Late Ebola virus relapse causing meningoencephalitis: a case report.

BACKGROUND: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). METHODS: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. FINDINGS: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. INTERPRETATION: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern. FUNDING: Royal Free London NHS Foundation Trust.

Plasmodium knowlesi: clinical presentation and laboratory diagnosis of the first human case in a Scottish traveler.

The first imported case of Plasmodium knowlesi in Scotland is described in a 33-year-old female with a travel history to Borneo. The patient ceased to take antimalarial prophylaxis after 4 days of her 10-day visit and presented with a history of fever, rigor, vomiting, and diarrhea after 13 days on her return to the UK. Malaria antigen detection using the Optimal-IT and Binax-NOW kits was negative. Unusual trophozoite-like structures were observed under microscopic examination and the identification of P. knowlesi performed by a nested polymerase chain reaction (PCR) gel-based approach was confirmed by using a PCR-sequencing assay.

Potential therapeutic agents for the prevention and treatment of haemolytic uraemic syndrome in shiga toxin producing Escherichia coli infection.

PURPOSE OF REVIEW: Shiga toxin producing Escherichia coli (STEC) cause a wide spectrum of disease ranging from asymptomatic carriage through to haemorrhagic colitis and the haemolytic uraemic syndrome. There are no current therapeutic interventions available in clinical practice that can prevent the development of haemolytic uraemic syndrome. A number of newly developed agents offer the potential for the treatment of STEC-associated disease. RECENT FINDINGS: Three different classes of agent designed to bind and inactivate shiga toxin have now been developed. Synthetic toxin binders, recombinant bacteria and monoclonal antibodies provide potentially potent agents that could prevent the development of haemolytic uraemic syndrome. These agents have been shown in animal models of STEC disease to be effective. A recent clinical trial of one synthetic toxin binder showed no benefit in established haemolytic uraemic syndrome. More potent toxin binders, however, have since been developed and await human clinical trials. It is likely to be important that these agents are administered early in the course of disease in order to have maximum efficacy. Although rapid diagnostic techniques are available for the diagnosis of STEC disease, they still rely on stool culture. SUMMARY: Clinicians need to maintain a high level of suspicion of STEC disease as the diagnosis is often made on epidemiological and clinical grounds. This will allow potential cases to be identified early and treated appropriately.