#Serological #Evidence of #Yersiniosis, #TBE, #WNV, #Hepatitis E, #CCHF, Lyme #Borreliosis, and #Brucellosis in Febrile Patients Presenting at Diverse Hospitals in #Kenya (Vector Borne Zoo Dis., abstract)

[Source: Vector-Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

Serological Evidence of Yersiniosis, Tick-Borne Encephalitis, West Nile, Hepatitis E, Crimean-Congo Hemorrhagic Fever, Lyme Borreliosis, and Brucellosis in Febrile Patients Presenting at Diverse Hospitals in Kenya

Josphat Nyataya, Moureen Maraka, Allan Lemtudo, Clement Masakhwe, Beth Mutai, Kariuki Njaanake, Benson B. Estambale, Nancy Nyakoe, Joram Siangla, and John Njenga Waitumbi

Published Online: 13 Jan 2020 / DOI: https://doi.org/10.1089/vbz.2019.2484



Data on pathogen prevalence is crucial for informing exposure and disease risk. We evaluated serological evidence of tick-borne encephalitis (TBE), West Nile (WN), Hepatitis E virus (HEV), Crimean-Congo Hemorrhagic Fever (CCHF), Yersiniosis, Lyme Disease (LD), and brucellosis in 1033 patients presenting with acute febrile illness at 9 health care facilities from diverse ecological zones of Kenya: arid and semiarid (Garissa District Hospital, Lodwar District Hospital, Marigat District Hospital, Gilgil District Hospital), Lake Victoria basin (Kisumu District Hospital, Alupe District Hospital, Kombewa Sub-County Hospital), Kisii highland (Kisii District Hospital), and coastal (Malindi District Hospital). Epidemiological information of the patients such as geography, age, gender, and keeping animals were analyzed as potential risk factors. Of the 1033 samples, 619 (59.9%) were seropositive to at least one pathogen by IgM (current exposure), IgG/IgM (recent exposure), and IgG (past exposure). Collective seroprevalence for current, recent, and past to the pathogens was 9.4%, 5.1%, and 21.1% for LD; 3.6%, 0.5%, and 12.4% for WN; 0.9%, 0.5%, and 16.9% for HEV; 5.8%, 1.3%, and 3.9% for brucellosis; 5.7%, 0.2%, and 2.3% for yersiniosis; 1.7%, 0%, and 6.2% for TBE; and 0.4%, 0%, and 1.9% for CCHF. Brucellosis risk was higher in patients recruited at Garissa District Hospital (odds ratio [OR] = 3.41), HEV (OR = 2.45) and CCHF (OR = 5.46) in Lodwar District Hospital, LD in Alupe District Hospital (OR = 5.73), Kombewa Sub-district hospital (OR = 8.17), and Malindi District hospital (OR = 3.3). Exposure to LD was highest in the younger age group, whereas yersiniosis did not vary with age. Age was a significant risk for WN, brucellosis, CCHF, TBE, and HEV and in those aged >14 years there was an increased risk to WN (OR = 2.30, p < 0.0001), brucellosis (OR = 1.84, p = 0.005), CCHF (OR = 4.35, p = 0.001), TBE (OR = 2.78, p < 0.0001), and HEV (OR = 1.94, p = 0.0001). We conclude that LD is pervasive and constitutes a significant health burden to the study population, whereas yersiniosis and CCHF are not significant threats. Going forward, community-based studies will be needed to capture the true seroprevalence rates and the associated risk factors.

Keywords: Arbovirus; WNV; CCHF; Borreliosis; TBE; Brucellosis; Seroprevalence; Kenya.


Fluorescent #CCHF virus illuminates tissue #tropism patterns and identifies early mononuclear phagocytic cell targets in IFNAR-/- mice (PLOS Pathog., abstract)

[Source: PLOS Pathogens, full page: (LINK). Abstract, edited.]


Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in IFNAR-/- mice

Stephen R. Welch, Jana M. Ritter, Anita K. McElroy, Jessica R. Harmon, JoAnn D. Coleman-McCray, Florine E. M. Scholte, Gary P. Kobinger, Éric Bergeron, Sherif R. Zaki, Stuart T. Nichol, Jessica R. Spengler , Christina F. Spiropoulou


Published: December 2, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1008183 / This is an uncorrected proof.



Crimean-Congo hemorrhagic fever virus (CCHFV, order Bunyavirales, family Nairoviridae, genus Orthonairovirus) is the tick-borne etiological agent of Crimean-Congo hemorrhagic fever (CCHF) in humans. Animals are generally susceptible to CCHFV infection but refractory to disease. Small animal models are limited to interferon-deficient mice, that develop acute fatal disease following infection. Here, using a ZsGreen1- (ZsG) expressing reporter virus (CCHFV/ZsG), we examine tissue tropism and dissemination of virus in interferon-α/β receptor knock-out (Ifnar-/-) mice. We demonstrate that CCHFV/ZsG retains in vivo pathogenicity comparable to wild-type virus. Interestingly, despite high levels of viral RNA in all organs assessed, 2 distribution patterns of infection were observed by both fluorescence and immunohistochemistry (IHC), corresponding to the permissiveness of organ tissues. To further investigate viral dissemination and to temporally define cellular targets of CCHFV in vivo, mice were serially euthanized at different stages of disease. Flow cytometry was used to characterize CCHFV-associated alterations in hematopoietic cell populations and to classify infected cells in the blood, lymph node, spleen, and liver. ZsG signal indicated that mononuclear phagocytic cells in the lymphatic tissues were early targets of infection; in late-stage infection, overall, the highest levels of signal were detected in the liver, and ZsG was found in both antigen-presenting and lymphocyte cell populations.


Author summary

Human infection by tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) can result in severe disease with up to 30% case fatality rates. While CCHFV is known to be hepatotropic, the presence and implications of virus in other tissues are less clear. Furthermore, to date, early cellular targets of infection in a CCHFV disease model have not been investigated in detail. Here, using a recombinant reporter CCHFV expressing the fluorescent protein ZsGreen1 (ZsG; CCHFV/ZsG) in interferon-α/β receptor knock-out (Ifnar-/-) mice, which develop acute fatal disease following infection, we investigate both cellular and tissue targets of infection. Importantly, we find that CCHFV/ZsG infection demonstrated comparable pathogenicity to wild-type virus in Ifnar-/- mice. We used in situ visualization of fluorescent signal in tissues to assess viral dissemination throughout the course of infection, and found robust viral signal in reproductive tissues, previously unrecognized as sites of CCHFV infection. We also used flow cytometry to detect intracellular fluorescent signal, and identified initial target cells of CCHFV infection as macrophage and monocyte populations in lymphatic tissues. These findings support a central role of immune cells in early virus dissemination, and a need for further investigations into reproductive tract involvement in human CCHFV infection.


Citation: Welch SR, Ritter JM, McElroy AK, Harmon JR, Coleman-McCray JD, Scholte FEM, et al. (2019) Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in IFNAR-/- mice. PLoS Pathog 15(12): e1008183. https://doi.org/10.1371/journal.ppat.1008183

Editor: Veronika von Messling, Federal Ministry of Education and Research, GERMANY

Received: June 4, 2019; Accepted: November 1, 2019; Published: December 2, 2019

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was partially supported by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC (S.R.W.), by a CDC foundation project funded by NIAID grant R01AI109008 (E.B.), and by CDC Emerging Infectious Disease Research Core Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: CCHF; Viral pathogenesis.


Crimean-Congo hemorrhagic fever [#CCHF]: An #update (Med Mal Infect., abstract)

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

Med Mal Infect. 2019 Oct 10. pii: S0399-077X(18)30853-9. doi: 10.1016/j.medmal.2019.09.005. [Epub ahead of print]

Crimean-Congo hemorrhagic fever: An update.

Fillâtre P1, Revest M2, Tattevin P2.

Author information: 1 Service de réanimation polyvalente, centre hospitalier St-Brieuc, 10, rue Marcel-Proust, 22000 St-Brieuc, France. Electronic address: pierre.fillatre@ch-stbrieuc.fr. 2 Service des maladies infectieuses et de réanimation médicale, CHU de Rennes, Rennes, France.



Crimean-Congo hemorrhagic fever (CCHF) is a severe form of hemorrhagic fever caused by a virus of the genus Nairovirus. The amplifying hosts are various mammal species that remain asymptomatic. Humans are infected by tick bites or contact with animal blood. CCHF has a broad geographic distribution and is endemic in Africa, Asia (in particular the Middle East) and South East Europe. This area has expanded in recent years with two indigenous cases reported in Spain in 2016 and 2018. The incubation period is short with the onset of symptoms in generally less than a week. The initial symptoms are common to other infectious syndromes with fever, headache, myalgia and gastrointestinal symptoms. The hemorrhagic syndrome occurs during a second phase with sometimes major bleeding in and from the mucous membranes and the skin. Strict barrier precautionary measures are required to prevent secondary and nosocomial spread. CCHF may be documented by PCR detection of the virus genome during the first days after the onset of illness, and then by serological testing for IgM antibodies as from the 2nd week after infection. Patient management is mainly based on supportive care. Despite a few encouraging retrospective reports, there is no confirmed evidence that supports the use of ribavirin for curative treatment. Nevertheless, the World Health Organization continues to recommend the use of ribavirin to treat CCHF, considering the limited medical risk related to short-term treatment. The prescription of ribavirin should however be encouraged post-exposure for medical professionals, to prevent secondary infection.

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

KEYWORDS: Crimean-Congo hemorrhagic fever; Fièvre hémorragique de Crimée-Congo; Fièvre hémorragique virale; Health professionals; Professionnels de santé; Ribavirin; Ribavirine; Ticks; Tiques; Viral hemorrhagic fever

PMID: 31607406 DOI: 10.1016/j.medmal.2019.09.005

Keywords: Nairovirus; CCHF.


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.




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.


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


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.


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.


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.


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.]


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.




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.


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.


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.


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




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.


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.


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%).


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.


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

Keywords: CCHF; Coagulopathy.


#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)



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.