Transfusion risk associated with recent arbovirus outbreaks in French Polynesia.

BACKGROUND AND OBJECTIVES: French Polynesia, where dengue virus (DENV) has been present for a long time, experienced two successive outbreaks of Zika (ZIKV) and chikungunya viruses (CHIKV) between 2013 and 2015. To avoid the transmission of these viruses by transfusion, nucleic acid testing (NAT) has been in place for DENV since 2013 and for ZIKV and CHIKV during epidemics. The objective was to compare the estimated risk of viraemic blood donation with NAT results and to discuss the impact on the prevention of transfusion-related infectious risk. MATERIALS AND METHODS: The average risks of viraemic blood donation were estimated per year for DENV, and during the epidemic periods for ZIKV and CHIKV, using the Biggerstaff and Petersen model based on the incidence rate, the mean length of viraemia and the frequency of asymptomatic infection. The estimated risks were compared with the number of viraemic blood donations detected by NAT. RESULTS: According to the different assumptions, risks estimates ranged from 11·2 to 53·1/100 000 donations for DENV, 746 to 1924/100 000 for ZIKV and 1083 /100 000 for CHIKV. When compared to the number of donations collected during the study periods, these estimates match NAT results (5 blood donors reactive for DENV, 42 for ZIKV and 34 for CHIKV). CONCLUSION: The risks of viraemic blood donation were related to the viral incidence in the general population and concordant with NAT results. These findings suggest that the screening may be optimized by a targeted NAT implementation based on incidence data.

Molecular detection of Zika virus in blood and RNA load determination during the French Polynesian outbreak.

Zika virus (ZIKV) viremia is reported as low and transient; however, these estimates rely on limited data. We report RNA loads in sera collected from symptomatic patients during the 2013-2014 French Polynesian ZIKV outbreak. We performed molecular detection of ZIKV RNA in sera from 747 patients presenting with suspected acute phase ZIKV infection. Among patients with confirmed infection, we analyzed the duration of viremia, assessed viral RNA loads and recorded the main clinical symptoms. A total of 210/747 (28.1%) sera tested positive using a ZIKV-specific RT-PCR. Viral RNA loads in symptomatic patients that ranged from 5 to 3.7 × 106 copies/mL (mean 9.9 × 104 copies/mL) were not related to a particular clinical presentation, and were significantly lower than those previously obtained from asymptomatic ZIKV infected blood donors. The rate of detection of ZIKV RNA in sera from suspected cases of acute phase ZIKV infection was low. ZIKV RNA loads were lower in symptomatic patients compared to asymptomatic blood donors and were lower than RNA loads usually reported in dengue infections. As there is no abrupt onset of symptoms in ZIKV infections, we suggest that infected patients sought for medical attention when viremia was already decreasing or had resolved.

Zika virus and blood transfusion: the experience of French Polynesia.

BACKGROUND: Between October 2013 and March 2014, French Polynesia experienced the largest Zika virus (ZIKV) outbreak ever described before the emergence of ZIKV in the Americas in 2015. As arbovirus transfusion-transmitted (TT) infections have been previously reported, we hypothesized that transfusion of blood products could also transmit ZIKV. STUDY DESIGN AND METHODS: Mitigation strategies to prevent ZIKV-TT infections included nonspecific measures and the implementation of a laboratory developed ZIKV-specific nucleic acid testing (NAT) assay. Donor sera were tested in pools of 3 and constitutive sera of ZIKV-reactive pools were tested individually. Donor sera were tested prospectively and retrospectively. A posttransfusion follow-up of a patient transfused with ZIKV RNA-reactive blood products was implemented. RESULTS: NAT detected 42 blood donor sera as ZIKV RNA reactive of 1505 tested (2.8%). Thirty ZIKV RNA-reactive blood products collected before the implementation of NAT were transfused to 26 recipients. Posttransfusion investigations were conducted by the hemovigilance unit and data were available for 12 recipients. Symptomatic ZIKV-TT infections were not reported. CONCLUSION: Predonation screening of blood donors, postdonation information, products discard, and quarantine of blood products were not effective enough to prevent transfusion of ZIKV RNA-reactive blood products. ZIKV NAT was an effective measure once implemented to prevent transfusion of ZIKV RNA-reactive blood products but it is difficult to evaluate the effectiveness of this measure to prevent ZIKV-TT infection, which is a rare event.

Amustaline (S-303) treatment inactivates high levels of Zika virus in red blood cell components.

BACKGROUND: The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH). STUDY DESIGN AND METHODS: RBC components were spiked with a high titer of ZIKV. Viral titers (infectivity) and ZIKV RNA loads (reverse transcription-polymerase chain reaction) were measured in spiked RBCs before and after S-303 and GSH treatment and confirmed using repetitive passages in cell culture. A mock-treated arm validated the approach by demonstrating stability of the virus (infectivity and RNA load) during the process. RESULTS: The mean ZIKV infectivity titer and RNA load in RBCs were 5.99 ± 0.2 log 50% tissue culture infectious dose (TCID50 )/mL and 7.75 ± 0.16 log genomic equivalents/mL before inactivation. No infectivity was detected immediately after S-303 and GSH treatment and after five serial passages in cell culture. CONCLUSION: Complete ZIKV inactivation of more than 5.99 log TCID50 /mL in RBCs was achieved using S-303 and GSH at levels higher than those found in asymptomatic ZIKV-infected blood donors. Therefore, the S-303 and GSH PI system is promising for mitigating the risk of ZIKV TT.

Inactivation of Zika virus in plasma with amotosalen and ultraviolet A illumination.

BACKGROUND: Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted by mosquitoes. The potential for ZIKV transmission through blood transfusion was demonstrated during the ZIKV outbreak that occurred in French Polynesia from October 2013 to April 2014. Pathogen inactivation of blood products is a proactive strategy that provides the potential to reduce transfusion-transmitted diseases. Inactivation of arboviruses by amotosalen and ultraviolet A (UVA) illumination was previously demonstrated for chikungunya, West Nile, and dengue viruses. We report here the efficiency of this process for ZIKV inactivation of human plasma. STUDY DESIGN AND METHODS: Plasma units were spiked with ZIKV. Viral titers and RNA loads were measured in plasma before and after amotosalen and UVA photochemical treatment. RESULTS: The mean ZIKV titers and RNA loads in plasma before inactivation were respectively 6.57 log TCID50 /mL and 10.25 log copies/mL. After inactivation, the mean ZIKV RNA loads was 9.51 log copies/mL, but cell cultures inoculated with inactivated plasma did not result in infected cells and did not produce any replicative virus after one passage, nor detectable viral RNA from the second passage. CONCLUSION: In this study we demonstrate that amotosalen combined with UVA light inactivates ZIKV in fresh-frozen plasma. This inactivation process is of particular interest to prevent plasma transfusion-transmitted ZIKV infections in areas such as French Polynesia, where several arboviruses are cocirculating.

Inactivation of dengue virus in plasma with amotosalen and ultraviolet A illumination.

BACKGROUND: Dengue virus (DENV) is the most prevalent arbovirus in tropical and subtropical regions. Transfusion-transmitted DENV infections have already been reported and the risk for blood products to be contaminated by DENV needs to be considered in dengue-endemic areas, especially during outbreaks. Blood product inactivation processes, including amotosalen and ultraviolet A (UVA) illumination, have been developed to reduce transfusion-transmitted infections. In this study we demonstrate the efficiency of using amotosalen and UVA illumination for DENV inactivation in human plasma. STUDY DESIGN AND METHODS: Plasma units from volunteer blood donors were spiked with DENV. Viral titers and viral RNA loads were measured in plasma before and after amotosalen and UVA photochemical treatment. RESULTS: The mean DENV titer in plasma before inactivation was 5.61 log 50% tissue culture infectious dose (TCID50)/mL and the mean viral RNA load was 10.21 log copies/mL. In inactivated plasma, the mean DENV RNA load was 9.37 log copies/mL, but cell cultures inoculated with inactivated plasma did not result in infected cells and did not produce any replicative virus nor detectable viral RNA. CONCLUSION: We report here that amotosalen combined with UVA light inactivated DENV in fresh-frozen plasma (5.61 log inactivation of viral titer). This inactivation process is an efficient method to prevent plasma transfusion-transmitted DENV infections.

Absence of antibodies to Rickettsia spp., Bartonella spp., Ehrlichia spp. and Coxiella burnetii in Tahiti, French Polynesia.

BACKGROUND: In the Pacific islands countries and territories, very little is known about the incidence of infectious diseases due to zoonotic pathogens. To our knowledge, human infections due to Rickettsia spp., Coxiella burnetii, Ehrlichia spp. and Bartonella spp. have never been reported in French Polynesia; and infections due to C. burnetti have been reported worldwide except in New Zealand. To evaluate the prevalence of this disease, we conducted a serosurvey among French Polynesian blood donors. METHODS: The presence of immunoglobulin G antibodies against R. felis, R. typhi, R. conorii, C. burnetii, B. henselae, B. quintana, and E. chaffeensis was evaluated by indirect immunofluorescence assay in sera from 472 French Polynesian blood donors collected from 2011 to 2013. In addition, 178 ticks and 36 cat fleas collected in French Polynesia were also collected and tested by polymerase chain reaction to detect Rickettsia spp., B. henselae and Ehrlichia spp. RESULTS: None of the blood donors had antibodies at a significant level against Rickettsia spp., Coxiella burnetii, Ehrlichia spp. and Bartonella spp. All tested ticks and cat fleas were PCR-negative for Rickettsia spp., B. henselae, and Ehrlichia spp. CONCLUSION: We cannot conclude that these pathogens are absent in French Polynesia but, if present, their prevalence is probably very low. C. burnetii has been reported worldwide except in New Zealand. It may also be absent from French Polynesia.

Hepatitis E prevalence in French Polynesian blood donors.

The HEV seroprevalence in mainland France is elevated (22.4%). In contrast, anti-HEV seroprevalence appears to be lower in Oceania. However, none is available for French Polynesia. We assessed the anti-HEV IgG and IgM prevalence on samples from 300 consecutive blood donors living on Tahiti and Moorea islands. Epidemiological information was collected using a specific questionnaire. Overall IgM seroprevalence was 0.6% and overall IgG seroprevalence was 7.7%. The presence of anti-HEV IgG was associated with increasing age (p = 0.01), eating chicken offal (p = 0.01) and cooked rabbit (p = 0.02). Conversely, eating fafaru-traditional Polynesian condiment-was associated with a lower rate of anti-HEV IgG (p<0.01).). All donors who surfed or practiced va'a (traditional outrigger canoë) were HEV seronegative. The Polynesian lifestyle and the particular food consumption patterns-especially the very well cooked pork-may be the key to understand the low HEV seroprevalence in French Polynesia.

Zika virus in French Polynesia 2013-14: anatomy of a completed outbreak.

The Zika virus crisis exemplified the risk associated with emerging pathogens and was a reminder that preparedness for the worst-case scenario, although challenging, is needed. Herein, we review all data reported during the unexpected emergence of Zika virus in French Polynesia in late 2013. We focus on the new findings reported during this outbreak, especially the first description of severe neurological complications in adults and the retrospective description of CNS malformations in neonates, the isolation of Zika virus in semen, the potential for blood-transfusion transmission, mother-to-child transmission, and the development of new diagnostic assays. We describe the effect of this outbreak on health systems, the implementation of vector-borne control strategies, and the line of communication used to alert the international community of the new risk associated with Zika virus. This outbreak highlighted the need for careful monitoring of all unexpected events that occur during an emergence, to implement surveillance and research programmes in parallel to management of cases, and to be prepared to the worst-case scenario.

Seroprevalence of arboviruses among blood donors in French Polynesia, 2011-2013.

OBJECTIVES: French Polynesia is a high epidemic/endemic area for arthropod-borne viruses (arboviruses). We recently reported the silent circulation of Ross River virus and absence of active transmission of chikungunya virus (CHIKV) among blood donors sampled before the emergence of Zika virus (ZIKV) and CHIKV in French Polynesia. In this study, the prevalence of the four serotypes of dengue virus (DENV) and the occurrence of circulation of other arboviruses were investigated in blood donors in French Polynesia. METHODS: Serum samples from 593 blood donors collected between July 2011 and October 2013 were tested by ELISA for the presence of immunoglobulin G antibodies against each of the four DENV serotypes, ZIKV, Japanese encephalitis virus (JEV), and West Nile virus (WNV). RESULTS: It was found that 80.3%, 0.8%, 1.3%, and 1.5% of blood donors were seropositive for at least one DENV serotype, ZIKV, JEV, and WNV, respectively. CONCLUSIONS: These results corroborate the expected high transmission of DENV and conversely suggest that no active circulation of ZIKV, JEV, and WNV occurred in French Polynesia before 2011. Information provided by this study may be useful for public health authorities to improve surveillance and implement strategies to prevent the transmission of arboviruses.

Silent Circulation of Ross River Virus in French Polynesia.

OBJECTIVES: Ross River is an emerging mosquito-borne disease in the Western Pacific. Ross River virus (RRV) circulation has been sporadically reported in some Pacific Island Countries and Territories but never in French Polynesia. To determine if RRV has circulated locally among the French Polynesian population, we conducted a seroprevalence study on blood donors. METHODS: Sera of 593 blood donors were collected from July 2011 to October 2013 and tested by ELISA for the presence of RRV-specific Immunoglobulin G (IgG) antibodies. RESULTS: A total of 204 (34.40%) blood donors were found seropositive for RRV. Among the 132 blood donors that were born in French Polynesia and had never travelled abroad, 56 (42.42%) had RRV-specific IgGs. DISCUSSION: Our results support the existence of autochthonous RRV transmission and suggest that this pathogen has silently circulated in French Polynesia. These findings raise the question of possible undetected circulation of RRV in other Pacific Island Countries and Territories.