https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645580/

. 2019 Jul; 13(7): e0007571.
Published online 2019 Jul 10. doi: 10.1371/journal.pntd.0007571
PMCID: PMC6645580
PMID: 31291242

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, Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing – original draft, Writing – review & editing,1,2,*Mubarak El Karsany, Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing,3,4, Mazza Alzain, Data curation, Formal analysis, Investigation, Writing – review & editing,5Benedict Gannon, Data curation, Investigation, Methodology, Resources, Supervision, Writing – review & editing,1,6Rehab Mohamed, Data curation, Investigation, Writing – review & editing,4 Iman Mahmoud, Data curation, Investigation, Writing – review & editing,4 Mawahib Eldegail, Data curation, Investigation, Writing – review & editing,4Rihab Taha, Data curation, Investigation, Writing – review & editing,4 Abdalla Osman, Project administration, Writing – review & editing,4 Salim Mohamednour, Conceptualization, Methodology, Writing – review & editing,5,¤aAmanda Semper, Conceptualization, Data curation, Methodology, Resources, Supervision, Writing – original draft, Writing – review & editing,7 Barry Atkinson, Investigation, Methodology, Writing – review & editing,7,¤b Daniel Carter, Investigation, Methodology, Writing – review & editing,7 Stuart Dowall, Investigation, Methodology, Writing – review & editing,7 Jenna Furneaux, Investigation, Methodology, Writing – review & editing,7 Victoria Graham, Investigation, Methodology, Writing – review & editing,7 Jack Mellors, Investigation, Methodology, Writing – review & editing,7Jane Osborne, Investigation, Methodology, Writing – review & editing,7 Steven T. Pullan, Investigation, Methodology, Writing – review & editing,7 Gillian S. Slack, Investigation, Methodology, Writing – review & editing,7 Tim Brooks, Conceptualization, Methodology, Writing – review & editing,7 Roger Hewson, Methodology, Writing – review & editing,7Nicholas J. Beeching, Conceptualization, Writing – review & editing,8 Jimmy Whitworth, Conceptualization, Writing – review & editing,1,2 Daniel G. Bausch, Writing – review & editing,1,6,9 and Tom E. Fletcher, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing – original draft, Writing – review & editing8,
Darci Smith, Editor

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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More on CCHF: https://madisonarealymesupportgroup.com/2019/07/03/deadly-ticks-carrying-ebola-like-congo-fever-found-in-uk-after-spreading-across-europe/

https://madisonarealymesupportgroup.com/2018/08/19/monster-ticks-found-in-germany-threaten-europe-with-deadly-disease-crimean-congo-fever/

https://madisonarealymesupportgroup.com/2019/05/23/crimean-congo-hemorrhagic-fever-outbreak-in-africa/

H. rufipes on the UK horse:  https://madisonarealymesupportgroup.com/2019/04/11/african-tick-found-on-untraveled-u-k-horse/

https://madisonarealymesupportgroup.com/2018/06/14/crimean-congo-the-asian-ebola-virus/

 

Not to be confused with SFTS, CCHF is often treated with Ribavirin: http://infectious-diseases-and-treatment.imedpub.com/research-advances-on-epidemiology-of-severefever-with-thrombocytopenia-syndrome-asystematic-review-of-the-literature.php?aid=17986

Ribavirin is reported to be effective for treating Crimean-Congo Hemorrhagic Fever (CCHF) infections and hemorrhagic fever with renal syndrome, but it is still inadequate to judge the effect of ribavirin on SFTS patients because of the study limitation without adequate parameters were investigated [45]. Host immune responses play an important role in determining the severity and clinical outcome in patients with infection by SFTSV