Thierry Carmoi

Severe Ebola Virus Infection With Encephalopathy: Evidence for Direct Virus Involvement

TO THE EDITOR—Major neurological signs are infrequent in Ebola virus (EV) disease. When present, they consist mainly of meningitis, encephalopathy, and seizures [1, 2]. The physiopathology of brain impairment in EV disease is not well understood. Here, we report the case of an EV disease patient with encephalitis and meningitis from whom cerebrospinal fluid (CSF) was obtained. A 21-year-old man without any remarkable medical history was referred to our Ebola healthcare center with a 5-day history of severe febrile gastroenteritis and headache. At admission, the patient complained of diarrhea, vomiting, and abdominal pain and had signs of dehydration without neurological impairment or hemorrhagic symptoms. Throughout his stay, the patient’s core body temperature was ≤38°C and his systolic blood pressure was >100 mmHg. He tested positive for EV (blood subjected to polymerase chain reaction; cycle threshold, 14.4); an immunochromatographic rapid test for malaria was negative. A routine blood panel revealed an elevated partial thromboplastin time (PTT) that was 4.4-fold the upper limit of normal values (ULN), an international normalized ratio (INR) of 1.9, a serum creatinine level of 173 μmol/L, and a high aspartate aminotransferase level (23-fold ULN). Twentyfour hours after being admitted, the patient worsened, exhibiting signs of hemorrhagic syndrome onset (ie, including hematuria, hemoptysis, and bleeding gums) and demonstrating an INR that had increased to 2.9. He was given 4 units of French lyophilized plasma. The next day, the patient was stuporous with nuchal stiffness and seizures but remained without focal neurologic signs. A lumbar puncture performed to test for bacterial meningitis revealed sterile CSF with no red or white blood cells. The patient’s viral load was 10 copies/mL CSF and 6 × 10 copies/ mL blood. His blood and CSF glucose levels were both 3.7 mmol/L. Proteinorachia could not be assessed due to the lack of an appropriate device. The patient died within 24 hours of the lumbar puncture. A few hours before the patient died, biologic analyses disclosed coagulopathy with a normal platelet count (PTT, 7.2-foldULN; INR, 6.2), renal impairment (high serum creatinine [234 μmol/L] and urea [10.1 mmol/ L]), and hyponatremia (130 mmol/L). The demonstration of a detectable CSF viral load in this case indicates that EV can cross the blood-brain barrier and thusmay have a pathogenic role in the onset of encephalitis. In this case, there was no evidence of metabolic impairment such as hyponatremia or acute renal/hepatic encephalitis. The absence of focal neurologic signs and of red bloods cell in the patient’s CSF ruled out a significant brain hemorrhage. EV-related physiopathology of the brain has not been characterized. In cynomolgus macaques, EV has a ubiquitous distribution, infecting endothelial cells of all organs, including brain venules and capillaries, from the fifth day of infection onward [3]. Necropsy, immunohistochemistry, and in situ hybridization findings have thus far been unremarkable in nonhuman primates up to 6 days after infection. However, our patient showed signs of encephalopathy 7 days after the onset of symptoms [4]. Edema and widespread glial nodules suggestive of encephalitis have been documented previously in human patients infected with the Marburg virus, another filovirus, but not in EVinfected patients [5]. The findings of the present case report suggest that EV can exist in the brain and thus that the brain should be a target for EV treatment.

Risk of Enterically Transmitted Hepatitis A, Hepatitis E, and Plasmodium falciparum Malaria in Afghanistan

positivity. In total, 102 anicteric patients were included. The ratio of male to female subjects was 3:4, and the median age of patients was 32.5 years (range, 5‐65 years). Hepatitis A virus IgG was detected in 101 (99%) of the specimens; the only sample with negative results had been obtained from a child aged 5 years (table 1). Twenty-nine specimens tested positive for hepatitis E virus IgG (28.4%); hepatitis E virus IgM and hepatitis E virus RNA were not detected. The seroprevalence of P. falciparum malaria was 4.9%. The cohort of subjects included in this study is not representative of the Afghan population. However, as expected, hepatitis A is highly endemic in Afghanistan; the country displays the usual pattern of feco-orally transmitted agents in childhood. Hepatitis E is highly endemic in the urban area of Kabul, with a high risk of sporadic cases and outbreaks among

Moderate Thermal Strain in Healthcare Workers Wearing Personal Protective Equipment During Treatment and Care Activities in the Context of the 2014 Ebola Virus Disease Outbreak

The extent of thermal strain while wearing personal protective equipment (PPE) during care activities for Ebola virus disease patients has not yet been characterized. From January to March 2015, 25 French healthcare workers (HCWs) in Conakry, Guinea, volunteered to be monitored while wearing PPE using an ingestible thermal sensor. The mean (standard deviation) working ambient temperature and relative humidity were 29.6 °C (2.0 °C) and 65.4% (10.3%), respectively; the mean time wearing PPE was 65.7 (13.5) minutes; and the mean core body temperature increased by 0.46 °C (0.20 °C). Four HCWs reached or exceeded a mean core body temperature of ≥ 38.5 °C. HCWs wearing PPE for approximately 1 hour exhibited moderate but safe thermal strain.

Occupational Exposures to Ebola Virus in Ebola Treatment Center, Conakry, Guinea

We report 77 cases of occupational exposures for 57 healthcare workers at the Ebola Treatment Center in Conakry, Guinea, during the Ebola virus disease outbreak in 2014−2015. Despite the high incidence of 3.5 occupational exposures/healthcare worker/year, only 18% of workers were at high risk for transmission, and no infections occurred.

Organ failures on admission in patients with Ebola virus disease

Dear Editor, The actual outbreak of Ebola virus disease (EVD) started in December 2013 in West Africa, and spread from Guinea to Sierra Leone and Liberia. Organ dysfunctions during EVD have only been described through case reports managed in high income countries, and data are still lacking [1]. The Sepsis-related Organ Failure Assessment (SOFA) score has been developed to quantitatively describe the degree of organ dysfunction in intensive care unit septic patients [2]. We aimed to characterize the severity of Ebola patients admitted to our center by calculating the SOFA score on admission. After approval by the local ethics committee, SOFA score was calculated in Ebola-infected patients using the most abnormal values from the first 24 h after admission. Data were collected between January and April 2015. A total of 38 patients were admitted, of whom 22 were infected with Ebola. Results are expressed as mean ± standard deviation. The mean age of confirmed cases was 33 years (±9). Mean viral load expressed as cycle threshold (CT) at admission was 21.6 (±3.9). On the 22 patients, six died (mortality rate of 27.3 %). Mean SOFA score at admission was 2.6 (±1.7). SOFA score at admission was significantly higher in non-survivors than in survivors (4.8 ± 1.7 versus 1.7 ± 1, P = 0.001). Mean viral load was also higher in non-survivors (CT at 17.7 ± 3.8 versus 23 ± 3.1, P = 0.006). Renal dysfunction was the most frequent dysfunction on admission in non-survivors (Fig. 1). Relationships between admission patients’ conditions and outcome have never been explored during EVD, except for age and viral load [3]. A study analyzing the WHO case investigation form data of 3343 infected patients reported a high mortality rate above 70 %, but patients’ organ dysfunctions could not have been scored [4]. In this study, hemorrhage, coma, and ‘‘difficulty breathing’’ were not commonly reported in patients who died, suggesting that massive fluid loss due to gastrointestinal disorders may be the main factor of worse outcome. Another study reported a lower mortality rate of 43 % [3]. Risk of death was associated with an older age, but this study failed in identifying other factors, mainly because biological data on admission were also limited as no routine clinical laboratory testing was available. Presented data showed that patients were hemodynamically stable on admission and had no respiratory dysfunction (3 % of patients with oxygen therapy). Our results highlighted two main points. The first is that cardiovascular, respiratory, and neurological dysfunctions were not common on admission in Ebola patients, even in non-survivors. The second is the frequency of renal dysfunction. Acute kidney injury during EVD may be promoted by several factors: hypovolemia due to gastrointestinal fluid loss, inflammatory response, viral injury as suggested by histopathological examination of tissues from infected animals showing indications of interstitial nephritis [5]. Larger studies are needed to describe objectively organ dysfunction in Ebola patients and evolution during stay. It may also help to optimize the preparation of treatment facilities according to local available resources for the next outbreaks.