A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates

Multidisciplinary Prospective Study of Mother-to-Child Chikungunya Virus Infections on the Island of La Réunion

In a prospective study on the island of La Réunion, Marc Lecuit and colleagues find frequent transmission of Chikungunya virus by viremic mothers giving birth during an outbreak, resulting in serious infant illness

Low Clinical Burden of 2009 Pandemic Influenza A (H1N1) Infection during Pregnancy on the Island of La Réunion

BACKGROUND: Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic (pdm). The purpose of this prospective register-based cohort-study was to characterize the clinical virulence of the pdm (H1N1/09)v during pregnancy in La Réunion. METHODS/PRINCIPAL FINDINGS: Over a twelve-week pdm wave (13 July to 3 October 2009), 294 pregnant women presented with an influenza-like illness (ILI) to one of the three maternity departments of the South Reunion area, Indian Ocean. Out of these, 278 were checked by RT-PCR for influenza viruses (157 positive and 121 negative, of whom, 141 with pdm flu and 132 with ILIs of non pdm origin, 5 untyped). The median body temperature was higher in women experiencing pdm flu than in those with non pdm ILI (38.9 degrees C versus 38.3 degrees C, P<0.0001), without evidence linked to circulating viremia. Oseltamivir was given for 86% of pdm flu cases in a median time inferior than 48 hrs (range 0-7 days). The hospitalization rate for pdm flu was of 60% and not associated with underlying conditions. Six viral pneumonia and fourteen asthma attacks were observed among 84 hospitalized pdm flu cases, of whom, only one led to the ICU for an acute lung injury. No maternal death occurred during the pdm wave. None adverse pregnancy outcome was associated with pdm flu. No congenital birth defect, nor early-onset neonatal influenza infection was attributable to pdm flu exposure. CONCLUSIONS/SIGNIFICANCE: This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy. The reasons for which the clinical burden of H1N1/09 influenza virus may differ worldwide raise questions about a differential local viral-strain effect and public health preparedness, notably in timely access to special care and antiviral treatments

Infection maternelle à Chikungunya (étude descriptive dans un contexte d'épidémie en 2005-2006 à l'île de la Réunion)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

LA PLACE DE L'ECLAMPSIE DANS LES ACCIDENTS VASCULAIRES CEREBRAUX GRAVES DE LA GROSSESSE (APPORT DE L'IMAGERIE ; A PROPOS DE SIX OBSERVATIONS AU CENTRE HOSPITALIER SUD-REUNION)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Obstetric and neonatal outcomes of adolescent primiparous singleton pregnancies: a cohort study in the South of Reunion Island, Indian Ocean

International audienceOBJECTIVES: To describe the maternal and neonatal outcomes of a large cohort of adolescent pregnancies in a tertiary care hospital at Reunion Island. METHODS: Retrospective study of all primiparous singleton pregnancies over 10.5 years. Adolescent (\textless18 years) were compared to 18-29 years pregnancies. The maternal outcomes were obstetric illness, labor complications, and way of delivery. Neonatal outcomes were preterm birth, low birth weight (LBW), small for gestational age, birth asphyxia, need for mechanical ventilation, and mortality. RESULTS: We analyzed 1839 adolescent pregnancies and 11,445 controls. Adolescents had worse prenatal care than older mothers, (4.4 vs. 1.4%; p \textless 0.0001), higher rates of smoking and alcohol assumption (13 vs. 11% and 0.7 vs. 0.4%, both p \textless 0.05). They showed less pregnancy-related illness and labor complications and higher rates of normal vaginal delivery (80 vs. 69%; p \textless 0.0001), without increased risk of episiotomy or postpartum hemorrhage. Offspring mortality, preterm birth, and LBW were higher in adolescent pregnancies (3.3 vs. 2.2%; p = 0.001, 14 vs. 12%; p = 0.0008; 17 vs. 14%; p = 0.002). CONCLUSIONS: In this population, adolescents had an obstetrical outcome better than controls, but their offspring short-term outcomes were unfavorable. Furthers studies are needed to better elucidate the link between adolescent pregnancy and impaired neonatal outcome

Longitudinal health outcome and wellbeing of mother–infant pairs after adolescent pregnancy in Reunion Island, Indian Ocean

International audienceAbstract Objective : To evaluate longitudinal care needs and health service access among mother–infant pairs after adolescent pregnancy. Methods : In a case–control study, data were analyzed from primiparous adolescent and adult mother–infant pairs who delivered at Reunion Island University Hospital, France, between January 2004 and December 2006, and were followed-up from maternity discharge until December 2011. Infant outcomes were hospitalization during the first 2 years of life, hospital access for “non-medical” reasons, and neuropsychiatric care. Maternal outcomes were number of pregnancies and childbirths, rapid repeat pregnancy (RRP) rate, pregnancy morbidities, and use of health services. Results : Data from 476 cases and 476 controls were analyzed. Adolescent and control offspring did not differ in the measured outcomes. Adolescent and control mothers had, respectively, 2.4 ± 1.3 and 1.9 ± 1.1 pregnancies; 1.9 ± 0.8 and 1.6 ± 0.7 childbirths; and RRP rates of 7.6% and 2.7% (all P &lt; 0.001). Adolescents had less pregnancy-related pathologies at the index pregnancy and more frequently had natural deliveries (P &lt; 0.05). Younger mothers exhibited higher rates (19.7% versus 6.9%, P = 0.001) of care for psychosocial reasons (suicide attempt, acute alcohol or drug intoxication, road accident, psychiatric problems, physical abuse). Conclusion : Concerns arise from the long-term psychosocial risk among adolescent mothers

Morbidité et mortalité périnatale des jumeaux et influence de la chorionicité : expérience de 10ans dans le Sud-Réunion. Étude de 775 grossesses

International audienceOBJECTIVES: To compare the perinatal mortality and morbidity of infants born from monochorionic versus dichorionic twin pregnancies (TP). PATIENTS AND METHODS: Retrospective, comparative study of monochorionic and dichorionic TP over 10 years in the south of Reunion Island. Information regarding demographic, gestational and perinatal variables of mothers and infants was collected from the hospital perinatal database. RESULTS: Six hundred and twenty dichorionic and 155 monochorionic TP were analyzed. In case of monochorionic TP, mothers had higher rates of pregnancy-related hypertension (OR=1.82, 95%CI=[1.02-3.29] ; P=0.03) and hospitalization (OR=1.48, 95%CI=[1.02-2.16]; P=0.03). Newborns from monochorionic TP had higher morbidity for : very preterm birth (birth before 33 weeks gestation) (OR=1.65, 95%CI=[1.02-2.66]; P=0.02), very low birth weight (birth weight\textless1500g) (OR=1.73, 95%CI=[1.57-3.13]; P\textless0.001), Apgar\textless7 at 1 minute (OR=1.76, 95%CI=[1.18-2.61]; P\textless0.01) and hospitalization (OR=2.08, 95%CI=[1.58-2.73]; P\textless0.001). Perinatal mortality was also significantly higher (OR=2.47, 95%CI=[1.54-3.94]; P\textless0.001), as well intrauterine fetal death (OR=3.96, 95%CI=[1.95-8.05]; P\textless0.001) CONCLUSION: This study confirms that few differences exist among dichorionic and monochorionic TP with regard to maternal morbidity, while neonatal morbidity and mortality are higher in twins born from monochorionic pregnancies

Development of a sensitive real-time reverse transcriptase PCR assay with an internal control to detect and quantify chikungunya virus

International audienceBackground: The chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged in the south Western Indian Ocean since early 2005. A major outbreak of CHIKV infection occurred in Reunion Island, where the virus is transmitted by Aedes albopictus mosquitoes. Facing an outbreak of unprecedented magnitude, we developed a rapid, sensitive, and reliable assay for the detection and quantification of CHIKV in plasma samples. Methods: A dual-color TaqMan 1-step reverse transcriptase PCR assay was developed in a LightCycler 2.0 system. A coextd. and coamplified chimerical RNA sequence was used as an internal control (IC) to eliminate false-neg. results. The CHIKV-specific and IC probes were labeled with 6-carboxyfluorescein (530 nm) and the wide span dye DYXL (705 nm), resp., eliminating the need for color compensation. A synthetic RNA was used as an external calibrator for CHIKV abs. quantification. Results: The detection limit was 350 copies/mL (3 copies/capillary). A further improvement to ∼40 copies/mL was obtained by use of a larger vol. of plasma. The assay specificity was confirmed in vitro and in silico. CHIKV in 343 patients was present at viral loads \textgreater108 copies/mL, mainly in newborns and seniors \textgreater60 years old. Long viremic phases of up to 12 days were seen in 6 patients. Conclusions: The assay is rapid, CHIKV-specific, and highly sensitive, and it includes an IC. It proved useful to detect and quantify CHIKV during the Reunion Island epidemic. The assay might be applicable to other CHIKV epidemics, esp. in the Indian subcontinent, where an extensive outbreak is ongoing. [on SciFinder(R)