A Holistic Approach to Cardiometabolic and Infectious Health in the General Population of Reunion Island: The REUNION Study.

INTRODUCTION: Reunion Island is a French overseas department in the South West Indian Ocean with a unique multi-ethnic population. Cardiovascular diseases are the most common chronic conditions with higher prevalences of hypertension and diabetes compared to mainland France. Moreover, Reunion Island is particularly exposed to vector-borne diseases such as chikungunya and dengue. Our objective is to describe the prevalence of cardiometabolic and infectious diseases in Reunion Island and explore causal mechanisms linking these diseases. METHODS: The REUNION study is an ongoing French prospective study. From January 2022, 2,000 consenting participants (18-68 years old) are being recruited from the general population according to polling lists and random generation of cellphone number. Baseline examination consists of (i) general health examination, assessment of cardiovascular risk factors, markers of subclinical atherosclerosis, bronchial obstruction, neuropathic and autonomic dysfunction, (ii) questionnaires to determine sociodemographic characteristics, diet, exposure to vector-borne diseases, mental health and cognitive functions, social inequalities in health and ethnic origins, (iii) biological sampling for determination of cardiovascular risk factors, seroprevalence of infectious diseases, innovative lipid biomarkers, advanced omics, composition of intestinal, periodontal and skin microbiota, and biobanking. CONCLUSIONS: The REUNION study should provide new insights into the prevalence of cardiometabolic and infectious diseases, as well as their potential associations through the examination of various environmental pathways and a wide range of health aspects.

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.

Diagnostic performance of the WHO definition of probable dengue within the first 5 days of symptoms on Reunion Island.

The relevance of the World Health Organization (WHO) criteria for defining probable dengue had not yet been evaluated in the context of dengue endemicity on Reunion Island. The objective of this retrospective diagnostic study was to evaluate the diagnostic performance of the 2009 WHO definition of probable dengue and to propose an improvement thereof. From the medical database, we retrieved the data of subjects admitted to the emergency department of the University Hospital of Reunion Island in 2019 with suspected dengue fever (DF) within a maximum of 5 days post symptom onset, and whose diagnosis was confirmed by a Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The intrinsic characteristics of probable dengue definitions were reported in terms of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), using RT-PCR as the gold standard. Of the 1,181 subjects who exhibited a positive RT-PCR, 652 (55%) were classified as probable dengue. The WHO definition of probable dengue yielded a sensitivity of 64% (95%CI 60-67%), a specificity of 57% (95%CI 52-61%), a LR+ of 1.49 (95%CI 1.33-1.67), and a LR- of 0.63 (95%CI 0.56-0.72). The sensitivity and LR- for diagnosing and ruling out probable dengue could be improved by the addition of lymphopenia on admission (74% [95%CI: 71-78%] and 0.54 [95%CI: 0.46-0.63] respectively), at the cost of slight reductions of specificity and LR+ (48% [95%CI: 44-53%] and 1.42 [95%CI: 1.29-1.57], respectively). In the absence of, or when rapid diagnostic testing is unreliable, the use of the improved 2009 WHO definition of probable dengue could facilitate the identification of subjects who require further RT-PCR testing, which should encourage the development of patient management, while also optimizing the count and quarantine of cases, and guiding disease control.

Harness risk stratification of diabetic patients with dengue in a cohort study.

BACKGROUND: Identifying predictors of severe dengue (SD) is key for triage and management of patients as well as for advising travellers to countries where dengue is endemic. In this, meta-analyses have raised diabetes mellitus as a risk factor for SD and a prognostic factor for dengue-related mortality. The purpose of this study was to assess whether diabetic patients (DPs) are at increased risk for SD in comparison to non-diabetic patients (NDPs) in a setting of high prevalence of type 2 diabetes mellitus and increasing endemicity for dengue. METHODS: In a cohort study conducted during the 2019 dengue epidemic on Reunion Island, we estimated the risk ratios (RR) of DPs for SD (WHO 2009 definition), hospitalisation, intensive care unit (ICU) admission, critical care need or death in the ICU, and scales rating severity or multiple organ dysfunction syndrome (MODS), among confirmed cases of dengue (positive RT-PCR or NS1 antigen). RESULTS: In a Poisson regression model adjusted for age, gender and comorbidity, DPs were more likely to develop SD (adjusted RR: 1.46, 95%CI 1.10-1.95), to be hospitalised, admitted to the ICU, and need critical care or die in the ICU. Subgroup analyses identified female DPs, non-elderly DPs (< 65 years) and DPs with low Charlson score (< 3) to be at higher risk for SD, the two first subgroups trough more severe presentation (higher Simplified Acute Physiology Score-2 values; higher MODS scores, respectively). Male gender, age less than 65 years and mixed comorbidity were identified as prognostic factors for critical care need or death in the ICU, male and non-elderly DPs being more likely to develop MODS than their non-diabetic counterparts. CONCLUSIONS: Together, these data highlight the role of diabetes mellitus in the progression from dengue to SD through higher severity per se or the event of MODS.

Clinical and Epidemiological Aspects of Acute Q Fever in Reunion Island over Fourteen Years: A Retrospective Cohort Study.

The clinical characteristics and epidemiology of Q fever in the Tropics are poorly described. We performed a retrospective cohort study of hospitalized cases between 2004 and 2017 in Reunion Island. Acute Q fever was defined in presence of a positive serology (phase II IgG ≥ 200 and phase II IgM ≥ 50), or a seroconversion (4-fold increase in phase II IgG between paired samples), or a positive PCR (blood or serum). Forty-two cases matched the diagnostic criteria. The most common clinical manifestations were fever (85.7%) and pulmonary symptoms (61.9%), including pneumonia (45.2%). Ninety percent of the patients were living in a farming area. Cumulative incidence was estimated at 9.3 per 100,000 inhabitants (95%CI: 6.4-12.1) with cases diagnosed yearly all throughout the study period except in 2006. Together with the seroprevalence figures, these data suggest that Q fever reaches low to moderate endemic levels on Reunion Island. As previously reported, pulmonary symptoms are in the foreground.

Beyond TORCH: A narrative review of the impact of antenatal and perinatal infections on the risk of disability.

Infections and inflammation during pregnancy or early life can alter child neurodevelopment and increase the risk for structural brain abnormalities and mental health disorders. There is strong evidence that TORCH infections (i.e., Treponema pallidum, Toxoplasma gondii, rubella virus, cytomegalovirus, herpes virus) alter fetal neurodevelopment across multiple developmental domains and contribute to motor and cognitive disabilities. However, the impact of a broader range of viral and bacterial infections on fetal development and disability is less well understood. We performed a literature review of human studies to identify gaps in the link between maternal infections, inflammation, and several neurodevelopmental domains. We found strong and moderate evidence respectively for a higher risk of motor and cognitive delays and disabilities in offspring exposed to a range of non-TORCH pathogens during fetal life. In contrast, there is little evidence for an increased risk of language and sensory disabilities. While guidelines for TORCH infection prevention during pregnancy are common, further consideration for prevention of non-TORCH infections during pregnancy for fetal neuroprotection may be warranted.

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.

Dengue clinical features and harbingers of severity in the diabetic patient: A retrospective cohort study on Reunion island, 2019.

AIM: Diabetes mellitus is associated with both the risks of severe dengue and dengue-related deaths, however the factors characterizing dengue in the diabetic patient are ill-recognized. The objective of this hospital-based cohort study was to identify the factors characterizing dengue and those able to early identify dengue severity in the diabetic patient. METHODS: We retrospectively analysed demographic, clinical and biological parameters at admission in the cohort of patients who consulted at the university hospital between January and June 2019 with confirmed dengue. Bivariate and multivariate analyses were conducted. RESULTS: Of 936 patients, 184 patients (20%) were diabetic. One hundred and eighty-eight patients (20%) developed severe dengue according to the WHO 2009 definition. Diabetic patients were older and had more comorbidities than non-diabetics. In an age-adjusted logistic regression model, loss of appetite, altered mental status, high neutrophil to platelet ratios (>14.7), low haematocrit (≤ 38%), upper-range serum creatinine (>100 µmol/l) and high urea to creatinine ratio (>50) were indicative of dengue in the diabetic patient. A modified Poisson regression model identified four key independent harbingers of severe dengue in the diabetic patient: presence of diabetes complications, non-severe bleeding, altered mental status and cough. Among diabetes complications, diabetic retinopathy and neuropathy, but not diabetic nephropathy nor diabetic foot, were associated with severe dengue. CONCLUSION: At hospital first presentation, dengue in the diabetic patient is characterized by deteriorations in appetite, mental and renal functioning, while severe dengue can be early identified by presence of diabetes complications, dengue-related non-severe haemorrhages, cough, and dengue-related encephalopathy.

Factors Associated with Chikungunya Infection among Pregnant Women in Grenada, West Indies.

Neonates are vulnerable to vector-borne diseases given the potential for mother-to-child congenital transmission. To determine factors associated with chikungunya virus (CHIKV) infection among pregnant women in Grenada, West Indies, a retrospective cohort study enrolled women who were pregnant during the 2014 CHIKV epidemic. In all, 520/688 women (75.5%) were CHIKV IgG positive. Low incomes, use of pit latrines, lack of home window screens, and subjective reporting of frequent mosquito bites were associated with increased risk of CHIKV infection in bivariate analyses. In the multivariate modified Poisson regression model, low income (adjusted relative risk [aRR]: 1.05 [95% CI: 1.01-1.10]) and frequent mosquito bites (aRR: 1.05 [95% CI: 1.01-1.10]) were linked to increased infection risk. In Grenada, markers of low socioeconomic status are associated with CHIKV infection among pregnant women. Given that Grenada will continue to face vector-borne outbreaks, interventions dedicated to improving living conditions of the most disadvantaged will help reduce the incidence of arboviral infections.

Associated risk factors of severe dengue in Reunion Island: A prospective cohort study.

BACKGROUND: Since 2018, a dengue epidemic has been raging annually in Reunion Island, which poses the major problem of its morbidity and mortality. However, there is no consensus in the literature on factors associated with severity of illness. The objective of this study was to identify the factors associated with the occurrence of severe dengue (SD) according to the criteria adopted in 2009 by the World Health Organization (WHO), during the 2019 epidemic. METHODOLOGY/PRINCIPAL FINDINGS: A total of 163 patients with RT-PCR-confirmed dengue were included in a multicenter prospective cohort study in Reunion Island between January and June 2019. Of these, 37 (23%) were classified as SD, which involves presentation dominated by at least one organ failure, and 126 (77%) classified as non-SD (of which 90 (71%) had warning signs). Confusion, dehydration, and relative hypovolemia were significantly associated with SD in bivariate analysis (p < 0.05). The factors associated with SD in multivariate analysis were a time from first symptom to hospital consultation over 2 days (OR: 2.46, CI: 1.42-4.27), a history of cardiovascular disease (OR: 2.75, 95%CI: 1.57-4.80) and being of Western European origin (OR: 17.60, CI: 4.15-74). CONCLUSIONS/SIGNIFICANCE: This study confirms that SD is a frequent cause of hospitalization during dengue epidemics in Reunion Island. It suggests that cardiovascular disease, Western European origin, and delay in diagnosis and management are risk factors associated with SD fever, and that restoration of blood volume and correction of dehydration must be performed early to be effective. TRIAL REGISTRATION: NCT01099852; clinicaltrials.gov.

Early diagnosis of dengue: Diagnostic utility of the SD BIOLINE Dengue Duo rapid test in Reunion Island.

BACKGROUND: In Reunion Island, dengue outbreaks have been occurring since 2018. The healthcare facilities are facing the problem of managing a massive influx of patients and a growing care burden. The aim of this study was to evaluate the performance of the SD Bioline Dengue Duo rapid diagnostic test in adults consulting at an emergency department during the 2019 epidemic. METHODOLOGY/PRINCIPAL FINDINGS: This retrospective study of diagnostic accuracy included patients over 18 years old, suspected of dengue, who were admitted to emergency units of the University Hospital of Reunion between the 1st of January and 30th of June, 2019, and were tested for dengue fever with the SD Bioline Dengue Duo rapid diagnostic test and reverse transcriptase polymerase chain reaction. Over the study period, 2099 patients were screened retrospectively. Of them, 671 patients matched the inclusion criteria. The overall rapid diagnostic test performance was 42% for sensitivity and 15% for specificity. The non-structural 1 antigen component had a good specificity of 82% but a low sensitivity of 12%. The immunoglobulin M component had a sensitivity of 28% and a specificity of 33%. Sensitivities were slightly improved beyond the 5th day of illness compared to the early stage for all components, but only the non-structural 1 antigen component had a better specificity of 91%. Furthermore, predictive values were low and post-test probabilities never improved pre-test probabilities in our setting. CONCLUSIONS/SIGNIFICANCE: These results suggest that the SD Bioline Dengue Duo RDT did not achieve sufficient performance levels to rule in, or discard, an early point of care dengue diagnosis in the emergency department during the 2019 epidemic in Reunion.

Health Impacts of the COVID-19 Lockdown Measure in a Low Socio-Economic Setting: A Cross-Sectional Study on Reunion Island.

In March 2020, the French government implemented nation-wide measures to reduce social contact and slow the progression of the emerging coronavirus responsible for COVID-19, the most significant being a complete home lockdown that lasted 8 weeks. Reunion Island is a French overseas department marked by large social inequalities. We draw the hypothesis that distancing and lockdown measures may have contributed to an increase in the social inequalities in health (SIH) on Reunion Island. The aim of our study was to describe the SIH during lockdown in the Reunionese population. We implemented a cross-sectional telephone survey conducted between 13 May and 22 July 2020, using a retrospective data collection on the lockdown period. A total of 892 adult participants (≥18 years) were recruited in the 114 large Reunionese neighborhoods using the quota method within the national "White Pages" telephone directory. Degraded psychological states, an increase in addictive behaviors, difficulties in accessing food, a decrease in physical activity, delayed medical appointments, violence against women, and health problems in children were driven by the socio-economic characteristics of the population, most often to the disadvantage of social groups exposed to poor living conditions. These results suggest that the COVID-19 lockdown contributed to an increase in SIH.

Correction: Vertical transmission of chikungunya virus: A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0249166.].

Differentiating COVID-19 and dengue from other febrile illnesses in co-epidemics: Development and internal validation of COVIDENGUE scores.

OBJECTIVES: The purpose of this cohort study was to develop two scores able to differentiate coronavirus 2019 (COVID-19) from dengue and other febrile illnesses (OFIs). METHODS: All subjects suspected of COVID-19 who attended the SARS-CoV-2 testing center of Saint-Pierre hospital, Reunion, between March 23 and May 10, 2020, were assessed for identifying predictors of both infectious diseases from a multinomial logistic regression model. Two scores were developed after weighting the odd ratios then validated by bootstrapping. RESULTS: Over 49 days, 80 COVID-19, 60 non-severe dengue and 872 OFIs were diagnosed. The translation of the best fit model yielded two scores composed of 11 criteria: contact with a COVID-19 positive case (+3 points for COVID-19; 0 point for dengue), return from travel abroad within 15 days (+3/-1), previous individual episode of dengue (+1/+3), active smoking (-3/0), body ache (0/+5), cough (0/-2), upper respiratory tract infection symptoms (-1/-1), anosmia (+7/-1), headache (0/+5), retro-orbital pain (-1/+5), and delayed presentation (>3 days) to hospital (+1/0). The area under the receiver operating characteristic curve was 0.79 (95%CI 0.76-0.82) for COVID-19 score and 0.88 (95%CI 0.85-0.90) for dengue score. Calibration was satisfactory for COVID-19 score and excellent for dengue score. For predicting COVID-19, sensitivity was 97% at the 0-point cut-off and specificity 99% at the 10-point cut-off. For predicting dengue, sensitivity was 97% at the 3-point cut-off and specificity 98% at the 11-point cut-off. CONCLUSIONS: COVIDENGUE scores proved discriminant to differentiate COVID-19 and dengue from OFIs in the context of SARS-CoV-2 testing center during a co-epidemic.

Usefulness of Home Screening for Promoting Awareness of Impaired Glycemic Status and Utilization of Primary Care in a Low Socio-Economic Setting: A Follow-Up Study in Reunion Island.

BACKGROUND: Low socio-economic settings are characterized by high prevalence of diabetes and difficulty in accessing healthcare. In these contexts, proximity health services could improve healthcare access for diabetes prevention. Our primary objective was to evaluate the usefulness of home screening for promoting awareness of impaired glycemic status and utilization of primary care among adults aged 18-79 in a low socio-economic setting. METHODS: This follow-up study was conducted in 2015-2016 in Reunion Island, a French overseas department in the Indian Ocean. Enrollment and screening occurred on the same day at the home of participants (N=907). Impaired glycemic status was defined as [glycated hemoglobin (HbA1c) ≥5.7%] OR [fasting capillary blood glucose (FCBG) ≥1.10 g/L] OR [HbA1c=5.5-5.6% and FCBG=1.00-1.09 g/L]. Medical, socio-cultural, and socio-economic characteristics were collected via a face-to-face questionnaire. A one-month telephone follow-up survey was conducted to determine whether participants had consulted a general practitioner (GP) for confirmation of screening results. A multinomial polytomous logistic regression model was used to identify factors independently associated with non-use of GP consultation for confirmation of screening results and nonresponse to the telephone follow-up survey. RESULTS: Prevalence of glycemic abnormalities was 46.0% (95% CI = 42.7-49.2%). Among participants with impaired glycemic status (N=417), 77.7% (95% CI=73.7-81.7%) consulted a GP for confirmation of screening results, 12.5% (95% CI=9.3-15.6%) did not, and 9.8% failed to respond to the follow-up survey. Factors independently associated with non-use of GP consultation for confirmation of screening results were self-reported unwillingness to consult a GP (adjusted odds ratio [OR]: 4.86, 95% CI=1.70-13.84), usual GP consultation frequency of less than once a year (adjusted OR: 4.13, 95% CI=1.56-10.97), and age 18-39 years (adjusted OR: 3.09, 95% CI=1.46-6.57). CONCLUSION: Home screening for glycemic abnormalities is a useful proximity health service for diabetes prevention in low socio-economic settings. Further efforts, including health literacy interventions, are needed to increase utilization of primary care.

Prevalence and risk factors of Mycoplasma genitalium infection in patients attending a sexually transmitted infection clinic in Reunion Island: a cross-sectional study (2017-2018).

BACKGROUND: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection (STI) for whose management remains controversial. We aimed to assess the prevalence and risk factors of MG infection in patients attending an STI clinic in Reunion Island. METHODS: Between January 2017 and December 2018, all patients attending the Saint-Pierre STI clinic in Reunion Island were screened for MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Urogenital, pharyngeal and/or anal samples were collected based on sexual behaviour and analysed by triplex PCR. Risk factors were identified using a Poisson regression for binary outcome. RESULTS: Among 2069 screened subjects, the overall prevalence of MG was 4.88% [95% Confidence Interval (CI) 3.98-5.93]. The prevalence of urogenital MG was 4.38%, with women being more affected than men (5.33% vs 3.22%, prevalence ratio (PR) 1.66, p = 0.02). The prevalence of anal MG was 3.06% and that of pharyngeal MG was 0.61%, with men being more affected in both cases. Infection with MG was independently associated with multiple partners (6-10 partners: adjusted prevalence ratio-aPR 2.55, p < 0.048; > 10 partners: aPR 4.33, p < 0.004), previous history of STI (aPR 1.89, p = 0.026), non-use of condoms (aPR 2.56, p < 0.003) and co-infection with CT (aPR 2.56, p < 0.017). CONCLUSION: Compared to other countries, the prevalence of MG is high in Reunion Island, especially in women aged under 25 years, and co-infection with CT is common. Routine MG screening and treatment should be performed in at-risk women and co-infection with MG should be considered when deciding on treatment for CT, particularly in regions where azithromycin is still in use.

Distinguishing non severe cases of dengue from COVID-19 in the context of co-epidemics: A cohort study in a SARS-CoV-2 testing center on Reunion island.

BACKGROUND: As coronavirus 2019 (COVID-19) is spreading globally, several countries are handling dengue epidemics. As both infections are deemed to share similarities at presentation, it would be useful to distinguish COVID-19 from dengue in the context of co-epidemics. Hence, we performed a retrospective cohort study to identify predictors of both infections. METHODOLOGY/PRINCIPAL FINDINGS: All the subjects suspected of COVID-19 between March 23 and May 10, 2020, were screened for COVID-19 within the testing center of the University hospital of Saint-Pierre, Reunion island. The screening consisted in a questionnaire surveyed in face-to-face, a nasopharyngeal swab specimen for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) reverse transcription polymerase chain-reaction and a rapid diagnostic orientation test for dengue. Factors independently associated with COVID-19 or with dengue were sought using multinomial logistic regression models, taking other febrile illnesses (OFIs) as controls. Adjusted Odds ratios (OR) and 95% Confidence Intervals (95%CI) were assessed. Over a two-month study period, we diagnosed 80 COVID-19, 61 non-severe dengue and 872 OFIs cases eligible to multivariate analysis. Among these, we identified delayed presentation (>3 days) since symptom onset (Odds ratio 1.91, 95% confidence interval 1.07-3.39), contact with a COVID-19 positive case (OR 3.81, 95%CI 2.21-6.55) and anosmia (OR 7.80, 95%CI 4.20-14.49) as independent predictors of COVID-19, body ache (OR 6.17, 95%CI 2.69-14.14), headache (OR 5.03, 95%CI 1.88-13.44) and retro-orbital pain (OR 5.55, 95%CI 2.51-12.28) as independent predictors of dengue, while smoking was less likely observed with COVID-19 (OR 0.27, 95%CI 0.09-0.79) and upper respiratory tract infection symptoms were associated with OFIs. CONCLUSIONS/SIGNIFICANCE: Although prone to potential biases, these data suggest that non-severe dengue may be more symptomatic than COVID-19 in a co-epidemic setting with higher dengue attack rates. At clinical presentation, nine basic clinical and epidemiological indicators may help to distinguish COVID-19 or dengue from each other and other febrile illnesses.

Vertical transmission of chikungunya virus: A systematic review.

OBJECTIVES: To describe and estimate the frequency of pregnancy outcomes, clinical and laboratory characteristics of vertical transmission of CHIKV in the neonate. STUDY DESIGN: We performed a systematic review evaluating the clinical presentation of perinatally-acquired CHIKV infection in neonates. The search was performed using Medline (via PubMed), LILACS, Web of Science, Scielo, Google Scholar and Open grey to identify studies assessing vertical transmission of CHIKV up to November 3, 2020. There were no search restrictions regarding the study type, the publication date or language. Studies with no documented evidence of CHIKV infection in neonates (negative RT-PCR or absence of IgM) were excluded. RESULTS: From the 227 studies initially identified, 42 were selected as follows: 28 case reports, 7 case series, 2 cross-sectional studies and 5 cohort studies, for a total of 266 CHIKV infected neonates confirmed by serological and/or molecular tests. The vertical transmission rate was 50% in the Reunion Island outbreak, which was the subject of the majority of the studies; the premature delivery were reported in 19 (45.2%) studies; the rate of fetal distress was 19.6% of infected babies and fetal loss occurred in 2% of the cases. Approximately 68.7% of newborns were diagnosed with encephalopathy or encephalitis after perinatally acquired CHIKV. Most of the infected neonates were born healthy, developing CHIKV sepsis clinical syndrome within the first week of life. CONCLUSIONS: We alert neonatologists to the late manifestations of neonatal CHIKV infection, relevant to the management and reduction of morbidity. A limitation of our review was that it was not possible to carry out meta-analysis due to differences in study design and the small number of participants.