Measurement of innate immune response biomarkers in peritoneal dialysis effluent using a rapid diagnostic point-of-care device as a diagnostic indicator of peritonitis.

Peritonitis is the commonest complication of peritoneal dialysis and a major reason for treatment failure. Current diagnosis is based on clinical symptoms, cloudy effluent and a dialysate white cell count (over 100 cells/µl). A rapid point-of-care diagnostic test would accelerate diagnosis and potentially improve outcomes from infection. Here, in a clinical audit project, we used PERiPLEX®, a point-of-care device which detects when levels of matrix metalloproteinase-8 and interleukin-6 are elevated above a threshold within minutes in dialysis effluent, to assess whether it could confirm or exclude peritonitis in 107 patients undergoing peritoneal dialysis. Mean patient age was 64.6 years with a median duration of peritoneal dialysis of 13.3 months (interquartile range 6.3 - 33.5 months). Presence of peritonitis was confirmed by clinical criteria. There were 49 positive tests of which 41 patients had peritonitis, three had other causes of intra-peritoneal inflammation, three had severe urosepsis and two patients required no treatment. Fifty-eight tests were negative with one patient having a false negative result. The positive predictive value of the test was 83.7% (95% confidence interval 72.8 - 90.8) and the negative predictive value was 98.3% (89.1 - 99.8). Sensitivity and specificity were 97.6% (87.4 - 99.9) and 87.7% (77.2 - 94.5) respectively. Thus, PERiPLEX® could be used as a rapid point-of-care test that can aid the diagnosis or exclusion of peritonitis with a high negative predictive value.

Aeromedical Transfer of Patients with Viral Hemorrhagic Fever.

For >40 years, the British Royal Air Force has maintained an aeromedical evacuation facility, the Deployable Air Isolator Team (DAIT), to transport patients with possible or confirmed highly infectious diseases to the United Kingdom. Since 2012, the DAIT, a joint Department of Health and Ministry of Defence asset, has successfully transferred 1 case-patient with Crimean-Congo hemorrhagic fever, 5 case-patients with Ebola virus disease, and 5 case-patients with high-risk Ebola virus exposure. Currently, no UK-published guidelines exist on how to transfer such patients. Here we describe the DAIT procedures from collection at point of illness or exposure to delivery into a dedicated specialist center. We provide illustrations of the challenges faced and, where appropriate, the enhancements made to the process over time.

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.

Febrile illness in healthcare workers caring for Ebola virus disease patients in a high-resource setting.

Ebola virus disease (EVD) patients treated in high-resource facilities are cared for by large numbers of healthcare staff. Monitoring these healthcare workers (HCWs) for any illness that may represent transmission of Ebola virus is important both for the individuals and to minimise the community risk. International policies for monitoring HCWs vary considerably and their effectiveness is unknown. Here we describe the United Kingdom (UK) experience of illness in HCWs who cared for three patients who acquired EVD in West Africa. Five of these 93 high-level isolation unit (HLIU) HCWs presented with fever within 21 days of working on the unit; one of these five presented outside of the UK. This article discusses different approaches to monitoring of HCW symptom reporting. The potential impact of these approaches on HLIU staff recruitment, including travel restrictions, is also considered. An international surveillance system enhancing collaboration between national public health authorities may assist HLIU HCW monitoring in case they travel.

Thromboelastography in the Management of Coagulopathy Associated With Ebola Virus Disease.

Here, we describe the first use of thromboelastography (TEG) in the management of 2 cases of Ebola virus disease. Early in their illness, both patients had evidence of a consumptive coagulopathy. As this resolved, TEG demonstrated that both developed a marked hypercoagulable state, which was treated with low-molecular-weight heparin.

Ebola Virus Disease: An Update on Epidemiology, Symptoms, Laboratory Findings, Diagnostic Issues, and Infection Prevention and Control Issues for Laboratory Professionals.

The 2014 to 2016 Ebola virus disease (EVD), through the sheer size of the outbreak and combined experience within both resource-rich and resource-poor settings, allowed for more information to be gained about the clinical and pathologic features of EVD. This review highlights the range of aspects of EVD that the authors find are relevant to laboratory medicine, including the need for robust prediagnostic and laboratory processing algorithms to inform sampling of suspect patients, the vast majority of whom, in resource-rich settings, will have another diagnosis.

Terminal decontamination of the Royal Free London's high-level isolation unit after a case of Ebola virus disease using hydrogen peroxide vapor.

We report the decontamination of the high-level isolation unit at the Royal Free London after the discharge of a patient with Ebola virus disease, who was repatriated from West Africa. Hydrogen peroxide vapor (HPV) was used to decontaminate the patient care isolators and the rooms housing them. HPV decontamination was completed without incident and allowed the unit to be returned to service more quickly than the previous protocol of using formaldehyde.

Diagnostics in Ebola Virus Disease in Resource-Rich and Resource-Limited Settings.

The Ebola virus disease (EVD) outbreak in West Africa was unprecedented in scale and location. Limited access to both diagnostic and supportive pathology assays in both resource-rich and resource-limited settings had a detrimental effect on the identification and isolation of cases as well as individual patient management. Limited access to such assays in resource-rich settings resulted in delays in differentiating EVD from other illnesses in returning travellers, in turn utilising valuable resources until a diagnosis could be made. This had a much greater impact in West Africa, where it contributed to the initial failure to contain the outbreak. This review explores diagnostic assays of use in EVD in both resource-rich and resource-limited settings, including their respective limitations, and some novel assays and approaches that may be of use in future outbreaks.

Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers.

BACKGROUND: Although a few international health-care workers who have assisted in the current Ebola outbreak in west Africa have been medically evacuated for treatment of Ebola virus disease, more commonly they were evacuated after potential accidental exposure to Ebola virus. An urgent need exists for a consensus about the risk assessment of Ebola virus transmission after accidental exposure, and to investigate the use of post-exposure prophylaxis (PEP). Experimental vaccines have occasionally been used for Ebola PEP, but newly developed experimental antiviral agents have potential advantages. Here, we describe a new method for risk assessment and management of health-care workers potentially exposed to Ebola virus and report the use of experimental antiviral therapies for Ebola PEP in people. METHODS: We devised a risk assessment and management algorithm for health-care workers potentially exposed to Ebola virus and applied this to eight consecutive individuals who were medically evacuated to the UK from west Africa between January, and March, 2015. PEP with antiviral agents was given to health-care workers assessed to have had substantial risk exposures to Ebola virus. Participants were followed up for 42 days after potential exposure. FINDINGS: Four of eight health-care workers were classified as having had low risk exposures and managed by watchful waiting in the community. None of these health-care workers developed Ebola virus disease. The other four health-care workers had intermediate or maximum risk exposures and were given PEP with antiviral agents. PEP was well tolerated with no serious adverse effects. None of these four health-care workers, including two with maximum risk exposures from penetrating injuries with freshly used hollow-bore needles, developed Ebola virus disease. INTERPRETATION: Standardised risk assessment should be adopted and consensus guidelines developed to systematically study the efficacy and safety of PEP with experimental agents. New experimental antiviral treatments are a viable option for PEP against Ebola. FUNDING: Royal Free London NHS Foundation Trust.

Infant feeding modes and determinants among HIV-1-infected African Women in the Kesho Bora Study.

OBJECTIVE: To assess breastfeeding modes and determinants in a prevention of mother-to-child transmission study. DESIGN: HIV-1-infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the study that comprised 2 prospective cohorts and 1 randomized controlled trial. Women were counseled to either breastfeed exclusively up to 6 months or formula feed from birth. METHODS: Determinants of breastfeeding initiation and continuation by 3 months postpartum were investigated using multiple logistic regression analysis. Neonatal morbidity was defined as mother-reported fever, diarrhea, or vomiting during the first month of life. RESULTS: Among 1028, 781 women (76%) initiated breastfeeding and 565 of 995 (56%) were still breastfeeding at 3 months postpartum (30% exclusively, 18% predominantly, and 8% partially). Study site (Durban, Mombasa, and Nairobi compared with Bobo-Dioulasso), CD4 cell count (<200 cells/mm), secondary schooling (compared with none), and emergency cesarean delivery (compared with vaginal delivery) were independently associated with a lower probability of ever breastfeeding. The odds of still breastfeeding by 3 months postpartum (among those breastfeeding by 1 month) were lower in Mombasa, Nairobi, and Somkhele (compared with Bobo-Dioulasso) and among infants with neonatal morbidity [0.60 (0.37-0.976)]. The odds of exclusive breastfeeding (EBF) by 3 months (if EBF by 1 month) were lower in Mombasa and Nairobi, in ill neonates [0.54 (0.31-0.93)] and boys [0.51 (0.34-0.77)]. CONCLUSIONS: EBF was of short duration, particularly for boys. The importance of neonatal morbidity for breastfeeding cessation requires further investigation. Infant feeding counseling might need adaptation to better support mothers of boys and ill neonates.