Rapid Diagnostic Tests for Non-Malarial Febrile Illness in the Tropics

The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy

Predictive value of clinical and laboratory features for the main febrile diseases in children living in Tanzania: A prospective observational study.

To construct evidence-based guidelines for management of febrile illness, it is essential to identify clinical predictors for the main causes of fever, either to diagnose the disease when no laboratory test is available or to better target testing when a test is available. The objective was to investigate clinical predictors of several diseases in a cohort of febrile children attending outpatient clinics in Tanzania, whose diagnoses have been established after extensive clinical and laboratory workup. From April to December 2008, 1005 consecutive children aged 2 months to 10 years with temperature ≥38°C attending two outpatient clinics in Dar es Salaam were included. Demographic characteristics, symptoms and signs, comorbidities, full blood count and liver enzyme level were investigated by bi- and multi-variate analyses (Chan, et al., 2008). To evaluate accuracy of combined predictors to construct algorithms, classification and regression tree (CART) analyses were also performed. 62 variables were studied. Between 4 and 15 significant predictors to rule in (aLR+>1) or rule out (aLR+<1) the disease were found in the multivariate analysis for the 7 more frequent outcomes. For malaria, the strongest predictor was temperature ≥40°C (aLR+8.4, 95%CI 4.7-15), for typhoid abdominal tenderness (5.9,2.5-11), for urinary tract infection (UTI) age ≥3 years (0.20,0-0.50), for radiological pneumonia abnormal chest auscultation (4.3,2.8-6.1), for acute HHV6 infection dehydration (0.18,0-0.75), for bacterial disease (any type) chest indrawing (19,8.2-60) and for viral disease (any type) jaundice (0.28,0.16-0.41). Other clinically relevant and easy to assess predictors were also found: malaria could be ruled in by recent travel, typhoid by jaundice, radiological pneumonia by very fast breathing and UTI by fever duration of ≥4 days. The CART model for malaria included temperature, travel, jaundice and hepatomegaly (sensitivity 80%, specificity 64%); typhoid: age ≥2 years, jaundice, abdominal tenderness and adenopathy (46%,93%); UTI: age <2 years, temperature ≥40°C, low weight and pale nails (20%,96%); radiological pneumonia: very fast breathing, chest indrawing and leukocytosis (38%,97%); acute HHV6 infection: less than 2 years old, (no) dehydration, (no) jaundice and (no) rash (86%,51%); bacterial disease: chest indrawing, chronic condition, temperature ≥39.7°c and fever duration >3 days (45%,83%); viral disease: runny nose, cough and age <2 years (68%,76%). A better understanding of the relative performance of these predictors might be of great help for clinicians to be able to better decide when to test, treat, refer or simply observe a sick child, in order to decrease morbidity and mortality, but also to avoid unnecessary antimicrobial prescription. These predictors have been used to construct a new algorithm for the management of childhood illnesses called ALMANACH

The crustal structure of the north-eastern Gulf of Aden continental margin: insights from wide-angle seismic data

International audienceThe wide-angle seismic (WAS) and gravity data of the Encens survey allow us to determinethe deep crustal structure of the north-eastern Gulf of Aden non-volcanic passive margin.The Gulf of Aden is a young oceanic basin that began to open at least 17.6 Ma ago. Itscurrent geometry shows first- and second-order segmentation: our study focusses on theAshawq–Salalah second-order segment, between Alula–Fartak and Socotra–Hadbeen fracturezones. Modelling of theWAS and gravity data (three profiles across and three along the margin)gives insights into the first- and second-order structures. (1) Continental thinning is abrupt(15–20 km thinning across 50–100 km distance). It is accommodated by several tilted blocks.(2) The ocean–continent transition (OCT) is narrow (15 km wide). The velocity modellingprovides indications on its geometry: oceanic-type upper-crust (4.5 km s−1) and continentaltypelower crust (>6.5 km s−1). (3) The thickness of the oceanic crust decreases from West(10 km) to the East (5.5 km). This pattern is probably linked to a variation of magma supplyalong the nascent slow-spreading ridge axis. (4) A 5 km thick intermediate velocity body (7.6to 7.8 kms−1) exists at the crust-mantle interface below the thinned margin, the OCT and theoceanic crust. We interpret it as an underplated mafic body, or partly intruded mafic materialemplaced during a ‘post-rift’ event, according to the presence of a young volcano evidencedby heat-flow measurement (Encens-Flux survey) and multichannel seismic reflection (Encenssurvey). We propose that the non-volcanic passive margin is affected by post-rift volcanismsuggesting that post-rift melting anomalies may influence the late evolution of non-volcanicpassive margins

Application of Automated Throw Backstripping Method to Characterize Recent Faulting Activity Migration in the Al Hoceima Bay (Northeast Morocco): Geodynamic Implications

This study was supported by projects CGL2016-80687-R AEI/FEDER, P18-RT-3275, B-RNM-301-UGR18 and RNM148 (Junta de Andalucia/FEDER); ALBAMAR JCJC ANR-17-CE030004; the EUROFLEETS program (FP7/2007-2013; no 228344); project FICTS-2011-03-01; and the FPU PhD grant (16/04038), and also by the Spanish Government through the 'Severo Ochoa Centre of Excellence' accreditation (CEX2019-000928-S).The IHS KINGDOM software package was utilized in the present study. We also to the marine surveys, MARLBORO2 and SARAS (https://campagnes.flotteoceanographique.fr/ campagnes/12450090/; https://campagnes.flotteoceanographique. fr/campagnes/12000010/).Automation of the throw backstripping method has proven to be an effective tool for the determination of the evolution of tectonic activity in wide fault zones. This method has been applied to the Al Hoceima Bay (southwesternmost Mediterranean, Alboran Sea) for a time period covering the last 280 kyr on 672 faults imaged on 265 high-resolution seismic reflection profiles. This area was affected by major earthquakes and corresponds to a transtensional basin deformed by growth faults. The automated application of throw backstripping allowed for a faster deciphering of the migration of tectonic activity. Results show a westward migration of the deformation with quickly increasing deformation rates in the most recent time frames near Al Hoceima, one of the most populated cities. This migration is in agreement with the current seismicity, the GPS data, and recent brittle deformation data. Vertical throw rates of up to 0.47 mm/year have been calculated, for the most recent time periods, in segments of the Bokkoya fault zone. The westward migration of the deformation fits with the reconstruction suggested by the westernmost Mediterranean geodynamic models during the Pleistocene epoch, and it might be the consequence of the interaction between the northwest (NW) movement of the South Alboran indenter and the back Rif south-westward displacement. The highly accurate constraints of the evolution of the tectonic activity offered by this automation will substantially improve the seismic hazard assessment.Junta de Andalucia European Commission CGL2016-80687-R AEI/FEDER P18-RT-3275 B-RNM-301-UGR18 RNM148ALBAMAR JCJC ANR-17-CE030004EUROFLEETS program (FP7/2007-2013) 228344German Research Foundation (DFG) 16/04038Spanish Government through the 'Severo Ochoa Centre of Excellence' accreditation CEX2019-000928-SFICTS-2011-03-0

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility

Beyond malaria--causes of fever in outpatient Tanzanian children.

BACKGROUND: As the incidence of malaria diminishes, a better understanding of nonmalarial fever is important for effective management of illness in children. In this study, we explored the spectrum of causes of fever in African children. METHODS: We recruited children younger than 10 years of age with a temperature of 38°C or higher at two outpatient clinics--one rural and one urban--in Tanzania. Medical histories were obtained and clinical examinations conducted by means of systematic procedures. Blood and nasopharyngeal specimens were collected to perform rapid diagnostic tests, serologic tests, culture, and molecular tests for potential pathogens causing acute fever. Final diagnoses were determined with the use of algorithms and a set of prespecified criteria. RESULTS: Analyses of data derived from clinical presentation and from 25,743 laboratory investigations yielded 1232 diagnoses. Of 1005 children (22.6% of whom had multiple diagnoses), 62.2% had an acute respiratory infection; 5.0% of these infections were radiologically confirmed pneumonia. A systemic bacterial, viral, or parasitic infection other than malaria or typhoid fever was found in 13.3% of children, nasopharyngeal viral infection (without respiratory symptoms or signs) in 11.9%, malaria in 10.5%, gastroenteritis in 10.3%, urinary tract infection in 5.9%, typhoid fever in 3.7%, skin or mucosal infection in 1.5%, and meningitis in 0.2%. The cause of fever was undetermined in 3.2% of the children. A total of 70.5% of the children had viral disease, 22.0% had bacterial disease, and 10.9% had parasitic disease. CONCLUSIONS: These results provide a description of the numerous causes of fever in African children in two representative settings. Evidence of a viral process was found more commonly than evidence of a bacterial or parasitic process. (Funded by the Swiss National Science Foundation and others.)

Oblique basin inversion and strain partitioning in back-arc context: example from the Moroccan Alboran Margin (Western Mediterranean)

EUROPEAN GEOPHYSICAL UNIO

Increased Nasopharyngeal Density and Concurrent Carriage of Streptococcus Pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Are Associated with Pneumonia in Febrile Children.

We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p<0.002; Hi p<0.001; Mc, p = 0.014). Accordingly, concurrent carriage of Sp+, Hi+, and Mc+, in the absence of Sa- and Nm-, was significantly more prevalent in children with ARI (p = 0.03), or clinical pneumonia (p<0.001) than non-ARI, and in children with clinical pneumonia (p = 0.0007) than URTI. Furthermore, Sp+, Hi+, and Mc+ differentiated children with pneumonia with normal CXR, or endpoint pneumonia, from those with URTI, and non-ARI cases. Concurrent NP carriage of Sp, Hi, and Mc was a predictor of clinical pneumonia and identified children with pneumonia with normal CXR and endpoint pneumonia from those with febrile URTI, or non-ARI episodes

Interacción entre procesos sedimentarios longitudinales y transversales en el Mar de Alborán durante el Plioceno y Cuaternario

Several morphosedimentary signatures produced by the interaction between alongslope and downslope sedimentary processes have been identified in the Pliocene and Quaternary records as well as on the present-day seafloor of the Alboran Sea. The scenarios of interaction move between two-end-members: from bottom currents dominating gravity flows to gravity flows dominating contour currents. In between these extreme cases, the alternation and balancing of both processes can occur; bottom current activity influencing the gravity flows has been also detected. Although interaction occurs in the Spanish and Moroccan margins, it is especially complex and varied on the Spanish margin, with regional and local effects on the turbidite systems. In contrast, the interaction on the Moroccan margin primarily inhibits the formation of canyons and related fan lobe deposits.Versión del edito