Mucocutaneous Manifestations in Patients with Dengue Fever: From the EPIDENGUE Cohort on Reunion Island.

Nearly 4 billion people live in a dengue risk area worldwide. The prevalence of dengue-related mucocutaneous manifestations and their association with severe dengue differ across studies. The aim of the study was to describe the characteristics of patients with dengue-related mucocutaneous manifestations and to investigate those were associated with severe dengue. A retrospective study was conducted in 2019 among patients with a positive RT-PCR for dengue at the University Hospital of Reunion, which has been experiencing a re-emergence of dengue since 2018. Of 847 patients with confirmed dengue, 283 (33.4%) developed mucocutaneous manifestations. Only manifestations of dehydration such as glossitis, dysgeusia, or conjunctivitis were associated with severe dengue, unlike pruritus and rash, in bivariate analysis but not in multivariate analysis. The rash and pruritus of dengue appear to be accompanied by a pronounced flu-like syndrome in younger people without comorbidity or severity, although careful examination of mucous membranes would better identify signs of dehydration and thus cases likely to worsen.

Methodological quality of systematic reviews of the local management of anogenital warts: a systematic review using AMSTAR II, ROBIS and PRISMA.

INTRODUCTION: Anogenital warts (AGWs) are among the most common STDs. Many therapy options are available but are not codified. Systematic reviews (SRs) and meta-analyses (MAs) are helpful to elaborate recommendations on the management of AGWs. The objective of our study was to assess the quality and consistency of SRs for the local management of AGWs using three international tools. METHODS: Seven electronic databases were searched from inception to 10 January 2022 for this SR. The intervention of interest was any local treatment of AGWs. There was no restriction on language and population. The methodological quality, reporting quality and risk of bias (ROB) of the included SRs for the local treatments of AGWs were assessed independently by two investigators with A Measurement Tool to Assess systematic Reviews version II (AMSTAR II), Risk of Bias in Systematic Reviews (ROBIS) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: Twenty-two SRs/MAs met all inclusion criteria. According to the results of the AMSTAR II, nine included reviews were rated critically as being of low quality, and only five were of high quality. Based on the ROBIS tool, only nine SRs/MAs had a low ROB. The domain-assessed 'study eligibility criteria' were mostly rated at a low ROB, unlike the other domains. With PRISMA, the reporting checklist was relatively complete for ten SRs/MAs, but some reporting weaknesses remained in the topics of the abstract, protocol and registration, ROB and funding. DISCUSSION: Several therapy options are available for the local management of AGWs and are widely studied. However, due to the many ROB and low quality of these SRs/MAs, only a few of them have the sufficient methodological quality to support guidelines. PROSPERO REGISTRATION NUMBER: CRD42021265175.

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.

Genetic characterization of dengue virus serotype 1 circulating in Reunion Island, 2019-2021, and the Seychelles, 2015-2016.

BACKGROUND: An unprecedent increase in the number of cases and deaths reported from dengue virus (DENV) infection has occurred in the southwestern Indian ocean in recent years. From 2017 to mid-2021 more than 70,000 confirmed dengue cases were reported in Reunion Island, and 1967 cases were recorded in the Seychelles from 2015 to 2016. Both these outbreaks displayed similar trends, with the initial circulation of DENV-2 which was replaced by DENV-1. Here, we aim to determine the origin of the DENV-1 epidemic strains and to explore their genetic characteristics along the uninterrupted circulation, particularly in Reunion. METHODS: Nucleic acids were extracted from blood samples collected from dengue positive patients; DENV-1 was identified by RT-qPCR. Positive samples were used to infect VERO cells. Genome sequences were obtained from either blood samples or infected-cell supernatants through a combination of both Illumina or MinION technologies. RESULTS: Phylogenetic analyses of partial or whole genome sequences revealed that all DENV-1 sequences from Reunion formed a monophyletic cluster that belonged to genotype I and were closely related to one isolate from Sri Lanka (OL752439.1, 2020). Sequences from the Seychelles belonged to the same major phylogenetic branch of genotype V, but fell into two paraphyletic clusters, with greatest similarity for one cluster to 2016-2017 isolate from Bangladesh, Singapore and China, and for the other cluster to ancestral isolates from Singapore, dating back to 2012. Compared to publicly available DENV-1 genotype I sequences, fifteen non-synonymous mutations were identified in the Reunion strains, including one in the capsid and the others in nonstructural proteins (NS) (three in NS1, two in NS2B, one in NS3, one in NS4B, and seven in NS5). CONCLUSION: In contrast to what was seen in previous outbreaks, recent DENV-1 outbreaks in Reunion and the Seychelles were caused by distinct genotypes, all likely originating from Asia where dengue is (hyper)endemic in many countries. Epidemic DENV-1 strains from Reunion harbored specific non-synonymous mutations whose biological significance needs to be further investigated.

Use of healthcare reimbursement data to monitor bacterial sexually transmitted infection testing in France, 2006 to 2020.

BackgroundDiagnoses of bacterial sexually transmitted infections (STIs) have increased in France since the 2000s. The main strategy to control STI transmission is recommending/facilitating access to condom use, testing, and antibiotic treatments.AimThis study analyses the evolution of STI testing in the private sector in France from 2006 to 2020.MethodsNational health insurance reimbursement data were used to determine numbers and rates of individuals aged ≥ 15 years tested for diagnoses of chlamydia, gonorrhoea and syphilis in the private sector in France and to describe their evolution from 2006 to 2020.ResultsUpward tendencies in testing were observed from 2006 to 2019 for all three STIs. The highest testing rates were identified in people aged 25‒29-years old. The observed testing-increase from 2017 to 2019 was twice as high in young people (< 25 years old) as in older people. In 2019, chlamydia, gonorrhoea and syphilis testing rates were respectively 45.4 (+ 21% since 2017), 41.3 (+ 60%), and 47.2 (+ 22%) per 1,000 inhabitants. For all STIs combined, the number of tested individuals decreased by 37% between March and April 2020 during the first COVID-19 epidemic wave and lockdown in France.ConclusionImprovements found in STI testing rates may have resulted from better awareness, especially among young people and health professionals, of the importance of testing, following prevention campaigns. Nevertheless, testing levels remain insufficient considering increasing diagnoses. In 2020, the COVID-19 pandemic had a considerable impact on STI testing. Partner notification and offering diverse testing opportunities including self-sampling are essential to control STI epidemics particularly in exposed populations.

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.

Assessment of Non-cultured Autologous Epidermal Cell Grafting Resuspended in Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism Lesions: A Randomized Clinical Trial.

The aim of this study was to assess the efficacy of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid, performed using a ready-to-use kit, compared with hyaluronic acid alone (neutral comparator) for repigmenting vitiligo and piebaldism lesions at 6 months. Two identified paired lesions per patient were randomized to be treated by either device. Devices with a ready-to-use kit were prepared by separate health professionals, to maintain blinding. A skin biopsy was digested using trypsin, and cells resuspended in hyaluronic acid solution. Among 38 patients screened, 36 (94.7%) patients, corresponding to 72 lesions, were analysed. For difficult-to-treat lesions, defined as those located on the wrist, elbow, and hands (n = 30), no repigmentation ≥ 50% was observed. For all other locations (n = 42), the success rate was significantly higher (p = 0.021) in the ready-to-use kit group (47.6% vs 9.5%) at 6 months and was maintained until 12 months. In conclusion, a single application of non-cultured epidermal cellular grafting using a ready-to-use kit was efficient at 6 months and at 1-year follow-up.

Single Dose of Azithromycin for Treatment of Patients with Asymptomatic Rectal Chlamydia trachomatis.

is missing (Short communication).

Pregnancy outcomes of Q fever: prospective follow-up study on Reunion island.

BACKGROUND: Q fever has been associated with perinatal complications. We conducted a prospective follow-up study to assess both the incidence of adverse pregnancy outcomes (APOs) associated with Coxiella burnetii infection and the contribution of Q fever to APOs. METHODS: Between May 1 and October 31, 2013, within the regional perinatal health care centre of Saint Pierre, Reunion island, we investigated unexplained miscarriages, stillbirths, preterm births or small-for-gestational age children. Seropositivity for C. burnetii antibodies was defined using indirect immunofluorescence for a phase 2 IgG titre ≥1:64. Acute Q fever was defined for a high phase 2 IgG titre ≥1:256 (compatible with recent or active infection) or the detection of C. burnetii genome in miscarriage products and placentas. Incidence rate ratios (IRR) for Q fever related APOs (taken as a composite outcome or individually) were assessed using Poisson regression models for dichotomous outcomes controlling major confounders. RESULTS: Over a 6-month period, 179 pregnant women suspected or diagnosed with an APO were investigated for Q fever, of whom 118 met the definition for an APO. Of these, 19 were seropositive and 10 presented a profile indicative of an acute infection. For three women with an acute Q fever, the chronology between the onset of infection, the APO (2 miscarriages, 1 preterm birth) and the seroconversion suggested causality in the pathogenesis. The cumulative incidence of Q fever related APOs was estimated between 2.2‰ and 5.2‰, whether causality was required or not. Both C. burnetii exposure and acute Q fever were independently associated with APOs (IRR 1.55, 95% CI 1.31-1.84; IRR 1.47, 95% CI 1.15-1.89, respectively). CONCLUSIONS: In the endemic context of Reunion island, acute Q fever may lead to APOs. To limit the burden of Q fever on reproduction, pregnant women should be kept away from farms and avoid direct contact with ruminants.

Cryotherapy to treat anogenital warts in nonimmunocompromised adults: Systematic review and meta-analysis.

BACKGROUND: Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent international recommendations. OBJECTIVE: To compare the efficacy and safety of cryotherapy versus other AGW treatments. METHODS: Through a systematic search of 12 electronic databases, we identified 11 randomized controlled trials, screened from database inception through October 2016, that met the inclusion criteria (including immunocompetent adults with AGWs receiving cryotherapy in 1 of the comparison groups). Primary endpoint was complete clearance of AGW. Risk-for-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.3 software. RESULTS: Cryotherapy efficacy did not appear to differ from that of trichloroacetic acid, podophyllin, or imiquimod. Electrosurgery was weakly associated with better AGW clearance than cryotherapy (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.65-0.99). Cryotherapy was associated with more immediate low-level adverse events (erythema, stinging, or irritation; RR 3.02, 95% CI 1.38-6.61) and immediate pain requiring oral analgesics (RR 2.11, 95% CI 1.07-4.17) but fewer erosions (RR 0.57, 95% CI 0.36-0.90). LIMITATIONS: All but 1 randomized-controlled trial had a high risk for bias. CONCLUSION: With low-level quality of the evidence, cryotherapy is an acceptable first-line therapy to treat AGWs.

Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

[Determinants of papillomavirus vaccination in Mayotte: A qualitative study among general practitioners]. / Déterminants et leviers de la vaccination papillomavirus à Mayotte : une étude qualitative chez les médecins généralistes.

OBJECTIVES: In Mayotte, cervical cancer represents the second cause of cancer mortality in women. Vaccination coverage against papillomavirus and screening rates are difficult to quantify but among the lowest in France. Added to this is an under-calibrated health system, which does not allow optimal treatment of cancers on site. The objective of the study was to study the elements that would increase papillomavirus vaccination among general practitioners. METHODS: We carried out a qualitative study of phenomenological inspiration using semi-directed open interviews. The target population was private general practitioners based in Mayotte. The analysis was done by coding verbatim statements, from which emerged general themes, to build a model. RESULTS: Twenty-two interviews were conducted. Vaccination was part of a context and was organized around the trio doctor-patient-institutions. The main pillar to vaccination was information, which could concern doctors or patients. The information delivered to patients through the media, campaigns in schools, and vaccination obligation were the main elements. The study revealed positive emotional dynamics of on-site HPV vaccination. CONCLUSION: This study made it possible to better understand the ecosystem in which papillomavirus vaccination takes place in Mayotte, and to identify elements of vaccination promotion. Vaccination school campaigns should keep going on to increase vaccination uptake.

[Determinants of human papillomavirus vaccine amongst boys in Reunion Island: survey of parents and general practitioners.] / Les déterminants de la vaccination anti-papillomavirus humain des garçons à La Réunion : enquête auprès des parents et des médecins généralistes.

OBJECTIVES: To describe the knowledge, barriers and acceptability factors of parents and general practitioners about HPV vaccination amoungts boys in Reunion Island, in order to adapt primary prevention locally. METHODS: This was a quantitative, descriptive, cross-sectional, observational study involving 88 parents of boys aged 11 to 19 and 81 general practitioners based in Reunion Island. Both populations volunteered to answer a questionnaire available online or on paper. RESULTS: Parents' knowledge about HPV was insufficient. In Reunion Island, social media and the precarious status of parents play a particularly negative role in the vaccine intention. The number of doctors who have started HPV vaccination on boys is low despite awareness of the recommendation, particularly older doctors who practice alone, in certain sectors of the island. CONCLUSIONS: The young and precarious population of Reunion Island is particularly at risk of pathologies related to HPV and requires adapted prevention to the territory's specificities. It seems necessary to continue to inform general practitioners, in order to promote vaccination and to fight against the misinformation of media about the HPV vaccine.

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.

PRESOLRE: study protocol for a primary school-based, cluster randomised controlled trial of three sun exposure risk prevention strategies on Reunion Island.

INTRODUCTION: Reunion Island, a French overseas department, is located in the southern hemisphere, close to the Capricorn tropic. This island has a multicultural and multiethnic population of 860 000 inhabitants, a quarter of whom are at high risk of developing skin cancer due to intense ultraviolet radiation. Melanoma is responsible for the majority of skin cancer deaths. The early prevention of melanoma is based on sun protection in childhood, but French regulations are not adapted to the environmental conditions of this tropical region.The main objective of our study is to evaluate the effectiveness of three sun protection programs conducted in Reunionese primary schools through a pupil knowledge questionnaire. METHODS AND ANALYSIS: PRESOLRE is an interventional, open-label, cluster-randomised controlled trial, in four parallel arms, that is being conducted throughout 2022-2023 on Reunion Island. The trial design assumes an escalation interventional effect using: first, a control arm without proposed intervention (arm 1); second, an arm whose classes are encouraged to use the validated educational programme 'Living With the Sun' (LWS) (arm 2); third, an arm whose classes are encouraged to use both 'LWS' combined with 'Mission Soleil Réunion's sun protection awareness programme (arm 3); fourth, an arm benefiting from an intervention similar to arm 3, combined with the distribution of hats, sunglasses and sun creams (arm 4). In all, 1780 pupils from 18 classes of 20 pupils, on average, will be included. Randomisation applies to the classes of pupils (so defined as clusters). The primary outcome is based on the proportion of correct answers to the knowledge questions after the awareness programme, compared between the four arms using a linear mixed model with random intercept. ETHICS AND DISSEMINATION: The study obtained ethics approval in 2022 (ID: 2022-A00350-43). Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05367180.