Detection of Marburg virus disease in Guinea

For the editor:

Timeline and map of Marburg virus (MARV) infection in Guinea.

Panel A shows the timeline of events in the diagnosis of MARV infection in a 46-year-old man in Guéckédou prefecture in Guinea in August 2021. On September 3, the Guéckédou Viral Hemorrhagic Fevers Laboratory shared the footage MARV genetics with the public (https://virological.org/t/marburg-virus-sequence-from-guinea-2021/755) to support the public health response as well as the development and evaluation of diagnostic tests and therapeutic agents for MARV infection. IPD designates the Pasteur Institute of Dakar. Panel B shows a map depicting parts of Guinea, Sierra Leone, Liberia and Côte d’Ivoire, with an emphasis on the Guinean forests (Guinea Forestière) and Guéckédou prefecture, where the case of MARV infection appeared. Relevant locations of sites with reported evidence of MARV circulation in bats and humans in Sierra Leone are shown, along with sites in Guinea where bat species known to be potential reservoir hosts of MARV have been identified, including Méliandou (the location of the 2014-2016 Ebola virus disease outbreak), as well as Mongo Forest, Koundou Forest, Bakama Cave, and Ziama Massif. Details regarding the mapping procedure are provided in the supplementary appendix.

On August 2, 2021, a 46-year-old man from Temessadou M’Boké, a village in Guéckédou prefecture in Guinea, died after hemorrhaging from several natural orifices. On August 3, an initial diagnosis of Marburg virus (MARV) infection was made after a real-time reverse transcriptase–polymerase chain reaction test of a post-mortem buccal specimen obtained from the patient revealed a cycle threshold value of 13.4 (Figure 1A). Field investigation teams were deployed and the diagnostic result was validated in two additional laboratories within days. In-country next-generation metagenomic sequencing resulted in the recovery of the complete MARV genome (99.3%), and phylogenetic analysis indicated that the new Guinea MARV strain that was identified in the patient was grouped with strains MARVs isolated from bats in Sierra Leone and humans in Angola (Fig. S1 and Table S1 in the Supplementary Appendix, available with the full text of this letter on NEJM.org). Close monitoring for a period of 21 days confirmed that all of the patient’s contacts remained asymptomatic, and no additional cases were detected.

The forests of Guinea, as well as other regions of West Africa, including Sierra Leone, are considered suitable for the zoonotic transmission of Marburg virus disease by bats and in particular by bats. Rousettus aegyptiacus (Egyptian fruit bat), which has been identified as a natural reservoir host of MARV (Figure 1B).1-3 Among the MARV bat reservoirs is Koundou, which is close to where the case arose. The patient had limited social interactions and lived in a household of four. There was no evidence of a history of travel outside of Guinea for the patient or his close contacts or contact with returning travellers. He was a farmer living in close contact with nature and wildlife and therefore may have been repeatedly exposed to an environment or food contaminated with feces from MARV-infected bats. Community surveys have shown that although he may have harvested wild fruit for personal consumption, there was no evidence that he had visited caves or participated in hunting activities for bushmeat, including bats. mouse. Traditional practices of eating or preparing bushmeat (i.e. direct exposure to bodily fluids) cannot be fully ruled out, as such exposures are unlikely to have been disclosed due to the nationwide ban on such consumption that was enforced after the 2021 Ebola outbreak. viral disease.

The New Guinea MARV clade and the Angola MARV clade share a common ancestor that probably existed in 1965 (95% confidence interval, 1944 to 1981 on Bayesian molecular clock analysis). This finding indicates that approximately 55 years ago, these lineages diverged from a common ancestor, and each evolved independently in its respective reservoir host, with the presence of Guinea MARV remaining undetected until this spillover event. 2021. This multi-decade timescale provided ample opportunity for the virus to be dispersed over large distances by bat migration. A parallel could be drawn with the emergence of the West African Ebola virus lineage (Makona) which diverged from a central African ancestor and evolved independently in its host until the overflow event to occur.4 In the case of MARV, the basal clustering of bat MARV in Sierra Leone suggests that even the Angola epidemic may have its roots in West Africa.

Epidemiological characteristics and phylogenetic history argue against the possibility that the newly emerging MARV could have been imported. Overall, it seems plausible that the viral emergence in Guinea was due to a zoonotic transmission event from a bat reservoir in late July 2021.

The patient’s isolated lifestyle likely played a role in minimizing the risk of secondary infections. Notably, timely laboratory diagnosis has been facilitated by the establishment of capacity building programs, long-term collaborative partnerships, and decentralized laboratories with well-trained staff. The same capabilities proved essential during the recent re-emergence of Ebola virus disease in Guinea.5

Farah R., M.Sc.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Liana E. Kafetzopoulou, Ph.D.
KU Leuven, Leuven, Belgium

Martin Faye, Ph.D.
Pastoral Institute of Dakar, Dakar, Senegal

Annick Renevey, Ph.D.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Barrè Soropogui, M.Sc.
Gamal Abdel Nasser University, Conakry, Guinea

Kekoura Ifono, B.Sc.
Emily V. Nelson, Ph.D.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Aly A. Relationship, MPH, MD
World Health Organization Guinea, Conakry, Guinea

Charles Tolno, MPH, MD
Doctors Without Borders Belgium, Conakry, Guinea

Giuditta Annibaldis, Ph.D.
Saa L. Millimono, B.Sc.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Jacob Camara, Pharm.D.
Gamal Abdel Nasser University, Conakry, Guinea

Karifa Kourouma, B.Sc.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Ahmadou Doré, B.Sc.
Gamal Abdel Nasser University, Conakry, Guinea

Tamba E. Millimouno, B.Sc.
Fernand MB Tolno, B.Sc.
Julia Hinzmann, MLT
Hugo Soubrier, M.Sc.
Mette Hinrichs, MLT
Anke Thielebein, Ph.D.
Glaucia Herzer, M.Sc.
Meike Pahlmann, Ph.D.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Georges A. Ki-Zerbo, MD
World Health Organization Guinea, Conakry, Guinea

Pierre Formenty, DVM
Anaïs Legand, MPH
World Health Organization, Geneva, Switzerland

Michael R. Wiley, Ph.D.
University of Nebraska Medical Center, Omaha, NE

Ousmane Faye, Ph.D.
Moussa M. Diagne, Ph.D.
Amadou A. Sall, Ph.D.
Pastoral Institute of Dakar, Dakar, Senegal

Philippe Lemey, Ph.D.
KU Leuven, Leuven, Belgium

Aïssatou Bah, B.Sc.
Gamal Abdel Nasser University, Conakry, Guinea

Stephan Günther, MD, Ph.D.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany

Sakoba Keita, MD
National Health Security Agency, Conakry, Guinea

Sophie Duraffour, Ph.D.
Bernhard Nocht Institute of Tropical Medicine, Hamburg, Germany
[email protected]

N’Faly Magassouba, Ph.D.
Guinea Viral Hemorrhagic Fevers Laboratory, Conakry, Guinea

Supported by the German Federal Ministry of Health under an agreement (ZMV I1-2517WHO005) with the World Health Organization (WHO) Collaborating Center for Arboviruses and Hemorrhagic Fever Viruses at the Bernhard Nocht Institute for Tropical Medicine and agreements (ZMV I1-2517GHP-704, ZMVI1-2519GHP704 and ZMI1-2521GHP921) with the Global Health Protection Program; by grants (GU883/5-1 and GU883/5-2) from the German Research Foundation; by a research and innovation aid agreement (871029-EVA-GLOBAL) with the European Union Horizon 2020; speak Coalition for Epidemic Preparedness Innovations (CEPI-ENABLE); and by grant agreement (RIA2016E-1609) with the European and Developing Countries Clinical Trials Partnership PANDORA-ID-NET. The Bernhard Nocht Institute for Tropical Medicine is a member of the German Center for Infection Research (partner site in Hamburg, Germany), which provided support for this study. The European Mobile Laboratory in coordination with the Bernhard Nocht Institute of Tropical Medicine is a technical partner of the WHO Global Outbreak Alert and Response Network (GOARN); the deployment of the European mobile laboratory in Guinea was coordinated and supported by the GOARN operational support team in WHO. Dr. Lemey is supported by a grant agreement (725422-ReservoirDOCS) with the European Research Council under the European Union’s Horizon 2020 and through grants (G066215N, G0D5117N and G0B9317N) from the Research Foundation – Flanders and with funding from the Welcome Trustthrough the Arctic Network project (206298/Z/17/Z). The work of Institut Pasteur de Dakar was supported in part by PraesensBio of Lincoln, NE, and by the University of Nebraska Medical Center. Mr. Koundouno, Mr. Ifono, Mr. Millimono, Mr. Kourouma, Mr. Millimouno, and Mr. F. Tolno operate the Laboratoire des Fièvres Hémorrhagiques Virales de Guéckédou and are supported by the Ministry of Health and Public Hygiene in Guinea and the Direction Préfectorale de la Santé of Guéckédou.

The disclosure forms provided by the authors are available with the full text of this letter on NEJM.org.

Mrs Koundouno and Dr Kafetzopoulou and Drs. Duraffour and Magassouba also contributed to this letter.

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