Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data.

When responding to infectious disease outbreaks, rapid and accurate estimation of the epidemic trajectory is critical. However, two common data collection problems affect the reliability of the epidemiological data in real time: missing information on the time of first symptoms, and retrospective revision of historical information, including right censoring. Here, we propose an approach to construct epidemic curves in near real time that addresses these two challenges by 1) imputation of dates of symptom onset for reported cases using a dynamically-estimated "backward" reporting delay conditional distribution, and 2) adjustment for right censoring using the NobBS software package to nowcast cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020. We evaluate how these real-time estimates compare with more complete epidemiological data that became available later. We explore the impact of the different assumptions on the estimates, and compare our estimates with those obtained from commonly used surveillance approaches. Our framework can help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health systems in other locations.

Intramedullary percutaneous fixation of metacarpal fractures: screw versus connected K-wires.

The purpose of the present study was to determine clinical and radiographic outcomes in patients treated with limited-open retrograde intramedullary headless screw fixation for metacarpal neck and shaft fractures (group I) versus percutaneous antegrade and retrograde intramedullary double pinning linked by a connector (group II). We designed a retrospective comparative study, with the inclusion of two groups (20 patients each) of metacarpal unstable fractures. Both groups showed similar outcomes at the final follow-up, except for extension lag (significantly better in group II) and return to sport (significantly better in group I). Intramedullary screw fixation did not accelerate bone union and range of motion recovery in the early follow-up. In conclusion, limited-open retrograde intramedullary headless screw fixation and percutaneous connected antegrade and retrograde intramedullary double pinning are both reliable techniques of fixation for metacarpal neck and shaft fractures. LEVEL OF EVIDENCE: III.

Dirofilaria immitis possesses molecules with anticoagulant properties in its excretory/secretory antigens.

Dirofilaria immitis is a parasitic nematode that survives in the circulatory system of suitable hosts for many years, causing the most severe thromboembolisms when simultaneous death of adult worms occurs. The two main mechanisms responsible for thrombus formation in mammals are the activation and aggregation of platelets and the generation of fibrin through the coagulation cascade. The aim of this work was to study the anticoagulant potential of excretory/secretory antigens from D. immitis adult worms (DiES) on the coagulation cascade of the host. Anticoagulant and inhibition assays respectively showed that DiES partially alter the coagulation cascade of the host and reduce the activity of the coagulation factor Xa, a key enzyme in the coagulation process. In addition, a D. immitis protein was identified by its similarity to the homologous serpin 6 from Brugia malayi as a possible candidate to form an inhibitory complex with FXa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and mass spectrometry. These results indicate that D. immitis could use the anticoagulant properties of its excretory/secretory antigens to control the formation of blood clots in its immediate intravascular habitat as a survival mechanism.

The Canary Islands as a model of risk of pulmonary dirofilariasis in a hyperendemic area.

We assessed the risk of human pulmonary dirofilariasis in the Canary Islands, hyperendemic for canine heartworm (Dirofilaria immitis), a zoonotic vector-borne infection. For this purpose, 1479 inhabitants were tested for anti-D. immitis antibodies. Four of the 7 islands presented high seroprevalences (from 6.2 to 12.7%), therefore high exposure to the parasite and risk of zoonotic infection. These corresponded to those islands with high canine prevalences of dirofilariasis and favourable climatic conditions for the development of mosquito vectors. The lowest prevalences (from 0 to 1.6%) were found in the desert islands and those with low canine prevalences of heartworm. Seroprevalences were very variable inside each island as well, being related to the climate and demographic factors. Human pulmonary dirofilariasis is an emerging zoonosis worldwide which frequently goes undiagnosed. Serological studies could be useful for the correct evaluation of the risk of infection among the human population, and study of the health implications of the continuous contact with the parasite in endemic areas. Sanitary authorities should be aware of the current epidemiological data, and physicians should include human dirofilariasis in the differential diagnosis of pulmonary nodules.

Thirty cases of human subcutaneous dirofilariasis reported in Rostov-on-Don (Southwestern Russian Federation).

INTRODUCTION: Different species of the genus Dirofilaria, mainly D. immitis and D. repens, are responsible for emergent vector borne transmitted zoonotic diseases in the Old World. Human D. repens infections are characterized by the appearance of benign subcutaneous nodules that mimic skin malignant tumors or due to live worms in the ocular area. METHODS: Thirty patients presenting superficial or deep nodules were treated at the Rostov Regional Diagnostic Center (Southwestern Russian Federation). Anatomical characteristics of the nodules were studied by non-invasive ultrasound and color and power Doppler techniques. Worms were surgically removed from every nodule and their DNA analyzed by polymerase chain reaction (PCR). RESULTS: Twenty-four out of the 30 nodules were located in the hypodermis, two in a retro-ocular location and four in scrotal location. Image techniques allowed the identification of the helminthic origin of all nodules, based on their oval and regular shape, peripheral vasculature, and the existence of internal linear winding hyperechoic structures with or without movements, indicating the presence of live or dead worms, respectively. Specific adscription to D. repens was achieved by the PCR analysis. CONCLUSION: The series described in the present paper confirms the increasing risk of infection by D. repens in humans living in endemic areas of Eastern Europe. The use of non-invasive ultrasounds and Doppler techniques can contribute to an appropriate management of human dirofilariasis. Moreover, awareness of the medical community in the endemic areas influences the report of cases, and consequently the current epidemiological picture of human dirofilariasis.

Evaluation of the plan for surveillance and controlling of the effects of heat waves in Madrid.

This paper presents evaluation of a plan for surveillance of and controlling the effects of heat-related mortality (PSCEHW), implemented in Madrid in 2004 through a time series analysis conducted with ARIMA modeling. From the public health point of view, prevention plans should be implemented as adaptive measures to heat waves. In 2003, the impact attributable to the heat wave was an increase in mortality per °C of 22.39 %. All heat waves since 2003 have been of lower intensity, and yet, in 2005 there was a heat wave of lower intensity that had a greater impact, i.e. an increase in mortality per °C of 45.71 %. With the methodology used here, we cannot say whether implementation of PSCEHW has resulted in a decrease of mortality attributable to high temperatures in the city of Madrid.

Human and animal dirofilariasis: the emergence of a zoonotic mosaic.

Dirofilariasis represents a zoonotic mosaic, which includes two main filarial species (Dirofilaria immitis and D. repens) that have adapted to canine, feline, and human hosts with distinct biological and clinical implications. At the same time, both D. immitis and D. repens are themselves hosts to symbiotic bacteria of the genus Wolbachia, the study of which has resulted in a profound shift in the understanding of filarial biology, the mechanisms of the pathologies that they produce in their hosts, and issues related to dirofilariasis treatment. Moreover, because dirofilariasis is a vector-borne transmitted disease, their distribution and infection rates have undergone significant modifications influenced by global climate change. Despite advances in our knowledge of D. immitis and D. repens and the pathologies that they inflict on different hosts, there are still many unknown aspects of dirofilariasis. This review is focused on human and animal dirofilariasis, including the basic morphology, biology, protein composition, and metabolism of Dirofilaria species; the climate and human behavioral factors that influence distribution dynamics; the disease pathology; the host-parasite relationship; the mechanisms involved in parasite survival; the immune response and pathogenesis; and the clinical management of human and animal infections.

The influence of parental education on child mental health in Spain.

PURPOSE: To analyze the association between parental education and offspring's mental health in a nationally representative Spanish sample, and assess the contribution of other socioeconomic factors to the association. METHODS: We conducted a secondary analysis of data on 4- to 15-year-olds participating in the 2006 Spanish National Health Survey. Mental health was assessed using the parent-reported Strengths & Difficulties Questionnaire. Parents' respective educational levels were summarized in a single variable. Univariate and multivariate analyses, controlling for family-, child- and parent-related characteristics, were used to study the association. RESULTS: The final sample comprised 5,635 children. A strong association between parental education and parent-reported child mental health was observed among 4- to 11-year-olds, with odds ratios (ORs) increasing as parental educational level decreased. Where both parents had a sub-university level, maternal education showed a stronger association than did paternal education. Following adjustment for covariates, parental education continued to be the strongest risk factor for parent-reported child mental health problems, OR = 3.7 (95% CI 2.4-5.8) for the lowest educational level, but no association was found among 12- to 15-year-olds. Male sex, immigrant status, activity limitation, parent's poor mental health, low social support, poor family function, single-parent families, low family income and social class were associated with parent-reported child mental health problems in both age groups. CONCLUSIONS: Our results show that there is a strong association between parental education and parent-reported child mental health, and that this is indeed stronger than that for income and social class. Among adolescents, however, the effect of parental education would appear to be outweighed by other factors.

How Healthcare Systems Negatively Impact Environmental Health? The Need for Institutional Commitment to Reduce the Ecological Footprint of Medical Services.

The global healthcare industry plays a crucial role in preserving human health and well-being [...].

Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism.

BACKGROUND: The trematode Fasciola hepatica is the most widespread causative agent of fasciolosis, a parasitic disease that mainly affects humans and ruminants worldwide. During F. hepatica infection, newly excysted juveniles (FhNEJ) emerge in the duodenum of the mammalian host and migrate towards their definitive location, the intra-hepatic biliary ducts. Understanding how F. hepatica traverses the intestinal wall and migrates towards the liver is pivotal for the development of more successful strategies against fasciolosis. The central enzyme of the mammalian fibrinolytic system is plasmin, a serine protease whose functions are exploited by a number of parasite species owing to its broad spectrum of substrates, including components of tissue extracellular matrices. The aim of the present work is to understand whether FhNEJ co-opt the functions of their host fibrinolytic system as a mechanism to facilitate trans-intestinal migration. METHODOLOGY/PRINCIPAL FINDINGS: A tegument-enriched antigenic extract of FhNEJ (FhNEJ-Teg) was obtained in vitro, and its capability to bind the zymogen plasminogen (PLG) and enhance its conversion to the active protease, plasmin, were analyzed by a combination of enzyme-linked immunosorbent, chromogenic and immunofluorescence assays. Additionally, PLG-binding proteins in FhNEJ-Teg were identified by bidimensional electrophoresis coupled to mass spectrometry analysis, and the interactions were validated using FhNEJ recombinant proteins. CONCLUSIONS/SIGNIFICANCE: Our results show that FhNEJ-Teg contains proteins that bind PLG and stimulate its activation to plasmin, which could facilitate the traversal of the intestinal wall by FhNEJ and contribute to the successful establishment of the parasite within its mammalian host. Altogether, our findings contribute to a better understanding of host-parasite relationships during early fasciolosis and may be exploited from a pharmacological and/or immunological perspective for the development of treatment and control strategies against this global disease.

Interaction of helminth parasites with the haemostatic system of their vertebrate hosts: a scoping review.

Helminth parasitoses are among the most prevalent health issues worldwide. Their control depends largely on unravelling host-parasite interactions, including parasitic exploitation of the host haemostatic system. The present study undertakes a scoping review of the research carried out in this field with the aim of unifying and updating concepts. Multiple keywords combined with Boolean operators were employed to design the literature search strategy. Two online databases were used to identify original peer-reviewed articles written in English and published before 1st January 2020 describing molecular interactions between helminth parasites and the host haemostatic system. Relevant data from the selected sources of evidence were extracted and analysed. Ninety-six publications reporting 259 interactions were selected. Fifty-three proteins belonging to 32 species of helminth parasites were involved in interactions with components of the host haemostatic system. Many of these proteins from both parasite and host were conserved among the different interactions identified. Most of these interactions were related to the inhibition of the coagulation system and the activation of fibrinolysis. This was associated mainly with a potential of parasites to reduce the formation of blood clots in the host and attributed to biological processes, such as parasite nutrition, survival, invasion, evasion and migration or the appearance of pathological mechanisms in the host. A wide range of helminth parasites have developed similar strategies to exploit the haemostatic system of their hosts, which could be regarded as an evolutionary conserved mechanism that could confer benefits to parasites in terms of survival and establishment in their vertebrate hosts.

Title: Interaction des helminthes parasites avec le système hémostatique de leurs hôtes vertébrés : un examen exploratoire. Abstract: Les parasitoses par les helminthes sont à l'origine de problèmes de santé parmi les plus répandus dans le monde. Leur contrôle dépend en grande partie du démêlage des interactions hôte-parasite, y compris l'exploitation par les parasites du système hémostatique de l'hôte. La présente étude entreprend un examen exploratoire des recherches menées dans ce domaine dans le but d'unifier et d'actualiser les concepts. Plusieurs mots-clés combinés à des opérateurs booléens ont été utilisés pour concevoir la stratégie de recherche documentaire. Deux bases de données en ligne ont été utilisées pour identifier des articles originaux évalués par des pairs rédigés en anglais et publiés avant le 1er janvier 2020, décrivant les interactions moléculaires entre les helminthes parasites et le système hémostatique de l'hôte. Les données pertinentes des sources sélectionnées ont été extraites et analysées. Quatre-vingt-seize publications rapportant 259 interactions ont été sélectionnées. Cinquante-trois protéines appartenant à 32 espèces d'helminthes parasites ont été impliquées dans des interactions avec des composants du système hémostatique de l'hôte. Beaucoup de ces protéines du parasite et de l'hôte ont été conservées parmi les différentes interactions identifiées. La plupart de ces interactions étaient liées à l'inhibition du système de coagulation et à l'activation de la fibrinolyse. Ceci était principalement associé à un potentiel des parasites à réduire la formation de caillots sanguins chez l'hôte et attribué à des processus biologiques, tels que la nutrition, la survie, l'invasion, l'évasion et la migration des parasites ou l'apparition de mécanismes pathologiques chez l'hôte. Un large éventail d'helminthes parasites ont développé des stratégies similaires pour exploiter le système hémostatique de leurs hôtes, ce qui pourrait être considéré comme un mécanisme évolutif conservé qui pourrait conférer des avantages aux parasites en termes de survie et d'établissement chez leurs hôtes vertébrés.

Human dirofilariosis in the 21st century: A scoping review of clinical cases reported in the literature.

Human dirofilariosis is a clinical entity caused by infection with nematode species of the genus Dirofilaria. The traditional picture depicts the disease as a sporadic event associated with the presence of a single immature worm causing a nodular lesion. With the aim to reassess this paradigm, establishing a more accurate picture of the disease and homogenize criteria, a scoping review was conducted by searching, screening and analysing published clinical cases of human dirofilariosis worldwide during the 21st century. After extracting data from 305 publications containing 576 case reports, results showed that human dirofilariosis is currently caused by five Dirofilaria species (mainly D. repens). Maturation was not uncommon, since 42.95% of the parasites recovered were described as mature worms, most of them females, 26.42% of which contained micofilariae in the uterus. Moreover, six microfilaremic cases have been described. The predominant clinical manifestation was the presence of a worm encapsulated within a nodule, but there is a considerable variety of accompanying symptoms depending on anatomical location and type of dirofilariosis. Parasites/nodules were found in 71 different anatomical locations, being the traditional nomenclature of human dirofilariosis unable to properly cover this complex situation. Delay in seeking medical assistance (patient perception) and the frequency of wrong clinical suspicions (doctor knowledge), strongly influenced clinical management. The initial suspicion in cases of subcutaneous and pulmonary dirofilariosis is predominantly a tumour, while in the ocular dirofilariosis a parasite (but not directly Dirofilaria) is mostly suspected. Surgery is usually applied, regardless of the use of non-invasive techniques during preoperative management and although its use is still limited, molecular approach is the most accurate technique to establish a species-level diagnosis. Accurate epidemiological, parasitological and clinical information while handling and reporting human clinical cases is a need for physicians and researchers to improve and standardize the clinical management of human dirofilariosis.

Proteomics coupled with in vitro model to study the early crosstalk occurring between newly excysted juveniles of Fasciola hepatica and host intestinal cells.

Fasciolosis caused by the trematode Fasciola hepatica is a zoonotic neglected disease affecting animals and humans worldwide. Infection occurs upon ingestion of aquatic plants or water contaminated with metacercariae. These release the newly excysted juveniles (FhNEJ) in the host duodenum, where they establish contact with the epithelium and cross the intestinal barrier to reach the peritoneum within 2-3 h after infection. Juveniles crawl up the peritoneum towards the liver, and migrate through the hepatic tissue before reaching their definitive location inside the major biliary ducts, where they mature into adult worms. Fasciolosis is treated with triclabendazole, although resistant isolates of the parasite are increasingly being reported. This, together with the limited efficacy of the assayed vaccines against this infection, poses fasciolosis as a veterinary and human health problem of growing concern. In this context, the study of early host-parasite interactions is of paramount importance for the definition of new targets for the treatment and prevention of fasciolosis. Here, we develop a new in vitro model that replicates the first interaction between FhNEJ and mouse primary small intestinal epithelial cells (MPSIEC). FhNEJ and MPSIEC were co-incubated for 3 h and protein extracts (tegument and soma of FhNEJ and membrane and cytosol of MPSIEC) were subjected to quantitative SWATH-MS proteomics and compared to respective controls (MPSIEC and FhNEJ left alone for 3h in culture medium) to evaluate protein expression changes in both the parasite and the host. Results show that the interaction between FhNEJ and MPSIEC triggers a rapid protein expression change of FhNEJ in response to the host epithelial barrier, including cathepsins L3 and L4 and several immunoregulatory proteins. Regarding MPSIEC, stimulation with FhNEJ results in alterations in the protein profile related to immunomodulation and cell-cell interactions, together with a drastic reduction in the expression of proteins linked with ribosome function. The molecules identified in this model of early host-parasite interactions could help define new tools against fasciolosis.

[Effectiveness of vaccines against SARS-CoV-2 used in Spain: infection, hospitalization and mortality in people aged fifty/fifty-nine.] / Efectividad de las vacunas frente a SARS-CoV-2 utilizadas en España: infección, hospitalización y mortalidad en personas de cincuenta a cincuenta y nueve años.

In this paper we compared brand-specific COVID-19 vaccine effectiveness (VE) during August 2021 in persons born 1962-1971 and vaccinated during June. For SARS-CoV-2 symptomatic infection, protection was lower for Janssen (56%; CI95%: 53-59) or AstraZeneca [Vaxzevria] (68%; CI95%: 65-70), compared to Pfizer-BioNTech [Comirnaty] (78%; CI95%: 77-78), AstraZeneca/Pfizer (86%; CI95%: 80-90) or Moderna [Spikevax] (89%; CI95%: 88-90). VE against hospitalization was ranged 86% for Janssen to 97%-98% for other vaccines.

En este trabajo se comparó la efectividad de la vacuna contra la COVID-19 (EV) durante agosto de 2021, en personas nacidas entre 1962 y 1971 y vacunadas durante junio, según la marca utilizada. La protección frente a infección por SARS-CoV-2 sintomática fue menor para la vacuna de Janssen (56%; IC95%: 53-59) y AstraZeneca [Vaxzevria] (68%; IC95%: 65-70), en comparación con Pfizer [Comirnaty] (78%; IC95%: 77-78), AZ/Pfizer (86%; IC95%: 80-90) y Moderna [Spikevax] (89%; IC95%: 88-90). La EV contra la hospitalización osciló entre el 86% de Janssen y el 97%-98% de las demás vacunas.

Study of the migration of Fasciola hepatica juveniles across the intestinal barrier of the host by quantitative proteomics in an ex vivo model.

Fasciola hepatica is a trematode parasite that infects animals and humans causing fasciolosis, a worldwide-distributed disease responsible for important economic losses and health problems. This disease is of growing public health concern since parasite isolates resistant to the current treatment (triclabendazole) have increasingly been described. F. hepatica infects its vertebrate host after ingestion of the encysted parasite (metacercariae), which are found in the water or attached to plants. Upon ingestion, newly excysted juveniles of F. hepatica (FhNEJ) emerge in the intestinal lumen and cross the intestinal barrier, reach the peritoneum and migrate to the biliary ducts, where adult worms fully develop. Despite the efforts made to develop new therapeutic and preventive tools, to date, protection against F. hepatica obtained in different animal models is far from optimal. Early events of host-FhNEJ interactions are of paramount importance for the infection progress in fasciolosis, especially those occurring at the host-parasite interface. Nevertheless, studies of FhNEJ responses to the changing host environment encountered during migration across host tissues are still scarce. Here, we set-up an ex vivo model coupled with quantitative SWATH-MS proteomics to study early host-parasite interaction events in fasciolosis. After comparing tegument and somatic fractions from control parasites and FhNEJ that managed to cross a mouse intestinal section ex vivo, a set of parasite proteins whose expression was statistically different were found. These included upregulation of cathepsins L3 and L4, proteolytic inhibitor Fh serpin 2, and a number of molecules linked with nutrient uptake and metabolism, including histone H4, H2A and H2B, low density lipoprotein receptor, tetraspanin, fatty acid binding protein a and glutathione-S-transferase. Downregulated proteins in FhNEJ after gut passage were more numerous than the upregulated ones, and included the heath shock proteins HSP90 and alpha crystallin, amongst others. This study brings new insights into early host-parasite interactions in fasciolosis and sheds light on the proteomic changes in FhNEJ triggered upon excystment and intestinal wall crossing, which could serve to define new targets for the prevention and treatment of this widespread parasitic disease.

Host-Parasite Relationships in Porcine Ascariosis: Anticoagulant Potential of the Third Larval Stage of Ascaris suum as a Possible Survival Mechanism.

In order to evade the response of their hosts, helminth parasites have evolved precise and highly regulated mechanisms, including migration strategies of the larval stages. In regard to porcine ascariosis caused by Ascaris suum, its infective third-stage larvae (AsL3) undergo a complex migratory route through the bloodstream of their host before establishing in the small intestine to reach maturation. Despite the benefits attributed to this migration, blood clots formation could compromise larvae survival. The aim of this work was to study the interaction between the cuticle and excretory/secretory antigens of AsL3 and the host coagulation cascade. Larvae were obtained after incubating and hatching A. suum eggs, after which the antigenic extracts were produced. Their ability to disrupt the coagulation cascade was studied using anticoagulation and chromogenic assays, and techniques based on electrophoresis. The obtained results showed that both antigenic extracts possessed anticoagulant potential, being able to inhibit the intrinsic, extrinsic and/or common pathways of the blood coagulation cascade as well as the activated factor X. Moreover, three A. suum serpin proteins were identified as candidates to inhibit this host coagulation factor. To the best of our knowledge, this study shows, for the first time, the anticoagulant potential of the infective larvae of A. suum, which could be used by the parasite as a mechanism to facilitate its invasion and survival in the host.

Phlebovirus-associated diseases transmitted by phlebotominae in Spain: Are we at risk?

The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness.

Canine dirofilariosis caused by Dirofilaria immitis is a risk factor for the human population on the island of Gran Canaria, Canary Islands, Spain.

The aim of the present study was compare the prevalence of D. immitis in dogs and seroprevalence in humans of Gran Canaria (Canary Islands, Spain) taking into consideration the four isoclimatic areas of the island. A close relationship between the prevalence of Dirofilaria immitis in dogs and the seroprevalence in humans, in each isoclimatic area, was observed. The highest seroprevalence of infection in both canine and human hosts were found in a strip of mid-range altitude with 25.47% and 30.4% in dogs and 25.66% and 29.73% in humans, respectively. The coastal zone and the highest part of the island have prevalences significantly lower. These results demonstrate that the risk of infection by D. immitis in the human population in each area is tied to the prevalence in the canine population. Physicians should be alerted to the possibility of finding cases of human pulmonary dirofilariosis amongst the inhabitants of the island.