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.

Acute Hemolytic Anemia Caused by G6PD Deficiency in Children in Mayotte: A Frequent and Severe Complication.

Severe hemolytic anemia is a rare complication of glucose-6-phosphate dehydrogenase (G6PD) deficiency. It occurs with the Mediterranean (Med) variant corresponding to a class 2 deficiency according to the World Health Organization (WHO) classification, and it correlates with a severe deficiency in G6PD activity. In Mayotte, the majority of patients have the African (A-) variant as a WHO class 3 deficiency. Yet we have observed numerous cases of severe hemolytic anemia defined by a hemoglobin level of <6 g/dL. In this study, we aimed to describe the epidemiological, clinical, and biological features as well as the treatment modalities of children presenting with a severe hemolytic crisis secondary to G6PD deficiency in Mayotte. The secondary objective was to study the disease genotype when this information was available. Between April 2013 and September 2020, 73 children presented with severe anemia because of G6PD deficiency in Mayotte. The median hemoglobin level during the hemolytic crises was 3.9 g/dL. All of the patients underwent a transfusion and hospitalization. Twenty patients had a disease genotype: 11 had the African mutation and 9 had the Med mutation. Although they are among the most common triggers of G6PD acute hemolytic anemia, drugs were found to not be present and fava bean ingestion was found in only 1 child. One of the specific triggers was traditional medicine, including Acalypha indica . Severe hemolytic crisis in children because of G6PD deficiency is a frequent occurrence in Mayotte. The patients had severe disease symptoms, but the severity did not correlate with the genotype: the African (A-) variant and the Med variant resulted in the same level of disease severity.

Major decrease in malaria transmission on Mayotte Island.

BACKGROUND: Plasmodium falciparum is responsible for most malaria cases on Mayotte Island, in the Comorian Archipelago. Malaria is endemic and a major public health problem in the archipelago with an intense, stable and permanent transmission. This study reports results of 8 years of malaria surveillance from 2007 to 2014 after the strengthening of malaria control activities in Mayotte and the neighbouring islands. METHODS: Surveillance was based on physicians' reports of malaria cases between January 2007 and December 2014. Malaria cases were confirmed by at least a positive rapid diagnostic test and/or demonstration of Plasmodium sp. in a blood smear. The date, and the patients' age, sex, address, presentation of symptoms, biology, treatment and recent history of travel were collected by verbal questioning during consultation and/or hospitalization. Monthly rainfall data were also compiled during the study period. RESULTS: From 2007 to 2014, 2073 cases were reported on Mayotte Island: 977 imported cases, 807 autochthonous cases and 289 cases of unknown origin. The total malaria annual parasite incidence lowered from 3.0 in 2007 to 0.07 per 1,000 inhabitants in 2014 as the autochthonous malaria incidence decreased from 1.6 to 0.004 per 1,000 inhabitants in the same period and in all age groups. Most of the imported cases came from Comoros (94 %). Severe forms represented approximately 11 % of cases, and only two deaths have been recorded among the imported cases. Approximately 19 % of cases were hospitalized (3 % in an intensive care unit). There is clearly a decrease in malaria transmission in Mayotte since 2007 and the goal of elimination seems more achievable than ever. In 2011, Mayotte entered the elimination phase when P. falciparum API passed under 1 case per 1,000 people at risk. CONCLUSIONS: The combination of vector control measures, active surveillance and case management, including effective treatment with artemisinin-based combination therapy, has been essential to achieve a present status of low and decreasing malaria transmission on the island. Mayotte has entered the elimination phase, but some goals remain to be accomplished before a programme re-orientation toward malaria elimination is contemplated. Moreover, a regional management policy is crucial because this would allow control measures to be targeted and based on a regional surveillance-response system rather than isolated.

Induction of a G1-S checkpoint in fission yeast.

Entry into S phase is carefully regulated and, in most organisms, under the control of a G(1)-S checkpoint. We have previously described a G(1)-S checkpoint in fission yeast that delays formation of the prereplicative complex at chromosomal replication origins after exposure to UV light (UVC). This checkpoint absolutely depends on the Gcn2 kinase. Here, we explore the signal for activation of the Gcn2-dependent G(1)-S checkpoint in fission yeast. If some form of DNA damage can activate the checkpoint, deficient DNA repair should affect the length of the checkpoint-induced delay. We find that the cell-cycle delay differs in repair-deficient mutants from that in wild-type cells. However, the duration of the delay depends not only on the repair capacity of the cells, but also on the nature of the repair deficiency. First, the delay is abolished in cells that are deficient in the early steps of repair. Second, the delay is prolonged in repair mutants that fail to complete repair after the incision stage. We conclude that the G(1)-S delay depends on damage to the DNA and that the activating signal derives not from the initial DNA damage, but from a repair intermediate(s). Surprisingly, we find that activation of Gcn2 does not depend on the processing of DNA damage and that activated Gcn2 alone is not sufficient to delay entry into S phase in UVC-irradiated cells. Thus, the G(1)-S delay depends on at least two different inputs.

Genetic Modifiers of Sickle Cell Disease: A Genotype-Phenotype Relationship Study in a Cohort of 82 Children on Mayotte Island.

Sickle cell disease presents a great clinical variability that remains largely misunderstood. New disease protective genetic modifiers acting mainly through an increased Hb F level have recently been described. We studied relations between clinical and hematological phenotypes and known sickle cell disease genetic modifiers in patients from Mayotte Island, a remote French territory located in the Indian Ocean. Eighty-two children with sickle cell disease were enrolled; their median age was 5.9 years (range 1-18). Clinical and hematological features of sickle cell disease were retrospectively collected. Genetic studies included determination of ß-globin genotypes [Hb SS, Hb S-ß(0)-thalassemia (Hb S-ß(0)-thal), Hb S-ß(+)-thal], ß(S)-globin locus haplotype, α-thalassemia (α-thal), and single nucleotide polymorphisms (SNPs) located in quantitative trait loci for Hb F expression (XmnI polymorphism, BCL11A rs4671393 and rs11886868, intergenic region of HBS1L-MYB rs28384513, rs4895441 and rs9399137). Univariate and multivariate analyses were conducted. Twenty-eight percent of the patients had Hb S-ß-thal (eight different mutations in 21 patients), 55.0% had the -α(3.7) (rightward) deletion and 88.0% of the homozygous Hb SS patients were carrying a homozygous Bantu haplotype. In the multivariate model, the prognosis role of the SNP BCL11A rs4671393 was confirmed in the studied population showing a significant association with an elevated Hb F level and with a low hospitalization rate. The -α(3.7) deletion, XmnI polymorphism and intergenic region HBS1L-MYB SNPs were not significantly linked to any clinical criteria of severity. This report, the first to describe the main features of children with sickle cell disease on Mayotte Island, highlights the protective effect of the BCL11A polymorphism in this population.

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.

Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase.

AIM OF THE STUDY: The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. METHODS: We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. RESULTS: A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). CONCLUSION: The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

A Comparative Study of Human Leptospirosis between Mayotte and Reunion Islands Highlights Distinct Clinical and Microbial Features Arising from Distinct Inter-Island Bacterial Ecology.

Leptospirosis is a neglected zoonosis for which investigations assessing host-pathogen interaction are scarce. The aim of this study was to compare the severity and bacterial species involved in human cases of leptospirosis on Reunion and Mayotte islands, territories located in the southwest Indian Ocean that have recorded high human leptospirosis incidence but display fairly distinct epidemiological situations. A retrospective multicentric study including all patients over 18 years of age from Mayotte or Reunion with proven leptospirosis was conducted from January 2018 to April 2020. This study collected demographic, geographical, clinical, and biological data. Overall, 490 patients were included, 222 on Mayotte and 268 on Reunion. More patients were hospitalized on Reunion (n = 215, 80%) compared with Mayotte (n = 102, 46%). Severe disease was more common on Reunion (n = 75, 28%) than on Mayotte (n = 22, 10%). The dominant Leptospira species on Reunion was Leptospira interrogans (79%) followed by Leptospira borgpetersenii (21%), contrasting with the epidemiological situation on Mayotte where L. interrogans was found in only a minority of patients (10%). The high frequency of severe cases on Reunion could be explained not only by higher comorbidities but also by the higher occurrence of L. interrogans infections compared with Mayotte. Finally, the distribution of cases linked to L. borgpetersenii was found almost exclusively on the west coast of Reunion, raising the potential role of a ruminant reservoir.

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.

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.

Clinical manifestations of human leptospirosis: bacteria matter.

Introduction: A high incidence of human leptospirosis is recorded on Mayotte, an oceanic island located in southwestern Indian Ocean, but the severity of the disease appears relatively mild in terms of mortality rate and admission to the intensive care unit. It has been proposed that mild leptospirosis may result from a limited virulence of some of the occurring Leptospira species to which the population is exposed. Methods: Clinical and biological data of patients admitted to the Centre Hospitalier de Mayotte were collected and the infecting Leptospira species were determined through molecular typing. Results: Leptospira interrogans was detected in the minority of admitted patients but most of these patients suffered from severe forms, with 50% admitted to intensive care unit and suffering from organ failures. Nineteen percent of patients infected with Leptospira borgpetersenii were admitted to the intensive care, with 13% displaying organ failures, and one patient died. Leptospira mayottensis was found in 28% of the patients and not a single severe case was observed. Discussion: The distribution of Leptospira species in patients was not different from that reported 10-15 years ago and bacterial genotypes were very closely related to those previously reported. These results highlight the importance of the diversity of pathogenic Leptospira circulating on Mayotte island and are in keeping with distinct outcome of the disease depending on the infecting Leptospira. Altogether, presented data support that the infecting Leptospira species is an important driver of disease severity in humans.

C-reactive protein: An easy marker for early differentiation between leptospirosis and dengue fever in endemic area.

In tropical regions, leptospirosis and dengue fever (DF) are infectious diseases of epidemiological importance and have overlapping symptomatic features. The objective of this study was to identify the factors associated to diagnosing leptospirosis that differentiate it to DF at the initial hospital evaluation. A multicenter retrospective study was conducted comparing confirmed leptospirosis to DF cases. Clinical/laboratory findings were compiled at hospital admission on Reunion Island between 2018 and 2019. Multivariable logistic regression was used to identify the predictors of leptospirosis. In total, 98 leptospirosis and 673 DF patients were included with a mean age of 47.8 (±17.1) and 48.9 (±23.3) years, respectively. In the multivariate analyses, the main parameters associated with leptospirosis were: i) increased neutrophil counts, ii) C-reactive protein values, iii) the absence of prolonged partial thromboplastin time, and iv) a decrease of platelets. The most discriminating parameter was C-reactive protein (CRP). With a threshold of 50mg/L, CRP taken alone had a sensitivity of 94% and a specificity of 93.5%. The positive and negative likelihood ratios were 14.5 and 0.06, respectively. In the setting of an early presumptive diagnosis, we found that an increased CRP value (>50 mg/L) could help diagnose leptospirosis and aid the decision process for hospital surveillance and/or a potential antibiotic treatment regimen.

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.

DNA repair triggered by sensors of helical dynamics.

Nucleotide excision repair is a constitutive stress response that eliminates DNA lesions induced by multiple genotoxic agents. Unlike the immune system, which generates billions of immunoglobulins and T cell receptors for antigen recognition, the nucleotide excision repair complex uses only a few generic factors to detect an astounding diversity of DNA modifications. New data favor an unexpected strategy whereby damage recognition is initiated by the detection of abnormal oscillations in the undamaged strand opposite to DNA lesions. Another core subunit recognizes the increased susceptibility of DNA to be kinked at injured sites. We suggest that early nucleotide excision repair factors gain substrate versatility by avoiding direct contacts with modified residues and exploiting instead the altered dynamics of damaged DNA duplexes.

Reliability and difference in neck extensor muscles strength measured by a portable dynamometer in individuals with and without chronic neck pain.

OBJECTIVE: There are limited reports about the reliability of measuring neck extensor muscle strength using a portable dynamometer in neck pain patients. The aims of the current study were 1) to investigate intra- and inter-rater reliability of neck extensor isometric strength measurement using a portable dynamometer in patients with chronic nonspecific neck pain (CNSNP) and 2) to compare neck extensor isometric strength in participants with and without CNSNP. METHODS: Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were followed. Two examiners received a 15-minute training before enrollment. Inter-rater reliability was assessed with a 10-minute interval between measurements, and intra-rater reliability was assessed with a 10-day interval. Three trials were assessed and examiners were blind to the strength values (in Newtons) from other sessions of 20 individuals with CNSNP (mean±SD= 37.9 ± 9.8y; Neck Disability Index 29.2 ± 7.4%) and 20 individuals with other musculoskeletal disorders (mean ± SD = 32.8 ± 46.2y). RESULTS: Intra-rater reliability was excellent with intraclass correlation coefficient (ICC)(3,1) of 0.95 (CI:0.90-0.97) and inter-rater reliability was good to excellent with ICC(2,1) of 0.88 (CI:0.77-0.94) in CNSNP. No significant difference of neck extensor strength was found between CNSNP (93.27N±31.94) and Individuals without CNSNP (111.43N±40.11) (p > 0.05). CONCLUSION: A portable dynamometer is a reliable tool for measuring maximal isometric neck extension strength in individuals with CNSNP. Slightly but no significant differences of neck extensor strength values between individuals with and without CNSNP. Future studies are needed to assess the generalizability of the findings in patients with other muscle deconditioning.

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.

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.

Diagnostic accuracy of upper limb neurodynamic tests in the diagnosis of cervical radiculopathy.

BACKGROUND: Upper limb neurodynamic tests (ULNT) are used to diagnose neuropathic conditions such as cervical radiculopathy (CR). Within the literature, a positive ULNT is defined in markedly variable ways, which is likely why the diagnostic accuracy of these tests lacks consistency across studies. OBJECTIVES: To determine the diagnostic accuracy of single and combined upper limb neurodynamic tests ((ULNT)1,2a, 2b and 3) for cervical radiculopathy using test findings that are similar to those used in practice. DESIGN: Diagnostic accuracy study (prospective) design following the updated STARD 2015 reporting guideline. METHOD: From 109 consecutively enrolled individuals with suspected CR. Of the 85 participants included, 27 (31.7%) were diagnosed with CR (mean age, 43.9years; Neck Disability Index 38,16%). ULNTs test were performed by a blind examiner to a CR reference standard of clinical diagnosis and magnetic resonance imaging verification provided by a neurosurgeon. RESULTS: In general, the single tests were better at ruling in CR versus ruling out. Of the single ULNT, the ULNT3 demonstrated the strongest post-test probability change with a positive finding (73.28%). Three of four test combinations demonstrated the highest clinical utility for changing the post-test probability with a positive finding at 83.29% and with LR+ = 12.89 (95%CI: 3.10-53.62). Having none of the test's positive was able to rule out CR with LR- = 0.08 (95%CI: 0.01-0.56). CONCLUSION: ULNTs fail to significantly alter post-test probability when used singularly for diagnosis of CR. However, combinations of ULNT (3 out of 4 positive) can rule in CR, and rule out CR when all ULNT are negative.

An aromatic sensor with aversion to damaged strands confers versatility to DNA repair.

It was not known how xeroderma pigmentosum group C (XPC) protein, the primary initiator of global nucleotide excision repair, achieves its outstanding substrate versatility. Here, we analyzed the molecular pathology of a unique Trp690Ser substitution, which is the only reported missense mutation in xeroderma patients mapping to the evolutionary conserved region of XPC protein. The function of this critical residue and neighboring conserved aromatics was tested by site-directed mutagenesis followed by screening for excision activity and DNA binding. This comparison demonstrated that Trp690 and Phe733 drive the preferential recruitment of XPC protein to repair substrates by mediating an exquisite affinity for single-stranded sites. Such a dual deployment of aromatic side chains is the distinctive feature of functional oligonucleotide/oligosaccharide-binding folds and, indeed, sequence homologies with replication protein A and breast cancer susceptibility 2 protein indicate that XPC displays a monomeric variant of this recurrent interaction motif. An aversion to associate with damaged oligonucleotides implies that XPC protein avoids direct contacts with base adducts. These results reveal for the first time, to our knowledge, an entirely inverted mechanism of substrate recognition that relies on the detection of single-stranded configurations in the undamaged complementary sequence of the double helix.