Phylogenetic Investigations of Dengue 2019-2021 Outbreak in Guadeloupe and Martinique Caribbean Islands.

Dengue fever has been a public health problem in the Caribbean region since 1981, when it first reappeared in Cuba. In 1989, it was reported in Martinique and Guadeloupe (two French islands 200 km apart); since then, DENV has caused several epidemics locally. In 2019-2021, DENV-1, DENV-2, and DENV-3 were detected. Serotype distribution was differentiated, with DENV-2 and DENV-3 predominating in Guadeloupe and Martinique, respectively. Complete genome sequencing was carried out on 32 specimens, and phylogenic analysis identified the circulation of genotype V for DENV-1, cosmopolitan genotype for DENV-2, and genotype III for DENV-3. However, two distinct circulating groups were identified for DENV-1 and DENV-3, suggesting independent introductions. Overall, despite the context of the COVID-19 pandemic and the associated travel restrictions, these results confirm the active circulation of DENV and specific epidemiological features on each of the two islands. Such differences may be linked to the founder effect of the various introduction events, and to local factors such as the population immunity and the transmission capacity of the vectors. Further genomic and epidemiological characterization of DENV strains remains essential to understand how dengue spreads in each specific geographical context and to prevent future epidemics.

The Role of Heterogenous Real-world Data for Dengue Surveillance in Martinique: Observational Retrospective Study.

BACKGROUND: Traditionally, dengue prevention and control rely on vector control programs and reporting of symptomatic cases to a central health agency. However, case reporting is often delayed, and the true burden of dengue disease is often underestimated. Moreover, some countries do not have routine control measures for vector control. Therefore, researchers are constantly assessing novel data sources to improve traditional surveillance systems. These studies are mostly carried out in big territories and rarely in smaller endemic regions, such as Martinique and the Lesser Antilles. OBJECTIVE: The aim of this study was to determine whether heterogeneous real-world data sources could help reduce reporting delays and improve dengue monitoring in Martinique island, a small endemic region. METHODS: Heterogenous data sources (hospitalization data, entomological data, and Google Trends) and dengue surveillance reports for the last 14 years (January 2007 to February 2021) were analyzed to identify associations with dengue outbreaks and their time lags. RESULTS: The dengue hospitalization rate was the variable most strongly correlated with the increase in dengue positivity rate by real-time reverse transcription polymerase chain reaction (Pearson correlation coefficient=0.70) with a time lag of -3 weeks. Weekly entomological interventions were also correlated with the increase in dengue positivity rate by real-time reverse transcription polymerase chain reaction (Pearson correlation coefficient=0.59) with a time lag of -2 weeks. The most correlated query from Google Trends was the "Dengue" topic restricted to the Martinique region (Pearson correlation coefficient=0.637) with a time lag of -3 weeks. CONCLUSIONS: Real-word data are valuable data sources for dengue surveillance in smaller territories. Many of these sources precede the increase in dengue cases by several weeks, and therefore can help to improve the ability of traditional surveillance systems to provide an early response in dengue outbreaks. All these sources should be better integrated to improve the early response to dengue outbreaks and vector-borne diseases in smaller endemic territories.

Fundus Changes in the Offspring of Mothers With Confirmed Zika Virus Infection During Pregnancy in French Guiana, Guadeloupe, and Martinique, French West Indies.

Importance: Most ocular lesions have been described for children with congenital Zika syndrome. The frequency of finding ocular abnormalities is unknown among children exposed to Zika virus (ZIKV) during pregnancy. This study was conducted on newborns whose mothers were positive for ZIKV, confirmed with reverse-transcription polymerase chain reaction (RT-PCR) testing. Objective: To report ocular fundus manifestations in newborns with congenital ZIKV exposure in French Guiana, Martinique, and Guadeloupe, French West Indies, to assess its prevalence. Risk factors, such as the presence of extraocular fetopathies and the gestational term at infection, were sought. Design, Setting, and Participants: This was a cross-sectional multicentric study, conducted from August 1, 2016, to April 30, 2019, for which data were collected prospectively. The study inception was at the beginning of 2016 from the onset of the ZIKV epidemic in the French West Indies. Newborns whose mothers tested positive (by RT-PCR) for ZIKV during pregnancy were included. Interventions: Fundus examination was performed using widefield retinal imaging after pupil dilation. Infection date, delivery mode, and newborn measurements were collected. Main Outcomes and Measures: Anomalies of the vitreous, choroid, retina, and optic disc. Results: A total of 330 children (mean [SD] age, 68 [IQR, 22-440] days; 170 girls [51.5%]) were included. Eleven children (3.3%) had perivascular retinal hemorrhages, and 3 (0.9%) had lesions compatible with congenital ZIKV infection: 1 child had torpedo maculopathy, 1 child had a chorioretinal scar with iris and lens coloboma, and 1 child had a chorioretinal scar. Retinal hemorrhages were found at childbirth during early screening. Lesions compatible with congenital ZIKV infection were not associated with the presence of extraocular fetopathy. Microcephaly was not associated with lesions compatible with congenital ZIKV infection (odds ratio [OR], 9.1; 95% CI, 0.8-105.3; P = .08), but severe microcephaly was associated with an OR of 81 (95% CI, 5.1-1297.8; P = .002). Conclusions and Relevance: Results of this cross-sectional study suggest that the ocular anomalies found may be associated with ZIKV in 0.9% of the exposed population. Ocular lesions were rare, affected mostly the choroid and retina, and seemed to be associated with choroiditis-related scarring that developed during fetal growth.

Genotype distribution of cervical HPV among Caribbean women in a population-based study in Martinique: The DEPIPAPUFR study.

The Caribbean ranks seventh among the world regions most affected by cervical cancer. HPV-prevalence and genotype distributions also differ from regions. Knowledge of HPV genotype profiles is important for patients care and HPV vaccination implementation. The objective of this study was to describe HPV genotype distribution and risk factors in a population-based cohort of women in Martinique. In this study, 1312 women were included and underwent cervical cancer screening with successful sample collection between 2009 and 2014. Sociodemographic and clinical variables were recorded. Cytological examination of cervical vaginal smear was performed and classified(Bethesda). Detection of HPV DNA was performed with the PapilloCheck© Kit from Greiner Bio-one. Genotypes were analyzed for18 high-risk HPV (hrHPV) and 6low-risk HPV(lrHPV) types. A total of 1075 women were included with a mean age of 49.1±10.5 years. HPV prevalence was 27.6% (297/1075) with 19.4% (209/1075) women with only hrHPV, 5.3% (57/1075) with only lrHPV. Multiple infections (hrHPV/lrHPV) were detected in 31/240 cases of hrHPV (12.9%). A total of 353 hrHPV genotypes were analyzed; the most common HPV types were HPV51 (11.0%), HPV68 (10.8%), HPV53 (9.1%) and HPV 52 (7.1%). HPV16 and HPV18 represented respectively 4.8% and 4.0% of hrHPV genotypes. Abnormal cytology was observed in 34 cases (3.2%), with 14 ASCUS (1.3%), 10 LSIL (0.9%), 5 HSIL (0.5%), 3 ASC-H (0.3%) and 2 AGC (0.2%). Fifteen (44.1%) were hrHPV and 4 (14.7%) lrHPV; 7 cases of hrPHV were in the age-group 25-34 years. Among 1041cases of normal cytology, 225 had positive hrHPV detection (21.6%). This is the first population-based study of HPV profiles in our country, and we found a high prevalence of hrHPV. The most common genotypes were HPV51, 68, 53. These results could serve for cancer vaccination strategies and HPV surveillance in Martinique.

Contribution of Research in the West Indies and Northeast Amazonia to Knowledge of the 2014-2015 Chikungunya Epidemic in the Americas.

PURPOSE OF REVIEW: Although the chikungunya virus was discovered more than 60 years ago, it has only really been studied since the outbreak in La Reunion in 2005-2006. Ten years later, between 2014 and 2015, the chikungunya virus spread throughout the Americas, affecting millions of people. The objective of this review is to describe the contributions of research on chikungunya virus infection gained from epidemic in the West Indies and the Guiana Shield. RECENT FINDINGS: Prevalence data were similar to those found in the Indian Ocean or Asia during epidemics. Clinically, there is now a better understanding of the typical, atypical, and severe forms. Several studies have insisted on the presence of neurological forms of chikungunya infection, such as encephalitis or Guillain-Barré syndrome. Cases of septic shock due to chikungunya virus as well as thrombotic thrombocytopenic purpura were described for the first time. Given the magnitude of the epidemic and the large number of people affected, this has led to a better description and new classifications of chikungunya virus infections in specific populations such as pregnant women, the elderly, and children. Several studies also described the behavior of populations faced with an emerging disease. SUMMARY: Current epidemiological data from tropical regions highlights the risk of spreading emerging diseases at higher latitudes, especially concerning arboviruses, since the vector Aedes albopictus is already established in many parts of northern countries. A better understanding of the disease and its epidemic dynamics will foster better management, the crucial importance of which was demonstrated during the COVID-19 epidemic.

Adaptation of WHO Definitions of Clinical Forms of Chikungunya Virus Infection for the Elderly.

The WHO defined three clinical forms for chikungunya virus infection (CHIKV, namely, acute, atypical, and severe cases) and a chronic form. These definitions seemed inappropriate for the elderly. So, we propose an adapted definition for elderly people. A cross-sectional analysis was performed including patients aged ≥ 65 years, who attended the emergency department with a positive biological diagnosis of CHIKV in 2014. A total of 267 elderly patients (80 ± 8 years) were included. When using the 2015 WHO definitions, 114 patients could not be classified (42.7%) in any of the category, of whom 43 (37.7%) reported absence of fever, 85 (74.6%) reported absence of joint pain, and 14 (12.3%) reported absence of both fever and joint pain. After adaptation of the WHO definitions, the 114 unclassifiable patients were reclassified as follows: eight as typical cases, 50 as atypical cases, 42 as severe cases, and 14 remained unclassifiable. The atypical clinical form was the most common form. The 2015 WHO definitions of the clinical forms at the acute phase of CHIKV are ill suited to the elderly. The adapted definition we propose here appears to be more appropriate and could help improved management of older patients with CHIKV.

E6/E7 Sequence Diversity of High-Risk Human Papillomaviruses in Two Geographically Isolated Populations of French Guiana.

Amerindian and Maroon populations of French Guiana have been living in isolation for generations and sexual networks remained mostly endogamous. The present study aimed to describe the phylogeny of E6 and E7 sequences of the most common high-risk HPV genotypes in these regions, to ascertain the diversity of intra-type variants and describe evolutionary relationships. There were 106 women with at least one of HPV16, 18, 31, 52, 58, and 68 genotypes. The most clear-cut phylogenetic pattern was obtained for HPV18 and HPV58 for which the major branches were crisply divided between Amerindian villages on the Oyapock and Maroon villages on the Maroni. Such clustering was less clear for HPV31 and 52. For HPV16, there was also some evidence of clustering on the Oyapock with type A European viruses and on the Maroni with type B and C African viruses among Maroon women. HPV68 showed the largest sequence heterogeneity of the six genotypes at both nucleotide and amino acid levels and was restricted to Maroon women. The present results show that there were significant geographically based differences of E6 and E7 oncogenes. These differences were compatible with different ancestral virus populations and local virus evolution in a context of prolonged population isolation.

Zika Virus Infection Promotes Local Inflammation, Cell Adhesion Molecule Upregulation, and Leukocyte Recruitment at the Blood-Brain Barrier.

The blood-brain barrier (BBB) largely prevents toxins and pathogens from accessing the brain. Some viruses have the ability to cross this barrier and replicate in the central nervous system (CNS). Zika virus (ZIKV) was responsible in 2015 to 2016 for a major epidemic in South America and was associated in some cases with neurological impairments. Here, we characterized some of the mechanisms behind its neuroinvasion using an innovative in vitro human BBB model. ZIKV efficiently replicated, was released on the BBB parenchyma side, and triggered subtle modulation of BBB integrity as well as an upregulation of inflammatory and cell adhesion molecules (CAMs), which in turn favored leukocyte recruitment. Finally, we showed that ZIKV-infected mouse models displayed similar CAM upregulation and that soluble CAMs were increased in plasma samples from ZIKV-infected patients. Our observations suggest a complex interplay between ZIKV and the BBB, which may trigger local inflammation, leukocyte recruitment, and possible cerebral vasculature impairment.IMPORTANCE Zika virus (ZIKV) can be associated with neurological impairment in children and adults. To reach the central nervous system, viruses have to cross the blood-brain barrier (BBB), a multicellular system allowing a tight separation between the bloodstream and the brain. Here, we show that ZIKV infects cells of the BBB and triggers a subtle change in its permeability. Moreover, ZIKV infection leads to the production of inflammatory molecules known to modulate BBB integrity and participate in immune cell attraction. The virus also led to the upregulation of cellular adhesion molecules (CAMs), which in turn favored immune cell binding to the BBB and potentially increased infiltration into the brain. These results were also observed in a mouse model of ZIKV infection. Furthermore, plasma samples from ZIKV-infected patients displayed an increase in CAMs, suggesting that this mechanism could be involved in neuroinflammation triggered by ZIKV.

Is Chikungunya Virus Infection an Independent Risk Factor for 2-Year Mortality in Older Afro-Caribbean Subjects?

PURPOSE: The aim of this study was to investigate whether Chikungunya virus infection (CVI) was an independent risk factor for 2-year mortality in Afro-Caribbean subjects aged 65 years or older. PATIENTS AND METHODS: A retrospective cohort study was performed from January 2014 to December 2016 in the University Hospital of Martinique. Subjects aged ≥65 years admitted to the hospital were included. Baseline characteristics and concurrent manifestations at admission were collected. Subjects were followed up by phone for 2 years. RESULTS: A total of 687 old Afro-Caribbean subjects (80.4±8.0 years) were included: 467 positive for CVI (Chik+) and 220 negative for CVI (Chik-). During the follow-up, 180 (26.2%) died. The proportion of deaths was higher among Chik- (40.9%) than among Chik+ subjects (21.6%) (p<0.0001). By multivariable analysis, when adjusted for age polyarthralgia, neurological troubles, cardiovascular disorders, absence of neutrophilia, thrombocytopenia, hypernatremia, and hospital stay, Chik+ subjects had significantly higher survival rates (HR: 0.58; 95% CI: 0.40-0.85) than Chik- ones. CONCLUSION: Within the two years following hospital admission of subjects aged ≥65 years or older, Chik+ subjects had significantly higher survival rates than Chik- ones.

Seasonality and coinfection of bronchiolitis: epidemiological specificity and consequences in terms of prophylaxis in tropical climate.

OBJECTIVE: To describe the viruses involved, seasonality and coinfection in hospitalised children with suspected bronchiolitis. METHODS: Over the period 1/07/2007 to 31/12/2008, all children hospitalised for bronchiolitis in the paediatric ward were prospectively included, and had respiratory syncytial virus (RSV) screenings. We retrospectively tested all samples for RSVA, RSVB, rhinovirus (RV), human metapneumovirus, parainfluenza 1, 2, 3, 4, influenza A and influenza B. RESULTS: 198 children were tested, and 23% were negative for all viruses. RSVA was predominant in 2008 (64% of all viruses) and RSVB in 2007 (66% of all viruses). RV was frequent during both seasons (24% of all viruses). Flu was not found during the study period. Virus distribution was similar regardless of season or age, and identical to typical patterns in temperate countries. Coinfections were less frequent than in temperate regions because respiratory virus seasons seem to be better separated. The bronchiolitis season started in August and finished in December with a peak in October. CONCLUSION: The specific seasonality of bronchiolitis infection requires palivizumab prophylaxis starting in early July for high-risk infants.

OBJECTIF: Décrire les virus impliqués, la saisonnalité et la coinfection chez les enfants hospitalisés avec une suspicion de bronchiolite. MÉTHODES: Au cours de la période du 01/07/2007 au 31/12/2008, tous les enfants hospitalisés pour bronchiolite dans le service de pédiatrie ont été prospectivement inclus et soumis à un dépistage du virus respiratoire syncytial (VRS). Nous avons testé rétrospectivement tous les échantillons pour RSVA, RSVB, rhinovirus (RV), métapneumovirus humain, Parainfluenza 1, 2, 3, 4, Influenza A, et Influenza B. RÉSULTATS: 198 enfants ont été testés et 23% étaient négatifs pour tous les virus. RSVA était prédominant en 2008 (64% de tous les virus) et RSVB en 2007 (66% de tous les virus). RV était fréquent pendant les deux saisons (24% de tous les virus). La grippe n'a pas été trouvée pendant la période d'étude. La distribution des virus était similaire quelle que soit la saison ou l'âge, et identique aux modèles typiques dans les pays tempérés. Les coinfections étaient moins fréquentes que dans les régions tempérées car les saisons virales respiratoires semblent mieux séparées. La saison des bronchiolites a commencé en août et s'est terminée en décembre avec un pic en octobre. CONCLUSION: La saisonnalité spécifique de l'infection bronchiolite nécessite une prophylaxie au palivizumab débutant en juillet pour les nourrissons à haut risque.

The effects of chikungunya virus infection on people living with HIV during the 2014 Martinique outbreak.

Our objective was to describe the clinical presentation of chikungunya virus (CHIKV) infection in patients living with HIV (PLHIV) during the 2014 Martinique outbreak. During the outbreak and the 6 following months, all PLHIV coming in our unit for a medical evaluation answered questions about potential CHIKV related symptoms, and had blood tests to assess the diagnosis. For patients coming in at the acute phase of infection, we are able to provide and analyze CD4+, CD8+ T-cells and HIV viral load evolution before, during and after CHIK infection. Among the 1 003 PLHIV in care in the center at the time of the outbreak, 188 (94 men and 94 women) had confirmed (following the WHO definition) CHIKV infection. Clinical presentation was common in 63% of the cases, severe and atypical forms were scarce. During the acute phase, CD4+ and CD8+ T-cells (evaluated in 30 PLHIV, 15 men and 15 women) absolute numbers dropped significantly, but returned to pre-CHIKV values after the acute phase. Reassuringly, CD4 and CD8 T cells proportions did not decrease during the acute phase. CHIKV infection had no significant impact on this anti-retroviral treated population.

International cooperation in public health in Martinique: geostrategic utility for cancer surveillance in the Caribbean.

BACKGROUND: Cooperation in public health and in oncology in particular, is currently a major issue for the island of Martinique, given its geopolitical position in the Caribbean region. The region of Martinique shares certain public health problems with other countries of the Caribbean, notably in terms of diagnostic and therapeutic management of patients with cancer. We present here a roadmap of cooperation priorities and activities in cancer surveillance and oncology in Martinique. MAIN BODY: The fight against cancer is a key public health priority that features high on the regional health policy for Martinique. In the face of these specific epidemiological conditions, Martinique needs to engage in medical cooperation in the field of oncology within the Caribbean, to improve skills and knowledge in this field, and to promote the creation of bilateral relations that will help to improve cancer management in an international healthcare environment. CONCLUSIONS: These collaborative exchanges will continue throughout 2020 and will lead to the implementation of mutual research projects across a larger population basin, integrating e-health approaches and epidemiological e-cohorts.

Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique): A prospective cohort study.

BACKGROUND: The chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic and potentially incapacitating rheumatic musculoskeletal disorders known as chronic chikungunya arthritis (CCA). We conducted a prospective cohort study of CHIKV-infected subjects during the 2013 chikungunya outbreak in Martinique. The aim of this study was to assess the prevalence of CCA at 12 months and to search for acute phase factors significantly associated with chronicity. METHODOLOGY/PRINCIPAL FINDINGS: A total of 193 patients who tested positive for CHIKV RNA via qRT-PCR underwent clinical investigations in the acute phase (<21 days), and then 3, 6, and 12 months after inclusion. The Asian lineage was identified as the circulating genotype. A total of 167 participants were classified as either with or without CCA, and were analyzed using logistic regression models. The overall prevalence of CCA at 12 months was 52.1% (95%CI: 44.5-59.7). In univariate analysis, age (RD 9.62, 95% CI, 4.87;14.38, p<0.0001), female sex (RD 15.5, 95% CI, 1.03;30.0, p = 0.04), headache (RD 15.42, 95% CI, 0.65;30.18 p = 0.04), vertigo (RD 15.33, 95% CI, 1.47;29.19, p = 0.03), vomiting (RD 12.89, 95% CI, 1.54;24.24, p = 0.03), dyspnea (RD 13.53, 95% CI, 0.73;26.33, p = 0.04), intravenous rehydration (RD -16.12, 95% CI, -31.58; -0.66 p = 0.04) and urea (RD 0.66, 95% CI, 0.12;1.20, p = 0.02) were significantly associated with the development of CCA. For the subpopulation with data on joint involvement in the acute phase, the risk factors significantly associated with CCA were at least one 1 enthesitis (RD 16.7, 95%CI, 2.8; 30.7, p = 0.02) and at least one tenosynovitis (RD 16.8, 95% CI, 1.4-32.2, p = 0.04). CONCLUSIONS: This cohort study conducted in Martinique confirms that CCA is a common complication of acute chikungunya disease. Our analysis emphasized the importance of age and female sex for CCA occurrence, and highlighted the aggravating role of dehydration during the acute phase. Early and adequate hydration were found to reduce the risk chronic chikungunya disorders. TRIAL REGISTRATION: clinicaltrials.gov (NCT01099852).

High prevalence of human papillomavirus infection in HIV-infected women living in French Antilles and French Guiana.

An association between HIV infection and cervical cancer, a major public health issue worldwide, has been reported. The aim of this study was to estimate the prevalence of human papillomavirus (HPV) infection and the distribution of HPV genotypes in HIV-infected women living in French Antilles and Guiana and to determine HIV-related characteristics associated with HPV infection. This cross-sectional study included 439 HIV-infected women who were followed between January 2011 and May 2014. Variables related to HIV infections were collected, and cervical samples were analysed to determine HPV genotypes. The median age of the population was 46 years. Estimated prevalence of HPV and high-risk (HR)-HPV infection were 50.1% IC95 [45.4-54.7] and 42% IC95 [37.3-46.6], respectively. HR-HPV 16, 52, 53 or intermediate risk-HPV-68 were found in 25% to 30% of the HPV-infected patients. Gynaecological screening revealed abnormal cervical smear in 24% and 42% of HR-HPV-negative and HPV-positive women, respectively (p = 0.003). Approximately 90% of women were on antiretroviral therapy (ART). Demographic characteristics associated with a higher prevalence of HPV infection included alcohol consumption. Regarding HIV-related characteristics, current therapy on ART, its duration, and undetectable plasma concentrations of RNA-HIV1 were associated with a lower risk of HPV infection. Infection rate with HR-HPV was higher than what is commonly reported in HIV-negative women worldwide and was more likely in women with incomplete HIV suppression. These results highlight the need for supporting adherence to ART, cervical cytology, HPV testing and HPV vaccination.

Assessing Zika Virus Transmission Within Households During an Outbreak in Martinique, 2015-2016.

Since 2015, Zika virus (ZIKV) has caused large epidemics in the Americas. Households are natural targets for control interventions, but quantification of the contribution of household transmission to overall spread is needed to guide policy. We developed a modeling framework to evaluate this contribution and key epidemic features of the ZIKV epidemic in Martinique in 2015-2016 from the joint analysis of a household transmission study (n = 68 households), a study among symptomatic pregnant women (n = 281), and seroprevalence surveys of blood donors (n = 457). We estimated that the probability of mosquito-mediated within-household transmission (from an infected member to a susceptible one) was 21% (95% credible interval (CrI): 5, 51), and the overall probability of infection from outside the household (i.e., in the community) was 39% (95% CrI: 27, 50). Overall, 50% (95% CrI: 43, 58) of the population was infected, with 22% (95% CrI: 5, 46) of infections acquired in households and 40% (95% CrI: 23, 56) being asymptomatic. The probability of presenting with Zika-like symptoms due to another cause was 16% (95% CrI: 10, 23). This study characterized the contribution of household transmission in ZIKV epidemics, demonstrating the benefits of integrating multiple data sets to gain more insight into epidemic dynamics.

Long-term outcome in neuroZika: When biological diagnosis matters.

OBJECTIVE: To characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection. METHODS: We conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak. RESULTS: Eighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13-17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12-75.22; p = 0.039). CONCLUSIONS: NeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients.

Long-term survival and clinical forms in the acute phase of Chikungunya virus infection in older Caribbeans.

OBJECTIVE: To investigate whether the long-term survival in elderly patients with prior Chikungunya virus infection (CVI) is associated with the clinical form presented in the acute phase, as defined by the WHO classification. METHODS: Retrospective cohort study performed in Martinique University Hospitals. Patients who attended the emergency department for suspected CVI, and who had a positive biological diagnosis of CVI by reverse transcription-polymerase chain reaction on a plasma sample between 10 January and 31 December 2014 were eligible for inclusion. Time-to-death was the primary outcome. The independent relationship between clinical forms and time-to-death was analysed using a Cox model. RESULTS: In total, 268 patients were included. Mean age was 80 ± 8 years, 53% were women. Median length of follow-up was 28 months (range: 0-39). During follow-up, 53 (19.8%) patients died. Median survival time was 13.2 months (range: 0-33.6). At the end of follow-up, death rates were 4.6% for acute clinical cases, 19.0% for atypical cases, 19.2% for severe acute cases and 23.5% for unclassifiable cases. By multivariable analysis, the clinical form of CVI at admission was found to be independently associated with long-term survival (atypical form: HR = 2.38; 95% CI = 2.15-2.62; severe acute form: HR = 2.40; 95% CI = 2.17-2.64; unclassifiable form: HR = 2.28; 95% CI = 2.06-2.51). CONCLUSION: The clinical form at presentation with CVI has a significant impact on long-term survival. Management of CVI patients should be tailored according to their clinical form at admission.

OBJECTIF: Etudier si la survie à long terme chez les patients âgés avec une infection antérieure par le virus du chikungunya (IVC) est associée à la forme clinique présente dans la phase aiguë, telle que définie par la classification de l'OMS. MÉTHODES: Etude de cohorte rétrospective réalisée dans les hôpitaux universitaires de la Martinique. Les patients qui se présentaient au service des urgences en cas de suspicion d'IVC et qui avaient un diagnostic biologique positif d'ICV par la PCR à transcription inverse sur un échantillon plasmatique entre le 10 janvier et le 31 décembre 2014 étaient éligibles à l'inclusion. Le temps jusqu'au décès était le résultat principal. La relation indépendante entre les formes cliniques et le temps jusqu'au décès a été analysée à l'aide d'un modèle de Cox. RÉSULTATS: Au total, 268 patients ont été inclus. L'âge moyen était de 80 ± 8 ans, 53% étaient des femmes. La durée médiane du suivi était de 28 mois (intervalle: 0 à 39 ans). Au cours du suivi, 53 patients (19,8%) sont décédés. La durée médiane de survie était de 13,2 mois (intervalle: 0 à 33,6). A la fin du suivi, les taux de décès étaient de 4,6% pour les cas cliniques aigus, 19,0% pour les cas atypiques, 19,2% pour les cas aigus sévères et 23,5% pour les cas non classifiables. L'analyse multivariée a révélé que la forme clinique de l'IVC à l'admission était indépendamment associée à la survie à long terme (forme atypique: HR = 2,38; IC95%: 2,15-2,62; forme aiguë sévère: HR = 2,40; IC95%: 2,17-2,64; forme inclassable: HR = 2,28; IC95%: 2,06-2,51). CONCLUSION: La forme clinique lors de la présentation avec IVC a un impact significatif sur la survie à long terme. La prise en charge des patients atteints d'ICV devrait être adaptée à la forme clinique lors de l'admission.

Congenital Zika virus syndrome what else? Two case reports of severe combined fetal pathologies.

BACKGROUND: Zika virus (ZIKV) has recently emerged as a teratogenic infectious agent associated with severe fetal cerebral anomalies. Other microorganisms (TORCH agents) as well as genetic disorders and toxic agents may lead to similar anomalies. In case of fetal anomalies, the exact etiology might be difficult to establish, especially in ZIKV endemic countries. As the risks associated with maternal infection remain unclear adequate parental counseling is difficult. CASE PRESENTATION: We present two cases of severe fetal pathologies managed in our multidisciplinary center during the ZIKV outbreak in Martinique, a French Caribbean Island. Both fetuses had congenital ZIKV infection confirmed by RT-PCR. While one case presented with significant cerebral anomalies, the other one presented with hydrops fetalis. A complete analysis revealed that the fetal lesions observed resulted from a combination of ZIKV congenital infection and a genetic disorder (trisomy 18) in case 1 or congenital Parvovirus B19 infection in case 2. CONCLUSIONS: We highlight the difficulties related to adequate diagnosis in case of suspected ZIKV congenital syndrome. Additional factors may contribute to or cause fetal pathology, even in the presence of a confirmed ZIKV fetal infection. An exact diagnosis is mandatory to draw definitive conclusions. We further emphasize that, similarly to other congenital infections, it is very likely that not all infected fetuses will become symptomatic.

Misdiagnosis of Chikungunya Virus Infection: Comparison of Old and Younger Adults.

OBJECTIVES: To assess the frequency of diagnostic errors in older adults presenting to the emergency department (ED) with symptoms suggestive of Chikungunya virus infection (CVI) and to compare the rates of misdiagnosis of older and younger adults. DESIGN: Cross-sectional study performed in the University Hospitals of Martinique from retrospective cases. SETTING: Emergency department. PARTICIPANTS: Individuals aged 65 and older who attended the ED and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for CVI between January and December 2014 (n=333, mean age 80±8) were considered eligible and were compared with a randomly selected sample of younger adults (< 65) (n=143, mean age 45±13). MEASUREMENTS: Misdiagnosis rates. RESULTS: The rate of misdiagnosis of CVI in the ED was 30.6% in individuals aged 65 and older and 6.3% in those younger than 65 (p<.001). The overdiagnosis rate was 9.0% in individuals aged 65 and older and 3.5% in those younger than 65 (p=.04). The underdiagnosis rate was significantly higher (p<.001) in individuals aged 65 and older (21.6%) than in those younger than 65 (2.8%). CONCLUSION: Misdiagnosis of CVI during an epidemic is statistically more frequent in older than younger adults because clinical presentation is often atypical in older adults. Specific diagnostic tools for older adults and better awareness of ED physicians of different presentations in different age groups could help to reduce the rate of misdiagnosis of CVI in the ED.