Pierre Gallian

Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

BACKGROUNDnIn the wake of the recent outbreak of Ebola virus disease (EVD) in several African countries, the World Health Organization prioritized the evaluation of treatment with convalescent plasma derived from patients who have recovered from the disease. We evaluated the safety and efficacy of convalescent plasma for the treatment of EVD in Guinea.nnnMETHODSnIn this nonrandomized, comparative study, 99 patients of various ages (including pregnant women) with confirmed EVD received two consecutive transfusions of 200 to 250 ml of ABO-compatible convalescent plasma, with each unit of plasma obtained from a separate convalescent donor. The transfusions were initiated on the day of diagnosis or up to 2 days later. The level of neutralizing antibodies against Ebola virus in the plasma was unknown at the time of administration. The control group was 418 patients who had been treated at the same center during the previous 5 months. The primary outcome was the risk of death during the period from 3 to 16 days after diagnosis with adjustments for age and the baseline cycle-threshold value on polymerase-chain-reaction assay; patients who had died before day 3 were excluded. The clinically important difference was defined as an absolute reduction in mortality of 20 percentage points in the convalescent-plasma group as compared with the control group.nnnRESULTSnA total of 84 patients who were treated with plasma were included in the primary analysis. At baseline, the convalescent-plasma group had slightly higher cycle-threshold values and a shorter duration of symptoms than did the control group, along with a higher frequency of eye redness and difficulty in swallowing. From day 3 to day 16 after diagnosis, the risk of death was 31% in the convalescent-plasma group and 38% in the control group (risk difference, -7 percentage points; 95% confidence interval [CI], -18 to 4). The difference was reduced after adjustment for age and cycle-threshold value (adjusted risk difference, -3 percentage points; 95% CI, -13 to 8). No serious adverse reactions associated with the use of convalescent plasma were observed.nnnCONCLUSIONSnThe transfusion of up to 500 ml of convalescent plasma with unknown levels of neutralizing antibodies in 84 patients with confirmed EVD was not associated with a significant improvement in survival. (Funded by the European Unions Horizon 2020 Research and Innovation Program and others; ClinicalTrials.gov number, NCT02342171.).

A nationwide survey of hepatitis E virus infection in French blood donors

Most cases of hepatitis E viral (HEV) infection in developed countries are autochthonous. Nevertheless, the reported seroprevalence of HEV varies greatly depending on the geographical area and the performance of the immunoassay used. We used validated assays to determine the prevalence of anti‐HEV immunoglobulin G (IgG) and IgM among 10,569 French blood donors living in mainland France and three overseas areas. Epidemiological information was collected using a specific questionnaire. We found an overall IgG seroprevalence of 22.4% (8%‐86.4%) depending on the geographical area (P < 0.001). The presence of anti‐HEV IgG was associated with increasing age (P < 0.001) and eating pork meat (P = 0.03), pork liver sausages (P < 0.001), game meat (P < 0.01), offal (P < 0.001), and oysters (P = 0.02). Conversely, drinking bottled water was associated with a lower rate of anti‐HEV IgG (P = 0.02). Overall IgM seroprevalence was 1% (0%‐4.6%). The frequency of anti‐HEV IgM was higher in donors living in a high anti‐HEV IgG seroprevalence area (1.9% versus 0.7%, P < 0.001) and in those eating pork liver sausage (1.4% versus 0.7%, P < 0.01), pâté (1% versus 0.4, P = 0.04), and wild boar (1.3% versus 0.7%, P < 0.01). Conclusion: HEV is endemic in France and hyperendemic in some areas; eating habits alone cannot totally explain the exposure to HEV, and contaminated water could contribute to the epidemiology of HEV infection in France. (Hepatology 2016;63:1145–1154)

Prospective detection of chikungunya virus in blood donors, Caribbean 2014.

To the editor:nnOn December 5, 2013, chikungunya virus (CHIKV) was introduced into the Western Hemisphere. The first cases of autochthonous chikungunya fever were reported in Saint Martin, French West Indies (FWI), demonstrating local transmission.[1][1] As of March 30, 2014, autochthonous cases

Hepatitis E and blood donation safety in selected European countries: a shift to screening?

The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk for such immunosuppressed patients is exposure to undercooked infected pork products and blood transfusion. We summarised the epidemiology of HEV infections among blood donors and also outlined any strategies to prevent transfusion-transmitted HEV, in 11 European countries. In response to the threat posed by HEV and related public and political concerns, most of the observed countries determined seroprevalence of HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain and the United Kingdom (UK) reported cases of transfusion-transmitted HEV. Ireland and the UK have already implemented HEV RNA screening of blood donations; the Netherlands will start in 2017. Germany and France perform screening for HEV RNA in several blood establishments or plasma donations intended for use in high-risk patients respectively and, with Switzerland, are considering implementing selective or universal screening nationwide. In Greece, Portugal, Italy and Spain, the blood authorities are evaluating the situation. Denmark decided not to implement the HEV screening of blood donations.

Epidemiology of Chikungunya Virus Outbreaks in Guadeloupe and Martinique, 2014: An Observational Study in Volunteer Blood Donors

Background During Dec-2013, a chikungunya virus (CHIKV) outbreak was first detected in the French-West Indies. Subsequently, the virus dispersed to other Caribbean islands, continental America and many islands in the Pacific Ocean. Previous estimates of the attack rate were based on declaration of clinically suspected cases. Methods/Principal findings Individual testing for CHIKV RNA of all (n = 16,386) blood donations between Feb-24th 2014 and Jan-31st 2015 identified 0·36% and 0·42% of positives in Guadeloupe and Martinique, respectively. The incidence curves faithfully correlated with those of suspected clinical cases in the general population of Guadeloupe (abrupt epidemic peak), but not in Martinique (flatter epidemic growth). No significant relationship was identified between CHIKV RNA detection and age-classes or blood groups. Prospective (Feb-2014 to Jan-2015; n = 9,506) and retrospective (Aug-2013 to Feb-2014; n = 6,559) seroepidemiological surveys in blood donors identified a final seroprevalence of 48·1% in Guadeloupe and 41·9% in Martinique. Retrospective survey also suggested the absence or limited silent CHIKV circulation before the outbreak. Parameters associated with increased seroprevalence were: Gender (M>F), KEL-1, [RH+1/KEL-1], [A/RH+1] and [A/RH+1/KEL-1] blood groups in Martiniquan donors. A simulation model based on observed incidence and actual seroprevalence values predicted 2·5 and 2·3 days of asymptomatic viraemia in Martiniquan and Guadeloupian blood donors respectively. Conclusions/Significance This study, implemented promptly with relatively limited logistical requirements during CHIKV emergence in the Caribbean, provided unique information regarding retrospective and prospective epidemiology, infection risk factors and natural history of the disease. In the stressful context of emerging infectious disease outbreaks, blood donor-based studies can serve as robust and cost-effective first-line tools for public health surveys.

Low seroprevalence of Zika virus in Cameroonian blood donors

A Zika virus seroepidemiology study was performed in 1084 blood donors collected from August to October 2015 in six sites of Cameroon representing a large panel of eco-environments. Samples were tested using an anti-NS1 IgG ELISA detection kit and positives were further confirmed by seroneutralization. The observed global seroprevalence was low (around 5%, peaking at 10% and 7.7% in Douala and Bertoua, respectively) with risk factors associated with seropositivity pointing to the existence of a local (peri-)sylvatic cycle of transmission. These results call attention to the potential introduction and subsequent spread in African urban areas of Asian genotype Zika virus currently circulating in the Americas and adapted to transmission by peri-domestic mosquitoes. They should leverage reinforced surveillance efforts in Africa.

Complete coding sequence of Zika virus from Martinique outbreak in 2015.

Zika virus is an Aedes-borne Flavivirus causing fever, arthralgia, myalgia rash, associated with Guillain–Barré syndrome and suspected to induce microcephaly in the fetus. We report here the complete coding sequence of the first characterized Caribbean Zika virus strain, isolated from a patient from Martinique in December, 2015.

Risk Factors Associated with Ebola and Marburg Viruses Seroprevalence in Blood Donors in the Republic of Congo.

Background Ebola and Marburg viruses (family Filoviridae, genera Ebolavirus and Marburgvirus) cause haemorrhagic fevers in humans, often associated with high mortality rates. The presence of antibodies to Ebola virus (EBOV) and Marburg virus (MARV) has been reported in some African countries in individuals without a history of haemorrhagic fever. In this study, we present a MARV and EBOV seroprevalence study conducted amongst blood donors in the Republic of Congo and the analysis of risk factors for contact with EBOV. Methodology and Findings In 2011, we conducted a MARV and EBOV seroprevalence study amongst 809 blood donors recruited in rural (75; 9.3%) and urban (734; 90.7%) areas of the Republic of Congo. Serum titres of IgG antibodies to MARV and EBOV were assessed by indirect double-immunofluorescence microscopy. MARV seroprevalence was 0.5% (4 in 809) without any identified risk factors. Prevalence of IgG to EBOV was 2.5%, peaking at 4% in rural areas and in Pointe Noire. Independent risk factors identified by multivariate analysis were contact with bats and exposure to birds. Conclusions/Significance This MARV and EBOV serological survey performed in the Republic of Congo identifies a probable role for environmental determinants of exposure to EBOV. It highlights the requirement for extending our understanding of the ecological and epidemiological risk of bats (previously identified as a potential ecological reservoir) and birds as vectors of EBOV to humans, and characterising the protection potentially afforded by EBOV-specific antibodies as detected in blood donors.

Estimation d’un risque transfusionnel émergent : l’exemple du VHE

BACKGROUNDnThe risk assessment for blood transfusion is an essential step that must precede any screening strategy of a pathogen transmitted by transfusion. After several cases of HEV transmission by transfusion in France, a risk assessment for this virus was performed.nnnMETHODSnWe used a method based on the prevalence of HEV-RNA in plasmas collected for the preparation of SD-plasma. To estimate the rate of HEV-RNA positive among all blood donations, data on SD-plasma were adjusted on the following HEV risk factors: gender, age group and region of residence. We assumed that HEV risk factors were the same in plasma donors and whole blood donors.nnnRESULTSnAmong 57,101 plasma donations tested for HEV-RNA in 2013, 24 were positive (crude rate of 4.2 per 10,000 donations). After adjustment, the total number of HEV-RNA positive blood donations was estimated at 788, accounting for a rate of 2.65 per 10,000 donations (95% CI: 1.6-3.7) or 1 in 3800 donations (1 in 6,200-1 in 2,700). This rate was 12 times higher in men than in women, increased with age, and varied according to region of residence.nnnCONCLUSIONnThe risk of blood donation contamination by HEV has been estimated to be 1 in 3800 donations in 2013. An essential input is still missing to assess now the risk in recipients: the minimum infectious dose. Furthermore, the risk in recipients has to be analyzed according to characteristics of transfused patients: presence of anti-HEV immunity, existence of chronic liver disease or immunodeficiency.

Convalescent Plasma for Ebola Virus Disease REPLY

n engl j med 374;25 nejm.org June 23, 2016 2498 cizumab according to two definitions of refractoriness.2,3 Regardless of the definition, a lower percentage of patients in the caplacizumab group than in the placebo group had disease that was refractory to treatment, which suggests that caplacizumab might prevent refractory TTP and its associated worse outcomes.1 To clarify, Table 3 of our article reports the cumulative number of patients with at least one adverse event that was considered to be related or possibly related to the investigational medicinal product, whereas the text separately reports the number of patients with at least one adverse event that was considered to be either related or possibly related to treatment. We confirm that the data regarding patients with relapse during the 12-month follow-up include those with relapse during the 1-month follow-up: 11 patients in the caplacizumab group, as compared with 3 in the placebo group, had a relapse during the entire follow-up period. Overall, 13 patients in each treatment group had at least one recurrence of TTP (exacerbation or relapse). Flora Peyvandi, M.D., Ph.D.n engl j med 374;25 nejm.org June 23, 2016 2498 cizumab according to two definitions of refractoriness.2,3 Regardless of the definition, a lower percentage of patients in the caplacizumab group than in the placebo group had disease that was refractory to treatment, which suggests that caplacizumab might prevent refractory TTP and its associated worse outcomes.1 To clarify, Table 3 of our article reports the cumulative number of patients with at least one adverse event that was considered to be related or possibly related to the investigational medicinal product, whereas the text separately reports the number of patients with at least one adverse event that was considered to be either related or possibly related to treatment. We confirm that the data regarding patients with relapse during the 12-month follow-up include those with relapse during the 1-month follow-up: 11 patients in the caplacizumab group, as compared with 3 in the placebo group, had a relapse during the entire follow-up period. Overall, 13 patients in each treatment group had at least one recurrence of TTP (exacerbation or relapse). Flora Peyvandi, M.D., Ph.D.