A case of #CCHF imported in #Greece: #Contact #tracing and #management of exposed #HCWs (J Infect Prev., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Infect Prev. 2019 Jul;20(4):171-178. doi: 10.1177/1757177419852666. Epub 2019 Jun 6.

A case of Crimean-Congo haemorrhagic fever imported in Greece: Contact tracing and management of exposed healthcare workers.

Maltezou HC1, Papa A2, Ventouri S3, Tseki C4, Pervanidou D5, Pavli A1, Panagopoulos P3,6, Markatou P7, Gavana E2, Maltezos E3,6.

Author information: 1 Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece. 2 Department of Microbiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. 3 Department of Infection Control, University Hospital of Alexandroupolis, Alexandroupolis, Greece. 4 Department of Infection Control, General Hospital of Xanthi, Xanthi, Greece. 5 Department for Epidemiological Surveillance and Intervention, Hellenic Center for Disease Control and Prevention, Athens, Greece. 6 Second Department of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 7 Department of Internal Medicine, University Hospital of Alexandroupolis, Alexandroupolis, Greece.

 

Abstract

BACKGROUND:

Nosocomial transmission is a major mode of infection of Crimean-Congo haemorrhagic fever (CCHF). In May 2018, a patient with CCHF was hospitalised in Greece.

OBJECTIVE:

Our aim was to present the management of healthcare workers (HCWs) to the CCHF case.

METHODS:

Contact tracing, risk assessment and follow-up of exposed HCWs were performed. Testing (RT-PCR and/or serology) was offered to contacts. Post-exposure prophylaxis (PEP) with ribavirin was considered for high-risk exposures.

RESULTS:

Ninety-one HCWs were exposed to the case. Sixty-six HCWs were grouped as high-risk exposures. Ribavirin PEP was offered to 29 HCWs; seven agreed to receive prophylaxis. Forty-one HCWs were tested for CCHF infection; none was found positive. Gaps in infection control occurred.

DISCUSSION:

CCHF should be considered in patients with compatible travel history and clinical and laboratory findings. Early clinical suspicion and laboratory confirmation are imperative for the implementation of appropriate infection control measures. Ribavirin should be considered for high-risk exposures. Infection control capacity for highly pathogenic agents should increase.

KEYWORDS: Crimean-Congo haemorrhagic fever; contact tracing; healthcare workers; infection control; ribavirin

PMID: 31428197 PMCID: PMC6683607 [Available on 2020-07-01] DOI: 10.1177/1757177419852666

Keywords: CCHF; HCWs; Greece.

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Detection of #CCHF cases in a severe undifferentiated febrile #illness #outbreak in the Federal Republic of #Sudan: a retrospective epidemiological and diagnostic cohort study (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Detection of Crimean-Congo Haemorrhagic Fever cases in a severe undifferentiated febrile illness outbreak in the Federal Republic of Sudan: a retrospective epidemiological and diagnostic cohort study

Hilary Bower  , Mubarak El Karsany , Mazza Alzain, Benedict Gannon, Rehab Mohamed, Iman Mahmoud, Mawahib Eldegail, Rihab Taha, Abdalla Osman, Salim Mohamednour, Amanda Semper, Barry Atkinson, Daniel Carter,  [ … ], Tom E. Fletcher

Published: July 10, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007571 / This is an uncorrected proof.

 

Abstract

Background

Undifferentiated febrile illness (UFI) is one of the most common reasons for people seeking healthcare in low-income countries. While illness and death due to specific infections such as malaria are often well-quantified, others are frequently uncounted and their impact underappreciated. A number of high consequence infectious diseases, including Ebola virus, are endemic or epidemic in the Federal Republic of Sudan which has experienced at least 12 UFI outbreaks, frequently associated with haemorrhage and high case fatality rates (CFR), since 2012. One of these occurred in Darfur in 2015/2016 with 594 cases and 108 deaths (CFR 18.2%). The aetiology of these outbreaks remains unknown.

Methodology/Principal findings

We report a retrospective cohort study of the 2015/2016 Darfur outbreak, using a subset of 65 of 263 outbreak samples received by the National Public Health Laboratory which met selection criteria of sufficient sample volume and epidemiological data. Clinical features included fever (95.8%), bleeding (95.7%), headache (51.6%) and arthralgia (42.2%). No epidemiological patterns indicative of person-to-person transmission or health-worker cases were reported. Samples were tested at the Public Health England Rare and Imported Pathogens Laboratory using a bespoke panel of likely pathogens including haemorrhagic fever viruses, arboviruses and Rickettsia, Leptospira and Borrelia spp. Seven (11%) were positive for Crimean-Congo haemorrhagic fever virus (CCHFV) by real-time reverse transcription PCR. The remaining samples tested negative on all assays.

Conclusions/Significance

CCHFV is an important cause of fever and haemorrhage in Darfur, but not the sole major source of UFI outbreaks in Sudan. Prospective studies are needed to explore other aetiologies, including novel pathogens. The presence of CCHFV has critical infection, prevention and control as well as clinical implications for future response. Our study reinforces the need to boost surveillance, lab and investigative capacity to underpin effective response, and for local and international health security.

 

Author summary

The Federal Republic of Sudan has had at least 12 outbreaks of febrile illness of unknown cause associated with symptoms of haemorrhage and high case fatality rates since 2012. Outbreaks without clear diagnosis are concerning, particularly in countries such as Sudan where a range of high consequence diseases, including viral haemorrhagic fevers, are endemic or epidemic, and local laboratory capacity is limited. We transferred historical samples stored in the National Public Health Authority from one of these outbreaks that occurred in Darfur 2015–2016 to the Public Health England Laboratory at Porton, UK, and tested them against a wide range of infectious diseases to try to identify the cause, and to help the Sudanese Federal Ministry of Health to develop and target their limited laboratory capacity. We found that Crimean-Congo Haemorrhagic Fever was an important cause but not the only source of cases in this outbreak. This has implications for prevention and control as well as for treating cases. Our study also highlighted the need for future studies to explore other possible causes, including new pathogens, and reinforced the need to boost surveillance, lab and investigative capacity for more timely and complete outbreak response.

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Citation: Bower H, El Karsany M, Alzain M, Gannon B, Mohamed R, Mahmoud I, et al. (2019) Detection of Crimean-Congo Haemorrhagic Fever cases in a severe undifferentiated febrile illness outbreak in the Federal Republic of Sudan: a retrospective epidemiological and diagnostic cohort study. PLoS Negl Trop Dis 13(7): e0007571. https://doi.org/10.1371/journal.pntd.0007571

Editor: Darci Smith, Naval Medical Research Center; Biological Defense Research Directorate, UNITED STATES

Received: February 25, 2019; Accepted: June 22, 2019; Published: July 10, 2019

Copyright: © 2019 Bower et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Genetic sequencing data is available on GenBank Accession nos. S Segment: MK442893; M Segment: MK442894; L Segment: MK442895

Funding: The study was funded by UK aid from the Department of Health and Social Care via the UK Public Health Rapid Support Team Research Programme. The grant (EPIDZK3819) was awarded to HB. The funder had no role in the study design, data collection and analysis,decision to publish or preparation of the manuscript.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HB, BG, JW & DB are members of the UK Public Health Rapid Support Team. AS, NJB, RH, SD and TB are affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with PHE, in collaboration with the Liverpool School of Tropical Medicine. The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health and Social Care, or Public Health England.

Keywords: CCHF; Sudan; Darfur.

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Rotational #thromboelastometry alongside conventional #coagulation testing in #patients with #CCHF: an observational cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Rotational thromboelastometry alongside conventional coagulation testing in patients with Crimean–Congo haemorrhagic fever: an observational cohort study

Tom E Fletcher, MRCP, Prof Hakan Leblebicioglu, MD, Ilkay Bozkurt, MD, Prof Mustafa Sunbul, MD, Heval Bilek, MD, Zahide Asik, MD, Prof Sener Barut, MD, Ferdi Gunes, MD, Umit Gemici, MD, Prof Roger Hewson, PhD, Duncan Wilson, MD, Matt K O’Shea, PhD, Prof Tom Woolley, MD, Prof Brian Faragher, PhD, Kiran Parmar, MSc, Prof David G Lalloo, MD, Nick J Beeching, FRCP †, Prof Beverley J Hunt, MD †

Open Access / Published: June 28, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30112-4

 

Summary

Background

Data describing the coagulopathy of Crimean–Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean–Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease.

Methods

We did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean–Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38–79 s), clot formation time (34–159 s), amplitude at 10 min after clotting time (43–65 mm), maximum clot firmness (50–72 mm), and maximum lysis (>15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7–23 mm) and maximum clot firmness (9–25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS.

Findings

Between May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean–Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11·1–31·8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42–81; IQR 48–64) versus 69 s (range 48–164; IQR 54–75; p=0·01); mean amplitude at 10 min after clotting time 45·1 mm (SD 7·0) versus 33·9 mm (SD 8·6; p<0·0001); median clot formation time 147 s (range 72–255; IQR 101–171) versus 197 s (range 98–418; IQR 156–296; p=0·006); and maximum clot firmness 54·4 mm (SD 7·2) versus 45·1 mm (SD 12·5; p=0·003). The EXTEM S variables were compared at different time points; maximum clot firmness (p=0·024) and amplitude at 10 min after clotting time (p=0·090) were lowest on days 4–6 of illness. We found no significant differences in FIBTEM variables between mild and moderate to severe cases (median amplitude at 10 min, 13 mm [range 8–20; IQR 11–15] vs 12 mm [range 6–25; IQR 10–15; p=0·68]; and median maximum clot firmness, 15 mm [range 9–60; IQR 13–21] vs 17 mm [range 7–39; IQR 13–23; p=0·21]); and no hyperfibrinolysis (maximum lysis >15%).

Interpretation

Coagulopathy of Crimean–Congo haemorrhagic fever is related to defects in clot development and stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean–Congo haemorrhagic fever relates to platelet dysfunction.

Funding

Wellcome Trust, UK Ministry of Defence, and National Institute for Health Research Health Protection Research Unit.

Keywords: CCHF; Coagulopathy.

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#CCHF, Herat Province, #Afghanistan, 2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 8—August 2019 / Research Letter

Crimean-Congo Hemorrhagic Fever, Herat Province, Afghanistan, 2017

Aziz-ur-Rahman Niazi, Mohammad Jawed Jawad, Ahmad Amirnajad, Peter A. Durr, and David T. Williams

Author affiliations: Herat University, Herat, Afghanistan (A.-u.-R. Niazi, M.J. Jawad); Department of Public Health, Herat (A. Amirnajad); CSIRO,; Australian Animal Health Laboratory, Geelong, Victoria, Australia (P.A. Durr, D.T. Williams)

 

Abstract

We studied the clinical and epidemiologic features of an outbreak of Crimean-Congo hemorrhagic fever in Herat Province, Afghanistan. The study comprised 63 patients hospitalized in 2017. The overall case-fatality rate was 22.2%; fatal outcome was significantly associated with a negative IgM test result, longer prothrombin time, and nausea.

Keywords: CCHF; Afghanistan.

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#CCHF Virus #Genome in #Tick from Migratory #Bird, #Italy (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 7—July 2019 / Research Letter

Crimean-Congo Hemorrhagic Fever Virus Genome in Tick from Migratory Bird, Italy

Elisa Mancuso, Luciano Toma, Andrea Polci, Silvio G. d’Alessio, Marco Di Luca, Massimiliano Orsini, Marco Di Domenico, Maurilia Marcacci, Giuseppe Mancini, Fernando Spina, Maria Goffredo, and Federica Monaco

Author affiliations: Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise “G. Caporale,” Teramo, Italy (E. Mancuso, A. Polci, S.G. D’Alessio, M. Orsini, M. Di Domenico, M. Marcacci, G. Mancini, M. Goffredo, F. Monaco); Istituto Superiore di Sanità, Rome, Italy (L. Toma, M. Di Luca); Istituto Superiore per la Protezione e la Ricerca Ambientale, Bologna, Italy (F. Spina)

 

Abstract

We detected Crimean-Congo hemorrhagic fever virus in a Hyalomma rufipes nymph collected from a whinchat (Saxicola rubetra) on the island of Ventotene in April 2017. Partial genome sequences suggest the virus originated in Africa. Detection of the genome of this virus in Italy confirms its potential dispersion through migratory birds.

Keywords: Wild Birds; Ticks; CCHF; Italy.

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Rescue of infectious recombinant #Hazara #nairovirus from cDNA reveals the nucleocapsid protein DQVD caspase #cleavage motif performs an essential role other than cleavage (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Rescue of infectious recombinant Hazara nairovirus from cDNA reveals the nucleocapsid protein DQVD caspase cleavage motif performs an essential role other than cleavage.

J. Fuller, R. A. Surtees, G.S. Slack, J. Mankouri, R. Hewson, J. N. Barr

DOI: 10.1128/JVI.00616-19

 

ABSTRACT

The Nairoviridae family of the Bunyavirales order comprises tick-borne tri-segmented negative strand RNA viruses, with several members associated with serious or fatal disease in humans and animals. A notable member is Crimean-Congo hemorrhagic fever virus (CCHFV), which is the most widely-distributed tick-borne pathogen, and associated with devastating human disease with case/fatality rates averaging 30%. Hazara virus (HAZV) is closely-related to CCHFV, sharing the same serogroup and many structural, biochemical and cellular properties. To improve understanding of HAZV and nairovirus multiplication cycles, we developed for the first time a rescue system permitting efficient recovery of infectious HAZV from cDNA. This system now allows reverse genetics analysis of nairoviruses without the need for high biosafety containment, as is required for CCHFV. We used this system to test the importance of a DQVD caspase cleavage site exposed on the apex of the HAZV nucleocapsid protein arm domain that is cleaved during HAZV infection, and for which the equivalent DEVD sequence was recently shown to be important for CCHFV growth in tick but not mammalian cells. Infectious HAZV bearing an un-cleavable DQVE sequence was rescued and exhibited equivalent growth parameters to wild-type in both mammalian and tick cells, showing this site was dispensable for virus multiplication. In contrast, substitution of the DQVD motif with the similarly un-cleavable AQVA sequence could not be rescued despite repeated efforts. Together, this work highlights the importance of this caspase cleavage site in the HAZV lifecycle, but reveals the DQVD sequence performs a critical role aside from caspase cleavage.

 

IMPORTANCE

Hazara virus is classified within the Nairoviridae family along with Crimean-Congo hemorrhagic fever virus (CCHFV), which is one of the most lethal human pathogens in existence, requiring the highest biosafety level (BSL) containment (BSL-4). In contrast, HAZV is not associated with human disease and thus can be studied using less-restrictive BSL-2 protocols. Here, we report a system able to rescue Hazara virus (HAZV) from cDNAs, thus permitting reverse genetic interrogation of the HAZV replication cycle. We used this system to examine the role of a caspase cleavage site, DQVD, within the HAZV nucleocapsid protein that is also conserved in CCHFV. By engineering mutant viruses, we showed caspase cleavage at this site was not required for productive infection, and furthermore that this sequence performs a critical role in the virus lifecycle aside from caspase cleavage. This system will accelerate nairovirus research due to its efficiency and utility under amenable BSL-2 protocols.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Bunyavirus; Hazara virus; CCHF virus; Nairovirus.

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#EPIDEMIOLOGY, #CLINICAL AND #LABORATORY FEATURES OF #CCHF IN #GEORGIA (Georgian Med News., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Georgian Med News. 2015 Oct;(247):54-8.

EPIDEMIOLOGY, CLINICAL AND LABORATORY FEATURES OF CRIMEAN-CONGO HEMORRHAGIC FEVER IN GEORGIA.

Vashakidze E1, Mikadze I1.

Author information: 1 Tbilisi State Medical University, Department of Infectious Disease, Georgia.

 

Abstract

Crimean-Congo hemorrhagic fever virus transmitted to humans by Hyalomma ticks or by direct contact with the blood of infected humans or domestic animals. The most common clinical signs of CCHF are fever, nausea, headache, diarrhea, myalgia, petechial rash, and bleeding. CCHF is a severe disease in humans with a fatality rate up to 15-85%. This study was undertaken to determine the predictors of fatality among patients with CCHF based on epidemiological, clinical, and laboratory findings. 34 patients were enrolled in the study, aged 4 to 77; 17 – male and 17 female. 3 of them were fatal cases. All of them were from Shua Kartli: Khashuri, Gori and Kaspi districts, involved in farming/handling livestock and the history of tick bite was present in most of patients. Evaluation of the epidemiological characteristics of this cases showed that the female to male ratio was nearly similar. The disease is common in the rural areas of the region, mostly in the actively working age group and almost all patients were farmers. The results of our study show that the most cardinal clinical and laboratory features of Crimean-Congo hemorrhagic fever are – acute beginning of disease, high fever, intoxication and hemorrhagic symptoms, thrombocytopenia, high level of aminotransferases and creatine. Predictors of fatality are: an altered mental status, in early stage of disease dramatic decreased thrombocytes count and significantly high level of aspartate aminotransferase, also longer the mean prothrombin time and INR.

PMID:  26483375 [Indexed for MEDLINE]

Keywords: CCHF; Georgia.

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