[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.
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.
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.
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.