Liver involvement in dengue: A systematic review.

Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.

Dynamics of emergence and genetic diversity of dengue virus in Reunion Island from 2012 to 2022.

BACKGROUND: Dengue is a major public health concern in Reunion Island, marked by recurrent epidemics, including successive outbreaks of dengue virus serotypes 1 and 2 (DENV1 and DENV2) with over 70,000 cases confirmed since 2017. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used Oxford Nanopore NGS technology for sequencing virologically-confirmed samples and clinical isolates collected between 2012 and 2022 to investigate the molecular epidemiology and evolution of DENV in Reunion Island. Here, we generated and analyzed a total of 499 DENV1, 360 DENV2, and 18 DENV3 sequences. By phylogenetic analysis, we show that different genotypes and variants of DENV have circulated in the past decade that likely originated from Seychelles, Mayotte and Southeast Asia and highly affected areas in Asia and Africa. CONCLUSIONS/SIGNIFICANCE: DENV sequences from Reunion Island exhibit a high genetic diversity which suggests regular introductions of new viral lineages from various Indian Ocean islands. The insights from our phylogenetic analysis may inform local health authorities about the endemicity of DENV variants circulating in Reunion Island and may improve dengue management and surveillance. This work emphasizes the importance of strong local coordination and collaboration to inform public health stakeholders in Reunion Island, neighboring areas, and mainland France.

Molecular epidemiology identifies the expansion of the DENV2 epidemic lineage from the French Caribbean Islands to French Guiana and mainland France, 2023 to 2024.

In 2023, dengue virus serotype 2 (DENV2) affected most French overseas territories. In the French Caribbean Islands, viral circulation continues with > 30,000 suspected infections by March 2024. Genome sequence analysis reveals that the epidemic lineage in the French Caribbean islands has also become established in French Guiana but not Réunion. It has moreover seeded autochthonous circulation events in mainland France. To guide prevention of further inter-territorial spread and DENV introduction in non-endemic settings, continued molecular surveillance and mosquito control are essential.

Comparing the Performance of Three Models Incorporating Weather Data to Forecast Dengue Epidemics in Reunion Island, 2018-2019.

We developed mathematical models to analyze a large dengue virus (DENV) epidemic in Reunion Island in 2018-2019. Our models captured major drivers of uncertainty including the complex relationship between climate and DENV transmission, temperature trends, and underreporting. Early assessment correctly concluded that persistence of DENV transmission during the austral winter 2018 was likely and that the second epidemic wave would be larger than the first one. From November 2018, the detection probability was estimated at 10%-20% and, for this range of values, our projections were found to be remarkably accurate. Overall, we estimated that 8% and 18% of the population were infected during the first and second wave, respectively. Out of the 3 models considered, the best-fitting one was calibrated to laboratory entomological data, and accounted for temperature but not precipitation. This study showcases the contribution of modeling to strengthen risk assessments and planning of national and local authorities.

Ophthalmic complications during the dengue epidemic in Reunion Island in 2020: a case series and review of the literature.

INTRODUCTION: Dengue is an arboviral disease transmitted by the dengue virus, whose vectors are Aedes aegypti and Aedes albopictus. The acute phase with its cohort of well-known symptoms is usually spontaneously favorable. Since 2020 in Reunion Island, a new symptom has appeared: the ocular damage of dengue fever, which has already been described in South Asia and South-East Asia. We therefore decided to describe the clinical, biological, ophthalmological, therapeutic, and outcomes of patients with ocular manifestations during dengue fever in Reunion Island in 2020. PATIENTS AND METHODS: This was a retrospective observational study. Patients were included from January 2020 to August 2020 and then reassessed by teleconsultation 1 year later. The patients were identified from the French public health surveillance network by all ophthalmologists on the island. Medical data were collected directly from medical records. RESULTS: Twenty-eight patients were included. The mean age was 41.9 years. Ocular involvement occurred approximately 9.2 days after the onset of dengue symptoms. The main symptoms were scotoma (71.4%) and sudden decrease of visual acuity (39.2%). Eighteen patients (64.2%) had macular involvement. Fourteen patients were treated with oral or intravenous corticosteroids. Twenty-two (78.5%) patients were evaluated by telephone one year later. Scotoma and decreased visual acuity persisted in 15 patients. Thirteen patients (59%) were bothered by night driving, 32% of patients had reading difficulties and 27% of patients became sensitive to prolonged exposure to screens. CONCLUSION: Ocular complications of dengue require early and collegial management to limit the risk of long-term sequelae. Further studies on the characteristics and complications of dengue fever are needed to better understand this disease.

From dengue outbreaks to endemicity: Reunion Island, France, 2018 to 2021.

BackgroundAfter 40 years of limited viral circulation, Reunion Island has since 2018 experienced recurrent dengue outbreaks of increasing intensity and severity.AimWe aimed to report on the epidemiology and characteristics of dengue in Reunion Island between 2018 and 2021.MethodsBetween 2018 and August 2021, we systematically collected data on dengue cases via an automated transmission system between the health authorities and the medical laboratories. We set up additional surveillance systems for dengue-related activity in primary care, in emergency departments and in inpatient departments.ResultsUntil 2020, despite numerous cases, outbreaks had a limited public health impact because of few severe cases, low lethality and no heavy burden for the health care system. In 2021, however, the number of severe cases increased (from 0.4% of all cases in 2018 to 0.8% in 2021), as did the number of paediatric cases (from 8% in 2018 to 15% in 2021) and atypical clinical forms of dengue (108 cases of post-dengue maculopathy). Of note, haemorrhagic forms were rare and multi-organ failure was the most frequent severity throughout the study period. In parallel, the dominant serotype switched from DENV2 to DENV1 in 2020 and DENV1 became the only serotype detected in 2021.ConclusionThese findings indicate that dengue is becoming endemic in Reunion Island. Since comorbidities associated with severity of dengue are common in the population, health authorities should carefully consider the impact of dengue when addressing public health policies.

Accuracy of FDG-PET/CT for Response Evaluation of Muscle-Invasive Bladder Cancer following Neoadjuvant or Induction Chemotherapy.

INTRODUCTION: The aim of the study was to confirm the diagnostic accuracy of a second FDG-PET/CT following neoadjuvant or induction chemotherapy (NAIC) prior to radical cystectomy for patients with localized muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 62 consecutive patients with MIBC, that had a first FDG-PET/CT between April 2016 and September 2021. Patients then underwent NAIC, followed by a second FDG-PET/CT and radical cystectomy. Patients with no hypermetabolism in the bladder and lymph nodes on the second FDG-PET/CT were considered metabolic complete responders, while patients with no evidence of residual disease on histopathology were considered pathologic complete responders. The accuracy of the second FDG-PET/CT to distinguish complete responders from patients with residual disease was calculated, with histopathology as gold standard. RESULTS: Of 62 patients, 1 was lost to follow-up, 5 died before radical cystectomy, 5 had delay >2 months between the second FDG-PET/CT and radical cystectomy, and 6 did not undergo radical cystectomy and instead underwent alternative treatment. The study cohort comprised 45 patients, 39 males and 6 females, with an age of 66 ± 6 years. In comparison to histopathology, FDG-PET/CT provided (i) sensitivity of 95% and specificity of 42%, for the overall disease; (ii) sensitivity of 100% and specificity of 36%, for the primary tumor only; and (iii) sensitivity of 97% and specificity of 30%, for the lymph nodes only. CONCLUSION: FDG-PET/CT has over 95% sensitivity for distinguishing complete responders from patients with residual disease. Thus, FDG-PET/CT can be used for early response evaluation following NAIC to identify patients that did not completely respond to chemotherapy and may require alternative treatment pathways.

Overview of dengue outbreaks in the southwestern Indian Ocean and analysis of factors involved in the shift toward endemicity in Reunion Island: A systematic review.

BACKGROUND: Dengue is the world's most prevalent mosquito-borne viral disease. It is endemic in many tropical and subtropical countries and represents a significant global health burden. The first reports of dengue virus (DENV) circulation in the South West Indian Ocean (SWIO) islands date back to the early 1940s; however, an increase in DENV circulation has been reported in the SWIO in recent years. The aim of this review is to trace the history of DENV in the SWIO islands using available records from the Comoros, Madagascar, Mauritius, Mayotte, Seychelles, and Reunion. We focus in particular on the most extensive data from Reunion Island, highlighting factors that may explain the observed increasing incidence, and the potential shift from one-off outbreaks to endemic dengue transmission. METHODS: Following the PRISMA guidelines, the literature review focused queried different databases using the keywords "dengue" or "Aedes albopictus" combined with each of the following SWIO islands the Comoros, Madagascar, Mauritius, Mayotte, Seychelles, and Reunion. We also compiled case report data for dengue in Mayotte and Reunion in collaboration with the regional public health agencies in these French territories. References and data were discarded when original sources were not identified. We examined reports of climatic, anthropogenic, and mosquito-related factors that may influence the maintenance of dengue transmission independently of case importation linked to travel. FINDINGS AND CONCLUSIONS: The first report of dengue circulation in the SWIO was documented in 1943 in the Comoros. Then not until an outbreak in 1976 to 1977 that affected approximately 80% of the population of the Seychelles. DENV was also reported in 1977 to 1978 in Reunion with an estimate of nearly 30% of the population infected. In the following 40-year period, DENV circulation was qualified as interepidemic with sporadic cases. However, in recent years, the region has experienced uninterrupted DENV transmission at elevated incidence. Since 2017, Reunion witnessed the cocirculation of 3 serotypes (DENV-1, DENV-2 and DENV-3) and an increased number of cases with severe forms and deaths. Reinforced molecular and serological identification of DENV serotypes and genotypes circulating in the SWIO as well as vector control strategies is necessary to protect exposed human populations and limit the spread of dengue.

From the threat to the large outbreak: dengue on Reunion Island, 2015 to 2018.

BackgroundWith more than 300 million infections estimated annually worldwide, dengue is the most prevalent arboviral infection. On Reunion Island, after a large outbreak in 1977-78, only limited episodes of viral circulation or sporadic cases were reported till 2015.AimOur objective was to document and report on the circulation of dengue virus after the occurrence of a small outbreak during austral summer 2015/16 and until the large outbreak of 2018.MethodsBeside the mandatory notification of biologically confirmed dengue cases, additional systems of surveillance were set up: estimation of dengue-like syndrome in people seeking care by their family doctor, surveillance of emergency department visits related to dengue, surveillance of hospitalised dengue patients and deaths classifications.ResultsAfter a moderate outbreak during summer 2015/16 with 231 cases, 2017 was characterised by limited viral circulation (97 cases) which, however, persisted during the austral winter. By February 2018, the number of cases had increased and led to a peak at the beginning of May 2018. More than 6,000 cases were reported this year (dengue virus type 2 only). In addition, six deaths of dengue patients were notified.ConclusionIn 2017, the persistence of transmission during winter created favourable conditions for the emergence of an epidemic during summer 2018. After this moderate epidemic wave, the viral circulation persisted during winter 2018 for the second year, opening the door for the second wave in 2019 and for potential endemisation of the disease on Reunion Island in the near future.

Relationship between mold exposure, specific IgE sensitization, and clinical asthma: A case-control study.

BACKGROUND: Most of the findings related to the noxious effect of mold sensitization on asthma come from investigations based on Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus. However, species such as Penicillium spp, Cladosporium sphaerospermum, Cladosporium cladosporioides, or Aspergillus versicolor display a more pronounced indoor tropism, and their potential harmful respiratory effects cannot be neglected. OBJECTIVE: The goal of this work was to relate mold sensitizations with asthma severity and with the level of indoor mold contamination among mold-sensitized patients with asthma and nonsensitized patients with asthma. METHODS: A case-control study was conducted and several asthma severity markers were compared between patients with asthma with and without mold sensitization. Indoor contamination of patients' dwellings was also investigated. RESULTS: Our findings confirmed the association between sensitization to A fumigatus and severity for patients with asthma in contrast with sensitization to other species. Indoor mold contamination was detected in approximately 90% of dwellings. Overall mold exposure was not associated with asthma severity. However, regardless of the sensitization, exposure to A fumigatus and Penicillium spp in dust was linked to an increased risk of severe asthma. CONCLUSION: The harmful nature of mold sensitization and mold exposure for patients with asthma was not confirmed in this study. However, sensitization to A fumigatus was associated with an increased risk for severe asthma. A better investigation of the properties of Penicillium spp is recommended because its exposure was found to be associated with a more pronounced impairment of lung function.

Development of a Dot-Blot Assay for the Detection of Mould-Specific IgE in the Belgian Population.

BACKGROUND: Data on mould sensitization in the general population are scarce and mostly on Aspergillus fumigatus, Alternaria alternata and Cladosporium herbarum. OBJECTIVES: To validate a dot-blot assay for the detection of specific IgE and evaluate the prevalence of mould sensitization in a healthy population. METHODS: The dot-blot assay was validated against the CAP test. Sensitization rate to ten common indoor and outdoor mould species in 344 serum samples was calculated. For each serum with more than one reactivity, the "major sensitization" defined as the strongest response against a single mould species was calculated. RESULTS: Intra- and inter-assay variations were both below 20%, and the positivity threshold of the test was of 0.418 kU/L for A. fumigatus. Correlation with CAP results was strong. The overall prevalence of sensitization was 32.8%, and the commonest sensitizations were against A. alternaria, A. flavus and A. niger (around 15%). The most frequent "major reactivities" were against A. niger and A. alternata (20-30%). In 25.1% of the samples, "major reactivities" were directed against a group of moulds commonly found indoor (Penicillium spp., Aspergillus versicolor, Cladosporium sphaerospermum and Cladosporium cladosporioides). CONCLUSIONS: The dot-blot assay was validated for the detection of mould-specific IgE. In the general population, sensitization to indoor species was common and accounted for 25% of overall mould sensitizations.

Induction of the specific allergic immune response is independent of proteases from the fungus Alternaria alternata.

We have analyzed the importance of proteases for the induction of allergic responses against the mold Alternaria alternata. Responses induced in vivo with untreated or heat treated (protease inactivated) extracts were compared in BALB/c, C57BL/6, TLR4 KO, and MyD88 KO mice. In BALB/c mice, both extracts induced similar lung inflammation, upregulation of inflammatory mediators, Th2 cytokines, and Alternaria-specific antibodies. However heat inactivation abrogated polyclonal IgE production. Similar results were obtained in C57BL/6 albeit lung expression of some Th2 mediators was decreased in mice stimulated with the heat-treated extract. Treatment of the extract with protease inhibitors did not affect the induction of the allergic response either, except again for the polyclonal IgE response. Th2 responses and lung inflammation were readily induced in TLR4 knockout mice. In contrast, lung inflammation, Th2 responses, cytokine productions, and antibody synthesis were strongly suppressed in MyD88-deficient mice. Early lung IL-33 and IL-1-α expression were also suppressed. In conclusion, albeit some heat labile proteases are required for the stimulation of the polyclonal IgE secretion, fungal proteases, and TLR4 signaling are not required while MyD88 is essential for triggering the systemic immune response and for the development of lung allergic inflammation in response to Alternaria extracts.

Pertussis serodiagnosis in Belgium from 1990 to 2009.

Diagnosis of pertussis by culture and PCR is most sensitive when performed on nasopharyngeal specimens collected <2 weeks and <3 weeks, respectively, after the onset of clinical disease. Conversely, serological testing allows the diagnosis of patients (mostly adults) with less typical whooping cough symptoms, for whom clinical samples are often collected at later time points. Here, we report on a 20-year serodiagnostic survey of pertussis in Belgium from 1990 to 2009. In total, 13,163 patients were analyzed for Bordetella pertussis-specific antibodies by agglutination, complement fixation, immunofluorescence, and ELISA. The number of positive pertussis cases detected by serodiagnosis ranged between 50 and 150 annually. The mean age of positive cases increased from 9.9 years in 1990 to 33.9 years in 2009. Whereas from 1990 to 2003, children and young adolescents made up the majority of cases, from 2004 onwards, cases were detected in all age groups and the distribution became bimodal, with a first peak at the age of 10 to 20 years and a second at the age of 35 to 50 years. In contrast, patients diagnosed since 2001 by PCR and/or culture were mostly children younger than 1 year of age. Despite extensive childhood vaccination campaigns, whooping cough is still present in Belgium. Our findings confirm the potential role of adults in the continued transmission of pertussis and strongly warrant booster or cocoon vaccinations in older age groups.