreaks. We based our recommendations on epidemic management practices employed during recent outbreaks in East, Central and West Africa, and synthesis of peer-reviewed publications as well as published "field" information from individuals and organizations recently involved in the management of Ebola epidemics. The current epidemic management approaches are largely "reactive", with containment efforts aimed at halting spread of existing outbreaks. We recommend that for better outcomes, in addition to "reactive" interventions, "pre-emptive" strategies also need to be instituted. We conclude that emphasizing both "reactive" and "pre-emptive" strategies is more likely to lead to better epidemic preparedness and response at individual, community, institutional, and government levels, resulting in timely containment of future Ebola outbreaks.

  14. Alterations in favipiravir (T-705) pharmacokinetics and biodistribution in a hamster model of viral hemorrhagic fever.

    PubMed

    Gowen, Brian B; Sefing, Eric J; Westover, Jonna B; Smee, Donald F; Hagloch, Joseph; Furuta, Yousuke; Hall, Jeffery O

    2015-09-01

    Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, including the Arenaviridae. Several members of the Arenaviridae family of viruses are significant human pathogens that cause viral hemorrhagic fever, a severe systemic syndrome where vascular leak is a cardinal feature. Because arenaviral infections are unlikely to be diagnosed and treated until the illness has progressed to a more advanced state, it is important to understand the effects of the disease state on favipiravir pharmacokinetics (PK) and biodistribution to help guide therapeutic strategy. During acute arenavirus infection in hamsters, we found reduced plasma favipiravir concentrations and altered kinetics of absorption, elimination and time to maximum drug concentration. In addition, the amounts of the favipiravir M1 primary metabolite were higher in the infected animals, suggesting that favipiravir metabolism may favor the formation of this inactive metabolite during viral infection. We also discovered differences in favipiravir and M1 PK parameters associated with arenavirus infection in a number of hamster tissues. Finally, analysis at the individual animal level demonstrated a correlation between reduced plasma favipiravir concentration with increased disease burden as reflected by weight loss and viral load. Our study is the first to show the impact of active viral infection and disease on favipiravir PK and biodistribution, highlighting the need to consider alterations in these parameters when treating individuals with viral hemorrhagic fever of arenavirus or other etiology.

  15. Mean platelet volume in acute rheumatic fever.

    PubMed

    Sert, Ahmet; Aypar, Ebru; Odabas, Dursun

    2013-01-01

    Acute rheumatic fever (ARF) is still an endemic disease, especially among school-aged children in developing countries. Mean platelet volume (MPV), which is commonly used as a measure of platelet size, indicates the rate of platelet production and platelet activation. We aimed to investigate MPV in children with ARF. The study population consisted of 40 children with ARF (32 patients with carditis and 8 patients without carditis) and 40 healthy control subjects. White blood cell (WBC) and platelet counts were significantly higher and MPV values were significantly lower in patients with ARF during the acute stage when compared to controls. Erythrocyte sedimentation rate (ESR) and C-reactive protein values significantly decreased in patients with ARF after the treatment when compared to baseline, whereas MPV values increased. MPV values were negatively correlated with ESR and WBC, and platelet counts. In conclusion, during the acute stage of ARF, MPV values were lower when compared to controls.

  16. TRAINING PROGRAM FOR NURSING STAFF REGARDING VIRAL HEMORRHAGIC FEVERS IN A MILITARY HOSPITAL.

    PubMed

    El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Saleh, Halla Ahmed Abdullah; Abdelfattah, Magda Abdelhamid; Morsy, Tosson Aly

    2015-08-01

    Viral hemorrhagic fevers (VHFs) refer to a group of illnesses caused by several distinct families of viruses. In general, the term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome (multisystem in that multiple organ systems in the bpdy are affected). Characteristically, the overall vascular system is damaged, and the body's ability to regulate itself is impaired. These symptoms are often accompanied by hemorrhage (bleeding); however, the bleeding is it rarely life-threatening. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease. The selected disaster diseases for this study included: 1-Crimean-Congo hemorrhagic Fever, 2-Dengue Fever, 3-Ebola Fever, 4-Hem-orrhagic Fever with renal syndrome (HFRS), 5-Hantavirus Pulmonary Syndrome, 6-Lassa Fever, 7-Marburg Fever, 8-Rift Valley Fever and 9-Yellow Fever. The educational training program was given over ten sessions to a group of Staff Nurses. The results showed that the program succeeded in enhancing nurse' knowledge, awareness, responsibility, and obligations toward patients with the Viral Hemorrhagic Fevers The results showed a significant impact of training sessions illuminated in the follow-up test on the knowledge score of nurses in all types of diseases except for the Congo hemorrhagic fever, while, statistical significance varied in some diseases in the study when it comes to the comparison between pretest and post-test. All results confirmed on the positive impact of the training program in enhancing the knowledge of nurses toward VHFs patients and their relevant. There was a significant positive impact of the training sessions on changing the attitude of nurses toward patients with VHFs. This result was confirmed on the collective level since the total scores on tests revealed significant positive impact of the study on changing the attitude of nurses toward relevant patients. The relationship

  17. [Enteroviruses responsible for acute hemorrhagic conjunctivitis].

    PubMed

    Lévêque, N; Huguet, P; Norder, H; Chomel, J-J

    2010-04-01

    Acute hemorrhagic conjunctivitis (AHC) is an epidemic form of highly contagious conjunctivitis, characterized by conjunctival hemorrhages. The first AHC outbreak was described in 1969 in Ghana, West Africa, and was called Apollo disease, from the Apollo landing on the moon. This outbreak was caused by Enterovirus 70 (EV70) together with a Coxsackievirus A24 (CVA24v) variant, which are the major etiological agents involved in AHC outbreaks worldwide. AHC is known to be directly transmitted by close person-to-person contact or indirectly through soiled ophthalmological materials or unsafe recreational water. Recently, a possible airborne virus spread was suggested which could explain the high transmission rate of the disease. In the absence of a specific antiviral therapy, a rapid diagnosis of the causative agent is required to distinguish AHC due to enteroviruses from other ocular infectious diseases, for there are active drugs, or to quickly implement proper public health measures to limit the extension of the outbreak. However, virus identification remains difficult and time-consuming. Moreover, virological diagnosis is difficult to implement in developing countries where AHC has recently become a major problem for public health.

  18. [Study of the circulation of Crimean hemorrhagic fever virus in Turkmenistan].

    PubMed

    Smirnova, S E; Mamaev, V I; Nepesova, N M; Filipenko, P I; Kalieva, V Ia

    1978-01-01

    Final results of the virological and serological investigations of the circulation of the Crimean hemorrhagic fever virus in the Turkmenian SSR carried out in 1968-1976 are presented in this report. In the examination of 2294 blood serum samples of human beings complement binding antibodies against the Crimean hemorrhagic fever were revealed in 0.4% of cases. It was revealed that five species of ixodes ticks could he infected with this virus; for the first time its strains were also isolated from the Hyalomma dromedarii ticks. Isolation of the Crimean hemorrhagic fever virus from ticks and determination of the precipitating antibodies against this virus in agricultural animals--from 6.2 to 11.1%--in all the regions of the republic pointed out that the natural nidi zones were widespread at the territory of the Turkmenian SSR, and that it was necessary to carry out further study of the given focus.

  19. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses

    PubMed Central

    Westover, Jonna B.; Sefing, Eric J.; Bailey, Kevin W.; Van Wettere, Arnaud J.; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F.; Furuta, Yousuke; Bray, Mike; Gowen, Brian B.

    2016-01-01

    Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin. PMID:26711718

  20. Ebola hemorrhagic fever associated with novel virus strain, Uganda, 2007-2008.

    PubMed

    Wamala, Joseph F; Lukwago, Luswa; Malimbo, Mugagga; Nguku, Patrick; Yoti, Zabulon; Musenero, Monica; Amone, Jackson; Mbabazi, William; Nanyunja, Miriam; Zaramba, Sam; Opio, Alex; Lutwama, Julius J; Talisuna, Ambrose O; Okware, Sam I

    2010-07-01

    During August 2007-February 2008, the novel Bundibugyo ebolavirus species was identified during an outbreak of Ebola viral hemorrhagic fever in Bundibugyo district, western Uganda. To characterize the outbreak as a requisite for determining response, we instituted a case-series investigation. We identified 192 suspected cases, of which 42 (22%) were laboratory positive for the novel species; 74 (38%) were probable, and 77 (40%) were negative. Laboratory confirmation lagged behind outbreak verification by 3 months. Bundibugyo ebolavirus was less fatal (case-fatality rate 34%) than Ebola viruses that had caused previous outbreaks in the region, and most transmission was associated with handling of dead persons without appropriate protection (adjusted odds ratio 3.83, 95% confidence interval 1.78-8.23). Our study highlights the need for maintaining a high index of suspicion for viral hemorrhagic fevers among healthcare workers, building local capacity for laboratory confirmation of viral hemorrhagic fevers, and institutionalizing standard precautions.

  1. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

    PubMed

    Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Van Wettere, Arnaud J; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F; Furuta, Yousuke; Bray, Mike; Gowen, Brian B

    2016-02-01

    Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin.

  2. Epidemiology and Epizootiological Investigations of Hemorrhagic Fever Viruses in Kenya

    DTIC Science & Technology

    1988-05-30

    Virus Research Centre (VRC) permitting the safe handling of specimens suspected to contain haemorrhagic fever viruses . Incidence and prevalence rates of...in Kenya Research work done in Kenya has shown that three naemorrnagic fever viruses occur in the country. These are Rift Valley Fever Virus , Crimean... viruses are nazardous to culture and handle in conventional type I and two oiohazard hoods. It wds therefore necessary to construct an absolute virus

  3. Application of the pseudo-plaque assay for detection and titration of Crimean-Congo hemorrhagic fever virus.

    PubMed

    Berber, Engin; Canakoglu, Nurettin; Yoruk, Mustafa D; Tonbak, Sukru; Aktas, Munir; Ertek, Mustafa; Bolat, Yusuf; Kalkan, Ahmet; Ozdarendeli, Aykut

    2013-01-01

    A pseudo-plaque assay was developed for detection and quantitation of Crimean-Congo hemorrhagic fever virus Turkey-Kelkit06. Enzyme-catalyzed color development of infected cells probed with anti-Crimean-Congo hemorrhagic fever virus antibodies was used for determining the titer of Crimean-Congo hemorrhagic fever Turkey-Kelkit06 and for its detection in samples from persons infected with the Crimean-Congo hemorrhagic fever virus. The pseudo-plaque assay accuracy was confirmed by comparing pseudo-plaque assay titers with fluorescent immunofocus assay and focus formation assay titers using three stocks of virus. No significant difference in virus titers of Crimean-Congo hemorrhagic fever Turkey-Kelkit06 among the three methods was observed. The pseudo-plaque assay is more sensitive than the fluorescent immunofocus assay for detecting the virus in primary isolates of Crimean-Congo hemorrhagic fever virus collected from humans, but no difference in sensitivity between the two methods was observed in the cell-adapted strain of Crimean-Congo hemorrhagic fever Turkey-Kelkit06. The pseudo-plaque assay is suitable for titration of Crimean-Congo hemorrhagic fever Turkey-Kelkit06, which does not develop plaques, suggesting it may also be suitable for the detection of other viruses.

  4. Inhibitors of cellular kinases with broad-spectrum antiviral activity for hemorrhagic fever viruses.

    PubMed

    Mohr, Emma L; McMullan, Laura K; Lo, Michael K; Spengler, Jessica R; Bergeron, Éric; Albariño, César G; Shrivastava-Ranjan, Punya; Chiang, Cheng-Feng; Nichol, Stuart T; Spiropoulou, Christina F; Flint, Mike

    2015-08-01

    Host cell kinases are important for the replication of a number of hemorrhagic fever viruses. We tested a panel of kinase inhibitors for their ability to block the replication of multiple hemorrhagic fever viruses. OSU-03012 inhibited the replication of Lassa, Ebola, Marburg and Nipah viruses, whereas BIBX 1382 dihydrochloride inhibited Lassa, Ebola and Marburg viruses. BIBX 1382 blocked both Lassa and Ebola virus glycoprotein-dependent cell entry. These compounds may be used as tools to understand conserved virus-host interactions, and implicate host cell kinases that may be targets for broad spectrum therapeutic intervention.

  5. [Crimean-Congo hemorrhagic fever virus in Stavropol region in 2011].

    PubMed

    Iashina, L N; Malyshev, B S; Netesova, N A; Volynkina, A S; Vasilenko, N F

    2014-01-01

    The genetic analysis of the Crimean-Congo hemorrhagic fever (CCHF) virus circulating in Stavropol region during 2011 year was suggested. A total of 14 RNA isolates from the Crimean hemorrhagic fever patients were genetically typed. The genetic analysis of the CCHF virus stains based on M-segment sequences (positions 2607-2932) supported the circulation of the genotype Europe 1 in the Stavropol region of Russia. In addition to previously known lineage STV-ROS, the second lineage VLG/ROS was observed in Stavropol region.

  6. Crimean-Congo hemorrhagic fever with hyperbilirubinemia and ascites: An unusual presentation.

    PubMed

    Ture, Zeynep; Ulu Kılıç, Ayşegül; Celik, Ilhami; Tok, Tugba; Yağcı-Çağlayık, Dilek

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a fatal systemic viral infection which is an important health problem in Turkey. Many systemic symptoms have been reported including fever, hemorrhage, headache, fatigue, muscle ache, abdominal pain, nausea and vomiting. A 45-year-old male farmer with CCHF presented with massive peritoneal effusion and hyperbilirubinemia. To our knowledge, this is the first case of peritoneal effusion and hyperbilirubinemia in an adult patient with CCHF. His clinical symptoms successfully improved with supportive therapy. In patients who live in endemic areas with atypical presentation for the diagnosis of CCHF should be kept in mind.

  7. New circulating genomic variant of Crimean-Congo hemorrhagic fever virus in Iran.

    PubMed

    Chinikar, Sadegh; Shah-Hosseini, Nariman; Bouzari, Saeid; Jalali, Tahmineh; Shokrgozar, Mohammad Ali; Mostafavi, Ehsan

    2013-05-01

    Crimean-Congo hemorrhagic fever is a viral infection that is caused by Crimean-Congo hemorrhagic fever virus (CCHFV). On May 27, 2012, a woman became ill after accidentally splashing cow's blood into her eyes. Serological and molecular investigations were carried out on the serum of the patient. The test results for serological testing were negative, but RT-PCR was strongly positive for CCHFV. A phylogenetic study on the CCHFV genome sequence showed 50 % similarity to a 520-bp region of Russian strains. By combining historical phylogenetic data and current data, it can be surmised that there are potentially more than five circulating CCHFV genomic variants in Iran.

  8. Dengue virus identification by transmission electron microscopy and molecular methods in fatal dengue hemorrhagic fever.

    PubMed

    Limonta, D; Falcón, V; Torres, G; Capó, V; Menéndez, I; Rosario, D; Castellanos, Y; Alvarez, M; Rodríguez-Roche, R; de la Rosa, M C; Pavón, A; López, L; González, K; Guillén, G; Diaz, J; Guzmán, M G

    2012-12-01

    Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.

  9. [The vaccines based on the replicon of the venezuelan equine encephalomyelitis virus against viral hemorrhagic fevers].

    PubMed

    Petrov, A A; Plekhanova, T M; Sidorova, O N; Borisevich, S V; Makhlay, A A

    2015-01-01

    The status of the various recombinant DNA and RNA-derived candidate vaccines, as well as the Venezuelan equine encephalomyelitis virus (VEEV) replicon vaccine system against extremely hazardous viral hemorrhagic fevers, were reviewed. The VEEV-based replication-incompetent vectors offer attractive features in terms of safety, high expression levels of the heterologous viral antigen, tropism to dendritic cells, robust immune responses, protection efficacy, low potential for pre-existing anti-vector immunity and possibility of engineering multivalent vaccines were tested. These features of the VEEV replicon system hold much promise for the development of new generation vaccine candidates against viral hemorrhagic fevers.

  10. Geospatial Analysis of Urban Land Use Pattern Analysis for Hemorrhagic Fever Risk - a Review

    NASA Astrophysics Data System (ADS)

    Izzah, L. N.; Majid, Z.; Ariff, M. A. M.; Fook, C. K.

    2016-09-01

    Human modification of the natural environment continues to create habitats in which vectors of a wide variety of human and animal pathogens (such as Plasmodium, Aedes aegypti, Arenavirus etc.) thrive if unabated with an enormous potential to negatively affect public health. Typical examples of these modifications include impoundments, dams, irrigation systems, landfills and so on that provide enabled environment for the transmission of Hemorrhagic fever such as malaria, dengue, avian flu, Lassa fever etc. Furthermore, contemporary urban dwelling pattern appears to be associated with the prevalence of Hemorrhagic diseases in recent years. These observations are not peculiar to the developing world, as urban expansion also contributes significantly to mosquito and other vectors habitats. This habitats offer breeding ground to some vector virus populations. The key to disease control is developing an understanding of the contribution of human landscape modification to vector-borne pathogen transmission and how a balance may be achieved between human development, public health, and responsible urban land use. A comprehensive review of urban land use Pattern Analysis for Hemorrhagic fever risk has been conducted in this paper. The study found that most of the available literatures dwell more on the impact of urban land use on malaria and dengue fevers; however, studies are yet to be found discussing the implications of urban land use on the risk of Ebola, Lassa and other non-mosquito borne VHFs. A relational model for investigating the influence of urban land use change pattern on the risk of Hemorrhagic fever has been proposed in this study.

  11. MassTag Polymerase Chain Reaction for Differential Diagnosis of Viral Hemorrhagic Fevers

    DTIC Science & Technology

    2006-04-01

    and Sabiá virus (Arenaviridae); Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHFV), and hantaviruses (Bunyaviridae); and...agents are encountered out of their natu- ral geographic context. Vaccines have been developed for YFV, RVFV, Junín virus, KFDV, and hantaviruses (3–7...239–61. 6. Hooper JW, Li D. Vaccines against hantaviruses . Curr Top Microbiol Immunol. 2001;256:171–91. 7. Dandawate CN, Desai GB, Achar TR, Banerjee K

  12. Hospital-Based Surveillance for Viral Hemorrhagic Fevers and Hepatitides in Ghana

    PubMed Central

    Bonney, Joseph Humphrey Kofi; Osei-Kwasi, Mubarak; Adiku, Theophilus Korku; Barnor, Jacob Samson; Amesiya, Robert; Kubio, Chrysantus; Ahadzie, Lawson; Ölschläger, Stephan; Lelke, Michaela; Becker-Ziaja, Beate; Pahlmann, Meike; Günther, Stephan

    2013-01-01

    Background Viral hemorrhagic fevers (VHF) are acute diseases associated with bleeding, organ failure, and shock. VHF may hardly be distinguished clinically from other diseases in the African hospital, including viral hepatitis. This study was conducted to determine if VHF and viral hepatitis contribute to hospital morbidity in the Central and Northern parts of Ghana. Methodology/Principal Findings From 2009 to 2011, blood samples of 258 patients with VHF symptoms were collected at 18 hospitals in Ashanti, Brong-Ahafo, Northern, Upper West, and Upper East regions. Patients were tested by PCR for Lassa, Rift Valley, Crimean-Congo, Ebola/Marburg, and yellow fever viruses; hepatitis A (HAV), B (HBV), C (HCV), and E (HEV) viruses; and by ELISA for serological hepatitis markers. None of the patients tested positive for VHF. However, 21 (8.1%) showed anti-HBc IgM plus HBV DNA and/or HBsAg; 37 (14%) showed HBsAg and HBV DNA without anti-HBc IgM; 26 (10%) showed anti-HAV IgM and/or HAV RNA; and 20 (7.8%) were HCV RNA-positive. None was positive for HEV RNA or anti-HEV IgM plus IgG. Viral genotypes were determined as HAV-IB, HBV-A and E, and HCV-1, 2, and 4. Conclusions/Significance VHFs do not cause significant hospital morbidity in the study area. However, the incidence of acute hepatitis A and B, and hepatitis B and C with active virus replication is high. These infections may mimic VHF and need to be considered if VHF is suspected. The data may help decision makers to allocate resources and focus surveillance systems on the diseases of relevance in Ghana. PMID:24069490

  13. Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy.

    PubMed

    Zivcec, Marko; Safronetz, David; Scott, Dana; Robertson, Shelly; Ebihara, Hideki; Feldmann, Heinz

    2013-06-15

    Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed viral hemorrhagic fever characterized by rapid onset of flu-like symptoms often followed by hemorrhagic manifestations. CCHF virus (CCHFV), a bunyavirus in the Nairovirus genus, is capable of infecting a wide range of mammalian hosts in nature but so far only causes disease in humans. Recently, immunocompromised mice have been reported as CCHF disease models, but detailed characterization is lacking. Here, we closely followed infection and disease progression in CCHFV-infected interferon α/β receptor knockout (IFNAR(-/-)) mice and age-matched wild-type (WT) mice. WT mice quickly clear CCHFV without developing any disease signs. In contrast, CCHFV infected IFNAR(-/-) mice develop an acute fulminant disease with high viral loads leading to organ pathology (liver and lymphoid tissues), marked proinflammatory host responses, severe thrombocytopenia, coagulopathy, and death. Disease progression closely mimics hallmarks of human CCHF disease, making IFNAR(-/-) mice an excellent choice to assess medical countermeasures.

  14. An Unusual Case of Crimean Congo Hemorrhagic Fever: Prolonged Bleeding with Successful Recovery.

    PubMed

    Hussain, Qurban; Shaikh, Bilal Hussain; Bhutto, Ali Raza; Sohaib, Muneebah

    2016-02-01

    Crimean Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease with a major reservoir in both domestic and wild animals. In Pakistan, it is endemic largely in rural areas and most cases occur in spring and autumn. Recently, cases are being reported throughout the year, including winter months, with some even from urban areas. Death from CCHF is most likely to occur during the hemorrhagic phase. We report a case presenting from an urban locality in December. Clinical presentation was characterized by a prolonged hemorrhagic phase and a delayed normalization of platelet counts.

  15. Acute transverse myelitis: an unusual complication of typhoid fever.

    PubMed

    Mishra, Kirtisudha; Kaur, Sharandeep; Basu, Srikanta; Gulati, Praveen; Parakh, Ankit

    2012-08-01

    Typhoid fever is associated with a wide spectrum of neurological complications. Acute transverse myelitis is a rare complication with only a few reports in adults and none in children. A 15-year-old boy with typhoid fever is reported who developed acute transverse myelitis in the 3rd week of illness. He was treated with antibiotics and corticosteroids and made a complete recovery.

  16. Acute Q Fever and Scrub Typhus, Southern Taiwan

    PubMed Central

    Lai, Chung-Hsu; Chen, Yen-Hsu; Lin, Jiun-Nong; Chang, Lin-Li; Chen, Wei-Fang

    2009-01-01

    Acute Q fever and scrub typhus are zoonoses endemic to southern Taiwan. Among the 137 patients with acute Q fever (89, 65.0%) or scrub typhus (43, 31.4%), we identified 5 patients (3.6%) who were co-infected with Coxiella burnetii and Orientia tsutsugamushi. PMID:19861068

  17. Development and evaluation of loop-mediated isothermal amplification assay for detection of Crimean Congo hemorrhagic fever virus in Sudan.

    PubMed

    Osman, Hana A M; Eltom, Kamal H; Musa, Nasreen O; Bilal, Nasreldin M; Elbashir, Mustafa I; Aradaib, Imadeldin E

    2013-06-01

    Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) activity has been detected in Kordufan region of the Sudan in 2008 with high case-fatality rates in villages and rural hospitals in the region. Therefore, in the present study, a reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay was developed and compared to nested RT-PCR for rapid detection of CCHFV targeting the small (S) RNA segment. A set of RT-LAMP primers, designed from a highly conserved region of the S segment of the viral genome, was employed to identify all the Sudanese CCHFV strains. The sensitivity studies indicated that the RT-LAMP detected 10fg of CCHFV RNA as determined by naked eye turbidity read out, which is more likely the way it would be read in a resource-poor setting. This level of sensitivity is good enough to detect most acute cases. Using agarose gel electrophoresis, the RT-LAMP assay detected as little as 0.1fg of viral RNA (equivalent to 50 viral particle). There was 100% agreement between results of the RT-LAMP and the nested PCR when testing 10-fold serial dilution of CCHFV RNA. The specificity studies indicated that there was no cross-reactivity with other related hemorrhagic fever viruses circulating in Sudan including, Rift Valley fever virus (RVFV), Dengue fever virus, and yellow fever virus. The RT-LAMP was performed under isothermal conditions at 63°C and no special apparatus was needed, which rendered the assay more economical and practical than real-time PCR in such developing countries, like Sudan. In addition, the RT-LAMP provides a valuable tool for rapid detection and differentiation of CCHFV during an outbreak of the disease in remote areas and in rural hospitals with resource-poor settings.

  18. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based

  19. A Simple Assay for Determining Antiviral Activity Against Crimean-Congo Hemorrhagic Fever Virus

    DTIC Science & Technology

    2004-01-01

    hemorrhagic fever virus isolates in China. Virology 296, 159–164. Nichol, S.T., 2001. Bunyaviruses. In: Knipe, D.M., Howley, P.M. (Eds.), Fields ... Virology , vol. 1, 4th ed. Lippincott Williams and Wikins, Philadephlia, pp. 1603–1633. Papa, A., Bozovi, B., Pavlidou, V., Papadimitriou, E., Pelemis, M

  20. Genetic detection and isolation of crimean-congo hemorrhagic fever virus, Kosovo, Yugoslavia.

    PubMed

    Papa, Anna; Bozovi, Bojana; Pavlidou, Vassiliki; Papadimitriou, Evangelia; Pelemis, Mijomir; Antoniadis, Aantonis

    2002-08-01

    Crimean-Congo hemorrhagic fever virus (C-CHFV) strains were isolated from a fatal case and the attending physician in Kosovo, Yugoslavia. Early, rapid diagnosis of the disease was achieved by reverse transcription-polymerase chain reaction. The physician was successfully treated with oral ribavirin. These cases yielded the first genetically studied C-CHFV human isolates in the Balkans.

  1. Lookback Exercise with Imported Crimean-Congo Hemorrhagic Fever, Senegal and France

    PubMed Central

    Nabeth, Pierre; Tattevin, Pierre; Michelet, Christian; Zeller, Hervé

    2006-01-01

    A patient with suspected malaria was hospitalized successively in 2 hospitals, first in Dakar, Senegal, then in Rennes, France, where tests diagnosed Crimean-Congo hemorrhagic fever. An international incident management group was set up in France and Senegal, which traced 181 contacts and analyzed 50 samples from 3 countries. No secondary cases were identified clinically. PMID:17073094

  2. Role of Migratory Birds in Spreading Crimean-Congo Hemorrhagic Fever, Turkey

    PubMed Central

    Eroglu, Cafer; Erciyas-Yavuz, Kiraz; Hokelek, Murat; Acici, Mustafa; Yilmaz, Hava

    2014-01-01

    We investigated migratory birds’ role in spreading Crimean-Congo hemorrhagic fever virus (CCHFV) through attached ticks. We detected CCHFV RNA in ticks on migratory birds in Turkey. Two isolates showed similarity with CCHFV genotype 4, suggesting a role for ticks in CCHFV epidemics in Turkey and spread of CCHFV by birds. PMID:25062428

  3. Role of migratory birds in spreading Crimean-Congo hemorrhagic fever, Turkey.

    PubMed

    Leblebicioglu, Hakan; Eroglu, Cafer; Erciyas-Yavuz, Kiraz; Hokelek, Murat; Acici, Mustafa; Yilmaz, Hava

    2014-08-01

    We investigated migratory birds' role in spreading Crimean-Congo hemorrhagic fever virus (CCHFV) through attached ticks. We detected CCHFV RNA in ticks on migratory birds in Turkey. Two isolates showed similarity with CCHFV genotype 4, suggesting a role for ticks in CCHFV epidemics in Turkey and spread of CCHFV by birds.

  4. Hemorrhagic Fever with Renal Syndrome, Zibo City, China, 2006–2014

    PubMed Central

    Wang, Ling; Wang, Tao; Cui, Feng; Zhai, Shen-Yong; Zhang, Ling; Yang, Shu-Xia; Wang, Zhi-Qiang

    2016-01-01

    Analysis of hemorrhagic fever with renal syndrome cases in Zibo City, China, during 2006–2014 showed that it occurred year-round. Peaks in spring and fall/winter were caused by Hantaan and Seoul viruses, respectively. Rodent hosts were the striped field mouse for Hantaan virus and the brown rat and house mouse for Seoul virus. PMID:26812444

  5. Syndrome of inappropriate antidiuretic hormone associated with Crimean-Congo hemorrhagic fever.

    PubMed

    Özer, Samet; Kazancı, Nafia Özlem; Sönmezgöz, Ergün; Karaaslan, Erhan; Yılmaz, Resul

    2014-12-01

    Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal systemic disease in children caused by a tick- borne virus. Many different clinical and laboratory findings are seen in CCHF. We report here an atypical presentation of CCHF with hyponatremia. CCHF with electrolyte imbalance is not reported before. A 4-year-old girl presented with fever, fatigue and unconsciousness with hyponatremia. Based on the clinical and epidemiological findings, virus infection was suspected. Hyponatremia is has never been reported in Crimean-Congo hemorrhagic fever (CCHF), as was observed in this case. The diagnosis was confirmed by detection of IgM antibody to CCHF virus and positive Real-Time PCR. We report the first case of imported CCHF presenting as hyponatremia. This electrolyte imbalance has never been reported before in CCHF in children, and the clinician should consider this entity in complications to explain unconsciousness.

  6. When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico.

    PubMed

    Acuna-Soto, Rodofo; Stahle, David W; Therrell, Matthew D; Griffin, Richard D; Cleaveland, Malcolm K

    2004-11-01

    During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60-70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.

  7. Role of ischemia in acute pancreatitis. Hemorrhagic shock converts edematous pancreatitis to hemorrhagic pancreatitis in rats.

    PubMed

    Kyogoku, T; Manabe, T; Tobe, T

    1992-09-01

    Ischemia has been considered to play a role in the development of acute pancreatitis. The aim of this study was to investigate the effect of ischemia, caused by hemorrhagic shock, on cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by the intravenous infusion of a supramaximally stimulating dose of cerulein (10 micrograms/kg/hr) for 6 hr. Hemorrhagic shock was induced by the removal of blood until the mean arterial blood pressure reached 35 mm Hg. This level was maintained for 30 min, after which time all the blood was reinfused. Hemorrhagic shock alone induced no morphological change in the pancreas. However, after the induction of hemorrhagic shock in animals treated with cerulein, hemorrhage and parenchymal necrosis were frequently observed in the pancreas. Seven of 20 rats (35%) receiving cerulein plus hemorrhagic shock had died by 48 hr after the start of cerulein infusion, whereas none of the rats in the cerulein or shock group died during this experiment. Cathepsin B activity in the pancreas of the cerulein plus shock group was significantly higher than in the other groups at 48 hr. These results suggest that ischemia may be a contributing factor in the pathogenesis of acute pancreatitis.

  8. Transient sinus bradycardia during the course of Crimean-Congo hemorrhagic fever in children.

    PubMed

    Gayretli Aydin, Zeynep Gokce; Tanir, Gonul; Metin, Ozge; Aydin Teke, Turkan; Bayhan, Gulsum Iclal; Oz, Fatma Nur; Caglayik, Dilek Yagci; Gençtürk, Zeynep

    2015-03-01

    Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne viral zoonotic disease which is endemic in Turkey. Bradycardia has been reported among pediatric and adult patients with CCHF. But, it remains unclear, whether bradycardia is associated with ribavirin treatment or the severity of CCHF. In this study 26 hospitalized CCHF patients were reviewed in terms of age, gender, history of tick bite, duration of hospitalization, presence of bradycardia, laboratory features, ribavirin treatment, and blood products requirement. The demographic, clinical, laboratory and treatment characteristics of CCHF patients with or without bradycardia were compared. The mean age of the patients was 126.42±48.21 months. There were 8 female and 18 male patients. Sinus bradycardia was noted in 15 patients (mean age was 120.20±50.59 months, 5 female). Ribavirin had been administered 18 (69.2%) patients and 11 of them had bradycardia. There was not statistically significant relationships between bradycardia and ribavirin treatment (p=0.683). Furthermore the occurrence of bradycardia was not associated with disease severity according to Swanepoel severity criteria (p=0.683). We concluded that independent of the disease severity and the ribavirin treatment, transient sinus bradycardia might occur during the clinical course of CCHF in pediatric patients. For this reason clinicians should be aware of this finding and all CCHF patients should be monitored closely.

  9. Sero-epidemiological survey of Crimean-Congo hemorrhagic fever virus in Tunisia

    PubMed Central

    Wasfi, Fares; Dowall, Stuart; Ghabbari, Tayssir; Bosworth, Andrew; Chakroun, Mohamed; Varghese, Anitha; Tiouiri, Hanene; Ben Jemaa, Mounir; Znazen, Abir; Hewson, Roger; Zhioua, Elyes; Letaief, Amel

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease associated with a high case fatality rate and transmitted mainly by Hyalomma marginatum. The geographical distribution of H. marginatum covers most of the Western Mediterranean basin. We aimed to investigate whether CCHF virus (CCHFv) is circulating in Tunisia. Samples from unexplained acute febrile patients (n = 181) and a high risk group of humans, mainly slaughter workers (n = 38), were collected in the summer of 2014 and analyzed for exposure to CCHFv using serological tests and real-time RT-PCR. Ticks were collected from Northern and Southern Tunisia during May–June 2014 and examined for the presence of CCHFv by real-time RT-PCR. Of the 181 febrile patients, 5 showed only high titers of IgM suggesting a recent exposure to CCHFv. Among 38 slaughter workers, 2 had IgG anti-CCHFv responses yielding a seroprevalence of 5.2%. No CCHFv was detected in ticks and sera. Our results provide evidence of human exposure to CCHFv in Tunisia. PMID:26956221

  10. Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus

    PubMed Central

    Lagerqvist, Nina; Hagström, Åsa; Lundahl, Malin; Nilsson, Elin; Juremalm, Mikael; Larsson, Inger; Alm, Erik; Bucht, Göran; Ahlm, Clas

    2016-01-01

    Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription-quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS. PMID:26962084

  11. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

    PubMed Central

    Golden, Joseph W.; Hammerbeck, Christopher D.; Mucker, Eric M.; Brocato, Rebecca L.

    2015-01-01

    Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs. PMID:26266264

  12. Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses.

    PubMed

    Golden, Joseph W; Hammerbeck, Christopher D; Mucker, Eric M; Brocato, Rebecca L

    2015-01-01

    Human pathogenic hantaviruses and arenaviruses are maintained in nature by persistent infection of rodent carrier populations. Several members of these virus groups can cause significant disease in humans that is generically termed viral hemorrhagic fever (HF) and is characterized as a febrile illness with an increased propensity to cause acute inflammation. Human interaction with rodent carrier populations leads to infection. Arenaviruses are also viewed as potential biological weapons threat agents. There is an increased interest in studying these viruses in animal models to gain a deeper understating not only of viral pathogenesis, but also for the evaluation of medical countermeasures (MCM) to mitigate disease threats. In this review, we examine current knowledge regarding animal models employed in the study of these viruses. We include analysis of infection models in natural reservoirs and also discuss the impact of strain heterogeneity on the susceptibility of animals to infection. This information should provide a comprehensive reference for those interested in the study of arenaviruses and hantaviruses not only for MCM development but also in the study of viral pathogenesis and the biology of these viruses in their natural reservoirs.

  13. Laboratory diagnosis of Ebola hemorrhagic fever during an outbreak in Yambio, Sudan, 2004.

    PubMed

    Onyango, Clayton O; Opoka, Martin L; Ksiazek, Thomas G; Formenty, Pierre; Ahmed, Abdullahi; Tukei, Peter M; Sang, Rosemary C; Ofula, Victor O; Konongoi, Samson L; Coldren, Rodney L; Grein, Thomas; Legros, Dominique; Bell, Mike; De Cock, Kevin M; Bellini, William J; Towner, Jonathan S; Nichol, Stuart T; Rollin, Pierre E

    2007-11-15

    Between the months of April and June 2004, an Ebola hemorrhagic fever (EHF) outbreak was reported in Yambio county, southern Sudan. Blood samples were collected from a total of 36 patients with suspected EHF and were tested by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G and M antibodies, antigen ELISA, and reverse-transcription polymerase chain reaction (PCR) of a segment of the Ebolavirus (EBOV) polymerase gene. A total of 13 patients were confirmed to be infected with EBOV. In addition, 4 fatal cases were classified as probable cases, because no samples were collected. Another 12 patients were confirmed to have acute measles infection during the same period that EBOV was circulating. Genetic analysis of PCR-positive samples indicated that the virus was similar to but distinct from Sudan EBOV Maleo 1979. In response, case management, social mobilization, and follow-up of contacts were set up as means of surveillance. The outbreak was declared to be over on 7 August 2004.

  14. Sero-epidemiological survey of Crimean-Congo hemorrhagic fever virus in Tunisia.

    PubMed

    Wasfi, Fares; Dowall, Stuart; Ghabbari, Tayssir; Bosworth, Andrew; Chakroun, Mohamed; Varghese, Anitha; Tiouiri, Hanene; Ben Jemaa, Mounir; Znazen, Abir; Hewson, Roger; Zhioua, Elyes; Letaief, Amel

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease associated with a high case fatality rate and transmitted mainly by Hyalomma marginatum. The geographical distribution of H. marginatum covers most of the Western Mediterranean basin. We aimed to investigate whether CCHF virus (CCHFv) is circulating in Tunisia. Samples from unexplained acute febrile patients (n = 181) and a high risk group of humans, mainly slaughter workers (n = 38), were collected in the summer of 2014 and analyzed for exposure to CCHFv using serological tests and real-time RT-PCR. Ticks were collected from Northern and Southern Tunisia during May-June 2014 and examined for the presence of CCHFv by real-time RT-PCR. Of the 181 febrile patients, 5 showed only high titers of IgM suggesting a recent exposure to CCHFv. Among 38 slaughter workers, 2 had IgG anti-CCHFv responses yielding a seroprevalence of 5.2%. No CCHFv was detected in ticks and sera. Our results provide evidence of human exposure to CCHFv in Tunisia.

  15. The prognostic significance of serum troponin T levels in Crimean-Congo hemorrhagic fever patients.

    PubMed

    Yilmaz, Hülya; Yilmaz, Gürdal; Kostakoğlu, Uğur; Yaman, Hüseyin; Örem, Asım; Köksal, İftihar

    2017-03-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a disease transmitted by the Crimean-Congo hemorrhagic fever virus (CCHFV), characterized by severe fever and hemorrhage and with a reported fatality level of 3-30%. Cerebral hemorrhage, gastrointestinal hemorrhage, severe anemia, shock, myocardial infarction, pulmonary edema, and pleural effusion may be seen as causes of death. Cardiac troponin T (cTn-T) is a biochemical marker with high sensitivity and specificity in myocardial injury. The purpose of this study was to determine the prognostic significance of serum troponin T levels in CCHF patients. Patients hospitalized with a diagnosis of CCHF and whose serum cTn-T was investigated were examined retrospectively. Patients were divided into two groups on the basis of presence or absence of hemorrhage. Data were subjected to statistical analysis. One hundred thirty-five CCHF patients and 72 control subjects were included. Hemorrhage was present in 48 (35.6%) patients. Mean serum cTn-T level was 17.3 ± 28.0 ng/L in the patients with hemorrhage, 9.98 ± 5.97 ng/L in the non-hemorrhage patients (P = 0.001) and 6.6P = 2.6 ng/L in the control samples (P < 0.001). At a cTn-T level cut-off point of 9 ng/L, area under the ROC curve was 0.797 (95%CI: 0.730-0.854), sensitivity 83.0%, specificity 87.5%, PPD 95.7%, and NPV 60.3%. At logistic regression analysis, a rise in cTn-T level above 14 ng/L increased the probability of hemorrhage in CCHF patients approximately threefold. An increased troponin T level may be a prognostic risk factor for hemorrhage in CCHF patients. This marker should therefore be borne in mind in determining treatment strategy in these patients. J. Med. Virol. 89:408-412, 2017. © 2015 Wiley Periodicals, Inc.

  16. Viral hemorrhagic fevers of animals caused by DNA viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we outline serious diseases of food and fiber animals that cause damaging economic effects on producers all over the world. The only vector-borne DNA virus is included here (i.e., African swine fever virus), and the herpesviruses discussed have a complex epidemiology characterized by outbreaks ...

  17. Viral hemorrhagic fevers of animals caused by DNA viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we outline serious diseases of food and fiber animals that cause damaging economic effect on products all over the world. The only vector-borne DNA virus is included here, such as African swine fever virus, and the herpes viruses discussed have a complex epidemiology characterized by outbreak...

  18. Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

    PubMed Central

    Rudd, Penny A.; Wilson, Jane; Gardner, Joy; Larcher, Thibaut; Babarit, Candice; Le, Thuy T.; Anraku, Itaru; Kumagai, Yutaro; Loo, Yueh-Ming; Gale, Michael; Akira, Shizuo; Khromykh, Alexander A.

    2012-01-01

    Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/− mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/− mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome. PMID:22761364

  19. Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

    SciTech Connect

    Jaing, C; Gardner, S

    2012-06-05

    The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genome wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.

  20. Typhoid fever presenting as acute cerebellar ataxia and severe thrombocytopenia.

    PubMed

    Cheong, B M K

    2008-03-01

    Typhoid fever being a systemic infection can present in a multitude of ways, involving various systems. Here we describe a case of typhoid fever presenting with acute cerebellar ataxia and marked thrombocytopenia. This atypical presentation is not common in typhoid fever and can lead to misdiagnosis as well as a delay in the initiation of appropriate therapy. Prompt clinical improvement and the return of platelet counts to normal were noted after the patient was started on IV Ceftriaxone.

  1. Various clinical conditions can mimic Crimean-Congo hemorrhagic fever in pediatric patients in endemic regions.

    PubMed

    Kara, Soner S; Kara, Duygu; Fettah, Ali

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with high mortality. Many disorders can mimic CCHF. It is important to recognize the condition and to perform differential diagnosis in endemic countries. Twenty-one children aged 18 years or less with a preliminary diagnosis of CCHF were retrospectively evaluated. Real-time PCR and a confirmatory indirect immunofluorescence assay for negative results were performed. The diagnoses determined that 9 patients had (42.9%) CCHF; 7 patients had (33.3%) viral upper respiratory tract infections (URTI); 2 patients had (9.5%) brucellosis; 1 patients had (4.7%) periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome episode; 1 patient had (4.7%) cerebral palsy, diabetes insipidus, acute gastroenteritis, and hypernatremic dehydration; and 1 patient had (4.7%) cellulitis after a tick bite. The mean age of patients with CCHF was greater than that of the other patients (116.1±53.6 vs. 94.1±52.1 months, p=0.02). Seventeen (81%) of the children included had a history of tick bites, 2 (9.5%) had a history of contact with a patient with CCHF, and 2 (9.5%) had no exposure, but were living in an endemic region. Three patients had an underlying disorder: cerebral palsy and diabetes insipidus, epilepsy, or PFAPA. All of the children experienced fever. Other frequent symptoms were malaise, diarrhea, vomiting, and abdominal pain, but none of these differed statistically between the patient groups. CCHF patients had a longer mean duration of symptoms (10.56±1.42 vs. 6.75±3.62 days, p=0.008) and a longer mean length of hospitalization (8.00±2.08 vs. 3.58±1.56 days, p<0.001) than the other patients. At laboratory examination, patients with CCHF had statistically significant lower leukocyte and platelet counts, more prolonged coagulation parameters, and greater AST, ALT, LDH, and CK levels than the other patients. No mortality or complications occurred in the study. Both infectious causes, such as

  2. [Acute vitreous hemorrhage--possibilities for differential diagnostic, echographic assessment].

    PubMed

    Hasenfratz, G

    1990-01-01

    In acute vitreal hemorrhage, echography is the method of choice for evaluation of the vitreous body. Echography ist capable of providing information on the localization, the density, and the mobility, and in certain diseases, also on the cause of the hemorrhage. The echographic findings (standardized echography) recorded in 216 patients with acute vitreal hemorrhage examined within 14 months (Jan. 1988 to Feb. 1989) were evaluated. In 91 patients (42%) diabetic retinopathy was known: in such cases echography can disclose proliferative changes and traction-detachment of the retina. In 58 patients (27%) echography revealed a posterior vitreous detachment, while in 17 patients (8%) an additional retinal detachment was found. In 39 patients (18%) a degenerative, disciform lesion of the macula was revealed as the cause of the hemorrhage, in 5 patients (2%) a malignant melanoma of the choroid, and in 2 patients a (large) retinal tear. In 5 patients, apart from the vitreous opacities no changes in the posterior segment could be found.

  3. Lassa fever presenting as acute abdomen: a case series.

    PubMed

    Dongo, Andrew E; Kesieme, Emeka B; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C; Akpede, George O

    2013-04-19

    Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission.

  4. Lassa fever presenting as acute abdomen: a case series

    PubMed Central

    2013-01-01

    Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission. PMID:23597024

  5. Interventions against West Nile virus, Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus: where are we?

    PubMed

    Kortekaas, Jeroen; Ergönül, Onder; Moormann, Rob J M

    2010-10-01

    ARBO-ZOONET is an international network financed by the European Commission's seventh framework program. The major goal of this initiative is capacity building for the control of emerging viral vector-borne zoonotic diseases, with a clear focus on West Nile virus, Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus. To evaluate the status quo of control measures against these viruses, an ARBO-ZOONET meeting was held in Istanbul, Turkey, from 19 to 20 November 2009. The symposium consisted of three themes: (1) vaccines: new and existing ones; (2) antivirals: existing and new developments; and (3) antivector vaccines. In addition, a satellite workshop was held on epidemiology and diagnosis. The meeting brought together foremost international experts on the subjects from both within and without the ARBO-ZOONET consortium. This report highlights selected results from these presentations and major conclusions that emanated from the discussions held.

  6. Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever

    DTIC Science & Technology

    1989-01-01

    Clamfication) Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever 𔃼 PERSONAL AjTHOR(S...FELD GROUP SUBGROUP Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever. 19...ABSTRAC7 (Continue on reverse if necessary and identify by block number) Serum specimens~collected during a prospective study of dengue infections among

  7. [Marburg, Lassa and Ebola viral hemorrhagic fevers (author's transl)].

    PubMed

    Ardouin, C; Chevalier, J M; Algayres, J P

    1981-01-01

    For each of these three fevers recently described, the authors report the history of their identification. The features of the three viruses, and the clinical aspects of the diseases they induce, are also indicated. The laboratory diagnosis is described. Practical indications are given for the transportation of the specimens to the only three high security laboratories in the world. The laboratory diagnosis is described. Some cautions are indicated handling and treating patients. It must be envisaged also to organize a four degrees quarantive cautions; compulsory for necropsies, burials, and occasionally for long distant transportations of patients are indicated.

  8. First report of sylvatic DENV-2-associated dengue hemorrhagic fever in West Africa.

    PubMed

    Franco, Leticia; Palacios, Gustavo; Martinez, José Antonio; Vázquez, Ana; Savji, Nazir; De Ory, Fernando; Sanchez-Seco, María Paz; Martín, Dolores; Lipkin, W Ian; Tenorio, Antonio

    2011-08-01

    Dengue virus (DENV) circulates in human and sylvatic cycles. Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses. Although sylvatic dengue cycles occur in West African countries and Malaysia, only a few cases of mild human disease caused by sylvatic strains and one single case of dengue hemorrhagic fever in Malaysia have been reported. Here we report a case of dengue hemorrhagic fever (DHF) with thrombocytopenia (13000/µl), a raised hematocrit (32% above baseline) and mucosal bleeding in a 27-year-old male returning to Spain in November 2009 after visiting his home country Guinea Bissau. Sylvatic DENV-2 West African lineage was isolated from blood and sera. This is the first case of DHF associated with sylvatic DENV-2 in Africa and the second case worldwide of DHF caused by a sylvatic strain.

  9. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

    PubMed

    Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

    2013-07-15

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

  10. The role of antigen-presenting cells in filoviral hemorrhagic fever: gaps in current knowledge

    PubMed Central

    Martinez, Osvaldo; Leung, Lawrence W.; Basler, Christopher F.

    2012-01-01

    The filoviruses, ebolavirus (EBOV) and marburgvirus (MARV), are highly lethal zoonotic agents of concern as emerging pathogens and potential bioweapons. Antigen-presenting cells (APCs), particularly macrophages and dendritic cells, are targets of filovirus infection in vivo. Infection of these cell types has been proposed to contribute to the inflammation, activation of coagulation cascades and ineffective immune responses characteristic of filovirus hemorrhagic fever. However, many aspects of filovirus-APC interactions remain to be clarified. Among the unanswered questions: What determines the ability of filoviruses to replicate in different APC subsets? What are the cellular signaling pathways that sense infection and lead to production of copious quantities of cytokines, chemokines and tissue factor? What are the mechanisms by which innate antiviral responses are disabled by these viruses, and how may these mechanisms contribute to inadequate adaptive immunity? A better understanding of these issues will clarify the pathogenesis of filoviral hemorrhagic fever and provide new avenues for development of therapeutics. PMID:22333482

  11. The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome

    PubMed Central

    Spiropoulou, Christina F; Srikiatkhachorn, Anon

    2013-01-01

    The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity. PMID:23841977

  12. Emergency Transcatheter Arterial Embolization for Acute Renal Hemorrhage.

    PubMed

    Wang, Hong Liang; Xu, Chun Yang; Wang, Hong Hui; Xu, Wei

    2015-10-01

    The aims of this study were to identify arteriographic manifestations of acute renal hemorrhage and to evaluate the efficacy of emergency embolization. Emergency renal artery angiography was performed on 83 patients with acute renal hemorrhage. As soon as bleeding arteries were identified, emergency embolization was performed using gelatin sponge, polyvinyl alcohol particles, and coils. The arteriographic presentation and the effect of the treatment for acute renal hemorrhage were analyzed retrospectively. Contrast extravasation was observed in 41 patients. Renal arteriovenous fistulas were found in 12 of the 41 patients. In all, 8 other patients had a renal pseudoaneurysm, 5 had pseudoaneurysm rupture complicated by a renal arteriovenous fistula, and 1 had pseudoaneurysm rupture complicated by a renal artery-calyceal fistula. Another 16 patients had tumor vasculature seen on arteriography. Before the procedure, 35 patients underwent renal artery computed tomography angiography (CTA). Following emergency embolization, complete hemostasis was achieved in 80 patients, although persistent hematuria was present in 3 renal trauma patients and 1 patient who had undergone percutaneous nephrolithotomy (justifying surgical removal of the ipsilateral kidney in this patient). Two-year follow-up revealed an overall effective rate of 95.18 % (79/83) for emergency embolization. There were no serious complications. Emergency embolization is a safe, effective, minimally invasive treatment for renal hemorrhage. Because of the diversified arteriographic presentation of acute renal hemorrhage, proper selection of the embolic agent is a key to successful hemostasis. Preoperative renal CTA plays an important role in diagnosing and localizing the bleeding artery.

  13. Emergency Transcatheter Arterial Embolization for Acute Renal Hemorrhage

    PubMed Central

    Wang, Hong Liang; Xu, Chun Yang; Wang, Hong Hui; Xu, Wei

    2015-01-01

    Abstract The aims of this study were to identify arteriographic manifestations of acute renal hemorrhage and to evaluate the efficacy of emergency embolization. Emergency renal artery angiography was performed on 83 patients with acute renal hemorrhage. As soon as bleeding arteries were identified, emergency embolization was performed using gelatin sponge, polyvinyl alcohol particles, and coils. The arteriographic presentation and the effect of the treatment for acute renal hemorrhage were analyzed retrospectively. Contrast extravasation was observed in 41 patients. Renal arteriovenous fistulas were found in 12 of the 41 patients. In all, 8 other patients had a renal pseudoaneurysm, 5 had pseudoaneurysm rupture complicated by a renal arteriovenous fistula, and 1 had pseudoaneurysm rupture complicated by a renal artery-calyceal fistula. Another 16 patients had tumor vasculature seen on arteriography. Before the procedure, 35 patients underwent renal artery computed tomography angiography (CTA). Following emergency embolization, complete hemostasis was achieved in 80 patients, although persistent hematuria was present in 3 renal trauma patients and 1 patient who had undergone percutaneous nephrolithotomy (justifying surgical removal of the ipsilateral kidney in this patient). Two-year follow-up revealed an overall effective rate of 95.18 % (79/83) for emergency embolization. There were no serious complications. Emergency embolization is a safe, effective, minimally invasive treatment for renal hemorrhage. Because of the diversified arteriographic presentation of acute renal hemorrhage, proper selection of the embolic agent is a key to successful hemostasis. Preoperative renal CTA plays an important role in diagnosing and localizing the bleeding artery. PMID:26496273

  14. Ecology and Epidemiology of Crimean-Congo Hemorrhagic Fever Virus Transmission in the Republic of Senegal

    DTIC Science & Technology

    1991-10-01

    during the fourth year of studies on the ecology of tick-borne Crimean-Congo hemorrhagic fever ( CCHF ) virus in the West African savannah. Prospectiv... CCHF virus transmitted virus to females during mating and cofeeding. Survival of uninfected, unfed adult ticks, monitored during more than one year...depended on temperature and humidity. In other studies, laboratory mice inoculated with CCHF virus differed in survival, viremia, and antibody

  15. Aetiology of PCR negative suspected Crimean-Congo hemorrhagic fever cases in an endemic area

    PubMed Central

    Sunbul, Mustafa; Fletcher, Tom E.

    2016-01-01

    Crimean–Congo hemorrhagic fever (CCHF) is a potentially fatal tick-borne viral infection that is widely distributed worldwide. The diagnosis is frequently missed due to the non-specific initial symptoms and the differential diagnosis included many infectious and non-infectious causes. This retrospective study describes the clinical features and final diagnoses of 116 suspect CCHF cases that were admitted to a tertiary CCHF center in Turkey, and were CCHF IgM and PCR negative. PMID:27677379

  16. Interferon Antagonism as a Common Virulence Factor of Hemorrhagic Fever Viruses

    DTIC Science & Technology

    2009-02-01

    inflammatory pathways. Hantaviruses can cause two distinct types of human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary...or of CCHFV. To examine this for hantaviruses , lung epithelial cells (A549) were mock-infected or infected with the HPS-causing hantavirus , Andes... author (s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation

  17. Gene Gun-Delivered DNA Vaccines for Hemorrhagic Fever With Renal Syndrome: Advancement to Clinical Trials

    DTIC Science & Technology

    2008-12-01

    bioterrorism pathogens that threaten troops. 1. INTRODUCTION Hantaviruses are RNA viruses belonging to the family Bunyaviridae, and are...the etiologic agents of hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome in the New World. The...viruses are carried by persistently infected rodents and are found worldwide. There are no licensed vaccines for hantaviruses ; thus, they continue to

  18. Crimean Congo Hemorrhagic Fever Virus and Alkhurma (Alkhumra) Virus in Ticks in Djibouti.

    PubMed

    Horton, Katherine C; Fahmy, Nermeen T; Watany, Noha; Zayed, Alia; Mohamed, Abro; Ahmed, Ammar Abdo; Rollin, Pierre E; Dueger, Erica L

    2016-10-01

    Crimean Congo hemorrhagic fever virus and Alkhumra virus, not previously reported in Djibouti, were detected among 141 (infection rate = 15.7 per 100, 95% CI: 13.4-18.1) tick pools from 81 (37%) cattle and 2 (infection rate = 0.2 per 100, 95% CI: 0.0-0.7) tick pools from 2 (1%) cattle, respectively, collected at an abattoir in 2010 and 2011.

  19. Aetiology of PCR negative suspected Crimean-Congo hemorrhagic fever cases in an endemic area.

    PubMed

    Tanyel, Esra; Sunbul, Mustafa; Fletcher, Tom E; Leblebicioglu, Hakan

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal tick-borne viral infection that is widely distributed worldwide. The diagnosis is frequently missed due to the non-specific initial symptoms and the differential diagnosis included many infectious and non-infectious causes. This retrospective study describes the clinical features and final diagnoses of 116 suspect CCHF cases that were admitted to a tertiary CCHF center in Turkey, and were CCHF IgM and PCR negative.

  20. Acute rheumatic fever and rheumatic heart disease in indigenous populations.

    PubMed

    Steer, Andrew C; Carapetis, Jonathan R

    2009-12-01

    Acute rheumatic fever and rheumatic heart disease are diseases of socioeconomic disadvantage. These diseases are common in developing countries and in Indigenous populations in industrialized countries. Clinicians who work with Indigenous populations need to maintain a high index of suspicion for the potential diagnosis of acute rheumatic fever, particularly in patients presenting with joint pain. Inexpensive medicines, such as aspirin, are the mainstay of symptomatic treatment of rheumatic fever; however, antiinflammatory treatment has no effect on the long-term rate of progression or severity of chronic valvular disease. The current focus of global efforts at prevention of rheumatic heart disease is on secondary prevention (regular administration of penicillin to prevent recurrent rheumatic fever), although primary prevention (timely treatment of streptococcal pharyngitis to prevent rheumatic fever) is also important in populations in which it is feasible.

  1. Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses

    PubMed Central

    Chang, Jinhong; Warren, Travis K.; Zhao, Xuesen; Gill, Tina; Guo, Fang; Wang, Lijuan; Comunale, Mary Ann; Du, Yanming; Alonzi, Dominic S.; Yu, Wenquan; Ye, Hong; Liu, Fei; Guo, Ju-Tao; Mehta, Anand; Cuconati, Andrea; Butters, Terry D.; Bavari, Sina; Xu, Xiaodong; Block, Timothy M.

    2013-01-01

    Host cellular endoplasmic reticulum α-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure-activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses. PMID:23578725

  2. Acute hemorrhagic pellagra in an Albanian refugee.

    PubMed

    Chaidemenos, George C; Mourellou, Olga; Karakatsanis, George; Koussidou, Thallia; Xenidis, Efthimios; Charalampidou, Haroula; Avgoloupis, Dimitris

    2002-02-01

    We report a peculiar case of hemorrhagic pellagra in an exhausted Albanian refugee who had walked for 3 days under sunny skies on his way from his country to Greece. The peculiarities of the case are the fulminant course of the disorder; the "terrifying" appearance of the patient (initially he was admitted to an emergency unit); the gangrenous appearance of the hemorrhagic lesions of the palms and fingernails; the disturbed hepatic function that gradually returned to normal; and the absence of a history of alcohol consumption, alcohol malabsorption, or drug intake.

  3. Investigation of Crimean-Congo hemorrhagic fever virus transmission from patients to relatives: a prospective contact tracing study.

    PubMed

    Gozel, Mustafa Gokhan; Bakir, Mehmet; Oztop, Atifet Yasemin; Engin, Aynur; Dokmetas, Ilyas; Elaldi, Nazif

    2014-01-01

    We investigated the possibility of transmission of Crimean-Congo hemorrhagic fever (CCHF) virus through respiratory and physical contact. In this prospective study, we traced 116 close relatives of confirmed CCHF cases who were in close contact with the patients during the acute phase of the infection and evaluated the type of contact between patients and their relatives. These relatives were followed for clinical signs or symptoms indicative of CCHF disease, blood samples of those with and without clinical signs were analyzed for CCHF virus immunoglobulin M and G (IgM and IgG, respectively) by enzyme-linked immunosorbent assay. No close relatives developed any signs or symptoms of CCHF and were negative for CCHF virus IgM and IgG. The results suggest that CCHF virus is not easily transmitted from person to person through respiratory or physical contact.

  4. Crimean-Congo hemorrhagic fever: An emerging threat for the intensivist

    PubMed Central

    Bhanot, Abhinav; Khanna, Arjun; Talwar, Deepak

    2015-01-01

    We present the case of a 55-year-old female, who presented with 15 days of fever with rash, pancytopenia, and altered behavior. She was investigated for routine causes of fever with rash and multi organ dysfunction and treated for the same. As she tested negative for all routine causes of such an illness and did not show improvement to therapy, she was investigated for Crimean-Congo hemorrhagic fever and tested positive for the same. She was started on ribavirin, but eventually succumbed to her illness. This disease has rarely been reported from the Northern India and we need to have high clinical suspicion for this deadly disease so that appropriate therapy can be started in time for the patient and prophylaxis given to all inadvertently exposed. PMID:26430344

  5. Hiding the evidence: two strategies for innate immune evasion by hemorrhagic fever viruses

    PubMed Central

    Hastie, Kathryn M.; Bale, Shridhar; Kimberlin, Christopher R.; Saphire, Erica Ollmann

    2013-01-01

    The innate immune system is one of the first lines of defense against invading pathogens. Pathogens have, in turn, evolved different strategies to counteract these responses. Recent studies have illuminated how the hemorrhagic fever viruses Ebola and Lassa fever prevent host sensing of double-stranded RNA (dsRNA), a key hallmark of viral infection. The ebolavirus protein VP35 adopts a unique bimodal configuration to mask key cellular recognition sites on dsRNA. Conversely, the Lassa fever virus nucleoprotein, NP, actually digests the dsRNA signature. Collectively, these structural and functional studies shed new light on the mechanisms of pathogenesis of these viruses and provide new targets for therapeutic intervention. PMID:22482712

  6. Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome

    PubMed Central

    2013-01-01

    Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. PMID:24305068

  7. Knowledge levels about Crimean-Congo hemorrhagic fever among midwifery and nursing students in Kahramanmaras, Turkey.

    PubMed

    Ozer, Ali; Miraloglu, Meral; Ekerbicer, Hasan Cetin; Cevik, Firdevs; Aloglu, Nihal

    2010-01-01

    The aim of this study was to determine the knowledge levels of students in the Midwifery and Nursing Departments of the School of Health Sciences in Kahramanmaras Sutcuimam University (KSU) about Crimean-Congo hemorrhagic fever (CCHF) and to examine the factors influencing those knowledge levels. The study was conducted between April-June 2009 in the School of Health Sciences, KSU, Turkey. All the midwifery and nursing students in the School of Health Sciences at that time, 296 individuals, were included in the study. Questionnaire forms, developed from literature data and comprised of 66 questions, were given to the students, and they were asked to fill them out. Twenty-four point seven percent of the students were not available, thus 223 students(75.3%) were included in the study. Seventy-five point three percent of students stated a viruse was the cause for CCHF, 78.9% stated CCHF is seen between April and September in Turkey, and 80.7% stated there was no vaccine avaiable against it. Ninety-three point three percent of the study group stated that CCHF was transmitted by tick bite, 75.8% and 53.4% stated CCHF can be transmitted by exposure to blood of an infected animal or direct contact with an acutely infected animal, respectively. Thirty-three point two percent of students stated CCHF had no specific treatment. The mean knowledge score of students regarding CCHF was 54.6 +/- 14.8. The CCHF scores of the nursing students were significantly higher than those of the midwifery students. The CCHF knowledge scores did not vary by age or college year.

  8. Immunopathogenesis of dengue hemorrhagic fever: contribution to the study of human liver lesions.

    PubMed

    Pagliari, Carla; Quaresma, Juarez Antonio Simões; Fernandes, Elaine Raniero; Stegun, Felipe Weisshaupt; Brasil, Roosecelis Araújo; de Andrade, Heitor Franco; Barros, Vera; Vasconcelos, Pedro Fernando C; Duarte, Maria Irma Seixas

    2014-07-01

    Dengue infection is an important tropical disease worldwide. The host immune response has been studied in order to better understand lesion mechanisms. It was performed an immunohistochemical study in 14 specimens of liver from patients with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors present in liver lesions and their possible role in the pathogenesis of hepatic injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3, IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF-beta. Cells expressing IL12, IL13, JAk1, STAT1, and NF-κB were rarely visualized. Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular activation and cytokine production. Cytotoxic response seems to play a role. Although TGF-beta promotes the activation of Foxp3+ regulatory T cells, IL6 can significantly suppresses their generation. The expression of Treg cells is diminished probably as a result of the high frequency of these cytokines. Both cytokines play a role in the increased vascular permeability and edema observed in dengue liver specimens, with consequent plasma leakage and severity of the disease. It was observed a regular expression of IL-18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury. At least in part, the increased number of cells expressing IL-18 could play a role of "up" regulation of FasL and correlate to the phenomenon of apoptosis, a mechanism of destruction of hepatocytes in DHF.

  9. Acute Hemorrhagic Edema of Infancy after Coronavirus Infection with Recurrent Rash

    PubMed Central

    Chambliss, Jeffrey M.

    2017-01-01

    Purpura, particularly when accompanied by fever, is a worrisome finding in children. Acute hemorrhagic edema of infancy (AHEI) is a benign type of small-vessel leukocytoclastic vasculitis that presents with progressive purpura and has an excellent prognosis. Patients with AHEI present with large, target-like purpuric plaques affecting the face, ear lobes, and extremities. While the rapid onset of these skin findings can be dramatic, the child with AHEI is usually well appearing with reassuring laboratory testing. We describe a case of a previously healthy 8-month-old female who presented with progressive purpura in a nondependent distribution, low-grade fevers, and extremity swelling. An extensive workup was performed prior to making the diagnosis of AHEI. Coronavirus was implicated as the likely triggering pathogen, and the patient suffered a recurrence of purpuric rash and swelling several weeks after her initial presentation. PMID:28243478

  10. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

    PubMed

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-09-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  11. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    PubMed Central

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-01-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729

  12. [Bacillus cereus sepsis and subarachnoid hemorrhage following consolidation chemotherapy for acute myelogenous leukemia].

    PubMed

    Kawatani, Eri; Kishikawa, Yuki; Sankoda, Chikahiro; Kuwahara, Nobuo; Mori, Daisuke; Osoegawa, Kouichi; Matsuishi, Eijo; Gondo, Hisashi

    2009-04-01

    A 64-year-old man with acute myelogenous leukemia (FAB classification, M7) in remission received consolidation chemotherapy with mitoxantrone/cytosine arabinoside. WBC counts decreased to 0/microl on day 14, and fever (39.3 degrees C) and epigastralgia developed on day 15. Cefozopran was instituted for febrile neutropenia; however, on day 16, he was found to be in cardiac arrest. CT scan on day 16 revealed subarachnoid hemorrhage. Gram-positive rods were isolated from blood cultures on day 15, and were later identified as B.cereus. He recovered transiently, but eventually died on day 19. Postmortem examination demonstrated many colonies of B. cereus in the cerebrum, cerebellum, lung, and liver. Hepatocyte necrosis was also observed in the liver. Bacterial aneurysms or septic emboli were not identified in the arachnoid vessels, but necrosis of cerebral vessels was prominent, which was considered to be the cause of subarachnoid hemorrhage. Fatal subarachnoid hemorrhage has been reported to be associated with B. cereus sepsis, which developed at nadir following chemotherapy for leukemia patients. Because of the aggressive clinical course of B. cereus sepsis, including the risk for subarachnoid hemorrhage, early treatment with effective antibiotics for B. cereus sepsis would be important in the management of leukemia patients after chemotherapy.

  13. Serosurvey of Crimean-Congo hemorrhagic fever virus in domestic animals, Gujarat, India, 2013.

    PubMed

    Mourya, Devendra T; Yadav, Pragya D; Shete, Anita; Majumdar, Triparna D; Kanani, Amit; Kapadia, Dhirendra; Chandra, Vartika; Kachhiapatel, Anantdevesh J; Joshi, Pravinchandra T; Upadhyay, Kamalesh J; Dave, Paresh; Raval, Dinkar

    2014-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease that causes a fatal hemorrhagic illness in humans. This disease is asymptomatic in animals. CCHF was first confirmed in a nosocomial outbreak in 2011 in Gujarat State. Another notifiable outbreak occurred in July, 2013, in Karyana Village, Amreli district, Gujarat State. Anti-CCHF virus (CCHFV) immunoglobulin G (IgG) antibodies were detected in domestic animals from the adjoining villages of the affected area, indicating a considerable amount of positivity against domestic animals. The present serosurvey was carried out to determine the prevalence of CCHFV among bovine, sheep, and goat populations from 15 districts of Gujarat State, India. A total of 1226 serum samples from domestic animals were screened for IgG antibodies using a CCHF animal IgG enzyme-linked immunosorbent assay (ELISA) kit from the Centers for Disease Control and Prevention. Antibodies were detected in all the 15 districts surveyed; with positivity of 12.09%, 41.21%, and 33.62% in bovine, sheep, and goat respectively. This necessitates the surveillance of CCHFV IgG antibodies in animals and hemorrhagic fever cases in human.

  14. Management dilemmas in a rare case of pituitary apoplexy in the setting of dengue hemorrhagic fever

    PubMed Central

    Balaparameswara Rao, S. J.; Savardekar, Amey R.; Nandeesh, B. N.; Arivazhagan, A.

    2017-01-01

    Background: Pituitary apoplexy occurs due to infarction or hemorrhage, within a pituitary adenoma or a nontumorous pituitary gland and can have catastrophic consequences. Dengue hemorrhagic fever (DHF) is a severe manifestation of the spectrum of dengue virus infection and is characterized by high-grade fever, thrombocytopenia, hemorrhagic tendencies, and increased vascular permeability. Cases of incidentalomas complicated by DHF and presenting with apoplexy are extremely rare. Case Description: We describe the case of a 45-year-old gentleman who suffered an attack of pituitary apoplexy while being treated for DHF. The issues pertaining to the management of hydrocephalus, timing of surgical intervention, and treatment of electrolyte imbalances encountered in the dual setting of DHF and pituitary apoplexy are discussed with reference to the outcome in our case. Conclusion: Although patients suffering from DHF harbor multiple factors, which may be precipitants of pituitary apoplexy, the association between these two conditions is rare and only few case reports document their coexistence. We review the pertinent literature and discuss the management dilemmas faced by us while dealing with these dual pathological states. PMID:28217383

  15. Case Studies in Cardiac Dysfunction After Acute Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Hamilton, Jason C.; Korn-Naveh, Lauren; Crago, Elizabeth A.

    2015-01-01

    Patients with acute aneurysmal subarachnoid hemorrhage (SAH) often present with more than just neurological compromise. A wide spectrum of complicating cardiopulmonary abnormalities have been documented in patients with acute SAH, presenting additional challenges to the healthcare providers who attempt to treat and stabilize these patients. The patients described in this article presented with both acute aneurysmal SAH and cardiopulmonary compromise. Education and further research on this connection is needed to provide optimal care and outcomes for this vulnerable population. Nurses play a key role in balancing the critical and diverse needs of patients presenting with these symptoms. PMID:18856247

  16. A historical look at the first reported cases of Lassa fever: IgG antibodies 40 years after acute infection.

    PubMed

    Bond, Nell; Schieffelin, John S; Moses, Lina M; Bennett, Andrew J; Bausch, Daniel G

    2013-02-01

    Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. One person was likely infected in 1952, 17 years before the first recognized outbreak. We briefly recount the fascinating stories of these three pioneers and their important contribution to our understanding of Lassa fever.

  17. A Historical Look at the First Reported Cases of Lassa Fever: IgG Antibodies 40 Years After Acute Infection.

    PubMed

    Bond, Nell; Schieffelin, John S; Moses, Lina M; Bennett, Andrew J; Bausch, Daniel G

    2012-12-31

    Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. One person was likely infected in 1952, 17 years before the first recognized outbreak. We briefly recount the fascinating stories of these three pioneers and their important contribution to our understanding of Lassa fever.

  18. Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17.

    PubMed

    Pagliari, Carla; Simões Quaresma, Juarez Antônio; Kanashiro-Galo, Luciane; de Carvalho, Leda Viegas; Vitoria, Webster Oliveira; da Silva, Wellington Luiz Ferreira; Penny, Ricardo; Vasconcelos, Barbara Cristina Baldez; da Costa Vasconcelos, Pedro Fernando; Duarte, Maria Irma Seixas

    2016-02-01

    Acute kidney injury is an unusual complication during dengue infection. The objective of this study was to better identify the characteristics of glomerular changes focusing on in situ immune cells and cytokines. An immunohistochemical assay was performed on 20 kidney specimens from fatal human cases of dengue hemorrhagic fever (DHF). It was observed a lymphomononuclear infiltrate, neutrophils and nuclear fragmentation in the glomeruli, hydropic degeneration, nuclear retraction, eosinophilic tubules and intense acute congestion. Sickle erythrocytes were frequent in glomeruli and inflammatory infiltrate. The glomeruli presented endothelial swelling and mesangial proliferation. Lymphocytes CD4+ predominated over CD8+ T cells, B cells and natural killer cells. There were also an expressive number of macrophagic CD68+ cells. S100, Foxp3 and CD123 cells were not identified. Cells expressing IL17 and IL18+ cytokines predominated in the renal tissues, while IL4, IL6, IL10, IL13, TNF-alpha and IFN-gamma were rarely visualized. The high number of cells expressing IL17 and IL18+ could reflect the acute inflammatory response and possibly contribute to the local lesion. CD8+ T cells could play a role in the cytotoxic response. DHF is a multifactorial disease of capillary leakage associated with a "Tsunami of cytokines expression". The large numbers of cells expressing IL17 seems to play a role favoring the increased permeability.

  19. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals

    PubMed Central

    Spengler, Jessica R.; Bergeron, Éric; Rollin, Pierre E.

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology. PMID:26741652

  20. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever

    PubMed Central

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J.; Scott, Dana P.; Feldmann, Heinz; Ebihara, Hideki

    2016-01-01

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF. PMID:27976688

  1. A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

    PubMed

    Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J; Scott, Dana P; Feldmann, Heinz; Ebihara, Hideki

    2016-12-15

    Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

  2. Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals.

    PubMed

    Spengler, Jessica R; Bergeron, Éric; Rollin, Pierre E

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, tick-borne viral disease. Humans are the only species known to develop illness after CCHF virus (CCHFV) infection, characterized by a nonspecific febrile illness that can progress to severe, often fatal, hemorrhagic disease. A variety of animals may serve as asymptomatic reservoirs of CCHFV in an endemic cycle of transmission. Seroepidemiological studies have been instrumental in elucidating CCHFV reservoirs and in determining endemic foci of viral transmission. Herein, we review over 50 years of CCHFV seroepidemiological studies in domestic and wild animals. This review highlights the role of livestock in the maintenance and transmission of CCHFV, and provides a detailed summary of seroepidemiological studies of wild animal species, reflecting their relative roles in CCHFV ecology.

  3. Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

    PubMed

    Chen, Zhi-Hai; Qin, Xin-Cheng; Song, Rui; Shen, Yi; Chen, Xiao-Ping; Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C; Zhang, Yong-Zhen

    2014-01-01

    Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

  4. Material Proximities and Hotspots: Toward an Anthropology of Viral Hemorrhagic Fevers

    PubMed Central

    Brown, Hannah; Kelly, Ann H

    2014-01-01

    This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human–animal entanglements with an ethnographic interest in the social production of space, we seek to enrich conceptualizations of viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact. We suggest that attention to the material proximities—between animals, humans, and objects—that constitute the hotspot opens a frontier site for critical and methodological development in medical anthropology and for future collaborations in VHF management and control. PMID:24752909

  5. Dengue virus serotype 2 from a sylvatic lineage isolated from a patient with dengue hemorrhagic fever.

    PubMed

    Cardosa, Jane; Ooi, Mong How; Tio, Phaik Hooi; Perera, David; Holmes, Edward C; Bibi, Khatijar; Abdul Manap, Zahara

    2009-01-01

    Dengue viruses circulate in both human and sylvatic cycles. Although dengue viruses (DENV) infecting humans can cause major epidemics and severe disease, relatively little is known about the epidemiology and etiology of sylvatic dengue viruses. A 20-year-old male developed dengue hemorrhagic fever (DHF) with thrombocytopenia (12,000/ul) and a raised hematocrit (29.5% above baseline) in January 2008 in Malaysia. Dengue virus serotype 2 was isolated from his blood on day 4 of fever. A phylogenetic analysis of the complete genome sequence revealed that this virus was a member of a sylvatic lineage of DENV-2 and most closely related to a virus isolated from a sentinel monkey in Malaysia in 1970. This is the first identification of a sylvatic DENV circulating in Asia since 1975.

  6. On the mathematical analysis of Ebola hemorrhagic fever: deathly infection disease in West African countries.

    PubMed

    Atangana, Abdon; Goufo, Emile Franc Doungmo

    2014-01-01

    For a given West African country, we constructed a model describing the spread of the deathly disease called Ebola hemorrhagic fever. The model was first constructed using the classical derivative and then converted to the generalized version using the beta-derivative. We studied in detail the endemic equilibrium points and provided the Eigen values associated using the Jacobian method. We furthered our investigation by solving the model numerically using an iteration method. The simulations were done in terms of time and beta. The study showed that, for small portion of infected individuals, the whole country could die out in a very short period of time in case there is not good prevention.

  7. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates.

    PubMed

    Geisbert, Thomas W; Daddario-DiCaprio, Kathleen M; Williams, Kinola J N; Geisbert, Joan B; Leung, Anders; Feldmann, Friederike; Hensley, Lisa E; Feldmann, Heinz; Jones, Steven M

    2008-06-01

    Recombinant vesicular stomatitis virus (VSV) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against Marburg virus when administered after exposure and can partially protect macaques after challenge with Zaire ebolavirus. Here, we administered a VSV vector expressing the Sudan ebolavirus (SEBOV) glycoprotein to four rhesus macaques shortly after exposure to SEBOV. All four animals survived SEBOV challenge, while a control animal that received a nonspecific vector developed fulminant SEBOV hemorrhagic fever and succumbed. This is the first demonstration of complete postexposure protection against an Ebola virus in nonhuman primates and provides further evidence that postexposure vaccination may have utility in treating exposures to filoviruses.

  8. Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges.

    PubMed

    Leblebicioglu, Hakan; Ozaras, Resat; Irmak, Hasan; Sencan, Irfan

    2016-02-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease of humans that affects a wide geographic area of Africa and Eurasia, including Turkey, Iran, Pakistan, Afghanistan and Russia. Since the first detection of CCHF cases in Turkey in 2002, more than 9700 patients have been reported, with an overall mortality rate just under 5%. This article assesses the present epidemiological situation of CCHF in Turkey, with an updated literature review, describes national practices and summarizes lessons learned in preparation for future outbreaks.

  9. Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever.

    PubMed

    Enria, D A; Briggiler, A M; Levis, S; Vallejos, D; Maiztegui, J I; Canonico, P G

    1987-07-01

    Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.

  10. Rodent-borne emerging viral zoonosis. Hemorrhagic fevers and hantavirus infections in South America.

    PubMed

    Enria, D A; Pinheiro, F

    2000-03-01

    Hantaviruses and arenaviruses are naturally occurring viruses of rodents. Four South American hemorrhagic fevers caused by arenaviruses have emerged in the last 5 decades. All have similar clinical manifestations, with a case-fatality rate as high as 15% to 30%. Hantavirus infections have been increasingly recognized in South America since the description in 1993 of Hantavirus pulmonary syndrome. Given the diversity of rodent species in the region, it can be foreseen that many other viruses will be discovered, and some of them will be causing human illnesses of high public health impact.

  11. Antibody responses to an immunodominant nonstructural 1 synthetic peptide in patients with dengue fever and dengue hemorrhagic fever.

    PubMed

    Huang, J H; Wey, J J; Sun, Y C; Chin, C; Chien, L J; Wu, Y C

    1999-01-01

    Two flaviviruses, dengue (DEN) virus and Japanese encephalitis (JE) virus, are important because of their global distribution and the frequency of epidemics in tropical and subtropical areas. To study the B-cell epitopes of nonstructural 1 (NS1) glycoprotein and anti-NS1 antibody response in DEN infection, a series of 15-mer synthetic peptides from the predicted B-cell linear epitopes of DEN-2 NS1 protein were prepared. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze antibody responses to these peptides from sera of both DEN and JE patients. One peptide derived from DEN-2 NS1, D2 NS1-P1 (amino acids 1-15), was identified as the immunodominant epitope that reacted with sera from dengue fever (DF) patients but not JE patients. The isotype of D2 NS1-P1-specific antibodies was mainly immunoglobulin M (IgM) in all sera that tested positive. A specificity study demonstrated that sera from all four DEN types reacted with D2 NS1-P1. A dynamics study showed that specific antibodies to this peptide could be detected as early as 2 days after the onset of symptoms. We observed significant anti-D2 NS1-P1 antibody responses in 45% of patients with primary and secondary infections with DF or with dengue hemorrhagic fever. This is the first report demonstrating that significant anti-DEN NS1 antibodies can be induced in the sera of patients with primary DEN infection.

  12. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL.

  13. Hemorrhagic Fever Occurs After Intravenous, But Not After Intragastric, Inoculation of Rhesus Macaques With Lymphocytic Choriomeningitis Virus

    PubMed Central

    Lukashevich, Igor S.; Djavani, Mahmoud; Rodas, Juan D.; Zapata, Juan C.; Usborne, Amy; Emerson, Carol; Mitchen, Jacque; Jahrling, Peter B.; Salvato, Maria S.

    2008-01-01

    Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriome-ningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.-inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease. PMID:11992578

  14. Acute Rheumatic Fever: Global Persistence of a Preventable Disease.

    PubMed

    Bono-Neri, Francine

    2016-10-21

    The persistence of acute rheumatic fever continues to be seen globally. Once thought to be eradicated in various parts of the world, the disease came back with a vengeance secondary to a lack of diligence on the part of providers. Today, the global burden of group A streptococcal infection, the culprit of the numerous sequelae manifested in acute rheumatic fever, is considerable. Although a completely preventable disease, rheumatic fever continues to exist. It is a devastating disease that involves long-term, multisystem treatment and monitoring for patients who were unsuccessful at eradicating the precipitating group A streptococcal infection. Prevention is the key to resolving the dilemma of the disease's global burden, yet the method to yield its prevention still remains unknown. Thus, meticulous attention to implementing proper treatment is the mainstay and remains a top priority.

  15. Marburg hemorrhagic fever in Durba and Watsa, Democratic Republic of the Congo: clinical documentation, features of illness, and treatment.

    PubMed

    Colebunders, Robert; Tshomba, Antoine; Van Kerkhove, Maria D; Bausch, Daniel G; Campbell, Pat; Libande, Modeste; Pirard, Patricia; Tshioko, Florimond; Mardel, Simon; Mulangu, Sabue; Sleurs, Hilde; Rollin, Pierre E; Muyembe-Tamfum, Jean-Jacques; Jeffs, Benjamin; Borchert, Matthias

    2007-11-15

    The objective of the present study was to describe day of onset and duration of symptoms of Marburg hemorrhagic fever (MHF), to summarize the treatments applied, and to assess the quality of clinical documentation. Surveillance and clinical records of 77 patients with MHF cases were reviewed. Initial symptoms included fever, headache, general pain, nausea, vomiting, and anorexia (median day of onset, day 1-2), followed by hemorrhagic manifestations (day 5-8+), and terminal symptoms included confusion, agitation, coma, anuria, and shock. Treatment in isolation wards was acceptable, but the quality of clinical documentation was unsatisfactory. Improved clinical documentation is necessary for a basic evaluation of supportive treatment.

  16. Interferon-β Therapy Prolongs Survival in Rhesus Macaque Models of Ebola and Marburg Hemorrhagic Fever

    PubMed Central

    Smith, Lauren M.; Hensley, Lisa E.; Geisbert, Thomas W.; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y.; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A.; Rubins, Kathleen H.; Karp, Christopher L.

    2013-01-01

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)–α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection. PMID:23255566

  17. Evidence for widespread infection of African bats with Crimean-Congo hemorrhagic fever-like viruses

    PubMed Central

    Müller, Marcel A.; Devignot, Stéphanie; Lattwein, Erik; Corman, Victor Max; Maganga, Gaël D.; Gloza-Rausch, Florian; Binger, Tabea; Vallo, Peter; Emmerich, Petra; Cottontail, Veronika M.; Tschapka, Marco; Oppong, Samuel; Drexler, Jan Felix; Weber, Friedemann; Leroy, Eric M.; Drosten, Christian

    2016-01-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is a highly virulent tick-borne pathogen that causes hemorrhagic fever in humans. The geographic range of human CCHF cases largely reflects the presence of ticks. However, highly similar CCHFV lineages occur in geographically distant regions. Tick-infested migratory birds have been suggested, but not confirmed, to contribute to the dispersal. Bats have recently been shown to carry nairoviruses distinct from CCHFV. In order to assess the presence of CCHFV in a wide range of bat species over a wide geographic range, we analyzed 1,135 sera from 16 different bat species collected in Congo, Gabon, Ghana, Germany, and Panama. Using a CCHFV glycoprotein-based indirect immunofluorescence test (IIFT), we identified reactive antibodies in 10.0% (114/1,135) of tested bats, pertaining to 12/16 tested species. Depending on the species, 3.6%–42.9% of cave-dwelling bats and 0.6%–7.1% of foliage-living bats were seropositive (two-tailed t-test, p = 0.0447 cave versus foliage). 11/30 IIFT-reactive sera from 10 different African bat species had neutralizing activity in a virus-like particle assay. Neutralization of full CCHFV was confirmed in 5 of 7 sera. Widespread infection of cave-dwelling bats may indicate a role for bats in the life cycle and geographic dispersal of CCHFV. PMID:27217069

  18. Retrospective Evaluation of Control Measures for Contacts of Patient with Marburg Hemorrhagic Fever

    PubMed Central

    Isken, Leslie D.; Willemse, Patricia; van den Berkmortel, Franchette; Koopmans, Marion P.G.; van Oudheusden, Danielle E.C.; Bleeker-Rovers, Chantal P.; Brouwer, Annemarie E.; Grol, Richard P.T.M.; Hulscher, Marlies E.J.L.; van Dissel, Jaap T.

    2012-01-01

    After an imported case of Marburg hemorrhagic fever was reported in 2008 in the Netherlands, control measures to prevent transmission were implemented. To evaluate consequences of these measures, we administered a structured questionnaire to 130 contacts classified as either having high-risk or low-risk exposure to body fluids of the case-patient; 77 (59.2%) of 130 contacts responded. A total of 67 (87.0%) of 77 respondents agreed that temperature monitoring and reporting was necessary, significantly more often among high-risk than low-risk contacts (p<0.001). Strict compliance with daily temperature monitoring decreased from 80.5% (62/77) during week 1 to 66.2% (51/77) during week 3. Contacts expressed concern about development of Marburg hemorrhagic fever (58.4%, 45/77) and infecting a family member (40.2%, 31/77). High-risk contacts had significantly higher scores on psychological impact scales (p<0.001) during and after the monitoring period. Public health authorities should specifically address consequences of control measures on the daily life of contacts. PMID:22710186

  19. Ebola hemorrhagic fever under scope, view of knowledge, attitude and practice from rural Sudan in 2015.

    PubMed

    Mohamed, Mohamed M G; Shwaib, Hussam M; Fahim, Monica M; Ahmed, Elhamy A; Omer, Mawadda K; Monier, Islam A; Balla, Siham A

    2016-07-05

    Ebola hemorrhagic fever (EHF) is an emerging threat to public health. The last epidemic in West Africa had a great effect on the affected communities. Timely and effective interventions were necessary in addition to community participation to control the epidemic. The knowledge, attitude and practices of vulnerable communities remain unknown, particularly in Sudan. The aim of this study was to explore the knowledge, attitude and practices of rural residents in Sudan regarding Ebola hemorrhagic fever. We conducted a cross sectional, community-based large-scale study in Al Gaziera state in rural Sudan in eight localities. In total, 1500 random adult participants were selected. The participants were assessed by a predesigned pretested questionnaire regarding their knowledge, attitude and practices regarding Ebola. Their sources of information were determined, and we assessed demographic factors as predictors of knowledge. We found poor knowledge, a fair attitude and suboptimal practices among the participants. The main sources of information were the press and media. Education was the only predictor of knowledge regarding Ebola. A lack of knowledge and suboptimal preventive practices mandates orientation and education programs to raise public awareness. Health care providers are advised to engage more in educating the community.

  20. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    PubMed

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

  1. Retrospective evaluation of control measures for contacts of patient with Marburg hemorrhagic fever.

    PubMed

    Timen, Aura; Isken, Leslie D; Willemse, Patricia; van den Berkmortel, Franchette; Koopmans, Marion P G; van Oudheusden, Danielle E C; Bleeker-Rovers, Chantal P; Brouwer, Annemarie E; Grol, Richard P T M; Hulscher, Marlies E J L; van Dissel, Jaap T

    2012-07-01

    After an imported case of Marburg hemorrhagic fever was reported in 2008 in the Netherlands, control measures to prevent transmission were implemented. To evaluate consequences of these measures, we administered a structured questionnaire to 130 contacts classified as either having high-risk or low-risk exposure to body fluids of the case-patient; 77 (59.2%) of 130 contacts responded. A total of 67 (87.0%) of 77 respondents agreed that temperature monitoring and reporting was necessary, significantly more often among high-risk than low-risk contacts (p<0.001). Strict compliance with daily temperature monitoring decreased from 80.5% (62/77) during week 1 to 66.2% (51/77) during week 3. Contacts expressed concern about development of Marburg hemorrhagic fever (58.4%, 45/77) and infecting a family member (40.2%, 31/77). High-risk contacts had significantly higher scores on psychological impact scales (p<0.001) during and after the monitoring period. Public health authorities should specifically address consequences of control measures on the daily life of contacts.

  2. Meeting report: First International Conference on Crimean-Congo hemorrhagic fever.

    PubMed

    Papa, Anna; Weber, Friedemann; Hewson, Roger; Weidmann, Manfred; Koksal, Iftihar; Korukluoglu, Gulay; Mirazimi, Ali

    2015-08-01

    Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tick-borne disease of humans, occurring from western China to the Balkans in Eurasia and south throughout the length of Africa. Its incidence has increased over the past decade, particularly in Turkey and Iran, and the disease has also emerged in India. Research has been hindered by limited laboratory capacity in many regions where the disease is prevalent, indicating the need for collaboration between investigators in endemic countries and those with greater scientific resources. In an effort to increase such collaboration, the First International Conference on Crimean-Congo hemorrhagic fever was held in Thessaloniki, Greece, from February 13 to 14, 2015. This meeting followed the conclusion of an EU-supported Collaborative Project under the Health Cooperation Work Programme of the 7th Framework Programme (Grant agreement No. 260427). It is expected to be the first in a series of meetings that will bring together researchers from around the world to exchange knowledge and experience on various aspects of CCHF. This report summarizes major presentations by the invited speakers at the First International Conference on CCHF.

  3. Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

    PubMed Central

    Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

    2015-01-01

    Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

  4. Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley and Congo-Crimean Hemorrhagic Fever in Kenya.

    DTIC Science & Technology

    1994-01-27

    AD-A280 198 I~hhumhhII AD_____ GRANT NO: DAMD17-90-Z-0005 (]’) TITLE: DIAGNOSIS AND CHEMOTHERAPY OF HUMAN TRYPANOSOMIASIS AND VECTOR ECOLOGY OF RIFT...Date OCONUS JUN 89 Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley Fever and Congo-Crimean Hemorrhagic Fever in...Kenya CONTENTS I. HUMAN TRYPANOSOMIASIS IN KENYA: DIAGNOSIS AND CHEMOTHERAPY Background

  5. Clinical symptoms and laboratory findings supporting early diagnosis of Crimean-Congo hemorrhagic fever in Iran.

    PubMed

    Mostafavi, Ehsan; Pourhossein, Behzad; Chinikar, Sadegh

    2014-07-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease, which is usually transmitted to humans by tick bites or contact with blood or other infected tissues of livestock. Patients suffering from CCHF demonstrate an extensive spectrum of clinical symptoms. As it can take considerable time from suspecting the disease in hospital until reaching a definitive diagnosis in the laboratory, understanding the clinical symptoms and laboratory findings of CCHF patients is of paramount importance for clinicians. The data were collected from patients who were referred to the Laboratory of Arboviruses and Viral Hemorrhagic Fevers at the Pasteur institute of Iran with a primary diagnosis of CCHF between 1999 and 2012 and were assessed by molecular and serologic tests. Referred patients were divided into two groups: patients with a CCHF positive result and patients with a CCHF negative result. The laboratory and clinical findings of these two groups were then compared. Two-thousand five hundred thirty-six probable cases of CCHF were referred to the laboratory, of which 871 cases (34.3%) were confirmed to be CCHF. Contact with infected humans and animals increased the CCHF infection risk (P < 0.001). A tick bite was not a risk factor. Fever; bleeding, vomiting, leucopoenia, thrombocytopenia, and increases in alanine transaminase (ALT) and aspartate transaminase (AST) levels were also indicative of CCHF infection. Accurate and speedy diagnosis of CCHF and appropriate treatment play an important role in patient survival and the application of the findings of this study can prove helpful as a key for early diagnosis.

  6. Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques

    PubMed Central

    Moncla, Louise H.; Weiler, Andrea M.; Charlier, Olivia; Rojas, Oscar; Byrum, Russell; Ragland, Dan R.; Cohen, Melanie; Sanford, Hannah B.; Qin, Jing

    2016-01-01

    ABSTRACT Simian hemorrhagic fever (SHF) is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV), has been isolated in cell culture. The natural reservoir(s) of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1), from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) sampled in Kibale National Park, Uganda. Intramuscular (i.m.) injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis) resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses. PMID:26908578

  7. Peripheral blood T and B lymphocytes during acute rheumatic fever.

    PubMed Central

    Lueker, R D; Abdin, Z H; Williams, R C

    1975-01-01

    Proportions and total numbers of thymus-derived (T) and bone marrow-derived (B) peripheral blood lymphocytes were studied in 53 patients with acute rheumatic fever, diagnosed on the basis of modifified Jones criteria. An elevation in both proportions and absolute numbers of cells bearing surface Ig was found in most patients, particularly during the first 7 days after onset. Conversely, T-cell proportions and numbers were often found to be depressed early in the acue phases of rheumatic fever. Proportions of cells bearing surface Ig did not correlate with another B-cell marker, the aggregated gamma globulin receptor, suggesting that such cells bearing surface Ig were not all B lymphocytes. Incuvation for 20 h at 37 per cent C of cells showing high proportions of surface Ig-bearing surface Ig in both normal and rheumatic fever subjects, although there was no appreciable increment in proportions of lymphocytes expressing T-cell markers. Patients with initial attacks showed higher percentages and total numbers of Ig-bearing lymphocytes (P smaller than 0.01) than did those with rneumatic fever recurrences. Elevations in numbers and proportions of peripheral blood lymphocytes bearing Ig appeared to correlate with the relative acute nature of the rheumatic fever attack. PMID:1091658

  8. Crimean-Congo hemorrhagic fever: Risk factors and control measures for the infection abatement

    PubMed Central

    ASLAM, SAADIA; LATIF, MUHAMMAD SHAHZAD; DAUD, MUHAMMAD; RAHMAN, ZIA UR; TABASSUM, BUSHRA; RIAZ, MUHAMMAD SOHAIL; KHAN, ANWAR; TARIQ, MUHAMMAD; HUSNAIN, TAYYAB

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a vector-borne viral disease, widely distributed in different regions of the world. The fever is caused by the CCHF virus (CCHFV), which belongs to the Nairovirus genus and Bunyaviridae family. The virus is clustered in seven genotypes, which are Africa-1, Africa-2, Africa-3, Europe-1, Europe-2, Asia-1 and Asia-2. The virus is highly pathogenic in nature, easily transmissible and has a high case fatality rate of 10–40%. The reservoir and vector of CCHFV are the ticks of the Hyalomma genus. Therefore, the circulation of this virus depends upon the distribution of the ticks. The virus can be transmitted from tick to animal, animal to human and human to human. The major symptoms include headache, high fever, abdominal pain, myalgia, hypotension and flushed face. As the disease progresses, severe symptoms start appearing, which include petechiae, ecchymosis, epistaxis, bleeding gums and emesis. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, antigen detection, serum neutralization and isolation of the virus by cell culture are the diagnostic techniques used for this viral infection. There is no specific antiviral therapy available thus far. However, ribavirin has been approved by the World Health Organization for the treatment of CCHFV infection. Awareness campaigns regarding the risk factors and control measures can aid in reducing the spread of this disease to a greater extent, particularly in developing countries. PMID:26870327

  9. An unusual cause of acute abdominal pain in dengue fever.

    PubMed

    Waseem, Tariq; Latif, Hina; Shabbir, Bilquis

    2014-07-01

    Dengue fever is an acute febrile viral disease caused by the bite of Aedes aegypti mosquito. It is a major health problem especially in tropical and subtropical areas including South East Asia and Pakistan. In the past few years, dengue fever has been endemic in Northern Punjab. Physicians managing dengue fever come across varied and uncommon complications of dengue fever. We report a case of dengue fever that developed severe right upper quadrant abdominal pain and induration after extreme retching and vomiting for 2 days. A rectus sheath hematoma was confirmed on noncontrast computed tomography (CT). Rectus sheath hematoma as a complication of dengue fever has rarely been reported before and never from this part of the world. Rectus sheath hematoma is an uncommon and often clinically misdiagnosed cause of abdominal pain. It is the result of bleeding into the rectus sheath from damage to the superior or inferior epigastric artery or their branches or from a direct tear of the rectus muscle. It can mimic almost any abdominal condition (See Fig.) (See Table).

  10. Detection of Crimean-Congo hemorrhagic fever, Hanta, and sandfly fever viruses by real-time RT-PCR.

    PubMed

    Ibrahim, Sofi M; Aitichou, Mohamed; Hardick, Justin; Blow, Jamie; O'Guinn, Monica L; Schmaljohn, Connie

    2011-01-01

    The development of sensitive and specific nucleic acid diagnostic assays for viral pathogens is essential for proper medical intervention. This chapter describes four fluorescence-based PCR assays to detect the Crimean-Congo Hemorrhagic Fever (CCHFV), Andes (ANDV), Hantaan (HANV), and Sandfly Fever Sicilian (SFSV) Viruses. These assays are based on species-specific hydrolysis probes targeting the nucleocapsid protein gene for CCHFV and SFSV and the glycoprotein gene for ANDV and HANV. All four assays were optimized for LightCycler 2.0 (Roche Diagnostics, Indianapolis, IN) or Ruggedized Advanced Pathogen Identification Device (R.A.P.I.D.; Idaho Technology Inc., Salt Lake City, UT). The assays were evaluated using the protocols described in the Subheading 3. The limits of detection were approximately 5, 2, 2, and 5 plaque-forming units (PFUs) for CCHFV, ANDV, HTNV, and SFSV assays, respectively. The sensitivity and specificity of the assays were evaluated with test panels that consisted of 20-60 known positive and 30-135 known negative samples, representing 7-34 genetically diverse bacterial and viral species. The CCHFV assay detected 59 out of the 60 positive samples and no false positives, resulting in 98.3% sensitivity at LOD of 5 PFU and 100% specificity. The ANDV and HTNV assays correctly identified all the positive samples with no false positive reactions; therefore, the sensitivity and specificity of these assays were determined to be 100% at LOD of 2 PFU. The SFSV assay missed three positive samples and cross-reacted with one of 48 negative samples, resulting in 95% sensitivity at LOD of 5 PFU and 98% specificity.

  11. Cross-sectional Serosurvey of Crimean-Congo Hemorrhagic Fever Virus IgG in Livestock, India, 2013-2014.

    PubMed

    Mourya, Devendra T; Yadav, Pragya D; Shete, Anita M; Sathe, Padmakar S; Sarkale, Prasad C; Pattnaik, Bramhadev; Sharma, Gaurav; Upadhyay, Kamlesh J; Gosavi, Surekha; Patil, Deepak Y; Chaubal, Gouri Y; Majumdar, Triparna D; Katoch, Vishwa M

    2015-10-01

    We conducted a cross-sectional serosurvey of Crimean-Congo hemorrhagic fever (CCHF) among livestock in 22 states and 1 union territory of India. A total of 5,636 samples from bovines, sheep, and goats were screened for CCHF virus IgG. IgG was detected in 354 samples, indicating that this virus is widespread in this country.

  12. Cross-sectional Serosurvey of Crimean-Congo Hemorrhagic Fever Virus IgG in Livestock, India, 2013–2014

    PubMed Central

    Yadav, Pragya D.; Shete, Anita M.; Sathe, Padmakar S.; Sarkale, Prasad C.; Pattnaik, Bramhadev; Sharma, Gaurav; Upadhyay, Kamlesh J.; Gosavi, Surekha; Patil, Deepak Y.; Chaubal, Gouri Y.; Majumdar, Triparna D.; Katoch, Vishwa M.

    2015-01-01

    We conducted a cross-sectional serosurvey of Crimean-Congo hemorrhagic fever (CCHF) among livestock in 22 states and 1 union territory of India. A total of 5,636 samples from bovines, sheep, and goats were screened for CCHF virus IgG. IgG was detected in 354 samples, indicating that this virus is widespread in this country. PMID:26402332

  13. Rhythm and conduction analysis of patients with acute rheumatic fever.

    PubMed

    Balli, Sevket; Oflaz, Mehmet Burhan; Kibar, Ayse Esin; Ece, Ibrahim

    2013-02-01

    Various rhythm and conduction abnormalities can develop in acute rheumatic fever. This study investigated rhythm and conduction abnormalities in children with acute rheumatic fever using a standard 12-lead electrocardiogram and 24-h rhythm Holter recordings. This multicenter retrospective study, performed between August 2011 and March 2012, enrolled 73 consecutive children with acute rheumatic fever. Standard electrocardiography was used to measure PR and corrected QT intervals. Holter recordings were evaluated for all the patients, and 52 of the patients (71.2 %) had carditis that was either isolated or together with other major criteria. A positive correlation was detected between carditis and the mean PR interval on standard electrocardiography, but this was not significant (p > 0.05). Standard electrocardiography showed a significant positive correlation between PR and corrected QT intervals (p = 0.03; r = 0.55). Standard electrocardiography showed only three patients (4.2 %) with premature contractions, whereas 24-h electrocardiography showed 26 patients (35.6 %) with premature contractions. Carditis was positively correlated with premature contractions (p < 0.01; r = 0.57). One patient with junctional rhythm and one patient with left bundle block were detected by standard electrocardiography. Whereas some patients with carditis exhibited no arrhythmic evidence on standard electrocardiograms, complete atrioventricular block, supraventricular tachycardia, and Mobitz type 1 block were observed on 24-h Holter recordings. A positive correlation also was observed between the presence of premature contractions and serum levels of acute-phase reactants (p = 0.03; r = 0.62). These findings led to the conclusion that rhythm and conduction disorders in acute rheumatic fever are more common than previously thought.

  14. Notes from the field: Increase in reported Crimean-Congo hemorrhagic fever cases--country of Georgia, 2014.

    PubMed

    Mamuchishvili, Nana; Salyer, Stephanie J; Stauffer, Kendra; Geleishvili, Marika; Zakhashvili, Khatuna; Morgan, Juliette

    2015-03-06

    During January-September 2014, Georgia's National Centers for Disease Control and Public Health (NCDC) detected 22 cases of Crimean-Congo hemorrhagic fever (CCHF) in the country. CCHF is caused by infection with a tickborne virus of the Bunyaviridae family. Transmission occurs from the bite of an infected tick or from crushing an infected tick with bare skin. Secondary transmission can result from contact with blood or tissues of infected animals and humans. CCHF initially manifests as a nonspecific febrile illness that progresses to a hemorrhagic phase, marked by rapidly developing symptoms leading to multiorgan failure, shock, and death in severe cases. The clinical severity, transmissibility, and infectiousness of CCHF are responsible for its categorization as a viral hemorrhagic fever high-priority bioterrorism agent.

  15. Serologic evidence of Crimean-Congo hemorrhagic fever virus infection in Hungary.

    PubMed

    Németh, Viktória; Oldal, Miklós; Egyed, László; Gyuranecz, Miklós; Erdélyi, Károly; Kvell, Krisztián; Kalvatchev, Nikolay; Zeller, Herve; Bányai, Krisztián; Jakab, Ferenc

    2013-04-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a typical tick-borne pathogen that causes an increasing number of severe infections in many parts of Africa, Asia, the Middle East, and the Balkans, as well as in some other parts of Europe. The virus is transmitted primarily by Hyalomma spp., and the spectrum of natural hosts for CCHFV is broad, including wild and domestic animals. Although, the presence of CCHFV was hypothesized in Hungary, no significant research activity has been carried out in the past 30 years. In the present study, we provide serological evidence of CCHFV infection in Lepus europeus using newly developed antibody detection assays. Of 198 samples, 12 (6%) were positive for immunoglobulin G antibody against CCHFV, with 2 independent detection assays. This observation indicates a need for a large-scale surveillance to estimate the potential public health risk of CCHFV in Hungary.

  16. Hospital Preparations for Viral Hemorrhagic Fever Patients and Experience Gained from Admission of an Ebola Patient.

    PubMed

    Haverkort, J J Mark; Minderhoud, A L C Ben; Wind, Jelte D D; Leenen, Luke P H; Hoepelman, Andy I M; Ellerbroek, Pauline M

    2016-02-01

    The Major Incident Hospital of the University Medical Centre of Utrecht has a longstanding history of preparing for the management of highly pathogenic and infectious organisms. An assessment of the hospital's preparations for an outbreak of viral hemorrhagic fever and its experience during admission of a patient with Ebola virus disease showed that the use of the buddy system, frequent training, and information sessions for staff and their relatives greatly increased the sense of safety and motivation among staff. Differing procedures among ambulance services limited the number of services used for transporting patients. Waste management was the greatest concern, and destruction of waste had to be outsourced. The admission of an Ebola patient proceeded without incident but led to considerable demands on staff. The maximum time allowed for wearing personal protective equipment was 45 minutes to ensure safety, and an additional 20 minutes was needed for recovery.

  17. Molecular epidemiology of Crimean-Congo hemorrhagic fever in Bulgaria--An update.

    PubMed

    Papa, Anna; Pappa, Styliani; Panayotova, Elitsa; Papadopoulou, Elpida; Christova, Iva

    2016-05-01

    Crimean-Congo hemorrhagic fever (CCHF) is endemic in Bulgaria. During 2013-2014, 11 confirmed CCHF cases have been reported in the country (seven in 2013 and four in 2014). The present study provides the CCHF molecular epidemiology in Bulgaria based on all currently available S, M, and L RNA segment nucleotide sequences spanning the years 1978-2014. A relatively low genetic difference (0-6%, the maximum seen in the M RNA segment) was seen among the CCHFV sequences suggesting that a slow evolving CCHFV strain belonging to "Europe 1" clade is present in Bulgaria. Although the virus emerged in new foci during the recent years, it is more active in the established endemic foci which seem to offer the most suitable ecosystem and environment. Understanding the CCHF epidemiology and virus evolution is the basis for public health programs and vaccine design.

  18. Hemorrhagic fever of bunyavirus etiology: disease models and progress towards new therapies.

    PubMed

    Gowen, Brian B; Hickerson, Brady T

    2017-03-01

    A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

  19. Analysis of the Spatiotemporal Characteristics of Hemorrhagic Fever with Renal Syndrome in Hubei Province, China

    NASA Astrophysics Data System (ADS)

    Fan, H.; Ge, L.; Song, L.; Zhao, Q.

    2015-07-01

    Hemorrhagic fever with renal syndrome(HFRS) is a worldwide fulminant infectious disease. Since the first HFRS cases in Hubei Province were reported in 1957, the disease has spread across the province and Hubei has become one of seriously affected areas in China. However, the epidemic characteristics of HFRS are still not entirely clear. Therefore, a systematic investigation of spatial and temporal distribution pattern of HFRS system is needed. In order to facilitate better prevention and control of HFRS in Hubei Province, in this paper, a GIS spatiotemporal analysis and modeling tool was developed to analyze the spatiotemporal dynamics of the HFRS epidemic, as well as providinga comprehensive examination the dynamic pattern of HFRS in Hubei over the past 30 years (1980-2009), to determine spatiotemporal change trends and the causes of HFRS. This paper describes the experiments and their results.

  20. Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group.

    PubMed

    Maiztegui, J I; McKee, K T; Barrera Oro, J G; Harrison, L H; Gibbs, P H; Feuillade, M R; Enria, D A; Briggiler, A M; Levis, S C; Ambrosio, A M; Halsey, N A; Peters, C J

    1998-02-01

    Argentine hemorrhagic fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious.

  1. Genetic analysis of Crimean-Congo hemorrhagic fever virus in Russia.

    PubMed

    Yashina, Lyudmila; Vyshemirskii, Oleg; Seregin, Sergei; Petrova, Irina; Samokhvalov, Evgeny; Lvov, Dmitry; Gutorov, Valery; Kuzina, Irina; Tyunnikov, Georgy; Tang, Yi-Wei; Netesov, Sergei; Petrov, Vladimir

    2003-02-01

    Genetic analysis of wild-type Crimean-Congo hemorrhagic fever (CCHF) virus strains recovered in the European part of Russia was performed. Reverse transcriptase PCR followed by direct sequencing was used to recover partial sequences of the CCHF virus medium (M) genome segment (M segment) from four pools of Hyalomma marginatum ticks and six human patients. Phylogenetic analysis of the M-segment sequences from Russian strains revealed a close relatedness of the strains (nucleotide sequence diversity,

  2. Time Series Analysis of Hemorrhagic Fever with Renal Syndrome: A Case Study in Jiaonan County, China

    PubMed Central

    Li, Shujuan; Cao, Wei; Ren, Hongyan; Lu, Liang; Zhuang, Dafang; Liu, Qiyong

    2016-01-01

    Exact prediction of Hemorrhagic fever with renal syndrome (HFRS) epidemics must improve to establish effective preventive measures in China. A Seasonal Autoregressive Integrated Moving Average (SARIMA) model was applied to establish a highly predictive model of HFRS. Meteorological factors were considered external variables through a cross correlation analysis. Then, these factors were included in the SARIMA model to determine if they could improve the predictive ability of HFRS epidemics in the region. The optimal univariate SARIMA model was identified as (0,0,2)(1,1,1)12. The R2 of the prediction of HFRS cases from January 2014 to December 2014 was 0.857, and the Root mean square error (RMSE) was 2.708. However, the inclusion of meteorological variables as external regressors did not significantly improve the SARIMA model. This result is likely because seasonal variations in meteorological variables were included in the seasonal characteristics of the HFRS itself. PMID:27706256

  3. Hospital Preparations for Viral Hemorrhagic Fever Patients and Experience Gained from Admission of an Ebola Patient

    PubMed Central

    Minderhoud, A.L.C. (Ben); Wind, Jelte D.D.; Leenen, Luke P.H.; Hoepelman, Andy I.M.; Ellerbroek, Pauline M.

    2016-01-01

    The Major Incident Hospital of the University Medical Centre of Utrecht has a longstanding history of preparing for the management of highly pathogenic and infectious organisms. An assessment of the hospital’s preparations for an outbreak of viral hemorrhagic fever and its experience during admission of a patient with Ebola virus disease showed that the use of the buddy system, frequent training, and information sessions for staff and their relatives greatly increased the sense of safety and motivation among staff. Differing procedures among ambulance services limited the number of services used for transporting patients. Waste management was the greatest concern, and destruction of waste had to be outsourced. The admission of an Ebola patient proceeded without incident but led to considerable demands on staff. The maximum time allowed for wearing personal protective equipment was 45 minutes to ensure safety, and an additional 20 minutes was needed for recovery. PMID:26812146

  4. Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with a positive maternal outcome: case report.

    PubMed

    Branco, Luis M; Boisen, Matt L; Andersen, Kristian G; Grove, Jessica N; Moses, Lina M; Muncy, Ivana J; Henderson, Lee A; Schieffellin, John S; Robinson, James E; Bangura, James J; Grant, Donald S; Raabe, Vanessa N; Fonnie, Mbalu; Zaitsev, Eleina M; Sabeti, Pardis C; Garry, Robert F

    2011-08-15

    Lassa fever (LF) is a devastating viral disease prevalent in West Africa. Efforts to take on this public health crisis have been hindered by lack of infrastructure and rapid field deployable diagnosis in areas where the disease is prevalent. Recent capacity building at the Kenema Government Hospital Lassa Fever Ward (KGH LFW) in Sierra Leone has lead to a major turning point in the diagnosis, treatment and study of LF. Herein we present the first comprehensive rapid diagnosis and real time characterization of an acute hemorrhagic LF case at KGH LFW. This case report focuses on a third trimester pregnant Sierra Leonean woman from the historically non-endemic Northern district of Tonkolili who survived the illness despite fetal demise. Employed in this study were newly developed recombinant LASV Antigen Rapid Test cassettes and dipstick lateral flow immunoassays (LFI) that enabled the diagnosis of LF within twenty minutes of sample collection. Deregulation of overall homeostasis, significant hepatic and renal system involvement, and immunity profiles were extensively characterized during the course of hospitalization. Rapid diagnosis, prompt treatment with a full course of intravenous (IV) ribavirin, IV fluids management, and real time monitoring of clinical parameters resulted in a positive maternal outcome despite admission to the LFW seven days post onset of symptoms, fetal demise, and a natural still birth delivery. These studies solidify the growing rapid diagnostic, treatment, and surveillance capabilities at the KGH LF Laboratory, and the potential to significantly improve the current high mortality rate caused by LF. As a result of the growing capacity, we were also able to isolate Lassa virus (LASV) RNA from the patient and perform Sanger sequencing where we found significant genetic divergence from commonly circulating Sierra Leonean strains, showing potential for the discovery of a newly emerged LASV strain with expanded geographic distribution

  5. Crimean-Congo hemorrhagic fever: aid of abdominal ultrasonography in prediction of severity.

    PubMed

    Ziraman, Ipek; Celikbas, Aysel; Ergonul, Onder; Degirmenci, Tulin; Uyanik, Sadik Ahmet; Koparal, Suha; Dokuzoguz, Basak

    2014-11-01

    Crimean-Congo hemorrhagic fever (CCHF) is a fatal viral infection that involves multiple organs, and endothelium. We described abdominal sonographic findings of the patients infected with the Crimean-Congo hemorrhagic fever virus (CCHFV) in relation to the severity of the disease. This is a prospective study performed among hospitalized patients infected with CCHF between 2005 and 2011. A total of 210 hospitalized patients with confirmed CCHF infection were included in the study. The mean age was 47 and 49.5% of the patients were female. Patients were classified as mild, moderate, or severe disease according to their clinical and laboratory findings. The relationship between the clinical severity of CCHF and the abdominal sonographic findings was analyzed. Sonographic findings of abdomen included gallbladder wall thickening (GBWT) in 44 (21%), splenomegaly in 39 (19%), hepatomegaly in 52 (25%), decrease in echo of liver parenchyma in nine (4%), increase in echo liver parenchyma in 13 (6%), intra-abdominal fluid collection/ascites in 23 (11%), and enlarged periportal lymph nodes in seven (3%) cases. GBWT was detected in 3% of mild patients, 23% of moderate patients, and 61% of severe patients (p<0.001). In multivariate analysis to predict the severity, GBWT (odds ratio [OR] 5.4, confidence interval [CI] 1.76-16.49, p=0.003) and intra-abdominal fluid collection/ascites (OR 3.5, CI 1.07-12.61, p=0.049) were found to be significantly associated with disease severity. In conclusion, ultrasonography is a reliable, useful, and noninvasive diagnostic tool for evaluation of the abdominal findings of the patients with CCHFV infection. GBWT and intra-abdominal fluid collection/ascites were found to be predictors of severity.

  6. Bayesian Phylogeography of Crimean-Congo Hemorrhagic Fever Virus in Europe

    PubMed Central

    Zehender, Gianguglielmo; Ebranati, Erika; Shkjezi, Renata; Papa, Anna; Luzzago, Camilla; Gabanelli, Elena; Lo Presti, Alessandra; Lai, Alessia; Rezza, Giovanni; Galli, Massimo; Bino, Silvia; Ciccozzi, Massimo

    2013-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 x 10-4 (95%HPD=1.6 and 4.7 x 10-4) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe. PMID:24223988

  7. Simultaneous detection of IgG antibodies associated with viral hemorrhagic fever by a multiplexed Luminex-based immunoassay.

    PubMed

    Wu, Wei; Zhang, Shuo; Qu, Jing; Zhang, Quanfu; Li, Chuan; Li, Jiandong; Jin, Cong; Liang, Mifang; Li, Dexin

    2014-07-17

    Viral hemorrhagic fevers (VHFs) are worldwide diseases caused by several kinds of viruses. With the emergence of new viruses, advanced diagnostic methods are urgently needed for identification of VHFs. Based on Luminex xMAP technology, a rapid, sensitive, multi-pathogen and high-throughput method which could simultaneously detect hemorrhagic fever viruses (HFVs) specific IgG antibodies was developed. Recombinant antigens of nine HFVs including Hantaan virus (HTNV), Seoul virus (SEOV), Puumala virus (PUUV), Andes virus (ANDV), Sin Nombre virus (SNV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) and dengue virus (DENV) were produced and purified from a prokaryotic expression system and the influence of the coupling amount was investigated. Cross-reactions among antigens and their rabbit immune sera were evaluated. Serum samples collected from 51 laboratory confirmed hemorrhagic fever with renal syndrome (HFRS) patients, 43 confirmed SFTS patients and 88 healthy donors were analyzed. Results showed that recombinant nucleocapsid protein of the five viruses belonging to the genus Hantavirus, had serological cross-reactivity with their corresponding rabbit immune sera, but not apparent with immune sera of other four viruses. Evaluation of this new method with clinical serum samples showed 98.04% diagnostic sensitivity for HFRS, 90.70% for SFTS detection and the specificity was ranging from 66.67% to 100.00%. The multiplexed Luminex-based immunoassay has firstly been established in our study, which provides a potentially reliable diagnostic tool for IgG antibody detection of VHFs.

  8. Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles

    PubMed Central

    Zivcec, Marko; Metcalfe, Maureen G.; Albariño, César G.; Guerrero, Lisa W.; Pegan, Scott D.; Spiropoulou, Christina F.; Bergeron, Éric

    2015-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is an often lethal, acute inflammatory illness that affects a large geographic area. The disease is caused by infection with CCHF virus (CCHFV), a nairovirus from the Bunyaviridae family. Basic research on CCHFV has been severely hampered by biosafety requirements and lack of available strains and molecular tools. We report the development of a CCHF transcription- and entry-competent virus-like particle (tecVLP) system that can be used to study cell entry and viral transcription/replication over a broad dynamic range (~4 orders of magnitude). The tecVLPs are morphologically similar to authentic CCHFV. Incubation of immortalized and primary human cells with tecVLPs results in a strong reporter signal that is sensitive to treatment with neutralizing monoclonal antibodies and by small molecule inhibitors of CCHFV. We used glycoproteins and minigenomes from divergent CCHFV strains to generate tecVLPs, and in doing so, we identified a monoclonal antibody that can prevent cell entry of tecVLPs containing glycoproteins from 3 pathogenic CCHFV strains. In addition, our data suggest that different glycoprotein moieties confer different cellular entry efficiencies, and that glycoproteins from the commonly used strain IbAr10200 have up to 100-fold lower ability to enter primary human cells compared to glycoproteins from pathogenic CCHFV strains. PMID:26625182

  9. Discovery Proteomics And Nonparametric Modeling Pipeline In The Development Of A Candidate Biomarker Panel For Dengue Hemorrhagic Fever

    PubMed Central

    Brasier, Allan R; Garcia, Josefina; Wiktorowicz, John E.; Spratt, Heidi M.; Comach, Guillermo; Ju, Hyunsu; Recinos, Adrian; Soman, Kizhake; Forshey, Brett M.; Halsey, Eric S.; Blair, Patrick J.; Rocha, Claudio; Bazan, Isabel; Victor, Sundar S; Wu, Zheng; Stafford, Susan; Watts, Douglas; Morrison, Amy C.; Scott, Thomas W.; Kochel, Tadeusz J.

    2013-01-01

    Secondary Dengue viral infection can produce capillary leakage associated with increased mortality known as Dengue Hemorrhagic Fever (DHF). Because the mortality of DHF can be reduced by early detection and intensive support, improved methods for its detection are needed. We applied multidimensional protein profiling to predict outcomes in a prospective Dengue surveillance study in South America. Plasma samples taken from initial clinical presentation of acute Dengue infection were subjected to proteomics analyses using ELISA and a recently developed biofluid analysis platform. Demographics, clinical laboratory measurements, 9 cytokines and 419 plasma proteins collected at the time of initial presentation were compared between the DF and DHF outcomes. Here, the subject’s gender, clinical parameters, 2 cytokines and 42 proteins discriminated between the outcomes. These factors were reduced by multivariate adaptive regression splines (MARS) that a highly accurate classification model based on 8 discriminant features with an AUC of 0.999. Model analysis indicated that the feature-outcome relationship were non-linear. Although this DHF risk model will need validation in a larger cohort, we conclude that approaches to develop predictive biomarker models for disease outcome will need to incorporate nonparametric modeling approaches. PMID:22376251

  10. Hepatocyte pathway alterations in response to in vitro Crimean Congo hemorrhagic fever virus infection.

    PubMed

    Fraisier, Christophe; Rodrigues, Raquel; Vu Hai, Vinh; Belghazi, Maya; Bourdon, Stéphanie; Paranhos-Baccala, Glaucia; Camoin, Luc; Almeras, Lionel; Peyrefitte, Christophe Nicolas

    2014-01-22

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus responsible for hemorrhagic manifestations and multiple organ failure, with a high mortality rate. In infected humans, damage to endothelial cells and vascular leakage may be a direct result of virus infection or an immune response-mediated indirect effect. The main target cells are mononuclear phagocytes, endothelial cells and hepatocytes; the liver being a key target for the virus, which was described as susceptible to interferon host response and to induce apoptosis. To better understand the early liver cell alterations due to virus infection, the protein profile of in vitro CCHFV-infected HepG2 cells was analyzed using two quantitative proteomic approaches, 2D-DIGE and iTRAQ. A set of 243 differentially expressed proteins was identified. Bioinformatics analysis (Ingenuity Pathways Analysis) revealed multiple host cell pathways and functions altered after CCHFV infection, with notably 106 proteins related to cell death, including 79 associated with apoptosis. Different protein networks emerged with associated pathways involved in inflammation, oxidative stress and apoptosis, ubiquitination/sumoylation, regulation of the nucleo-cytoplasmic transport, and virus entry. Collectively, this study revealed host liver protein abundances that were modified at the early stages of CCHFV infection, offering an unparalleled opportunity of the description of the potential pathogenesis processes and of possible targets for antiviral research.

  11. Knowledge Levels Regarding Crimean-Congo Hemorrhagic Fever Among Emergency Healthcare Workers in an Endemic Region

    PubMed Central

    Yolcu, Sadiye; Kader, Cigdem; Kayipmaz, Afsin Emre; Ozbay, Sedat; Erbay, Ayse

    2014-01-01

    Background In this study, we aimed to determine knowledge levels regarding Crimean-Congo hemorrhagic fever (CCHF) among emergency healthcare workers (HCWs) in an endemic region. Methods A questionnaire form consisting of questions about CCHF was applied to the participants. Results The mean age was 29.6 ± 6.5 years (range 19 - 45). Fifty-four (49.5%) participants were physicians, 39 (35.8%) were nurses and 16 (14.7%) were paramedics. All of the participants were aware of CCHF, and 48 (44%) of them had previously followed CCHF patients. Rates of the use of protective equipment (masks and gloves) during interventions for patients who were admitted to the emergency service with active hemorrhage were 100% among paramedics, 76.9% among nurses and 61.1% among physicians (P = 0.003). Among 86 (78.9%) HCWs who believed that their knowledge regarding CCHF was adequate, 62 (56.9%) declared that they would prefer not to care for patients with CCHF (P = 0.608). Conclusions The use of techniques to prevent transmission of this disease, including gloves, face masks, face visors and box coats, should be explained to emergency room HCWs, and encouragement should be provided for using these techniques. PMID:24734146

  12. An experimental study of the acute stage of subarachnoid hemorrhage.

    PubMed

    Kamiya, K; Kuyama, H; Symon, L

    1983-12-01

    A baboon model of subarachnoid hemorrhage (SAH) has been developed to study the changes in cerebral blood flow (CBF), intracranial pressure (ICP), and cerebral edema associated with the acute stage of SAH. In this model, hemorrhage was caused by avulsion of the posterior communicating artery via a periorbital approach, with the orbit sealed and ICP restored to normal before SAH was produced. Local CBF was measured in six sites in the two hemispheres, and ICP monitored by an implanted extradural transducer. Following sacrifice of the animal, the effect of the induced SAH on ICP, CBF, autoregulation, and CO2 reactivity in the two hemispheres was assessed. Brain water measurements were also made in areas of gray and white matter corresponding to areas of blood flow measurements, and also in the deep nuclei. Two principal patterns of ICP change were found following SAH; one group of animals showed a return to baseline ICP quite quickly and the other maintained high ICP for over an hour. The CBF was reduced after SAH to nearly 20% of control values in all areas, and all areas showed impaired autoregulation. Variable changes in CO2 reactivity were evident, but on the side of the hemorrhage CO2 reactivity was predominantly reduced. Differential increase in pressure lasting for over 7 minutes was evident soon after SAH on the side of the ruptured vessel. There was a significant increase of water in all areas, and in cortex and deep nuclei as compared to control animals.

  13. Mapping of the interaction domains of the Crimean–Congo hemorrhagic fever virus nucleocapsid protein

    PubMed Central

    Macleod, Jesica M. Levingston; Marmor, Hannah; Frias-Staheli, Natalia

    2015-01-01

    Crimean–Congo hemorrhagic fever virus (CCHFV) is a member of the genus Nairovirus of the family Bunyaviridae, that can cause severe haemorrhagic fever in humans, with mortality rates above 30 %. CCHFV is the most widespread of the tick-borne human viruses and it is endemic in areas of central Asia, the Middle East, Africa and southern Europe. Its viral genome consists of three negative-sense RNA segments. The large segment (L) encodes a viral RNA-dependent RNA polymerase (L protein), the small segment (S) encodes the nucleocapsid protein (N protein) and the medium segment (M) encodes the envelope proteins. The N protein of bunyaviruses binds genomic RNA, forming the viral ribonucleoprotein (RNP) complex. The L protein interacts with these RNP structures, allowing the initiation of viral replication. The N protein also interacts with actin, although the regions and specific residues involved in these interactions have not yet been described. Here, by means of immunoprecipitation and immunofluorescence assays, we identified the regions within the CCHFV N protein implicated in homo-oligomerization and actin binding. We describe the interaction of the N protein with the CCHFV L protein, and identify the N- and C-terminal regions within the L protein that might be necessary for the formation of these N–L protein complexes. These results may guide the development of potent inhibitors of these complexes that could potentially block CCHFV replication. PMID:25389186

  14. Hard ticks (Ixodidae) and Crimean-Congo hemorrhagic fever virus in south west of Iran.

    PubMed

    Sharifinia, Narges; Rafinejad, Javad; Hanafi-Bojd, Ahmad Ali; Chinikar, Sadegh; Piazak, Norayer; Baniardalan, Mojgan; Biglarian, Akbar; Sharifinia, Farhad

    2015-01-01

    Ticks are vectors of some important arthropod-borne diseases in both fields of veterinary and medicine, such as Lyme, tularemia, Rocky Mountain spotted fever, and some types of encephalitis as well as Crimean Congo hemorrhagic fever (CCHF). Iran is known as one of the main foci of CCHF in west of Asia. This study was conducted in DarrehShahr County because of the development of animal husbandry in this area to detect the fauna and viral infection of the hard ticks of livestock. A cross-sectional survey was conducted during 2011-2012 with random sampling in four villages. A sample of ticks was subjected to RT-PCR method for detection of viral infection. During the study period, 592 Ixodidae ticks were collected and identified as seven species of Hyalomma asiaticum, Hy. marginatum, Hy. anatolicum, Hy. dromedarii, Hy. detritum, Rhipicephalus bursa and Rh. sanguineus. More than 20% of these ticks were examined to detect the genome of CCHF virus while 6.6% were positive. All species of Hyalomma were found to be positive. A high rate of livestock was found to be infected with hard ticks, which can act as the vectors of the CCHF disease. Regarding infection of all five Hyalomma species captured in this area, this genus should be considered as the main vector of CCHF. Planning control program can be performed based on the obtained data on seasonal activity of Ixodidae to prevent animal infestation as well as to reduce the risk of CCHF transmission.

  15. Immunogenicity of Combination DNA Vaccines for Rift Valley Fever Virus, Tick-Borne Encephalitis Virus, Hantaan Virus, and Crimean Congo Hemorrhagic Fever Virus

    DTIC Science & Technology

    2005-08-22

    genus of the family Bunyaviridae and is one of four hantaviruses known to cause hemorrhagic fever with renal syndrome (HFRS). HFRS caused by HTNV...infection is found exclusively in Asia, with most cases occurring in China (reviewed in [2]). Hantaviruses are transmitted to humans by exposure to...before in our studies of antavirus DNA vaccines. We showed that although DNA accines for two hantaviruses , HTNV and Seoul virus, are ighly immunogenic

  16. Acute gastric changes after intracerebral hemorrhage in rats.

    PubMed

    Smelley, Christopher; Specian, Robert D; Tang, Jiping; Zhang, John H

    2005-03-21

    Severe intracerebral hemorrhage (ICH) produces gastric pathology in about 30% of the patient population, even after the standard treatment of H2 receptor blockers or proton pump inhibitors. This study was undertaken to establish a rat model of ICH-induced gastric ulcer. Adult male Sprague-Dawley rats (300-350 g) were divided into two hemorrhage groups and a sham control group. ICH was produced either by injection of 100 microl of autologous arterial blood or by injection of 4 microl saline containing 0.6 unit of bacterial collagenase VII into the right basal ganglia. Rats were sacrificed at 24, 48, 72 h, and 7 days after ICH to harvest brains and stomachs. Greater degrees of hemorrhage and brain edema were observed in collagenase-induced ICH. Motor behavior decreased significantly after 24 h in both models. The incidence of acute ulceration with destruction of the forestomach epithelium was extremely low at 8.7% in the collagenase injection model and 4.8% in the blood injection rats. Small, pinpoint hemorrhages (petechiae) were noticed in 38% of rats after blood injection and 22% after collagenase injection, in the glandular portion of the gastric mucosa with penetration of red blood cells and inflammatory cells into the gastric mucosa. Enhanced tumor necrosis factor alpha (TNFalpha) and cyclooxygenase 2 (COX-2) expressions were observed in gastric tissues after ICH with more intense staining occurring at 24 and 48 h. Due to the low incidence of ulceration, ICH-induced gastric ulceration in rodents may not appropriate for evaluating the potential human risk of gastric ulceration after ICH.

  17. Update on diagnosis of acute rheumatic fever: 2015 Jones criteria.

    PubMed

    Eroğlu, Ayşe Güler

    2016-03-01

    In the final Jones criteria, different diagnostic criteria were established for the diagnosis of acute rheumatic fever for low risk and moderate-high risk populations. Turkey was found to be compatible with moderate-high risk populations as a result of regional screenings performed in terms of acute rheumatic fever and rheumatic heart disease. The changes in the diagnostic criteria for low-risk populations include subclinical carditis found on echocardiogram as a major criterion in addition to carditis found clinically and a body temperature of 38.5°C and above as a minor criterion. In moderate-high risk populations including Turkey, subclinical carditis found on echocardiogram in addition to clinical carditis is used as a major criterion as a new amendment. In addition, aseptic monoarthritis and polyarthralgia are used as major criteria in addition to migratory arthritis and monoarhtralgia is used as a minor criterion among joint findings. However, differentiation of subclinical carditis from physiological valve regurgitation found in healthy individuals and exclusion of other diseases involving joints when aseptic monoarthritis and polyarthralgia are used as major criteria are very important. In addition, a body temperature of 38°C and above and an erythrocyte sedimentation rate of 30 mm/h and above have been accepted as minor criteria. The diagnostic criteria for the first attack have not been changed; three minor findings have been accepted in presence of previous sterptococcal infection in addition to the old cirteria for recurrent attacks. In the final Jones criteria, it has been recommended that patients who do not fully meet the diagnostic criteria of acute rheumatic fever should be treated as acute rheumatic fever if another diagnosis is not considered and should be followed up with benzathine penicilin prophylaxis for 12 months. It has been decided that these patients be evaluated 12 months later and a decision for continuation or discontinuation of

  18. Update on diagnosis of acute rheumatic fever: 2015 Jones criteria

    PubMed Central

    Eroğlu, Ayşe Güler

    2016-01-01

    In the final Jones criteria, different diagnostic criteria were established for the diagnosis of acute rheumatic fever for low risk and moderate-high risk populations. Turkey was found to be compatible with moderate-high risk populations as a result of regional screenings performed in terms of acute rheumatic fever and rheumatic heart disease. The changes in the diagnostic criteria for low-risk populations include subclinical carditis found on echocardiogram as a major criterion in addition to carditis found clinically and a body temperature of 38.5°C and above as a minor criterion. In moderate-high risk populations including Turkey, subclinical carditis found on echocardiogram in addition to clinical carditis is used as a major criterion as a new amendment. In addition, aseptic monoarthritis and polyarthralgia are used as major criteria in addition to migratory arthritis and monoarhtralgia is used as a minor criterion among joint findings. However, differentiation of subclinical carditis from physiological valve regurgitation found in healthy individuals and exclusion of other diseases involving joints when aseptic monoarthritis and polyarthralgia are used as major criteria are very important. In addition, a body temperature of 38°C and above and an erythrocyte sedimentation rate of 30 mm/h and above have been accepted as minor criteria. The diagnostic criteria for the first attack have not been changed; three minor findings have been accepted in presence of previous sterptococcal infection in addition to the old cirteria for recurrent attacks. In the final Jones criteria, it has been recommended that patients who do not fully meet the diagnostic criteria of acute rheumatic fever should be treated as acute rheumatic fever if another diagnosis is not considered and should be followed up with benzathine penicilin prophylaxis for 12 months. It has been decided that these patients be evaluated 12 months later and a decision for continuation or discontinuation of

  19. Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9).

    PubMed

    Weber, David J; Rutala, William A; Fischer, William A; Kanamori, Hajime; Sickbert-Bennett, Emily E

    2016-05-02

    Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility.

  20. Ngari Virus Is a Bunyamwera Virus Reassortant That Can Be Associated with Large Outbreaks of Hemorrhagic Fever in Africa

    PubMed Central

    Gerrard, Sonja R.; Li, Li; Barrett, Alan D.; Nichol, Stuart T.

    2004-01-01

    Two isolates of a virus of the genus Orthobunyavirus (family Bunyaviridae) were obtained from hemorrhagic fever cases during a large disease outbreak in East Africa in 1997 and 1998. Sequence analysis of regions of the three genomic RNA segments of the virus (provisionally referred to as Garissa virus) suggested that it was a genetic reassortant virus with S and L segments derived from Bunyamwera virus but an M segment from an unidentified virus of the genus Orthobunyavirus. While high genetic diversity (52%) was revealed by analysis of virus M segment nucleotide sequences obtained from 21 members of the genus Orthobunyavirus, the Garissa and Ngari virus M segments were almost identical. Surprisingly, the Ngari virus L and S segments showed high sequence identity with those of Bunyamwera virus, showing that Garissa virus is an isolate of Ngari virus, which in turn is a Bunyamwera virus reassortant. Ngari virus should be considered when investigating hemorrhagic fever outbreaks throughout sub-Saharan Africa. PMID:15280501

  1. Molecular Assay on Crimean Congo Hemorrhagic Fever Virus in Ticks (Ixodidae) Collected from Kermanshah Province, Western Iran

    PubMed Central

    Mohammadian, Maria; Chinikar, Sadegh; Telmadarraiy, Zakkyeh; Vatandoost, Hassan; Oshaghi, Mohammad Ali; Hanafi-Bojd, Ahmad Ali; Sedaghat, Mohammad Mehdi; Noroozi, Mehdi; Faghihi, Faezeh; Jalali, Tahmineh; Khakifirouz, Sahar; Shahhosseini, Nariman; Farhadpour, Firoozeh

    2016-01-01

    Background: Crimean-Congo Hemorrhagic Fever (CCHF) is a feverous and hemorrhagic disease endemic in some parts of Iran and caused by an arbovirus related to Bunyaviridae family and Nairovirusgenus. The main virus reservoir in the nature is ticks, however small vertebrates and a wide range of domestic and wild animals are regarded as reservoir hosts. This study was conducted to determine the infection rate of CCHF virus in hard ticks of Sarpole-Zahab County, Kermanshah province, west of Iran. Methods: From total number of 851 collected ticks from 8 villages, 131 ticks were selected randomlyand investigated for detection of CCHF virus using RT-PCR. Results: The virus was found in 3.8% of the tested ticks. Hyalommaanatolicum, H. asiaticum and Rhipicephalus sanguineus species were found to have viral infection, with the highest infection rate (11.11%) in Rh. sanguineus. Conclusion: These findings provide epidemiological evidence for planning control strategies of the disease in the study area. PMID:27308296

  2. Importance of serum adipokine and ghrelin levels in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Yilmaz, Gürdal; Mentese, Ahmet; Yilmaz, Hülya; Koksal, İftihar

    2015-02-01

    Crimean-Congo Hemorrhagic Fever (CCHF) may present with a mild clinical course or else exhibit a severe profile with potentially fatal hemorrhaging. The pathogenesis of the disease has not yet been well described. Cytokines have recently been investigated in order to explain the pathogenesis. The latest reports show that adipokines are powerful inflammation modulators. This study investigated the effect of adipokines (resistin, leptin, and adiponectin) and ghrelin on disease severity in CCHF patients by testing their serum levels. This retrospective study was conducted with patients with CCHF hospitalized at the Karadeniz Technical University, Medical Faculty in Turkey. Patients were divided into severe and non-severe groups. Serum adipokine levels of patients with CCHF were measured using enzyme-linked immunosorbent assay (ELISA). Fifty-three patients with confirmed CCHF were investigated. Twenty-five (47.2%) of these patients constituted the severe group. Serum resistin levels in the severe and non-severe groups were 108.9 ± 24.7 ng/ml and 77.5 ± 27.7 ng/ml (P < 0.001), leptin levels 15.5 ± 9.8 and 11.2 ± 5.1 ng/ml (P = 0.074), adiponectin levels 26.8 ± 18.9 and 27.4 ± 16.3 ng/ml (P = 0.903) and ghrelin levels 57.1 ± 48.7 and 200.9 ± 182.7 ng/ml (P = 0.001), all respectively. This study confirms that significant changes in serum levels of resistin and ghrelin take place in severe CCHF.

  3. Epidemiological survey of Crimean Congo hemorrhagic fever virus in cattle in East Darfur State, Sudan.

    PubMed

    Ibrahim, Alaa M; Adam, Ibrahim A; Osman, Badreldin T; Aradaib, Imadeldin E

    2015-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by CCHF virus (CCHFV) of the genus Nairovirus in the family Bunyaviridae. CCHFV causes subclinical infection in domestic livestock and an often fatal hemorrhagic illness in humans, with approximately 30% mortality rates. In the present study, a cross-sectional serosurvey was conducted in a total of 282 randomly selected cattle from five localities in East Darfur State, Sudan. The exposure status to CCHF was determined using enzyme-linked immunosorbent assay (ELISA) for detection of CCHFV-specific IgG antibodies in cattle serum samples. The CCHFV-specific IgG antibodies were detected in 54 out of 282 animals, accounting for a 19.14% prevalence rate. Older cattle (>2 years of age) were approximately five times more likely to be infected with the virus (OR=4.90, CI=1.28-18.98, p-value=0.02). Heavily tick-infested cattle (ticks all over the body) were at 11 times higher at risk compared to tick-free animals (OR=11.11, CI=2.86-43.25, p-value=0.01). Grazing system is another factor affecting CCHF, where cattle grazing on open system were 27 times more at risk compared to other grazing systems (OR=27.22, CI=7.46-99.24, p-value=0.001). There was an association between localities and CCHF cattle (OR=0.24, CI=0.07-0.83, p-value=0.02). This study confirms the exposure of cattle to CCHF in East Darfur and identifies potential risk factors associated with the disease. Further epidemiological studies and improved surveillance are urgently needed to prevent a possible outbreak of CCHF among humans in the Darfur region of Sudan.

  4. [The Alkhurma virus (family Flaviviridae, genus Flavivirus): an emerging pathogen responsible for hemorrhage fever in the Middle East].

    PubMed

    Charrel, R N; de Lamballerie, X

    2003-01-01

    To date tick-borne flaviviruses causing hemorrhagic fevers in humans have been isolated in Siberia (Omsk hemorrhagic fever virus), India (Kyasanur Forest disease virus), and Saudi Arabia (Akhurma virus). Because of their potential use as biological weapons for bioterrorism, these 3 viruses require level 4 biosafety handling facilities and have been listed as hypervirulent pathogens by the Center for Disease Control and Prevention. Alkhurma virus was isolated in 1995 from patients with hemorrhagic fever in Saudi Arabia. Current evidence suggests that transmission to humans can occur either transcutaneously either by contamination of a skin wound with the blood of an infected vertebrate or bites of an infected tick or orally by drinking unpasteurized contaminated milk. To date a total of 24 symptomatic human cases have been recorded with a mortality rate at 25% (6/24). Pauci-symptomatic or asymptomatic cases are likely but epidemiologic data are currently unavailable. The complete coding sequence of the prototype strain of Alkhurma virus was determined and published in 2001 based on international research project involving investigators from France, Great Britain, and Saudi Arabia. Phylogenetic studies demonstrate that closest known relative of Alkhurma virus is Kyasanur Forest disease virus and that both viruses share a common ancestor. Genetic analysis of several human strains sequentially isolated over a 5-year period showed a very low diversity. This finding has important potential implications for diagnosis and vaccination.

  5. Acute rheumatic fever and rheumatic heart disease among children--American Samoa, 2011-2012.

    PubMed

    Beaudoin, Amanda; Edison, Laura; Introcaso, Camille E; Goh, Lucy; Marrone, James; Mejia, Amelita; Van Beneden, Chris

    2015-05-29

    Acute rheumatic fever is a nonsuppurative, immune-mediated consequence of group A streptococcal pharyngitis (strep throat). Recurrent or severe acute rheumatic fever can cause permanent cardiac valve damage and rheumatic heart disease, which increases the risk for cardiac conditions (e.g., infective endocarditis, stroke, and congestive heart failure). Antibiotics can prevent acute rheumatic fever if administered no more than 9 days after symptom onset. Long-term benzathine penicillin G (BPG) injections are effective in preventing recurrent acute rheumatic fever attacks and are recommended to be administered every 3-4 weeks for 10 years or until age 21 years to children who receive a diagnosis of acute rheumatic fever. During August 2013, in response to anecdotal reports of increasing rates of acute rheumatic fever and rheumatic heart disease, CDC collaborated with the American Samoa Department of Health and the Lyndon B. Johnson Tropical Medical Center (the only hospital in American Samoa) to quantify the number of cases of pediatric acute rheumatic fever and rheumatic heart disease in American Samoa and to assess the potential roles of missed pharyngitis diagnosis, lack of timely prophylaxis prescription, and compliance with prescribed BPG prophylaxis. Using data from medical records, acute rheumatic fever incidence was calculated as 1.1 and 1.5 cases per 1,000 children aged ≤18 years in 2011 and 2012, respectively; 49% of those with acute rheumatic fever subsequently received a diagnosis of rheumatic heart disease. Noncompliance with recommended prophylaxis with BPG after physician-diagnosed acute rheumatic fever was noted for 22 (34%) of 65 patients. Rheumatic heart disease point prevalence was 3.2 cases per 1,000 children in August 2013. Establishment of a coordinated acute rheumatic fever and rheumatic heart disease control program in American Samoa, likely would improve diagnosis, treatment, and patient compliance with BPG prophylaxis.

  6. Is ribavirin prophylaxis effective for nosocomial transmission of Crimean-Congo hemorrhagic fever?

    PubMed

    Guner, Rahmet; Hasanoglu, Imran; Tasyaran, Mehmet Akin; Yapar, Derya; Keske, Siran; Guven, Tumer; Yilmaz, Gul Ruhsar

    2014-08-01

    Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonotic disease that is transmitted primarily through contact with ticks. Nosocomial cases and outbreaks of CCHF have been reported from many countries. Health care workers (HCWs) are at risk of exposure to CCHF. In our study, we evaluated seven HCWs' exposure to confirmed CCHF patients' infected blood and body fluids and prophylactic efficacy of the ribavirin on nosocomial transmission of CCHF retrospectively. Between 2007 and 2013, 150 CCHF cases were admitted to our clinic. During the follow-up of these patients, four doctors and three nurses had contact with infected blood and body fluids through needle stick injury, contact of skin and mucosal surfaces, and probable aerosolization. All of the index cases' diagnoses of CCHF were confirmed during the contact. Ribavirin prophylaxis was administered within 0.5-1 h in six out of seven cases. All of these cases' CCHF virus PCR results were negative. One physician had no contact with infected blood or body fluid, so ribavirin prophylaxis was not administered. The physician developed CCHF and diagnosis was confirmed. Although efficacy of ribavirin for prophylaxis is not clear and very few data exist on prophylactic usage of ribavirin, lack of clinical manifestations in our cases that were given ribavirin compared with the developed clinical manifestations in the physician may be explained by the prophylactic efficacy of the ribavirin.

  7. Plasma oxidative stress and total thiol levels in Crimean-Congo hemorrhagic fever.

    PubMed

    Karadag-Oncel, Eda; Erel, Ozcan; Ozsurekci, Yasemin; Caglayik, Dilek Yagci; Kaya, Ali; Gozel, Mustafa Gokhan; Icagasioglu, Fusun Dilara; Engin, Aynur; Korukluoglu, Gulay; Uyar, Yavuz; Elaldi, Nazif; Ceyhan, Mehmet

    2014-01-01

    In this study, we investigated the pro- and antioxidant status of patients with a pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) in terms of their role in its pathogenesis. During the study period, 34 children and 41 adults were diagnosed with CCHF. The control group consisted of healthy age- and gender-matched children and adults. Serum levels of the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and plasma total thiol (TTL) were evaluated and compared between groups. The difference in mean TAC values between CCHF patients and healthy controls was not statistically significant (P > 0.05). Mean TOS, OSI, and TTL values were significantly lower in CCHF patients than in healthy controls (P < 0.001). Comparisons between the 2 groups revealed that mean TOS and OSI values were significantly lower in adults with CCHF than in their healthy counterparts (P < 0.001). Similarly, mean TTL levels were lower in both children and adults with CCHF when compared separately with healthy controls (P < 0.05). There was no significant difference in the mean serum TTL levels between children and adults with CCHF (P > 0.05). Our results suggest that TTL may play a more important role in CCHF pathogenesis than the other parameters investigated. The mean TOS and OSI values were higher in the control group than in CCHF patients.

  8. A case report of crimean congo hemorrhagic Fever in ostriches in iran.

    PubMed

    Mostafavi, Ehsan; Chinikar, Sadegh; Moradi, Maryam; Bayat, Neda; Meshkat, Mohsen; Fard, Mohammad Khalili; Ghiasi, Seyyed Mojtaba

    2013-01-01

    Crimean Congo hemorrhagic fever (CCHF) is a viral zoonosis, which is usually transmitted via tick bites or close contact with infected blood or tissue. This disease can cause a case fatality rate of up to 25%-30% in humans. CCHF Infection in birds is less documented. An ostrich can reproduce viruses and can also play the role of a mechanical vector, by transporting infected ticks without becoming ill. In March 2007, three butchers and one worker in an ostrich farm were infected with CCHF in central part of Iran. Considering the role ostriches play in transmitting the disease, serum samples from five ostriches of that farm were taken and sent to the laboratory for CCHF ELISA tests. The result of the IgG test was positive for one (20%) of the ostriches. At the same time, serum samples of eight sheep from the same farm were sent for IgG testing, two (25%) of which were positive. This was the first report of CCHF infection of an ostrich in Iran and tracing CCHF IgG against this ostrich and the afore-mentioned sheep may have revealed that the disease in the worker was the cause of transmission of this disease from these animals or their ticks.

  9. Potential association of dengue hemorrhagic fever incidence and remote senses land surface temperature, Thailand, 1998.

    PubMed

    Nitatpattana, Narong; Singhasivanon, Pratap; Kiyoshi, Honda; Andrianasolo, Haja; Yoksan, Sutee; Gonzalez, Jean-Paul; Barbazan, Philippe

    2007-05-01

    A pilot study was designed to analyze a potential association between dengue hemorrhagic fever (DHF) incidence and, temperature computed by satellite. DHF is a mosquito transmitted disease, and water vapor and humidity are known to have a positive effect on mosquito life by increasing survival time and shortening the development cycle. Among other available satellite data, Land Surface Temperature (LST) was chosen as an indicator that combined radiated earth temperature and atmospheric water vapor concentration. Monthly DHF incidence was recorded by province during the 1998 epidemic and obtained as a weekly combined report available from the National Ministry of Public Health. Conversely, LST was calculated using remotely sensed data obtained from thermal infrared sensors of NOAA satellites and computed on a provincial scale. Out of nine selected study provinces, five (58.3%) exhibited an LST with a significant positive correlation with rainfall (p < 0.05). In four out of nineteen surveyed provinces (21.3%), LST showed a significant positive correlation with DHF incidence (p < 0.05). Positive association between LST and DHF incidence was significantly correlated in 75% of the cases during non-epidemic months, while no correlation was found during epidemic months. Non-climatic factors are supposed to be at the origin of this discrepancy between seasonality in climate (LST) and DHF incidence during epidemics.

  10. Dengue Hemorrhagic Fever at 60 Years: Early Evolution of Concepts of Causation and Treatment.

    PubMed

    Halstead, Scott B; Cohen, Sanford N

    2015-09-01

    During the decade of the 1960s, the epidemiology of a new dengue disease, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), was described by collaborative research performed by Thai scientists from many institutions and by workers at the U.S. Army's SEATO Medical Research Laboratory in Bangkok, Thailand. Careful clinical and physiological studies provided the initial description of DSS. DSS cases were caused by each of the four dengue viruses (DENV) and not chikungunya (CHIK) virus or DENV 5 and 6, were associated with a secondary-type dengue antibody response in children over the age of 1 year, were associated with a primary antibody response in infants less than 1 year old whose mothers had neutralizing antibodies to all four DENV, were associated more frequently with secondary DENV 2 infections than those due to DENV 1 and 3, and were more common in females than males over the age of 3 years. Robust laboratory methods for growth and recovery of DENV in tissue cultures were introduced. In addition, life-saving principles of fluid and plasma protein resuscitation of hypovolemia were described. Most epidemiological observations made during the decade of the 1960s have been confirmed in the succeeding 45 years. Much contemporary research on pathogenesis fails to address the two distinct immunological antecedents of DHF/DSS.

  11. T Cells and Pathogenesis of Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

    PubMed Central

    Terajima, Masanori; Ennis, Francis A.

    2011-01-01

    We previously hypothesized that increased capillary permeability observed in both hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) may be caused by hantavirus-specific cytotoxic T cells attacking endothelial cells presenting viral antigens on their surface based on clinical observations and in vitro experiments. In HCPS, hantavirus-specific T cell responses positively correlated with disease severity. In HFRS, in one report, contrary to HCPS, T cell responses negatively correlated with disease severity, but in another report the number of regulatory T cells, which are thought to suppress T cell responses, negatively correlated with disease severity. In rat experiments, in which hantavirus causes persistent infection, depletion of regulatory T cells helped infected rats clear virus without inducing immunopathology. These seemingly contradictory findings may suggest delicate balance in T cell responses between protection and immunopathogenesis. Both too strong and too weak T cell responses may lead to severe disease. It is important to clarify the role of T cells in these diseases for better treatment (whether to suppress T cell functions) and protection (vaccine design) which may need to take into account viral factors and the influence of HLA on T cell responses. PMID:21994770

  12. Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever.

    PubMed

    McLay, Lisa; Ansari, Aftab; Liang, Yuying; Ly, Hinh

    2013-02-01

    A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Africa, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies.

  13. Dengue Hemorrhagic Fever at 60 Years: Early Evolution of Concepts of Causation and Treatment

    PubMed Central

    Cohen, Sanford N.

    2015-01-01

    SUMMARY During the decade of the 1960s, the epidemiology of a new dengue disease, dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), was described by collaborative research performed by Thai scientists from many institutions and by workers at the U.S. Army's SEATO Medical Research Laboratory in Bangkok, Thailand. Careful clinical and physiological studies provided the initial description of DSS. DSS cases were caused by each of the four dengue viruses (DENV) and not chikungunya (CHIK) virus or DENV 5 and 6, were associated with a secondary-type dengue antibody response in children over the age of 1 year, were associated with a primary antibody response in infants less than 1 year old whose mothers had neutralizing antibodies to all four DENV, were associated more frequently with secondary DENV 2 infections than those due to DENV 1 and 3, and were more common in females than males over the age of 3 years. Robust laboratory methods for growth and recovery of DENV in tissue cultures were introduced. In addition, life-saving principles of fluid and plasma protein resuscitation of hypovolemia were described. Most epidemiological observations made during the decade of the 1960s have been confirmed in the succeeding 45 years. Much contemporary research on pathogenesis fails to address the two distinct immunological antecedents of DHF/DSS. PMID:26085471

  14. Crimean-Congo Hemorrhagic Fever Virus Clade IV (Asia 1) in Ticks of Western Iran.

    PubMed

    Kayedi, Mohammad Hassan; Chinikar, Sadegh; Mostafavi, Ehsan; Khakifirouz, Sahar; Jalali, Tahmineh; Hosseini-Chegeni, Asadolah; Naghizadeh, Ali; Niedrig, Matthias; Fooks, Anthony R; Shahhosseini, Nariman

    2015-09-01

    Crimean-Congo Hemorrhagic Fever virus (CCHFV) is transmitted through the bite of an infected tick, or by direct contact with CCHFV-infected patients' blood or the products of infected livestock. In 2012, ticks were collected in eight regions of Lorestan Province, Iran. In total, 434 ticks were collected. Reverse transcriptase polymerase chain reaction was used for the detection of CCHFV RNA. Of 434 ticks, 419 (96.6%) ticks were from the family Ixodidae (hard ticks) and 15 (3.5%) ticks were from the family Argasidae (soft ticks). The presence of CCHFV RNA was detected in 29 (6.7%) of 434 ticks. The infected tick species include Hyalomma asiaticum (n = 7, 7.4%), Hyalomma anatolicum (n = 12, 13.2%), Hyalomma marginatum (n = 1, 16.7%), and Rhipicephalus sanguineus (n = 9, 4.3%). These empirical data demonstrated that the majority of CCHFV-positive ticks belonged to the Ixodidae. None of the Argasidae and Haemaphysalis sulcata species was infected with CCHFV. The phylogenetic analyses of the tick-derived CCHFV strains revealed that all 29 viral strains fell in clade IV (Asia 1). The most abundant species of tick collected in this study was R. sanguineus followed by different species of Hyalomma. Given the infection rate among collected ticks, H. marginatum was the most abundant infected tick species (16.7%) followed by H. anatolicum (13.2%), H. asiaticum (7.4%), and R. sanguineus (4.3%).

  15. Pharmacotherapy of Ebola hemorrhagic fever: a brief review of current status and future perspectives.

    PubMed

    Olszanecki, Rafał; Gawlik, Grzegorz

    2014-01-01

    The 2014 outbreak clearly showed that Ebola viruses (EBOV) remain a substantial threat for public health. The mainstay of management of patients with Ebola disease is isolation of patients and use of strict barrier nursing procedures; the present treatment strategies are mainly symptomatic and supportive (fluid resuscitation, antypyretics, antidiarrheal drugs). Currently, there is no approved therapy for Ebola hemorrhagic fever (EHF), however several advanced treatment options were tested in animal models (on non-human primates or rodents). They include use of both symptomatic (e.g. use of tissue factor inhibitors - rhNAPc2, rhAPC - to abolish coagulopathy) and specific antiviral approaches: e.g. monoclonal anti EBOV antibodies (ZMapp, MB-003), phosphorodiamidate morpholino oligomers (PMOs), liposomes containing siRNA (LNP-siRNA:TKM-Ebola) and small molecule inhibitors (e.g. BCX4430, favipiravir). The scope of this article is to briefly review the most promising therapeutics for EHF, based on the data coming from rare clinical reports, studies on animals and results from in vitro models.

  16. The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses

    PubMed Central

    Kuiken, Carla; Thurmond, Jim; Dimitrijevic, Mira; Yoon, Hyejin

    2012-01-01

    Hemorrhagic fever viruses (HFVs) are a diverse set of over 80 viral species, found in 10 different genera comprising five different families: arena-, bunya-, flavi-, filo- and togaviridae. All these viruses are highly variable and evolve rapidly, making them elusive targets for the immune system and for vaccine and drug design. About 55 000 HFV sequences exist in the public domain today. A central website that provides annotated sequences and analysis tools will be helpful to HFV researchers worldwide. The HFV sequence database collects and stores sequence data and provides a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database [Kuiken, C., B. Korber, and R.W. Shafer, HIV sequence databases. AIDS Rev, 2003. 5: p. 52–61]. The database uses an algorithm that aligns each sequence to a species-wide reference sequence. The NCBI RefSeq database [Sayers et al. (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 39, D38–D51.] is used for this; if a reference sequence is not available, a Blast search finds the best candidate. Using this method, sequences in each genus can be retrieved pre-aligned. The HFV website can be accessed via http://hfv.lanl.gov. PMID:22064861

  17. The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses.

    PubMed

    Kuiken, Carla; Thurmond, Jim; Dimitrijevic, Mira; Yoon, Hyejin

    2012-01-01

    Hemorrhagic fever viruses (HFVs) are a diverse set of over 80 viral species, found in 10 different genera comprising five different families: arena-, bunya-, flavi-, filo- and togaviridae. All these viruses are highly variable and evolve rapidly, making them elusive targets for the immune system and for vaccine and drug design. About 55,000 HFV sequences exist in the public domain today. A central website that provides annotated sequences and analysis tools will be helpful to HFV researchers worldwide. The HFV sequence database collects and stores sequence data and provides a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database [Kuiken, C., B. Korber, and R.W. Shafer, HIV sequence databases. AIDS Rev, 2003. 5: p. 52-61]. The database uses an algorithm that aligns each sequence to a species-wide reference sequence. The NCBI RefSeq database [Sayers et al. (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 39, D38-D51.] is used for this; if a reference sequence is not available, a Blast search finds the best candidate. Using this method, sequences in each genus can be retrieved pre-aligned. The HFV website can be accessed via http://hfv.lanl.gov.

  18. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses

    SciTech Connect

    Abraham, Jonathan; Corbett, Kevin D.; Farzan, Michael; Choe, Hyeryun; Harrison, Stephen C.

    2010-08-18

    New World hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1-TfR1 interface clarify the importance of TfR1 residues implicated in New World arenavirus host specificity. Analysis of sequence variation among New World arenavirus GP1s and their host-species receptors, in light of the molecular structure, indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip of the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular New World arenaviruses. We propose that New World arenaviruses that are pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.

  19. A novel AP92-like Crimean-Congo hemorrhagic fever virus strain, Greece.

    PubMed

    Papa, Anna; Chaligiannis, Ilias; Kontana, Natasa; Sourba, Tatiana; Tsioka, Katerina; Tsatsaris, Andreas; Sotiraki, Smaragda

    2014-09-01

    Ticks were collected from various regions of northern Greece and tested for the presence of Crimean-Congo hemorrhagic fever virus (CCHFV) RNA. Human and animal sera were collected in the regions where CCHFV-positive ticks were detected, and they were tested for the presence of IgG antibodies against the virus. A CCHFV strain was detected in Rhipicephalus bursa ticks collected from sheep in Kastoria regional unit, differing by 9.7% at the nucleotide level from the AP92 strain, which was isolated in 1975 in another region of Greece. Up to date, CCHF cases have not been reported in these regions. The human seroprevalence in the area was estimated at 6%, while IgG-positive sheep was detected in two of the four neighboring farms tested. The circulation of this specific CCHFV lineage in Greece, especially in a region where the seroprevalence is high, together with the lack of human CCHF cases, suggests a probable antigenic, but non- or low-pathogenic character of this lineage. Further studies on these strains will increase our knowledge about the role of AP92-like strains in the CCHF epidemiology, which might be useful for drug and vaccine design.

  20. Clinical severity in forecasting platelet to lymphocyte ratio in Crimean-Congo hemorrhagic fever patients.

    PubMed

    Eren, Sevki Hakan; Zengin, Suat; Büyüktuna, Seyit Ali; Gözel, Mustafa Gökhan

    2016-10-01

    Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening disease that develops as a result of infection by a member of the Nairovirus genus of the Bunyaviridae family, and its initial symptoms are not specific. In patients with severe clinical progression, in particular, the neutrophil rate is high, whereas lymphocyte and monocyte levels are low. A total of 149 patients, in whom the diagnosis was confirmed with reverse transcriptase PCR, were included in the study. In order to compare patient clinical progression severity, we divided the patients into two groups. For group 1, Çevik's severity score was used. The patients who had a platelet/lymphocyte ratio (PLR) <41 constituted group 2. Of 149 patients, 20 (13.4 %) were determined as group 1 (Çevik's classification) and 38 (25.5 %) were determined as group 2 (PLR <41). Of 11 deaths, 4 (36.4 %) patients were from group 1 and 7 (63.6 %) were from group 2. This is the first study to our knowledge to analyse the relationship between severity and PLR in patients with CCHF. PLR is a simple laboratory test that can aid in determining the prognosis of individuals with this disease.

  1. Consensus report: Preventive measures for Crimean-Congo Hemorrhagic Fever during Eid-al-Adha festival.

    PubMed

    Leblebicioglu, Hakan; Sunbul, Mustafa; Memish, Ziad A; Al-Tawfiq, Jaffar A; Bodur, Hurrem; Ozkul, Aykut; Gucukoglu, Ali; Chinikar, Sadegh; Hasan, Zahra

    2015-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is endemic in Eurasian countries such as, Turkey, Pakistan, Afghanistan and Iran. CCHF virus is spread by the Hyalomma tick, which is found mainly on cattle and sheep. Muslim countries, in which these animals are sacrificed during Eid-Al-Adha, are among the countries where CCHF is endemic, and it has been observed that CCHF is associated with practices surrounding the Eid-ad-Adha festival. The dates for Eid-Al-Adha drift 10 days earlier in each year according to Georgian calendar. In previous years Eid-al-Adha occurred in autumn-winter months however in the next 10-15 years it will be take place in the summer months when CCHF is more prevalent. This may lead to a rise in the number of cases due to increased dissemination of CCHF virus with uncontrolled animal movements in and between countries. This consensus report focuses on the variable practices regarding animal handling in different regions and possible preventative measures to reduce the incidence of CCHF. Environmental hygiene and personal protection are essential parts of prevention. There is a need for international collaborative preparedness and response plans for prevention and management of CCHF during Eid-Al-Adha in countries where the disease is prevalent.

  2. [Preclinical assay of candid #1 vaccine against Argentine Hemorrhagic Fever made in Argentina].

    PubMed

    Ambrosio, Ana M; Riera, Laura M; Saavedra, María del Carmen; Sottosanti, María J

    2005-01-01

    Candid #1 vaccine against Argentine Hemorrhagic Fever produced in USA versus lots of the same vaccine made in Argentina were compared in guinea pigs regarding safety, immunogenicity and protective efficacy against a challenge with pathogenic Junin virus. Lots No Exp 3, 7A and 8A of Argentine origin as well as lot TSI 5-1-92 from USA were inoculated in guinea pigs of 250-400 g in two consecutive assays. Ten animals inoculated with saline performed as normal controls in each experiment. Parameters studied were: a) temperature; b) body weight; c) neutralizing antibodies to Junin virus; d) response to viral challenge. Animals gained weight and remained normothermic up to the challenge. Guinea pigs that received Candid #1 from any manufacturer elicited neutralizing antibodies to Junin virus (titles from 40 to 81920) and survived to challenge whilst 8/10 animals died in each control group. Data presented demonstrated that Candid #1 vaccines from USA or Argentine manufacturers were equally safe, immunogenic and protective in guinea pigs.

  3. Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of the Congo

    PubMed Central

    Borchert, Matthias; Grein, Thomas; Roth, Cathy; Swanepoel, Robert; Libande, Modeste L.; Talarmin, Antoine; Bertherat, Eric; Muyembe-Tamfum, Jean-Jacques; Tugume, Ben; Colebunders, Robert; Kondé, Kader M.; Pirard, Patricia; Olinda, Loku L.; Rodier, Guénaël R.; Campbell, Patricia; Tomori, Oyewale; Ksiazek, Thomas G.; Rollin, Pierre E.

    2003-01-01

    We conducted two antibody surveys to assess risk factors for Marburg hemorrhagic fever in an area of confirmed Marburg virus transmission in the Democratic Republic of the Congo. Questionnaires were administered and serum samples tested for Marburg-specific antibodies by enzyme-linked immunosorbent assay. Fifteen (2%) of 912 participants in a general village cross-sectional antibody survey were positive for Marburg immunoglobulin G antibody. Thirteen (87%) of these 15 were men who worked in the local gold mines. Working as a miner (odds ratio [OR] 13.9, 95% confidence interval [CI] 3.1 to 62.1) and receiving injections (OR 7.4, 95% CI 1.6 to 33.2) were associated with a positive antibody result. All 103 participants in a targeted antibody survey of healthcare workers were antibody negative. Primary transmission of Marburg virus to humans likely occurred via exposure to a still unidentified reservoir in the local mines. Secondary transmission appears to be less common with Marburg virus than with Ebola virus, the other known filovirus. PMID:14720391

  4. Prevalence of hemorrhagic fever with renal syndrome in Qingdao City, China, 2010–2014

    PubMed Central

    Jiang, Fachun; Zhang, Zhentang; Dong, Liyan; Hao, Bi; Xue, Zaifeng; Ma, Dongqiang; Su, Hang; Wen, Hong-ling; Yu, Hao; Yu, Xue-jie

    2016-01-01

    Hemorrhagic fever with renal syndrome (HFRS) was considered to be transmitted by Apodemus agrarius and Rattus norvegicus, the principal animal hosts of Hantaan virus and Seoul virus, respectively. The aim of this study is to determine the correlation of HFRS incidence with capture rate and hantavirus infection rate of rodent species in Qingdao City, China. We collected HFRS patients’ information and captured field and residential rodents in Qingdao City, China from 2010 to 2014. The correlations of HFRS incidence to rodent capture rate and hantavirus infection rate of rodents were analyzed statistically. The main findings of this study are that the high HFRS incidence (19.3/100,000) is correlated to the capture rate of field Mus musculus (p = 0.011, r = 0.037); but surprisingly it did not correlated to the capture rate of the principal rodent hosts Apodemus agrarius and Rattus norvegicus and the hantavirus infection rate of these rodent species in the field or residential area. These novel findings suggest that Mus musculus, a nontraditional animal host of hantavirus may play an important role in hantavirus transmission in Qingdao City. PMID:27786303

  5. Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Kosovo.

    PubMed

    Fajs, Luka; Jakupi, Xhevat; Ahmeti, Salih; Humolli, Isme; Dedushaj, Isuf; Avšič-Županc, Tatjana

    2014-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic agent that causes severe, life-threatening disease, with a case fatality rate of 10-50%. It is the most widespread tick-borne virus in the world, with cases reported in Africa, Asia and Eastern Europe. CCHFV is a genetically diverse virus. Its genetic diversity is often correlated to its geographical origin. Genetic variability of CCHFV was determined within few endemic areas, however limited data is available for Kosovo. Furthermore, there is little information about the spatiotemporal genetic changes of CCHFV in endemic areas. Kosovo is an important endemic area for CCHFV. Cases were reported each year and the case-fatality rate is significantly higher compared to nearby regions. In this study, we wanted to examine the genetic variability of CCHFV obtained directly from CCHF-confirmed patients, hospitalized in Kosovo from 1991 to 2013. We sequenced partial S segment CCHFV nucleotide sequences from 89 patients. Our results show that several viral variants are present in Kosovo and that the genetic diversity is high in relation to the studied area. We also show that variants are mostly uniformly distributed throughout Kosovo and that limited evolutionary changes have occurred in 22 years. Our results also suggest the presence of a new distinct lineage within the European CCHF phylogenetic clade. Our study provide the largest number of CCHFV nucleotide sequences from patients in 22 year span in one endemic area.

  6. [Prevalence of hepatitis C antibodies in plasma donors for the treatment of Argentine hemorrhagic fever].

    PubMed

    Saavedra, M C; Briggiler, A M; Enría, D; Riera, L; Ambrosio, A M

    1997-01-01

    For Argentine Hemorrhagic Fever, a disease caused by Junin virus (JV), there is an effective treatment, consisting of the transfusion of immune plasma (IP). This plasma is obtained from individuals who have had the disease. Since Hepatitis C virus (HCV) is transmitted parenterally, this study was aimed to estimate the prevalence of anti-HCV in a population of IP donors. In this study, 376 donors (47 females and 329 males) were studied: 95 individuals (24 females and 71 males) who had had FHA but had not received treatment and 88 laboratory workers (57 females and 31 males) who were included as controls. Serum samples were tested by EIA (Abbott, Germany) for HCV, and later confirmed by LIATEK (Organon, Ireland). Antibodies to HCV were detected in 29/376 donors (7.7%), in only 1/95 (1.0%) untreated convalescents of AHF and in 1/ 88 (1.1%) of laboratory workers. Retrospective analysis of the seroconversion for HCV in these individuals demonstrated that in 16/24 donors (66.6%) the infection by HCV was probably associated with the IP transfusion. The data presented herein show how the infection with HCV was disseminated among donors of IP, stressing the risk associated to transfusional practices, and emphasizing the need of vaccination to prevent AHF and also the risk inherent to its treatment.

  7. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

    PubMed Central

    Shao, Junjie; Liang, Yuying; Ly, Hinh

    2015-01-01

    Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens. PMID:26011826

  8. Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever

    PubMed Central

    McLay, Lisa; Ansari, Aftab; Liang, Yuying; Ly, Hinh

    2012-01-01

    A number of arenaviruses are pathogenic for humans, but they differ significantly in virulence. Lassa virus, found in West Afri ca, causes severe hemorrhagic fever (HF), while the other principal Old World arenavirus, lymphocytic choriomeningitis virus, causes mild illness in persons with normal immune function, and poses a threat only to immunocompromised individuals. The New World agents, including Junin, Machupo and Sabia virus, are highly pathogenic for humans. Arenaviral HF is characterized by high viremia and general immune suppression, the mechanism of which is unknown. Studies using viral reverse genetics, cell-based assays, animal models and human genome-wide association analysis have revealed potential mechanisms by which arenaviruses cause severe disease in humans. Each of the four viral gene products (GPC, L polymerase, NP, and Z matrix protein) and several host-cell factors (e.g., α-dystroglycan) are responsible for mediating viral entry, genome replication, and the inhibition of apoptosis, translation and interferon-beta (IFNβ) production. This review summarizes current knowledge of the role of each viral protein and host factor in the pathogenesis of arenaviral HF. Insights from recent studies are being exploited for the development of novel therapies. PMID:23261843

  9. [A case of brucellosis and Crimean-Congo hemorrhagic fever coinfection in an endemic area].

    PubMed

    Karakeçili, Faruk; Çıkman, Aytekin; Akın, Hicran; Gülhan, Barış; Özçiçek, Adalet

    2016-04-01

    Brucellosis, a zoonotic disease which is especially seen in developing countries is still an important public health problem worldwide. Crimean-Congo hemorrhagic fever (CCHF) is another zoonotic disease that transmits to humans by infected tick bites as well as exposure to blood or tissue from infected animals. Both of the diseases are common among persons who live in rural areas and deal with animal husbandry. Since brucellosis usually presents with non-specific clinical symptoms and may easily be confused with many other diseases, the diagnosis of those infections could be delayed or misdiagnosed. In this report, a case of coinfection of brucellosis and CCHF has been presented to emphasize the possibility of association of these infections. A 70-year-old female patient with a history of dealing with animal husbandry in a rural area admitted to our hospital with the complaints of fever, malaise, generalized body and joint pains, and headache. Her complaints had progressed within the past two days. She also reported nausea, vomiting, abdominal pain and bloody diarrhea. She denied any history of tick bites. Her physical examination was significant for the presence of 38.8°C fever, increased bowel sounds and splenomegaly. Laboratory analysis revealed leukopenia, thrombocytopenia and high levels of liver enzymes. The patient was admitted to our service with the prediagnosis of CCHF. Serum sample was sent to the Department of Microbiology Reference Laboratory at Public Health Agency of Turkey for CCHF testing. During patient's hospitalization in service, more detailed history was confronted and it was learned that she had fatigue, loss of appetite, sweating, joint pain, and intermittent fever complaints were continuing within a month and received various antibiotic treatments. The tests for brucellosis were conducted and positive results for Brucella Rose Bengal test, tube agglutination (1/160 titers) and immune capture test with Coombs (1/320 titers) were determined

  10. Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury.

    PubMed

    Shenkar, R; Coulson, W F; Abraham, E

    1994-03-01

    Acute pulmonary injury occurs frequently following hemorrhage and injury. In order to better examine the sequence of events leading to lung injury in this setting, we investigated lung histology as well as in vivo mRNA levels for cytokines with proinflammatory and immunoregulatory properties (IL-1 beta, IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) over the 3 days following hemorrhage and resuscitation. Significant increases in mRNA levels for IL-1 beta, IL-6, IL-10, and IFN-gamma, but not TNF-alpha, were present among intraparenchymal pulmonary mononuclear cells obtained 1 and 3 days after hemorrhage. Among alveolar macrophages, TNF-alpha and IL-1 beta mRNA levels were increased 3 days after hemorrhage. Few changes in cytokine mRNA levels, with the exception of TNF-alpha at 3 days after hemorrhage, were present among peripheral blood mononuclear cells. Histologic examination of lungs from hemorrhaged animals showed no alterations 1 day after hemorrhage, but neutrophil and mononuclear cell infiltrates, edema, intra-alveolar hemorrhage, and fibrin generation were present 3 days after hemorrhage. These results suggest that hemorrhage-induced enhancement of proinflammatory cytokine gene transcription may be an important mechanism contributing to the frequent development of acute lung injury following blood loss and injury.

  11. Severe thrombotic events associated with dengue fever, Brazil.

    PubMed

    da Costa, Paulo Sérgio Gonçalves; Ribeiro, Geyza Machado; Junior, Cleber Soares; da Costa Campos, Lenilton

    2012-10-01

    Dengue fever has been a major problem in hospital settings in Brazil for the past 15 years. The main concern has been the severe forms, i.e., dengue hemorrhagic fever and dengue shock syndrome. Hemorrhagic events of different degrees have also been a major concern. We report five cases of large vein thrombotic events associated with the acute phase of dengue fever, including a previously non-reported case of mesenteric vein thrombosis. Complications such as these could have been overlooked in the diagnosis of dengue fever, given that the major concern is the hemorrhagic event.

  12. Arterial Hypertension and Skin Allergy Are Risk Factors for Progression from Dengue to Dengue Hemorrhagic Fever: A Case Control Study

    PubMed Central

    Teixeira, Maria Glória; Paixão, Enny S.; Costa, Maria da Conceição N.; Cunha, Rivaldo V.; Pamplona, Luciano; Dias, Juarez P.; Figueiredo, Camila A.; Figueiredo, Maria Aparecida A.; Blanton, Ronald; Morato, Vanessa; Barreto, Maurício L.; Rodrigues, Laura C.

    2015-01-01

    Background Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF. Methods A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities. Results There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years. Conclusions Physicians attending patients with dengue fever should keep those with hypertension or skin allergies in health units to monitor progression for early intervention. This would reduce mortality by dengue. PMID:25996882

  13. Genetic Diversity of Crimean Congo Hemorrhagic Fever Virus Strains from Iran

    PubMed Central

    Chinikar, Sadegh; Bouzari, Saeid; Shokrgozar, Mohammad Ali; Mostafavi, Ehsan; Jalali, Tahmineh; Khakifirouz, Sahar; Nowotny, Norbert; Fooks, Anthony R.; Shah-Hosseini, Nariman

    2016-01-01

    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. PMID:27308271

  14. RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Spengler, Jessica R.; Patel, Jenish R.; Chakrabarti, Ayan K.; Zivcec, Marko; García-Sastre, Adolfo; Spiropoulou, Christina F.

    2015-01-01

    ABSTRACT In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative-sense RNA virus with a 5′-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV. IMPORTANCE CCHFV is a tick-borne virus with a significant public health impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I. PMID:26223644

  15. The geographic distribution of cases of Crimean-Congo hemorrhagic fever: Kastamonu, Turkey.

    PubMed

    Aker, Servet; Akıncı, Halil; Kılıçoğlu, Cem; Leblebicioglu, Hakan

    2015-09-01

    The purpose of this study was to analyze the epidemiological characteristics of cases diagnosed with Crimean-Congo Hemorrhagic Fever (CCHF) with the help of Geographic Information Systems (GIS) and to establish an epidemiological risk map. Data for 434 cases diagnosed with CCHF between 01.01.2004 and 31.12.2013 were subjected to statistical analysis SPSS 13.0 software. A digital map of Kastamonu was transferred onto ArcGIS 10.0 software in order to establish a risk map for CCHF. The highest cumulative incidence of CCHF is 41.29/10,000, and in people living at altitudes of 1001-1200 meters. ROC analysis of altitudes above sea level of residences with CCHF cases revealed an area under the curve of 74.5% (95% CI: 0.72-0.76, p<0.05). At a cut-off point of 836.5 meters, sensitivity was 0.74 and specificity 0.76. Cumulative incidence of CCHF was significantly positively correlated with number of animals per head (r=0.76) and area of agricultural land per head (r=0.59) (p<0.05). No significant correlation was determined between cumulative incidence and forested area percentages. This study reveals that both men and women living at more than 836.5 meters above sea level and working in agriculture and animal husbandry are at risk of CCHF between May and July. Detailed examination of the ecology of vector ticks is now needed in order to fully determine the epidemiology of the disease.

  16. Potential impacts of climate variability on dengue hemorrhagic fever in Honduras, 2010.

    PubMed

    Zambrano, L I; Sevilla, C; Reyes-García, S Z; Sierra, M; Kafati, R; Rodriguez-Morales, A J; Mattar, S

    2012-12-01

    Climate change and variability are affecting human health and disease direct or indirectly through many mechanisms. Dengue is one of those diseases that is strongly influenced by climate variability; however its study in Central America has been poorly approached. In this study, we assessed potential associations between macroclimatic and microclimatic variation and dengue hemorrhagic fever (DHF) cases in the main hospital of Honduras during 2010. In this year, 3,353 cases of DHF were reported in the Hospital Escuela, Tegucigalpa. Climatic periods marked a difference of 158% in the mean incidence of cases, from El Niño weeks (-99% of cases below the mean incidence) to La Niña months (+59% of cases above it) (p<0.01). Linear regression showed significantly higher dengue incidence with lower values of Oceanic Niño Index (p=0.0097), higher rain probability (p=0.0149), accumulated rain (p=0.0443) and higher relative humidity (p=0.0292). At a multiple linear regression model using those variables, ONI values shown to be the most important and significant factor found to be associated with the monthly occurrence of DHF cases (r²=0.649; βstandardized=-0.836; p=0.01). As has been shown herein, climate variability is an important element influencing the dengue epidemiology in Honduras. However, it is necessary to extend these studies in this and other countries in the Central America region, because these models can be applied for surveillance as well as for prediction of dengue.

  17. Favipiravir Pharmacokinetics in Nonhuman Primates and Insights for Future Efficacy Studies of Hemorrhagic Fever Viruses.

    PubMed

    Madelain, Vincent; Guedj, Jérémie; Mentré, France; Nguyen, Thi Huyen Tram; Jacquot, Frédéric; Oestereich, Lisa; Kadota, Takumi; Yamada, Koichi; Taburet, Anne-Marie; de Lamballerie, Xavier; Raoul, Hervé

    2017-01-01

    Favipiravir is an RNA polymerase inhibitor that showed strong antiviral efficacy in vitro and in small-animal models of several viruses responsible for hemorrhagic fever (HF), including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in nonhuman primates (NHPs) in order to guide future efficacy studies of favipiravir in large-animal models. Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n = 17) or Mauritian (n = 13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg of body weight twice a day (BID). A pharmacokinetic model was developed to predict the plasma concentrations obtained with different dosing regimens, and the model predictions were compared to the 50% effective concentration (EC50) of favipiravir against several viruses. Favipiravir pharmacokinetics were described by a model accounting for concentration-dependent aldehyde oxidase inhibition. The enzyme-dependent elimination rate increased over time and was higher in NHPs of Mauritian origin than in those of Chinese origin. Maintenance doses of 100 and 120 mg/kg BID in Chinese and Mauritian NHPs, respectively, are predicted to achieve median trough plasma free concentrations above the EC50 for Lassa and Marburg viruses until day 7. For Ebola virus, higher doses are required. After day 7, a 20% dose increase is needed to compensate for the increase in drug clearance over time. These results will help rationalize the choice of dosing regimens in future studies evaluating the antiviral effect of favipiravir in NHPs and support its development against a variety of HF viruses.

  18. Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers.

    PubMed

    Fukushi, Shuetsu; Tani, Hideki; Yoshikawa, Tomoki; Saijo, Masayuki; Morikawa, Shigeru

    2012-10-12

    The family Arenaviridae, genus Arenavirus, consists of two phylogenetically independent groups: Old World (OW) and New World (NW) complexes. The Lassa and Lujo viruses in the OW complex and the Guanarito, Junin, Machupo, Sabia, and Chapare viruses in the NW complex cause viral hemorrhagic fever (VHF) in humans, leading to serious public health concerns. These viruses are also considered potential bioterrorism agents. Therefore, it is of great importance to detect these pathogens rapidly and specifically in order to minimize the risk and scale of arenavirus outbreaks. However, these arenaviruses are classified as BSL-4 pathogens, thus making it difficult to develop diagnostic techniques for these virus infections in institutes without BSL-4 facilities. To overcome these difficulties, antibody detection systems in the form of an enzyme-linked immunosorbent assay (ELISA) and an indirect immunofluorescence assay were developed using recombinant nucleoproteins (rNPs) derived from these viruses. Furthermore, several antigen-detection assays were developed. For example, novel monoclonal antibodies (mAbs) to the rNPs of Lassa and Junin viruses were generated. Sandwich antigen-capture (Ag-capture) ELISAs using these mAbs as capture antibodies were developed and confirmed to be sensitive and specific for detecting the respective arenavirus NPs. These rNP-based assays were proposed to be useful not only for an etiological diagnosis of VHFs, but also for seroepidemiological studies on VHFs. We recently developed arenavirus neutralization assays using vesicular stomatitis virus (VSV)-based pseudotypes bearing arenavirus recombinant glycoproteins. The goal of this article is to review the recent advances in developing laboratory diagnostic assays based on recombinant viral proteins for the diagnosis of VHFs and epidemiological studies on the VHFs caused by arenaviruses.

  19. Structure, Function, and Evolution of the Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein

    PubMed Central

    Carter, Stephen D.; Surtees, Rebecca; Walter, Cheryl T.; Ariza, Antonio; Bergeron, Éric; Nichol, Stuart T.; Hiscox, Julian A.

    2012-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging tick-borne virus of the Bunyaviridae family that is responsible for a fatal human disease for which preventative or therapeutic measures do not exist. We solved the crystal structure of the CCHFV strain Baghdad-12 nucleocapsid protein (N), a potential therapeutic target, at a resolution of 2.1 Å. N comprises a large globular domain composed of both N- and C-terminal sequences, likely involved in RNA binding, and a protruding arm domain with a conserved DEVD caspase-3 cleavage site at its apex. Alignment of our structure with that of the recently reported N protein from strain YL04057 shows a close correspondence of all folds but significant transposition of the arm through a rotation of 180 degrees and a translation of 40 Å. These observations suggest a structural flexibility that may provide the basis for switching between alternative N protein conformations during important functions such as RNA binding and oligomerization. Our structure reveals surfaces likely involved in RNA binding and oligomerization, and functionally critical residues within these domains were identified using a minigenome system able to recapitulate CCHFV-specific RNA synthesis in cells. Caspase-3 cleaves the polypeptide chain at the exposed DEVD motif; however, the cleaved N protein remains an intact unit, likely due to the intimate association of N- and C-terminal fragments in the globular domain. Structural alignment with existing N proteins reveals that the closest CCHFV relative is not another bunyavirus but the arenavirus Lassa virus instead, suggesting that current segmented negative-strand RNA virus taxonomy may need revision. PMID:22875964

  20. Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention

    PubMed Central

    Han, Ziying; Madara, Jonathan J.; Herbert, Andrew; Prugar, Laura I.; Ruthel, Gordon; Lu, Jianhong; Liu, Yuliang; Liu, Wenbo; Liu, Xiaohong; Wrobel, Jay E.; Reitz, Allen B.; Dye, John M.; Harty, Ronald N.; Freedman, Bruce D.

    2015-01-01

    Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg) and arenaviruses (Lassa and Junín viruses), are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1) and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms. PMID:26513362

  1. Severe Hemorrhagic Fever in Strain 13/N Guinea Pigs Infected with Lujo Virus

    PubMed Central

    Bird, Brian H.; Dodd, Kimberly A.; Erickson, Bobbie R.; Albariño, César G.; Chakrabarti, Ayan K.; McMullan, Laura K.; Bergeron, Eric; Ströeher, Ute; Cannon, Deborah; Martin, Brock; Coleman-McCray, JoAnn D.; Nichol, Stuart T.; Spiropoulou, Christina F.

    2012-01-01

    Lujo virus (LUJV) is a novel member of the Arenaviridae family that was first identified in 2008 after an outbreak of severe hemorrhagic fever (HF). In what was a small but rapidly progressing outbreak, this previously unknown virus was transmitted from the critically ill index patient to 4 attending healthcare workers. Four persons died during this outbreak, for a total case fatality of 80% (4/5). The suspected rodent source of the initial exposure to LUJV remains a mystery. Because of the ease of transmission, high case fatality, and novel nature of LUJV, we sought to establish an animal model of LUJV HF. Initial attempts in mice failed, but infection of inbred strain 13/N guinea pigs resulted in lethal disease. A total of 41 adult strain 13/N guinea pigs were infected with either wild-type LUJV or a full-length recombinant LUJV. Results demonstrated that strain 13/N guinea pigs provide an excellent model of severe and lethal LUJV HF that closely resembles what is known of the human disease. All infected animals experienced consistent weight loss (3–5% per day) and clinical illness characterized by ocular discharge, ruffled fur, hunched posture, and lethargy. Uniform lethality occurred by 11–16 days post-infection. All animals developed disseminated LUJV infection in various organs (liver, spleen, lung, and kidney), and leukopenia, lymphopenia, thrombocytopenia, coagulopathy, and elevated transaminase levels. Serial euthanasia studies revealed a temporal pattern of virus dissemination and increasing severity of disease, primarily targeting the liver, spleen, lungs, and lower gastrointestinal tract. Establishing an animal LUJV model is an important first step towards understanding the high pathogenicity of LUJV and developing vaccines and antiviral therapeutic drugs for this highly transmissible and lethal emerging pathogen. PMID:22953019

  2. Crimean-Congo Hemorrhagic Fever Virus-Infected Hepatocytes Induce ER-Stress and Apoptosis Crosstalk

    PubMed Central

    Rodrigues, Raquel; Paranhos-Baccalà, Gláucia; Vernet, Guy; Peyrefitte, Christophe N.

    2012-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed tick-borne member of the Nairovirus genus (Bunyaviridae) with a high mortality rate in humans. CCHFV induces a severe disease in infected patients that includes, among other symptoms, massive liver necrosis and failure. The interaction between liver cells and CCHFV is therefore important for understanding the pathogenesis of this disease. Here, we described the in vitro CCHFV-infection and -replication in the hepatocyte cell line, Huh7, and the induced cellular and molecular response modulation. We found that CCHFV was able to infect and replicate to high titres and to induce a cytopathic effect (CPE). We also observed by flow cytometry and real time quantitative RT-PCR evidence of apoptosis, with the participation of the mitochondrial pathway. On the other hand, we showed that the replication of CCHFV in hepatocytes was able to interfere with the death receptor pathway of apoptosis. Furthermore, we found in CCHFV-infected cells the over-expression of PUMA, Noxa and CHOP suggesting the crosstalk between the ER-stress and mitochondrial apoptosis. By ELISA, we observed an increase of IL-8 in response to viral replication; however apoptosis was shown to be independent from IL-8 secretion. When we compared the induced cellular response between CCHFV and DUGV, a mild or non-pathogenic Nairovirus for humans, we found that the most striking difference was the absence of CPE and apoptosis. Despite the XBP1 splicing and PERK gene expression induced by DUGV, no ER-stress and apoptosis crosstalk was observed. Overall, these results suggest that CCHFV is able to induce ER-stress, activate inflammatory mediators and modulate both mitochondrial and death receptor pathways of apoptosis in hepatocyte cells, which may, in part, explain the role of the liver in the pathogenesis of CCHFV. PMID:22238639

  3. Rapid diagnosis of Argentine hemorrhagic fever by reverse transcriptase PCR-based assay.

    PubMed Central

    Lozano, M E; Enría, D; Maiztegui, J I; Grau, O; Romanowski, V

    1995-01-01

    Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus. This report demonstrates that a reverse transcriptase (RT) PCR-based assay developed in our laboratory to detect Junín virus in whole blood samples is sensitive and specific. The experiments were conducted in a double-blinded manner using 94 clinical samples collected in the area in which AHF is endemic. The RT-PCR-based assay was compared with traditional methodologies, including enzyme-linked immunosorbent assay, plaque neutralization tests, and occasionally viral isolation. The calculated parameters for RT-PCR diagnosis, with seroconversion as the "gold standard," were 98% sensitivity and 76% specificity. It is noteworthy that 94% of the patients with putative false-positive results (RT-PCR positive and no seroconversion detected) exhibited febrile syndromes of undefined etiology. These results could be interpreted to mean that most of those patients with febrile syndromes were actually infected with Junín virus but did not develop a detectable immune response. Furthermore, 8 laboratory-fabricated samples and 25 blood samples of patients outside the area in which AHF is endemic tested in a similar way were disclosed correctly (100% match). The RT-PCR assay is the only laboratory test available currently for the early and rapid diagnosis of AHF. It is sensitive enough to detect the low viremia found during the period in which immune plasma therapy can be used effectively, reducing mortality rates from 30% to less than 1%. PMID:7542268

  4. Systems Pharmacology Uncovers the Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever

    PubMed Central

    Liu, Jianling; Pei, Tianli; Mu, Jiexin; Zheng, Chunli; Chen, Xuetong; Huang, Chao; Fu, Yingxue; Liang, Zongsuo; Wang, Yonghua

    2016-01-01

    Background. Viral hemorrhagic fevers (VHF) are a group of systemic diseases characterized by fever and bleeding, which have posed a formidable potential threat to public health with high morbidity and mortality. Traditional Chinese Medicine (TCM) formulas have been acknowledged with striking effects in treatment of hemorrhagic fever syndromes in China's history. Nevertheless, their accurate mechanisms of action are still confusing. Objective. To systematically dissect the mechanisms of action of Chinese medicinal formula Xijiao Dihuang (XJDH) decoction as an effective treatment for VHF. Methods. In this study, a systems pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, drug targeting, network, and pathway analysis was developed. Results. 23 active compounds of XJDH were obtained and 118 VHF-related targets were identified to have interactions with them. Moreover, systematic analysis of drug-target network and the integrated VHF pathway indicate that XJDH probably acts through multiple mechanisms to benefit VHF patients, which can be classified as boosting immune system, restraining inflammatory responses, repairing the vascular system, and blocking virus spread. Conclusions. The integrated systems pharmacology method provides precise probe to illuminate the molecular mechanisms of XJDH for VHF, which will also facilitate the application of traditional medicine in modern medicine. PMID:27239215

  5. Acute intracranial hemorrhage secondary to thrombocytopenia: CT appearances unaffected by absence of clot retraction

    SciTech Connect

    Pierce, J.N.; Taber, K.H.; Hayman, L.A. )

    1994-02-01

    To describe the in vivo CT appearance of acute intracerebral blood clots formed from anemic platelet-depleted blood. Three patients with intracerebral hemorrhage secondary only to thrombocytopenia were examined with CT within 2 1/2 hours after the onset of clinical symptoms. There were no unusual CT features found in the intracerebral hemorrhages of patients with only thrombocytopenia. Specifically, a hyperdense zone(s) surrounded by areas of decreased density was identified. Clot retraction (which cannot occur in patients with severe thrombocytopenia) is not necessary for the CT appearance of acute intracerebral hemorrhage. 22 refs., 3 figs., 1 tab.

  6. Acute rheumatic fever outbreak in southern central European country.

    PubMed

    Kočevar, Urška; Toplak, Nataša; Kosmač, Blaž; Kopač, Luka; Vesel, Samo; Krajnc, Natalija; Homan, Matjaž; Rus, Rina; Avčin, Tadej

    2017-01-01

    A decline in the incidence of acute rheumatic fever (ARF) in developed countries over the past century can be attributed to the improved public hygiene and to widespread use of antibiotics. ARF seemed to be a rare disease in southern central European country, Slovenia, up to 2010 when we noticed an increase in the number of patients with ARF. In order to assess the current incidence of ARF, we performed a retrospective study of all patients with ARF treated at the University Children's Hospital Ljubljana from January 2008 until the end of December 2014. In a period of 7 years, 19 patients with ARF were identified. The estimated annual incidence of ARF during the study period was 1.25 cases per 100,000 children. Carditis was present in all patients, arthritis in 37 % and Sydenham chorea in 32 %.

  7. Early Blood Pressure Lowering Does Not Reduce Growth of Intraventricular Hemorrhage following Acute Intracerebral Hemorrhage: Results of the INTERACT Studies

    PubMed Central

    Chan, Edward; Anderson, Craig S.; Wang, Xia; Arima, Hisatomi; Saxena, Anubhav; Moullaali, Tom J.; Delcourt, Candice; Wu, Guojun; Wang, Jinchao; Chen, Guofang; Lavados, Pablo M.; Stapf, Christian; Robinson, Thompson; Chalmers, John

    2016-01-01

    Background Intraventricular hemorrhage (IVH) extension is common following acute intracerebral hemorrhage (ICH) and is associated with poor prognosis. Aim To determine whether intensive blood pressure (BP)-lowering therapy reduces IVH growth. Methods Pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and INTERACT2) computed tomography (CT) substudies; multicenter, open, controlled, randomized trials of patients with acute spontaneous ICH and elevated systolic BP, randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) BP management. Participants had blinded central analyses of baseline and 24-hour CT. Association of BP lowering to IVH growth was assessed in analysis of covariance. Results There was no significant difference in adjusted mean IVH growth following intensive (n = 228) compared to guideline-recommended (n = 228) BP treatment (1.6 versus 2.2 ml, respectively; p = 0.56). Adjusted mean IVH growth was nonsignificantly greater in patients with a mean achieved systolic BP ≥160 mm Hg over 24 h (3.94 ml; p trend = 0.26). Conclusions Early intensive BP-lowering treatment had no clear effect on IVH in acute ICH. PMID:27603933

  8. Dengue fever (image)

    MedlinePlus

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  9. Rift Valley fever vaccines

    PubMed Central

    Ikegami, Tetsuro; Makino, Shinji

    2009-01-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a tripartite RNA genome. RVFV is transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases, whereas ruminants experience abortions during outbreak. Effective vaccination of both humans and ruminants is the best approach to control Rift Valley fever. This article summarizes the development of inactivated RVFV vaccine, live attenuated vaccine, and other new generation vaccines. PMID:19837291

  10. Intracranial chordoma presenting as acute hemorrhage in a child: Case report and literature review

    PubMed Central

    Moore, Kenneth A.; Bohnstedt, Bradley N.; Shah, Sanket U.; Abdulkader, Marwah M.; Bonnin, Jose M.; Ackerman, Laurie L.; Shaikh, Kashif A.; Kralik, Stephen F.; Shah, Mitesh V.

    2015-01-01

    Background: Chordomas are rare, slow-growing malignant neoplasms derived from remnants of the embryological notochord. Pediatric cases comprise only 5% of all chordomas, but more than half of the reported pediatric chordomas are intracranial. For patients of all ages, intracranial chordomas typically present with symptoms such as headaches and progressive neurological deficits occurring over several weeks to many years as they compress or invade local structures. There are only reports of these tumors presenting acutely with intracranial hemorrhage in adult patients. Case Description: A 10-year-old boy presented with acute onset of headache, emesis, and diplopia. Head computed tomography and magnetic resonance imaging of brain were suspicious for a hemorrhagic mass located in the left petroclival region, compressing the ventral pons. The mass was surgically resected and demonstrated acute intratumoral hemorrhage. Pathologic examination was consistent with chordoma. Conclusion: There are few previous reports of petroclival chordomas causing acute intracranial hemorrhage. To the authors’ knowledge, this is the first case of a petroclival chordoma presenting as acute intracranial hemorrhage in a pediatric patient. Although uncommon, it is important to consider chordoma when evaluating a patient of any age presenting with a hemorrhagic lesion of the clivus. PMID:25949851

  11. Neurogenic Fever after Acute Traumatic Spinal Cord Injury: A Qualitative Systematic Review

    PubMed Central

    Savage, Katherine E.; Oleson, Christina V.; Schroeder, Gregory D.; Sidhu, Gursukhman S.; Vaccaro, Alexander R.

    2016-01-01

    Study Design  Systematic review. Objective  To determine the incidence, pathogenesis, and clinical outcomes related to neurogenic fevers following traumatic spinal cord injury (SCI). Methods  A systematic review of the literature was performed on thermodysregulation secondary to acute traumatic SCI in adult patients. A literature search was performed using PubMed (MEDLINE), Cochrane Central Register of Controlled Trials, and Scopus. Using strict inclusion and exclusion criteria, seven relevant articles were obtained. Results  The incidence of fever of all origins (both known and unknown) after SCI ranged from 22.5 to 71.7% with a mean incidence of 50.6% and a median incidence of 50.0%. The incidence of fever of unknown origin (neurogenic fever) ranged from 2.6 to 27.8% with a mean incidence of 8.0% and a median incidence of 4.7%. Cervical and thoracic spinal injuries were more commonly associated with fever than lumbar injuries. In addition, complete injuries had a higher incidence of fever than incomplete injuries. The pathogenesis of neurogenic fever after acute SCI is not thoroughly understood. Conclusion  Neurogenic fevers are relatively common following an acute SCI; however, there is little in the scientific literature to help physicians prevent or treat this condition. The paucity of research underscored by this review demonstrates the need for further studies with larger sample sizes, focusing on incidence rate, clinical outcomes, and pathogenesis of neurogenic fever following acute traumatic SCI. PMID:27556002

  12. Experimental Vector Incompetence of a Soft Tick, Ornithodoros sonrai (Acari: Argasidae), for Crimean-Congo Hemorrhagic Fever Virus

    DTIC Science & Technology

    1993-01-01

    hemorrhagic fever ( CCHF ) virus (IbAr 10200 strain). The mean viral titer Wof mouse blood at the time of tick feeding was 1)0:12 plaque-forming units (PFU...per ml. N Samples of ticks were assayed on 12 occasions between days 0 and 31 after the viremic blood meal. Mean CCHF viral titers were 102 A PFU per...more days. Ticks were allowed to feed on sets of three naive suckling mice on days 0, 2, 5, 8, 11, 14, 21, and 28 after the viremic blood meal, but CCHF

  13. Emergence of Crimean-Congo hemorrhagic fever in Amreli District of Gujarat State, India, June to July 2013.

    PubMed

    Yadav, Pragya D; Gurav, Yogesh K; Mistry, Madhulika; Shete, Anita M; Sarkale, Prasad; Deoshatwar, Avinash R; Unadkat, Vishwa B; Kokate, Prasad; Patil, Deepak Y; Raval, Dinkar K; Mourya, Devendra T

    2014-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) etiology was detected in a family cluster (nine cases, including two deaths) in the village of Karyana, Amreli District, and also a fatal case in the village of Undra, Patan District, in Gujarat State, India. Anti-CCHFV IgG antibodies were detected in domestic animals from Karyana and adjoining villages. Hyalomma ticks from households were found to be positive for CCHF viral RNA. This confirms the emergence of CCHFV in new areas and the wide spread of this disease in Gujarat State.

  14. Probable Crimean-Congo hemorrhagic fever virus transmission occurred after aerosol-generating medical procedures in Russia: nosocomial cluster.

    PubMed

    Pshenichnaya, Natalia Yurievna; Nenadskaya, Svetlana Alexeevna

    2015-04-01

    We report here a fatal case of laboratory confirmed Crimean-Congo hemorrhagic fever (CCHF), which caused nosocomial infection in eight health care workers (HCWs), who had provided medical care for the patient. All the HCWs survived. The report demonstrates that airborne transmission of CCHF is a real risk, at least when the CCHF patient is in a ventilator. During performance of any aerosol-generating medical procedures for any CCHF patient airborne precautions should always be added to standard precautions, in particular, airway protective N95 mask or equivalent standard, eye protection, single airborne precaution room, or a well-ventilated setting.

  15. Acute rheumatic fever in adults: case report together with an analysis of 25 patients with acute rheumatic fever.

    PubMed

    Kasitanon, Nuntana; Sukitawut, Waraporn; Louthrenoo, Worawit

    2009-07-01

    We reported the oldest acute rheumatic fever (ARF) patient with initial attack at the age of 90 years and experience with ARF in adults in 20 years of observation. The case files of all ARF patients treated by rheumatology unit, Chiang Mai University, were reviewed. Demographic data and clinical profile were recorded and compared between patients with initial attack and patients with recurrent attack. A total of 25 patients with ARF were included. There was no different incidence of arthritis and carditis between two groups. Initial attack patients have higher incidence of prolonged PR-interval (67 vs. 12%, P = 0.049) and longer duration of admission to diagnosis (5 vs. 2 days, P = 0.05). Thirty percent presented initial attack after 30 years of age. ARF is more common in adults than previously recognized. Therefore, clinicians should be aware of this condition and include it in their differential diagnosis of the febrile patients with arthritis.

  16. Lymphocyte surface markers in acute rheumatic fever and post-streptococcal acute glomerulonephritis.

    PubMed Central

    Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H

    1977-01-01

    Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301

  17. Acute Rheumatic Fever: An Evidence-Based Approach To Diagnosis And Initial Management.

    PubMed

    Khanna, Kajal; Liu, Deborah R

    2016-08-01

    Acute rheumatic fever is an inflammatory reaction involving the joints, heart, and nervous system that occurs after a group A streptococcal infection. It typically presents as a febrile illness with clinical manifestations that could include arthritis, carditis, skin lesions, or abnormal movements. Of these, the cardiac manifestations of acute rheumatic fever are most concerning, as children may present in acute heart failure and may go on to develop valvular insufficiency or stenosis. Because this is a rare presentation to emergency departments in developed countries, it is crucial for clinicians to keep a broad differential when presented with clinical presentations suspicious for acute rheumatic fever. This issue focuses on the clinical evaluation and treatment of patients with acute rheumatic fever by offering a thorough review of the literature on diagnosis and recommendations on appropriate treatment.

  18. Association between trauma and acute hemorrhage of cavernous malformations in children: report of 3 cases.

    PubMed

    Fanous, Andrew A; Jowdy, Patrick K; Lipinski, Lindsay J; Balos, Lucia L; Li, Veetai

    2016-09-01

    OBJECTIVE Cavernous hemangiomas are benign congenital vascular abnormalities. Intracerebral cavernous hemangiomas have an appreciable risk of spontaneous hemorrhage. Little is known as to whether head trauma increases the risk of bleeding for these lesions. In this study, the authors present a case series of 3 patients with posttraumatic nonspontaneous hemorrhage of intracerebral cavernous malformations (CMs). For the first time, to the authors' knowledge, they propose that trauma might constitute a risk factor for acute hemorrhage in intracerebral cavernomas. METHODS The authors reviewed the charts of all patients with a new diagnosis of intracerebral cavernoma at their pediatric hospital between 2010 and 2014. Patients with a history of head trauma prior to presentation were subsequently studied to identify features common to these posttraumatic, hemorrhage-prone lesions. RESULTS A history of head trauma was identified in 3 of 19 cases. These 3 patients presented with seizures and/or headaches and were found to have acute hemorrhage within a cavernous hemangioma. None of these patients had any history of abnormal neurological symptoms. All 3 abnormal vascular lesions had associated developmental venous anomalies (DVAs). The 3 patients underwent resection of their respective vascular abnormalities, and the diagnosis of cavernous hemangioma was confirmed with postsurgical tissue pathology. All 3 patients had complete resolution of symptoms following complete excision of their lesions. CONCLUSIONS Trauma may represent a risk factor for acute hemorrhage in patients with CMs. The presence of associated DVAs may represent a risk factor for posttraumatic hemorrhage of cavernomas. Excision should be considered in such cases, if feasible.

  19. YouTube videos as a source of medical information during the Ebola hemorrhagic fever epidemic.

    PubMed

    Nagpal, Sajan Jiv Singh; Karimianpour, Ahmadreza; Mukhija, Dhruvika; Mohan, Diwakar; Brateanu, Andrei

    2015-01-01

    The content and quality of medical information available on video sharing websites such as YouTube is not known. We analyzed the source and quality of medical information about Ebola hemorrhagic fever (EHF) disseminated on YouTube and the video characteristics that influence viewer behavior. An inquiry for the search term 'Ebola' was made on YouTube. The first 100 results were arranged in decreasing order of "relevance" using the default YouTube algorithm. Videos 1-50 and 51-100 were allocated to a high relevance (HR), and a low relevance (LR) video group, respectively. Multivariable logistic regression models were used to assess the predictors of a video being included in the HR vs. LR groups. Fourteen videos were excluded because they were parodies, songs or stand-up comedies (n = 11), not in English (n = 2) or a remaining part of a previous video (n = 1). Two scales, the video information and quality and index and the medical information and content index (MICI) assessed the overall quality, and the medical content of the videos, respectively. There were no videos from hospitals or academic medical centers. Videos in the HR group had a higher median number of views (186,705 vs. 43,796, p < 0.001), more 'likes' (1119 vs. 224, p < 0.001), channel subscriptions (208 vs. 32, p < 0.001), and 'shares' (519 vs. 98, p < 0.001). Multivariable logistic regression showed that only the 'clinical symptoms' component of the MICI scale was associated with a higher likelihood of a video being included in the HR vs. LR group.(OR 1.86, 95 % CI 1.06-3.28, p = 0.03). YouTube videos presenting clinical symptoms of infectious diseases during epidemics are more likely to be included in the HR group and influence viewers behavior.

  20. Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.

    PubMed

    Bente, Dennis A; Forrester, Naomi L; Watts, Douglas M; McAuley, Alexander J; Whitehouse, Chris A; Bray, Mike

    2013-10-01

    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

  1. Spatiotemporal Trends and Climatic Factors of Hemorrhagic Fever with Renal Syndrome Epidemic in Shandong Province, China

    PubMed Central

    Li, Yan-Li; Song, Shao-Xia; Zhang, Wen-Yi; Qian, Quan; Li, Ya-Pin; Wei, Lan; Wang, Zhi-Qiang; Yang, Hong; Cao, Wu-Chun

    2010-01-01

    Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantaviruses. It is endemic in all 31 provinces, autonomous regions, and metropolitan areas in mainland China where human cases account for 90% of the total global cases. Shandong Province is among the most serious endemic areas. HFRS cases in Shandong Province were first reported in Yutai County in 1968. Since then, the disease has spread across the province, and as of 2005, all 111 counties were reported to have local human infections. However, causes underlying such rapid spread and wide distribution remain less well understood. Methods and Findings Here we report a spatiotemporal analysis of human HFRS cases in Shandong using data spanning 1973 to 2005. Seasonal incidence maps and velocity vector maps were produced to analyze the spread of HFRS over time in Shandong Province, and a panel data analysis was conducted to explore the association between HFRS incidence and climatic factors. Results show a rapid spread of HFRS from its epicenter in Rizhao, Linyi, Weifang Regions in southern Shandong to north, east, and west parts of the province. Based on seasonal shifts of epidemics, three epidemic phases were identified over the 33-year period. The first phase occurred between 1973 and 1982 during which the foci of HFRS was located in the south Shandong and the epidemic peak occurred in the fall and winter, presenting a seasonal characteristic of Hantaan virus (HTNV) transmission. The second phase between 1983 and 1985 was characterized by northward and westward spread of HFRS foci, and increases in incidence of HFRS in both fall-winter and spring seasons. The human infections in the spring reflected a characteristic pattern of Seoul virus (SEOV) transmission. The third phase between 1986 and 2005 was characterized by the northeast spread of the HFRS foci until it covered all counties, and the HFRS incidence in the fall-winter season decreased while it remained high in the

  2. Review of Elephant Endotheliotropic Herpesviruses and Acute Hemorrhagic Disease

    PubMed Central

    Long, Simon Y.; Latimer, Erin M.; Hayward, Gary S.

    2016-01-01

    More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses—EEHV2, EEHV3, EEHV6, and EEHV7—found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species. PMID:26912715

  3. Leukoaraiosis, intracerebral hemorrhage, and functional outcome after acute stroke thrombolysis

    PubMed Central

    Kongbunkiat, Kannikar; Wilson, Duncan; Kasemsap, Narongrit; Tiamkao, Somsak; Jichi, Fatima; Palumbo, Vanessa; Hill, Michael D.; Buchan, Alastair M.; Jung, Simon; Mattle, Heinrich P.; Henninger, Nils

    2017-01-01

    Objective: To perform a systematic review and pooled meta-analysis of published studies to assess whether the presence of leukoaraiosis on neuroimaging before treatment with thrombolysis (IV or intra-arterial) is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome. Methods: We included studies of patients with acute ischemic stroke, treated with IV or intra-arterial thrombolysis, which assessed functional outcome (3-month modified Rankin Scale [mRS]) or sICH in relation to leukoaraiosis on pretreatment neuroimaging (CT or MRI). We used random-effects models to calculate pooled relative risks (RR) of sICH and poor functional outcome (mRS ≥ 2) for any vs no leukoaraiosis (using any rating scale) and for no to mild vs moderate to severe leukoaraiosis (using the Van Swieten or Fazekas Schmidt scale). Results: We identified 15 studies (total n = 6,967). For sICH outcome, the RR was 1.65 (n = 5,551; 95% confidence interval [CI] 1.26–2.16, p = 0.001) with an absolute risk (AR) increase of 2.5% for any leukoaraiosis vs none. The RR was 2.4 (n = 4,192; 95% CI 1.83–3.14, p = 0.001) with an AR increase of 6.2% for moderate to severe vs no to mild leukoaraiosis. For poor functional outcome; the RR was 1.30 (n = 3,401; 95% CI 1.19–1.42, p = 0.001) with an AR increase of 15.4% for any leukoaraiosis vs none. The RR was 1.31 (n = 3,659; 95% CI 1.22–1.42, p = 0.001) with an AR increase of 17.5% for moderate to severe vs no to mild leukoaraiosis. No statistical heterogeneity was noted for any of the analyses. Conclusions: Leukoaraiosis presence and severity are consistently associated with an increased risk of sICH and poor functional outcome after IV or intra-arterial thrombolysis for acute ischemic stroke. PMID:28130468

  4. High Genetic Diversity and Adaptive Potential of Two Simian Hemorrhagic Fever Viruses in a Wild Primate Population

    PubMed Central

    Weiler, Andrea; Sibley, Samuel D.; Dinis, Jorge M.; Bergman, Zachary; Nelson, Chase W.; Correll, Michael; Gleicher, Michael; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin; Kuhn, Jens H.; Hughes, Austin L.; Friedrich, Thomas C.; Goldberg, Tony L.; O'Connor, David H.

    2014-01-01

    Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 106–107 RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses. PMID:24651479

  5. High genetic diversity and adaptive potential of two simian hemorrhagic fever viruses in a wild primate population.

    PubMed

    Bailey, Adam L; Lauck, Michael; Weiler, Andrea; Sibley, Samuel D; Dinis, Jorge M; Bergman, Zachary; Nelson, Chase W; Correll, Michael; Gleicher, Michael; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin; Kuhn, Jens H; Hughes, Austin L; Friedrich, Thomas C; Goldberg, Tony L; O'Connor, David H

    2014-01-01

    Key biological properties such as high genetic diversity and high evolutionary rate enhance the potential of certain RNA viruses to adapt and emerge. Identifying viruses with these properties in their natural hosts could dramatically improve disease forecasting and surveillance. Recently, we discovered two novel members of the viral family Arteriviridae: simian hemorrhagic fever virus (SHFV)-krc1 and SHFV-krc2, infecting a single wild red colobus (Procolobus rufomitratus tephrosceles) in Kibale National Park, Uganda. Nearly nothing is known about the biological properties of SHFVs in nature, although the SHFV type strain, SHFV-LVR, has caused devastating outbreaks of viral hemorrhagic fever in captive macaques. Here we detected SHFV-krc1 and SHFV-krc2 in 40% and 47% of 60 wild red colobus tested, respectively. We found viral loads in excess of 10(6)-10(7) RNA copies per milliliter of blood plasma for each of these viruses. SHFV-krc1 and SHFV-krc2 also showed high genetic diversity at both the inter- and intra-host levels. Analyses of synonymous and non-synonymous nucleotide diversity across viral genomes revealed patterns suggestive of positive selection in SHFV open reading frames (ORF) 5 (SHFV-krc2 only) and 7 (SHFV-krc1 and SHFV-krc2). Thus, these viruses share several important properties with some of the most rapidly evolving, emergent RNA viruses.

  6. Atmospheric Moisture Variability and Transmission of Hemorrhagic Fever with Renal Syndrome in Changsha City, Mainland China, 1991–2010

    PubMed Central

    Li, Xiu-Jun; Tong, Shi-Lu; Gao, Li-Dong; Qin, Jian-Xin; Lin, Xiao-Ling; Liu, Hai-Ning; Zhang, Xi-Xing

    2013-01-01

    Background The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by environmental determinants. This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome (HFRS) for the period of 1991–2010 in Changsha, China. Methods and Findings Wavelet analyses were performed by using monthly reported time series data of HFRS cases to detect and quantify the periodicity of HFRS. A generalized linear model with a Poisson distribution and a log link model were used to quantify the relationship between climate and HFRS cases, highlighting the importance of moisture conditions. There was a continuous annual oscillation mode and multi-annual cycle around 3–4 years from 1994 to 1999. There was a significant association of HFRS incidence with moisture conditions and the Multivariate El Niño–Southern Oscillation Index (MEI). Particularly, atmospheric moisture has a significant effect on the propagation of HFRS; annual incidence of HFRS was positively correlated with annual precipitation and annual mean absolute humidity. Conclusions The final model had good accuracy in forecasting the occurrence of HFRS and moisture condition can be used in disease surveillance and risk management to provide early warning of potential epidemics of this disease. PMID:23755316

  7. Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model▿ †

    PubMed Central

    Bente, Dennis A.; Alimonti, Judie B.; Shieh, Wun-Ju; Camus, Gaëlle; Ströher, Ute; Zaki, Sherif; Jones, Steven M.

    2010-01-01

    Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation. PMID:20739514

  8. Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin.

    PubMed

    de Castro, Reynaldo Angelo C; de Castro, Jo-Anne A; Barez, Marie Yvette C; Frias, Melchor V; Dixit, Jitendra; Genereux, Maurice

    2007-04-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue hemorrhagic fever (DHF). An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF (see Saito et al., 2004, Clin Exp Immunol 138: 299-303; Mitrakul, 1979, Am J Trop Med Hyg 26: 975-984; and Boonpucknavig, 1979, Am J Trop Med Hyg 28: 881-884). The interim data of two randomized placebo controlled trials in patients (N = 47) meeting WHO criteria for dengue hemorrhagic fever (DHF) with severe thrombocytopenia (platelets < or = 50,000/mm(3)) reveal that the increase in platelet count with anti-D immune globulin (WinRho SDF), 50 microg/kg (250 IU/kg) intravenously is more brisk than the placebo group. The mean maximum platelet count of the anti-D-treated group at 48 hours was 91,500/mm(3) compared with 69,333/mm(3) in the placebo group. 75% of the anti-D-treated group demonstrated an increase of platelet counts > or = 20,000 compared with only 58% in the placebo group. These data suggest that treatment of severe thrombocytopenia accompanying DHF with anti-D may be a useful and safe therapeutic option.

  9. Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome: case report.

    PubMed

    Grove, Jessica N; Branco, Luis M; Boisen, Matt L; Muncy, Ivana J; Henderson, Lee A; Schieffellin, John S; Robinson, James E; Bangura, James J; Fonnie, Mbalu; Schoepp, Randal J; Hensley, Lisa E; Seisay, Alhassan; Fair, Joseph N; Garry, Robert F

    2011-06-20

    Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas.

  10. Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome: Case Report

    PubMed Central

    2011-01-01

    Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas. PMID:21689444

  11. Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy

    PubMed Central

    Harada, Yukinori; Hara, Yuuta

    2017-01-01

    Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE. PMID:28090058

  12. Herpes Simplex Encephalitis Complicated by Cerebral Hemorrhage during Acyclovir Therapy.

    PubMed

    Harada, Yukinori; Hara, Yuuta

    2017-01-01

    Herpes simplex encephalitis (HSE) can be complicated by adverse events in the acute phase. We herein present the case of a 71-year-old woman with HSE complicated by cerebral hemorrhage. She presented with acute deterioration of consciousness and fever and was diagnosed with HSE based on the detection of herpes simplex virus-1 in the cerebrospinal fluid by a polymerase chain reaction. The cerebral hemorrhage developed during acyclovir therapy; however, its diagnosis was delayed for 2 days. After the conservative treatment of the cerebral hemorrhage, the patient made a near-complete recovery. Cerebral hemorrhage should be considered as an acute-phase complication of HSE.

  13. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.

    PubMed

    Abraham, E; Carmody, A; Shenkar, R; Arcaroli, J

    2000-12-01

    Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.

  14. Acute rheumatic fever in First Nations communities in northwestern Ontario

    PubMed Central

    Gordon, Janet; Kirlew, Mike; Schreiber, Yoko; Saginur, Raphael; Bocking, Natalie; Blakelock, Brittany; Haavaldsrud, Michelle; Kennedy, Christine; Farrell, Terri; Douglas, Lloyd; Kelly, Len

    2015-01-01

    Abstract Objective To document a case series of 8 young First Nations patients diagnosed with acute rheumatic fever (ARF), a preventable disease that resulted in the death of 2 patients, in northwestern Ontario in the context of late diagnosis, overcrowded housing, and inadequate public health response. Design Retrospective case series over an 18-month period. Setting Remote First Nations communities in northwestern Ontario. Participants Eight patients with ARF. Main outcome measures Incidence, mortality, residual rheumatic heart disease, time to diagnosis, barriers to diagnosis and treatment, housing situation of patients, patient demographic characteristics (age, sex), and investigation results. Results The incidence of ARF in this population was 21.3 per 100 000, which is 75 times greater than the overall Canadian estimated incidence. The average patient age was 9.4 years. Most cases developed joint findings, and 5 of the surviving patients had rheumatic heart disease when they received echocardiography. The average time to diagnosis was 88 days. Two 4-year-old children died from ARF. Most patients lived in inadequate and crowded housing. Conclusion This rare disease still exists in remote First Nations communities. These communities demonstrate an incidence equal to that in aboriginal communities in Australia and New Zealand, which have among the highest international incidence of ARF. Primordial prevention, including improved on-reserve housing, is urgently needed. Case detection and ongoing surveillance for primary and secondary prophylaxis requires a well resourced regional strategy. PMID:26759842

  15. The role of viral agents in aetiopathogenesis of acute rheumatic fever.

    PubMed

    Olgunturk, Rana; Okur, Ilyas; Cirak, Meltem Y; Oguz, Ayse Deniz; Akalin, Nursel; Turet, Sevgi; Tunaoglu, Sedef

    2011-01-01

    The reason why abnormal immune response exists in acute rheumatic fever is not exactly explained. The influence of co-pathogens like certain viruses were mentioned regarding the initiation of the immunological reaction in acute rheumatic fever patients by several authors since 1970. This study was designed to find the role or effect of some viral infections in the development of rheumatic fever. In this study, 47 cases with acute rheumatic fever (acute rheumatic arthritis, acute rheumatic carditis, and chorea), 20 cases with chronic rheumatic fever, 20 cases with streptococcal pharyngitis, and 20 healthy age- and gender-matched control cases were involved. Serological and molecular tests were made including hepatitis B virus, hepatitis C virus, rubella virus, herpes simplex virus (HSV group 1), and Epstein-Barr virus (EBV). HBsAg, rubella IgM and EBV IgM positivity were not seen in any of patients with rheumatic fever. Although antiHBs seropositivity was higher in the control group, it was not statistically significant (p > 0.05). There was no difference in rubella IgG, HSV IgM seropositivity, either (p > 0.05). EBV DNA was searched by the polymerase chain reaction technique; due to the latent nature of the virus, no significant difference was found between the control group and the other groups (p > 0.05). In this study, no positive correlation could be found to support the synergism theories regarding the streptoccocus infection and viral infections in the development of acute rheumatic fever. Only EBV DNA positivity was found in all acute rheumatic fever cases but not in the control group may lead to further studies with larger series of patients.

  16. Fever

    MedlinePlus

    A fever is a body temperature that is higher than normal. It is not an illness. It is part of your body's defense against infection. Most bacteria ... cause infections do well at the body's normal temperature (98.6 F). A slight fever can make ...

  17. Fever

    MedlinePlus

    ... Shortfall Questionnaire FeverA fever is defined as a temperature 1° or more above the normal 98.6°. Minor infections may cause mild or short-term temperature elevations. Temperatures of 103° and above are considered ...

  18. Assessment of Recombination in the S-segment Genome of Crimean-Congo Hemorrhagic Fever Virus in Iran

    PubMed Central

    Chinikar, Sadegh; Shah-Hosseini, Nariman; Bouzari, Saeid; Shokrgozar, Mohammad Ali; Mostafavi, Ehsan; Jalali, Tahmineh; Khakifirouz, Sahar; Groschup, Martin H; Niedrig, Matthias

    2016-01-01

    Background: Crimean-Congo Hemorrhagic Fever Virus (CCHFV) belongs to genus Nairovirus and family Bunyaviridae. The main aim of this study was to investigate the extent of recombination in S-segment genome of CCHFV in Iran. Methods: Samples were isolated from Iranian patients and those available in GenBank, and analyzed by phylogenetic and bootscan methods. Results: Through comparison of the phylogenetic trees based on full length sequences and partial fragments in the S-segment genome of CCHFV, genetic switch was evident, due to recombination event. Moreover, evidence of multiple recombination events was detected in query isolates when bootscan analysis was used by SimPlot software. Conclusion: Switch of different genomic regions between different strains by recombination could contribute to CCHFV diversification and evolution. The occurrence of recombination in CCHFV has a critical impact on epidemiological investigations and vaccine design. PMID:27047968

  19. Molecular and cell biology of the prototypic arenavirus LCMV: implications for understanding and combating hemorrhagic fever arenaviruses.

    PubMed

    de la Torre, Juan C

    2009-09-01

    Arenaviruses merit interest as experimental model systems to study virus-host interactions and as clinically important human pathogens. Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever (HF) in humans. In addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen. Moreover, arenaviruses pose a biodefense threat. No licensed arenavirus vaccines are available, and current therapy is limited to the use of ribavirin, which is only partially effective and associated with significant side effects. The development of arenavirus reverse genetics systems has made it possible to manipulate the arenavirus genome, which is contributing to significant progress in understanding arenavirus molecular and cell biology, as well as arenavirus-host interactions underlying arenavirus-induced HF disease in humans. This, in turn, should facilitate the development of novel both vaccines and antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced arenavirus infections.

  20. [The manifestation of necrophagy in the populations of rodents carrying the virus of hemorrhagic fever with renal syndrome].

    PubMed

    Tarasov, M A; Sonin, K A; Tolokonnikova, S I; Iakovlev, S A; Bil'ko, E A; Popov, N V

    2006-01-01

    The role of necrophagy in the epizootic manifestations of hemorrhagic fever with renal syndrome (HFRS) is first shown. By analyzing a great body of data obtained in the Saratov Region in 1982-2000, it has been established that the frequency of manifestations of necrophagy depends on many factors, the most important of which are a season, the size (density) of populations of small mammals, their species composition and the type of biotopes inhabited by these animals. Necrophagy is ascertained to be of great importance in HFRS foci as one of the alimentary routes of infection transmission in the parasitic systems. The presence or absence of necrophagy may serve as a preliminary test for the activity of HFRS foci.

  1. Effects of Humidity Variation on the Hantavirus Infection and Hemorrhagic Fever with Renal Syndrome Occurrence in Subtropical China

    PubMed Central

    Xiao, Hong; Huang, Ru; Gao, Li-Dong; Huang, Cun-Rui; Lin, Xiao-Ling; Li, Na; Liu, Hai-Ning; Tong, Shi-Lu; Tian, Huai-Yu

    2016-01-01

    Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS. PMID:26711521

  2. [Genetic variants of the Crimean-Congo hemorrhagic fever virus circulating in endemic areas of the southern Tajikistan in 2009].

    PubMed

    Petrova, I D; Kononova, Iu V; Chausov, E V; Shestopalov, A M; Tishkova, F Kh

    2013-01-01

    506 Hyalomma anatolicum ticks were collected and assayed in two Crimean-Congo hemorrhagic fever (CCHF) endemic regions of Tajikistan. Antigen and RNA of CCHF virus were detected in 3.4% of tick pools from Rudaki district using ELISA and RT-PCR tests. As of Tursunzade district, viral antigen was identified in 9.0% of samples and viral RNA was identified in 8.1% of samples. The multiple alignment of the obtained nucleotide sequences of CCHF virus genome S-segment 287-nt region (996-1282) and multiple alignment of deduced amino acid sequences of the samples, carried out to compare with CCHF virus strains from the GenBank database, as well as phylogenetic analysis, enabled us to conclude that Asia 1 and Asia 2 genotypes of CCHF virus are circulating in Tajikistan. It is important to note that the genotype Asia 1 virus was detected for the first time in Tajikistan.

  3. Relationship between Crimean-Congo hemorrhagic fever virus strains circulating in Iran and Turkey: possibilities for transborder transmission.

    PubMed

    Mahzounieh, Mohammadreza; Dincer, Ender; Faraji, Alireza; Akin, Humay; Akkutay, Ayse Zeynep; Ozkul, Aykut

    2012-09-01

    Crimean-Congo hemorrhagic fever (CCHF) is an important zoonotic viral disease that is asymptomatic in infected livestock, but poses a serious threat to humans. The high fatality rate may be due to phylogenetic variations in the virus, transmission routes, and a lack of an efficient surveillance system for the disease. The geographical features of the eastern and southeastern borders of Turkey may facilitate transmission of viruses between countries of the region. Therefore in this study we focused on the genetic relationship between Turkish and Iranian CCHF viruses based on their S-segment sequences. The research was performed on a total of 104 blood samples from small ruminants reared in southwest Iran. The results of phylogenetic analysis showed that Iranian CCHF virus isolates were closely related to human-originating Turkish Group II viruses from a European lineage reported previously.

  4. Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and tubulointerstitial nephritis.

    PubMed

    Korkmaz, Serdal; Elaldi, Nazif; Kayatas, Mansur; Sencan, Mehmet; Yildiz, Esin

    2012-05-18

    Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a strict intracellular bacterium. It may be manifested by some of the autoimmune events and is classified into acute and chronic forms. The most frequent clinical manifestation of acute form is a self-limited febrile illness which is associated with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis, thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic anemia, and nephritis are rare manifestations. Here we present a case of acute Q fever together with Coombs' positive autoimmune hemolytic anemia (AIHA) and tubulointerstitial nephritis treated with chlarithromycin, steroids and hemodialysis. Clinicians should be aware of such rare manifestations of the disease.

  5. Multiple circulating infections can mimic the early stages of viral hemorrhagic fevers and possible human exposure to filoviruses in Sierra Leone prior to the 2014 outbreak.

    PubMed

    Boisen, Matthew L; Schieffelin, John S; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B; Shaffer, Jeffrey G; Hastie, Kathryn M; Hartnett, Jessica N; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K; Andersen, Kristian G; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W; Geisbert, Joan B; Pitts, Kelly R; Geisbert, Thomas W; Kulakoski, Peter; Wilson, Russell B; Henderson, Lee; Sabeti, Pardis C; Grant, Donald S; Garry, Robert F; Saphire, Erica O; Branco, Luis M; Khan, Sheik Humarr

    2015-02-01

    Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction-based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak.

  6. A Virus-Like Particle System Identifies the Endonuclease Domain of Crimean-Congo Hemorrhagic Fever Virus

    PubMed Central

    Devignot, Stephanie; Bergeron, Eric; Nichol, Stuart; Mirazimi, Ali

    2015-01-01

    ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV; genus Nairovirus) is an extremely pathogenic member of the Bunyaviridae family. Since handling of the virus requires a biosafety level 4 (BSL-4) facility, little is known about pathomechanisms and host interactions. Here, we describe the establishment of a transcriptionally competent virus-like particle (tc-VLP) system for CCHFV. Recombinant polymerase (L), nucleocapsid protein (N) and a reporter minigenome expressed in human HuH-7 cells resulted in formation of transcriptionally active nucleocapsids that could be packaged by coexpressed CCHFV glycoproteins into tc-VLPs. The tc-VLPs resembled authentic virus particles in their protein composition and neutralization sensitivity to anti-CCHFV antibodies and could recapitulate all steps of the viral replication cycle. Particle attachment, entry, and primary transcription were modeled by infection of naive cells. The subsequent steps of genome replication, secondary transcription, and particle assembly and release can be obtained upon passaging the tc-VLPs on cells expressing CCHFV structural proteins. The utility of the VLP system was demonstrated by showing that the endonuclease domain of L is located around amino acid D693, as was predicted in silico by B. Morin et al. (PLoS Pathog 6:e1001038, 2010, http://dx.doi.org/10.1371/journal.ppat.1001038). The tc-VLP system will greatly facilitate studies and diagnostics of CCHFV under non-BSL-4 conditions. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is an extremely virulent pathogen of humans. Since the virus can be handled only at the highest biosafety level, research is restricted to a few specialized laboratories. We developed a plasmid-based system to produce virus-like particles with the ability to infect cells and transcribe a reporter genome. Due to the absence of viral genes, the virus-like particles are unable to spread or cause disease, thus allowing study of aspects of CCHFV biology under relaxed

  7. Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin

    PubMed Central

    Bergeron, Éric; Zivcec, Marko; Chakrabarti, Ayan K.; Nichol, Stuart T.; Albariño, César G.; Spiropoulou, Christina F.

    2015-01-01

    Crimean Congo hemorrhagic fever virus (CCHFV) is a negative-strand RNA virus of the family Bunyaviridae (genus: Nairovirus). In humans, CCHFV causes fever, hemorrhage, severe thrombocytopenia, and high fatality. A major impediment in precisely determining the basis of CCHFV’s high pathogenicity has been the lack of methodology to produce recombinant CCHFV. We developed a reverse genetics system based on transfecting plasmids into BSR-T7/5 and Huh7 cells. In our system, bacteriophage T7 RNA polymerase produced complementary RNA copies of the viral S, M, and L segments that were encapsidated with the support, in trans, of CCHFV nucleoprotein and L polymerase. The system was optimized to systematically recover high yields of infectious CCHFV. Additionally, we tested the ability of the system to produce specifically designed CCHFV mutants. The M segment encodes a polyprotein that is processed by host proprotein convertases (PCs), including the site-1 protease (S1P) and furin-like PCs. S1P and furin cleavages are necessary for producing the non-structural glycoprotein GP38, while S1P cleavage yields structural Gn. We studied the role of furin cleavage by rescuing a recombinant CCHFV encoding a virus glycoprotein precursor lacking a functional furin cleavage motif (RSKR mutated to ASKA). The ASKA mutation blocked glycoprotein precursor’s maturation to GP38, and Gn precursor’s maturation to Gn was slightly diminished. Furin cleavage was not essential for replication, as blocking furin cleavage resulted only in transient reduction of CCHFV titers, suggesting that either GP38 and/or decreased Gn maturation accounted for the reduced virion production. Our data demonstrate that nairoviruses can be produced by reverse genetics, and the utility of our system uncovered a function for furin cleavage. This viral rescue system could be further used to study the CCHFV replication cycle and facilitate the development of efficacious vaccines to counter this biological and public

  8. Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection

    PubMed Central

    2011-01-01

    Background Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Results Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Conclusion Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In

  9. [New transmission scenarios of the Argentine hemorrhagic fever since the introduction of the live attenuated junin virus vaccine (Candid #1): an experience in migrant workers].

    PubMed

    Briggiler, Ana; Sinchi, Anabel; Coronel, Florencia; Sánchez, Zaida; Levis, Silvana; Taylor, Jorge; Enria, Delia

    2015-01-01

    The Argentine hemorrhagic fever (AHF) is a severe acute viral disease caused by the Junin virus of the Arenaviridae family. The AHF endemic area coincides geographically with the largest grain export agro-industrial complex of the country [Argentina]. Since the implementation of vaccination with the Candid #1 vaccine, a significant reduction in incidence was achieved and risk patterns were modified. A previous study allowed characterizing these changes and identifying three transmission scenarios: classic, emergent-reemergent, and traveler. The latter scenario includes seasonal migrant workers who move each year, mainly from the province of Santiago del Estero, the endemic area to work in the detasseling of maize. With the objective of protecting this group of workers, a prevention campaign was initiated which included: capacity building of health personnel in the province, health education, and immunization with the vaccine Candid #1. 3,021 workers were vaccinated. Prior to vaccination, serum samples were taken from a group of 104 volunteers. Tests for neutralizing antibodies specific to the Junin virus were performed and 6 (5.76%) tested positive. The unexpected finding of a high percentage of workers with antibodies suggests the need to evaluate several hypotheses: a) that the result is the product of non-probabilistic sampling; b) that it could be people who fell ill in previous travels, c) or who were vaccinated in previous travels; or d) consider this region as an emerging scenario.

  10. Identification of highly conserved regions in L-segment of Crimean–Congo hemorrhagic fever virus and immunoinformatic prediction about potential novel vaccine

    PubMed Central

    Oany, Arafat Rahman; Ahmad, Shah Adil Ishtiyaq; Hossain, Mohammad Uzzal; Jyoti, Tahmina Pervin

    2015-01-01

    Crimean–Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease with a disease fatality rate between 15% and 70%. Despite the wide range of distribution, the virus (CCHFV) is basically endemic in Africa, Asia, eastern Europe, and the Middle East. Acute febrile illness associated with petechiae, disseminated intravascular coagulation, and multiple-organ failure are the main symptoms of the disease. With all these fatal effects, CCHFV is considered a huge threat as no successful therapeutic approach is currently available for the treatment of this disease. In the present study, we have used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of CCHFV. Both the T-cell and B-cell epitopes were assessed, and the epitope “DCSSTPPDR” was found to be the most potential one, with 100% conservancy among all the strains of CCHFV. The epitope was also found to interact with both type I and II major histocompatibility complex molecules and is considered nonallergenic as well. In vivo study of our proposed peptide is advised for novel universal vaccine production, which might be an effective path to prevent CCHF disease. PMID:25609983

  11. Crimean-Congo hemorrhagic fever nosocomial infection in a immunosuppressed patient, Pakistan: case report and virological investigation.

    PubMed

    Hasan, Zahra; Mahmood, Faisal; Jamil, Bushra; Atkinson, Barry; Mohammed, Murtaza; Samreen, Azra; Altaf, Lamia; Moatter, Tariq; Hewson, Roger

    2013-03-01

    Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Baluchistan province, Pakistan. Sporadic outbreaks of CCHF occur throughout the year especially in individuals in contact with infected livestock. Nosocomial transmission remains a risk due to difficulties in the diagnosis of CCHF and limited availability of facilities for the isolation of suspected patients. Rapid diagnosis of CCHF virus infection is required for early management of the disease and to prevent transmission. This study describes the case of a 43-year-old surgeon who contracted CCHF during a surgical procedure in Quetta, Baluchistan and who was transferred to a tertiary care facility at the Aga Khan University Hospital, Karachi within 1 week of contracting the infection. Diagnosis of CCHF was made using a rapid real-time reverse transcription polymerase chain reaction (RT-PCR) assay for CCHF viral RNA. The patient had chronic hepatitis B and hepatitis D infection for which he had previously received a liver transplant. He proceeded to develop classic hemorrhagic manifestations and succumbed to the infection 14 days post-onset of disease. There was no further nosocomial transmission of the CCHF during the hospital treatment of the surgeon. Early diagnosis of CCHF enables rapid engagement of appropriate isolation, barrier nursing and infection control measures thus preventing nosocomial transmission of the virus.

  12. Evaluation of Crimean-Congo hemorrhagic fever virus in vitro inhibition by chloroquine and chlorpromazine, two FDA approved molecules.

    PubMed

    Ferraris, O; Moroso, M; Pernet, O; Emonet, S; Ferrier Rembert, A; Paranhos-Baccalà, G; Peyrefitte, C N

    2015-06-01

    Crimean-Congo hemorrhagic virus (CCHFV) causes hemorrhagic fever with high case mortality rates and is endemic in south-eastern Europe, Africa, and Asia. The limited catalog of specific treatment, highlight the necessity to look for additional therapeutic solutions. Previous experiments suggested that CCHFV enters the cells via a clathrin dependent pathway. Therefore, we have evaluated the potential anti-CCHFV activity of several molecules targeting this entry possibility. We identified two molecules chloroquine and chlorpromazine. Neutralization and virus yield reduction assays were tested in Vero E6 and Huh7 cells on two different CCHFV strains. Several combinations, including ribavirin, were assayed to test a potential synergistic effect. The two molecules inhibited CCHFV, and depending on the virus and the cell lines, the 50% inhibitory concentration (IC50) values for chloroquine and chlorpromazine ranged from 28 to 43 and 10.8-15.7 μM, respectively. Time-of-addition studies demonstrated that these molecules had a direct effect on CCHFV infectivity and spread. The antiviral activity of the two molecules was still effective even when added up to 6h post-infection and up to 24h. The selectivity index ranging from 3 to 35 lead us to evaluate combinations with ribavirin. Combinations of ribavirin and chloroquine or chlorpromazine were synergistic against CCHFV. Though the low chlorpromazine selectivity index suggests the need for a chemical improvement, our present study highlights chloroquine as the main drug having the potential for drug repurposing.

  13. Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system.

    PubMed

    Suda, Yuto; Fukushi, Shuetsu; Tani, Hideki; Murakami, Shin; Saijo, Masayuki; Horimoto, Taisuke; Shimojima, Masayuki

    2016-06-01

    Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.

  14. The prognostic significance of serum TGF-β1 levels in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Yilmaz, Gürdal; Yilmaz, Hülya; Arslan, Mustafa; Kostakoğlu, Uğur; Menteşe, Ahmet; Karahan, Süleyman Caner; Köksal, İftihar

    2017-03-01

    Crimean-Congo Hemorrhagic Fever (CCHF) may exhibit a mild clinical course or a severe profile like mortal bleeding. The pathogenesis of the illness and reason of bleeding are unclear. However, endothelial injury is a key factor in the pathogenesis of the illness. Transforming growth factor beta (TGF-β) is one of the materials involved in repairing injured endothelium. This is a significant polypeptide released in pretty much all cells and important for the regulation of cellular events, epithelium formation, inflammation, blood coagulation, and collagen synthesis. This study aimed to determine the prognostic significance of serum TGF-β1 levels in CCHF patients. We examined 120 patients hospitalized with CCHF diagnosis and their serum TGF-β1 was investigated, retrospectively. Patients were put into two groups according to the existence of hemorrhage. Forty-four (36.7%) patients had hemorrhage. TGF-β1 levels in patients with bleeding were 5.2 ± 1.8, and 7.1 ± 2.2 for non-bleeding (P < 0.0001). When ROC analysis was performed in patients with CCHF alone in order to identify patients with bleeding, at a TGF-β1 cut-off point of 4.9, AUC was 0.762 (0.675-0.835), sensitivity 59.1%, specificity 85.5%, PPV 70.3%, and NPV 78.3%. We summarize that TGF-β1 level and endothelial dysfunction can be related. A decreased TGF-β1 level is a likely prognostic and diagnostic factor for bleeding in CCHF patients. Therefore, this marker should be considered in the treatment strategy for these patients. J. Med. Virol. 89:413-416, 2017. © 2016 Wiley Periodicals, Inc.

  15. Spontaneous acute hemorrhage of intraspinal canal cellular schwannoma with paraplegia: A case report.

    PubMed

    Zhang, Heng-Zhu; Li, Yuping; Han, Yang; Wang, Xiaodong; She, Lei; Yan, Zhengcun; Dong, Lun

    2015-06-01

    Cellular schwannoma, an unusual histological subtype of schwannoma, is a benign hypercellular variant of a peripheral nerve sheath tumor. We report a 48-year-old woman with sudden onset of paraplegia. The complete surgical resection was achieved. This is the first report about intraspinal canal cellular schwannoma following spontaneous acute hemorrhage and paraplegia.

  16. Venous Return and Clinical Hemodynamics: How the Body Works during Acute Hemorrhage

    ERIC Educational Resources Information Center

    Shen, Tao; Baker, Keith

    2015-01-01

    Venous return is a major determinant of cardiac output. Adjustments within the venous system are critical for maintaining venous pressure during loss in circulating volume. This article reviews two factors that are thought to enable the venous system to compensate during acute hemorrhage: 1) changes in venous elastance and 2) mobilization of…

  17. Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia.

    PubMed

    Porter, Kevin R; Beckett, Charmagne G; Kosasih, Herman; Tan, Ratna Irsiana; Alisjahbana, Bachti; Rudiman, Pandji Irani Fianza; Widjaja, Susana; Listiyaningsih, Erlin; Ma'Roef, Chairin Nisa; McArdle, James L; Parwati, Ida; Sudjana, Primal; Jusuf, Hadi; Yuwono, Djoko; Wuryadi, Suharyono

    2005-01-01

    A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.

  18. Serological characterization of dengue virus infections observed among dengue hemorrhagic fever/dengue shock syndrome cases in upper Myanmar.

    PubMed

    Ngwe Tun, Mya Myat; Thant, Kyaw Zin; Inoue, Shingo; Kurosawa, Yae; Lwin, Yee Yee; Lin, Sanda; Aye, Kay Thi; Thet Khin, Pe; Myint, Tin; Htwe, Khin; Mapua, Cynthia A; Natividad, Filipinas F; Hirayama, Kenji; Morita, Kouichi

    2013-07-01

    In Myanmar, dengue fever (DF)/dengue hemorrhagic fever (DHF) is one of the leading causes of morbidity and mortality among children. From Pyinmana Hospital in 2004 and Mandalay Children Hospital in 2006, 160 patients diagnosed clinically to have DHF/dengue shock syndrome (DSS) were examined for immunoglobulin M (IgM) and IgG levels. A focus reduction neutralization test was also used to determine primary or secondary dengue virus (DENV) infection. By using IgM-capture ELISA, 139 cases were confirmed as DENV infections. Of these IgM-positives, 94 samples were collected 7-24 days from the onset of illness, to which 13 (14%) and 81 (86%) were determined to be primary and secondary DENV infections, respectively. The 13 primary DENV infection cases were spread among the various severity groups (DHF grade I-IV and DSS) and represented age groups ranging from <1 year of age to 9 years of age. The patients in these primary infection cases showed a remarkably high IgM with a low IgG titer response compared with the secondary infection cases. No significant differences were observed in IgG titers with clinical severity. The data obtained in this study suggest that primary DENV infection cases exist certainly among DHF/DSS cases in Myanmar, and that additional mechanism(s) aside from the antibody-dependent enhancement mechanism could have influenced the clinical severity in DHF/DSS cases.

  19. Profiling the Humoral Immune Response of Acute and Chronic Q Fever by Protein Microarray*

    PubMed Central

    Vigil, Adam; Chen, Chen; Jain, Aarti; Nakajima-Sasaki, Rie; Jasinskas, Algimantas; Pablo, Jozelyn; Hendrix, Laura R.; Samuel, James E.; Felgner, Philip L.

    2011-01-01

    Antigen profiling using comprehensive protein microarrays is a powerful tool for characterizing the humoral immune response to infectious pathogens. Coxiella burnetii is a CDC category B bioterrorist infectious agent with worldwide distribution. In order to assess the antibody repertoire of acute and chronic Q fever patients we have constructed a protein microarray containing 93% of the proteome of Coxiella burnetii, the causative agent of Q fever. Here we report the profile of the IgG and IgM seroreactivity in 25 acute Q fever patients in longitudinal samples. We found that both early and late time points of infection have a very consistent repertoire of IgM and IgG response, with a limited number of proteins undergoing increasing or decreasing seroreactivity. We also probed a large collection of acute and chronic Q fever patient samples and identified serological markers that can differentiate between the two disease states. In this comparative analysis we confirmed the identity of numerous IgG biomarkers of acute infection, identified novel IgG biomarkers for acute and chronic infections, and profiled for the first time the IgM antibody repertoire for both acute and chronic Q fever. Using these results we were able to devise a test that can distinguish acute from chronic Q fever. These results also provide a unique perspective on isotype switch and demonstrate the utility of protein microarrays for simultaneously examining the dynamic humoral immune response against thousands of proteins from a large number of patients. The results presented here identify novel seroreactive antigens for the development of recombinant protein-based diagnostics and subunit vaccines, and provide insight into the development of the antibody response. PMID:21817167

  20. Typhoid fever as a triggering factor in acute and intractable bronchial asthma attack.

    PubMed

    Wardhana; Surachmanto, Eko E; Datau, E A

    2013-10-01

    Typhoid fever is an enteric infection caused by Salmonella typhi. In Indonesia, typhoid fever is endemic with high incidence of the disease. In daily practice we frequently have patients with bronchial asthma, and it is becoming worse when these patients get typhoid fever. After oral ingestion, Salmonella typhi invades the the intestine mucosa after conducted by microbial binding to epithelial cells, destroying the microfold cells (M cell) then passed through the lamina propria and detected by dendritic cells (DC) which express a variety of pathogen recognition receptors on the surfaces, including Toll-Like Receptor (TLR). expressed on macrophages and on intestinal epithelial cells inducing degradation of IB, and translocation of NF-B (Nuclear Factor-Kappa Beta). This process initiates the induction of pro-inflammatory gene expression profile adhesion molecules, chemokines, adhesion molecules, and other proteins that induce and perpetuate the inflammation in host cells then will induce acute ant intractable attack of bronchial asthma. The role of typhoid fever in bronchial asthma, especially in persons with acute attack of bronchial asthma, is not well understood. In this article, we will discuss the role of typhoid fever in the bronchial asthma patients which may cause bronchial asthma significantly become more severe even triggering the acute and intractable attack of bronchial asthma. This fact makes an important point, to treat completely the typhoid fever in patients with bronchial asthma.

  1. Acute Q fever in Portugal. Epidemiological and clinical features of 32 hospitalized patients

    PubMed Central

    Palmela, Carolina; Badura, Robert; Valadas, Emília

    2012-01-01

    Introduction Q fever is a worldwide zoonosis caused by Coxiella burnetii. The main characteristic of acute Q fever is its clinical polymorphism, usually presenting as a febrile illness with varying degrees of hepatitis and/or pneumonia. Q fever is endemic in Portugal, and it is an obligatory notifiable disease since 1999. However, its epidemiological and clinical characteristics are still incompletely described. Methods We performed a retrospective study of 32 cases admitted in the Infectious Diseases Department, Santa Maria’s University Hospital, from January 2001 to December 2010, in whom acute Q fever was diagnosed by the presence of antibodies to phase II Coxiella burnetii antigens associated with a compatible clinical syndrome. Results Out of the 32 cases recorded, 29 (91%) were male, with a male:female ratio of 9.7:1. Individuals at productive age were mainly affected (88%, n=28, with ages between 25 and 64 years). Clinically, the most common manifestation of acute Q fever was hepatic involvement (84%, n=27), which occurred isolated in 53% (n=17) of the cases. Hepatitis was more severe, presenting with higher values of liver function tests, in patients presenting both pulmonary and hepatic involvement. Additionally, we report one case of myocarditis and another one with neurological involvement. Empiric but appropriate antibiotic therapy was given in 66% (n=21) of the cases. There was a complete recovery in 94% (n=30) of the patients, and one death. We confirmed the sub-notification of this disease in Portugal, with only 47% (n=15) of the cases notified. Conclusion In Portugal further studies are needed to confirm our results. From the 32 cases studied, acute Q fever presented more frequently as a febrile disease with hepatic involvement affecting mainly young male individuals. Furthermore, acute Q fever is clearly underdiagnosed and underreported in Portugal, which suggests that an increased awareness of the disease is needed, together with a broader use

  2. Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs

    NASA Technical Reports Server (NTRS)

    O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

    1993-01-01

    The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.

  3. Thrombotic and hemorrhagic strokes complicating early therapy for childhood acute lymphoblastic leukemia.

    PubMed

    Priest, J R; Ramsay, N K; Latchaw, R E; Lockman, L A; Hasegawa, D K; Coates, T D; Coccia, P F; Edson, J R; Nesbit, M E; Krivit, W

    1980-10-01

    Sudden cerebrovascular insults occurred during or immediately following remission induction therapy in 4 children with acute lymphoblastic leukemia. In 3, cerebral infarction was due to thrombosis. In the fourth, an intracerebral hematoma developed representing either frank hemorrhaging or a hemorrhagic infarction. None of the patients had central nervous system leukemia or extreme leukocytosis at the time of diagnosis. Symptoms were obtundation, hemiparesis, seizures, and headache. The induction chemotherapy included L-asparaginase which causes deficiencies of antithrombin, plasminogen, fibrinogen, and factors IX and XI. These hemostatic abnormalities may explain the thromboses and bleeding observed in these children.

  4. Mucosal arenavirus infection of primates can protect them from lethal hemorrhagic fever.

    PubMed

    Rodas, Juan D; Lukashevich, Igor S; Zapata, Juan C; Cairo, Cristiana; Tikhonov, Ilia; Djavani, Mahmoud; Pauza, C David; Salvato, Maria S

    2004-03-01

    Arenaviruses are transmitted from rodents to human beings by blood or mucosal exposure. The most devastating arenavirus in terms of human disease is Lassa fever virus, causing up to 300,000 annual infections in West Africa. We used a model for Lassa fever in which Rhesus macaques were infected with a related virus, lymphocytic choriomeningitis virus (LCMV). Our goals were to determine the outcome of infection after mucosal inoculation and later lethal challenge, to characterize protective immune responses, and to test cross-protection between a virulent (LCMV-WE) and an avirulent (LCMV-ARM) strain of virus. Although intravenous infections in the monkey model were uniformly lethal, intragastric infections recapitulated the spectrum of clinical outcomes seen in human exposure to Lassa fever virus: death, recovery from disease, and most often, subclinical infection. Plaque neutralization, ELISA, lymphocyte proliferation, and chromium-release assays were used to monitor humoral and cellular immune responses. Cross protection between the two strains was observed. The three out of seven monkeys that experienced protection were also the three with the strongest cell-mediated immunity.

  5. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

    PubMed Central

    Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

  6. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    PubMed

    Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

  7. Evaluation of Crimean-Congo hemorrhagic fever virus infection in children.

    PubMed

    Kızılgun, Murat; Ozkaya-Parlakay, Aslınur; Tezer, Hasan; Gulhan, Belgin; Yuksek, Saliha Kanık; Celikel, Elif; Tunc, Bahattin

    2013-11-01

    Crimean-Congo haemorrhagic fever (CCHF) is a fatal viral infection and an important public health issue in Turkey because of its high case fatality rate. Severity criteria of CCHF were defined previously in adults on the basis of epidemiological, clinical, and laboratory findings,. This study evaluated the course of CCHF in children. Between January, 2009, and November, 2012, 41 patients aged between 1 and 17 years (mean 9.78 ± 4.85) with a diagnosis of CCHF were included in the study. According to results of our study, Turkish pediatric patients had a milder course of CCHF.

  8. Research and Development of Human and Primate Antibodies for Immunotherapy of Viral Hemorrhagic Fever Infections

    DTIC Science & Technology

    1989-06-01

    Diseases (USAMRIID) testing of these products. Each preparation has viral neutralizing activity and is a safe, stable, well tolerated solution...Army Medical Research Institute of Infectious Diseases (USAMRIID), there were five different human anti-Lassa fever (ALF) preparations, two monkey...include: 1) Human ALF IgG containing all four subclasses IgG1 , IgG2 , IgG3 , IgG4 ; 2) Human ALF IgG containing only the three subclasses IgG1

  9. Crimean-Congo Hemorrhagic Fever Virus Subunit Vaccines Induce High Levels of Neutralizing Antibodies But No Protection in STAT1 Knockout Mice.

    PubMed

    Kortekaas, Jeroen; Vloet, Rianka P M; McAuley, Alexander J; Shen, Xiaoli; Bosch, Berend Jan; de Vries, Laura; Moormann, Rob J M; Bente, Dennis A

    2015-12-01

    Crimean-Congo hemorrhagic fever virus is a tick-borne bunyavirus of the Nairovirus genus that causes hemorrhagic fever in humans with high case fatality. Here, we report the development of subunit vaccines and their efficacy in signal transducer and activator of transcription 1 (STAT1) knockout mice. Ectodomains of the structural glycoproteins Gn and Gc were produced using a Drosophila insect cell-based expression system. A single vaccination of STAT129 mice with adjuvanted Gn or Gc ectodomains induced neutralizing antibody responses, which were boosted by a second vaccination. Despite these antibody responses, mice were not protected from a CCHFV challenge infection. These results suggest that neutralizing antibodies against CCHFV do not correlate with protection of STAT1 knockout mice.

  10. Interventions to control virus transmission during an outbreak of Ebola hemorrhagic fever: experience from Kikwit, Democratic Republic of the Congo, 1995.

    PubMed

    Kerstiëns, B; Matthys, F

    1999-02-01

    On 6 May 1995, the Médecins sans Frontières (MSF) coordinator in Kinshasa, Democratic Republic of the Congo (DRC), received a request for assistance for what was believed to be a concurrent outbreak of bacillary dysentery and viral hemorrhagic fever (suspected Ebola hemorrhagic fever [EHF]) in the town of Kikwit, DRC. On 11 May, the MSF intervention team assessed Kikwit General Hospital. This initial assessment revealed a nonfunctional isolation ward for suspected EHF cases; a lack of water and electricity; no waste disposal system; and no protective gear for medical staff. The priorities set by MSF were to establish a functional isolation ward to deal with EHF and to distribute protective supplies to individuals who were involved with patient care. Before the intervention, 67 health workers contracted EHF; after the initiation of control measures, just 3 cases were reported among health staff and none among Red Cross volunteers involved in body burial.

  11. Preliminary evaluation of near infrared spectroscopy as a method to detect plasma leakage in children with dengue hemorrhagic fever

    PubMed Central

    2014-01-01

    Background Dengue viral infections are prevalent in the tropical and sub-tropical regions of the world, resulting in substantial morbidity and mortality. Clinical manifestations range from a self-limited fever to a potential life-threatening plasma leakage syndrome (dengue hemorrhagic fever). The objective of this study was to assess the utility of near infrared spectroscopy (NIRS) measurements of muscle oxygen saturation (SmO2) as a possible continuous measure to detect plasma leakage in children with dengue. Methods Children ages 6 months to 15 years of age admitted with suspected dengue were enrolled from the dengue ward at Queen Sirikit National Institute for Child Health. Children were monitored daily until discharge. NIRS data were collected continuously using a prototype CareGuide Oximeter 1100 with sensors placed on the deltoid or thigh. Daily ultrasound of the chest and a right lateral decubitus chest x-ray the day after defervescence were performed to detect and quantitate plasma leakage in the pleural cavity. Results NIRS data were obtained from 19 children with laboratory-confirmed dengue. Average minimum SmO2 decreased for all subjects prior to defervescence. Average minimum SmO2 subsequently increased in children with no ultrasound evidence of pleural effusion but remained low in children with pleural effusion following defervescence. Average minimum SmO2 was inversely correlated with pleural space fluid volume. ROC analysis revealed a cut-off value for SmO2 which yielded high specificity and sensitivity. Conclusions SmO2 measured using NIRS may be a useful guide for real-time and non-invasive identification of plasma leakage in children with dengue. Further investigation of the utility of NIRS measurements for prediction and management of severe dengue syndromes is warranted. PMID:25033831

  12. Development of Infectious Clones for Virulent and Avirulent Pichinde Viruses: a Model Virus To Study Arenavirus-Induced Hemorrhagic Fevers ▿ †

    PubMed Central

    Lan, Shuiyun; McLay Schelde, Lisa; Wang, Jialong; Kumar, Naveen; Ly, Hinh; Liang, Yuying

    2009-01-01

    Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and the lack of molecular clones. A safe, convenient, and economical small animal model of arenavirus hemorrhagic fever is based on guinea pigs infected by the arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2) remains avirulent in infected animals. In order to identify the virulence determinants within the PICV genome, we developed the molecular clones for both the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by transfecting plasmids that contain the antigenomic L and S RNA segments of PICV under the control of the T7 promoter into BSRT7-5 cells, which constitutively express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and virulence in vivo, we show that the recombinant viruses accurately recapitulate the replication and virulence natures of their respective parental viruses. Both parental and recombinant virulent viruses led to high levels of viremia and titers in different organs of the infected animals, whereas the avirulent viruses were effectively controlled and cleared by the hosts. These novel infectious clones for the PICV provide essential tools to identify the virulence factors that are responsible for the severe VHF-like disease in infected animals. PMID:19386714

  13. Minigenomes, transcription and replication competent virus-like particles and beyond: reverse genetics systems for filoviruses and other negative stranded hemorrhagic fever viruses.

    PubMed

    Hoenen, Thomas; Groseth, Allison; de Kok-Mercado, Fabian; Kuhn, Jens H; Wahl-Jensen, Victoria

    2011-08-01

    Reverse-genetics systems are powerful tools enabling researchers to study the replication cycle of RNA viruses, including filoviruses and other hemorrhagic fever viruses, as well as to discover new antivirals. They include full-length clone systems as well as a number of life cycle modeling systems. Full-length clone systems allow for the generation of infectious, recombinant viruses, and thus are an important tool for studying the virus replication cycle in its entirety. In contrast, life cycle modeling systems such as minigenome and transcription and replication competent virus-like particle systems can be used to simulate and dissect parts of the virus life cycle outside of containment facilities. Minigenome systems are used to model viral genome replication and transcription, whereas transcription and replication competent virus-like particle systems also model morphogenesis and budding as well as infection of target cells. As such, these modeling systems have tremendous potential to further the discovery and screening of new antivirals targeting hemorrhagic fever viruses. This review provides an overview of currently established reverse genetics systems for hemorrhagic fever-causing negative-sense RNA viruses, with a particular emphasis on filoviruses, and the potential application of these systems for antiviral research.

  14. Yellow fever

    MedlinePlus

    ... liver, and kidney. Bleeding disorders, seizures, coma, and delirium may also occur. Symptoms may include: Fever, headache, ... tongue Yellow skin and eyes (jaundice) Decreased urination Delirium Irregular heartbeats (arrhythmias) Bleeding (may progress to hemorrhage) ...

  15. Acute Generalized Exanthematous Pustulosis: An Uncommon Cause of Fever and Rash.

    PubMed

    Gordon, Jeffrey

    2016-03-01

    Fever and rash are common presenting complaints to the Emergency Department. This report documents an uncommon diagnosis involving this presentation. The patient presented with signs and symptoms consistent with severe sepsis. Once the diagnosis of Acute Generalized Exanthematous Pustulosis was recognized, the outcome was favorable.

  16. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease

    PubMed Central

    Seckeler, Michael D; Hoke, Tracey R

    2011-01-01

    Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are significant public health concerns around the world. Despite decreasing incidence, there is still a significant disease burden, especially in developing nations. This review provides background on the history of ARF, its pathology and treatment, and the current reported worldwide incidence of ARF and prevalence of RHD. PMID:21386976

  17. Acute Tetraplegia Caused by Rat Bite Fever in Snake Keeper and Transmission of Streptobacillus moniliformis

    PubMed Central

    Eisenberg, Tobias; Poignant, Simon; Jouan, Youenn; Fawzy, Ahmad; Nicklas, Werner; Ewers, Christa; Mereghetti, Laurent

    2017-01-01

    We report acute tetraplegia caused by rat bite fever in a 59-year old man (snake keeper) and transmission of Streptobacillus moniliformis. We found an identical characteristic bacterial pattern in rat and human samples, which validated genotyping-based evidence for infection with the same strain, and identified diagnostic difficulties concerning infection with this microorganism. PMID:28322713

  18. Acute rheumatic fever and rheumatic heart disease in resource-limited settings.

    PubMed

    Watson, Gabriella; Jallow, Bintou; Le Doare, Kirsty; Pushparajah, Kuberan; Anderson, Suzanne T

    2015-04-01

    Poststreptococcal complications, such as acute rheumatic fever (ARF) and rheumatic heart disease (RHD), are common in resource-limited settings, with RHD recognised as the most common cause of paediatric heart disease worldwide. Managing these conditions in resource-limited settings can be challenging. We review the investigation and treatment options for ARF and RHD and, most importantly, prevention methods in an African setting.

  19. Emergency anesthesia for evacuating a traumatic acute subdural hemorrhage in a child overdosed with hypertonic saline

    PubMed Central

    Goonasekera, Chulananda; Bedford, James; Harpreet, Sodhi; Giombini, Mariangela; Sheikh, Asme

    2016-01-01

    A previously healthy 1-year-old child with a traumatic acute subdural hemorrhage received 10 times higher dose of hypertonic saline inadvertently immediately before surgery. This case report describes deviations in fluid management needed to alleviate salt toxicity and its adverse effects during surgery under anesthesia perioperatively. The child made an uneventful recovery with no evident residual damage at follow-up. PMID:28217157

  20. Acute Hemorrhagic Myositis in Inflammatory Myopathy and Review of the Literature

    PubMed Central

    Van Gelder, Howard; Wu, Kim M.; Gharibian, Nayiri; Patel, Dharmi B.; Clements, Philip J.; Heinze, Emil R.; Morris, Robert I.; Wong, Andrew L.

    2014-01-01

    We describe two patients with dermatomyositis that presented with interstitial lung disease, positive V and Shawl sign who developed acute spontaneous abdominal/retroperitoneal bleed. Both patients expired despite aggressive treatment and resuscitation. Hemorrhagic myositis in these two patients with inflammatory myopathy is a very rare complication. The association of anti-Ro52 with this potentially very serious complication remains unclear. This potential relationship should be further evaluated in future studies. PMID:25379317

  1. Abdominal varices mimicking an acute gastrointestinal hemorrhage during technetium-99m red blood cell scintigraphy

    SciTech Connect

    Moreno, A.J.; Byrd, B.F.; Berger, D.E.; Turnbull, G.L.

    1985-04-01

    Abdominal varices consisting of a caput medusae and dilated mesenteric veins resulted in pooling of Tc-99m tagged red blood cells (RBC) within these dilated vessels in a 57-year-old man with severe Laennec's cirrhosis. The atypical radiotracer localization within the abdomen mimicked an acute gastrointestinal hemorrhage. Clinical suspicion and careful evaluation of scintigraphic gastrointestinal bleeding studies will avoid false-positive interpretations.

  2. Fiber-optic immunosensor for detection of Crimean-Congo hemorrhagic fever IgG antibodies in patients.

    PubMed

    Algaar, Fairoz; Eltzov, Evgeni; Vdovenko, Marina M; Sakharov, Ivan Yu; Fajs, Luka; Weidmann, Manfred; Mirazimi, Ali; Marks, Robert S

    2015-08-18

    Crimean-Congo hemorrhagic fever (CCHF) is a severe viral disease with high fatality rate. CCHF virus is endemic in parts of Africa, Asia, the Middle East, and southeastern Europe. Rapid diagnostics of CCHF is vital for appropriate clinical management and prevention of secondary spread from human-to-human. Currently, diagnostics relies on real-time RT-PCR and antibody or antigen detection using ELISA. These methods require trained personnel and expensive equipment and are not appropriate for point-of-care (POC) diagnostics. Furthermore, there are no POC assays available for CCHF. We developed a fiber-optic biosensor for the detection of CCHF IgG antibodies. In order to improve sensitivity, we optimized both the bioreceptor immobilization protocol and the chemiluminescence substrate formulation. The resulting protocol showed a 100-fold greater sensitivity for detection of CCHF antibodies. Finally, we evaluated the fiber-optic biosensor with two CCHF patient sera. We showed that the fiber-optic biosensor is 10-times more sensitive than colorimetric ELISA and is able to detect both patients with high and low levels of IgG antibodies. We believe that the fiber-optic biosensor is a suitable alternative to ELISA as it is much more sensitive and makes it possible to detect a small amount of antibodies at an early stage of infection and can be integrated as a point-of-care diagnostic system of CCHF.

  3. Evaluation of Prognostic Values of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Crimean-Congo Hemorrhagic Fever Patients

    PubMed Central

    Gurbuz, Yunus; Ozturk, Baris; Tutuncu, Emin Ediz; Sencan, Irfan; Cicek Senturk, Gonul; Altay, Fatma Aybala

    2015-01-01

    Background: Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease in Turkey, and was responsible for many deaths in endemic regions during the last decade. The pathogenesis of the disease is not fully understood yet. Objectives: In this study we aimed to determine the levels of tissue plasminogen activator (tPA) and Plasminogen activator inhibitor-1 (PAI-1) as predictors of prognosis in CCHF. Patients and Methods: Patients who were diagnosed by the polymerase chain reaction (PCR) and IgM positivity in the reference laboratory were included in this study. Tissue Plasminogen activator and PAI-1 levels were measured by the enzyme linked immunosorbent assay (ELISA) using a commercial kit (human t-PA ELISA and human PAL-1 ELISA; BioVendor research and diagnostic products, BioVendor-Laboratorni medicina a.s., Brno, Czech Republic). Results: A total of 46 patients participated in this study. The significant differences between recovering patients and the patients who died, regarding Aspartate aminotransferase (AST), Creatine Phosphokinase (CPK), Lactate Dehydrogenase (LDH), Prothrombin Time (PT), activated Partial Thromboplastin time (aPTT), and thrombocyte and fibrinogen levels, were consistent with many clinical studies in the literature. The fatal cases were found to have higher tPA and PAI-1 levels in contrast to the patients who completely recovered. Conclusions: We think that these findings may help the progress of understanding of CCHF pathogenesis. PMID:26587219

  4. Transstadial Transmission and Long-term Association of Crimean-Congo Hemorrhagic Fever Virus in Ticks Shapes Genome Plasticity

    PubMed Central

    Xia, Han; Beck, Andrew S.; Gargili, Aysen; Forrester, Naomi; Barrett, Alan D. T.; Bente, Dennis A.

    2016-01-01

    The trade-off hypothesis, the current paradigm of arbovirus evolution, proposes that cycling between vertebrate and invertebrate hosts presents significant constraints on genetic change of arboviruses. Studying these constraints in mosquito-borne viruses has led to a new understanding of epizootics. The trade-off hypothesis is assumed to be applicable to tick-borne viruses too, although studies are lacking. Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the family Bunyaviridae, is a major cause of severe human disease worldwide and shows an extraordinary amount of genetic diversity compared to other arboviruses, which has been linked to increased virulence and emergence in new environments. Using a transmission model for CCHFV, utilizing the main vector tick species and mice plus next generation sequencing, we detected a substantial number of consensus-level mutations in CCHFV recovered from ticks after only a single transstadial transmission, whereas none were detected in CCHFV obtained from the mammalian host. Furthermore, greater viral intra-host diversity was detected in the tick compared to the vertebrate host. Long-term association of CCHFV with its tick host for 1 year demonstrated mutations in the viral genome become fixed over time. These findings suggest that the trade-off hypothesis may not be accurate for all arboviruses. PMID:27775001

  5. Effects of Climate and Rodent Factors on Hemorrhagic Fever with Renal Syndrome in Chongqing, China, 1997-2008.

    PubMed

    Bai, Yuntao; Xu, Zhiguang; Lu, Bo; Sun, Qinghua; Tang, Wenge; Liu, Xiaobo; Yang, Weizhong; Xu, Xinyi; Liu, Qiyong

    2015-01-01

    China has the highest global incidence of hemorrhagic fever with renal syndrome (HFRS), constituting 90% of the cases in the world. Chongqing, located in the Three Gorges Reservoir Region, has been experiencing differences in the occurrence of HFRS from 1997 to 2008. The current study was designed to explore the effects of climate and rodent factors on the transmission of HFRS in Chongqing. Data on monthly HFRS cases, rodent strains, and climatic factors were collected from 1997 to 2008. Spatio-temporal analysis indicated that most HFRS cases were clustered in central Chongqing and that the incidence of HFRS decreased from 1997 to 2008. Poisson regression models showed that temperature (with lagged months of 0 and 5) and rainfall (with 2 lagged months) were key climatic factors contributing to the transmission of HFRS. A zero-inflated negative binomial model revealed that rodent density was also significantly associated with the occurrence of HFRS in the Changshou district. The monthly trend in HFRS incidence was positively associated with rodent density and rainfall and negatively associated with temperature. Possible mechanisms are proposed through which construction of the dam influenced the incidence of HFRS in Chongqing. The findings of this study may contribute to the development of early warning systems for the control and prevention of HFRS in the Three Gorges Reservoir Region.

  6. Phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex PCR-based next generation sequencing

    PubMed Central

    Kim, Won-Keun; Kim, Jeong-Ah; Song, Dong Hyun; Lee, Daesang; Kim, Yong Chul; Lee, Sook-Young; Lee, Seung-Ho; No, Jin Sun; Kim, Ji Hye; Kho, Jeong Hoon; Gu, Se Hun; Jeong, Seong Tae; Wiley, Michael; Kim, Heung-Chul; Klein, Terry A.; Palacios, Gustavo; Song, Jin-Won

    2016-01-01

    Emerging and re-emerging infectious diseases caused by RNA viruses pose a critical public health threat. Next generation sequencing (NGS) is a powerful technology to define genomic sequences of the viruses. Of particular interest is the use of whole genome sequencing (WGS) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. Hantaviruses, Bunyaviridae, cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans. We propose to use WGS for the phylogeographic analysis of human hantavirus infections. A novel multiplex PCR-based NGS was developed to gather whole genome sequences of Hantaan virus (HTNV) from HFRS patients and rodent hosts in endemic areas. The obtained genomes were described for the spatial and temporal links between cases and their sources. Phylogenetic analyses demonstrated geographic clustering of HTNV strains from clinical specimens with the HTNV strains circulating in rodents, suggesting the most likely site and time of infection. Recombination analysis demonstrated a genome organization compatible with recombination of the HTNV S segment. The multiplex PCR-based NGS is useful and robust to acquire viral genomic sequences and may provide important ways to define the phylogeographical association and molecular evolution of hantaviruses. PMID:27221218

  7. Isolation and characterization of two phenotypically distinct dengue type-2 virus isolates from the same dengue hemorrhagic Fever patient.

    PubMed

    Kinoshita, Hitomi; Mathenge, Edward Gitau Matumbi; Hung, Nguyen Thanh; Huong, Vu Thi Que; Kumatori, Atsushi; Yu, Fuxun; Parquet, Maria Carmen; Inoue, Shingo; Matias, Ronald Roll; Natividad, Filipinas Florendo; Morita, Kouichi; Hasebe, Futoshi

    2009-09-01

    Dengue is the one of the most prevalent arthropod-borne viral diseases. Dengue virus circulates between humans and mosquitoes, and causes a wide range of disease in humans. To elucidate the link between the cell tropism of dengue virus and its pathogenesis, peripheral blood cells of infected patients were analyzed by flow cytometry. The dengue virus antigen was detected in peripheral CD19+ cells (B cells) in one dengue hemorrhagic fever patient. Two dengue type-2 virus isolates were recovered from this patient using mosquito cell line C6/36 and human hematopoietic cell line K562, and designated VNHCM18-C/02 and VNHCM18-K/02, respectively. VNHCM18-K/02 exhibited strong binding ability and high infectivity to a B-lymphocyte cell line (RPMI8226) but showed poor growth in C6/36 cells, while VNHCM18-C/02 more efficiently and dominantly grew in C6/36 cells but did not efficiently bind to nor infect the B-cell line. Three amino acid differences were detected; one in an envelope protein (E-62) and two in nonstructural proteins. The distinct cell-binding to RPMI8226 was attributed to the difference between the two isolates in envelope protein E-62. Thus, we isolated two dengue type-2 virus variants with different cell-tropisms from the same patient, suggesting possible co-circulation in the patient.

  8. Inherent dynamics within the Crimean-Congo Hemorrhagic fever virus protease are localized to the same region as substrate interactions

    SciTech Connect

    Eisenmesser, Elan Z.; Capodagli, Glenn; Armstrong, Geoffrey S.; Holliday, Michael; Isern, Nancy G.; Zhang, Fengli; Pegan, Scott D.

    2015-05-01

    Crimean-Congo Hemorrhagic fever virus (CCHFV) is one of several lethal viruses that encodes for a viral ovarian tumor domain (vOTU), which serves to cleave and remove multiple proteins involved in cellular signaling such as ubiquitin (Ub) and interferon stimulated gene produce 15 (ISG15). Such manipulation of the host cell machinery serves to downregulate the host response and, therefore, complete characterization of these proteases is important. While several structures of the CCHFV vOTU protease have been solved, both free and bound to Ub and ISG15, few structural differences have been found and little insight has been gained as to the dynamic plasticity of this protease. Therefore, we have used NMR relaxation experiments to probe the dynamics of CCHV vOTU, both alone and in complex with Ub, thereby discovering a highly dynamic protease that exhibits conformational exchange within the same regions found to engage its Ub substrate. These experiments reveal a structural plasticity around the N-terminal regions of CCHV vOTU, which are unique to vOTUs, and provide a rationale for engaging multiple substrates with the same binding site.

  9. Meteorological factors are associated with hemorrhagic fever with renal syndrome in Jiaonan County, China, 2006-2011

    NASA Astrophysics Data System (ADS)

    Lin, Hualiang; Zhang, Zhentang; Lu, Liang; Li, Xiujun; Liu, Qiyong

    2014-08-01

    This study examined the effect of meteorological factors on the occurrence of hemorrhagic fever with renal syndrome (HFRS) using a generalized additive model with penalized smoothing splines in Jiaonan, China, from 2006 to 2011. The dose-response relationship was first examined, and then the association between daily meteorological variables and HFRS occurrence was investigated according to the dose-response curves. There were two linear segments in the temperature-HFRS relationship curve. When daily temperature was lower than 17 °C, a positive association was found [with excessive risk (ER) for 1 °C increase on the current day being 2.56 %, 95 % confidence interval (CI): 0.36 % to 4.80 %]. An inverse association was found when daily temperature was higher than 17 °C [ER for 1 °C increase on the current day was -12.82 % (95 % CI: -17.51 % to -7.85 %)]. Inverse associations were observed for relative humidity [ER for 1 % increase on lag day 4 was -1.21 % (95 % CI: -1.63 % to -0.79 %)] and rainfall [ER for 1 mm increase on lag day 1 was -2.20 % (95 % CI: -3.56 % to -0.82 %)]. Meteorological factors might be important predictor of HFRS epidemics in Jiaonan County.

  10. Analysis of an Outbreak of Hemorrhagic Fever with Renal Syndrome in College Students in Xi’an, China

    PubMed Central

    Ma, Chaofeng; Wang, Zengguo; Li, Shen; Xing, Yuan; Wu, Rui; Wei, Jing; Nawaz, Muhammad; Tian, Huaiyu; Xu, Bing; Wang, Jingjun; Yu, Pengbo

    2014-01-01

    The aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (HFRS), caused by a Hantavirus, in college students in the northern urban area of Xi’an in 2012. The outbreak affected six students and included two deaths. The epidemiological survey revealed that both of the deceased cases were misdiagnosed initially, and treatment was delayed. Furthermore, a higher rodent population density and lower HFRS vaccine coverage were observed in the affected area, which indicates a possible role in the outbreak. Rattus norvegicus (Rn) and Mus musculus (Mm) were the predominant host populations in the area. Genotyping revealed that all HVs from patients and rodents were Hantaan virus (HTNV). Sequence analysis of the S segments revealed that the HTNVs reported in this study had high similarity with strains reported in 2011 and 1985, but these viruses diverged from a strain isolated in 1984 and the HTNV prototype strain 76-118. Detection of anti-HV IgG and amplification of the S segment of HTNV from a non-natural HTNV reservoir indicates that further investigations by increased rodent trapping are necessary. PMID:24481251

  11. Dobrava virus carried by the yellow-necked field mouse Apodemus flavicollis, causing hemorrhagic fever with renal syndrome in Romania.

    PubMed

    Panculescu-Gatej, Raluca Ioana; Sirbu, Anca; Dinu, Sorin; Waldstrom, Maria; Heyman, Paul; Murariu, Dimitru; Petrescu, Angela; Szmal, Camelia; Oprisan, Gabriela; Lundkvist, Ake; Ceianu, Cornelia S

    2014-05-01

    Hemorrhagic fever with renal syndrome (HFRS) has been confirmed by serological methods during recent years in Romania. In the present study, focus-reduction neutralization tests (FRNT) confirmed Dobrava hantavirus (DOBV) as the causative agent in some HFRS cases, but could not distinguish between DOBV and Saaremaa virus (SAAV) infections in other cases. DOBV was detected by a DOBV-specific TaqMan assay in sera of nine patients out of 22 tested. Partial sequences of the M genomic segment of DOBV were obtained from sera of three patients and revealed the circulation of two DOBV lineages in Romania. Investigation of rodents trapped in Romania found three DOBV-positive Apodemus flavicollis out of 83 rodents tested. Two different DOBV lineages were also detected in A. flavicollis as determined from partial sequences of the M and S genomic segments. Sequences of DOBV in A. flavicollis were either identical or closely related to the sequences obtained from the HFRS patients. The DOBV strains circulating in Romania clustered in two monophyletic groups, together with strains from Slovenia and the north of Greece. This is the first evidence for the circulation of DOBV in wild rodents and for a DOBV etiology of HFRS in Romania.

  12. [The disposition of natural foci of hemorrhagic fever with renal syndrome in different landscape areas of Tyumen Province].

    PubMed

    Miasnikov, Iu A; Apekina, N S; Zuevskiĭ, A P; Khitrin, A V; Bernshteĭn, A D

    1992-01-01

    Lungs of 3159 animals of the forest complex from 90 areas of 30 administrative districts of Tyumen Province were examined by enzyme immunoassays for antigen of hemorrhagic fever with renal syndrome (HFRS) during 5 years, 1985-1989. The antigen of HERS virus was detected in the lungs of mammals of 8 species: Clethrionomys glareolus and Cl. rutilus, Siberian and Arctic lemmings (first findings in the world), M. oeconomus, field mouse, common and pygmy shrews. Nearly all the findings refer to the subzone of southern taiga and adjacent areas of subtaiga subzone where Cl. glareolus is the main reservoir of infection and Cl. rutilus an additional one. In the tundra zone, Siberian lemming is the main reservoir of infection and Arctic lemming an additional one. No natural foci of HFRS were found in forest steppe and forest tundra zones. In the subzone of the northern and middle taiga, the antigen was found only on 4 occasions: 3 in common shrews and one in Cl. glareolus (near the town of Khanty-Mansisk). An irregular annual infection rate with HFRS virus was observed in Cl. glareolus as well as its decline from spring to autumn. It cannot be ruled out that lemmings are carriers of a distinct HFRS virus serotype.

  13. Tofla virus: A newly identified Nairovirus of the Crimean-Congo hemorrhagic fever group isolated from ticks in Japan

    PubMed Central

    Shimada, Satoshi; Aoki, Kotaro; Nabeshima, Takeshi; Fuxun, Yu; Kurosaki, Yohei; Shiogama, Kazuya; Onouchi, Takanori; Sakaguchi, Miako; Fuchigami, Takeshi; Ono, Hokuto; Nishi, Kodai; Posadas-Herrera, Guillermo; Uchida, Leo; Takamatsu, Yuki; Yasuda, Jiro; Tsutsumi, Yutaka; Fujita, Hiromi; Morita, Kouichi; Hayasaka, Daisuke

    2016-01-01

    Ixodid ticks transmit several important viral pathogens. We isolated a new virus (Tofla virus: TFLV) from Heamaphysalis flava and Heamaphysalis formsensis in Japan. The full-genome sequences revealed that TFLV belonged to the genus Nairovirus, family Bunyaviridae. Phylogenetic analyses and neutralization tests suggested that TFLV is closely related to the Hazara virus and that it is classified into the Crimean-Congo hemorrhagic fever group. TFLV caused lethal infection in IFNAR KO mice. The TFLV-infected mice exhibited a gastrointestinal disorder, and positron emission tomography-computed tomography images showed a significant uptake of 18F-fluorodeoxyglucose in the intestinal tract. TFLV was able to infect and propagate in cultured cells of African green monkey-derived Vero E6 cells and human-derived SK-N-SH, T98-G and HEK-293 cells. Although TFLV infections in humans and animals are currently unknown, our findings may provide clues to understand the potential infectivity and to develop of pre-emptive countermeasures against this new tick-borne Nairovirus. PMID:26863911

  14. Viremia and antibody response of small African and laboratory animals to Crimean-Congo hemorrhagic fever virus infection.

    PubMed

    Shepherd, A J; Leman, P A; Swanepoel, R

    1989-05-01

    Eleven species of small African wild mammals, laboratory rabbits, guinea pigs, and Syrian hamsters were infected with Crimean-Congo hemorrhagic fever (CCHF) virus. Low-titered viremia followed by development of antibody was observed in scrub hares (Lepus saxatilis), Cape ground squirrels (Xerus inauris), red veld rats (Aethomys chrysophilus), white tailed rats (Mystromys albicaudatus), bushveld gerbils (Tatera leucogaster), striped mice (Rhabdomys pumilio), and guinea pigs. The maximum viremic titer in 4 scrub hares was 10(1.7-4.2) 50% mouse lethal doses/ml. Viremia was detected in 1/17 infected laboratory rabbits. Antibody response was only detected in South African hedgehogs (Atelerix frontalis), highveld gerbils (T. brantsii), Namaqua gerbils (Desmodillus auricularis), 2 species of multimammate mouse (Mastomys natalensis and M. coucha), and Syrian hamsters. The results of the study indicate that a proportion of infected scrub hares develop CCHF viremia of an intensity shown in the Soviet Union to be sufficient for infection of feeding immature ixodid ticks, but that South African hedgehogs and wild rodents are unlikely to be of importance as maintenance hosts of the virus in southern Africa.

  15. Medical Acute Complications of Intracerebral Hemorrhage in Young Adults

    PubMed Central

    Koivunen, Riku-Jaakko; Haapaniemi, Elena; Satopää, Jarno; Niemelä, Mika; Tatlisumak, Turgut; Putaala, Jukka

    2015-01-01

    Background. Frequency and impact of medical complications on short-term mortality in young patients with intracerebral hemorrhage (ICH) have gone unstudied. Methods. We reviewed data of all first-ever nontraumatic ICH patients between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 to identify medical complications suffered. Logistic regression adjusted for known ICH prognosticators was used to identify medical complications associated with mortality. Results. Among the 325 eligible patients (59% males, median age 42 [interquartile range 34–47] years), infections were discovered in 90 (28%), venous thrombotic events in 13 (4%), cardiac complications in 4 (1%), renal failure in 59 (18%), hypoglycemia in 15 (5%), hyperglycemia in 165 (51%), hyponatremia in 146 (45%), hypernatremia in 91 (28%), hypopotassemia in 104 (32%), and hyperpotassemia in 27 (8%). Adjusted for known ICH prognosticators and diabetes, the only independent complication associated with 3-month mortality was hyperglycemia (plasma glucose >8.0 mmol/L) (odds ratio: 5.90, 95% confidence interval: 2.25–15.48, P < 0.001). Three or more separate complications suffered also associated with increased mortality (7.76, 1.42–42.49, P = 0.018). Conclusions. Hyperglycemia is a frequent complication of ICH in young adults and is independently associated with increased mortality. However, multiple separate complications increase mortality even further. PMID:25722917

  16. Transjugular intrahepatic portosystemic shunt for the management of acute variceal hemorrhage

    PubMed Central

    Loffroy, Romaric; Estivalet, Louis; Cherblanc, Violaine; Favelier, Sylvain; Pottecher, Pierre; Hamza, Samia; Minello, Anne; Hillon, Patrick; Thouant, Pierre; Lefevre, Pierre-Henri; Krausé, Denis; Cercueil, Jean-Pierre

    2013-01-01

    Acute variceal hemorrhage, a life-threatening condition that requires a multidisciplinary approach for effective therapy, is defined as visible bleeding from an esophageal or gastric varix at the time of endoscopy, the presence of large esophageal varices with recent stigmata of bleeding, or fresh blood visible in the stomach with no other source of bleeding identified. Transfusion of blood products, pharmacological treatments and early endoscopic therapy are often effective; however, if primary hemostasis cannot be obtained or if uncontrollable early rebleeding occurs, transjugular intrahepatic portosystemic shunt (TIPS) is recommended as rescue treatment. The TIPS represents a major advance in the treatment of complications of portal hypertension. Acute variceal hemorrhage that is poorly controlled with endoscopic therapy is generally well controlled with TIPS, which has a 90% to 100% success rate. However, TIPS is associated with a mortality of 30% to 50% in such a setting. Emergency TIPS should be considered early in patients with refractory variceal bleeding once medical treatment and endoscopic sclerotherapy failure, before the clinical condition worsens. Furthermore, admission to specialized centers is mandatory in such a setting and regional protocols are essential to be organized effectively. This review article discusses initial management and then focuses on the specific role of TIPS as a primary therapy to control acute variceal hemorrhage, particularly as a rescue therapy following failure of endoscopic approaches. PMID:24115809

  17. [Medical treatment of acute hemorrhagic stroke--observation of 44 cases with FCMCK therapy].

    PubMed

    Wang, J

    1990-02-01

    Based on the analysis of heritable autoregulatory functions and adaptive developments which occur long course of in response to inner and outer environment, FCMCK therapy was first designed to mobilize the autoregulatory system and resist the stress of acute hemorrhagic cerebral stroke. In this paper, 44 cases of acute hemorrhagic cerebral stroke were treated with FCMCK therapy, with another 44 cases treated with mannitol as control. The result showed that the mortality rate of the treated group was 4.5% (2/44), significantly lower than that of the control (47.7%, 21/44, P less than 0.01). FCMCK therapy in acute hemorrhagic cerebral stroke has the following advantages: 1) effectiveness in maintenance of adequate blood pressure; 2) effectiveness in reduction of cardiac arrhythmias and other complications; 3) i.v. drip of Ca and repeated use of digitalis shows atoxic effect; and 4) respiratory failure improves without stopping i.v. drip of Mg. The mechanism of FCMCK therapy is briefly discussed by the authors.

  18. Asymptomatic rhythm and conduction abnormalities in children with acute rheumatic fever: 24-hour electrocardiography study.

    PubMed

    Karacan, Mehmet; Işıkay, Sedat; Olgun, Haşim; Ceviz, Naci

    2010-12-01

    Some rhythm and conduction abnormalities can occur in children with acute rheumatic fever. These abnormalities have been defined based on standard electrocardiography; however, the real prevalence of these abnormalities has not been investigated previously by the evaluation of long-term electrocardiographic recordings. In this study, we evaluated the asymptomatic rhythm and conduction abnormalities in children with acute rheumatic fever by evaluating the 24-hour electrocardiography. We evaluated the standard electrocardiography and the 24-hour electrocardiography of 64 children with acute rheumatic fever. On standard electrocardiography, the frequency of the first-degree atrioventricular block was found to be 21.9%. Electrocardiography at 24 hours detected three additional and separate patients with a long PR interval. Mobitz type I block and atypical Wenckebach periodicity were determined in one patient (1.56%) on 24-hour electrocardiography. While accelerated junctional rhythm was detected in three patients on standard electrocardiography, it was present in nine patients according to 24-hour electrocardiography. Premature contractions were present in 1.7% of standard electrocardiography, but in 29.7% of 24-hour electrocardiography. Absence of carditis was found to be related to the presence of accelerated junctional rhythm (p > 0.05), and the presence of carditis was found to be related to the presence of premature contractions (p = 0.000). In conclusion, our results suggest that in children with acute rheumatic fever, the prevalence of rhythm and conduction abnormalities may be much higher than determined on standard electrocardiography. Further studies are needed to clarify whether or not these abnormalities are specific to acute rheumatic fever.

  19. Acute Lung Injury Accompanying Alveolar Hemorrhage Associated with Flu Vaccination in the Elderly.

    PubMed

    Satoh, Etsuko; Nei, Takahito; Kuzu, Shinichi; Chubachi, Kumi; Nojima, Daisuke; Taniuchi, Namiko; Yamano, Yoshimitsu; Gemma, Akihiko

    2015-01-01

    Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

  20. Can lumbar hemorrhagic synovial cyst cause acute radicular compression? Case report

    PubMed Central

    Timbó, Luciana Sátiro; Rosemberg, Laercio Alberto; Brandt, Reynaldo André; Peres, Ricardo Botticini; Nakamura, Olavo Kyosen; Guimarães, Juliana Frota

    2014-01-01

    Lumbar synovial cysts are an uncommon cause of back pain and radiculopathy, usually manifesting with gradual onset of symptoms, secondary to involvement of the spinal canal. Rarely, intracyst hemorrhage occurs, and may acutely present as radicular - or even spinal cord - compression syndrome. Synovial cysts are generally associated with degenerative facets, although the pathogenesis has not been entirely established. We report a case of bleeding complication in a synovial cyst at L2-L3, adjacent to the right interfacet joint, causing acute pain and radiculopathy in a patient on anticoagulation therapy who required surgical resection. PMID:25628207

  1. Relationship between IFNA1, IFNA5, IFNA10, and IFNA17 gene polymorphisms and Crimean-Congo hemorrhagic fever prognosis in a Turkish population range.

    PubMed

    Elaldi, Nazif; Yilmaz, Meral; Bagci, Binnur; Yelkovan, Izzet; Bagci, Gokhan; Gozel, Mustafa Gokhan; Engin, Aynur; Bakir, Mehmet; Dokmetas, Ilyas

    2016-07-01

    Crimean-Congo hemorrhagic fever (CCHF) is a fatal emerging acute viral infection. Not much is known regarding the pathogenic mechanisms and the reasons behind severe or mild disease courses in CCHF. IFN-alpha (IFNA) is one of the essential cytokines in the immune system. Existence of single nucleotide gene polymorphisms (SNPs) in cytokines can cause susceptibility or resistance to viral agents and different clinical courses. Hence, the relationship between SNPs in genes encoding cytokines (IFNA1 -1823G/A (rs1332190), IFNA5 -2529T/A (rs758236), IFNA10 Cys20stop (rs10119910), and IFNA17 Ile184Arg (rs9298814) SNPs and disease susceptibility were investigated. The associations between SNPs and CCHF prognosis were also studied. Total 150 patients with CCHF and 170 healthy individuals were enrolled. Genotyping was performed by PCR-RFLP methods. The frequency of IFNA1 -1823 (rs1332190) GG genotype was significantly higher in control subjects than CCHF patients (20% vs. 8%; P = 0.01). For IFNA17 Ile184Arg (rs9298814) polymorphism, CCHF patients having TG genotype had a higher frequency than the control subjects (38% vs. 32.4%; P = 0.039). The distribution of TT + TG genotype frequencies was also significantly higher in CCHF group than the controls (97.3% vs. 91.8%; P = 0.049). Genotype and allele frequencies for IFNA subtypes between fatal and survivors were the same (P > 0.05). Genotype and allele frequencies between severe and mild/moderate CCHF patients were also the same (P > 0.05). The results show that IFNA1 rs1332190 and IFNA17 rs9298814 SNPs may play an important role in CCHF susceptibility. Determining the existence of other connections for IFNA SNPs and CCHF severity and fatality requires further investigations.

  2. Hemorrhagic transformation and cerebral edema in acute ischemic stroke: Link to cerebral autoregulation

    PubMed Central

    Castro, Pedro; Azevedo, Elsa; Serrador, Jorge; Rocha, Isabel; Sorond, Farzaneh

    2017-01-01

    Background Hemorrhagic transformation and cerebral edema are feared complications of acute ischemic stroke but mechanisms are poorly understood and reliable early markers are lacking. Early assessment of cerebrovascular hemodynamics may advance our knowledge in both areas. We examined the relationship between dynamic cerebral autoregulation (CA) in the early hours post ischemia, and the risk of developing hemorrhagic transformation and cerebral edema at 24 h post stroke Methods We prospectively enrolled 46 patients from our center with acute ischemic stroke in the middle cerebral artery territory. Cerebrovascular resistance index was calculated. Dynamic CA was assessed by transfer function analysis (coherence, phase and gain) of the spontaneous blood flow velocity and blood pressure oscillations. Infarct volume, hemorrhagic transformation, cerebral edema, and white matter changes were collected from computed tomography performed at presentation and 24 h. Results At admission, phase was lower (worse CA) in patients with hemorrhagic transformation [6.6 ± 30 versus 45 ± 38°; adjusted odds ratio 0.95 (95% confidence internal 0.94–0.98), p = 0.023] and with cerebral edema [6.6 ± 30 versus 45 ± 38°, adjusted odds ratio 0.96 (0.92–0.999), p = 0.044]. Progression to edema was associated with lower cerebrovascular resistance (1.4 ± 0.2 versus 2.3 ± 1.5 mm Hg/cm/s, p = 0.033) and increased cerebral blood flow velocity (51 ± 25 versus 42 ± 17 cm/s, p = 0.033) at presentation. All hemodynamic differences resolved at 3 months Conclusions Less effective CA in the early hour post ischemic stroke is associated with increased risk of hemorrhagic transformation and cerebral edema, possibly reflecting breakthrough hyperperfusion and microvascular injury. Early assessment of dynamic CA could be useful in identifying individuals at risk for these complications. PMID:28017224

  3. Transient stabbing headache from an acute thalamic hemorrhage.

    PubMed

    Robbins, Matthew S

    2011-06-01

    Stabbing headache can be encountered in both primary and secondary forms, but has been infrequently reported among patients with stroke, and is not known to be associated with a small well-circumscribed brain lesion. A 95-year-old woman taking warfarin presented with the sudden onset of stabbing headache strictly in the right frontal and supraorbital regions, along with gait imbalance and dysarthria. Neuroimaging revealed a small left thalamic hematoma. This association of an acute thalamic lesion with stabbing headache in the contralateral trigeminal distribution is discussed, along with a brief review of stabbing headache occurring in cerebrovascular disease.

  4. [Candid#1 vaccine against Argentine hemorrhagic fever produced in Argentina. Immunogenicity and safety].

    PubMed

    Enria, Delia A; Ambrosio, Ana M; Briggiler, Ana M; Feuillade, María Rosa; Crivelli, Eleonora

    2010-01-01

    A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slightly higher than the efficacy estimated from previous studies (95.5%). There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine) were found for both vaccines. These included: headache, weakness, myalgias, mild low blood cell (< 4,000/mm(3)) and platelet (< 150,000/mm(3)) counts, nausea and/or vomiting, fever, retroocular pain, dizziness, microhematuria, low backache and exantema. These results indicate that the vaccine Candid#1 manufactured in Argentina is equivalent to the manufactured in USA. These results allowed the National Institute of Human Viral Diseases (INEVH) to register the vaccine produced locally under the National Regulatory Authority (ANMAT).

  5. Tropical fevers: Management guidelines.

    PubMed

    Singhi, Sunit; Chaudhary, Dhruva; Varghese, George M; Bhalla, Ashish; Karthi, N; Kalantri, S; Peter, J V; Mishra, Rajesh; Bhagchandani, Rajesh; Munjal, M; Chugh, T D; Rungta, Narendra

    2014-02-01

    Tropical fevers were defined as infections that are prevalent in, or are unique to tropical and subtropical regions. Some of these occur throughout the year and some especially in rainy and post-rainy season. Concerned about high prevalence and morbidity and mortality caused by these infections, and overlapping clinical presentations, difficulties in arriving at specific diagnoses and need for early empiric treatment, Indian Society of Critical Care Medicine (ISCCM) constituted an expert committee to develop a consensus statement and guidelines for management of these diseases in the emergency and critical care. The committee decided to focus on most common infections on the basis of available epidemiologic data from India and overall experience of the group. These included dengue hemorrhagic fever, rickettsial infections/scrub typhus, malaria (usually falciparum), typhoid, and leptospira bacterial sepsis and common viral infections like influenza. The committee recommends a 'syndromic approach' to diagnosis and treatment of critical tropical infections and has identified five major clinical syndromes: undifferentiated fever, fever with rash / thrombocytopenia, fever with acute respiratory distress syndrome (ARDS), fever with encephalopathy and fever with multi organ dysfunction syndrome. Evidence based algorithms are presented to guide critical care specialists to choose reliable rapid diagnostic modalities and early empiric therapy based on clinical syndromes.

  6. Treatments for reversing warfarin anticoagulation in patients with acute intracranial hemorrhage: a structured literature review

    PubMed Central

    2011-01-01

    Study objective The acute management of patients on warfarin with spontaneous or traumatic intracranial hemorrhage continues to be debated in the medical literature. The objective of this paper was to conduct a structured review of the medical literature and summarize the advantages and risks of the available treatment options for reversing warfarin anticoagulation in patients who present to the emergency department with acute intracranial hemorrhage. Methods A structured literature search and review of articles relevant to intracranial hemorrhage and warfarin and treatment in the emergency department was performed. Databases for PubMed, CINAHL, and Cochrane EBM Reviews were electronically searched using keywords covering the concepts of anticoagulation drugs, intracranial hemorrhage (ICH), and treatment. The results generated by the search were limited to English- language articles and reviewed for relevance to our topic. The multiple database searches revealed 586 papers for review for possible inclusion. The final consensus of our comprehensive search strategy was a total of 23 original studies for inclusion in our review. Results Warfarin not only increases the risk of but also the severity of ICH by causing hematoma expansion. Prothrombin complex concentrate is statistically significantly faster at correcting the INR compared to fresh frozen plasma transfusions. Recombinant factor VIIa appears to rapidly reverse warfarin's effect on INR; however, this treatment is not FDA-approved and is associated with a 5% thromboembolic event rate. Slow intravenous dosing of vitamin K is recommended in patients with ICH. The 30-day risk for ischemic stroke after discontinuation of warfarin therapy was 3-5%. The risks of not reversing the anticoagulation in ICH generally outweigh the risk of thrombosis in the acute setting. Conclusions Increasing numbers of patients are on anticoagulation including warfarin. There is no uniform standard for reversing warfarin in intracranial

  7. Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

    PubMed

    Osawa, Aiko; Maeshima, Shinichiro

    2016-04-01

    Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

  8. First Identification and Description of Rickettsioses and Q Fever as Causes of Acute Febrile Illness in Nicaragua

    PubMed Central

    Reller, Megan E.; Chikeka, Ijeuru; Miles, Jeremy J.; Dumler, J. Stephen; Woods, Christopher W.; Mayorga, Orlando; Matute, Armando J.

    2016-01-01

    Background Rickettsial infections and Q fever present similarly to other acute febrile illnesses, but are infrequently diagnosed because of limited diagnostic tools. Despite sporadic reports, rickettsial infections and Q fever have not been prospectively studied in Central America. Methodology/Principal Findings We enrolled consecutive patients presenting with undifferentiated fever in western Nicaragua and collected epidemiologic and clinical data and acute and convalescent sera. We used ELISA for screening and paired sera to confirm acute (≥4-fold rise in titer) spotted fever and typhus group rickettsial infections and Q fever as well as past (stable titer) infections. Characteristics associated with both acute and past infection were assessed. Conclusions/Significance We enrolled 825 patients and identified acute rickettsial infections and acute Q fever in 0.9% and 1.3%, respectively. Clinical features were non-specific and neither rickettsial infections nor Q fever were considered or treated. Further study is warranted to define the burden of these infections in Central America. PMID:28036394

  9. Acute Q fever infection in Thuringia, Germany, after burial of roe deer fawn cadavers (Capreolus capreolus): a case report

    PubMed Central

    Schleenvoigt, B.T.; Sprague, L.D.; Mertens, K.; Moog, U.; Schmoock, G.; Wolf, G.; Neumann, M.; Pletz, M.W.; Neubauer, H.

    2015-01-01

    We report on a case of a 48-year-old man who presented with acute Q fever infection after burying two fawn cadavers (Capreolus capreolus). Recent outbreaks of Q fever in Europe have been traced back to intensive goat breeding units, sheep flocks in the proximity of highly populated urban areas or to farmed deer. To our knowledge, this is the first case report describing Q fever infection in a human linked to roe deer as a source of infection. PMID:26566445

  10. Determination of nasal mucociliary clearance time and nasal symptom in patients with crimean-congo hemorrhagic fever.

    PubMed

    Durmuş, Kasım; Engin, Aynur; Karataş, Tuba Doğan; Gözel, Mustafa Gökhan; Altuntas, Emine Elif

    2016-11-03

    Crimean-Congo hemorrhagic fever (CCHF) is an important health problem in Turkey. Number of studies on symptoms of ear nose throat system and indicating whether or not the organs are affected in patients with CCHF is limited. The aim of the present study was to investigate whether CCHF infections caused any change in nasal physiology in adult patients or not by using saccharin transit time (STT) and nasal symptom scoring. Twenty subjects with laboratory-confirmed diagnosis of CCHF and 28 healthy control subjects were included in the present study. A saccharin test was used to evaluate nasal mucociliary clearance time (NMCT) and the nasal symptom scoring used in allergic rhinitis was modified and used to examine the symptoms of the patients. The average STT of CCHF and control groups were 472.70 ± 151.58 and 276.07 ± 89.65 sec, respectively. The difference between them was statistically significant (P = 0.00, P < 0.05). When those in CCHF group were classified according to timing of the test, STT average of those undergoing the test on the 1st-3rd days (n = 10) and 4th-6th (n = 10) days was 547.00 ± 154.37 and 398.40 ± 111.39 sec, respectively. The difference between them was statistically significant (P = 0.024; P < 0.05). The results of the present study showed that NMCT prolonged in adult patients with CCHF compared to those in the control group despite the fact that it was within normal limits. For these reasons, clinicians should follow-up CCHF patients more closely for respiratory tract diseases and sinonasal and middle ear infections. J. Med. Virol. © 2016 Wiley Periodicals, Inc.

  11. Crimean-Congo Hemorrhagic Fever in the One-Humped Camel (Camelus dromedarius) in East and Northeast of Iran

    PubMed Central

    Champour, Mohsen; Chinikar, Sadegh; Mohammadi, Gholamreza; Razmi, Gholamreza; Mostafavi, Ehsan; Shah-Hosseini, Nariman; Khakifirouz, Sahar; Jalali, Tahmineh

    2016-01-01

    Background: This comprehensive study was conducted on multi-purpose one-humped camel (Camelus dromedarius) sera and ticks to assess the epidemiological aspects of the Crimean-Congo hemorrhagic fever virus (CCHFV) in northeast Iran. Methods: From May 2012 to January 2013, eleven cities were randomly selected in the Khorasan Provinces of Iran as “clusters,” and at least 14 one-humped camels were sampled from each area. Reverse transcriptase polymerase chain reaction was used for the detection of the CCHFV genome in ticks. Sera were analyzed using specific enzyme-linked immunosorbent assay tests. Results: Four hundred and eighty ixodid ticks were collected, and the genome of the CCHFV was detected in 49 (10.2%) out of 480 ticks. The CCHFV genome was detected in two out of four tick species, and in tick samples from three cities in Khorassan-e-Jonoobi. All three provinces, and six out of eleven cities, were CCHFV-specific IgG-positive. In total, nine (5.3%) out of 170 one-humped camels were IgG-positive. The highest rate of IgG-positive samples was found in Nehbandan (16.67%). Conclusion: Continued surveillance and strictly enforced importation and quarantine practices should be implemented to prevent human exposure and the on-going dispersal of infected ticks and livestock in these regions. It is recommended that acaricides be used to prevent CCHF transmission to humans, and to reduce the tick population. In addition, care should be taken by abattoirs workers and people who work with one-humped camels. PMID:27308275

  12. Crimean-Congo hemorrhagic fever virus clades V and VI (Europe 1 and 2) in ticks in Kosovo, 2012.

    PubMed

    Sherifi, Kurtesh; Cadar, Daniel; Muji, Skender; Robaj, Avni; Ahmeti, Salih; Jakupi, Xhevat; Emmerich, Petra; Krüger, Andreas

    2014-09-01

    Despite being a small country, Kosovo represents one of the few foci of Crimean-Congo hemorrhagic fever (CCHF) in Europe. The distribution of Kosovar tick vectors and the evolution of CCHF virus in ticks are both as yet unknown. A better description of the extent and the genetic diversity of CCHFV in ticks from endemic settings is essential, in order to be controlled. We investigated the 2012 distribution of Kosovar ticks alongside the prevalence and the phylogeography of tick-derived CCHFV. Hyalomma marginatum dominated in the endemic municipalities with 90.2% versus 24.3% in the non-endemic regions. Of 1,102 tested ticks, 40 (3.6%) were CCHFV-positive, belonging to H. marginatum (29), Rhipicephalus bursa (10), and Ixodes ricinus (1). The virus strains clustered with clade V and VI related sequences. They fell into two lineages: Kosovo I and II. Kosovo I comprised strains recovered exclusively from R. bursa ticks and was closely related to AP92 prototype strain. Kosovo II clustered into Kosovo IIa, including human-derived strains, and IIb including only strains detected in H. marginatum and I. ricinus. Our phylogeographic reconstruction suggests two temporally distinct CCHFV introductions: the most probable location of the most recent common ancestor of Kosovo I lineage was in Greece (63 years ago) and that of lineages IIa-b in Turkey (35 years ago). After each CCHFV introduction into Kosovo, subsequent lineage expansions suggest periods of in situ evolution. The study provides the first insight into the genetic variability and the origin of CCHFV in ticks from Kosovo. Our findings indicate the spreading of CCHFV to non-endemic areas, which underlines the importance of further studies in order to monitor and predict future CCHF outbreaks in Kosovo. The AP92-like strains appear to be more widespread than previously thought and may provide a promising target for experimental studies due to their assumed low pathogenicity.

  13. Relationship of plasma cell-free DNA level with mortality and prognosis in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Bakir, Mehmet; Engin, Aynur; Kuskucu, Mert Ahmet; Bakir, Sevtap; Gündag, Omür; Midilli, Kenan

    2016-07-01

    Crimean-Congo hemorrhagic fever (CCHF) is a viral infection. Circulating plasma cell-free DNA (pcf-DNA) is a novel marker indicating cellular damage. So far, the role of pcf-DNA did not investigate in CCHF patients. In the current study, pcf-DNA levels were investigated in CCHF patients with different clinical severity grades to explore the relationship between circulating pcf-DNA level, virus load, and disease severity. Seventy-two patients were categorized as mild, intermediate, and severe based on severity grading scores. The pcf-DNA level was obtained from all participants on admission and from the survivors on the day of the discharge. The controls consisted of 31 healthy. Although the pcf-DNA level at admission was higher in patients than in the controls, the difference was not statistically significant (P = 0.291). However, at admission and in the convalescent period, the difference between pcf-DNA levels in mild, intermediate, and severe patient groups was significant. The pcf-DNA level in severe patients was higher than in the others. Furthermore, compared to survivors, non-survivors had higher pcf-DNA levels at admission (P = 0.001). A direct relationship was found between the pcf-DNA level and the viral load on the day of discharge in surviving patients. ROC curve analysis identified a pcf-DNA level of 0.42 as the optimal cut-off for prediction of mortality. The positive predictive value, negative predictive value, specificity, and sensitivity for predicting mortality was 100%, 72%, 100%, and 79%, respectively. In summary, our findings revealed that pcf-DNA levels may be used as a biomarker in predicting CHHF prognosis.

  14. Seroprevalence of Crimean-Congo Hemorrhagic Fever Virus in Erzincan Province, Turkey, Relationship with Geographic Features and Risk Factors.

    PubMed

    Cikman, Aytekin; Aydin, Merve; Gulhan, Baris; Karakecili, Faruk; Kesik, Ozan Arif; Ozcicek, Adalet; Akin, Hicran; Kara, Murat

    2016-03-01

    To determine the seroprevalence and risk factors associated with Crimean-Congo hemorrhagic fever virus (CCHFV) in residents of Erzincan, Turkey. Although CCHFV is endemic in Erzincan, this is the first study to evaluate its seroprevalence in this region. This study included a total of 372 subjects, 174 of whom had been exposed to or bitten by ticks, 145 of whom worked with livestock, and 53 of whom resided in the city and did not have exposure to livestock. Data on CCHFV IgG and IgM antibodies were extracted from serum samples collected from all subjects using an ELISA. All samples were tested for CCHFV IgG and CCHFV IgM. Only IgM-positive samples were processed for detection of viral RNA through RT-PCR. Using seropositive cases only, we performed spatial analyses to evaluate correlations between seroprevalence and geographic location (i.e., proximity to rivers, altitude, and slope angle of land). In this study, 14.0% (52/322) of the total subjects were positive for CCHFV IgG. Seven of the individuals were positive both for CCHFV IgG and CCHFV IgM. Of these seven, only one sample tested positive for CCHFV RNA. Individuals who worked with livestock in the rural areas and had a history of tick exposure were statistically more likely to test positive for CCHFV IgG than individuals from the city and not exposed to ticks (p < 0.05). Seroprevalence was affected by geographic characteristics, including distance to rivers, altitude, and slope angle of land. We observed a high seroprevalence of CCHFV in Erzincan, which is similar to that observed in other endemic regions of Turkey. CCHFV seroprevalence rates are found to be quite high in the people who live in the sloping fields at certain heights and where there are a lot of rivers and streams.

  15. Fine Epitope Mapping of the Central Immunodominant Region of Nucleoprotein from Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

    PubMed Central

    Liu, Dongliang; Li, Yang; Zhao, Jing; Deng, Fei; Duan, Xiaomei; Kou, Chun; Wu, Ting; Li, Yijie; Wang, Yongxing; Ma, Ji; Yang, Jianhua; Hu, Zhihong; Zhang, Fuchun; Zhang, Yujiang; Sun, Surong

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF), a severe viral disease known to have occurred in over 30 countries and distinct regions, is caused by the tick-borne CCHF virus (CCHFV). Nucleocapsid protein (NP), which is encoded by the S gene, is the primary antigen detectable in infected cells. The goal of the present study was to map the minimal motifs of B-cell epitopes (BCEs) on NP. Five precise BCEs (E1, 247FDEAKK252; E2a, 254VEAL257; E2b, 258NGYLNKH264; E3, 267EVDKA271; and E4, 274DSMITN279) identified through the use of rabbit antiserum, and one BCE (E5, 258NGYL261) recognized using a mouse monoclonal antibody, were confirmed to be within the central region of NP and were partially represented among the predicted epitopes. Notably, the five BCEs identified using the rabbit sera were able to react with positive serum mixtures from five sheep which had been infected naturally with CCHFV. The multiple sequence alignment (MSA) revealed high conservation of the identified BCEs among ten CCHFV strains from different areas. Interestingly, the identified BCEs with only one residue variation can apparently be recognized by the positive sera of sheep naturally infected with CCHFV. Computer-generated three-dimensional structural models indicated that all the antigenic motifs are located on the surface of the NP stalk domain. This report represents the first identification and mapping of the minimal BCEs of CCHFV-NP along with an analysis of their primary and structural properties. Our identification of the minimal linear BCEs of CCHFV-NP may provide fundamental data for developing rapid diagnostic reagents and illuminating the pathogenic mechanism of CCHFV. PMID:25365026

  16. Crimean-Congo Hemorrhagic Fever Virus Clades V and VI (Europe 1 and 2) in Ticks in Kosovo, 2012

    PubMed Central

    Muji, Skender; Robaj, Avni; Ahmeti, Salih; Jakupi, Xhevat; Emmerich, Petra; Krüger, Andreas

    2014-01-01

    Despite being a small country, Kosovo represents one of the few foci of Crimean-Congo hemorrhagic fever (CCHF) in Europe. The distribution of Kosovar tick vectors and the evolution of CCHF virus in ticks are both as yet unknown. A better description of the extent and the genetic diversity of CCHFV in ticks from endemic settings is essential, in order to be controlled. We investigated the 2012 distribution of Kosovar ticks alongside the prevalence and the phylogeography of tick-derived CCHFV. Hyalomma marginatum dominated in the endemic municipalities with 90.2% versus 24.3% in the non-endemic regions. Of 1,102 tested ticks, 40 (3.6%) were CCHFV-positive, belonging to H. marginatum (29), Rhipicephalus bursa (10), and Ixodes ricinus (1). The virus strains clustered with clade V and VI related sequences. They fell into two lineages: Kosovo I and II. Kosovo I comprised strains recovered exclusively from R. bursa ticks and was closely related to AP92 prototype strain. Kosovo II clustered into Kosovo IIa, including human-derived strains, and IIb including only strains detected in H. marginatum and I. ricinus. Our phylogeographic reconstruction suggests two temporally distinct CCHFV introductions: the most probable location of the most recent common ancestor of Kosovo I lineage was in Greece (63 years ago) and that of lineages IIa-b in Turkey (35 years ago). After each CCHFV introduction into Kosovo, subsequent lineage expansions suggest periods of in situ evolution. The study provides the first insight into the genetic variability and the origin of CCHFV in ticks from Kosovo. Our findings indicate the spreading of CCHFV to non-endemic areas, which underlines the importance of further studies in order to monitor and predict future CCHF outbreaks in Kosovo. The AP92-like strains appear to be more widespread than previously thought and may provide a promising target for experimental studies due to their assumed low pathogenicity. PMID:25255381

  17. Benign Sphenoid Wing Meningioma Presenting with an Acute Intracerebral Hemorrhage – A Case Report

    PubMed Central

    Frič, Radek; Hald, John K.; Antal, Ellen-Ann

    2016-01-01

    BACKGROUND AND STUDY OBJECT We report an unusual case of a benign lateral sphenoid wing meningioma that presented with, and was masked by, an acute intracerebral hemorrhage. CASE REPORT A 68-year-old woman was admitted after sudden onset of coma. Computed tomography (CT) revealed an intracerebral hemorrhage, without any underlying vascular pathology on CT angiography. During the surgery, we found a lateral sphenoid wing meningioma with intratumoral bleeding that extended into the surrounding brain parenchyma. RESULTS We removed the hematoma and resected the tumor completely in the same session. The histopathological classification of the tumor was a WHO grade I meningothelial meningioma. The patient recovered very well after surgery, without significant neurological sequelae. CONCLUSIONS: Having reviewed the relevant references from the medical literature, we consider this event as an extremely rare presentation of a benign sphenoid wing meningioma in a patient without any predisposing medical factors. The possible mechanisms of bleeding from this tumor type are discussed. PMID:27127413

  18. [Fever and lymphadenopathy: acute toxoplasmosis in an immunocompetent patient].

    PubMed

    Kaparos, Nikolaos; Favrat, Bernard; D'Acremont, Valérie

    2014-11-26

    Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii. In Switzerland about a third of the population has antibodies against this pathogen and has thus already been in contact with the parasite or has contracted the disease. Immunocompetent patients are usually asymptomatic (80-90%) during primary infection. The most common symptom is neck or occipital lymphadenopathy. Serology is the diagnostic gold standard in immunocompetent individuals. The presence of IgM antibodies is however not sufficient to make a definite diagnosis of acute toxoplasmosis. Distinction between acute and chronic toxoplasmosis requires additional serological tests (IgG avidity test). If required, the most used and probably most effective treatment is the combination of pyrimethamine and sulfadiazine, with folinic acid.

  19. Acute hemorrhage in a colloid cyst of the third ventricle: A rare cause of sudden deterioration

    PubMed Central

    Carrasco, Rodrigo; Pascual, José M.; Medina-López, Diego; Burdaspal-Moratilla, Ana

    2012-01-01

    Background: Acute neurological deterioration and death in a patient harboring a colloid cyst of the third ventricle remains a poorly understood phenomenon. Sudden neurological derangement caused by spontaneous bleeding within a colloid cyst is a rare and potentially fatal event, usually requiring immediate diagnosis and emergency surgical treatment. Case Description: A 47-year-old male presented with acute right-sided hemiparesis and speech impediment, followed by rapid deterioration of consciousness. Neuroimaging studies showed a rounded mass at the roof of the anterior third ventricle, causing biventricular hydrocephalus along with a left-sided basal ganglia hematoma. The lesion showed scattered foci of a recent hemorrhage which extended into the left lateral ventricle. Surgical treatment involved emergency external ventricular drainage followed by the prompt elective total resection of the lesion via a transcallosal route. Pathological findings confirmed the diagnosis of a colloid cyst with focal areas of vascular congestion and blood extravasation within its wall. Conclusions: Spontaneous bleeding into a colloid cyst of the third ventricle may cause acute obstructive hydrocephalus and intracranial hypertension due to rapid enlargement of the lesion. This event may account for the sudden neurological deterioration and/or death observed in a previously asymptomatic patient. The diagnosis of hemorrhagic phenomena within a colloid cyst represents a challenge due to the variable signal usually displayed by these lesions on computed tomography (CT) and magnetic resonance imaging (MRI). Emergency ventricular drainage followed by elective tumoral removal constitutes a valid and safe treatment strategy. PMID:22439115

  20. Simian Hemorrhagic Fever Virus Cell Entry Is Dependent on CD163 and Uses a Clathrin-Mediated Endocytosis-Like Pathway

    PubMed Central

    McCluskey, Adam; Robinson, Phillip J.; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L.; Lauck, Michael; Friedrich, Thomas C.; Goldberg, Tony L.

    2014-01-01

    ABSTRACT Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. IMPORTANCE Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low

  1. IgA-dominant acute poststreptococcal glomerulonephritis with concomitant rheumatic fever successfully treated with steroids: a case report

    PubMed Central

    Rus, Rina R; Toplak, Nataša; Vizjak, Alenka; Mraz, Jerica; Ferluga, Dušan

    2015-01-01

    There are only a few reports of the co-occurrence of acute poststreptococcal glomerulonephritis (APGN) and acute rheumatic fever. We report an unusual case of a 3-year-old boy with nephrotic syndrome and acute renal failure with the transitional need for peritoneal dialysis, biopsy-proven atypical IgA-dominant APGN, and concomitant acute rheumatic fever, successfully treated by steroids. Aggressive treatment with pulses of methylprednisolone proved to be successful and we recommend its use in this type of cases. PMID:26718763

  2. Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

    PubMed

    Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

    2015-01-01

    We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

  3. The effect of phenylbutazone on acute hemorrhagic pancreatitis in the rat.

    PubMed

    Louagie, Y; Hancotte-Lahaye, C; Delloye, C; Mairy, Y; De Muylder, C

    1984-01-01

    The effect of phenylbutazone on acute experimental pancreatitis was investigated in the rat. Severe necrotico-hemorrhagic pancreatitis was produced by intraductal injection of trypsin. Pretreatment by phenylbutazone did not alter the mortality rate but reduced the severity of pancreatitis as was demonstrated by histological quantification (total score 13.35 +/- 0.80 in treated rats versus 17.67 +/- 0.69 in the control group; P less than 0.01). The protective effect of phenylbutazone seems to be related to the specific anti-inflammatory properties of the drug and not to inhibition of prostaglandin synthesis.

  4. [Pathogenetic bases of the use alpha-tocopherol and emoxypin in acute hemorrhage].

    PubMed

    Matveev, S B; Marchenko, V V; Golikov, P P

    1991-01-01

    The accumulation of lipid peroxidation (LP) products and decrease of alpha-tocopherol (TP) content were demonstrable in the heart, lungs, kidneys and liver after acute blood loss. Injection of TP acetate inhibited LP and raised the content of endogenous TP in the heart, lungs and liver. The antioxidant emoxypin increased the reduced oxygen tension in the liver and kidneys after blood loss. The drug prevented the reduction of the glucocorticoid type II receptor level and increased the content of the type III receptors in liver cytosol of hemorrhagic animals.

  5. [Effectiveness of the use of solcoseryl after surgery of acute hemorrhage in gastroduodenal ulcer].

    PubMed

    Fomin, P D; Zaplavskiĭ, A V; Ivanchov, P V; Peresh, E E; Lissov, A I; Tikhonenko, A M

    1998-01-01

    The experience of solcoseryl application in 70 patients, operated on for an acute hemorrhage from gastroduodenal ulcer, was summarized. The preparation was injected intravenously in the dose of 10 ml in 5% solution of glucose every other day during 6 days and then in the dose of 5 ml intramuscularly during 4-5 days. High efficacy of solcoseryl, manifesting by more earlier elimination of pain and oedema, healing of mucosa by first intention, shortening of the treatment duration in stationary by 3-5 days, was established.

  6. A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease

    PubMed Central

    Dowall, SD; Buttigieg, KR; Findlay-Wilson, SJD; Rayner, E; Pearson, G; Miloszewska, A; Graham, VA; Carroll, MW; Hewson, R

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model. PMID:26309231

  7. The Major Determinant of Attenuation in Mice of the Candid1 Vaccine for Argentine Hemorrhagic Fever Is Located in the G2 Glycoprotein Transmembrane Domain▿

    PubMed Central

    Albariño, César G.; Bird, Brian H.; Chakrabarti, Ayan K.; Dodd, Kimberly A.; Flint, Mike; Bergeron, Éric; White, David M.; Nichol, Stuart T.

    2011-01-01

    Candid1, a live-attenuated Junin virus vaccine strain, was developed during the early 1980s to control Argentine hemorrhagic fever, a severe and frequently fatal human disease. Six amino acid substitutions were found to be unique to this vaccine strain, and their role in virulence attenuation in mice was analyzed using a series of recombinant viruses. Our results indicate that Candid1 is attenuated in mice through a single amino acid substitution in the transmembrane domain of the G2 glycoprotein. This work provides insight into the molecular mechanisms of attenuation of the only arenavirus vaccine currently available. PMID:21795336

  8. Factors associated with IgG positivity to Crimean-Congo hemorrhagic fever virus in the area with the highest seroprevalence in Greece.

    PubMed

    Papa, Anna; Sidira, Persefoni; Kallia, Sotiria; Ntouska, Maria; Zotos, Nikolaos; Doumbali, Eleni; Maltezou, Helena C; Demiris, Nikos; Tsatsaris, Andreas

    2013-09-01

    In order to gain insight into the factors playing a role for the high seroprevalence of Crimean-Congo hemorrhagic fever virus in the human population of Thesprotia prefecture, Greece, serum samples were collected from residents of the area together with a questionnaire about demographic and epidemiological factors. A 14.4% seroprevalence was detected, with increased age, agro-pastoral activities, slaughtering, and contact with animals (especially sheep) among the factors associated with seropositivity. The high seroprevalence with the absence of any clinical cases needs further investigation.

  9. A Crimean-Congo hemorrhagic fever (CCHF) viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease.

    PubMed

    Dowall, S D; Buttigieg, K R; Findlay-Wilson, S J D; Rayner, E; Pearson, G; Miloszewska, A; Graham, V A; Carroll, M W; Hewson, R

    2016-01-01

    Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15-70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model.

  10. Postthrombolysis intracranial hemorrhage risk of cerebral microbleeds in acute stroke patients: a systematic review and meta-analysis

    PubMed Central

    Shoamanesh, Ashkan; Kwok, Chun Shing; Lim, Patricia Annabelle; Benavente, Oscar R.

    2014-01-01

    It has been questioned whether patients with cerebral microbleeds are at a greater risk for the development of symptomatic intracerebral hemorrhage following thrombolytic therapy in the management of acute ischemic stroke. Thus far, observational studies have not shown a statistically significant increased risk; however, these have been limited by small sample size. The aim is to better quantify the risk of postthrombolysis intracerebral hemorrhage in patients with acute ischemic stroke and cerebral microbleeds on magnetic resonance imaging. A systematic review of controlled studies investigating the presence of microbleeds on magnetic resonance imaging as a risk factor for intracerebral hemorrhage following thrombolysis in acute stroke patients was conducted. A random effects model meta-analysis was performed. In pooled analysis of five studies totaling 790 participants, the prevalence of microbleeds was 17%. The presence of microbleeds revealed a trend toward an increased risk of postthrombolysis symptomatic intracerebral hemorrhage [odds ratio: 1·98 (95% confidence interval, 0·90 to 4·35; P = 0·09), I2 = 0%]. Adjusted analysis minimizing potential bias resulted in an increased absolute risk of 4·6% for the development of symptomatic intracerebral hemorrhage in patients with cerebral microbleeds [odds ratio: 2·29 (95% confidence interval, 1·01 to 5·17), I2 = 0%] reaching borderline significance (P = 0·05). A significant relationship between increasing microbleed burden and symptomatic intracerebral hemorrhage (P = 0·0015) was observed. Isolated analysis of studies using exclusively intravenous tissue plasminogen activator was insignificant. Our data suggest that patients with cerebral microbleeds are at increased risk for symptomatic intracerebral hemorrhage following thrombolysis for acute ischemic stroke. However, current data are insufficient to justify withholding thrombolytic therapy from acute ischemic stroke patients solely of the basis of

  11. Association between retinal hemorrhagic pattern and macular perfusion status in eyes with acute branch retinal vein occlusion

    PubMed Central

    Muraoka, Yuki; Uji, Akihito; Tsujikawa, Akitaka; Murakami, Tomoaki; Ooto, Sotaro; Suzuma, Kiyoshi; Takahashi, Ayako; Iida, Yuto; Miwa, Yuko; Hata, Masayuki; Yoshimura, Nagahisa

    2016-01-01

    This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28, and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P < 0.001). Parallelism in eyes with a flame-shaped hemorrhage was higher than in those with a non-flame-shaped hemorrhage (P < 0.001), and in those with a nonischemic macula versus those with an ischemic macula (P < 0.001). The area under the curve for parallelism was 0.975 (P < 0.001), suggesting an accurate diagnostic parameter for macular perfusion differentiation. In conclusion, we objectively evaluated retinal hemorrhagic patterns at the posterior pole in BRVO using the parallelism method, which was useful in differentiating macular perfusion status. PMID:27334338

  12. Intravenous tPA Therapy Does Not Worsen Acute Intracerebral Hemorrhage in Mice

    PubMed Central

    Foerch, Christian; Rosidi, Nathanael L.; Schlunk, Frieder; Lauer, Arne; Cianchetti, Flor A.; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Steinmetz, Helmuth; Schaffer, Chris B.; Lo, Eng H.

    2013-01-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy. PMID:23408937

  13. Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice.

    PubMed

    Foerch, Christian; Rosidi, Nathanael L; Schlunk, Frieder; Lauer, Arne; Cianchetti, Flor A; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Steinmetz, Helmuth; Schaffer, Chris B; Lo, Eng H

    2013-01-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.

  14. An outbreak of acute fever among steam turbine condenser cleaners.

    PubMed

    Lauderdale, J F; Johnson, C C

    1983-03-01

    Ten of twelve men who participated in the cleaning of an electric power steam turbine condenser clogged with freshwater sponge experienced an acute febrile illness. Two similar outbreaks have been previously described, one of which has been attributed to the Legionnaires' Disease bacterium. Epidemiologic studies of this case showed a syndrome very similar to the two previously reported episodes. However, the exact etiology for this outbreak has not been identified. Environmental sampling was not initiated until after the cleaning was completed. Subsequent testing did not reveal any likely cause for the outbreak. The delayed onset of symptoms and the nature of the illness pointed to an infectious agent. In the absence of any suitable criteria for employee exposure evaluation, it is suggested that crews cleaning condensers under unusually dirty conditions, especially if eye or respiratory symptoms are reported, should be provided with respiratory protection.

  15. An outbreak of acute fever among steam turbine condenser cleaners

    SciTech Connect

    Lauderdale, J.F.; Johnson, C.C.

    1983-01-01

    Ten of twelve men who participated in the cleaning of an electric power steam turbine condenser clogged with freshwater sponge experienced an acute febrile illness. Two similar outbreaks have been previously described, one of which has been attributed to the Legionnaires Disease bacterium. Epidemiologic studies of this case showed a syndrome very similar to the two previously reported episodes. However, the exact etiology for this outbreak has not been identified. Environmental sampling was not initiated until after the cleaning was completed. Subsequent testing did not reveal any likely cause for the outbreak. The delayed onset of symptoms and the nature of the illness pointed to an infectious agent. In the absence of any suitable criteria for employee exposure evaluation, it is suggested that crews cleaning condensers under unusually dirty conditions, especially if eye or respiratory symptoms are reported, should be provided with respiratory protection.

  16. Bilateral pallidal hemorrhage in toxoplasmosis update of acute symmetric lesions of deep nuclei

    PubMed Central

    Wrubel, Gregory L

    2015-01-01

    As acute symmetric lesions of deep gray nuclei are often associated with an impaired level of consciousness and neuroimaging by itself cannot distinguish between etiologies, diagnosis may be problematic. Appreciation of the cause of the various neuroimaging patterns in conjunction with the history, examination and laboratory investigations allows for accurate diagnosis in the vast majority of cases. Given the metabolic vulnerability of deep gray nuclei, other than bi-thalamic infarction, it follows that toxic-metabolic and hypoxic-ischemic events account for the majority of cases. Nevertheless, the differential diagnosis is broad and diverse. We here describe two cases of bilateral pallidal hemorrhage in AIDS-associated toxoplasmosis, and review conditions recently described with acute symmetric deep gray nuclei lesions on neuroimaging. PMID:26427898

  17. Repetitive hyperbaric oxygen treatment increases insulin sensitivity in diabetes patients with acute intracerebral hemorrhage

    PubMed Central

    Xu, Qian; Wei, Yi-ting; Fan, Shuang-bo; Wang, Liang; Zhou, Xiao-ping

    2017-01-01

    Aim The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT. Methods Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m−2 min−1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. Results In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05). Conclusion Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment. PMID:28228657

  18. Endovascular Treatment of Acute Arterial Hemorrhage in Trauma Patients Using Ethylene Vinyl Alcohol Copolymer (Onyx)

    SciTech Connect

    Mueller-Wille, R. Heiss, P.; Herold, T.; Jung, E. M. Schreyer, A. G. Hamer, O. W. Rennert, J. Hoffstetter, P. Stroszczynski, C.; Zorger, N.

    2012-02-15

    Purpose: This study was designed to determine the feasibility and efficacy of endovascular embolization with liquid embolic agent ethylene vinyl alcohol copolymer (Onyx) in patients with acute traumatic arterial bleeding. Methods: This is a retrospective review of 13 patients (9 men and 4 women; mean age 45 years) with severe trauma who underwent embolotherapy using Onyx from November 2003 to February 2009. Bleeding was located in the pelvis (5 patients), kidney (3 patients), mesenteric region (2 patients), retroperitoneal space (2 patients), neck (1 patient), and thigh (1 patient). In three cases (23.1%), Onyx was used in conjunction with coils. We evaluate the technical and clinical success, procedural and embolization time, occurrence of rebleeding, and embolotherapy-related complications, such as necrosis or migration of Onyx into nontarget vessels. Results: In all patients, embolotherapy was technically and clinically successful on the first attempt. Control of bleeding could be reached with a mean time of 19 (range, 4-63) min after correct placement of the microcatheter in the feeding artery. No recurrent bleeding was detected. No unintended necrosis or migration of Onyx into a nontarget region was observed. During the follow-up period, three patients (23.1%) died due to severe intracranial hemorrhage, cardiac arrest, and sepsis. Conclusions: Transcatheter embolization with new liquid embolic agent Onyx is technically feasible and effective in trauma patients with acute arterial hemorrhage.

  19. Acute fever and delayed leukoencephalopathy following low dose intraventricular methotrexate.

    PubMed Central

    Boogerd, W; vd Sande, J J; Moffie, D

    1988-01-01

    Nine out of 14 patients treated with intraventricular methotrexate (MTX) for meningeal carcinomatosis from breast carcinoma and surviving more than 4 months developed disseminated necrotising leukoencephalopathy (DNL). All four patients who had received both intraventricular MTX and whole brain radiotherapy developed DNL. Five of the six patients who experienced an acute febrile reaction with mild encephalopathic signs following intraventricular administration of MTX developed DNL after a mean time of 5 months and a low mean dose of 44 mg MTX. DNL was also noted in two patients without a previous febrile reaction or whole brain radiotherapy, following prolonged intraventricular MTX therapy after a mean time of 19.5 months and a mean dose of 147 mg MTX. These findings confirm the hazards of (1) high cumulative doses of intrathecal MTX and (2) combined intrathecal chemotherapy and whole brain radiotherapy. This study also suggests a possible relationship between an early and transient febrile reaction during intraventricular administration of MTX and the development of DNL. Images PMID:3225584

  20. Acute fever and delayed leukoencephalopathy following low dose intraventricular methotrexate.

    PubMed

    Boogerd, W; vd Sande, J J; Moffie, D

    1988-10-01

    Nine out of 14 patients treated with intraventricular methotrexate (MTX) for meningeal carcinomatosis from breast carcinoma and surviving more than 4 months developed disseminated necrotising leukoencephalopathy (DNL). All four patients who had received both intraventricular MTX and whole brain radiotherapy developed DNL. Five of the six patients who experienced an acute febrile reaction with mild encephalopathic signs following intraventricular administration of MTX developed DNL after a mean time of 5 months and a low mean dose of 44 mg MTX. DNL was also noted in two patients without a previous febrile reaction or whole brain radiotherapy, following prolonged intraventricular MTX therapy after a mean time of 19.5 months and a mean dose of 147 mg MTX. These findings confirm the hazards of (1) high cumulative doses of intrathecal MTX and (2) combined intrathecal chemotherapy and whole brain radiotherapy. This study also suggests a possible relationship between an early and transient febrile reaction during intraventricular administration of MTX and the development of DNL.

  1. Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

    SciTech Connect

    Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.; Masters, Emily M.; Brunzelle, Joseph S.; Pegan, Scott D.

    2014-10-02

    Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

  2. Epidemiological analysis of hemorrhagic fever with renal syndrome in China with the seasonal-trend decomposition method and the exponential smoothing model

    PubMed Central

    Ke, Guibao; Hu, Yao; Huang, Xin; Peng, Xuan; Lei, Min; Huang, Chaoli; Gu, Li; Xian, Ping; Yang, Dehua

    2016-01-01

    Hemorrhagic fever with renal syndrome (HFRS) is one of the most common infectious diseases globally. With the most reported cases in the world, the epidemic characteristics are still remained unclear in China. This paper utilized the seasonal-trend decomposition (STL) method to analyze the periodicity and seasonality of the HFRS data, and used the exponential smoothing model (ETS) model to predict incidence cases from July to December 2016 by using the data from January 2006 to June 2016. Analytic results demonstrated a favorable trend of HFRS in China, and with obvious periodicity and seasonality, the peak of the annual reported cases in winter concentrated on November to January of the following year, and reported in May and June also constituted another peak in summer. Eventually, the ETS (M, N and A) model was adopted for fitting and forecasting, and the fitting results indicated high accuracy (Mean absolute percentage error (MAPE) = 13.12%). The forecasting results also demonstrated a gradual decreasing trend from July to December 2016, suggesting that control measures for hemorrhagic fever were effective in China. The STL model could be well performed in the seasonal analysis of HFRS in China, and ETS could be effectively used in the time series analysis of HFRS in China. PMID:27976704

  3. Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic

    PubMed Central

    Wielders, Cornelia C. H.; van Loenhout, Joris A. F.; Morroy, Gabriëlla; Rietveld, Ariene; Notermans, Daan W.; Wever, Peter C.; Renders, Nicole H. M.; Leenders, Alexander C. A. P.; van der Hoek, Wim; Schneeberger, Peter M.

    2015-01-01

    Background Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007–2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever. Methods A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever. Results Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months. Conclusions A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever. PMID:26161658

  4. Dengue hemorrhagic fever

    MedlinePlus

    ... a severe, potentially deadly infection spread by some mosquitos. Causes Four different dengue viruses are known to ... occurs when a person is bitten by a mosquito that is infected with the virus. The mosquito ...

  5. Q fever in Spain: acute and chronic cases, 1981-1985.

    PubMed

    Tellez, A; Sainz, C; Echevarria, C; de Carlos, S; Fernandez, M V; Leon, P; Brezina, R

    1988-01-01

    Two hundred forty-nine cases of Q fever were documented at the laboratories of the Centro Nacional de Microbiología, Virología e Inmunología Sanitarias (CNMVIS) during the 5-year period 1981-1985. Two hundred thirty-four cases corresponded to acute infections, mostly sporadic but including two epidemics. The clinical presentation was respiratory in 74% of the cases and febrile in 18%. Fifteen cases, all but one of which were endocarditis, were categorized as chronic. The cases studied were referred from almost every region of Spain. The clinical and epidemiologic analyses and the number of cases reported permit only an approximation of the true incidence and characteristics of Q fever in Spain.

  6. Efficacy of Transcutaneous Transseptal Orbital Decompression in Treating Acute Retrobulbar Hemorrhage and a Literature Review

    PubMed Central

    Zimmerer, Rüdiger; Schattmann, Katrin; Essig, Harald; Jehn, Philipp; Metzger, Marc; Kokemüller, Horst; Gellrich, Nils-Claudius; Tavassol, Frank

    2013-01-01

    Decreasing visual acuity secondary to orbital trauma may be caused by sudden space-occupying or expanding intraorbital lesions, including retrobulbar hemorrhage (RBH), herniation, or swelling. RBH must be diagnosed and treated immediately. This article addresses the efficacy of transcutaneous transseptal orbital decompression in a combination with a systematic review of the literature for a comparison of this method with existing treatment options. For this study the department's database was retrospectively screened for patients with acute RBH who were treated between 2009 and 2011 using the authors' approach. Patients presenting with RBH were classified into RBH classes I to III according to three different clinical and radiological manifestations of acute RBH. The efficacy of transcutaneous transseptal orbital decompression was assessed by postoperative visual acuities. The literature review was performed by using the MEDLINE database. The time period for the study was between 2009 and 2011 during which 10 patients were diagnosed with suspected RBH and 9 were treated with the authors' technique. Visual acuities were reconstituted or maintained in almost 86% of patients who were diagnosed and treated according to the authors approach and who survived initial trauma. It was concluded that transcutaneous transseptal orbital decompression provides an efficient and rapid approach for treating patients with acute RBH. By distinguishing three different manifestations of acute RBH, the authors present a diagnostic tool that may facilitate classification of RBH and determination of treatment options. PMID:24624253

  7. Multi-Center Prediction of Hemorrhagic Transformation in Acute Ischemic Stroke using Permeability Imaging Features

    PubMed Central

    Scalzo, Fabien; Alger, Jeffry R.; Hu, Xiao; Saver, Jeffrey L.; Dani, Krishna A.; Muir, Keith W.; Demchuk, Andrew M.; Coutts, Shelagh B.; Luby, Marie; Warach, Steven; Liebeskind, David S.

    2013-01-01

    Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood-brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a crossvalidation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke. PMID:23587928

  8. Efficacy and safety of penetration acupuncture on head for acute intracerebral hemorrhage

    PubMed Central

    Wang, Hai-Qiao; Bao, Chun-Ling; Jiao, Zhi-Hua; Dong, Gui-Rong

    2016-01-01

    Abstract Background: Acupuncture, especially acupuncture treatment on head for acute intracerebral hemorrhage (ICH), has long been disputable. The aim of this study was to evaluate the efficacy and safety of penetration acupuncture on head in patients with acute ICH. Methods: Eighty-two patients with acute ICH were randomized to receive penetration acupuncture treatment on head combined with conventional treatment (treatment group [TG]) or conventional treatment only (control group [CG]). Acupuncture treatments were given in 24 sessions over 4 weeks, with 3-month follow-up period. Measures included Clinical Neurological Function Deficit Scale (CNFDS), Barthel Index (BI), vital signs (respiration, heart rate, blood pressure, and oxygen saturation), and hematoma absorption ratio. Results: Both groups showed a progressively improvement in CNFDS and BI scores from day 7 to 90. The TG showed a significantly greater improvement in CNFDS than CG over time (P < 0.05). However, BI failed to show significant difference between the 2 groups (P > 0.05). The vital signs were stable and no expansion of hematoma occurred over the course of acupuncture treatment. Conclusion: Penetration acupuncture treatment on head appeared to be safe over the course of treatment on acute ICH and may result in additional functional improvements detected in the CNFDS but not reflected in the BI. A larger-scale clinical trial with longer follow-up assessments is required to confirm these findings. PMID:27902622

  9. Nationwide survey of antihypertensive treatment for acute intracerebral hemorrhage in Japan.

    PubMed

    Koga, Masatoshi; Toyoda, Kazunori; Naganuma, Masaki; Kario, Kazuomi; Nakagawara, Jyoji; Furui, Eisuke; Shiokawa, Yoshiaki; Hasegawa, Yasuhiro; Okuda, Satoshi; Yamagami, Hiroshi; Kimura, Kazumi; Okada, Yasushi; Minematsu, Kazuo

    2009-09-01

    Acute hypertension is associated with hematoma enlargement and poor clinical outcomes in patients with intracerebral hemorrhage (ICH). However, the method of controlling blood pressure (BP) during the acute phase of ICH remains unknown. The aim of this study is to show current strategies about this issue in Japan. Questionnaires regarding antihypertensive treatment (AHT) strategies were sent to neurosurgeons, neurologists and others responsible for ICH management in 1424 hospitals. Of 600 respondents, 550 (92%) worked at hospitals wherein acute ICH patients are managed and 548 (99.6%) of them agreed with the application of AHT within 24 h of ICH onset. Most answered that the systolic BP threshold for starting AHT was 180 mm Hg (36%) or 160 mm Hg (31%), which differed significantly between neurosurgeons (median, 160 mm Hg) and neurologists/others (180 mm Hg, P<0.001). The goal of lowering systolic BP was to reach a maximum of 140, 150 or 160 mm Hg according to 448 respondents (82%) and 209 (38%) intensively lowered systolic BP to acute ICH patients. Nicardipine was the most frequent choice of antihypertensive agent.

  10. High seroprevalence of Mycoplasma pneumoniae IgM in acute Q fever by enzyme-linked immunosorbent assay (ELISA).

    PubMed

    Lai, Chung-Hsu; Chang, Lin-Li; Lin, Jiun-Nong; Chen, Wei-Fang; Kuo, Li-Li; Lin, Hsi-Hsun; Chen, Yen-Hsu

    2013-01-01

    Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.

  11. Dengue fever: a Wikipedia clinical review.

    PubMed

    Heilman, James M; De Wolff, Jacob; Beards, Graham M; Basden, Brian J

    2014-01-01

    Dengue fever, also known as breakbone fever, is a mosquito-borne infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles. In a small proportion of cases, the disease develops into life-threatening dengue hemorrhagic fever, which results in bleeding, thrombocytopenia, and leakage of blood plasma, or into dengue shock syndrome, in which dangerously low blood pressure occurs. Treatment of acute dengue fever is supportive, with either oral or intravenous rehydration for mild or moderate disease and use of intravenous fluids and blood transfusion for more severe cases. Along with attempts to eliminate the mosquito vector, work is ongoing to develop a vaccine and medications targeted directly at the virus.

  12. Climate and climate change and infectious disease risk in Thailand: A spatial study of dengue hemorrhagic fever using GIS and remotely-sensed imagery

    NASA Astrophysics Data System (ADS)

    Kuzera, Kristopher

    The scientific community has widely accepted that climate plays a key role in the sustainability and transmission of many infectious diseases. Global climate change can potentially trigger the spread of disease into new regions and increase the intensity of disease in regions where it is endemic. This study explores the association between monthly conditions of climate change to changes in disease risk, emphasizing the potential spread of dengue fever due to climate change in Thailand. This study also develops techniques new to GIS and remote sensing that generate surfaces of daily minimum temperature toward identifying areas at greater transmission risk. Dengue fever expansion due to global warming is a serious concern for Thailand where warming temperatures may increase the size of the habitat of the disease-spreading vector, Aedes aegypti, particularly during cooler months when transmission is limited by environmental conditions. In this study, first, the association between past dengue hemorrhagic fever (DHF) and climate in Thailand is determined. Second, evidence of recent climate change is related to changes in DHF rates. Third, daily minimum temperature is derived from remote sensing toward identifying the spatial and temporal limitations of potential transmission risk. The results indicate that minimum temperature has recently experienced a rapid increase, particularly in the winter months when transmission is low. This is associated with a recent rise in winter DHF cases. As increasing minimum temperatures in these regions are anticipated to continue, we can expect dengue transmission rates to also increase throughout the year.

  13. Theoretical Analysis of the Relative Impact of Obesity on Hemodynamic Stability During Acute Hemorrhagic Shock

    PubMed Central

    Sterling, Sarah A.; Jones, Alan E.; Coleman, Thomas G.; Summers, Richard L.

    2015-01-01

    Background: Evidence suggests that morbid obesity may be an independent risk factor for adverse outcomes in patients with traumatic injuries. Objectives: In this study, a theoretic analysis using a derivation of the Guyton model of cardiovascular physiology examines the expected impact of obesity on hemodynamic changes in Mean Arterial Pressure (MAP) and Cardiac Output (CO) during Hemorrhagic Shock (HS). Patients and Methods: Computer simulation studies were used to predict the relative impact of increasing Body Mass Index (BMI) on global hemodynamic parameters during HS. The analytic procedure involved recreating physiologic conditions associated with changing BMI for a virtual subject in an In Silico environment. The model was validated for the known effect of a BMI of 30 on iliofemoral venous pressures. Then, the relative effect of changing BMI on the outcome of target cardiovascular parameters was examined during simulated acute loss of blood volume in class II hemorrhage. The percent changes in these parameters were compared between the virtual nonobese and obese subjects. Model parameter values are derived from known population distributions, producing simulation outputs that can be used in a deductive systems analysis assessment rather than traditional frequentist statistical methodologies. Results: In hemorrhage simulation, moderate increases in BMI were found to produce greater decreases in MAP and CO compared to the normal subject. During HS, the virtual obese subject had 42% and 44% greater falls in CO and MAP, respectively, compared to the nonobese subject. Systems analysis of the model revealed that an increase in resistance to venous return due to changes in intra-abdominal pressure resulting from obesity was the critical mechanism responsible for the differences. Conclusions: This study suggests that obese patients in HS may have a higher risk of hemodynamic instability compared to their nonobese counterparts primarily due to obesity

  14. Paediatric Dengue Fever diagnosed through parents' epidemiologic report and preventive strategy during the acute phase of infection.

    PubMed

    Poddighe, Dimitri; Bonomelli, Irene; Giardinetti, Silvia; Nedbal, Marco; Bruni, Paola

    2016-01-01

    In Europe, Dengue Fever is one of the most frequent imported diseases and also autochthonous cases occurred in areas where the insect vector is present. Here, we describe a child returning from Philippines and diagnosed with Dengue Fever, through the information provided by parents about an ongoing outbreak in their municipality. An appropriate clinical management in the hospital was established to monitor the occurrence of complications and to cancel the risk of dengue virus transmission in the acute phase of infection.

  15. Mesenteric lymph drainage alleviates acute kidney injury induced by hemorrhagic shock without resuscitation.

    PubMed

    Zhao, Zi-Gang; Zhu, Hong-Xia; Zhang, Li-Min; Zhang, Yu-Ping; Niu, Chun-Yu

    2014-01-01

    This study aimed to investigate the effect of mesenteric lymph drainage on the acute kidney injury induced by hemorrhagic shock without resuscitation. Eighteen male Wistar rats were randomly divided into sham, shock, and drainage groups. The hemorrhagic shock model (40 mmHg, 3 h) was established in shock and drainage groups; mesenteric lymph drainage was performed from 1 h to 3 h of hypotension in the drainage group. The results showed that renal tissue damage occurred; the levels of urea, creatinine, and trypsin in the plasma as well as intercellular adhesion molecule-1 (ICAM-1), receptor of advanced glycation end-products (RAGE), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), lactic acid (LA), and 2,3-DPG in the renal tissue were increased in the shock group after 3 h of hypotension. Mesenteric lymph drainage lessened the following: renal tissue damage; urea and trypsin concentrations in the plasma; ICAM-1, RAGE, TNF-α, MDA, and LA levels in the renal tissue. By contrast, mesenteric lymph drainage increased the 2,3-DPG level in the renal tissue. These findings indicated that mesenteric lymph drainage could relieve kidney injury caused by sustained hypotension, and its mechanisms involve the decrease in trypsin activity, suppression of inflammation, alleviation of free radical injury, and improvement of energy metabolism.

  16. Relationship of plasma matrix metalloproteinase-9 and hematoma expansion in acute hypertensive cerebral hemorrhage.

    PubMed

    Yang, Qingwei; Zhuang, Xiaorong; Peng, Feng; Zheng, Weihong

    2016-01-01

    In the present study, we aimed to investigate the relationship of plasma matrix metalloproteinase-9 (MMP-9) and hematoma expansion (HE) in acute hypertensive cerebral hemorrhage (AHCH) (HE-in-AHCH). Patients with hypertensive cerebral hemorrhage, confirmed by head computed tomography (CT) within 12 h of onset, were prospectively collected. Venous blood was sampled within 4 h of the confirmation to determine the serum MMP-9 concentration. The blood pressure and National Institute of Health Stroke Score of the patients were recorded on hospital admission. CT re-scanning was performed within 42-54 h of the first head CT examination or immediately after worsening of the patients' consciousness disorder. The relationship between MMP-9 level and HE was analyzed. A total of 186 patients were included. Of these patients, 41 had HE (22.0%). Multivariate logistic regression analysis showed that, in addition to the short interval between onset and the first CT examination, and the irregularity of hematoma shape, increasing MMP-9 level was an independent risk factor for HE-in-AHCH (OR value = 15.65, 95% CI: 5.30-46.15). Moreover, increasing plasma MMP-9 level was identified as an independent risk factor in patients with HE-in-AHCH.

  17. Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage.

    PubMed

    Cetas, J S; Lee, D R; Alkayed, N J; Wang, R; Iliff, J J; Heinricher, M M

    2009-10-06

    Symptomatic ischemia following aneurysmal subarachnoid hemorrhage (SAH) is common but poorly understood and inadequately treated. Severe constriction of the major arteries at the base of the brain, termed vasospasm, traditionally has been thought to be a proximal event underlying these ischemias, although microvascular changes also have been described. The vast majority of studies aimed at understanding the pathogenesis of ischemic deficits, and vasospasm have focused on the interaction of the "spasmogen" of the extravasated blood with the smooth muscle and endothelium of the arteries. This has led to a comparative neglect of the contribution of the CNS to the maintenance of cerebral perfusion. In the present study, we focused on the role of the rostral ventromedial medulla (RVM) in modulating cerebral perfusion at rest and following an experimental SAH in the rat. Changes in cerebral blood flow (CBF) were measured using laser-Doppler flowmetry and three-dimensional optical microangiography. Focal application of a GABA(A) receptor agonist and antagonist was used to respectively inactivate and activate the RVM. We show here that the RVM modulates cerebral blood flow under resting conditions, and further, contributes to restoration of cerebral perfusion following a high-grade SAH. Failure of this brainstem compensatory mechanism could be significant for acute perfusion deficits seen in patients following subarachnoid hemorrhage.

  18. Risk Factors for Hemorrhagic Transformation in Patients with Acute Middle Cerebral Artery Infarction

    PubMed Central

    ÖCEK, Levent; GÜNER, Derya; ULUDAĞ, İrem Fatma; TİFTİKÇİOĞLU, Bedile İrem; ZORLU, Yaşar

    2015-01-01

    Introduction Hemorrhagic transformation (HT) after acute ischemic stroke (AIS) can be seen at any time following ischemic stroke. Although HT usually occurs as a complication of antithrombotic, anticoagulant, or thrombolytic treatments, it can also occur spontaneously. We aimed to investigate the occurrence of early HT and its relevant risk factors in patients diagnosed with acute middle cerebral artery (MCA) infarction who were not treated with thrombolytic agents. Methods We recruited 171 patients with acute MCA infarction between January 2011 and July 2012 who were not treated with thrombolytic agents and were suitable to our inclusion criteria. Controlled neuroimaging was performed immediately in patients with deterioration, otherwise on day 7 following stroke. All patients were investigated for AIS risk factors and biochemical analyses were performed. Patients with HT in controlled neuroimaging were grouped both clinically (i.e., symptomatic or asymptomatic) and radiologically, according to “European Cooperative Acute Stroke Radiological Study” (ECASS), and risk factors were examined. Results We enrolled 171 patients [94 men (55%) and 77 women (45%)] in the study. HT developed in 37 patients (21.63%). In terms of risk factor analysis, the most frequent etiological factor was atherosclerosis in AIS patients (50.3%). National Institutes of Health Stroke Scale scores were significantly higher both in sHT patients according to asHT patients and in HT patients on day 7 compared with their initial scores. Serum low-density lipoprotein (LDL-C), triglycerides (TG), and total cholesterol (TC) levels were significantly lower in patients with HT (p<.001). Conclusion HT is a major complication in AIS that considerably increases the morbidity and mortality. To reduce the occurrence of HT, risk factors for each patient population should be determined. Acute thrombolytic therapy should be used cautiously in high-risk patients, and appropriate alternative therapies should

  19. Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments.

    PubMed

    Kameneva, Marina V; Wu, Zhongjun J; Uraysh, Arkady; Repko, Brandon; Litwak, Kenneth N; Billiar, Timothy R; Fink, Mitchell P; Simmons, Richard L; Griffith, Bartley P; Borovetz, Harvey S

    2004-01-01

    Over the past several decades, blood-soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200), which possesses no drag-reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19% (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the Control and PEG-200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG-3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

  20. Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley Fever and Congo-Crimean Hemorrhagic Fever in Kenya

    DTIC Science & Technology

    1991-11-06

    AD-A259 524 AD GRANT NO: DAMD17-90-Z-0005 TITLE: DIAGNOSIS AND CHEMOTHERAPY OF HUMAN TRYPANOSOMIASIS AND VECTOR ECOLOGY OF RIFT VALLEY FEVER AND...62787A 62787A870 AN 014 11. TITLE (dud Secufity Claniflcat•)n) Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley...OCONUS JUN 89 - -- .- . . .- . . .. ’-..." -. . :- -•- ... , .-. ,. I Diagnosis and Chemotherapy of Human Trypanosomiasis a. Screening of WRAIR